Design, Synthesis, and Biological Evaluation of Pyridazinone-Containing Derivatives As Novel Protoporphyrinogen IX Oxidase Inhibitor.

Protoporphyrinogen IX oxidase (PPO, E.C. 1.3.3.4) plays a pivotal role in chlorophyll biosynthesis in plants, making it a prime target for herbicide development. In this study, we conducted an investigation aimed at discovering PPO-inhibiting herbicides. Through this endeavor, we successfully identified a series of novel compounds based on the pyridazinone scaffold. Following structural optimization and biological assessment, compound 10ae, known as ethyl 3-((6-fluoro-5-(6-oxo-4-(trifluoromethyl)pyridazin-1(6H)-yl)benzo[d]thiazol-2-yl)thio)propanoate, emerged as a standout performer. It exhibited robust activity against Nicotiana tabacum PPO (NtPPO) with an inhibition constant (Ki) value of 0.0338 µM. Concurrently, we employed molecular simulations to obtain further insight into the binding mechanism with NtPPO. Additionally, another compound, namely, ethyl 2-((6-fluoro-5-(5-methyl-6-oxo-4-(trifluoromethyl)pyridazin-1(6H)-yl)benzo[d]thiazol-2-yl)thio)propanoate (10bh), demonstrated broad-spectrum and highly effective herbicidal properties against all six tested weeds (Leaf mustard, Chickweed, Chenopodium serotinum, Alopecurus aequalis, Poa annua, and Polypogon fugax) at the dosage of 150 g a.i./ha through postemergence application in a greenhouse. This work identified a novel lead compound (10bh) that showed good activity in vitro and excellent herbicidal activity in vivo and had promising prospects as a new PPO-inhibiting herbicide lead.

Ligand-controlled exposure of active sites on the Pd1Ag14 nanocluster surface to boost electrocatalytic CO2 reduction.

Advancing catalyst design requires meticulous control of nanocatalyst selectivity at the atomic level. Here, we synthesized two Pd1Ag14 nanoclusters: Pd1Ag14(PPh3)8(SPh(CF3)2)6 and Pd1Ag14(P(Ph-p-OMe)3)7(SPh)6, each with well-defined structures. Notably, in Pd1Ag14(P(Ph-p-OMe)3)7(SPh)6, the detachment of a phosphine ligand from the top silver atom facilitates the exposure of singular active sites. This exposure significantly enhances its selectivity for the electrocatalytic reduction of CO2 to CO, achieving a Faraday efficiency of 83.3% at -1.3 V, markedly surpassing the 28.1% performance at -1.2 V of Pd1Ag14(PPh3)8(SPh(CF3)2)6. This work underscores the impact of atomic-level structural manipulation on enhancing nanocatalyst performance.

Synthesis and Biological Activity Evaluation of Benzoxazinone-Pyrimidinedione Hybrids as Potent Protoporphyrinogen IX Oxidase Inhibitor.

Protoporphyrinogen IX oxidase (PPO/Protox, E.C. 1.3.3.4) is recognized as one of the most important targets for herbicide discovery. In this study, we report our ongoing research efforts toward the discovery of novel PPO inhibitors. Specifically, we identified a highly potent new compound series containing a pyrimidinedione moiety and bearing a versatile building block-benzoxazinone scaffold. Systematic bioassays resulted in the discovery of compound 7af, ethyl 4-(7-fluoro-6-(3-methyl-2,6-dioxo-4-(trifluoromethyl)-3,6-dihydropyrimidin-1(2H)-yl)-3-oxo-2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)butanoate, which exhibited broad-spectrum and excellent herbicidal activity at the dosage of 37.5 g a.i./ha through postemergence application. The inhibition constant (Ki) value of 7af to Nicotiana tabacum PPO (NtPPO) was 14 nM, while to human PPO (hPPO), it was 44.8 µM, indicating a selective factor of 3200, making it the most selective PPO inhibitor to date. Moreover, molecular simulations further demonstrated the selectivity and the binding mechanism of 7af to NtPPO and hPPO. This study not only identifies a candidate that showed excellent in vivo bioactivity and high safety toward humans but also provides a paradigm for discovering PPO inhibitors with improved performance through molecular simulation and structure-guided optimization.

Discovery of a Subnanomolar Inhibitor of Protoporphyrinogen IX Oxidase via Fragment-Based Virtual Screening.

Protoporphyrinogen IX oxidase (PPO, E.C. 1.3.3.4), a key functional enzyme existing in various organisms, is acknowledged to be one of the most important action targets in the development of herbicides due to its pivotal roles in chlorophyll and heme biosynthesis pathways. As our persistent research work on the discovery of novel PPO-inhibiting herbicides, a new compound methyl 2-((5-(3-chloro-4,5,6,7-tetrahydro-2H-indazol-2-yl)-6-fluorobenzo[d]thiazol-2-yl)thio)acetate (8aj, Ki = 16 nM) was screened out as a hit compound via a fragment-based virtual screening method performed in the Auto Core Fragment in silico Screening web server. Subsequently, through a fused process of "hit-to-lead" optimization guided by molecular simulation, a total of 30 3-chloro-4,5,6,7-tetrahydro-2H-indazol-benzo[d]thiazole derivatives were synthesized and characterized. The results of the enzymatic inhibition bioassay showed that more than half of the newly synthesized compounds displayed higher activity against Nicotiana tabacum PPO (NtPPO) than oxadiazon, a commercial PPO-inhibiting herbicide. In particular, compound 8ab, a subnanomolar inhibitor with a Ki value of 380 pM against NtPPO, was discovered, which showed to be 71-fold more active than the commercial control oxadiazon (Ki = 27 nM), and was proven to be the most potent PPO inhibitor so far. Furthermore, the greenhouse assay demonstrated that most of the synthetic compounds showed good herbicidal activity toward the tested weeds. Especially, compound 8ad (Ki = 670 pM) showed the most promising post-emergence herbicidal activity with a broad spectrum of weed control even at a concentration as low as 37.5 g a.i./ha and relatively safe to rice at a dosage of 150 g a.i./ha, indicating that 8ad has the greatest potential to be developed as a new herbicide for weed control in paddy fields. This work provides a paradigm for the rational design and discovery of a novel PPO-inhibiting herbicide guided by the fragment-based drug design.

Squat Detection of Railway Switches and Crossings Using Point Machine Vibration Measurements.

Railway switches and crossings (S&C) are among the most important high-value components in a railway network and a failure of such an asset could result in severe network disturbance. Therefore, potential defects need to be detected at an early stage to prevent traffic-disturbing downtime or even severe accidents. A squat is a common defect of S&Cs that has to be monitored and repaired to reduce such risks. In this study, a testbed including a full-scale S&C and a bogie wagon was developed. Vibrations were measured for different squat sizes by an accelerometer mounted at the point machine. A method of processing the vibration data and the speed data is proposed to investigate the possibility of detecting and quantifying the severity of a squat. One key technology used is wavelet denoising. The study shows that it is possible to monitor the development of the squat size on the rail up to around 13 m from the point machine. The relationships between the normalised peak-to-peak amplitude of the vibration signal and the squat depth were also estimated.

Multiplexed Target Enrichment Enables Efficient and In-Depth Analysis of Antimicrobial Resistome in Metagenomes.

Antibiotic resistance genes (ARGs) pose a serious threat to public health and ecological security in the 21st century. However, the resistome only accounts for a tiny fraction of metagenomic content, which makes it difficult to investigate low-abundance ARGs in various environmental settings. Thus, a highly sensitive, accurate, and comprehensive method is needed to describe ARG profiles in complex metagenomic samples. In this study, we established a high-throughput sequencing method based on targeted amplification, which could simultaneously detect ARGs (n = 251), mobile genetic element genes (n = 8), and metal resistance genes (n = 19) in metagenomes. The performance of amplicon sequencing was compared with traditional metagenomic shotgun sequencing (MetaSeq). A total of 1421 primer pairs were designed, achieving extremely high coverage of target genes. The amplicon sequencing significantly improved the recovery of target ARGs (~9 × 104-fold), with higher sensitivity and diversity, less cost, and computation burden. Furthermore, targeted enrichment allows deep scanning of single nucleotide polymorphisms (SNPs), and elevated SNPs detection was shown in this study. We further performed this approach for 48 environmental samples (37 feces, 20 soils, and 7 sewage) and 16 clinical samples. All samples tested in this study showed high diversity and recovery of targeted genes. Our results demonstrated that the approach could be applied to various metagenomic samples and served as an efficient tool in the surveillance and evolution assessment of ARGs. Access to the resistome using the enrichment method validated in this study enabled the capture of low-abundance resistomes while being less costly and time-consuming, which can greatly advance our understanding of local and global resistome dynamics. IMPORTANCE ARGs, an increasing global threat to human health, can be transferred into health-related microorganisms in the environment by horizontal gene transfer, posing a serious threat to public health. Advancing profiling methods are needed for monitoring and predicting the potential risks of ARGs in metagenomes. Our study described a customized amplicon sequencing assay that could enable a high-throughput, targeted, in-depth analysis of ARGs and detect a low-abundance portion of resistomes. This method could serve as an efficient tool to assess the variation and evolution of specific ARGs in the clinical and natural environment.

Development of an unsupervised cycle contrastive unpaired translation network for MRI-to-CT synthesis.

PURPOSE: The purpose of this work is to develop and evaluate a novel cycle-contrastive unpaired translation network (cycleCUT) for synthetic computed tomography (sCT) generation from T1-weighted magnetic resonance images (MRI). METHODS: The cycleCUT proposed in this work integrated the contrastive learning module from contrastive unpaired translation network (CUT) into the cycle-consistent generative adversarial network (cycleGAN) framework to effectively achieve unsupervised CT synthesis from MRI. The diagnostic MRI and radiotherapy planning CT images of 24 brain cancer patients were obtained and reshuffled to train the network. For comparison, the traditional cycleGAN and CUT were also implemented. The sCT images were then imported into a treatment planning system to verify their feasibility for radiotherapy planning. The mean absolute error (MAE), peak signal-to-noise ratio (PSNR), and structural similarity index (SSIM) between the sCT and the corresponding real CT images were calculated. Gamma analysis between sCT- and CT-based dose distributions was also conducted. RESULTS: Quantitative evaluation of an independent test set of six patients showed that the average MAE was 69.62 ± 5.68 Hounsfield Units (HU) for the proposed cycleCUT, significantly (p-value < 0.05) lower than that for cycleGAN (77.02 ± 6.00 HU) and CUT (78.05 ± 8.29). The average PSNR was 28.73 ± 0.46 decibels (dB) for cycleCUT, significantly larger than that for cycleGAN (27.96 ± 0.49 dB) and CUT (27.95 ± 0.69 dB). The average SSIM for cycleCUT (0.918 ± 0.012) was also significantly higher than that for cycleGAN (0.906 ± 0.012) and CUT (0.903 ± 0.015). Regarding gamma analysis, cycleCUT achieved the highest passing rate (97.95 ± 1.24% at the 2%/2 mm criteria and 10% dose threshold) but was not significantly different from the others. CONCLUSION: The proposed cycleCUT could be effectively trained using unaligned image data, and could generate better sCT images than cycleGAN and CUT in terms of HU number accuracy and fine structural details.

Squat Detection of Railway Switches and Crossings Using Wavelets and Isolation Forest.

Railway switches and crossings (S&Cs) are critical, high-value assets in railway networks. A single failure of such an asset could result in severe network disturbance and considerable economical losses. Squats are common rail surface defects of S&Cs and need to be detected and estimated at an early stage to minimise maintenance costs and increase the reliability of S&Cs. For practicality, installation of wired or wireless sensors along the S&C may not be reliable due to the risk of damages of power and signal cables or sensors. To cope with these issues, this study presents a method for collecting and processing vibration data from an accelerometer installed at the point machine to extract features related to the squat defects of the S&C. An unsupervised anomaly-detection method using the isolation forest algorithm is applied to generate anomaly scores from the features. Important features are ranked and selected. This paper describes the procedure of parameter tuning and presents the achieved anomaly scores. The results show that the proposed method is effective and that the generated anomaly scores indicate the health status of an S&C regarding squat defects.

Quantitative x-ray fluorescence imaging system for non-destructive 3D tumor histology.

An in-house dual-modality x-ray fluorescence tomography (XFT) and x-ray computed tomography (XCT) system was developed to quantify iodine contrast distribution through the whole tumor volume ex vivo. The quantitative XFT was calibrated with water phantoms containing iodine solutions of various concentrations (0.0175-1.4 wt.%). The vasculature distribution was reflected by the iodine perfusion, which was validated with histology. This technique may open a new, to the best of our knowledge, route to the non-destructive three-dimensional-imaging-based histological analysis of tumor samples.

Contrast-Enhanced Cone-Beam Breast CT: An Analysis of Diagnostic Value in Predicting Breast Lesion With Rim Enhancement Malignancy.

Background: The objective of the current study was to investigate the diagnostic value of contrast-enhanced cone-beam breast computed tomography (CE-CBBCT) for breast lesion with rim enhancement (RE). Methods: All 36 patients were examined by non-contrast (NC-CBBCT) and contrast-enhanced CBBCT (CE-CBBCT) after contrast media (CM) injection. Qualitative morphological enhancement parameters and quantitative enhancement parameters were compared between malignant and benign groups. Multivariable logistic regression analysis was performed to identify independent factors that could predict breast lesion with RE malignancy. Receiver operating curve (ROC) was used to evaluate prediction performance. Results: A total of 36 patients with 40 lesions underwent breast CE-CBBCT were enrolled. There were significant differences in most qualitative morphological enhancement parameters between the two groups. A multivariate logistic regression model showed that △standardized HU (INRphase 2-INRpreCM) [odds ratio (OR) = 1.148, 95% CI = 1.034-1.276, p = 0.01] and △standardized HU (RPphase 2 - RPphase 1) (OR = 0.891, 95% CI = 0.814-0.976, p = 0.013) were independent indicators in predicting breast lesion with RE malignancy. △standardized HU (INRphase 2 - INRpreCM) combined with △standardized HU (RPphase 2 - RPphase 1) showed significant larger area under the receiver operating curve (AUC) and higher sensitivity than each alone (p < 0.001, AUC = 0.932, sensitivity = 92.59%, specificity = 92.31%). The regression equation of the prediction model was as follows: Logit (p) = 0.351 + 0.138X × â–³standardized HU (INRphase 2 - INRpreCM) - 0.115 × â–³standardized HU (RPphase 2 - RPphase 1). Conclusion: With the observation of qualitative morphological enhancement parameters and the comparison of quantitative enhancement parameters of CBBCT, a reliable basis for the diagnostic accuracy in predicting breast lesion with RE could be provided. These conclusions should be verified in large, well-designed studies.

Multiparametric cardiac18F-FDG PET in humans: pilot comparison of FDG delivery rate with82Rb myocardial blood flow.

Myocardial blood flow (MBF) and flow reserve are usually quantified in the clinic with positron emission tomography (PET) using a perfusion-specific radiotracer (e.g.82Rb-chloride). However, the clinical accessibility of existing perfusion tracers remains limited. Meanwhile,18F-fluorodeoxyglucose (FDG) is a commonly used radiotracer for PET metabolic imaging without similar limitations. In this paper, we explore the potential of18F-FDG for myocardial perfusion imaging by comparing the myocardial FDG delivery rateK1with MBF as determined by dynamic82Rb PET in fourteen human subjects with heart disease. Two sets of FDGK1were derived from one-hour dynamic FDG scans. One was the original FDGK1estimates and the other was the correspondingK1values that were linearly normalized for blood glucose levels. A generalized Renkin-Crone model was used to fit FDGK1with Rb MBF, which then allowed for a nonlinear extraction fraction correction for converting FDGK1to MBF. The linear correlation between FDG-derived MBF and Rb MBF was moderate (r= 0.79) before the glucose normalization and became much improved (r> 0.9) after glucose normalization. The extraction fraction of FDG was also similar to that of Rb-chloride in the myocardium. The results from this pilot study suggest that dynamic cardiac FDG-PET with tracer kinetic modeling has the potential to provide MBF in addition to its conventional use for metabolic imaging.

Observation of void formation patterns in SnAg films undergoing electromigration and simulation using random walk methods.

With the ever-reducing sizes of electronic devices, the problem of electromigration (EM) has become relevant and requires attention. However, only the EM behavior of Sn-Ag solders within the solder joint structure has been focused on thus far. Therefore, in this study, a thin metallic film composed of Sn-3.5Ag (wt.%) was subjected to a current density of 7.77 × 104 A/cm2 at a temperature of 15 °C to test the ability of existing EM models to predict the nucleation and evolution of voids generated by the resulting atomic migration. A computer simulation was then used to compute the coupled current distribution, thermal distribution, and atomic migration problems. It relied on an original random walk (RW) method, not previously applied to this problem, that is particularly well suited for modelling domains that undergo changes owing to the formation of voids. A comparison of the experimental results and computer simulations proves that the RW method can be applied successfully to this class of problems, but it also shows that imperfections in the film can lead to deviations from predicted patterns.

The complete chloroplast genome of Polygala japonica Houtt. (Polygalaceae), a medicinal plant in China.

Polygala japonica Houtt. (Polygalaceae) is a perennial herbaceous plant widely distributed in south China. Here, we assembled and characterized the complete chloroplast (cp) genome of P. japonica using sequencing data. The complete cp genome of P. japonica was 165,439 bp in length, with a GC content of 36.7%. The complete cp genome shows a typical quadripartite structure with a pair of inverted repeats (IRs) of 36,786 bp, separated by a large single copy region (LSC) of 83,722 bp, and a small single copy region (SSC) of 8,145 bp. A total of 135 genes were annotated in the cp genome of P. japonica, consisting of 89 protein-coding genes, 8 rRNA genes, and 38 tRNA genes. The phylogenetic analysis showed P. japonica had a closer relationship with P. tenuifolia.

Comparable survival outcome between transplantation from haploidentical donor and matched related donor or unrelated donor for severe aplastic anemia patients aged 40 years and older: A retrospective multicenter cohort study.

This retrospective multicenter cohort study aimed to compare the outcome of haploidentical hematopoietic stem cell transplantation (HID-HSCT) with matched sibling donor (MSD) and unrelated donor (URD) transplantation in severe aplastic anemia (SAA) patients 40 years of age and older. With a median follow-up time of 17.6 months, 85 consecutive patients were enrolled in the study, and the median patient age was 45 years (40, 58). The cumulative engraftment rates of neutrophil and platelet were 98.8 ± 0.0% and 92.9 ± 0.1%. The cumulative incidences of Grade 2-4 acute graft-versus-host disease (aGvHD) and chronic graft-versus-host disease (cGvHD) at 3 years were 14.1 ± 0.1% and 17.3 ± 0.2%. The 3-year estimated overall survival (OS) and failure-free survival (FFS) were 91.2 ± 3.2% and 89.7 ± 3.5%. In multivariate analysis, the only factor associated with inferior survival was an ECOG score ≥2. HID-HSCT was associated with a higher incidence of GvHD, but the difference of 3-year estimated OS between HID group and the other two cohorts was not significant (86.7 ± 6.4% for HID vs 92.1% ± 4.4% for MSD and 100% for URD, P = .481). HID-HSCT might be a feasible alternative option for selected SAA patients aged 40 years and older without a matched donor.

Multiparametric Cardiac 18F-FDG PET in Humans: Kinetic Model Selection and Identifiability Analysis.

Cardiac 18F-FDG PET has been used in clinics to assess myocardial glucose metabolism. Its ability for imaging myocardial glucose transport, however, has rarely been exploited in clinics. Using the dynamic FDG-PET scans of ten patients with coronary artery disease, we investigate in this paper appropriate dynamic scan and kinetic modeling protocols for efficient quantification of myocardial glucose transport. Three kinetic models and the effect of scan duration were evaluated by using statistical fit quality, assessing the impact on kinetic quantification, and analyzing the practical identifiability. The results show that the kinetic model selection depends on the scan duration. The reversible two-tissue model was needed for a one-hour dynamic scan. The irreversible two-tissue model was optimal for a scan duration of around 10-15 minutes. If the scan duration was shortened to 2-3 minutes, a one-tissue model was the most appropriate. For global quantification of myocardial glucose transport, we demonstrated that an early dynamic scan with a duration of 10-15 minutes and irreversible kinetic modeling was comparable to the full one-hour scan with reversible kinetic modeling. Myocardial glucose transport quantification provides an additional physiological parameter on top of the existing assessment of glucose metabolism and has the potential to enable single tracer multiparametric imaging in the myocardium.

Structural and practical identifiability of dual-input kinetic modeling in dynamic PET of liver inflammation.

Dynamic 18F-FDG PET with tracer kinetic modeling has the potential to noninvasively evaluate human liver inflammation using the FDG blood-to-tissue transport rate K 1. Accurate kinetic modeling of dynamic liver PET data and K 1 quantification requires the knowledge of dual-blood input function from the hepatic artery and portal vein. While the arterial input function can be derived from the aortic region on dynamic PET images, it is difficult to extract the portal vein input function accurately from PET images. The optimization-derived dual-input kinetic modeling approach has been proposed to overcome this problem by jointly estimating the portal vein input function and FDG tracer kinetics from time activity curve fitting. In this paper, we further characterize the model properties by analyzing the structural identifiability of the model parameters using the Laplace transform and practical identifiability using computer simulation based on fourteen patient datasets. The theoretical analysis has indicated that all the kinetic parameters of the dual-input kinetic model are structurally identifiable, though subject to local solutions. The computer simulation results have shown that FDG K 1 can be estimated reliably in the whole-liver region of interest with reasonable bias, standard deviation, and high correlation between estimated and original values, indicating of practical identifiability of K 1. The result has also demonstrated the correlation between K 1 and histological liver inflammation scores is reliable. FDG K 1 quantification by the optimization-derived dual-input kinetic model is promising for assessing liver inflammation.

Relative Patlak plot for dynamic PET parametric imaging without the need for early-time input function.

The Patlak graphical method is widely used in parametric imaging for modeling irreversible radiotracer kinetics in dynamic PET. The net influx rate of radiotracer can be determined from the slope of the Patlak plot. The implementation of the standard Patlak method requires the knowledge of full-time input function from the injection time until the scan end time, which presents a challenge for use in the clinic. This paper proposes a new relative Patlak plot method that does not require early-time input function and therefore can be more efficient for parametric imaging. Theoretical analysis proves that the effect of early-time input function is a constant scaling factor on the Patlak slope estimation. Thus, the parametric image of the slope of the relative Patlak plot is related to the parametric image of standard Patlak slope by a global scaling factor. This theoretical finding has been further demonstrated by computer simulation and real patient data. The study indicates that parametric imaging of the relative Patlak slope can be used as a substitute of parametric imaging of standard Patlak slope for tasks that do not require absolute quantification, such as lesion detection and tumor volume segmentation.

Computational Discovery of Potent and Bioselective Protoporphyrinogen IX Oxidase Inhibitor via Fragment Deconstruction Analysis.

Tuning the binding selectivity through appropriate ways is a primary goal in the design and optimization of a lead toward agrochemical discovery. However, how to achieve rational design of selectivity is still a big challenge. Herein, we developed a novel computational fragment generation and coupling (CFGC) strategy that led to a series of highly potent and bioselective inhibitors targeting protoporphyrinogen IX oxidase. This enzyme plays a vital role in heme and chlorophyll biosynthesis, which has been proven to be associated with many drugs and agrochemicals. However, existing agrochemicals are nonbioselective, resulting in a great threat to nontargeted organisms. To the best of our knowledge, this is the first bioselective inhibitor targeting the tetrapyrrole biosynthesis pathway. In addition, the candidate showed excellent in vivo bioactivity and much better safety toward humans.

The Divergence of Flowering Time Modulated by FT/TFL1 Is Independent to Their Interaction and Binding Activities.

FLOWERING LOCUS T (FT) and TERMINAL FLOWER1 (TFL1) proteins share highly conserved amino acid residues but they play opposite regulatory roles in promoting and repressing the flowering response, respectively. Previous substitution models and functional analysis have identified several key amino acid residues which are critical for the promotion of flowering. However, the precise relationship between naturally occurring FT/TFL1 homologs and the mechanism of their role in flowering is still unclear. In this study, FT/TFL1 homologs from eight Rosaceae species, namely, Spiraea cantoniensis, Pyracantha fortuneana, Photinia serrulata, Fragaria ananassa, Rosa hybrida, Prunus mume, Prunus persica and Prunus yedoensis, were isolated. Three of these homologs were further characterized by functional analyses involving site-directed mutagenesis. The results showed that these FT/TFL1 homologs might have diverse functions despite sharing a high similarity of sequences or crystal structures. Functional analyses were conducted for the key FT amino acids, Tyr-85 and Gln-140. It revealed that TFL1 homologs cannot promote flowering simply by substitution with key FT amino acid residues. Mutations of the IYN triplet motif within segment C of exon 4 can prevent the FT homolog from promoting the flowering. Furthermore, physical interaction of FT homologous or mutated proteins with the transcription factor FD, together with their lipid-binding properties analysis, showed that it was not sufficient to trigger flowering. Thus, our findings revealed that the divergence of flowering time modulating by FT/TFL1 homologs is independent to interaction and binding activities.

Biochemical changes in the serum and placenta of rats with gestational diabetes after transplantation of human placental mesenchymal stem cells / 中国组织工程研究

BACKGROUND: Human placental mesenchymal stem cells can improve the blood glucose level of diabetes mellitus rats and gestational diabetes rats, but little is reported on its effect on glucagon, adiponectin, and tumor necrosis factor-α in the serum and placental tissues. OBJECTIVE: To investigate the effects of human placental mesenchymal stem cells on the levels of glucagon, adiponectin and tumor necrosis factor-α in the serum and placental tissues in gestational diabetes rats. METHODS: A rat model of gestational diabetes was made by high-fat and high-sugar diet plus low-dose injection of streptozotocin. Passage 3 human placental mesenchymal stem cell suspension (1×1010 cells/L, 0.5 mL) was injected into gestational diabetes rats at gestational days 4 and 11 (4- and 11-day intervention groups). Meanwhile, control rats were given the same amount of normal saline. At 20 days of gestation, blood samples from the abdominal aorta were extracted, and then cesarean section was made to remove the placenta in the gestational diabetes rats. ELISA and real-time PCR were used to detect the levels of glucagon, adiponectin and tumor necrosis factor-α in the serum and placental tissues, respectively. RESULTS AND CONCLUSION: (1) The serum and placental levels of glucagon, adiponectin and tumor necrosis factor-α showed no differences between the 4- and 11-day intervention groups (P > 0.05). (2) Compared with the control group, significantly increased serum adiponectin level and significantly decreased placental glucagon mRNA expression were found in the 4-day intervention group (P < 0.05). (3) Compared with the control group, the serum adiponectin level and the placental glucagon level both had a significant decrease in the 11-day intervention group (P < 0.01), while the serum level of tumor necrosis factor-α was significantly decreased (P < 0.01). To conclude, transplantation of human placental mesenchymal stem cells can vary the adiponectin and glucagon levels, which provides a new research idea and basis for the further study on the possible mechanism of placental mesenchymal stem cells to improve blood glucose level in gestational diabetes rats. Additionally, it is worthy while to notice that gestational diabetes rats given placental mesenchymal stem cells in the early or late pregnancy show no effects on the above indicators.