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Inflammatory bowel disease (IBD) is a chronic and progressive condition with a significant global burden. Currently, available treatments primarily provide symptomatic relief and retard disease progression, yet they do not offer a cure and are frequently associated with adverse effects. Therefore, the discovery of new targets and therapeutic drugs for IBD is crucial. Phosphodiesterase 4 (PDE4) inhibitors have emerged as promising candidates in the search for effective IBD treatments, although dose-dependent side effects hamper their clinical utility. In this study, building upon heterocyclic biaryl derivatives (TPA16), we designed and synthesized a series of N2-substituted indazole-based PDE4D inhibitors, emphasizing improving safety profiles. An enzyme activity screening discovered an optimized compound, LZ-14 (Z21115), which exhibited high PDE4D7 (IC50 = 10.5 nM) inhibitory activity and good selectivity. More interestingly, LZ-14 has demonstrated promising effects in treating IBD in mouse models by improving the inflammatory response and colon injury. Furthermore, LZ-14 displayed low emetogenic potential in ketamine/xylazine anesthesia mice alternative models.
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The CRISPR/Cas9 technology revolutionizes targeted gene knockout in diverse organisms including plants. However, screening edited alleles, particularly those with multiplex editing, from herbicide- or antibiotic-resistant transgenic plants and segregating out the Cas9 transgene represent two laborious processes. Current solutions to facilitate these processes rely on different selection markers. Here, by taking advantage of the opposite functions of a d-amino acid oxidase (DAO) in detoxifying d-serine and in metabolizing non-toxic d-valine to a cytotoxic product, we develop a DAO-based selection system that simultaneously enables the enrichment of multigene edited alleles and elimination of Cas9-containing progeny in Arabidopsis thaliana. Among five DAOs tested in Escherichia coli, the one encoded by Trigonopsis variabilis (TvDAO) could confer slightly stronger d-serine resistance than other homologs. Transgenic expression of TvDAO in Arabidopsis allowed a clear distinction between transgenic and non-transgenic plants in both d-serine-conditioned positive selection and d-valine-conditioned negative selection. As a proof of concept, we combined CRISPR-induced single-strand annealing repair of a dead TvDAO with d-serine-based positive selection to help identify transgenic plants with multiplex editing, where d-serine-resistant plants exhibited considerably higher co-editing frequencies at three endogenous target genes than those selected by hygromycin. Subsequently, d-valine-based negative selection successfully removed Cas9 and TvDAO transgenes from the survival offspring carrying inherited mutations. Collectively, this work provides a novel strategy to ease CRISPR mutant identification and Cas9 transgene elimination using a single selection marker, which promises more efficient and simplified multiplex CRISPR editing in plants. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-023-00132-6.
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Aflatoxin B1 (AFB1), a pernicious constituent of the aflatoxin family, predominantly contaminates cereals, oils, and their derivatives. Acknowledged as a Class I carcinogen by the World Health Organization (WHO), the expeditious and quantitative discernment of AFB1 remains imperative. This investigation delineates that aluminum ions can precipitate the coalescence of iodine-modified silver nanoparticles, thereby engendering hot spots conducive for label-free AFB1 identification via Surface-Enhanced Raman Spectroscopy (SERS). This methodology manifests a remarkable limit of detection (LOD) at 0.47 fg/mL, surpassing the sensitivity thresholds of conventional survey techniques. Moreover, this method has good anti-interference ability, with a relative error of less than 10% and a relative standard deviation of less than 6% in quantitative results. Collectively, these findings illuminate the substantial application potential and viability of this approach in the quantitative analysis of AFB1, underpinning a significant advancement in food safety diagnostics.
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PURPOSE: Associations were assessed between demographic/lifestyle factors and tear film breakup time (TBUT) defined dry eye disease (DED) in China. METHODS: The cross-sectional study involved 50,280 subjects (54 ± 17 y) in 217 clinics (25 provinces). Data included sleep disorders; digital screen exposure; and use of cosmetics, contact lenses, and eye drops (for asthenopia). Clinical examinations included TBUT; Schirmer I test; meibomian gland plug status. TBUT-defined DED was TBUT <10 s, with TBUT ≤5 s also considered (i.e., short TBUT-type DED), either unilateral or bilateral. RESULTS: TBUT-defined DED was present in 81.6 % overall. The highest rates were in those 71 years or older, living in the north, with chronic daily sleep disorder, or daily cosmetic application; or daily digital screen exposure for 5 years, contact lenses 4 h, or 3 months eye drops. Compared with those without TBUT-defined DED, those with TBUT-defined DED showed lower Schirmer I results and more severe meibomian gland plug status (each, P < 0.001). Independent risk factors of DED were: aging; living in the southwest; daily digital screen exposure ≥3 h; and occasional cosmetic use. Risk factors of DED TBUT ≤5 s were: living in the southwest; wearing contact lenses (>3 y); and using eye drops. Rates of unilateral and bilateral DED were comparable. CONCLUSIONS: DED in China is more likely in the aged and those in the north/southwest. DED rates increase with digital screen exposure, and use of cosmetics, contact lenses, or eye drops for asthenopia. Unilateral DED should be treated as promptly as bilateral.
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Pekin ducks and Shaoxing ducks are 2 Chinese local duck breeds, both domesticated from mallard, but after domestication and long-term artificial selection, the body weight of Pekin ducks is significantly higher than that of Shaoxing ducks. It is no debate that genetic factors are the main factors responsible for this difference, but whether intestinal microbiota contribute to this difference is yet unknown. Thus, we performed comparative intestinal metagenomics and metabolomics analysis between Pekin ducks and Shaoxing ducks. We found obvious differentiation of intestinal metagenome and metabolome between the 2 breeds. Four cecal microbial genera, including Fusobacterium, Methanobrevibacter, Butyricicoccus, and Anaerotignum showed higher abundance in Pekin ducks. Among them, Methanobrevibacter and Butyricicoccus may positively correlate with fat deposition and body weight. A total of 310 metabolites showed difference between the 2 breeds. Functions of these differential metabolites were mainly enriched in amino acid metabolism, including energy metabolism-related histidine metabolism. Integrated omics analysis showed that microbial changes were closely related to altered metabolites. Especially, Butyricicoccus showing higher abundance in Pekin ducks was significantly negatively correlated with D-glucosamine-6-phosphate, which has been reported to prevent body weight gains. These findings may contribute to further understand the difference in body weight between Pekin ducks and Shaoxing ducks.
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Aim: Atopic dermatitis (AD) often accompanies skin infections, and bacterial skin infections often cause persistent and worsening symptoms. In this study, we explored the key changes in the microbiota of AD patients, as well as the effects of different ages and the severity of rash on changes in the microbiota. Patients and Methods: A total of 95 AD patients and 77 healthy volunteers were recruited. The AD patients were divided into three groups based age and three groups according to the EASI score. Microorganisms collected from the skin were analyzed through 16S rRNA gene sequencing, revealing species diversity via α and ß diversity analyses. Species compositions were compared at the phylum and genus levels. The significance of skin microbiota at the genus level was assessed using the random forest algorithm. Finally, the impact of relationships between different microbial communities on the microbial community composition and the pathogenesis of AD was explored using Pearson correlation coefficients. Results: The species diversity of the skin microbiota in the AD group significantly decreased. Compared with that in the healthy volunteers (HV) group, the bacterial diversity in the two groups of samples significantly differed. Staphylococcus dominated the bacterial communities, and as AD symptoms gradually worsened, the abundance of Staphylococcus gradually increased. Among all bacterial genera with a relative abundance greater than 1%, Staphylococcus showed a negative correlation with other genera, and showed significant consistency in specimens from different age groups. Conclusion: Changes in the abundance of Staphylococcus in the skin bacterial colonies are the main cause of AD. Brevundimonas, Paracoccus, Corynebacterium, and Veillonella may serve as characteristic biomarkers for AD. These results indicate that altering the microbiota composition of the skin may aid in the treatment of AD.
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PURPOSE: Achieving a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT) remains a challenge for most patients with rectal cancer. Exploring the potential of combining NCRT with immunotherapy or targeted therapy for those achieving a partial response (PR) offers a promising avenue to enhance treatment efficacy. This study investigated the impact of NCRT on the tumor microenvironment in locally advanced rectal cancer (LARC) patients who exhibited a PR. METHODS: This was a retrospective, observational study. Five patients demonstrating a PR after neoadjuvant treatment for LARC were enrolled in the study. Biopsy samples before treatment and resected specimens after treatment were stained with a panel of 26 antibodies targeting various immune and tumor-related markers, each labeled with distinct metal tags. The labeled samples were then analyzed using the Hyperion imaging system. RESULTS: Heterogeneity within the tumor microenvironment was observed both before and after NCRT. Notably, tumor-associated macrophages, CD4 + T cells, CD8 + T cells, CD56 + natural killer cells, tumor-associated neutrophils, cytokeratin, and E-cadherin exhibited slight increase in abundance within the tumor microenvironment following treatment (change ratios = 0.78, 0.2, 0.27, 0.32, 0.17, 0.46, 0.32, respectively). Conversely, the number of CD14 + monocytes, CD19 + B cells, CD45 + CD4 + T cells, collagen I, α-smooth muscle actin, vimentin, and ß-catenin proteins displayed significant decreases post-treatment (change ratios = 1.73, 1.92, 1.52, 1.25, 1.52, 1.12, 2.66, respectively). Meanwhile, Foxp3 + regulatory cells demonstrated no significant change (change ratio = 0.001). CONCLUSIONS: NCRT has diverse effects on various components of the tumor microenvironment in LARC patients who achieve a PR after treatment. Leveraging combination therapies may optimize treatment outcomes in this patient population.
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Traitement néoadjuvant , Tumeurs du rectum , Microenvironnement tumoral , Humains , Tumeurs du rectum/thérapie , Tumeurs du rectum/anatomopathologie , Tumeurs du rectum/traitement médicamenteux , Mâle , Femelle , Adulte d'âge moyen , Sujet âgé , Chimioradiothérapie , Résultat thérapeutique , Études rétrospectivesRÉSUMÉ
Soil salinization is a major abiotic stress factor that negatively impacts plant growth, development, and crop yield, severely limiting agricultural production and economic development. Cotton, a key cash crop, is commonly cultivated as a pioneer crop in regions with saline-alkali soil due to its relatively strong tolerance to salt. This characteristic renders it a valuable subject for investigating the molecular mechanisms underlying plant salt tolerance and for identifying genes that confer salt tolerance. In this study, focus was placed on examining a salt-tolerant variety, E991, and a salt-sensitive variety, ZM24. A combined analysis of transcriptomic data from these cotton varieties led to the identification of potential salt stress-responsive genes within the glutathione S-transferase (GST) family. These versatile enzyme proteins, prevalent in animals, plants, and microorganisms, were demonstrated to be involved in various abiotic stress responses. Our findings indicate that suppressing GhGSTF9 in cotton led to a notably salt-sensitive phenotype, whereas heterologous overexpression in Arabidopsis plants decreases the accumulation of reactive oxygen species under salt stress, thereby enhancing salt stress tolerance. This suggests that GhGSTF9 serves as a positive regulator in cotton's response to salt stress. These results offer new target genes for developing salt-tolerant cotton varieties.
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Arabidopsis , Régulation de l'expression des gènes végétaux , Gossypium , Protéines végétales , Végétaux génétiquement modifiés , Tolérance au sel , Arabidopsis/génétique , Gossypium/génétique , Végétaux génétiquement modifiés/génétique , Tolérance au sel/génétique , Protéines végétales/génétique , Protéines végétales/métabolisme , Stress salin/génétique , Espèces réactives de l'oxygène/métabolisme , Glutathione transferase/génétique , Glutathione transferase/métabolisme , Stress physiologique/génétique , Plantes tolérantes au sel/génétiqueRÉSUMÉ
What is already known on this topic?: In China, there is limited data available on the use and coverage of the non-program, combined diphtheria, tetanus toxoid, acellular pertussis adsorbed, inactivated poliovirus and haemophilus influenzae type b (DTaP-IPV/Hib) pentavalent vaccine, and its role as a substitute for the separately administered standalone program vaccines. What is added by this report?: We evaluated the use and coverage of the pentavalent vaccine in nine provincial-level administrative divisions (PLADs) spanning eastern, central, and western China from 2019 to 2021. Initial use and coverage were low, but demonstrated annual growth albeit with regional and urban-rural discrepancies. The pentavalent vaccine was increasingly substituted for standalone vaccines over the course of this period. What are the implications for public health practice?: Parents in China are increasingly opting to replace the standard program vaccines with voluntarily purchased combination vaccines, particularly the pentavalent vaccine. The development of combination vaccines should thus be promoted in China, as it could enhance utilization and coverage rates, and decrease the economic burden.
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We examine the relationship between BMI and food purchase behavior using a unique dataset that links individual-level food purchases to health data. We find that individuals with higher BMI are significantly more sensitive to price changes in vice categories but do not show similar sensitivity in comparable nonvice categories. We rely on past literature that defines and identifies vice categories as those that are tempting and purchased impulsively. We explore the effectiveness of a 10% price increase on vice food categories, a hypothetical policy similar in spirit to a fat tax or sugar tax. We predict that such a tax would substantially reduce consumption of these foods, and would be particularly effective in reducing consumption by individuals with higher BMI.
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Background: Elevated expression of SLC7A11, in conjunction with glucose deprivation, has revealed disulfidptosis as an emerging cell death modality. However, the prevalence of disulfidptosis across tumor cell lines, irrespective of SLC7A11 levels, remains uncertain. Additionally, deletion of the ribophorin I (RPN1) gene imparts resistance to disulfidptosis, yet the precise mechanism linking RPN1 to disulfidptosis remains elusive. The aim of this study is to determine the mechanism of RPN1-induced disulfidptosis and to determine the possibility of RPN1 as a pan-cancer marker. Methods: We hypothesized the widespread occurrence of disulfidptosis in various tumor cells, and proposed that RPN1-mediated disulfidptosis may be executed through cell skeleton breakdown. Experimental validation was conducted via flow cytometry, immunofluorescence, and western blot techniques. Furthermore, given RPN1's status as an emerging cell death marker, we utilized bioinformatics to analyze its expression in tumor tissues, clinical relevance, mechanisms within the tumor microenvironment, and potential for immunotherapy. Results: Conducting experiments on breast cancer (MDA-MB-231) and lung cancer (A549) cell lines under glucose-starved conditions, we found that RPN1 primarily induces cell skeleton breakdown to facilitate disulfidptosis. RPN1 demonstrated robust messenger RNA (mRNA) expression across 16 solid tumors, validated by data from 12 tumor types in the Gene Expression Omnibus (GEO). Across 12 cancer types, RPN1 exhibited significant diagnostic potential, particularly excelling in accuracy for glioblastoma (GBM). Elevated RPN1 expression in tumor tissues was found to correlate with improved overall survival (OS) in certain cancers [diffuse large B-cell lymphoma (DLBC) and thymoma (THYM)] but poorer prognosis in others [adrenocortical carcinoma (ACC), kidney chromophobe (KICH), brain lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), and pancreatic adenocarcinoma (PAAD)]. RPN1 is enriched in immune-related pathways and correlates with immune scores in tumor tissues. In urothelial carcinoma (UCC), RPN1 demonstrates potential in predicting the efficacy of anti-programmed cell death ligand 1 (PD-L1) immune therapy. Conclusions: This study underscores RPN1's role in facilitating disulfidptosis, its broad relevance as a pan-cancer biomarker, and its association with the efficacy of anti-PD-L1 immune therapy.
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AIMS: Understanding the inhibitory effects of natural organic substances on soil-borne pathogenic fungi and the relevant molecular mechanisms are highly important for future development of green prevention and control technology against soil-borne diseases. Our study elucidates the inhibitory effect of the combined application of humic acids (HAs) and chitosan on Alternariasolani and the light on the corresponding mechanism. METHODS AND RESULTS: The effect on A. solani growth by HAs incorporated with chitosan was investigated by plate culture and the corresponding mechanism was revealed using transcriptomics. The colony growth of A. solani was suppressed with the highest inhibition rate 33.33% when swine manure HAs was compounded with chitosan at a ratio of 1:4. Chitosan changed the colony morphology from round to irregularly. RNA-seq in the HAs and chitosan (HC) treatment revealed 239 differentially expressed genes compared with the control. The unigenes associated with enzymes activities related to growth and biological processes closely related to mycelial growth and metabolism were downregulated. RNA-seq also revealed that chitosan altered the expression of genes related to secondary metabolism, fungal cell wall formation and polysaccharide synthesis, and metabolism. Meanwhile, weighted gene co-expression network analysis showed that, genes expression in the module positively correlated with mycelial growth was significantly reduced in the HC treatment; and the results were verified by real-time quantitative polymerase chain reaction. CONCLUSIONS: The co-inhibition effect of HAs and chitosan on A. solani is associated with downregulated genes expression correlated with mycelial growth.
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Alternaria , Chitosane , Analyse de profil d'expression de gènes , Substances humiques , Chitosane/pharmacologie , Alternaria/effets des médicaments et des substances chimiques , Alternaria/génétique , Alternaria/croissance et développement , Animaux , Transcriptome , Suidae , Fumier/microbiologie , Microbiologie du sol , Mycelium/croissance et développement , Mycelium/effets des médicaments et des substances chimiques , Mycelium/génétiqueRÉSUMÉ
In the past decades, the amount of biomass waste has continuously increased in human living environments, and it has attracted more and more attention. Biomass is regarded as the most high-quality and cost-effective precursor material for the preparation carbon of adsorbents and catalysts. The application of biomass carbon has extensively explored. The efficient application of biomass carbon in organic wastewater purification were reviewed. With briefly introducing biomass types, the latest progress of Machine learning in guiding the preparation and application of biomass carbon was emphasized. The key factors in constructing efficient biomass carbon for adsorption and catalytic applications were discussed. Based on the functional groups, rich pore structure and active site of biomass carbon, it exhibits high efficiency in water purification performance in the fields of adsorption and catalysis. In addition, out of a firm belief in the enormous potential of biomass carbon, the remaining challenges and future research directions were discussed.
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Biomasse , Carbone , Apprentissage machine , Eaux usées , Purification de l'eau , Eaux usées/composition chimique , Carbone/composition chimique , Adsorption , Purification de l'eau/méthodes , Élimination des déchets liquides/méthodes , Catalyse , Polluants chimiques de l'eau/analyseRÉSUMÉ
Evodiamine (EVO), the main active alkaloid in Evodia rutaecarpa, was shown to exert various pharmacological activities, especially anti-tumor. Currently, it is considered a potential anti-cancer drug due to its excellent anti-tumor activity, which unfortunately has adverse reactions, such as the risk of liver and kidney injury, when Evodia rutaecarpa containing EVO is used clinically. In the present study, we aim to clarify the potential toxic target organs and toxicity mechanism of EVO, an active monomer in Evodia rutaecarpa, and to develop mitigation strategies for its toxicity mechanism. Transcriptome analysis and related experiments showed that the PI3K/Akt pathway induced by calcium overload was an important step in EVO-induced apoptosis of renal cells. Specifically, intracellular calcium ions were increased, and mitochondrial calcium ions were decreased. In addition, EVO-induced calcium overload was associated with TRPV1 receptor activation. In vivo TRPV1 antagonist and calcium chelator effects were observed to significantly reduce body weight loss and renal damage in mice due to EVO toxicity. The potential nephrotoxicity of EVO was further confirmed by an in vivo test. In conclusion, TRPV1-mediated calcium overload-induced apoptosis is one of the mechanisms contributing to the nephrotoxicity of EVO due to its toxicity, whereas maintaining body calcium homeostasis is an effective measure to reduce toxicity. These studies suggest that the clinical use of EVO-containing herbal medicines should pay due attention to the changes in renal function of patients as well as the off-target effects of the drugs.
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Apoptose , Calcium , Evodia , Homéostasie , Rein , Quinazolines , Quinazolines/toxicité , Quinazolines/pharmacologie , Animaux , Homéostasie/effets des médicaments et des substances chimiques , Calcium/métabolisme , Souris , Apoptose/effets des médicaments et des substances chimiques , Rein/effets des médicaments et des substances chimiques , Rein/anatomopathologie , Evodia/composition chimique , Mâle , Canaux cationiques TRPV/métabolisme , Agents chélateurs du calcium/pharmacologieRÉSUMÉ
BACKGROUND: Previously, several studies have indicated that pediatric IgA nephropathy (IgAN) might be different from adult IgAN, and treatment strategies might be also different between pediatric IgAN and adult IgAN. METHODS: We analyzed two prospective cohorts established by pediatric and adult nephrologists, respectively. A comprehensive analysis was performed investigating the difference in clinical and pathological characteristics, treatment, and prognosis between children and adults with IgAN. RESULTS: A total of 1015 children and 1911 adults with IgAN were eligible for analysis. More frequent gross hematuria (88% vs. 20%, p < 0.0001) and higher proteinuria (1.8 vs. 1.3 g/d, p < 0.0001) were seen in children compared to adults. In comparison, the estimated glomerular filtration rate (eGFR) was lower in adults (80.4 vs. 163 ml/min/1.73 m2, p < 0.0001). Hypertension was more prevalent in adult patients. Pathologically, a higher proportion of M1 was revealed (62% vs. 39%, p < 0.0001) in children than in adults. S1 (62% vs. 28%, p < 0.0001) and T1-2 (34% vs. 8%, p < 0.0001) were more frequent in adults. Adjusted by proteinuria, eGFR, and hypertension, children were more likely to be treated with glucocorticoids than adults (87% vs. 45%, p < 0.0001). After propensity score matching, in IgAN with proteinuria > 1 g/d, children treated with steroids were 1.87 (95% CI 1.16-3.02, p = 0.01) times more likely to reach complete remission of proteinuria compared with adults treated with steroids. CONCLUSIONS: Children present significantly differently from adults with IgAN in clinical and pathological manifestations and disease progression. Steroid response might be better in children.
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Débit de filtration glomérulaire , Glomérulonéphrite à dépôts d'IgA , Protéinurie , Humains , Glomérulonéphrite à dépôts d'IgA/traitement médicamenteux , Glomérulonéphrite à dépôts d'IgA/physiopathologie , Glomérulonéphrite à dépôts d'IgA/diagnostic , Glomérulonéphrite à dépôts d'IgA/anatomopathologie , Glomérulonéphrite à dépôts d'IgA/complications , Glomérulonéphrite à dépôts d'IgA/thérapie , Mâle , Femelle , Enfant , Adulte , Protéinurie/étiologie , Protéinurie/diagnostic , Adolescent , Études prospectives , Jeune adulte , Pronostic , Adulte d'âge moyen , Facteurs âges , Hématurie/étiologie , Hématurie/diagnostic , Hypertension artérielle/traitement médicamenteux , Hypertension artérielle/épidémiologie , Hypertension artérielle/diagnostic , Rein/anatomopathologie , Rein/physiopathologie , Évolution de la maladie , Glucocorticoïdes/usage thérapeutiqueRÉSUMÉ
Stimuli-responsive crystalline materials have received much attention for being potential candidates of smart materials. However, the occurrence of polymorphism-driven stimuli responses in crystalline materials remains interesting but rare. Herein, three polymorphs of an acylhydrazone derivative, N'-[(E)-(1-benzofuran-2-yl) methylidene] pyridine -4-carbohydrazide (BFMP) were prepared. Form-1 undergoes a photomechanical response via EâZ photoisomerization under UV irradiation, accompanied by a decrease in fluorescence intensity and a change from colorless to yellow. Two types of ZâE thermal isomerization mechanisms with significant differences in conversion rate were observed at different temperatures in form-1. The solid-melt-solid transition has a faster conversion rate compared to the solid-solid transition due to freedom from lattice confinement. The transition from form-2 to form-3 can be achieved under grinding, coupled with a significant decrease in fluorescence intensity. The similar molecular stacking pattern of form-2 and form-3 provides a structural basis for the grinding-induced crystalline transition behavior. In addition, the presence of the pyridine moiety imparts an acidochromic property. The combination of photochromism and acidochromism explores the possible applications of acylhydrazone derivatives in information encryption.
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BACKGROUND: China has been working towards measles elimination, but in 2017, measles outbreaks occurred in Ganzi and Aba prefectures of Sichuan province, representing 95% of all provincial cases and jeopardizing measles elimination. METHODS: During March and April 2017, high-performing prefectures were paired with outbreak and other interested counties to jointly conduct a measles-rubella (MR) catch-up campaign, build population immunity, and strengthen the counties' programs. RESULTS: House-to-house search identified 88,383 children in Ganzi that lacked MCV vaccination; 85,144 (96.34%) were vaccinated. Search identified 33,683 children in Aba who were not vaccinated against measles; 33,074 (98.19%) were vaccinated. The supporting prefectures helped install Immunization Information Systems and enroll unvaccinated children into the immunization program.The outbreak ended within a month and incidence has remained low for the subsequent six years. CONCLUSION: A paired catch-up campaign represents an effective model of using measles elimination strategies to strengthen local immunization programs for long-term program effectiveness.
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Rougeole , Rubéole , Enfant , Humains , Nourrisson , Rougeole/épidémiologie , Rougeole/prévention et contrôle , Rubéole/prévention et contrôle , Programmes de vaccination , Épidémies de maladies/prévention et contrôle , Vaccination , Chine/épidémiologie , Vaccin contre la rougeoleRÉSUMÉ
Plants have evolved sophisticated signaling networks to adjust flowering time, ensuring successful reproduction. Two crucial flowering regulators, FLOWERING LOCUS T (FT) and CONSTANS (CO), play pivotal roles in regulating flowering across various species. Previous studies have indicated that suppressing Gossypium hirsutum CONSTANS-LIKE 2 (GhCOL2), a homolog of Arabidopsis CO, leads to delayed flowering in cultivated cotton. However, the underlying regulatory mechanisms remain unknown. In this study, a yeast one-hybrid and dual-LUC expression assays were used to elucidate the molecular mechanism through which GhCOL2 regulates the transcription of GhHD3A. RT-qPCR was used to examine the expression of GhCOL2 and GhHD3A. Our findings reveal that GhCOL2 directly binds to CCACA cis-elements and atypical CORE (TGTGTATG) cis-elements in the promoter regions of HEADING DATE 3 A (HD3A), thereby activating GhHD3A transcription. Notably, GhCOL2 and GhHD3A exhibited high expression levels in the adult stage and low levels in the juvenile stage. Interestingly, the expression of GhCOL2 and GhHD3A varied significant between the two cotton varieties (Tx2094 and Maxxa). In summary, our study enhances the understanding of the molecular mechanism by which cotton GhCOL2-GhHD3A regulates flowering at the molecular level. Furthermore, it contributes to a broader comprehension of the GhCOL2-GhHD3A model in G. hirsutum.
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Glioblastoma (GBM), deep in the brain, is more challenging to diagnose and treat than other tumors. Such challenges have blocked the development of high-impact therapeutic approaches that combine reliable diagnosis with targeted therapy. Herein, effective cyanine dyes (IRLy) with the near-infrared two region (NIR-II) adsorption and aggregation-induced emission (AIE) have been developed via an "extended conjugation & molecular rotor" strategy for multimodal imaging and phototherapy of deep orthotopic GBM. IRLy was synthesized successfully through a rational molecular rotor modification with stronger penetration, higher signal-to-noise ratio, and a high photothermal conversion efficiency (PCE) up to â¼60%, which can achieve efficient NIR-II photo-response. The multifunctional nanoparticles (Tf-IRLy NPs) were further fabricated to cross the blood-brain barrier (BBB) introducing transferrin (Tf) as a targeting ligand. Tf-IRLy NPs showed high biosafety and good tumor enrichment for GBM in vitro and in vivo, and thus enabled accurate, efficient, and less invasive NIR-II multimodal imaging and photothermal therapy. This versatile Tf-IRLy nanosystem can provide a reference for the efficient, precise and low-invasive multi-synergistic brain targeted photo-theranostics. In addition, the "extended conjugation & molecular rotor" strategy can be used to guide the design of other photothermal agents.
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Glioblastome , Nanoparticules , Tumeurs , Humains , Glioblastome/imagerie diagnostique , Glioblastome/thérapie , Photothérapie/méthodes , Encéphale , Barrière hémato-encéphalique , Agents colorants , Nanomédecine théranostique/méthodes , Nanoparticules/usage thérapeutique , Lignée cellulaire tumoraleRÉSUMÉ
OBJECTIVE: The purpose of the present study was to formulate a menantine hydrochloride (MH) sustained-release suspension. METHODS: Menantine hydrochloride drug resin complex (MH-DRC) was prepared with strong acid cation exchange resin as carrier using water bath method. The MH-DRC was characterized using scanning electron microscopy, X-ray diffraction and infrared spectroscopy. The MH-coated microcapsule (MH-CM) with optimized formulation was further dispersed in a suitable medium to obtain a sustained-release suspension. The rats were given both the MH sustained-release suspension and the commercial MH sustained-release capsule by intragastric administration. The plasma concentration-time curves and related pharmacokinetic parameters were also investigated using a non-atrioventricular model. RESULTS: MH and ion-exchange resin were ionically bonded. AmberliteIRP®69 had a higher affinity for MH at the initial concentration of 5 mg·mL-1 and a reaction temperature of 25.0 ± 0.5 °C. In vitro drug release profile showed that both the drug resin complex and the coated microcapsules had a certain level of sustained-release effect. The t1/2 of MH sustained-release suspension was extended from 68.44 h to 72.79 h with the peak blood concentration being decreased to 3.56 µg·mL-1 and the Tmax extended to 12 h compared with the commercial MH sustained-release capsule. The concentration-time curve of the self-made MH sustained-release suspension was flattened and the average relative bioavailability (Fr) was 116.65% compared with the commercial MH sustained-release capsules. CONCLUSIONS: The findings showed that the MH sustained-release suspension was successfully formulated with acceptable pharmacokinetic indices for effective treatment of Alzheimer's disease.