Single-Molecule Real-Time Transcript Sequencing Identified Flowering Regulatory Genes in Crocus Sativus

Background: Saffron crocus (Crocus sativus) is a valuable spice with medicinal uses in gynaecopathia and nervous system diseases. Identify flowering regulatory genes plays a vital role in increasing flower numbers, thereby resulting in high saffron yield. Results: Two full length transcriptome gene sets of flowering and non-flowering saffron crocus were established separately using the single-molecule real-time (SMRT) sequencing method. A total of sixteen SMRT cells generated 22.85 GB data and 75,351 full-length saffron crocus unigenes on the PacBio RS II panel and further obtained 79,028 SSRs, 72,603 lncRNAs and 25,400 alternative splicing (AS) events. Using an Illumina RNA-seq platform, an additional fifteen corms with different flower numbers were sequenced. Many differential expression unigenes (DEGs) were screened separately between flowering and matched non-flowering top buds with cold treatment (1677), flowering top buds of 20 g corms and non-flowering top buds of 6 g corms (1086), and flowering and matched nonflowering lateral buds (267). A total of 62 putative flower-related genes that played important roles in vernalization (VRNs), gibberellins (G3OX, G2OX), photoperiod (PHYB, TEM1, PIF4), autonomous (FCA) and age (SPLs) pathways were identified and a schematic representation of the flowering gene regulatory network in saffron crocus was reported for the first time. After validation by real-time qPCR in 30 samples, two novel genes, PB.20221.2 (p = 0.004, r = 0.52) and PB.38952.1 (p = 0.023, r = 0.41), showed significantly higher expression levels in flowering plants. Tissue distribution showed specifically high expression in flower organs and time course expression analysis suggested that the transcripts increasingly accumulated during the flower development period. Conclusions: Full-length transcriptomes of flowering and non-flowering saffron crocus were obtained using a combined NGS short-read and SMRT long-read sequencing approach. This report is the first to describe the flowering gene regulatory network of saffron crocus and establishes a reference full-length transcriptome for future studies on saffron crocus and other Iridaceae plants

Comparison of Exenatide and Metformin Monotherapy in Overweight/Obese Patients with Newly Diagnosed Type 2 Diabetes

Aims. The present study assessed the therapeutic effect of exenatide and metformin as the initial therapy on overweight/obese patients with newly diagnosed type 2 diabetes (T2D). Methods. The prospective, nonrandomized, interventional study enrolled a total of 230 overweight or obese patients with newly diagnosed T2D who were administrated exenatide or metformin hydrochloride for 12 weeks. Results. 224/230 patients, including 106 in the exenatide group and 118 in the metformin group, completed the 12-week treatment. Both exenatide and metformin significantly decreased the HbA1c levels in overweight/obese patients with newly diagnosed T2D (all P<0.05). The reduction in HbA1c and the proportion of patients with HbA1c < 7.0% (53 mmol/mol) were higher in the exenatide group than in the metformin group (all P<0.05). The exenatide treatment caused a greater decline in the body weight and BMI as compared to the metformin treatment (all P<0.01). The exenatide treatment (β = 0.41, P<0.01) and baseline HbA1c level (β = −0.84, P<0.01) were independent influencing factors for the decrease in HbA1c level. Conclusions. For an initial therapy in overweight/obese patients with newly diagnosed T2D, exenatide causes a better glycemic control than metformin. This trial is registered with NCT03297879

SiNiSan Ameliorates the Depression-Like Behavior of Rats That Experienced Maternal Separation Through 5-HT1A Receptor/CREB/BDNF Pathway

Background: Early adverse life stress is an important dangerous factor in the development of psychiatric disorders, particularly depression. Available clinical antidepressant agents, such as fluoxetine, [a selective serotonin reuptake inhibitor (SSRI)], are unsatisfactory because of their side effects. SiNiSan (SNS) is a classic Chinese medicine prescription regarded to disperse stagnated liver qi to relieve qi stagnation. Therefore, this study was designed to detect the effects and molecular mechanism of SNS treatment in rats subjected to maternal separation (MS).Method: Male neonatal Wistar rats were divided into six groups including control + ddH2O, MS + ddH2O, MS + fluoxetine (5 g/kg), MS + SNS -low dose (2.5 g/kg), MS + SNS -medium dose (5 g/kg), MS + SNS -high dose (10 g/kg). The volume of drugs and ddH2O in each group are according to the weight of rats every day (10 mL/kg). Each group comprised 16 pups with 8 young and 8 adult pups. Except for the control group, all MS groups were separated from their mothers for 4 h/day from 9:00 to 13:00 during postnatal days (PNDs) 1 to 21. After MS, the six groups were intragastrically administered with ddH2O, fluoxetine, and different doses of SNS until PND 28 (for young pups) and PND 56 (for adult pups). The pups were weighed every day, and depression-like behavior was assessed by sucrose preference test, open field test, and forced swimming test. Serotonin 1A (5-HT1A) receptor, phosphorylated protein kinase A (p-PKA) substrate, cAMP response element-binding protein (CREB), p-CREB and brain-derived neurotrophic factor (BDNF) in the hippocampus were examined by Western blot, and in situ 5-HT1A receptor expression was measured by IHC.Results: Young and adult MS rats exhibited depression-like behavior. However, the depression-like behavior was ameliorated by SNS in both age groups. The levels of 5-HT1A receptor, p-CREB, and BDNF in the hippocampus were reduced in young and adult MS rats. SNS treatment significantly up-regulated the expression of 5-HT1A receptor, p-CREB, and BDNF in the hippocampus of adult MS rats. However, few significant effects on the protein expression were observed in the young MS rats.Conclusion: MS in infancy could develop depression-like behavior in young and adult. SNS treatment may perform antidepressant effects on young and adult MS rats through the BDNF/PKA/CREB pathway

Spin-Peierls transition in an anisotropic two-dimensional XY model

The two-dimensional Jordan-Wigner transformation is used to investigate the zero temperature spin-Peierls transition for an anisotropic two-dimensional XY model in adiabatic limit. The phase diagram between the dimerized (D) state and uniform (U) state is shown in the parameter space of dimensionless interchain coupling $h$ $(=J_{\perp}/J)$ and spin-lattice coupling $\eta$. It is found that the spin-lattice coupling $\eta$ must exceed some critical value $\eta_c$ in order to reach the D phase for any finite $h$. The dependence of $\eta_c$ on $h$ is given by $-1/\ln h$ for $h\to 0$ and the transition between U and D phase is of first-order for at least $h>10^{-3}$.Comment: 2 eps figures, considerable revisions were mad

Development and validation of a nomogram for the risk prediction of malignant cerebral edema after acute large hemispheric infarction involving the anterior circulation

BackgroundMalignant cerebral edema (MCE) is a life-threatening complication of large hemisphere infarction (LHI). Therefore, a fast, accurate, and convenient tool for predicting MCE can guide triage services and facilitate shared decision-making. In this study, we aimed to develop and validate a nomogram for the early prediction of MCE risk in acute LHI involving the anterior circulation and to understand the potential mechanism of MCE.MethodsThis retrospective study included 312 consecutive patients with LHI from 1 January 2019 to 28 February 2023. The patients were divided into MCE and non-MCE groups. MCE was defined as an obvious mass effect with ≥5 mm midline shift or basal cistern effacement. Least absolute shrinkage and selection operator (LASSO) and logistic regression were performed to explore the MCE-associated factors, including medical records, laboratory data, computed tomography (CT) scans, and independent clinic risk factors. The independent factors were further incorporated to construct a nomogram for MCE prediction.ResultsAmong the 312 patients with LHI, 120 developed MCE. The following eight factors were independently associated with MCE: Glasgow Coma Scale score (p = 0.007), baseline National Institutes of Health Stroke Scale score (p = 0.006), Alberta Stroke Program Early CT Score (p &lt; 0.001), admission monocyte count (p = 0.004), white blood cell count (p = 0.002), HbA1c level (p &lt; 0.001), history of hypertension (p = 0.027), and history of atrial fibrillation (p = 0.114). These characteristics were further used to establish a nomogram for predicting prognosis. The nomogram achieved an AUC-ROC of 0.89 (95% CI, 0.82–0.96).ConclusionOur nomogram based on LASSO-logistic regression is accurate and useful for the early prediction of MCE after LHI. This model can serve as a precise and practical tool for clinical decision-making in patients with LHI who may require aggressive therapeutic approaches

Genome dynamics and diversity of Shigella species, the etiologic agents of bacillary dysentery

The Shigella bacteria cause bacillary dysentery, which remains a significant threat to public health. The genus status and species classification appear no longer valid, as compelling evidence indicates that Shigella, as well as enteroinvasive Escherichia coli, are derived from multiple origins of E.coli and form a single pathovar. Nevertheless, Shigella dysenteriae serotype 1 causes deadly epidemics but Shigella boydii is restricted to the Indian subcontinent, while Shigella flexneri and Shigella sonnei are prevalent in developing and developed countries respectively. To begin to explain these distinctive epidemiological and pathological features at the genome level, we have carried out comparative genomics on four representative strains. Each of the Shigella genomes includes a virulence plasmid that encodes conserved primary virulence determinants. The Shigella chromosomes share most of their genes with that of E.coli K12 strain MG1655, but each has over 200 pseudogenes, 300∼700 copies of insertion sequence (IS) elements, and numerous deletions, insertions, translocations and inversions. There is extensive diversity of putative virulence genes, mostly acquired via bacteriophage-mediated lateral gene transfer. Hence, via convergent evolution involving gain and loss of functions, through bacteriophage-mediated gene acquisition, IS-mediated DNA rearrangements and formation of pseudogenes, the Shigella spp. became highly specific human pathogens with variable epidemiological and pathological features