Antihypertensive treatment during pregnancy induces long-term changes in gut microbiota and the behaviors of the attention deficit hyperactivity disorder offspring.

The pathogenesis of attention-deficit/hyperactivity disorder (ADHD) has not been fully elucidated. Gestational hypertension could double the probability of ADHD in the offspring, while the initial bacterial communication between the mother and offspring has been associated with psychiatric disorders. Thus, we hypothesize that antihypertensive treatment during pregnancy may abate the impairments in neurodevelopment of the offspring. To test this hypothesis, we chose Captopril and Labetalol, to apply to pregnant spontaneously hypertensive rat (SHR) dams and examined the outcomes in the male offspring. Our data demonstrated that maternal treatment with Captopril and Labetalol had long-lasting changes in gut microbiota and behavioral alterations, including decreased hyperactivity and increased curiosity, spatial learning and memory in the male offspring. Increased diversity and composition were identified, and some ADHD related bacteria were found to have the same change in the gut microbiota of both the dam and offspring after the treatments. LC-MS/MS and immunohistochemistry assays suggested elevated expression of brain derived neurotrophic factor (BDNF) and dopamine in the prefrontal cortex and striatum of offspring exposed to Captopril/ Labetalol, which may account for the improvement of the offspring's psychiatric functions. Therefore, our results support the beneficial long-term effects of the intervention of gestational hypertension in the prevention of ADHD.

Taurocholic acid ameliorates hypertension through the activation of TGR5 in the hypothalamic paraventricular nucleus.

Diets rich in taurine can increase the production of taurine-conjugated bile acids, which are known to exert antihypertensive effects. Despite their benefits to the heart, kidney and arteries, their role in the central nervous system during the antihypertensive process remains unclear. Since hypothalamic paraventricular nucleus (PVN) plays a key role in blood pressure regulation, we aimed to investigate the function of bile acids in the PVN. The concentration of bile acids in the PVN of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKY) fed with normal chow was measured using LC-MS/MS, which identified taurocholic acid (TCA) as the most down-regulated bile acid. To fully understand the mechanism of TCA's functions in the PVN, bi-lateral PVN micro-infusion of TCA was carried out. TCA treatment in the PVN led to a significant reduction in the blood pressure of SHRs, with decreased plasma levels of norepinephrine and improved morphology of cardiomyocytes. It also decreased the number of c-fos+ neurons, reduced the inflammatory response, and suppressed oxidative stress in the PVN of the SHRs. Most importantly, the TGR5 receptors in neurons and microglia were activated. PVN infusion of SBI-115, a TGR5 specific antagonist, was able to counteract with TCA in the blood pressure regulation of SHRs. In conclusion, TCA supplementation in the PVN of SHRs can activate TGR5 in neurons and microglia, reduce the inflammatory response and oxidative stress, suppress activated neurons, and attenuate hypertension.

Mediterranean diet associated with lower frailty risk: A large cohort study of 21,643 women admitted to hospitals.

BACKGROUND: Mediterranean diet is traditionally considered as a healthy dietary pattern, while its association with frailty has not been confirmed. This study investigated associations between Mediterranean diet and risk of frailty among women admitted to hospitals in England from an older-aged women's cohort study. METHODS: A modified Mediterranean diet was evaluated from a validated 217-item food frequency questionnaire. Incident frailty was determined using a hospital frailty risk score based on linkage to Hospital Episode Statistics up to March 2019. Cox proportional hazard models were conducted to estimate hazard ratios (HR) and 95% confidence intervals (CI). Further subgroup analyses stratified by age and body mass index (BMI), and sensitivity analyses were additionally explored. RESULTS: Over a mean follow-up of 13 years, there were 14,838 (68.6%) cases of frailty out of 21,643 individuals included in this study. Compared with low adherence to Mediterranean diet, moderate adherence was associated with 5% (HR = 0.95, 95%CI: 0.91, 0.99) lower risk of frailty, with high adherence associated with even lower risk (HR = 0.89, 95%CI: 0.85, 0.94). The magnitude of above associations remained consistent in subgroups stratified by age and BMI, except the association between moderate adherence and risk of frailty was attenuated in the ≥60-year (HR = 0.99, 95%CI: 0.93, 1.06) and the BMI > 24.9 kg/m2 (HR = 0.97, 95%CI: 0.91, 1.03) subgroups. CONCLUSIONS: Adherence to Mediterranean diet was associated with lower risk of frailty. The better the adherence, the greater the magnitude of the protective association. Older and overweight women may potentially benefit from greater adherence to the Mediterranean diet regarding frailty prevention.

Facile preparation of low temperature carbon dots with long-wavelength emission and their sensing applications for crystal violet.

Crystal violet (CV) is one of the main components of common fungicides in daily life, which has inhibitory effect on gram-positive bacteria. However, CV remains in the environment for a long time and have potential risk of disease. Therefore, it is necessary to develop effective methods for detecting CV. Low-temperature carbon dots (LT-CDs) are studied to provide a new idea for the development of CDs green preparation technology from the perspective of low energy consumption. In this experiment, LT-CDs with long-wavelength emission were prepared based on the oxidation, cross-linking polymerization and Schiff base reaction using o-phenylenediamine and hydroquinone as carbon source at low temperature, and were characterized by various techniques. It was found that LT-CDs could be used as a fluorescent probe for quantitative detection of CV based on the inner filter effect, and the practicability of the method was verified by real samples.

Acute Symptomatic Seizures and Risk of Seizure Recurrence in Patients with Anti-NMDAR, Anti-LGI1, and Anti-GABABR Encephalitis.

AIMS: To analyze the clinical characteristics of acute symptomatic seizures and predict the risk factors for seizure recurrence in patients with anti-N-methyl-D-aspartate receptor (NMDAR), anti-leucine-rich glioma-inactivated 1 (LGI1), and anti-gamma-aminobutyric acid B receptor (GABABR) encephalitis. METHODS: In this retrospective study, we included hospitalized patients who had been diagnosed with anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis between November 2014 and April 2021. Binary logistic regression analysis was performed to identify the potential risk factors for seizure recurrence. RESULTS: In total, 262 patients with anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis were included, 197 (75.2%) of whom presented with acute symptomatic seizures. During follow-up, 42 patients exhibited seizure recurrence. In anti-NMDAR encephalitis, frontal lobe abnormality on brain magnetic resonance imaging, delayed immunotherapy, early seizures, and focal motor onset were associated with seizure recurrence. CONCLUSIONS: Acute symptomatic seizure is a common clinical feature observed in patients with anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis, with 50% of patients presenting with seizures as an initial symptom. The prognosis of patients with acute symptomatic seizures can be improved after receiving immunotherapy. Nevertheless, a minority of patients will experience seizure recurrence; therefore, restarting immunotherapy is recommended.

Green syntheses of silk fibroin/wool keratin-protected AuAg nanoclusters with enhanced fluorescence for multicolor and patterned anti-counterfeiting.

Counterfeiting is a serious worldwide issue that threatens human health and economic security. How to apply anti-counterfeiting techniques to textile materials remains a great challenge. Herein, we report bimetallic AuAg nanoclusters (NCs) synthesized by one-step reduction of chloroauric acid (HAuCl4) and silver nitrate (AgNO3) with wool keratin (WK) as reducer and silk fibroin (SF) as stabilizer. The strongest orange-red fluorescence under ultraviolet light as well as the highest zeta potential absolute values of -27.97 mV were simultaneously realized in the optimal proportion Au-AgNCs2 (WK/SF is 3/2), which was further processed to a series of anti-counterfeiting films by blending with SF, silk sericin (SS), and polyvinyl alcohol (PVA). After successfully being numbered into fifteen colors, a dark blue-orange-dark red-dark blue cyclic fluorescent anti-counterfeiting color chart was designed. In addition, a two-Maxwell-unit model was constructed to assist with the microstructure analysis, which found that the formation of hydrogen bonds and the secondary structure transition from α-helices to ß-sheets during stretching were responsible for improving the mechanical properties and the two-staged fracture curves of films, respectively. Finally, a patterned and multicolor fluorescence anti-counterfeiting fabric application was demonstrated by combining the color chart and screen printing, indicating the great potential in textile anti-counterfeiting.

Types of On-Screen Content and Mental Health in Kindergarten Children.

Importance: Excessive screen time has been associated with a higher risk for mental health problems, but whether the associations differ by screen content types is unclear. Objective: To examine the allocation of and longitudinal changes in screen exposure across different content types and to explore their associations with mental health in children aged 3 to 6 years. Design, Setting, and Participants: This cohort study used 3-wave, lagged generalized estimating equation models to analyze data from the Shanghai Children's Health, Education and Lifestyle Evaluation-Preschool (SCHEDULE-P) study in Shanghai, China. The cohort was a representative sample of kindergarten children. Data were collected between November 2016 and May 2019 when children were aged 3 to 4 years (wave 1), 4 to 5 years (wave 2), and 5 to 6 years (wave 3). Data analysis was performed between June 2022 and May 2023. Exposure: Screen exposure (total daily time and time with each type of content, including educational programs, entertainment programs, non-child-directed programs, electronic games, and social media) was collected when children were aged 3, 5, and 6 years. Main Outcomes and Measures: Mental health of children at age 3, 5, and 6 years was reported by parents using the Strengths and Difficulties Questionnaire. Results: Of the 15 965 children included in the representative sample, 8270 were males (51.7%) and the mean (SD) age at wave 1 was 3.73 (0.30) years. As children developed from ages 3 to 6 years, the proportion of screen exposure to educational programs (≤1 hour per day: 45.0% [95% CI, 43.5%-46.5%] to 26.8% [95% CI, 25.3%-28.3%]) and entertainment programs (≤1 hour per day: 44.4% [95% CI, 42.8%-45.9%] to 32.1% [95% CI, 30.4%-33.9%]) decreased, whereas exposure to social media increased (≤1 hour per day: 1.5% [95% CI, 1.2%-1.9%] to 27.1% [95% CI, 25.5%-28.7%]). The associations between on-screen content and mental health varied. For a given total screen time, a higher proportion of screen exposure to educational programs was associated with a lower risk for mental health problems (adjusted odds ratio [AOR], 0.73; 95% CI, 0.60-0.90), whereas non-child-directed programs were associated with a higher risk for such problems (AOR, 2.82; 95% CI, 1.91-4.18). Regardless of the content, total screen time was consistently associated with mental health problems. Conclusions and relevance: Results of this study indicated that both total screen time and different types of content were associated with mental health problems in children aged 3 to 6 years. Limiting children's screen time, prioritizing educational programs, and avoiding non-child-directed programs are recommended.

Seasonal variation and dissolved organic matter influence on the distribution, transformation, and environmental risk of pharmaceuticals and personal care products in coastal zone: A case study of Tianjin, China.

Pharmaceuticals and personal care products (PPCPs) are emerging contaminants that have raised urgent environmental issues. The dissolved organic matter (DOM) plays a pivotal role on PPCPs' migration and transformation. To obtain a comprehensive understanding of the occurrence and distribution of PPCPs, a seasonal sampling focused on the riverine system in coastal zone, Tianjin, Bohai Rim was conducted. The distribution and transformation of thirty-three PPCPs and their interaction with DOM were investigated, and their sources and ecological risks were further evaluated. The total concentration of PPCPs ranges from 0.01 to 197.20 µg/L, and such value is affected by regional temperature, DOM and land use types. PPCPs migration at soil-water interface is controlled by temperature, sunlight, water flow and DOM. PPCPs have a high affinity to the protein-like DOM, while the humus-like DOM plays a negative influence and facilitates PPCPs' degradation. It is also found that protein-like DOM can represent point source pollution, while humus-like substances indicate non-point source (NPS) emission. Specific PPCPs can be used as markers to trace the source of domestic discharge. Additionally, daily use PPCPs such as ketoprofen, caffeine and iopromide are estimated to be the main risk substances, and their ecological risk varies on space, season and river hydraulic condition.

Prolyl isomerase Pin1 promotes autophagy and cancer cell viability through activating FoxO3 signalling.

Pin1-directed prolyl isomerization is a central common oncogenic mechanism to drive tumorigenic processes. However, the role of Pin1 in cellular autophagy is still poorly understood. Here we report that pharmacological inhibition of Pin1 decreased the formation of autophagosome/autolysosomes upon nutrient starvation. Inhibition of Pin1 reduced, whereas forced expression of Pin1 increased, the level of LC3 and viability of U2OS and PANC-1 cells. Pin1 could augment the accumulation of LC3 upon chloroquine treatment, while chloroquine also disturbed its function on cell viability. RNA-Seq and qPCR identified altered autophagic pathway upon Pin1 silencing. Mechanistically, FoxO3 was identified critical for Pin1-mediated autophagy. Knockdown of FoxO3 could rescue the changes of LC3 level and cellular viability caused by Pin1 overexpression. In xenograft mouse model, Pin1 reduced the sensitivity of PANC-1 to chloroquine while FoxO3 silencing could inhibit Pin1's function. Moreover, Pin1 could bind FoxO3 via its pS284-P motif, reduce its phosphorylation at T32, facilitate its nuclear retention, and therefore increased its transcriptional activity. S284A mutation of FoxO3 interfered with its T32 phosphorylation, reduced its nuclear localization and disrupted its function to support cell viability upon nutrient starvation. Furthermore, the protein level of Pin1 positively correlated with FoxO3 nuclear localization and LC3 level in pancreatic adenocarcinoma and osteosarcoma samples. Together, this study highlights an important role for Pin1-FoxO3 axis in regulating autophagy and cancer cell viability. Intervening in the Pin1-FoxO3 interaction would serve as an effective therapeutic strategy and the pS284-P motif of FoxO3 provides a potential target for drug design.

Genome-Wide Identification and Comprehensive Analysis of the FtsH Gene Family in Soybean (Glycine max).

The filamentation temperature-sensitive H (FtsH) gene family is critical in regulating plant chloroplast development and photosynthesis. It plays a vital role in plant growth, development, and stress response. Although FtsH genes have been identified in a wide range of plants, there is no detailed study of the FtsH gene family in soybean (Glycine max). Here, we identified 34 GmFtsH genes, which could be categorized into eight groups, and GmFtsH genes in the same group had similar structures and conserved protein motifs. We also performed intraspecific and interspecific collinearity analysis and found that the GmFtsH family has large-scale gene duplication and is more closely related to Arabidopsis thaliana. Cis-acting elements analysis in the promoter region of the GmFtsH genes revealed that most genes contain developmental and stress response elements. Expression patterns based on transcriptome data and real-time reverse transcription quantitative PCR (qRT-PCR) showed that most of the GmFtsH genes were expressed at the highest levels in leaves. Then, GO enrichment analysis indicated that GmFtsH genes might function as a protein hydrolase. In addition, the GmFtsH13 protein was confirmed to be localized in chloroplasts by a transient expression experiment in tobacco. Taken together, the results of this study lay the foundation for the functional determination of GmFtsH genes and help researchers further understand the regulatory network in soybean leaf development.

Epidemiology and transmission of hepatitis A in Shaanxi (western China) after more than ten years of universal vaccination.

Background: Hepatitis A (HepA) vaccination and economic factors can change the epidemiology of HepA. In China, the implementation of free vaccination for children under 1.5 years of age in 2008 has resulted in a decline in the overall incidence of HepA. Nevertheless, further investigation is required to comprehensively understand the epidemiological patterns of HepA in economically disadvantaged regions of China. Method: In this study, we evaluated the incidence, seroprevalence, and transmission characteristics of HepA in Shaanxi with less economically developed. We obtained data on reported cases of HepA from 2005 to 2020. Blood samples from 1,559 individuals aged 0 to 60 years were tested for anti-hepatitis A (HAV) antibodies. A questionnaire survey and blood sample collection were conducted in two sentinel sites from 2019 to 2021. Result: Between 2008 to 2020, the number of reported cases of HepA decreased from 3.44/100,000 person-years to 0.65/100,000 person-years, indicating an 81.1% decrease, which was particularly pronounced among younger age groups (0-19 years). From 2015-2020, infections were more likely to occur in people in their 40s and those over the age of 60. Farmers were still the most common occupation of HepA in the last decade. The results of the serological investigation showed the highest anti-HAV seroprevalence was observed in adults aged 39-60 years (94.6%) and those aged 28-38 years (87.8%). The 10-15 years group had the lowest seroprevalence at 49.3%. During the study period, a total of 22 cases were reported by sentinel sites, but the common risk factors (like raw food exposure, travel history, and closed contact with patients) were not identified. Conclusion: Given the greater severity of illness in the adult population and the ambiguous transmission routine, enhanced surveillance for HepA and evaluations that identify feasible approaches to mitigate the risk of HAV transmission are urgent priorities.

Foods, Nutrients, and Risk of In-Hospital Frailty in Women: Findings from a Large Prospective Cohort Study.

Frailty is increasingly prevalent worldwide because of aging populations. Diet may play a role as a modifiable risk factor. This study aimed to investigate associations between dietary factors and risk of frailty in the UK Women's Cohort admitted to hospitals in England. Consumption of foods and nutrients was estimated using a validated 217-item food frequency questionnaire at baseline. Incident frailty was assessed via a hospital frailty risk score based on linkage with hospital episode statistics. Out of 25,186 participants admitted to hospitals, 6919 (27%) were identified with frailty and 10,562 (42%) with pre-frailty over a mean follow-up of 12.7 years. After adjustment for confounding, we observed a 12% increase in risk of frailty with each additional 10 g/MJ intake of total meat (HR = 1.12, 95%CI: 1.07, 1.17), with the highest risk observed for processed meats (HR = 1.45, 95%CI: 1.21, 1.73). Similar associations were observed with pre-frailty. Vegetable intake was associated with slightly lower risk of frailty (HR = 0.98, 95%CI: 0.97, 1.00). There was no evidence of association between most nutrient intakes and in-hospital frailty risk. Overall, our findings suggest that reducing consumption of meat, especially processed meat, in adults may be beneficial regarding the development of frailty.

CePP2C19 confers tolerance to drought by regulating the ABA sensitivity in Cyperus esculentus.

BACKGROUND: Tiger nut (Cyperus esculentus) is widely known as an additional source of food, oil and feed worldwide. The agricultural production of tiger nut has been greatly hindered by drought stress, reducing both yield and quality. Protein phosphatase 2 C (PP2Cs) plays an important role in plant responses to drought stress however, the molecular mechanism of PP2Cs in tiger nuts still unclear. RESULTS: In this study, we identified a putative group A PP2C-encoding gene (CePP2C19) from tiger nut using transcriptome analysis, which is highly induced by drought stress. The transient expression assay suggested that CePP2C19 was localized to nucleus. Furthermore, the interaction between CePP2C19 and CePYR1, a coreceptor for ABA signaling, was first detected using a yeast two-hybrid assay and then verified using a bimolecular fluorescence complementation (BiFC) analysis. In addition, the transgenic Arabidopsis lines overexpressing CePP2C19 exhibited extreme tolerance to ABA and mannitol stresses during seed germination and root growth. At the mature stage, overexpression of CePP2C19 resulted in a higher tolerance to drought stress in transgenic Arabidopsis, as confirmed by a visible phenotype and several physiological parameters. Noticeably, the silencing of CePP2C19 by virus-induced gene silencing (VIGS) showed obvious reduction in drought tolerance in tiger nut plants. CONCLUSIONS: The CePP2C19 emerges as a pivotal gene involved in the ABA signaling pathway, which likely reduce ABA sensitivity and thus enhances drought tolerance in Cyperus esculentus.

Prevalence and factors associated with pentavalent vaccination: a cross-sectional study in Southern China.

BACKGROUND: Immunization is one of the most far-reaching and cost-effective strategies for promoting good health and saving lives. A complex immunization schedule, however, may be burdensome to parents and lead to reduced vaccine compliance and completion. Thus, it is critical to develop combination vaccines to reduce the number of injections and simplify the immunization schedule. This study aimed to investigate the current status of the pentavalent diphtheria-tetanus-acellular pertussis inactivated poliomyelitis and Haemophilus influenzae type B conjugate (DTaP-IPV/Hib) vaccination in Southern China as well as explore the factors in the general population associated with uptake and the differences between urban and rural populations. METHODS: A cross-sectional study was conducted with recently enrolled kindergarten students in Hainan Province between December 2022 and January 2023. The study employed a stratified multistage cluster random sampling method. Information regarding the demographic characteristics and factors that influence decisions were collected from the caregivers of children via an online questionnaire. Multivariate logistic regression was used to determine the factors associated with the status of DTap-IPV/Hib vaccinations. RESULTS: Of the 4818 valid responses, 95.3% of children were aged 3-4 years, and 2856 (59.3%) held rural hukou. Coverage rates of the DTaP-IPV/Hib vaccine, from 1 to 4 doses, were 24.4%, 20.7%, 18.5%, and 16.0%, respectively. Caregivers who are concerned about vaccine efficacy [adjusted odds ratio (aOR) = 1.53, 95% confidence interval (CI): 1.30-1.79], the manufacturer (aOR = 2.05, 95% CI: 1.69-2.49), and a simple immunization schedule (aOR = 1.26, 95% CI: 1.04-1.54) are factors associated with a higher likelihood of vaccinating children against DTaP-IPV/Hib. In addition, caregivers in urban areas showed more concern about the vaccine price (P = 0.010) and immunization schedule (P = 0.022) in regard to vaccinating children. CONCLUSIONS: The DTaP-IPV/Hib vaccine coverage rate in Hainan Province remains low. Factors such as lower socioeconomic status, cultural beliefs, concerns about vaccine safety, and cost may hinder caregivers from vaccinating their children. Further measures, such as health education campaigns to raise knowledge and awareness, and encouragement of domestic vaccine innovation, which would reduce out-of-pocket costs, could be implemented to improve the coverage of DTap-IPV/Hib vaccination.

A Soybean Sucrose Non-Fermenting Protein Kinase 1 Gene, GmSNF1, Positively Regulates Plant Response to Salt and Salt-Alkali Stress in Transgenic Plants.

Soybean is one of the most widely grown oilseed crops worldwide. Several unfavorable factors, including salt and salt-alkali stress caused by soil salinization, affect soybean yield and quality. Therefore, exploring the molecular basis of salt tolerance in plants and developing genetic resources for genetic breeding is important. Sucrose non-fermentable protein kinase 1 (SnRK1) belongs to a class of Ser/Thr protein kinases that are evolutionarily highly conserved direct homologs of yeast SNF1 and animal AMPKs and are involved in various abiotic stresses in plants. The GmPKS4 gene was experimentally shown to be involved with salinity tolerance. First, using the yeast two-hybrid technique and bimolecular fluorescence complementation (BiFC) technique, the GmSNF1 protein was shown to interact with the GmPKS4 protein. Second, the GmSNF1 gene responded positively to salt and salt-alkali stress according to qRT-PCR analysis, and the GmSNF1 protein was localized in the nucleus and cytoplasm using subcellular localization assay. The GmSNF1 gene was then heterologously expressed in yeast, and the GmSNF1 gene was tentatively identified as having salt and salt-alkali tolerance function. Finally, the salt-alkali tolerance function of the GmSNF1 gene was demonstrated by transgenic Arabidopsis thaliana, soybean hairy root complex plants overexpressing GmSNF1 and GmSNF1 gene-silenced soybean using VIGS. These results indicated that GmSNF1 might be useful in genetic engineering to improve plant salt and salt-alkali tolerance.

Corrosion Behavior of Alumina-Forming Austenitic Steel in Supercritical Carbon Dioxide Conditions: Effects of Nb Content and Temperature.

The corrosion behavior of alumina-forming austenitic (AFA) stainless steels with different Nb additions in a supercritical carbon dioxide environment at 500 °C, 600 °C, and 20 MPa was investigated. The steels with low Nb content were found to have a novel structure with a double oxide as an outer Cr2O3 oxide film and an inner Al2O3 oxide layer with discontinuous Fe-rich spinels on the outer surface and a transition layer consisting of Cr spinels and γ'-Ni3Al phases randomly distributed under the oxide layer. Oxidation resistance was improved by accelerating diffusion through refined grain boundaries after the addition of 0.6 wt.% Nb. However, the corrosion resistance decreased significantly at higher Nb content due to the formation of continuous thick outer Fe-rich nodules on the surface and an internal oxide zone, and Fe2(Mo, Nb) laves phases were also detected, which prevented the outward diffusion of Al ions and promoted the formation of cracks within the oxide layer, resulting in unfavorable effects on oxidation. After exposure at 500 °C, fewer spinels and thinner oxide scales were found. The specific mechanism was discussed.

Prevalence, co-occurring difficulties, and risk factors of developmental language disorder: first evidence for Mandarin-speaking children in a population-based study.

Background: Developmental language disorder (DLD) is a condition that significantly affects children's achievement but has been understudied. We aim to estimate the prevalence of DLD in Shanghai, compare the co-occurrence of difficulties between children with DLD and those with typical development (TD), and investigate the early risk factors for DLD. Methods: We estimated DLD prevalence using data from a population-based survey with a cluster random sampling design in Shanghai, China. A subsample of children (aged 5-6 years) received an onsite evaluation, and each child was categorized as TD or DLD. The proportions of children with socio-emotional behavior (SEB) difficulties, low non-verbal IQ (NVIQ), and poor school readiness were calculated among children with TD and DLD. We used multiple imputation to address the missing values of risk factors. Univariate and multivariate regression models adjusted with sampling weights were used to estimate the correlation of each risk factor with DLD. Findings: Of 1082 children who were approached for the onsite evaluation, 974 (90.0%) completed the language ability assessments, of whom 74 met the criteria for DLD, resulting in a prevalence of 8.5% (95% CI 6.3-11.5) when adjusted with sampling weights. Compared with TD children, children with DLD had higher rates of concurrent difficulties, including SEB (total difficulties score at-risk: 156 [17.3%] of 900 TD vs. 28 [37.8%] of 74 DLD, p < 0.0001), low NVIQ (3 [0.3%] of 900 TD vs. 8 [10.8%] of 74 DLD, p < 0.0001), and poor school readiness (71 [7.9%] of 900 TD vs. 13 [17.6%] of 74 DLD, p = 0.0040). After accounting for all other risk factors, a higher risk of DLD was associated with a lack of parent-child interaction diversity (adjusted odds ratio [aOR] = 3.08, 95% CI = 1.29-7.37; p = 0.012) and lower kindergarten levels (compared to demonstration and first level: third level (aOR = 6.15, 95% CI = 1.92-19.63; p = 0.0020)). Interpretation: The prevalence of DLD and its co-occurrence with other difficulties suggest the need for further attention. Family and kindergarten factors were found to contribute to DLD, suggesting that multi-sector coordinated efforts are needed to better identify and serve DLD populations at home, in schools, and in clinical settings. Funding: The study was supported by Shanghai Municipal Education Commission (No. 2022you1-2, D1502), the Innovative Research Team of High-level Local Universities in Shanghai (No. SHSMU-ZDCX20211900), Shanghai Municipal Health Commission (No.GWV-10.1-XK07), and the National Key Research and Development Program of China (No. 2022YFC2705201).

Effects of the retrieval-extinction paradigm with abstract reminders on fear memory extinction.

Reactivated fear memories may enter an unstable state that could be interrupted by behavioral interventions such as the retrieval-extinction procedure. Studies of pharmacological interventions have shown that retrieval cues are not necessarily an exact reduplication of initial conditioned stimuli (CSs); they can instead be abstract word cues. However, the effectiveness of using abstract reminder cues in behavioral intervention procedures remains unknown, as do the conditions under which they are effective. The typicality of CS and the abstraction level of reminders are also likely to be important in the paradigm but have not been investigated to date. Here, in three experiments (n = 107), we manipulate the fear conditioning process, including single CS-unconditioned stimulus (US) and multiple CS-US connections, as well as the CS typicality and abstraction level of reminder cues, to explore the conditions for adopting retrieval-extinction with abstract reminders. The results of Experiments 1 and 2 show that the abstract cue is ineffective for use as a reminder in the procedure; this is the case for single exemplar category learning and perceptual discriminative learning, independent of the typicality of CS+ or the abstraction level of reminder cues. Only the outcome of Experiment 3, which contains multiple CS-US connections, shows no indication of fear return. The limitations of the study and possible interpretations of the results are discussed.

Genome-Wide Identification of MADS-Box Family Genes in Safflower (Carthamus tinctorius L.) and Functional Analysis of CtMADS24 during Flowering.

Safflower is an important economic crop with a plethora of industrial and medicinal applications around the world. The bioactive components of safflower petals are known to have pharmacological activity that promotes blood circulation and reduces blood stasis. However, fine-tuning the genetic mechanism of flower development in safflower is still required. In this study, we report the genome-wide identification of MADS-box transcription factors in safflower and the functional characterization of a putative CtMADS24 during vegetative and reproductive growth. In total, 77 members of MADS-box-encoding genes were identified from the safflower genome. The phylogenetic analysis divided CtMADS genes into two types and 15 subfamilies. Similarly, bioinformatic analysis, such as of conserved protein motifs, gene structures, and cis-regulatory elements, also revealed structural conservation of MADS-box genes in safflower. Furthermore, the differential expression pattern of CtMADS genes by RNA-seq data indicated that type II genes might play important regulatory roles in floral development. Similarly, the qRT-PCR analysis also revealed the transcript abundance of 12 CtMADS genes exhibiting tissue-specific expression in different flower organs. The nucleus-localized CtMADS24 of the AP1 subfamily was validated by transient transformation in tobacco using GFP translational fusion. Moreover, CtMADS24-overexpressed transgenic Arabidopsis exhibited early flowering and an abnormal phenotype, suggesting that CtMADS24 mediated the expression of genes involved in floral organ development. Taken together, these findings provide valuable information on the regulatory role of CtMADS24 during flower development in safflower and for the selection of important genes for future molecular breeding programs.

Comprehensive metabolomic profiling of nutrients in fish and shrimp.

Although fish and shrimp are commonly consumed in daily life and recognized as nutrient-rich species, global profiling of the endogenous nutrients in these species is lacking. Here, we optimized the sample preparation and data acquisition methods of metabolomics to comprehensively characterize the nutrients in selected fish and shrimp species and compared them with those in beef, leading to the identification of 71 differentially expressed metabolites. Of these, docosahexaenoic acid, taurine, choline and (lyso)phosphatidylcholines were found to be abundant in the examined fish species, while several nonessential amino acids were rich in the analyzed shrimp samples. Subsequently, the biological functions of the metabolites rich in shrimp were queried. Intriguingly, the examined nutrients exemplified by proline can significantly mitigate the lipopolysaccharide (LPS)-stimulated inflammatory responses in BV2 cells and RAW264.7 cells. Collectively, our findings imply that the dietary intake of certain fish and shrimp species may benefit human health through alleviating inflammatory responses.