Myclobutanil induces neurotoxicity by activating autophagy and apoptosis in zebrafish larvae (Danio rerio).

Myclobutanil (MYC), a typical broad-spectrum triazole fungicide, is often detected in surface water. This study aimed to explore the neurotoxicity of MYC and the underlying mechanisms in zebrafish and in PC12 cells. In this study, zebrafish embryos were exposed to 0, 0.5 and 1 mg/L of MYC from 4 to 96 h post fertilization (hpf) and neurobehavior was evaluated. Our data showed that MYC decreased the survival rate, hatching rate and heart rate, but increased the malformation rate and spontaneous movement. MYC caused abnormal neurobehaviors characterized by decreased swimming distance and movement time. MYC impaired cerebral histopathological morphology and inhibited neurogenesis in HuC:egfp transgenic zebrafish. MYC also reduced the activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and downregulated neurodevelopment related genes (gfap, syn2a, gap43 and mbp) in zebrafish and PC12 cells. Besides, MYC activated autophagy through enhanced expression of the LC3-II protein and suppressed expression of the p62 protein and autophagosome formation, subsequently triggering apoptosis by upregulating apoptotic genes (p53, bax, bcl-2 and caspase 3) and the cleaved caspase-3 protein in zebrafish and PC12 cells. These processes were restored by the autophagy inhibitor 3-methyladenine (3-MA) both in vivo and in vitro, indicating that MYC induces neurotoxicity by activating autophagy and apoptosis. Overall, this study revealed the potential autophagy and apoptosis mechanisms of MYC-induced neurotoxicity and provided novel strategies to counteract its toxicity.

Positive and negative factors of parents vaccinating their children against COVID-19: An umbrella review.

Purpose: This umbrella review summarized the factors influencing parents' hesitancy to vaccinate their children against COVID-19 and the evidence to reduce it. Methods: The analysis included PubMed, Embase, Cochrane Library, Web of Science, and Scopus articles published before March 22, 2024. It considered all meta-analyses that investigated parental COVID-19 vaccine hesitancy. Results: Eight studies were included. Hesitancy rate of parents from five continents to vaccinate their children against COVID-19 was between 0.69 % and 95.0 %. The comprehensive synthesis in this review shows that the influencing factors originate from four aspects: Parents' attitudes, including their trust in the scientific community, concerns about COVID-19 complications, perceptions of children's susceptibility, and support from the social environment, including government incentives, low vaccination costs, and specific sociodemographic characteristics, were positive factors that reduced parental vaccine hesitancy in children. Conversely, negative aspects, including vaccine distrust, the spread of misinformation, poor economic status, and concern about unprecedentedly short development time, were associated with increased hesitancy. Conclusion: Our study identified positive and negative factors for parental COVID-19 vaccine hesitancy in children and highlighted that parental attitude was the most important determinant.

Impact of prior SARS-CoV-2 infection on college students' hesitancy to receive additional COVID-19 vaccine booster doses: A study from Taizhou, China.

Purpose: This study aimed to examine the impact of a history of SARS-CoV-2 infection on the hesitancy of college students to receive additional COVID-19 vaccine booster doses. Methods: A population-based self-administered online survey was conducted in July 2024 in Taizhou, China. A total of 792 respondents were included in this study. Logistic regression was conducted to identify factors associated with college students' hesitation to receive booster doses of the COVID-19 vaccine. Results: Of 792 respondents, 32.2 % hesitated to receive additional doses of the COVID-19 vaccine booster. Furthermore, 23.5 % of the respondents reported an increase in hesitancy to receiving additional COVID-19 vaccine booster doses compared to before they were infected with SARS-CoV-2. In the regression analyses, college students who had a secondary infection were more hesitant to receive additional COVID-19 vaccine booster doses (OR = 0.481, 95 % CI: (0.299-0.774), P = 0.003). Moreover, students with secondary infections who were male (OR = 0.417, 95 % CI: 0.221-0.784, P = 0.007), with lower than a bachelor's degree (OR = 0.471, 95 % CI: 0.272-0.815, P = 0.007), in non-medical majors (OR = 0.460, 95 % CI: 0.248-0.856, P = 0.014), and sophomores or below (OR = 0.483, 95 % CI: 0.286-0.817, P = 0.007) were more hesitant to receive additional COVID-19 vaccine booster doses. Conclusion: A history of SARS-CoV-2 infection affects college students' hesitation to receive additional COVID-19 vaccine booster doses, which was higher in those who experienced secondary infections.

Vitamin A ameliorates valproic acid-induced autism-like symptoms in developing zebrafish larvae by attenuating oxidative stress and apoptosis.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive/stereotyped behaviors. Prenatal exposure to valproic acid (VPA) has been reported to induce ASD-like symptoms in human and rodents. However, the etiology and pathogenesis of ASD have not been well elucidated. This study aimed to explore the mechanisms underlying VPA-induced ASD-like behaviors using zebrafish model and investigated whether vitamin A could prevent VPA-induced neurotoxicity. Here, zebrafish embryos were exposed to 0, 25 and 50 µM VPA from 4 to 96 h post fertilization (hpf) and the neurotoxicity was assessed. Our results showed that VPA affected the normal development of zebrafish larvae and induced ASD-like behaviors, including reduced locomotor activity, decreased distance near conspecifics, impaired social interaction and repetitive swimming behaviors. Exposure to VPA decreased the GFP signal in transgenic HuC:egfp zebrafish according to the negative effect of VPA on the expression of neurodevelopmental genes. In addition, VPA enhanced oxidative stress by promoting the production of reactive oxygen species (ROS) and hydrogen peroxide (H2O2) and inhibiting the activity of superoxide dismutase, then triggered apoptosis by upregulation of apoptotic genes. These adverse outcomes were mitigated by vitamin A, suggesting that vitamin A rescued VPA-induced ASD-like symptoms by inhibiting oxidative stress and apoptosis. Overall, this study identified vitamin A as a promising strategy for future therapeutic regulator of VPA-induced ASD-like behaviors.

Research on the relationship between common metabolic syndrome and meteorological factors in Wuhu, a subtropical humid city of China.

As climate conditions deteriorate, human health faces a broader range of threats. This study aimed to determine the risk of death from metabolic syndrome (MetS) due to meteorological factors. We collected daily data from 2014 to 2020 in Wuhu City, including meteorological factors, environmental pollutants and death data of common MetS (hypertension, hyperlipidemia and diabetes), as well as a total number of 15,272 MetS deaths. To examine the relationship between meteorological factors, air pollutants, and MetS mortality, we used a generalized additive model (GAM) combined with a distributed delay nonlinear model (DLNM) for time series analysis. The relationship between the above factors and death outcomes was preliminarily evaluated using Spearman analysis and structural equation modeling (SEM). As per out discovery, diurnal temperature range (DTR) and daily mean temperature (T mean) increased the MetS mortality risk notably. The ultra low DTR raised the MetS mortality risk upon the general people, with the highest RR value of 1.033 (95% CI: 1.002, 1.065) at lag day 14. In addition, T mean was also significantly associated with MetS death. The highest risk of ultra low and ultra high T mean occured on the same day (lag 14), RR values were 1.043 (95% CI: 1.010, 1.077) and 1.032 (95% CI: 1.003, 1.061) respectively. Stratified analysis's result showed lower DTR had a more pronounced effect on women and the elderly, and ultra low and high T mean was a risk factor for MetS mortality in women and men. The elderly need to take extra note of temperature changes, and different levels of T mean will increase the risk of death. In warm seasons, ultra high RH and T mean can increase the mortality rate of MetS patients.

Impact of household decision makers' hesitancy to vaccinate children against COVID-19 on other household members: A family-based study in Taizhou, China.

Background: Vaccination is the most effective means of preventing outbreaks of infectious diseases, and family ;decision makers play an important role in decision-making regarding family matters and may influence other family members to take an active role in vaccinating children against COVID-19. Purpose: This study examined the influence of family decision makers on the hesitation of other family members to vaccinate their children against COVID-19. Methods: A population-based, self-administered online questionnaire was administered in Taizhou, China, from September 1, 2021, to September 15, 2021. The questionnaire included demographic information, knowledge, attitudes, and perceptions about the COVID-19 vaccine as well as hesitation regarding the use of the COVID-19 vaccination in children. In total, 490 respondents were included in this study. Logistic regression was used to assess the factors associated with vaccine hesitancy. Results: In total, 490 respondents from 190 households were interviewed. Of the 190 family decision makers, 43.7% (83/190) were hesitant to vaccinate their children against COVID-19. When family decision makers were hesitant to vaccinate children against COVID-19, 65.1% (82/126) of the other family members expressed similar hesitancy regarding vaccination. When family decision makers were not hesitant to vaccinate children, only 21.3% (37/174) of other family members were hesitant to do so. In the regression analysis, family decision makers' hesitation to vaccinate their children was associated with other family members' hesitation (OR=6.264, 95% CI:3.132-12.526). In addition, decision makers' perceptions of the safety of the vaccine (OR=0.422, 95% CI:0.215-0.826) and hesitation to vaccinate themselves (OR=8.967, 95% CI:4.745-16.948) influenced their hesitation to vaccinate their children. Conclusion: The present study found that family decision makers' hesitation to vaccinate children against COVID-19 influenced other family members' hesitation to vaccinate children. In addition, family decision makers' perceptions of the safety of the vaccine and their hesitation to vaccinate themselves influenced other family members' hesitation to vaccinate their children.

Curcumin protects against fenvalerate-induced neurotoxicity in zebrafish (Danio rerio) larvae through inhibition of oxidative stress.

Fenvalerate (FEN), a typical type II pyrethroid pesticide, is widely used in agriculture. FEN has been detected in the environment and human body. However, the neurotoxicity of FEN has not been well elucidated. This study aimed to explore the mechanisms underlying FEN-induced neurotoxicity using the zebrafish (Danio rerio) model. We also investigated whether curcumin (CUR), a polyphenol antioxidant that exhibits neuroprotective properties, can prevent FEN-induced neurotoxicity. Here, zebrafish embryos were exposed to 0, 3.5, 7 and 14 µg/L of FEN from 4 to 96 h post fertilization (hpf) and neurotoxicity was assessed. Our results showed that FEN decreased the survival rate, heart rate, body length and spontaneous movement, and increased malformation rate. FEN caused neurobehavioral alterations, including decreased swimming distance and velocity, movement time and clockwise rotation times. FEN also suppressed neurogenesis in transgenic HuC:egfp zebrafish, reduced cholinesterase activity and downregulated the expression of neurodevelopment related genes (elavl3, gfap, gap43 and mbp). In addition, FEN enhanced oxidative stress via excessive reactive oxygen species and antioxidant enzyme inhibition, then triggered apoptosis by upregulation of apoptotic genes (p53, bcl-2, bax and caspase 3). These adverse outcomes were alleviated by CUR, indicating that CUR mitigated FEN-induced neurotoxicity by inhibiting oxidative stress. Overall, this study revealed that CUR ameliorated FEN-induced neurotoxicity via its antioxidant, indicating a promising protection of CUR against environmental pollutant-induced developmental anomalies.

Application of non-invasive prenatal testing to 91,280 spontaneous pregnancies and 3477 pregnancies conceived by in vitro fertilization.

BACKGROUND: Many clinical studies based on spontaneous pregnancies (SPs) have demonstrated the superiority of non-invasive prenatal testing (NIPT), and the question of whether this technology is suitable for offspring conceived by assisted reproductive technology has attracted attention. This study aimed to evaluate the application value of NIPT in screening for trisomy (T)21, T18, T13 and sex chromosome aneuploidy (SCA) in pregnant women who conceived by in vitro fertilization (IVF). RESULTS: In total, there were 804 high-risk cases [0.88% (804/91280), singleton = 795, twin = 9] in the SP group. Among the 558 invasive prenatal diagnosis (IPD) cases (singleton = 556, twin = 2), 343 (singleton = 342, twin = 1) were true positive, including 213 cases of T21, 28 of T18, 5 of T13 and 97 (singleton = 96, twin = 1) of SCA. The positive predictive values (PPVs) of T21, T18, T13, SCA and T21/T18/T13 combined in singleton pregnancy were 89.12% (213/239), 51.85% (28/54), 21.74% (5/23), 40.00% (96/240), and 77.85% (246/316), respectively, and the PPV of SCA in twin pregnancy was 100.00%. In the IVF group, IPD was performed in 19 (singleton = 16, twin = 3) of the 27 high-risk cases [0.78% (27/3477), singleton = 16, twin = 3], of which 9 (singleton = 8, twin = 1) were true positive, including 5 cases (singleton = 4, twin = 1) of T21 and 4 of SCA. The PPVs of singleton T21, SCA and T21/T18/T13 combined were 66.67% (4/6), 50.00% (4/8) and 57.14% (4/7), respectively, and the PPV of twin T21 was 100.00% (1/1). There were no significant differences in PPV among T21, SCA and T21/T18/T13 combined in singletons between the groups (89.12% vs. 66.67%, p = 0.09; 40.00% vs. 50.00%, p = 0.57; 77.85% vs. 57.14%, p = 0.20). The sensitivity and specificity were higher for singleton and twin pregnancies in the two groups. Based on follow-up results, 1 case of false negative T21 was found in the singleton SP group. Additionally, the mean foetal fraction (FF) of the IVF group was lower than that of the SP group (11.23% vs. 10.51%, p < 0.05). CONCLUSION: NIPT has high sensitivity and specificity in screening chromosomal aneuploidies in both IVF pregnancy and spontaneous pregnancy, so it is an ideal screening method for IVF pregnancy.

Clinical application value of expanded carrier screening in the population of childbearing age.

OBJECTIVE: The objective of this study was to explore the clinical utility of the implementation of expanded carrier screening (ECS) in Chinese population of childbearing age. MATERIALS AND METHODS: Based on capillary electrophoresis, a first-generation sequencing technology, a prospective screening study of carriers of 15 single-gene diseases was carried out in 327 subjects in Anhui Province, including 84 couples and 159 women of childbearing age, the disease carrier rate, types of screened pathogenic genes, and incidence of both partners carrying the same pathogenic genes were summarized and analyzed. RESULTS: In 320 people with normal phenotypes who underwent ECS for 15 genetic diseases and 7 spouses who underwent targeted gene sequencing, 65 carriers of at least one disease were detected, with a total carrier rate of 20.31% (65/320). Among the 65 carriers, 81.54% (53/65) carried one genetic variant, 16.92% (11/65) carried two genetic variants, and 1.54% (1/65) carried three genetic variants. In this study, the three diseases with the highest carrier rates were hereditary deafness (8.13%, 26/320), Wilson's disease (4.06%, 13/320), and phenylketonuria (3.13%, 10/320). One high-risk couple (1.19%, 1/84) was detected. CONCLUSIONS: It has certain clinical application value to implement ECS in the population of childbearing age in China.

Parental hesitancy against COVID-19 vaccination for children and associated factors in Taiwan.

BACKGROUND: Since July 2021, some countries and regions have initiated the vaccination of minors against coronavirus disease (COVID-19), and parental COVID-19 vaccine hesitancy will affect the vaccination of minors. We aimed to identify the level of parental hesitancy to vaccinate their children against COVID-19 in Taiwan and the factors associated with vaccine hesitancy. METHODS: We conducted a population-based, self-administered online questionnaire in Taiwan to assess parental hesitancy and the factors influencing their children's vaccination against COVID-19. RESULTS: Among 384 respondents, 64.1% were hesitant to have their children vaccinated against COVID-19. Mothers were more likely to hesitate to vaccinate their teens than their fathers (67.5% vs. 50%, P < 0.005). Multiple regression results showed that parents who were hesitant to vaccinate themselves (OR = 3.81, 95% CI:2.07-7.02) and those who scored lower on their perception of their children's vaccination (OR = 9.73, 95% CI:5.62-16.84) were more hesitant to vaccinate their children with COVID-19 vaccine. CONCLUSIONS: According to the study findings, 64.1% of Taiwanese parents were hesitant to vaccinate their children against COVID-19. Parents who were hesitant to receive the COVID-19 vaccine for themselves and had negative views of the vaccine for their children were more likely to be hesitant to vaccinate their children. An in-depth discussion of the factors affecting vaccine hesitancy and targeted health education is conducive to promoting vaccination in children with COVID-19.

Value of noninvasive prenatal testing in the detection of rare fetal autosomal abnormalities.

OBJECTIVES: To evaluate the value of noninvasive prenatal testing (NIPT) in the screening of rare autosomal abnormalities and provide further support for the clinical application of NIPT. STUDY DESIGN: A total of 81,518 pregnant women who underwent NIPT at the Anhui Maternal and Child Health Hospital between May 2018 and March 2022 were selected. The high-risk samples were analyzed using amniotic fluid karyotype and chromosome microarray analysis (CMA), and the pregnancy outcomes were followed up. RESULTS: NIPT detected 292 cases (0.36%) with rare autosomal abnormalities among the 81,518 cases sampled. Of these, 140 (0.17%) showed rare autosomal trisomies (RATs), and 102 of these patients agreed to undergo invasive testing. Five cases were true positives, with a positive predictive value (PPV) of 4.90%. Copy number variants (CNV) were detected in 152 samples of the total cases (0.19%), and 95 of the patients involved agreed to the use of CMA. Twenty-nine of these cases were confirmed to be true positive, with a PPV of 30.53%. Detailed follow-up information was obtained in 81 cases from 97 patients with false-positive results for RATs. Thirty-seven of these cases (45.68%) had adverse perinatal outcomes, with a higher incidence of small for gestational age (SGA), intrauterine growth retardation (IUGR), and preterm birth (PTB). CONCLUSIONS: NIPT is not recommended for screening for RATs. However, considering that positive results are associated with an increased risk of IUGR and PTB, additional fetal ultrasound examination should be performed to monitor fetal growth. In addition, NIPT has a reference value in screening for CNVs, especially pathogenic CNVs, but a comprehensive analysis of prenatal diagnosis combined with ultrasound and family history is still needed.

The influence of meteorological factors and total malignant tumor health risk in Wuhu city in the context of climate change.

With the increasing severity of the malignant tumors situation worldwide, the impacts of climate on them are receiving increasing attention. In this study, for the first time, all-malignant tumors were used as the dependent variable and absolute humidity (AH) was innovatively introduced into the independent variable to investigate the relationship between all-malignant tumors and meteorological factors. A total of 42,188 cases of malignant tumor deaths and meteorological factors in Wuhu City were collected over a 7-year (2014-2020) period. The analysis method combines distributed lagged nonlinear modeling (DLNM) as well as generalized additive modeling (GAM), with prior pre-analysis using structural equation modeling (SEM). The results showed that AH, temperature mean (T mean) and diurnal temperature range (DTR) all increased the malignant tumors mortality risk. Exposure to low and exceedingly low AH increases the malignant tumors mortality risk with maximum RR values of 1.008 (95% CI: 1.001, 1.015, lag 3) and 1.016 (95% CI: 1.001, 1.032, lag 1), respectively. In addition, low and exceedingly low T mean exposures also increased the risk of malignant tumors mortality, the maximum RR was 1.020 (95% CI: 1.006, 1.034) for low T mean and 1.035 (95% CI: 1.014, 1.058) for exceedingly low T mean. As for DTR, all four levels (exceedingly low, low, high, exceedingly high, from low to high) of exposure increased the risk of death from malignant tumors, from exceedingly low to exceedingly high maximum RR values of 1.018 (95% CI: 1.004, 1.032), 1.011 (95% CI: 1.005, 1.017), 1.006 (95% CI: 1.001, 1.012) and 1.019 (95% CI: 1.007, 1.031), respectively. The results of the stratified analysis suggested that female appear to be more sensitive to humidity, while male require additional attention to reduce exposure to high level of DTR.

NRXN1 depletion in the medial prefrontal cortex induces anxiety-like behaviors and abnormal social phenotypes along with impaired neurite outgrowth in rat.

BACKGROUND: Neurodevelopmental disorders (NDDs) are a group of disorders induced by abnormal brain developmental processes. The prefrontal cortex (PFC) plays an essential role in executive function, and its role in NDDs has been reported. NDDs are associated with high-risk gene mutations and share partially overlapping genetic abnormalities. METHODS: Neurexins (NRXNs) are related to autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). NRXN1, an essential susceptibility gene for NDDs, has been reported to be associated with NDDs. However, little is known about its key role in NDDs. RESULTS: NRXN1 downregulation in the medial PFC induced anxiety-like behaviors and abnormal social phenotypes with impaired neurite outgrowth in Sh-NRXN1 in prefrontal neurons. Moreover, tandem mass tag (TMT)-based proteomic analysis of rat brain samples showed that NRXN1 downregulation led to significant proteome alterations, including pathways related to the extracellular matrix, cell membrane, and morphologic change. Furthermore, full-automatic immunoblotting analysis verified the differently expressed proteins related to cell morphology and membrane structure. CONCLUSIONS: Our results confirmed the association of NRXN1 with abnormal behaviors in NDDs and provided richer insights into specific prefrontal knockdown in adolescence, potentially expanding the NRXN1 interactome and contributing to human health.

Relationship between COVID-19 vaccine hesitancy and willingness to pay for the booster dose of COVID-19 vaccine of oncology patients in Taizhou, China.

OBJECTIVE: This population-based study aimed to determine the hesitancy and willingness to pay (WTP) for the booster dose of a coronavirus disease (COVID-19) vaccine among patients with cancer in Taizhou, China. PATIENTS AND METHODS: A self-administered online questionnaire was administered to patients with cancer in Taizhou, China. The chi-square test, binary logistic regression model were used to evaluate the WTP for the booster dose of a COVID-19 vaccine. The minimum sample size was 218, determined by G*Power software (latest ver. 3.1.9.7). A total of 354 patients received the survey, and 256 (72.3%) patients responded. RESULTS: Overall, 69.9% (179/256) of respondents were willing to pay for the booster dose, and 78.8% (141/179) of these patients were willing to pay 1-99 CNY. Furthermore, 50.4% (129/256) of respondents were hesitant to receive a COVID-19 vaccine. Being unhesitant was significantly associated with WTP for the booster dose (aOR: 3.040; 95% CI: 1.669-5.540). CONCLUSION: Hesitant patients with cancer had a lower WTP for the booster dose against COVID-19 than non-hesitant participants. These results imply that further health education programmes are essential to decrease the hesitancy of patients with cancer and enhance booster dose vaccination rates for public health improvements.KEY MESSAGESOur research showed that 70% of patients with cancer are willing to pay for the booster dose of the COVID-19 vaccine, and most are willing to pay less than 100 CNY, and this result reflects the economic value and affordability of the third dose of vaccination.COVID-19 vaccine-hesitant patients with cancer had a lower willingness to pay for a booster dose against COVID-19 than non-hesitant participants and few patients are still unwilling to pay among patients do not hesitate to receive the third dose.Therefore, promoting willingness to pay among oncology patients and addressing vaccine hesitancy remains key.

Proteomics Investigation of Diverse Serological Patterns in COVID-19.

Serum antibodies IgM and IgG are elevated during Coronavirus Disease 2019 (COVID-19) to defend against viral attacks. Atypical results such as negative and abnormally high antibody expression were frequently observed whereas the underlying molecular mechanisms are elusive. In our cohort of 144 COVID-19 patients, 3.5% were both IgM and IgG negative, whereas 29.2% remained only IgM negative. The remaining patients exhibited positive IgM and IgG expression, with 9.3% of them exhibiting over 20-fold higher titers of IgM than the others at their plateau. IgG titers in all of them were significantly boosted after vaccination in the second year. To investigate the underlying molecular mechanisms, we classed the patients into four groups with diverse serological patterns and analyzed their 2-year clinical indicators. Additionally, we collected 111 serum samples for TMTpro-based longitudinal proteomic profiling and characterized 1494 proteins in total. We found that the continuously negative IgM and IgG expression during COVID-19 were associated with mild inflammatory reactions and high T cell responses. Low levels of serum IgD, inferior complement 1 activation of complement cascades, and insufficient cellular immune responses might collectively lead to compensatory serological responses, causing overexpression of IgM. Serum CD163 was positively correlated with antibody titers during seroconversion. This study suggests that patients with negative serology still developed cellular immunity for viral defense and that high titers of IgM might not be favorable to COVID-19 recovery.

Willingness of college students to receive COVID-19 heterologous vaccination in Taizhou, China.

This study aimed to determine the willingness of college students to choose COVID-19 heterologous vaccination and its associated influencing factors in Taizhou, China. A population-based, self-administered online questionnaire was conducted from March 15 to 17, 2022. Of the 2,463 participants who had received the invitation, 1,821 responded to the survey (response rate = 73.9%). Only 14% (86/614) of those willing to receive a booster would chose a heterologous vaccination; the perception of better effectiveness of a COVID-19 heterologous vaccination booster was the significant factor (X2 = 22.671, p < .001). Additionally, female college students'older age (χ2 = 7.523, P = .023), major of medical (χ2 = 6.294, P = .012), and better perceived effectiveness of COVID-19 heterologous vaccination booster (χ2 = 22.659, P < .001), were more willing to receive heterologous booster doses. Chinese college students have a strong willingness to receive booster shots, but the percentage of those willing to receive a heterologous vaccine is only 14.0%, and the lack of understanding of its effectiveness is an important factor in the low proportion of heterologous vaccine selection. Health education, public health awareness, and the disclosure of heterologous vaccine information can help improve the public's understanding of heterologous vaccines and provide them with more choices.

Parents' willingness to pay for their children's COVID-19 vaccine in Taiwan, China: A cross-sectional study.

Most COVID-19 studies aim to assess factors influencing willingness to pay for vaccines between the public and medical staff. However, few studies focus on parents' willingness to pay for their children's COVID-19 vaccine. The current study aimed to assess parents' willingness to pay for their children's vaccination against COVID-19 and its influencing factors. This population-based cross-sectional study used a self-administered questionnaire. The inclusion criterion was parents with at least one child younger than 18 years. The final analysis included 384 valid data points. A total of 89.1% of the parents indicated that they are willing to pay for their children's vaccination against COVID-19. Among them, both fathers' and mothers' willingness to pay for their children's COVID-19 vaccine was 89.6%. The mean and median willingness to pay were% would pay for their children. Excluding other confounding factors, willingness to pay for the COVID-19 vaccine for themselves and hesitation to vaccinate their children were significantly associated with parents' willingness to pay for their children's COVID-19 vaccine. We found that 89.1% of the parents in Taiwan would pay for their children's COVID-19 vaccine. Parents' willingness to pay for themselves and hesitation to vaccinate their children were associated with willingness to pay. Reducing hesitation about vaccines and developing policies for vaccine payment may have a positive impact on willingness to pay for vaccines and promoting COVID-19 vaccination.

Nano-TiO2 aggravates bioaccumulation and developmental neurotoxicity of difenoconazole in zebrafish larvae via oxidative stress and apoptosis: Protective role of vitamin C.

Titanium dioxide nanoparticles (n-TiO2) could enhance the bioavailability and toxicity of coexisting organic contaminants in the aquatic environment. This study attempted to investigate the combined effects of n-TiO2 and difenoconazole (DIF) on the neurodevelopment of zebrafish and the underlying mechanisms. In this study, zebrafish embryos were exposed to n-TiO2 (100 µg/L), DIF (0, 0.1 and 0.5 mg/L) and their mixtures from 4 to 96 h post fertilization (hpf) and neurotoxicity was evaluated. Our results indicated that n-TiO2 adsorbed DIF into the brain of zebrafish and significantly enhanced the bioaccumulation of DIF and n-TiO2 in the 0.5 mg/L co-exposure group. 100 µg/L n-TiO2 was not developmentally toxic to the zebrafish larvae, but it exacerbated DIF-induced neurobehavioral alterations in the zebrafish larvae. n-TiO2 also aggravated DIF-induced suppression of central nervous system (CNS) neurogenesis in Tg (HuC:egfp) zebrafish, motor neuron axon length in Tg (hb9:egfp) zebrafish, and downregulation of neurodevelopmental genes (elavl3, ngn1, gap43, gfap and mbp). In addition, DIF elevated oxidative stress by accumulation of reactive oxygen species (ROS) and inhibition of antioxidant enzymes, and triggered apoptosis by upregulation of p53, bax, bcl-2 and caspase-3, which were markedly intensified in the presence of n-TiO2. Moreover, vitamin C (VC) ameliorated n-TiO2/DIF-induced abnormal locomotor behaviors and neurotoxicity by inhibiting oxidative stress and apoptosis, indicating that oxidative stress and apoptosis are involved in n-TiO2/DIF-induced neurotoxicity. Taken together, our data indicated that n-TiO2 enhanced the accumulation of DIF and heightened oxidative stress and apoptosis, thereby inducing neurotoxicity. This study exemplifies the importance of the toxicity assessment of chemical mixtures and novel insights to mitigate their combined toxicity.

The role of meteorological factors in suicide mortality in Wuhu, a humid city along the Yangtze River in Eastern China.

As the climate continues to change, suicide is becoming more frequent. In this study, absolute humidity (AH) was included for the first time and Wuhu, a typical subtropical city along the Yangtze River, was taken as the research object to explore the impact of suicide death risk on meteorological factors. The daily meteorological factors and suicide mortality data of Wuhu city from 2014 to 2020 were collected. Guided by structural equation model (SEM), a time series analysis method combining distributed lag nonlinear model (DLNM) and generalized additive model (GAM) was adopted. To investigate the correlation among different populations, we stratified age and gender at different meteorological levels. A total of 1259 suicide deaths were collected in Wuhu. The results indicated that exceedingly low and low levels of AH short-term exposure increased suicide mortality, with the maximum effect occurring at lag 14 for both levels of exposure, when the relative risk (RR) was 1.131 (95% CI: 1.030, 1.242) and 1.065 (95% CI: 1.006, 1.127), respectively. Exposure to exceedingly high and exceedingly low levels of temperature mean (T mean) also increased suicide mortality, with maximum RR values of 1.132 (lag 14, 95% CI: 1.015, 1.263) and 1.203 (lag 0, 95% CI: 1.079, 1.340), sequentially. As for diurnal temperature range (DTR), low-level exposure decreased the risk of suicide, while high-level exposure increased this risk, with RR values of 0.955 (lag 0, 95% CI: 0.920, 0.991, minimum) and 1.060 (lag 0, 95% CI: 1.018, 1.104, maximum), sequentially. Stratified analysis showed that AH and DTR increased the suicide death risk in male and elderly people, while the risk effect of T mean have no effect on young people only. In summary, male and elderly people appear to be more vulnerable to adverse weather effects.

IgG response to spike protein of SARS-CoV-2 in healthy individuals and potential of intravenous IgG as treatment for COVID-19.

BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which is currently a worldwide pandemic. There are limited available treatments for severe COVID-19 patients. However, some evidence suggests that intravenous immunoglobulin (IVIg) provides clinical benefits for these patients. METHODS: We administered IVIg to 23 severe COVID-19 patients, and all of them survived. Four related coronaviruses can cause the common cold. We speculated that cross-reactivity of SARS-CoV-2 and other common coronaviruses might partially explain the clinical efficacy of IVIg therapy. Thus, we performed multiple alignment analysis of the spike (S), membrane (M), and nucleotide (N) proteins from SARS-CoV-2 and the common coronaviruses to identify conserved regions. Next, we synthesized 25 peptides that were conserved regions and tested their IVIg seropositivity. RESULTS: The results indicated four peptides had significant or nearly significant seropositivity, and all of them were associated with the S and M proteins. Examination of the immune responses of healthy volunteers to each synthetic peptide indicated high seropositivity to the two peptides from S protein. Blood samples from healthy individuals may have pre-existing anti-SARS-CoV-2 IgGs, and IVIg is a potentially effective therapy for severe COVID-19. CONCLUSION: In conclusion, blood samples from many healthy individuals have pre-existing anti-SARS-CoV-2 IgGs, and IVIg may be an effective therapy for severe COVID-19.