An R2R3-MYB network modulates stem strength by regulating lignin biosynthesis and secondary cell wall thickening in herbaceous peony.

Stem strength is an important agronomic trait affecting plant lodging, and plays an essential role in the quality and yield of plants. Thickened secondary cell walls in stems provide mechanical strength that allows plants to stand upright, but the regulatory mechanism of secondary cell wall thickening and stem strength in cut flowers remains unclear. In this study, first, a total of 11 non-redundant Paeonia lactiflora R2R3-MYBs related to stem strength were identified and isolated from cut-flower herbaceous peony, among which PlMYB43, PlMYB83 and PlMYB103 were the most upregulated differentially expressed genes. Then, the expression characteristics revealed that these three R2R3-MYBs were specifically expressed in stems and acted as transcriptional activators. Next, biological function verification showed that these P. lactiflora R2R3-MYBs positively regulated stem strength, secondary cell wall thickness and lignin deposition. Furthermore, yeast-one-hybrid and dual luciferase reporter assays demonstrated that they could bind to the promoter of caffeic acid O-methyltransferase gene (PlCOMT2) and/or laccase gene (PlLAC4), two key genes involved in lignin biosynthesis. In addition, the function of PlLAC4 in increasing lignin deposition was confirmed by virus-induced gene silencing and overexpression. Moreover, PlMYB83 could also act as a transcriptional activator of PlMYB43. The findings of the study propose a regulatory network of R2R3-MYBs modulating lignin biosynthesis and secondary cell wall thickening for improving stem lodging resistance, and provide a resource for molecular genetic engineering breeding of cut flowers.

Identification of key genes for triacylglycerol biosynthesis and storage in herbaceous peony (Paeonia lactifolra Pall.) seeds based on full-length transcriptome.

BACKGROUND: The herbaceous peony (Paeonia lactiflora Pall.) is extensively cultivated in China due to its root being used as a traditional Chinese medicine known as 'Radix Paeoniae Alba'. In recent years, it has been discovered that its seeds incorporate abundant unsaturated fatty acids, thereby presenting a potential new oilseed plant. Surprisingly, little is known about the full-length transcriptome sequencing of Paeonia lactiflora, limiting research into its gene function and molecular mechanisms. RESULTS: A total of 484,931 Reads of Inserts (ROI) sequences and 1,455,771 full-Length non-chimeric reads (FLNC) sequences were obtained for CDS prediction, TF analysis, SSR analysis and lncRNA identification. In addition, gene function annotation and gene structure analysis were performed. A total of 4905 transcripts were related to lipid metabolism biosynthesis pathway, belonging to 28 enzymes. We use these data to identify 10 oleosin (OLE) and 5 diacylglycerol acyltransferase (DGAT) gene members after de-redundancy. The analysis of physicochemical properties and secondary structure showed them similarity in gene family respectively. The phylogenetic analysis showed that the distribution of OLE and DGAT family members was roughly the same as that of Arabidopsis. Quantitative real-time polymerase chain reaction (qRT-PCR) analyses revealed expression changes in different seed development stages, and showed a trend of increasing and then decreasing. CONCLUSION: In summary, these results provide new insights into the molecular mechanism of triacylglycerol (TAG) biosynthesis and storage during the seedling stage in Paeonia lactiflora. It provides theoretical references for selecting and breeding oil varieties and understanding the functions of oil storage as well as lipid synthesis related genes in Paeonia lactiflora.

Kinetics of EBV antibody-based NPC risk scores in Taiwan NPC multiplex families.

Nasopharyngeal carcinoma (NPC) risk prediction models based on Epstein-Barr virus (EBV)-antibody testing have shown potential for screening of NPC; however, the long-term stability is unclear. Here, we investigated the kinetics of two EBV-antibody NPC risk scores within the Taiwan NPC Multiplex Family Study. Among 545 participants with multiple blood samples, we evaluated the stability of a 2-marker enzyme-linked immunosorbent assay score and 13-marker multiplex serology score using the intra-class correlation coefficient (ICC) by fitting a linear mixed model that accounted for the clustering effect of multiple measurements per subject and age. We also estimated the clustering of positive tests using Fleiss's kappa statistic. Over an average 20-year follow-up, the 2-marker score showed high stability over time, whereas the 13-marker score was more variable (p < .05). Case-control status is associated with the kinetics of the antibody response, with higher ICCs among cases. Positive tests were more likely to cluster within the same individual for the 2-marker score than the 13-marker score (p < .05). The 2-marker score had an increase in specificity from ~90% for single measurement to ~96% with repeat testing. The 13-marker score had a specificity of ~73% for a single measurement that increased to ~92% with repeat testing. Among individuals who developed NPC, none experienced score reversion. Our findings suggest that repeated testing could improve the specificity of NPC screening in high-risk NPC multiplex families. Further studies are required to determine the impact on sensitivity, establish optimal screening intervals, and generalize these findings to general population settings in high-risk regions.

The herbaceous peony transcription factor WRKY41a promotes secondary cell wall thickening to enhance stem strength.

Stem bending or lodging caused by insufficient stem strength is an important limiting factor for plant production. Secondary cell walls play a crucial role in plant stem strength, but whether WRKY transcription factors can positively modulate secondary cell wall thickness are remain unknown. Here, we characterized a WRKY transcription factor PlWRKY41a from herbaceous peony (Paeonia lactiflora), which was highly expressed in stems. PlWRKY41a functioned as a nucleus-localized transcriptional activator and enhanced stem strength by positively modulating secondary cell wall thickness. Moreover, PlWRKY41a bound to the promoter of the XYLOGLUCAN ENDOTRANSGLUCOSYLASE/HYDROLASE4 (PlXTH4) and activated the expression of PlXTH4. PlXTH4-overexpressing tobacco (Nicotiana tabacum) had thicker secondary cell walls, resulting in enhanced stem strength, while PlXTH4-silenced P. lactiflora had thinner secondary cell walls, showing decreased stem strength. Additionally, PlWRKY41a directly interacted with PlMYB43 to form a protein complex, and their interaction induced the expression of PlXTH4. These data support that the PlMYB43-PlWRKY41a protein complex can directly activate the expression of PlXTH4 to enhance stem strength by modulating secondary cell wall thickness in P. lactiflora. The results will enhance our understanding of the formation mechanism of stem strength and provide a candidate gene to improve stem straightness in plants.

Arabidopsis membrane protein AMAR1 interaction with type III effector XopAM triggers a hypersensitive response.

The efficient infection of plants by the bacteria Xanthomonas campestris pv. campestris (Xcc) depends on its type III effectors (T3Es). Although the functions of AvrE family T3Es have been reported in some bacteria, the member XopAM in Xcc has not been studied. As XopAM has low sequence similarity to reported AvrE-T3Es and different reports have shown that these T3Es have different targets in hosts, we investigated the functions of XopAM in the Xcc-plant interaction. Deletion of xopAM from Xcc reduced its virulence in cruciferous crops but increased virulence in Arabidopsis (Arabidopsis thaliana) Col-0, indicating that XopAM may perform opposite functions depending on the host species. We further found that XopAM is a lipase that may target the cytomembrane and that this activity might be enhanced by its membrane-targeted protein XOPAM-ACTIVATED RESISTANCE 1 (AMAR1) in Arabidopsis Col-0. The binding of XopAM to AMAR1 induced an intense hypersensitive response that restricted Xcc proliferation. Our results showed that the roles of XopAM in Xcc infection are not the same as those of other AvrE-T3Es, indicating that the functions of this type of T3E have differentiated during long-term bacterium‒host interactions.

Early adopters of doxycycline as post-exposure prophylaxis to prevent bacterial sexually transmitted infections in a real-world clinical setting.

OBJECTIVES: Doxycycline as post-exposure prophylaxis (DoxyPEP) is a novel prevention approach which has demonstrated efficacy in preventing bacterial sexually transmitted infections (STIs) in men who have sex with men (MSM) and transgender women (TGW) including people who are living with HIV and those on HIV pre-exposure prophylaxis (PrEP). We evaluated patient knowledge and interest in DoxyPEP, as well as early adopters of its use. METHODS: In 2023, patients presenting for HIV and STI services at a primary care and sexual health clinic were asked about DoxyPEP knowledge, interest and use. Bivariate and multivariate analyses were used to evaluate demographics and behaviours associated with these outcomes. RESULTS: A total of n=421 people presented for care. Of these, 314 were MSM/TGW. Fifteen percent were Black/African-American, and 21% were Hispanic/Latino. A total of 50% of MSM/TGW had heard of DoxyPEP, 49% were interested and 18% reported prior DoxyPEP use. Having a history of STI infection ever (adjusted OR (aOR) 5.95, 95% CI 2.69 to 13.13) and in the past 12 months (aOR 2.99, 95% CI 1.56 to 5.72) were both associated with DoxyPEP use. Individuals who had ever used HIV PrEP had nearly three times the odds of ever taking DoxyPEP (aOR 2.88, 95% CI 1.56 to 5.30). There was no association between the use of DoxyPEP and race, ethnicity or HIV status. CONCLUSIONS: Among MSM and TGW, there is already significant awareness, interest and use of DoxyPEP to prevent bacterial STIs. Public health efforts should focus on improving access and delivery of this STI prevention intervention to MSM and TGW.

Implementation of Point of Care Sexually Transmitted Infections Testing in a Community Clinic Setting.

ABSTRACT: The rates of sexually transmitted infections (STIs) in the United States, including chlamydia and gonorrhea, are rising. Point-of-care (POC) testing could increase access to testing and treatment. This evaluation found POC STI testing to be concordant with the results of traditional laboratory testing for 100% of patients who were tested. Ninety-five percent of the patients reported being satisfied with the experience, and 66% preferred it to traditional laboratory testing. The most commonly reported reason for preferring the test was the short amount of time it took to receive results. However, insurance reimbursed less than 30% of what was billed for the POC tests. Low insurance reimbursement rates could be a barrier to implementation long-term financial sustainability of POC STI testing.

A retrospective study of mineral and bone disorder in kidney transplant recipients: Single-center experience.

BACKGROUND: The status of mineral and bone disorder (MBD) after kidney transplantation is not fully understood, and the assessment of abnormal mineral and bone metabolism in kidney transplant recipients (KTRs) has not been standardized. MATERIALS AND METHODS: We performed a retrospective analysis of 292 KTRs in our center. The levels of biochemical markers of bone metabolism and bone mineral density (BMD) were assessed. We evaluated the influencing factors of BMD using linear regression analysis. And correlation test was used for the correlation analysis between bone metabolism indicators and other indicators. RESULTS: Postoperative MBD mainly manifested as hypercalcemia (8.9%), hypophosphatemia (27.1%), low levels of 25-hydroxyvitamin D(25(OH)vitD) (67.0%), hyperparathyroidism (50.6%), and high levels of bone turnover markers (BTMs). The prevalence of osteopenia/osteoporosis in the femoral neck (FN) and lumbar spine (LS) was 20.1%/2.8% and 26.1%/3.6%, respectively. Multivariate analysis indicated that FN BMD was positively associated with body mass index (BMI) and negatively associated with acute rejection history (p < 0.05); while LS BMD was positively associated with BMI, and negatively associated with intact parathyroid hormone (iPTH) (p < 0.05). Biochemical markers of bone metabolism were affected by age, sex, preoperative dialysis mode and time, postoperative time, transplanted kidney function, and iPTH levels. LS BMD was negatively correlated with iPTH and BTMs (p < 0.05). CONCLUSION: MBD persisted after kidney transplantation. Decreased bone mass was associated with persistent hyperparathyroidism, acute rejection history, low BMI, advanced age, and menopause. Dynamic monitoring of bone metabolism index and BMD helps to assess MBD after kidney transplantation.

Pgam5 aggravates hyperglycemia-induced myocardial dysfunction through disrupting Phb2-dependent mitochondrial dynamics.

This study aims to elucidate the roles of Phosphoglycerate Mutase Family Member 5 (Pgam5) and Prohibitin 2 (Phb2) in the context of hyperglycemia-induced myocardial dysfunction, a critical aspect of diabetic cardiomyopathy. The research employed primary cardiomyocytes, which were then subjected to hyperglycemia treatment to mimic diabetic conditions. We used siRNA transfection to knock down Pgam5 and overexpressed Phb2 using adenovirus transfection to assess their individual and combined effects on cardiomyocyte health. Mitochondrial function was evaluated through measurements of mitochondrial membrane potential using the JC-1 probe, and levels of mitochondrial reactive oxygen species (ROS) were assessed. Additionally, the study involved qPCR analysis to quantify the transcriptional changes in genes related to mitochondrial fission and mitophagy. Our findings indicate that hyperglycemia significantly reduces cardiomyocyte viability and impairs mitochondrial function, as evidenced by decreased mitochondrial membrane potential and increased ROS levels. Pgam5 knockdown was observed to mitigate these adverse effects, preserving mitochondrial function and cardiomyocyte viability. On the molecular level, Pgam5 was found to regulate genes associated with mitochondrial fission (such as Drp1, Mff, and Fis1) and mitophagy (including Parkin, Bnip3, and Fundc1). Furthermore, overexpression of Phb2 countered the hyperglycemia-induced mitochondrial dysfunction and normalized the levels of key mitochondrial antioxidant enzymes. The combined data suggest a protective role for both Pgam5 knockdown and Phb2 overexpression against hyperglycemia-induced cellular and mitochondrial damage. The study elucidates the critical roles of Pgam5 and Phb2 in regulating mitochondrial dynamics in the setting of hyperglycemia-induced myocardial dysfunction. By modulating mitochondrial fission and mitophagy, Pgam5 and Phb2 emerge as key players in preserving mitochondrial integrity and cardiomyocyte health under diabetic conditions. These findings contribute significantly to our understanding of the molecular mechanisms underlying diabetic cardiomyopathy and suggest potential therapeutic targets for mitigating myocardial dysfunction in diabetes.

Altered Gut Microbiota as a Potential Risk Factor for Coronary Artery Disease in Diabetes: A Two-Sample Bi-Directional Mendelian Randomization Study.

The current body of research points to a notable correlation between an imbalance in gut microbiota and the development of type 2 diabetes mellitus (T2D) as well as its consequential ailment, coronary artery disease (CAD). The complexities underlying the association, especially in the context of diabetic coronary artery disease (DCAD), are not yet fully understood, and the causal links require further clarification. In this study, a bidirectional Mendelian randomization (MR) methodology was utilized to explore the causal relationships between gut microbiota, T2D, and CAD. By analyzing data from the DIAGRAM, GERA, UKB, FHS, and mibioGen cohorts and examining GWAS databases, we sought to uncover genetic variants linked to T2D, CAD, and variations in gut microbiota and metabolites, aiming to shed light on the potential mechanisms connecting gut microbiota with DCAD. Our investigation uncovered a marked causal link between the presence of Oxalobacter formigenes and an increased incidence of both T2D and CAD. Specifically, a ten-unit genetic predisposition towards T2D was found to be associated with a 6.1% higher probability of an increase in the Oxalobacteraceae family's presence (ß = 0.061, 95% CI = 0.002-0.119). In a parallel finding, an augmented presence of Oxalobacter was related to an 8.2% heightened genetic likelihood of CAD (ß = 0.082, 95% CI = 0.026-0.137). This evidence indicates a critical pathway by which T2D can potentially raise the risk of CAD via alterations in gut microbiota. Additionally, our analyses reveal a connection between CAD risk and Methanobacteria, thus providing fresh perspectives on the roles of TMAO and carnitine in the etiology of CAD. The data also suggest a direct causal relationship between increased levels of certain metabolites - proline, lysophosphatidylcholine, asparagine, and salicylurate - and the prevalence of both T2D and CAD. Sensitivity assessments reinforce the notion that changes in Oxalobacter formigenes could pose a risk for DCAD. There is also evidence to suggest that DCAD may, in turn, affect the gut microbiota's makeup. Notably, a surge in serum TMAO levels in individuals with CAD, coinciding with a reduced presence of methanogens, has been identified as a potentially significant factor for future examination.

Experimental and theoretical studies on the compatibility of DNTF and typical hydrocarbon polymer binders.

3,4-bis(3-nitrofurazan-4-yl) furoxan (DNTF) is one of the third-generation energetic compounds with excellent comprehensive properties, which can be added to polymer bonded explosive (PBX) to improve energy levels and regulate sensitivity, so the compatibility of DNTF with other components in PBX, especially the binder, is the first question. Herein, two typical hydrocarbon polymers commonly used in PBX, which are hydroxyl-terminated polybutadiene (HTPB) and polyisobutylene (PIB), were selected as the binder, and the compatibility of HTPB and PIB with DNTF was investigated by differential scanning calorimetry (DSC), the vacuum stability test (VST), and in situ infrared spectroscopy (in situ IR). The results of compatibility experiments were verified by using the binding energy and solubility parameter criteria in molecular dynamics (MD). Experimental and MD simulation results showed that DNTF could be compatible with PIB but incompatible with HTPB. The frontier molecular orbital theory in quantum chemistry (QC) was adopted to explore the frontier orbital electron distribution and energy levels of DNTF/HTPB and DNTF/PIB composite systems to better understand the microscopic compatibility mechanism. The compatibility results of the two composite systems were explained from the perspective of electron transfer. All these can deduce that a hydrocarbon polymer binder with a saturated carbon-hydrogen bond at the end of the molecular chain has good compatibility with DNTF, compared with a hydroxyl group, which has bad compatibility with DNTF.

Left ventricular remodeling and its association with mineral and bone disorder in kidney transplant recipients.

BACKGROUND: The assessment of left ventricular (LV) remodeling and its association with mineral and bone disorder (MBD) in kidney transplant recipients (KTRs) have not been systematically studied. We aimed to evaluate LV remodeling changes one year after kidney transplantation (KT) and identify their influencing factors. METHODS: Ninety-five KTRs (68 males; ages 40.2 ± 10.8 years) were followed before and one year after KT. Traditional risk factors and bone metabolism indicators were assessed. Left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF) and left ventricular diastolic dysfunction (LVDD) were measured using two-dimensional transthoracic echocardiography. The relationship between MBD and LV remodeling and the factors influencing LV remodeling were analyzed. RESULTS: One year after KT, MBD was partially improved, mainly characterized by hypercalcemia, hypophosphatemia, hyperparathyroidism, 25-(OH) vitamin D deficiency, elevated bone turnover markers, and bone loss. LVMI, the prevalence of left ventricular hypertrophy (LVH), and the prevalence of LVDD decreased, while LVEF increased. LVH was positively associated with postoperative intact parathyroid hormone (iPTH) and iPTH nonnormalization. △LVMI was positively associated with preoperative type-I collagen N-terminal peptide and postoperative iPTH. LVEF was negatively associated with postoperative phosphorous. △LVEF was negatively associated with postoperative iPTH. LVDD was positively associated with postoperative lumbar spine osteoporosis. Preoperative LVMI was negatively associated with △LVMI and positively associated with △LVEF. Advanced age, increased BMI, diabetes, longer dialysis time, lower albumin level, and higher total cholesterol and low-density lipoprotein levels were associated with LV remodeling. CONCLUSIONS: LV remodeling partially improved after KT, showing a close relationship with MBD.

High-performance Pyroelectric Property Accompanied by Spin Crossover in a Single Crystal of Fe(II) Complex.

Pyroelectric materials hold significant potential for energy harvesting, sensing, and imaging applications. However, achieving high-performance pyroelectricity across a wide temperature range near room temperature remains a significant challenge. Herein, we demonstrate a single crystal of Fe(II) spin-crossover compound shows remarkable pyroelectric properties accompanied by a thermally controlled spin transition. In this material, the uniaxial alignment of polar molecules results in a polarization of the lattice. As the molecular geometry is modulated during a gradual spin transition, the polar axis experiences a colossal thermal expansion with a coefficient of 796×10-6 K-1. Consequently, the material's polarization undergoes significant modulation as a secondary pyroelectric effect. The considerable shift in polarization (pyroelectric coefficient, p=3.7-22 nC K-1cm-2), coupled with a low dielectric constant (ϵ'=4.4-5.4) over a remarkably wide temperature range of 298 to 400 K, suggests this material is a high-performance pyroelectric. The demonstration of pyroelectricity combined with magnetic switching in this study will inspire further investigations in the field of molecular electronics and magnetism.

Molecular Twist-Induced Single-Crystal Isomerization and Valence Tautomeric Transitions in a Cobalt-Dioxolene Complex.

A mononuclear valence tautomeric (VT) complex, [Co(pycz)2(Sq)(Cat)] (1-trans), where pycz = 9-(pyridin-4-yl)-9H-carbazole, Sq⋅- = 3,5-di-tert-butyl-semiquinonato, and Cat2- = 3,5-di-tert-butyl-catecholato, is synthesized in the trans configuration, which undergoes one-step valence tautomeric transition above room temperature. Remarkably, 1-trans can transform into its isomeric structure, [Co(pycz)2(Sq)(Sq)] (1-cis), at temperature above 350 K in a single-crystal-to-single-crystal way by in situ molecular twist, and the resulting 1-cis exhibits a pronounced two-step VT transition during magnetic measurements that is rare for mononuclear VT complexes. Such drastic solid-state structural transformation is reported in VT compounds for the first time, which is actuated by a crystal surface's melting-recrystallization induced phase transition process. DFT calculations offer an underlying mechanism suggesting a concerted bond rotation during the structural transformation. The results demonstrate an unconventional approach that realizes structural transformation of VT complexes and the control of VT performance.

Inversion of Molecular Chirality Associated with Ferroelectric Switching in a High-Temperature Two-Dimensional Perovskite Ferroelectric.

Controlling molecular chirality by external stimuli is of great significance in both fundamental research and technological applications. Herein, we report a high-temperature (384 K) molecular ferroelectric of a Cu(II) complex whose spontaneous polarization can be switched associated with flipping of molecular chirality. In this two-dimensional perovskite structure, the inorganic layer is separated by (NH3(CH2)2SS(CH2)2NH3)2+ organic cations skewed in a chiral conformation (P- or M-helicity in an individual crystal). As the stereodynamic disulfide bridge determines the molecular dipole moment along the polar axis, the chiral organic cation can be converted to its enantiomer as a consequence of an electric field-induced shift of the S-S moiety relative to its screw axis during the ferroelectric switching. The variation of the molecular chirality is examined with single-crystal X-ray diffraction and circular dichroism spectra. The simultaneous switching of molecular chirality and spontaneous polarization in this perovskite ferroelectric may lead to novel chiral electronic phenomena.

Unraveling the mechanism of ceftaroline-induced allosteric regulation in penicillin-binding protein 2a: insights for novel antibiotic development against methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) acquires high-level resistance against ß-lactam antibiotics by expressing penicillin-binding protein 2a (PBP2a). PBP2a is a cell wall-synthesizing protein whose closed active site exhibits a reduced binding affinity toward ß-lactam antibiotics. Ceftaroline (CFT), a fifth-generation cephalosporin, can effectively inhibit the PBP2a activity by binding to an allosteric site to trigger the active site opening, allowing a second CFT to access the active site. However, the essential mechanism behind the allosteric behavior of PBP2a remains unclear. Herein, computational simulations are employed to elucidate how CFT allosterically regulates the conformation and dynamics of the active site of PBP2a. While CFT stabilizes the allosteric domain surrounding it, it simultaneously enhances the dynamics of the catalytic domain. Specifically, the study successfully captured the opening process of the active pocket in the allosteric CFT-bound systems and discovered that CFT alters the potential signal-propagating pathways from the allosteric site to the active site. These findings reveal the implied mechanism of the CFT-mediated allostery in PBP2a and provide new insights into dual-site drug design or combination therapy against MRSA targeting PBP2a.

Andrographolide improves the dysfunction of endothelial progenitor cells from angiotensin II-induced hypertensive mice through SIRT1 signaling.

Endothelial progenitor cells (EPCs) are crucial for the maintenance of vascular homeostasis. The dysfunction of EPCs contributes to the endothelial damage in hypertension. Andrographolide (AGP) is a traditional Chinese patent medicine that has been reported to have protective effects on cardiovascular system. However, the effect of AGP on the function of EPCs in hypertension remains unknown. In this study, we aimed to elucidate the effect of AGP on EPCs and the underlying mechanisms. In vivo, the blood pressure and endothelial function (indicated by endothelial dependent vasodilation) of AGP-fed angiotensin II (Ang II)-infused hypertensive mice were examined. In vitro, the function of EPCs isolated from bone marrow were evaluated by tube formation, migration, and adhesion assay. Additionally, a silent information regulator 1 (SIRT1) inhibitor/agonist and a small interfering RNA (si-RNA) targeting SIRT1 were used to determine the pathway involved. The results showed that AGP not only reduced blood pressure, improved endothelial function in hypertensive mice but also restored the dysfunction of EPCs of hypertension in vitro. Mechanistically, AGP up-regulated SIRT1 expression, decreased the Bax/Bcl-2 ratio and the expression level of Cleaved caspase-3, thus inhibiting the apoptosis of Ang II induced EPCs. However, the beneficial effects of AGP on EPCs disappeared after the inhibition or the knockdown of SIRT1. To summarize, this study demonstrates for the first time that AGP improves the dysfunction of EPCs through SIRT1-mediated anti-apoptotic effects. Our findings might provide a novel therapeutic strategy for treating vascular damage in hypertension.

Intermediate complex morphophysiological dormancy in seeds of Aconitum barbatum (Ranunculaceae).

BACKGROUND: Seed dormancy and germination are key components of plant regeneration strategies. Aconitum barbatum is a plant commonly found in northeast China. Although it has potential for use in gardening and landscaping, its seed dormancy and regeneration strategy, which adapt to its natural habitat, are not well understood. Our aim was to identify conditions for breaking A. barbatum seed dormancy and determine its dormancy type. Embryo growth and germination were determined by collecting seeds over time in the field. Laboratory experiments that control light, temperature, and stratification period were conducted to assess dormancy breaking and germination, and GA3 was used to identify dormancy type. RESULTS: Seeds of A. barbatum have undeveloped embryos with physiological dormancy at maturity in autumn. The embryo-to-seed length ratio increases from 0.33 to 0.78 before the emergence of the radical. Under natural environmental conditions, embryo development begins in early winter. Laboratory experiments have shown that long-term incubation under 4 °C (cold stratification) promotes embryo development and seed dormancy break. With an extension of cold stratification, an increase in germination percentages was observed when seeds were transferred from 4 °C to warmer temperatures. Seeds exposed to light during incubation show a higher germination percentage than those kept in the dark. Seed germination can also be enhanced by a 100 mg/L GA3 concentration. CONCLUSIONS: Seeds of A. barbatum display intermediate complex morphophysiological dormancy at maturity. In addition to the underdeveloped embryo, there are also physiological barriers that prevent the embryo from germinating. Dormancy breaking of A. barbatum seeds can be achieved by natural winter cold stratification, allowing seeds to germinate and sprout seedlings at the beginning of the following growing season. Our findings provide valuable insights into the seed dormancy and regeneration strategy of A. barbatum, which could facilitate its effective utilization in gardening and landscaping.

An Evaluation of Gene-Diet Interaction Statistical Methods and Discovery of rs7175421-Whole Grain Interaction in Lung Cancer.

Dietary factors show different effects on genetically diverse populations. Scientific research uses gene-environment interaction models to study the effects of dietary factors on genetically diverse populations for lung cancer risk. However, previous study designs have not investigated the degree of type I error inflation and, in some instances, have not corrected for multiple testing. Using a motivating investigation of diet-gene interaction and lung cancer risk, we propose a training and testing strategy and perform real-world simulations to select the appropriate statistical methods to reduce false-positive discoveries. The simulation results show that the unconstrained maximum likelihood (UML) method controls the type I error better than the constrained maximum likelihood (CML). The empirical Bayesian (EB) method can compete with the UML method in achieving statistical power and controlling type I error. We observed a significant interaction between SNP rs7175421 with dietary whole grain in lung cancer prevention, with an effect size (standard error) of -0.312 (0.112) for EB estimate. SNP rs7175421 may interact with dietary whole grains in modulating lung cancer risk. Evaluating statistical methods for gene-diet interaction analysis can help balance the statistical power and type I error.

Tree peony PsMYB44 negatively regulates petal blotch distribution by inhibiting dihydroflavonol-4-reductase gene expression.

BACKGROUND AND AIMS: The tree peony (Paeonia suffruticosa Andr.) has been widely cultivated as a field plant, and petal blotch is one of its important traits, which not only promotes proliferation but also confers high ornamental value. However, the regulatory network controlling blotch formation remains elusive owing to the functional differences and limited conservation of transcriptional regulators in dicots. METHODS: We performed phylogenetic analysis to identify MYB44-like transcription factors in P. suffruticosa blotched cultivar 'High noon' petals. A candidate MYB44-like transcription factor, PsMYB44, was analysed via expression pattern analysis, subcellular localization, target gene identification, gene silencing in P. suffruticosa petals and heterologous overexpression in tobacco. KEY RESULTS: A blotch formation-related MYB44-like transcription factor, PsMYB44, was cloned. The C-terminal of the PsMYB44 amino acid sequence had a complete C2 motif that affects anthocyanin biosynthesis, and PsMYB44 was clustered in the MYB44-like transcriptional repressor branch. PsMYB44 was located in the nucleus, and its spatial and temporal expression patterns were negatively correlated with blotch formation. Furthermore, a yeast one-hybrid assay showed that PsMYB44 could target the promoter of the late anthocyanin biosynthesis-related dihydroflavonol-4-reductase (DFR) gene, and a dual-luciferase assay demonstrated that PsMYB44 could repress PsDFR promoter activity. On the one hand, overexpression of PsMYB44 significantly faded the red colour of tobacco flowers and decreased the anthocyanin content by 42.3 % by downregulating the expression level of the tobacco NtDFR gene. On the other hand, PsMYB44-silenced P. suffruticosa petals had a redder blotch colour, which was attributed to the fact that silencing PsMYB44 redirected metabolic flux to the anthocyanin biosynthesis branch, thereby promoting more anthocyanin accumulation in the petal base. CONCLUSION: These results demonstrated that PsMYB44 negatively regulated the biosynthesis of anthocyanin by directly binding to the PsDFR promoter and subsequently inhibiting blotch formation, which helped to elucidate the molecular regulatory network of anthocyanin-mediated blotch formation in plants.