Nomogram to Predict 90-Day All-Cause Mortality in Acute Ischemic Stroke Patients after Endovascular Thrombectomy.

OBJECTIVE: Although Endovascular Thrombectomy (EVT) significantly improves the prognosis of Acute Ischemic Stroke (AIS) patients with large vessel occlusion, the mortality rate remains higher. This study aimed to construct and validate a nomogram for predicting 90-day all-cause mortality in AIS patients with large vessel occlusion and who have undergone EVT. METHODS: AIS patients with large vessel occlusion in the anterior circulation who underwent EVT from May 2017 to December 2022 were included. 430 patients were randomly split into a training group (N=302) and a test group (N=128) for the construction and validation of our nomogram. In the training group, multivariate logistic regression analysis was performed to determine the predictors of 90-day all-cause mortality. The C-index, calibration plots, and decision curve analysis were applied to evaluate the nomogram performance. RESULTS: Multivariate logistic regression analysis revealed neurological deterioration during hospitalization, age, baseline National Institutes of Health Stroke Scale (NIHSS) score, occlusive vessel location, malignant brain edema, and Neutrophil-to-lymphocyte Ratio (NLR) as the independent predictors of 90-day all-cause mortality (all p ≤ 0.039). The C-index of the training and test groups was 0.891 (95%CI 0.848-0.934) and 0.916 (95% CI: 0.865-0.937), respectively, showing the nomogram to be well distinguished. The Hosmer-Lemeshow goodness-of-fit test revealed the p-values for both the internal and external verification datasets to be greater than 0.5. CONCLUSION: Our nomogram has incorporated relevant clinical and imaging features, including neurological deterioration, age, baseline NIHSS score, occlusive vessel location, malignant brain edema, and NLR ratio, to provide an accurate and reliable prediction of 90-day all-cause mortality in AIS patients undergoing EVT.

TGR5-mediated lateral hypothalamus-dCA3-dorsolateral septum circuit regulates depressive-like behavior in male mice.

Although bile acids play a notable role in depression, the pathological significance of the bile acid TGR5 membrane-type receptor in this disorder remains elusive. Using depression models of chronic social defeat stress and chronic restraint stress in male mice, we found that TGR5 in the lateral hypothalamic area (LHA) predominantly decreased in GABAergic neurons, the excitability of which increased in depressive-like mice. Upregulation of TGR5 or inhibition of GABAergic excitability in LHA markedly alleviated depressive-like behavior, whereas down-regulation of TGR5 or enhancement of GABAergic excitability facilitated stress-induced depressive-like behavior. TGR5 also bidirectionally regulated excitability of LHA GABAergic neurons via extracellular regulated protein kinases-dependent Kv4.2 channels. Notably, LHA GABAergic neurons specifically innervated dorsal CA3 (dCA3) CaMKIIα neurons for mediation of depressive-like behavior. LHA GABAergic TGR5 exerted antidepressant-like effects by disinhibiting dCA3 CaMKIIα neurons projecting to the dorsolateral septum (DLS). These findings advance our understanding of TGR5 and the LHAGABA→dCA3CaMKIIα→DLSGABA circuit for the development of potential therapeutic strategies in depression.

The Basic/Helix-Loop-Helix Transcription Factor Family Gene RcbHLH112 Is a Susceptibility Gene in Gray Mould Resistance of Rose (Rosa Chinensis).

The basic/helix-loop-helix (bHLH) family is a major family of transcription factors in plants. Although it has been reported that bHLH plays a defensive role against pathogen infection in plants, there is no comprehensive study on the bHLH-related defence response in rose (Rosa sp.). In this study, a genome-wide analysis of bHLH family genes (RcbHLHs) in rose was carried out, including their phylogenetic relationships, gene structure, chromosome localization and collinearity analysis. Via phylogenetic analysis, a total of 121 RcbHLH genes in the rose genome were divided into 21 sub-groups. These RcbHLHs are unevenly distributed in all 7 chromosomes of rose. The occurrence of gene duplication events indicates that whole-genome duplication and segmental duplication may play a key role in gene duplication. Ratios of non-synonymous to synonymous mutation frequency (Ka/Ks) analysis showed that the replicated RcbHLH genes mainly underwent purification selection, and their functional differentiation was limited. Gene expression analysis showed that 46 RcbHLHs were differentially expressed in rose petals upon B. cinerea infection. It is speculated that these RcbHLHs are candidate genes that regulate the response of rose plants to B. cinerea infection. Virus-induced gene silencing (VIGS) confirmed that RcbHLH112 in rose is a susceptibility factor for infection with B. cinerea. This study provides useful information for further study of the functions of the rose bHLH gene family.

Mitochondrial Membrane Potential Independent Near-Infrared Mitochondrial Viscosity Probes for Real-Time Tracking Mitophagy.

Mitophagy is a vital cellular process playing vital roles in regulating cellular metabolism and mitochondrial quality control. Mitochondrial viscosity is a key microenvironmental index, closely associated with mitochondrial status. To monitor mitophagy and mitochondrial viscosity, three molecular rotors (Mito-1, Mito-2, and Mito-3) were developed. All probes contain a cationic quinolinium unit and a C12 chain so that they can tightly bind mitochondria and are not affected by the mitochondrial membrane potential. Optical studies showed that all probes are sensitive to viscosity changes with an off-on fluorescence response, and Mito-3 shows the best fluorescence enhancement. Bioimaging studies showed that all these probes can not only tightly locate and visualize mitochondria with near-infrared fluorescence but also effectively monitor the mitochondrial viscosity changes in cells. Moreover, Mito-3 was successfully applied to visualize the mitophagy process induced by starvation, and mitochondrial viscosity was found to show an increase during mitophagy. We expect Mito-3 to become a useful imaging tool for studying mitochondrial viscosity and mitophagy.

Identification of long non-coding RNAs involved in floral scent of Rosa hybrida.

Long non-coding RNAs (lncRNAs) were found to play important roles in transcriptional, post-transcriptional, and epigenetic gene regulation in various biological processes. However, lncRNAs and their regulatory roles remain poorly studied in horticultural plants. Rose is economically important not only for their wide use as garden and cut flowers but also as important sources of natural fragrance for perfume and cosmetics industry, but presently little was known about the regulatory mechanism of the floral scent production. In this paper, a RNA-Seq analysis with strand-specific libraries, was performed to rose flowers in different flowering stages. The scented variety 'Tianmidemeng' (Rosa hybrida) was used as plant material. A total of 13,957 lncRNAs were identified by mining the RNA-Seq data, including 10,887 annotated lncRNAs and 3070 novel lncRNAs. Among them, 10,075 lncRNAs were predicted to possess a total of 29,622 target genes, including 54 synthase genes and 24 transcription factors related to floral scent synthesis. 425 lncRNAs were differentially expressed during the flowering process, among which 19 were differentially expressed among all the three flowering stages. Using weighted correlation network analysis (WGCNA), we correlate the differentially-expressed lncRNAs to synthesis of individual floral scent compounds. Furthermore, regulatory function of one of candidate lncRNAs for floral scent synthesis was verified using VIGS method in the rose. In this study, we were able to show that lncRNAs may play important roles in floral scent production in the rose. This study also improves our understanding of how plants regulate their secondary metabolism by lncRNAs.

Vaccination coverage determinants in low uptake areas of China: a qualitative study of provider perspectives in Sichuan, Guangdong, and Henan Provinces.

China's immunization programme is relatively strong, with latest WHO-UNICEF monitoring rates for 2019 showing national vaccination coverage over 90%. However, vaccination coverage is heterogeneous, varying across geographic regions, rural-urban communities, and sub-populations. We conducted a qualitative study from a critical realist perspective, analyzing semi-structured interviews with 26 vaccination providers in three provinces, selected to represent regional socioeconomic disparities across Eastern, Central, and Western China. We analyzed data thematically, using deductive and inductive coding. Providers reported vaccination coverage in their areas had increased significantly, but remained lower among migrant and left-behind children. Main coverage determinants were child-related (i.e. gender, number, health status), caregiver-related (i.e. socioeconomic status, role, education level, ethnicity), institution-related (i.e. vaccinator numbers, information system, appointment process), and system-related (i.e. vaccine supply, intersectoral cooperation, vaccine 'hesitancy'). Potentially effective measures to promote vaccination coverage included using routine maternal and child health-care visits for catch-up vaccination, providing additional health education, conducting follow-up family visits by village doctors, and requiring vaccination verification at school enrollment. This is the first qualitative study to examine potential determinants of low vaccination coverage in these areas of China. Findings can inform policies to strengthen the role of schools, develop the national immunization information system, and promote appointment apps. More consideration is needed to improve service quality and eliminating inequities, such as strengthening health education and service provision for migrant and left-behind children.

Global Investigation of TBL Gene Family in Rose (Rosa chinensis) Unveils RcTBL16 Is a Susceptibility Gene in Gray Mold Resistance.

The TRICHOME BIREFRINGENCE-LIKE (TBL) family is an important gene family engaged in the O-acetylation of cell wall polysaccharides. There have been a few reports showing that TBL participated in the resistance against phytopathogens in Arabidopsis and rice. However, no relevant studies in rose (Rosa sp.) have been published. In this study, a genome-wide analysis of the TBL gene family in rose was presented, including their phylogenetic relationships, gene structure, chromosomal positioning, and collinearity analysis. The phylogenetic analysis revealed a total of 50 RcTBL genes in the rose genome, and they are unevenly distributed across all seven chromosomes. The occurrence of gene duplication events suggests that both the whole genome duplication and partial duplication may play a role in gene duplication of RcTBLs. The analysis of Ka/Ks showed that the replicated RcTBL genes underwent mainly purifying selection with limited functional differentiation. Gene expression analysis indicated that 12 RcTBLs were down-regulated upon the infection of Botrytis cinerea, the causal agent of the gray mold disease of rose. These RcTBLs may be a sort of candidate genes for regulating the response of rose to B. cinerea. Through virus-induced gene silencing, RcTBL16 was shown to be associated with susceptibility to gray mold in rose. Through this study, meaningful information for further studies on the function of the TBL protein family in rose is provided.

The RNA Directed DNA Methylation (RdDM) Pathway Regulates Anthocyanin Biosynthesis in Crabapple (Malus cv. spp.) Leaves by Methylating the McCOP1 Promoter.

The synthesis of anthocyanin pigments in plants is known to be regulated by multiple mechanisms, including epigenetic regulation; however, the contribution of the RNA-directed DNA methylation (RdDM) pathway is not well understood. Here, we used bisulfite sequencing and Real Time (RT)-quantitative (q) PCR to analyze the methylation level of the promoter of constitutively photomorphogenic 1 (McCOP1) from Malus cv. spp, a gene involved in regulating anthocyanin biosynthesis. The CHH methylation level of the McCOP1 promoter was negatively correlated with McCOP1 RNA expression, and inhibiting DNA methylation caused decreased methylation of the McCOP1 promoter and asymmetric cytosine CHH methylation. We observed that the McCOP1 promoter was a direct target of the RdDM pathway argonaute RISC component 4 (McAGO4) protein, which bound to a McCOP1 promoter GGTTCGG site. Bimolecular fluorescence complementation (BIFC) analysis showed that RNA-directed DNA methylation (McRDM1) interacted with McAGO4 and another RdDM protein, domains rearranged methyltransferase 2 (McDRM2), to regulate the CHH methylation of the McCOP1 promoter. Detection of CHH methylation and COP1 gene expression in the Arabidopsis thalianaatago4, atdrm2 and atrdm1 mutants showed that RDM1 is the effector of the RdDM pathway. This was confirmed by silencing McRDM1 in crabapple leaves or apple fruit, which resulted in a decrease in McCOP1 CHH methylation and an increase in McCOP1 transcript levels, as well as in anthocyanin accumulation. In conclusion, these results show that the RdDM pathway is involved in regulating anthocyanin accumulation through CHH methylation of the McCOP1 promoter.

Characterization of wall-associated kinase/wall-associated kinase-like (WAK/WAKL) family in rose (Rosa chinensis) reveals the role of RcWAK4 in Botrytis resistance.

BACKGROUND: Wall-associated kinase (WAK)/WAK-like (WAKL) is one of the subfamily of receptor like kinases (RLK). Although previous studies reported that WAK/WAKL played an important role in plant cell elongation, response to biotic and abiotic stresses, there are no systematic studies on RcWAK/RcWAKL in rose. RESULTS: In this study, we identified a total of 68 RcWAK/RcWAKL gene family members within rose (Rosa chinensis) genome. The RcWAKs contained the extracellular galacturonan-binding domain and calcium-binding epidermal growth factor (EGF)-like domain, as well as an intracellular kinase domains. The RcWAKLs are missing either calcium-binding EGF-like domain or the galacturonan-binding domain in their extracellular region. The phylogenetic analysis showed the RcWAK/RcWAKL gene family has been divided into five groups, and these RcWAK/RcWAKL genes were unevenly distributed on the 7 chromosomes of rose. 12 of RcWAK/RcWAKL genes were significantly up-regulated by Botrytis cinerea-inoculated rose petals, where RcWAK4 was the most strongly expressed. Virus induced gene silencing of RcWAK4 increased the rose petal sensitivity to B. cinerea. The results indicated RcWAK4 is involved in the resistance of rose petal against B. cinerea. CONCLUSION: Our study provides useful information to further investigate the function of the RcWAK/RcWAKL gene family and breeding research for resistance to B. cinerea in rose.

Modifiable personal and environmental factors associated with anxiety in family caregivers of children with disabilities: A comparison between parents and grandparents.

BACKGROUND: Caregivers of children with disabilities might face high risk of anxiety, but the specific influencing factors may be different between parents and grandparents. This study is to explore the influencing modifiable factors from personal and environmental dimensions, so as to provide practical reference for effectively preventing and alleviating anxiety of this population. METHODS: A total of 504 primary caregivers were investigated in Shanghai, China, of which 496 parents and grandparents were included in the analysis. Risk of anxiety was measured by the Generalized Anxiety Disorder 7-item (GAD-7) Scale. Descriptive statistics, univariate analysis, and multivariable logistic regression were performed to describe the personal and environmental characteristics of parents and grandparents, risk of anxiety, and identify the significant factors. RESULTS: 35.1% of the total caregivers had the risk of anxiety, parents (35.8%) were slightly more anxious than grandparents (33.1%). Among parents, children's stable emotion (AOR=0.263, 95% CI=0.113, 0.611), higher household income (AOR=0.664; 95% CI=0.519, 0.850), owning a house (AOR=0.326; 95% CI=0.174, 0.610), and better barrier-free construction (AOR=0.400; 95% CI=0.170, 0.941) were associated with lower odds of anxiety. As for grandparents, significant association was merely found in caregiving time (AOR=2.936; 95% CI=1.064, 8.107). LIMITATIONS: Given the cross-sectional design, we would not infer causal relationships. CONCLUSIONS: Anxiety among family caregivers of children with disabilities was not encouraging and need to be urgently concerned. To reach optimal efficiency, intergenerational differences should be considered when health care providers and policy makers taking measures to facilitate the mental health of this population.

Associations of Elements of Parental Social Integration with Migrant Children's Vaccination: An Epidemiological Analysis of National Survey Data in China.

Our study explored the effects of parental social integration on migrant children's vaccination status in China. Using data obtained from the 2014 China Migrants Dynamic Survey, a total of 4915 participants were included in this study. Social integration was measured by economic, social, cultural, and internal identity. Univariate chi-square testing was used to calculate associations between all variables and migrant children's vaccination status. Binary logistic regression was employed to calculate the impacts of social integration on migrant children's vaccination status. In total, 94.7% of migrant children had complete vaccinations for their age. Migrants who had medical insurance, spoke the native language when communicating with locals, lived mainly with locals, and did not perceive discrimination were more likely to have their children completely vaccinated. Social integration was positively associated with migrant children's vaccination status. Our study indicated that to improve vaccination coverage of migrant children, more policy support for migrant employment and housing, promotion of health services for migrants, and language support in health institutions is needed.

Ferrite Nanoparticles-Based Reactive Oxygen Species-Mediated Cancer Therapy.

Ferrite nanoparticles have been widely used in the biomedical field (such as magnetic targeting, magnetic resonance imaging, magnetic hyperthermia, etc.) due to their appealing magnetic properties. In tumor acidic microenvironment, ferrite nanoparticles show intrinsic peroxidase-like activities, which can catalyze the Fenton reaction of hydrogen peroxide (H 2 O 2) to produce highly toxic hydroxyl free radicals (•OH), causing the death of tumor cell. Recent progresses in this field have shown that the enzymatic activity of ferrite can be improved via converting external field energy such as alternating magnetic field and near-infrared laser into nanoscale heat to produce more •OH, enhancing the killing effect on tumor cells. On the other hand, combined with other nanomaterials or drugs for cascade reactions, the production of reactive oxygen species (ROS) can also be increased to obtain more efficient cancer therapy. In this review, we will discuss the current status and progress of the application of ferrite nanoparticles in ROS-mediated cancer therapy and try to provide new ideas for this area.

The Effect of Parental Social Integration on the Physical Examination Utilization for Young Migrant Children: A National Cross-Sectional Study in China.

Purpose: Physical examination is a key component of child health management. Migrant children are a vulnerable group with lower healthcare service utilization, and this study aims to explore the effect of parental social integration on the physical examination service utilization for young migrant children under 6 years old in China. Method: This study conducted a secondary data analysis of the 2014 National Internal Migrant Dynamic Monitoring Survey in China. A total of 2,620 participants were included in this study. A total of 22 indicators were selected to measure social integration. Multivariate logistic regression was used to explore the association between parental social integration and physical examination use of young migrant children. Results: More than half (66.4%) of the migrant children aged 0-6 years had used free physical examination. Parental social integration, especially structural integration, was associated with the physical examination utilization of migrant children. Specifically, those migrant children's parents who had medical insurance (P < 0.05; OR = 1.29), who had participated in local activities (P < 0.001; OR = 1.98), who had registered local residents as neighbors (P < 0.05; OR = 1.34), and who had a deep sense of self-identity (P < 0.05; OR = 1.09) were more likely to take children to use physical examination. Conclusions: This study provided evidence that parental social integration was associated with migrant children's physical examination utilization, and this association was multifaceted, lying in the dimensions of economic, structural, and psychological integration. Improving the social integration of migrant parents would be effective to enhance the migrant children's healthcare service utilization.

Global analysis of the AP2/ERF gene family in rose (Rosa chinensis) genome unveils the role of RcERF099 in Botrytis resistance.

BACKGROUND: The AP2/ERFs belong to a large family of transcription factors in plants. The AP2/ERF gene family has been identified as a key player involved in both biotic and abiotic stress responses in plants, however, no comprehensive study has yet been carried out on the AP2/ERF gene family in rose (Rosa sp.), the most important ornamental crop worldwide. RESULTS: The present study comprises a genome-wide analysis of the AP2/ERF family genes (RcERFs) in the rose, involving their identification, gene structure, phylogenetic relationship, chromosome localization, collinearity analysis, as well as their expression patterns. Throughout the phylogenetic analysis, a total of 131 AP2/ERF genes in the rose genome were divided into 5 subgroups. The RcERFs are distributed over all the seven chromosomes of the rose, and genome duplication may have played a key role in their duplication. Furthermore, Ka/Ks analysis indicated that the duplicated RcERF genes often undergo purification selection with limited functional differentiation. Gene expression analysis revealed that 23 RcERFs were induced by infection of the necrotrophic fungal pathogen Botrytis cinerea. Presumably, these RcERFs are candidate genes which can react to the rose's resistance against Botrytis cinerea infection. By using virus-induced gene silencing, we confirmed that RcERF099 is an important regulator involved in the B.cinerea resistance in the rose petal. CONCLUSION: Overall, our results conclude the necessity for further study of the AP2/ERF gene family in rose, and promote their potential application in improving the rose when subjected to biological stress.

Carotenoid metabolite and transcriptome dynamics underlying flower color in marigold (Tagetes erecta L.).

Marigold (Tagetes erecta L.) is an important ornamental plant with a wide variety of flower colors. Despite its economic value, few biochemical and molecular studies have explored the generation of flower color in this species. To study the mechanism underlying marigold petal color, we performed a metabolite analysis and de novo cDNA sequencing on the inbred line 'V-01' and its petal color mutant 'V-01M' at four flower developmental stages. A total of 49,217 unigenes were identified from 24 cDNA libraries. Based on our metabolites and transcriptomic analyses, we present an overview of carotenoid biosynthesis, degradation, and accumulation in marigold flowers. The carotenoid content of the yellow mutant 'V-01M' was higher than that of the orange inbred line 'V-01', and the abundances of the yellow compounds lutein, neoxanthin, violaxanthin, zeaxanthin, and antheraxanthin were significantly higher in the mutant. During flower development, the carotenoid biosynthesis genes were upregulated in both 'V-01' and 'V-01M', with no significant differences between the two lines. By contrast, the carotenoid degradation genes were dramatically downregulated in the yellow mutant 'V-01M'. We therefore speculate that the carotenoid degradation genes are the key factors regulating the carotenoid content of marigold flowers. Our research provides a large amount of transcriptomic data and insights into the marigold color metabolome.

A Novel Multifunctional p-Type Semiconductor@MOFs Nanoporous Platform for Simultaneous Sensing and Photodegradation of Tetracycline.

p-Type semiconductors enable new opportunities for the development of photocatalysts. Metal-organic frameworks (MOFs) could now be manufactured for a wide range of applications. The zeolitic imidazolate framework-8 (ZIF-8), in particular, shows important desirable properties like good stability and a high surface area. Considering the p-type semiconducting intrinsic catalytic performance of CuBi2O4 (CBO) and the unique porous nanostructure and stability of ZIF-8, in this paper, we innovatively propose and investigate a new p-type semiconductor@MOFs (CBO@ZIF-8) material. Moreover, we focus on its application as a novel dual-function platform for simultaneous detection and degradation. The experimental results reveal that the platform is well suited for absorption, degradation, and fluorescent detection of certain targets. Using the contaminant, antibiotic tetracycline, as an example, the platform confirms excellent fluorescence sensing performance and good photodegradation properties under visible light. These results could aid the future design and implementation of novel and more sophisticated multifunction p-type semiconductor@MOFs platforms. The presented strategy represents the early stages of a future, genuine, general, multifunction platform.

Genome-wide characterization of the rose (Rosa chinensis) WRKY family and role of RcWRKY41 in gray mold resistance.

BACKGROUND: The WRKYs are a major family of plant transcription factors that play roles in the responses to biotic and abiotic stresses; however, a comprehensive study of the WRKY family in roses (Rosa sp.) has not previously been performed. RESULTS: In the present study, we performed a genome-wide analysis of the WRKY genes in the rose (Rosa chinensis), including their phylogenetic relationships, gene structure, chromosomal locations, and collinearity. Using a phylogenetic analysis, we divided the 56 RcWRKY genes into three subgroups. The RcWRKYs were unevenly distributed across all seven rose chromosomes, and a study of their collinearity suggested that genome duplication may have played a major role in RcWRKY gene duplication. A Ka/Ks analysis indicated that they mainly underwent purifying selection. Botrytis cinerea infection induced the expression of 19 RcWRKYs, most of which had undergone gene duplication during evolution. These RcWRKYs may regulate rose resistance against B. cinerea. Based on our phylogenetic and expression analyses, RcWRKY41 was identified as a candidate regulatory gene in the response to B. cinerea infection, which was confirmed using virus-induced gene silencing. CONCLUSIONS: This study provides useful information to facilitate the further study of the function of the rose WRKY gene family.

Dietary Supplement Use Among Chinese Primary School Students: A Cross-Sectional Study in Hunan Province.

Dietary supplement use is increasing globally, especially among children. However, few studies have been conducted to examine dietary supplement use among Chinese children. The aim of this study was to examine the prevalence of dietary supplement use and the associated factors in primary school students. A cross-sectional study was conducted in four primary schools in Hunan province, China. A total of 706 Chinese parents/caregivers of school children aged 6⁻12 years old were enrolled. Self-administrated questionnaires were used to collect information about the children's dietary supplement use, and their socio-demographic characteristics. The prevalence of dietary supplement use in primary school students was 20.4%. Calcium (16.7%), vitamin C (9.2%), and vitamin D (8.5%) were the most commonly used types of dietary supplement. The main reasons for parents/caregivers to purchase dietary supplements for their children were immunity improvement (43.6%), and for growth promotion (36.5%). Some caregivers (26.4%) purchased dietary supplements online, including from dubious or unknown sellers. However, 37.5% of caregivers did not receive formal guidance on supplementation even if they purchased their supplements through formal channels. Parents/caregivers were unclear about the appropriate choices for children's dietary supplement use. Guidelines and counseling regarding dietary supplements for children may be helpful in public health work.