AGAMOUS-LIKE 24 senses continuous inductive photoperiod in the inflorescence meristem to promote anthesis in chrysanthemum.

During the floral transition, many plant species including chrysanthemum (Chrysanthemum morifolium) require continuous photoperiodic stimulation for successful anthesis. Insufficient photoperiodic stimulation results in flower bud arrest or even failure. The molecular mechanisms underlying how continuous photoperiodic stimulation promotes anthesis are not well understood. Here, we reveal that in wild chrysanthemum (C. indicum), an obligate short-day (SD) plant, floral evocation is not limited to SD conditions. However, SD signals generated locally in the inflorescence meristem (IM) play a vital role in ensuring anthesis after floral commitment. Genetic analyses indicate that the florigen FLOWERING LOCUS T-LIKE3 (CiFTL3) plays an important role in floral evocation, but a lesser role in anthesis. Importantly, our data demonstrate that AGAMOUS-LIKE 24 (CiAGL24) is a critical component of SD signal perception in the IM to promote successful anthesis, and that floral evocation and anthesis are two separate developmental events in chrysanthemum. We further reveal that the central circadian clock component PSEUDO-RESPONSE REGULATOR 7 (CiPRR7) in the IM activates CiAGL24 expression in response to SD conditions. Moreover, our findings elucidate a negative feedback loop in which CiAGL24 and SUPPRESSOR OF OVEREXPRESSION OF CO 1 (CiSOC1) modulate LEAFY (CiLFY) expression. Together, our results demonstrate that the CiPRR7-CiAGL24 module is vital for sustained SD signal perception in the IM to ensure successful anthesis in chrysanthemum.

The F-box protein RhSAF destabilizes the gibberellic acid receptor RhGID1 to mediate ethylene-induced petal senescence in rose.

Roses are among the most popular ornamental plants cultivated worldwide for their great economic, symbolic, and cultural importance. Nevertheless, rapid petal senescence markedly reduces rose (Rosa hybrida) flower quality and value. Petal senescence is a developmental process tightly regulated by various phytohormones. Ethylene accelerates petal senescence, while gibberellic acid (GA) delays this process. However, the molecular mechanisms underlying the crosstalk between these phytohormones in the regulation of petal senescence remain largely unclear. Here, we identified SENESCENCE-ASSOCIATED F-BOX (RhSAF), an ethylene-induced F-box protein gene encoding a recognition subunit of the SCF-type E3 ligase. We demonstrated that RhSAF promotes degradation of the GA receptor GIBBERELLIN INSENSITIVE DWARF1 (RhGID1) to accelerate petal senescence. Silencing RhSAF expression delays petal senescence, while suppressing RhGID1 expression accelerates petal senescence. RhSAF physically interacts with RhGID1s and targets them for ubiquitin/26S proteasome-mediated degradation. Accordingly, ethylene-induced RhGID1C degradation and RhDELLA3 accumulation are compromised in RhSAF-RNAi lines. Our results demonstrate that ethylene antagonizes GA activity through RhGID1 degradation mediated by the E3 ligase RhSAF. These findings enhance our understanding of the phytohormone crosstalk regulating petal senescence and provide insights for improving flower longevity.

Abscisic acid-induced transcription factor PsMYB306 negatively regulates tree peony bud dormancy release.

Bud dormancy is a crucial strategy for perennial plants to withstand adverse winter conditions. However, the regulatory mechanism of bud dormancy in tree peony (Paeonia suffruticosa) remains largely unknown. Here, we observed dramatically reduced and increased accumulation of abscisic acid (ABA) and bioactive gibberellins (GAs) GA1 and GA3, respectively, during bud endodormancy release of tree peony under prolonged chilling treatment. An Illumina RNA sequencing study was performed to identify potential genes involved in the bud endodormancy regulation in tree peony. Correlation matrix, principal component, and interaction network analyses identified a downregulated MYB transcription factor gene, PsMYB306, the expression of which positively correlated with 9-CIS-EPOXYCAROTENOID DIOXYGENASE 3 (PsNCED3) expression. Protein modeling analysis revealed 4 residues within the R2R3 domain of PsMYB306 to possess DNA binding capability. Transcription of PsMYB306 was increased by ABA treatment. Overexpression of PsMYB306 in petunia (Petunia hybrida) inhibited seed germination and plant growth, concomitant with elevated ABA and decreased GA contents. Silencing of PsMYB306 accelerated cold-triggered tree peony bud burst and influenced the production of ABA and GAs and the expression of their biosynthetic genes. ABA application reduced bud dormancy release and transcription of ENT-KAURENOIC ACID OXIDASE 1 (PsKAO1), GA20-OXIDASE 1 (PsGA20ox1), and GA3-OXIDASE 1 (PsGA3ox1) associated with GA biosynthesis in PsMYB306-silenced buds. In vivo and in vitro binding assays confirmed that PsMYB306 specifically transactivated the promoter of PsNCED3. Silencing of PsNCED3 also promoted bud break and growth. Altogether, our findings suggest that PsMYB306 negatively modulates cold-induced bud endodormancy release by regulating ABA production.

SlBEL11 regulates flavonoid biosynthesis, thus fine-tuning auxin efflux to prevent premature fruit drop in tomato.

Auxin regulates flower and fruit abscission, but how developmental signals mediate auxin transport in abscission remains unclear. Here, we reveal the role of the transcription factor BEL1-LIKE HOMEODOMAIN11 (SlBEL11) in regulating auxin transport during abscission in tomato (Solanum lycopersicum). SlBEL11 is highly expressed in the fruit abscission zone, and its expression increases during fruit development. Knockdown of SlBEL11 expression by RNA interference (RNAi) caused premature fruit drop at the breaker (Br) and 3 d post-breaker (Br+3) stages of fruit development. Transcriptome and metabolome analysis of SlBEL11-RNAi lines revealed impaired flavonoid biosynthesis and decreased levels of most flavonoids, especially quercetin, which functions as an auxin transport inhibitor. This suggested that SlBEL11 prevents premature fruit abscission by modulating auxin efflux from fruits, which is crucial for the formation of an auxin response gradient. Indeed, quercetin treatment suppressed premature fruit drop in SlBEL11-RNAi plants. DNA affinity purification sequencing (DAP-seq) analysis indicated that SlBEL11 induced expression of the transcription factor gene SlMYB111 by directly binding to its promoter. Chromatin immunoprecipitation-quantitative polymerase chain reaction and electrophoretic mobility shift assay showed that S. lycopersicum MYELOBLASTOSIS VIRAL ONCOGENE HOMOLOG111 (SlMYB111) induces the expression of the core flavonoid biosynthesis genes SlCHS1, SlCHI, SlF3H, and SlFLS by directly binding to their promoters. Our findings suggest that the SlBEL11-SlMYB111 module modulates flavonoid biosynthesis to fine-tune auxin efflux from fruits and thus maintain an auxin response gradient in the pedicel, thereby preventing premature fruit drop.

Global scientific trends in research of epigenetic response to exercise: A bibliometric analysis.

The purpose of this work is to comprehensively understand the adaptive response of multiple epigenetic modifications on gene expression changes driven by exercise. Here, we retrieved literatures from publications in the PubMed and Web of Science Core Collection databases up to and including October 15, 2023. After screening with the exclusion criteria, 1910 publications were selected in total, comprising 1399 articles and 511 reviews. Specifically, a total of 512, 224, and 772 publications is involved in DNA methylation, histone modification, and noncoding RNAs, respectively. The correlations between publication number, authors, institutions, countries, references, and the characteristics of hotspots were explored by CiteSpace. Here, the USA (621 publications) ranked the world's most-influential countries, the University of California System (68 publications) was the most productive, and Tiago Fernandes (14 publications) had the most-published publications. A comprehensive keyword analysis revealed that cardiovascular disease, cancer, skeletal muscle development, and metabolic syndrome, and are the research hotspots. The detailed impact of exercise was further discussed in different aspects of these three categories of epigenetic modifications. Detailed analysis of epigenetic modifications in response to exercise, including DNA methylation, histone modification, and changes in noncoding RNAs, will offer valuable information to help researchers understand hotspots and emerging trends.

Identification and verification on prognostic index of glioblastoma immune-related lncRNAs.

BACKGROUND: Glioblastoma (GBM) is the most common cause of primary brain malignancy. Recently, many immune-related long noncoding ribonucleic acids (ir-lncRNAs) are indicated to be closely related to the regulation of the immune microenvironment and immune cell infiltration of GBM. OBJECTIVES: Through the joint analysis of multiple public databases, key ir-lncRNAs in GBM were screened. The ir-lncRNAs were used to construct risk-scoring models and promote the development of novel GBM biomarkers. MATERIAL AND METHODS: In this study, we performed a three-way Venn analysis combined with a least absolute shrinkage and selection operator (LASSO) regression analysis on all lncRNAs in The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA) and Imm-Lnc datasets, and identified 10 ir-lncRNAs. Multivariate Cox analysis was used to calculate the coefficient and construct a risk-scoring model. RESULTS: By plotting calibration curves and receiver operating characteristic (ROC) curves, the model showed excellent prediction results. Based on the Tumor Immune Estimation Resource (TIMER) database, the correlation analysis showed that 10 ir-lncRNAs risk scores were related to immune cell infiltration. The enrichment analysis was subsequently performed, which showed that these ir-lncRNAs played an important role in the progression of GBM. Among the 10 lncRNAs, we found that AL354993.1 was highly expressed in GBM, had not been reported, and was shown to be closely related to GBM progression. CONCLUSIONS: In conclusion, the 10 ir-lncRNAs have the potential to predict the prognosis of GBM patients and may play a vital role in the progression of the disease.

Effects of different curing concentrations and drying times on the microbial community structure and metabolites of dried Spanish mackerel.

Cured Spanish mackerel has a promising market owing to its nutritious nature as well as ease of transportation and preservation. However, the nutritional and flavor formation mechanism of Spanish mackerel after curing and drying is unclear. To overcome this problem, the effects of different processing conditions on the free amino acid, microbial community, and flavor of Spanish mackerel were explored. Staphylococcus and Cobetia are the main microorganisms in cured mackerel and are closely associated with the formation of their quality. Compared with fresh mackerel, cured mackerel contains increased levels of protein, fat, and chloride, contributing to its distinctive flavor. The contents of free amino acids in the BA64 group were substantially higher than those in other groups, particularly the contents of threonine, glycine, and tyrosine. These findings will contribute to the development of high-quality cured Spanish mackerel products and cured aquatic products.

Landscape of transcriptome-wide m6A modification in diabetic liver reveals rewiring of PI3K-Akt signaling after physical exercise.

AIM: Type 2 diabetes mellitus (T2DM) is one of the most common diseases, and epigenetic modification N6-methyladenosine (m6A) is essential for transcriptional modulation involved in its development. However, the precise role and landscape of transcriptome-wide m6A alterations in molecular adaptations after physical exercise have yet to be fully elucidated. METHODS: Four-week-old male C57BL/6J mice received a high-fat diet (HFD) for 12 weeks to establish a diabetic state, and HFD mice were simultaneously subjected to physical exercise (HFD + EX). The hepatic RNA m6A methylome was examined, the conjoint MeRIP-seq and RNA-seq was performed, and the exercise-modulated genes were confirmed. RESULTS: Physical exercise significantly ameliorates liver metabolic disorder and triggers a dynamic change in hepatic RNA m6A. By analyzing the distribution of m6A in transcriptomes, an abundance of m6A throughout mRNA transcripts and a pattern of conserved m6A after physical exercise was identified. It is noteworthy that conjoint MeRIP-seq and RNA-seq data revealed that both differentially methylated genes and differentially expressed genes were enriched in all stages of the PI3K-Akt signaling pathway, in particular the upstream nodes of this pathway, which are considered a valuable therapeutic target for T2DM. Moreover, in vivo and in vitro analyses showed that exercise-mediated methyltransferase Rbm15 positively regulated the expression of two upstream genes (Itga3 and Fgf21) in an m6A-dependent manner. CONCLUSION: These findings highlight the pivotal role of the exercise-induced m6A epigenetic network and contribute insights into the intricate epigenetic mechanism underlying insulin signaling.

Adverse event profile of memantine and donepezil combination therapy: a real-world pharmacovigilance analysis based on FDA adverse event reporting system (FAERS) data from 2004 to 2023.

Background: Donepezil in combination with memantine is a widely used clinical therapy for moderate to severe dementia. However, real-world population data on the long-term safety of donepezil in combination with memantine are incomplete and variable. Therefore, the aim of this study was to analyze the adverse events (AEs) of donepezil in combination with memantine according to US Food and Drug Administration Adverse Event Reporting System (FAERS) data to provide evidence for the safety monitoring of this therapy. Methods: We retrospectively analyzed reports of AEs associated with the combination of donepezil and memantine from 2004 to 2023 extracted from the FAERS database. Whether there was a significant association between donepezil and memantine combination therapy and AEs was assessed using four disproportionality analysis methods, namely, the reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker methods. To further investigate potential safety issues, we also analyzed differences and similarities in the time of onset and incidence of AEs stratified by sex and differences and similarities in the incidence of AEs stratified by age. Results: Of the 2,400 adverse drug reaction (ADR) reports in which the combination of donepezil and memantine was the primary suspected drug, most of the affected patients were female (54.96%) and older than 65 years of age (79.08%). We identified 22 different system organ classes covering 100 AEs, including some common AEs such as dizziness and electrocardiogram PR prolongation; fall, pleurothotonus and myoclonus were AEs that were not listed on the drug label. Moreover, we obtained 88 reports of AEs in men and 100 reports of AEs in women; somnolence was a common AE in both men and women and was more common in women, whereas pleurothotonus was a more common AE in men. In addition, we analyzed 12 AEs in patients younger than 18 years, 16 in patients between 18 and 65 years, and 113 in patients older than 65 years. The three age groups had distinctive AEs, but lethargy was the common AE among all age groups. Finally, the median time to AE onset was 19 days in all cases. In both men and women, most AEs occurred within a month of starting donepezil plus memantine, but some continued after a year of treatment. Conclusion: Our study identified potential and new AEs of donepezil in combination with memantine; some of these AEs were the same as in the specification, and some of the AE signals were not shown in the specification. In addition, there were sex and age differences in some of the AEs. Therefore, our findings may provide valuable insights for further studies on the safety of donepezil and memantine combination therapy, which are expected to contribute to the safe use of this therapy in clinical practice.

Rho A/ROCK signaling pathway involved in hyper responsiveness to aortic contraction in mice with type 2 diabetes / 中国药理学通报

Aim To investigate the mechanism of RhoA/ROCK signaling pathway in abnormal aortic contractility in type 2 diabetes (T2DM) mice. Methods The experiment was divided into two groups, the control group (db/m mice) and the model group (db/db mice). Changes of the response to different methods were measured in aorta rings using a Multi Myograph System. At the same time, the protein expression changes of aortic smooth muscle contraction signaling pathway in mice were determined by Western method. Results Compared with the control group, the blood glucose and body weight levels of the mice in the T2DM group significantly increased, and the cardiac function was abnormal (P <0. 01). The contractile response of the aorta of the diabetic mice induced by the contractile agents Phe, 5-HT and CaCl

Protective effect of omeprazole on gastric mucosal of cirrhotic portal hypertension rats

OBJECTIVE@#To observe the protective effect of omeprazole on gastric mucosal of cirrhotic portal hypertension rats.@*METHODS@#All rats were randomly divided into normal control group, cirrhosis and treatment group. Thioacetamide was used to establish rat model of cirrhotic portal hypertension. The necrotic tissue of gastric mucosa ulcer focus, degree of neutrophils infiltration at the ulcer margin, portal pressure, portal venous flow, abdominal aortic pressure, abdominal aortic blood flow at front end, gastric mucosal blood flow (GMBF), glycoprotein (GP) of gastric mucosa, basal acid secretion, H(+)back -diffusion, gastric mucosal damage index, NO, prostaglandin E2(PGE2) and tumor necrosis factor-α (TNF-α) were determined respectively, and the pathological changes of gastric mucosa were also observed by microscope.@*RESULTS@#Compared with cirrhosis group and the control group, the ulcer bottom necrotic material, gastric neutrophil infiltration and UI of the treatment group were all decreased significantly (P<0.01), GMBF value, GP values, serum NO, PGE2, TNF-α were all significantly increased.@*CONCLUSIONS@#Omeprazole has an important protective effect on gastric mucosal and it can increase gastric mucosal blood flow and related to many factors.

Expression of nm23 H(1) gene in childhood acute lymphoblastic leukemia and the relationship between nm23 H(1) expression and immunophenotype / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the expression of nm23-H(1) gene in children with acute lymphoblastic leukemia (ALL) and the relationship between nm23-H(1) expression and immunophenotype.</p><p><b>METHODS</b>nm23-H(1) expression was measured by semiquantitative RT-PCR in children with ALL (newly diagnosed, n = 40; remission, n = 32; relapse, n = 16; refractory, n = 3). Twenty normal children served as the control group. The relationship between nm23-H(1) expression and immunophenotype was evaluated.</p><p><b>RESULTS</b>The expression of nm23-H(1) in the newly diagnosed ALL group was significantly higher than that in the control (p<0.01) and the remission groups (p<0.01). There was no difference in the nm23-H(1) expression between the remission and the control groups. The expression of nm23-H(1) in the relapse group was significantly higher than that in the control (p<0.01) and the remission groups (p<0.01), and similar to that in the newly diagnosed ALL group. The three children with refractory ALL had higher nm23-H(1) expression. Both the positive rate and expression of nm23-H(1) in children with T-lineage ALL were higher than in children with B-lineage ALL (p<0.05).</p><p><b>CONCLUSIONS</b>The expression level of nm23-H(1) varies with the stages of ALL. Newly diagnosed, relapsed and refractory ALL children have higher nm23-H(1) expression. High nm23-H(1) expression may be associated with a poor prognosis and relapse. A higher expression of nm23-H(1) in children with T-ALL may be contributed to a low remission rate and a poor prognosis.</p>

Conservative surgery method of hypopharyngeal carcinoma / 上海第二医科大学学报

Objective To evaluate the feasibility of different kinds of surgeries to treat hypopharyngeal carcinoma and investigate the methods to conduct one-stage repair after hypopharyngeal carcinoma removal. Methods Thirty nine cases of hypopharyngeal carcinoma were treated from May 2000 to Mar 2007, of which 27 were originated from pyriform sinus, 8 from postcricoid and 4 from posterior pharyngeal wall. One-stage reconstruction for hypopharyngeal and esophageal defect was done with simple and less-damaged hypopharyngeal plasty by local sewing, infrahyoid muscle flap, pectoralis major flap and supplement of esophagus by stomach. Results The defect of 18 cases was repaired by sternohyoid muscle flap, including 13 from pyriform sinus, 4 from root of tongue and 1 from posterior pharyngeal wall. Seven were repaired by substitute of esophagus by stomach, 5 by local sewing, 4 by cervical flap and 2 by pectoralis major myocutaneous flap. All the patients were successfully followed up during the survival days. Half of the cases suffered from slight deglutitory disorder after operation and recovered soon, while 2 cases were still with worse deglutitory function. All the cases were recovered with laryngeal function, and 21 cases were decannulated with normal respiration and voice, and 18 with cannula. Thirteen cases survived for more than 3 years after operation and 5 cases more than 5 years, while 14 cases died within 1 year. Thirteen cases were carried out another operations for local recurrence or metastases of lymph nodes, one of whom experienced 6 operations. The estimated 3-year survival was 43.3% (13/30), and 5-year survival was 37.5%(3/8). Conclusion Hypopharyngeal carcinoma with different site and stage can be treated by different methods, and one-stage reconstruction can be done to repair the defect of pharynx and esophagus with satisfactory functional restoration and prognosis.

Nano-structured scaffold materials used in tissue engineering / 中国医学科学院学报

Micro- and nano-structured surfaces of scaffold materials have important effects on cells' adhesion and proliferation. Nano-structured surfaces can improve cells' adhesion and biocompatibility of materials. The effects of nano-biomaterials on the development of tissue engineering and the methods of preparation of nano-biomaterials such as molecular self-assemble and template technology are discussed.

Investigation of Factors for Retinopathy of Premature Infants / 实用儿科临床杂志

Objective To investigate the factors for retinopathy in premature infants. Methods Ophthalmologic mydri was conducted in premature infants and acording to the international classification of ROP, they were diagnosed as ROP. The risk factors of the incidence of ROP were statistically and respectively analyzed. Results Among total of 47 patients, 11 patients were found retinopathy of prematurity. Conclusion The body weight is lower, the gestation is shorter, incidence of ROP is the higher.

Clinical observation on treatment of chronic suppurative otitis media caused large tympanic membranes perforation by ear-dropping with combined Chinese and Western drugs / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the therapeutic effect of the self-prepared ear dropping made by combined Chinese and Western drugs in treating chronic suppurative otitis media caused large tympanic membrane perforation.</p><p><b>METHODS</b>Sixty-four patients were randomly divided into two groups, the treated group treated with the self-prepared ear-dropping and the control group treated with ear-dropping made by placebo, to observe the therapeutic effect and adverse reaction.</p><p><b>RESULTS</b>In the 32 patients of the treated group, 15 patients were cured, the cured tympanic membrane was normal in shape and thickness in 11, scarred in 3, and thin and transparent in 1. The hearing was improved in all patients with cured tympanic membrane. But no one was cured in the control group.</p><p><b>CONCLUSION</b>The self-prepared ear-dropping had good effect in treating tympanic membrane perforation, it is simple, cheap and no need of further operation.</p>

Preparation methods of nanocavity biomaterials with recognition specificity via template imprinting of proteins / 中国医学科学院学报

Nanocavity biomaterials with recognition specificity imprinted by using proteins as templates may successful serve as substitutes for antibodies, enzymes, and other native biological structures as well as cell bracket materials. It has numerous applications in biotechnology, medicine and so on. In this paper, the principle of template imprinting is introduced briefly, the specialty of template imprinting of proteins is analyzed, and the methods of template imprinting of proteins including protein entrapment, microbead surface imprinting, flat surface imprinting as well as the epitope are reviewed in details.