Dynamic Changes and Clinical Significance of Plasma Galectin-3 in Patients with Acute Ischemic Stroke Undergoing Endovascular Therapy.

Purpose: Galectin-3 is a key regulator of microglial proliferation and activation and may have dual and time-dependent effects on ischemic stroke. This study aimed to prospectively investigate the dynamic changes in Galectin-3 levels in patients with acute ischemic stroke receiving endovascular therapy and its clinical significance. Patients and Methods: A total of 105 patients with acute ischemic stroke who underwent endovascular therapy were prospectively enrolled. Plasma Galectin-3 was quantitatively detected by an enzyme-linked immunosorbent assay before the operation and at 1 day, 3 days and 7 days after the operation. A linear mixed-effect model, Pearson correlation analysis and receiver operating characteristic (ROC) curve analysis were used to evaluate the dynamic changes in the plasma Galectin-3 concentration and its relationship with clinical outcomes. Results: Increases in plasma Galectin-3 levels at 1 day and 3 days after surgery were associated with early neurological deterioration and death (both P <0.05). Increased Galectin-3 levels before surgery and at 1 day and 3 days after surgery were associated with poor prognosis (P <0.05). Pearson correlation analysis revealed that Galectin-3 levels before surgery (r =0.318, P =0.002), at 1 day (r =0.318, P =0.001), 3 days (r =0.429, P < 0.001) and 7 days after surgery (r =0.340, P =0.001) were positively correlated with NIHSS scores. The ROC curve results showed that Galectin-3 concentration had a certain predictive value for death at 1 day (AUC=0.707, P=0.013), 3 days (AUC=0.708, P=0.016) and 7 days after the operation (AUC=0.708, P=0.016), but this predictive value was lower than that of the NIHSS score. Conclusion: In acute ischemic stroke patients receiving endovascular therapy, an increase in the plasma Galectin-3 levels were associated with death, poor prognosis, and early neurological deterioration. Galectin-3 levels were significantly correlated with the NIHSS score and had a certain predictive value for death.

High-quality assembly and methylome of a Tibetan wild tree peony genome (Paeonia ludlowii) reveal the evolution of giant genome architecture.

Tree peony belongs to one of the Saxifragales families, Paeoniaceae. It is one of the most famous ornamental plants, and is also a promising woody oil plant. Although two Paeoniaceae genomes have been released, their assembly qualities are still to be improved. Additionally, more genomes from wild peonies are needed to accelerate genomic-assisted breeding. Here we assemble a high-quality and chromosome-scale 10.3-Gb genome of a wild Tibetan tree peony, Paeonia ludlowii, which features substantial sequence divergence, including around 75% specific sequences and gene-level differentials compared with other peony genomes. Our phylogenetic analyses suggest that Saxifragales and Vitales are sister taxa and, together with rosids, they are the sister taxon to asterids. The P. ludlowii genome is characterized by frequent chromosome reductions, centromere rearrangements, broadly distributed heterochromatin, and recent continuous bursts of transposable element (TE) movement in peony, although it lacks recent whole-genome duplication. These recent TE bursts appeared during the uplift and glacial period of the Qinghai-Tibet Plateau, perhaps contributing to adaptation to rapid climate changes. Further integrated analyses with methylome data revealed that genome expansion in peony might be dynamically affected by complex interactions among TE proliferation, TE removal, and DNA methylation silencing. Such interactions also impact numerous recently duplicated genes, particularly those related to oil biosynthesis and flower traits. This genome resource will not only provide the genomic basis for tree peony breeding but also shed light on the study of the evolution of huge genome structures as well as their protein-coding genes.

Pangenome analysis provides insight into the evolution of the orange subfamily and a key gene for citric acid accumulation in citrus fruits.

The orange subfamily (Aurantioideae) contains several Citrus species cultivated worldwide, such as sweet orange and lemon. The origin of Citrus species has long been debated and less is known about the Aurantioideae. Here, we compiled the genome sequences of 314 accessions, de novo assembled the genomes of 12 species and constructed a graph-based pangenome for Aurantioideae. Our analysis indicates that the ancient Indian Plate is the ancestral area for Citrus-related genera and that South Central China is the primary center of origin of the Citrus genus. We found substantial variations in the sequence and expression of the PH4 gene in Citrus relative to Citrus-related genera. Gene editing and biochemical experiments demonstrate a central role for PH4 in the accumulation of citric acid in citrus fruits. This study provides insights into the origin and evolution of the orange subfamily and a regulatory mechanism underpinning the evolution of fruit taste.

Herbaspirillum sp. ZXN111 Colonization Characters to Different Tea Cultivars and the Effects on Tea Metabolites Profiling on Zijuan (Camellia sinensis var. assamica).

Herbaspirillum sp. ZXN111 and its mutants (Δacc, Δtyrb, and Δacc-tyrb), which show PGP activity on Zijuan, were tested for tea plants' colonization characteristics and the strain-dependent response of tea metabolites. The results showed that strain ZXN111 could widely colonize in different tea cultivars of Zijuan, Yunkang-10, Longjin 43, and Shuchazao, but with significant colonization preference to Zijuan, which might be ascribed to anthocyanins' chemotaxis. After 9 weeks of co-cultivation, l-theanine and theobromine in Zijuan leaves that were inoculated with wild-type ZXN111 were decreased, while theobromine, caffeine, and l-theanine that were inoculated with mutant Δacc were increased; especially l-theanine increased much significantly. Metabolomics analysis showed that tea metabolite profiling of inoculant groups was clearly separated from the control; therein, the flavanols were downregulated in ZXN111 and Δacc groups, but the l-theanine of the Δacc group was significantly upregulated compared to control and ZXN111 groups. These results indicated that strain ZXN111, especially of mutant Δacc, improved Zijuan tea flavor.

Dynamic changes in the glycocalyx and clinical outcomes in patients undergoing endovascular treatments for large vessel occlusion.

Purpose: We aimed to verify the prognostic value of the glycocalyx as a marker of blood-brain barrier damage in patients with acute ischemic stroke undergoing endovascular therapy. Methods: We recruited patients with large vessel occlusion who were undergoing recanalization and tested their glycocalyx at multiple time points. On the basis of the 90-day follow-up data, the patients were divided into a survivor group and a nonsurvivor group. In addition, neurological function was tracked, and patients were divided into a neurological deterioration group and a group without neurological deterioration. Associations between outcomes and dynamic changes in the glycocalyx were determined using a linear mixed model, and significant factors were used as covariates. Results: Nonsurvivors and patients with neurological deterioration had significantly higher syndecan-1 concentrations than survivors and patients without neurological deterioration, and syndecan-1 tended to decline after endovascular therapy (p < 0.05). The increased level of syndecan-1 at 36 h after endovascular treatment was positively correlated with the National Institute of Health Stroke Scale score for neurological deterioration (r = 0.702, p = 0.005). However, there was no significant difference in the level of hyaluronic acid or heparan sulfate in the plasma of patients with different clinical outcomes. Conclusion: Pre-reperfusion syndecan-1 levels in patients with large vessel occlusion stroke are associated with 90-day mortality and the re-degradation of syndecan-1 is positively associated with neurological deterioration.

The content and diversity of carotenoids associated with high-altitude adaptation in Tibetan peach fruit.

Carotenoids are important secondary metabolites that may participate in response to extreme environments. Fruit color changes were observed in peaches growing at altitude on the Tibetan Plateau. Here, we qualitatively and quantitatively analyzed 43 kinds of carotenoids in 96 Tibetan peach and 12 cultivated peach fruit samples. Comparative analysis revealed that 25 kinds of carotenoids accumulated at significantly different levels between Tibetan peaches and cultivated peaches. Based on a population structure analysis, the carotenoid levels of Tibetan peaches were divided into two groups, which are mainly affected by the environmental factors light and temperature. The correlation analysis implied that the levels of 9 carotenoids were significantly correlated with altitude. qRT-PCR results showed that PSY, CCD4 and BCH were significantly differently expressed between the low and high altitude Tibetan peaches. In summary, this study showed that the abundant variation in carotenoids was highly associated with high-altitude adaptations in Tibetan peach fruit.

The correlation between enlarged perivascular spaces and cognitive impairment in Parkinson's disease and vascular parkinsonism.

INTRODUCTION: The widespread use of brain magnetic resonance imaging (MRI) has revealed the correlation between enlarged perivascular spaces (EPVS) and cognitive impairment (CI). However, few studies have examined the correlation between MRI-visible EPVS and CI in patients with Parkinson's disease (PD) and vascular parkinsonism (VaP). This study explored how the number and main location of EPVS in PD and VaP are correlated with the occurrence of CI in these diseases to provide radiology markers and other evidence for early clinical diagnosis in a Chinese cohort. METHODS: Clinical data were prospectively collected from 77 patients: 26 patients clinically diagnosed with PD or probable PD, 19 patients clinically diagnosed with VaP, and 32 control subjects with normal cognitive function and no stroke or parkinsonism. The patients with PD and VaP were divided into a CI group and a no CI (NCI) group according to the Montreal Cognitive Assessment Beijing version (MoCA-BJ). The relevant clinical data were statistically analysed. RESULTS: The centrum semiovale (CSO)-EPVS, lacunes, Fazekas scores, global cortical atrophy scale (GCA) scores, Koedam posterior atrophy visual scale (KS) scores, and medial temporal atrophy (MTA) scores were higher in the PD-CI and VaP-CI groups than in the control group (adjusted P < 0.017). The number of basal ganglia (BG)-EPVS in the VaP group was higher than that in the PD and control groups (adjusted P < 0.017). BG-EPVS, Fazekas scores, GCA scores, KS scores, and MTA scores were higher in the VaP-CI group than in the PD-CI group (adjusted P < 0.017). Multivariate logistic regression analysis showed that the differences in BG-EPVS and Fazekas scores were not significant between PD-CI and VaP-CI patients (P > 0.05). CONCLUSION: VaP-CI results from multiple factors and is significantly associated with BG-EPVS, lacunes, white matter hyperintensities and brain atrophy. BG-EPVS can be used as an imaging marker to distinguish VaP-CI from PD-CI.

Bacterial Signatures of Cerebral Thrombi in Large Vessel Occlusion Stroke.

It is important to understand the microbial features of the cerebral thrombus and its clinical relevance in stroke patients, of which data were scarce. We aimed to investigate the microbial features of cerebral thrombi retrieved via thrombectomy in stroke patients with large vessel occlusion (LVO) and their correlations with 3-month mortality. In a prospective cohort study, thrombus samples were collected during mechanical thrombectomy in LVO stroke patients with successful revascularization at a tertiary hospital. Oral, fecal, and isolated plasma samples were collected within 12 h of admission. The microbial compositions of all samples were compared using 16S rRNA gene amplicon next-generation sequencing. Fluorescent in situ hybridization (FISH) was used to detect bacteria in thrombus samples. The primary outcome was 3-month mortality. Perioperative adverse events (AEs) within 48 h were also recorded. Bacterial DNA was detected in 96.2% of thrombus samples from 104 patients, and clusters of bacterial signals were seen in the thrombi with FISH. Compared with fecal and oral samples, the thrombus microbiota was mainly characterized by excessive enrichment of Proteobacteria, mainly originating from plasma. The bacterial concentrations, dominant bacteria, and distribution patterns differed in thrombi obtained from cardioembolic and large-artery atherosclerotic strokes. Higher abundances of Acinetobacter and Enterobacteriaceae were associated with a higher risk of perioperative AEs, and a higher abundance of Acinetobacter was independently associated with a higher risk of 90-day mortality. This study demonstrated the presence of bacteria in cerebral thrombi retrieved with thrombectomy in LVO strokes, with some bacteria associated with patients' prognoses. IMPORTANCE In this study, we (i) checked for the presence of bacteria in cerebral thrombi in over 95% of the LVO stroke patients using 16S rRNA sequencing, in contrast with periprocedural control samples that are bacteria negative; (ii) visualized clusters of bacterial signals in the thrombi using FISH; and (iii) cultivated Lactobacillus vaginalis, Bacillus cereus, and Kocuria marina in the bacterial culture of the tissue fragment solution of thrombus aspirates. We found excessive enrichment of Proteobacteria in the thrombi, mainly originating from plasma, as indicated with fast expectation-maximization microbial source tracking (FEAST). Different bacterial concentrations, dominant bacteria, and distribution patterns were found in thrombi obtained from cardioembolic and large-artery atherosclerotic LVO strokes. There was an association between higher abundances of Acinetobacter and Enterobacteriaceae in the thrombi and a higher risk of perioperative adverse events and an association between a higher abundance of Acinetobacter in the thrombi and a higher risk of 90-day mortality.

Plant Growth-Promoting Activity of Herbaspirillum aquaticum ZXN111 on the Zijuan Tea Plant (Camellia sinensis var. assamica).

Herbaspirillum aquaticum ZXN111 which was isolated from the tea plant Zijuan can produce indole-3-acetic acid (IAA) and contain abiotic-stress tolerance gene 1-aminocyclopropane-1-carboxylate deaminase (accd). In this study, ZXN111 PGP activity and the molecular mechanism were investigated. The result showed that ACCD activity of wild-type ZXN111 was 0.4505 mM α-KB/mg·Pro·h, but mutants Δacc and Δacc-tyrb did not showed ACCD activity. IAA production by ZXN111 within 48 hrs was 20.4 µg/mL, while mutants of Δtyrb and Δacc-tyrb were lower than 3.6 µg/mL, indicating that indole-3-pyruvic acid is the primary IAA synthesis pathway. Potting tests found that ZXN111 displayed significant PGP activity to the tea plant Zijuan, but Δtyrb and Δacc-tyrb did not show PGP activity, indicating that IAA is critical to PGP activity. In a salt-stress test, ZXN111 did not enhance the tea plant NaCl tolerance by gene accd. The results of this study indicated that strain ZXN111 has potential for biofertilizer development on tea plantation.

Dl-3-n-butylphthalide attenuates brain injury caused by cortical infarction accompanied by cranial venous drainage disturbance.

BACKGROUND: Cerebral venous disorder may have a harmful effect on ischaemic stroke; however, the underlying mechanism remains to be elucidated. Although Dl-3-n-butylphthalide is a multitarget agent for antiischaemic stroke, its neuroprotective role in brain ischaemia accompanied by brain venous disturbance remains unclear. In this study, we induced cerebral venous disturbance by the occlusion of bilateral external jugular veins (EJVs) to explore the potential mechanism of the adverse effects of cerebrovenous disorders in cerebral infarction and explore the protective effect of Dl-3-n-butylphthalide on cerebral infarction accompanied through cerebral venous disturbance. METHODS: Cerebral venous disturbance was induced in Sprague-Dawley rats through the permanent occlusion of bilateral EJVs, and cerebral ischaemic stroke was induced through the permanent occlusion of the right cortical branches of the middle cerebral artery. 2,3,5-triphenyltetrazolium chloride staining, MRI, Evans blue extravasation and behavioural test were performed to evaluate infarction volume, cerebral blood flow (CBF), blood-brain barrier (BBB) integrity and neurological function. Immunofluorescence staining and western blot analysis were performed to detect loss of neuron, endothelial cells, pericytes and tight junctions. RESULTS: Bilateral EJVs occlusion did not cause cerebral infarction; however, it increased the infarction volume compared with the simple middle cerebral artery occlusion (MCAO) group, accompanied by severe neuron loss, worse neurological function, lower CBF, increased EJVs pressure, exacerbated Evans blue extravasation and brain oedema, as well as attenuated angiogenesis. Dl-3-n-butylphthalide displayed a neuroprotective effect in rats with MCAO accompanied by EJVs occlusion by reducing neuron loss, accelerating CBF restoration, promoting angiogenesis and relieving BBB damage. CONCLUSION: Bilateral EJVs occlusion did not significantly affect normal rats but aggravated brain damage in the case of ischaemic stroke. Dl-3-n-butylphthalide treatment plays a neuroprotective role in rats with MCAO accompanied by EJVs occlusion, mainly due to the promotion of CBF restoration and BBB protection.

Genomic basis of high-altitude adaptation in Tibetan Prunus fruit trees.

The Great Himalayan Mountains and their foothills are believed to be the place of origin and development of many plant species. The genetic basis of adaptation to high plateaus is a fascinating topic that is poorly understood at the population level. We comprehensively collected and sequenced 377 accessions of Prunus germplasm along altitude gradients ranging from 2,067 to 4,492 m in the Himalayas. We de novo assembled three high-quality genomes of Tibetan Prunus species. A comparative analysis of Prunus genomes indicated a remarkable expansion of the SINE retrotransposons occurred in the genomes of Tibetan species. We observed genetic differentiation between Tibetan peaches from high and low altitudes and that genes associated with light stress signaling, especially UV stress signaling, were enriched in the differentiated regions. By profiling the metabolomes of Tibetan peach fruit, we determined 379 metabolites had significant genetic correlations with altitudes and that in particular phenylpropanoids were positively correlated with altitudes. We identified 62 Tibetan peach-specific SINEs that colocalized with metabolites differentially accumualted in Tibetan relative to cultivated peach. We demonstrated that two SINEs were inserted in a locus controlling the accumulation of 3-O-feruloyl quinic acid. SINE1 was specific to Tibetan peach. SINE2 was predominant in high altitudes and associated with the accumulation of 3-O-feruloyl quinic acid. These genomic and metabolic data for Prunus populations native to the Himalayan region indicate that the expansion of SINE retrotransposons helped Tibetan Prunus species adapt to the harsh environment of the Himalayan plateau by promoting the accumulation of beneficial metabolites.

Rapid gut dysbiosis induced by stroke exacerbates brain infarction in turn.

OBJECTIVE: Stroke is a leading cause of death and disability worldwide. Neuroprotective approaches have failed in clinical trials, thus warranting therapeutic innovations with alternative targets. The gut microbiota is an important contributor to many risk factors for stroke. However, the bidirectional interactions between stroke and gut microbiota remain largely unknown. DESIGN: We performed two clinical cohort studies to capture the gut dysbiosis dynamics after stroke and their relationship with stroke prognosis. Then, we used a middle cerebral artery occlusion model to explore gut dysbiosis post-stroke in mice and address the causative relationship between acute ischaemic stroke and gut dysbiosis. Finally, we tested whether aminoguanidine, superoxide dismutase and tungstate can alleviate post-stroke brain infarction by restoring gut dysbiosis. RESULTS: Brain ischaemia rapidly induced intestinal ischaemia and produced excessive nitrate through free radical reactions, resulting in gut dysbiosis with Enterobacteriaceae expansion. Enterobacteriaceae enrichment exacerbated brain infarction by enhancing systemic inflammation and is an independent risk factor for the primary poor outcome of patients with stroke. Administering aminoguanidine or superoxide dismutase to diminish nitrate generation or administering tungstate to inhibit nitrate respiration all resulted in suppressed Enterobacteriaceae overgrowth, reduced systemic inflammation and alleviated brain infarction. These effects were gut microbiome dependent and indicated the translational value of the brain-gut axis in stroke treatment. CONCLUSIONS: This study reveals a reciprocal relationship between stroke and gut dysbiosis. Ischaemic stroke rapidly triggers gut microbiome dysbiosis with Enterobacteriaceae overgrowth that in turn exacerbates brain infarction.

Dysbiosis of Gut Microbiota and Short-Chain Fatty Acids in Acute Ischemic Stroke and the Subsequent Risk for Poor Functional Outcomes.

BACKGROUND: The intestinal microbiota and its metabolites have been reported to play an important role in stroke. Gut microbiota-originating short-chain fatty acids (SCFAs) modulate brain functions directly or indirectly through immune, endocrine, vagal, and other humoral pathways. However, relatively few investigations have evaluated the gut microbiome and SCFAs spectrum or their potential associations with stroke outcomes in acute ischemic stroke (AIS) patients with different stroke severities. METHODS: We used 16S rRNA gene sequencing and gas chromatography to compare the fecal microbial composition and SCFA spectrum between AIS patients (n = 140) and healthy controls (n = 92). Their associations with 90-day poor functional outcomes were evaluated by logistic regression models. RESULTS: We found that the intestinal microbiota distinguished AIS patients from healthy controls. A lack of SCFAs-producing bacteria and a low fecal SCFAs level defined dysbiosis in AIS patients, especially those with increased stroke severity. The SCFAs levels were negatively correlated with stroke severity and prognosis. Reduced SCFAs levels, especially acetate, were associated with an increased risk of 90-day poor functional outcomes even after adjustments. CONCLUSIONS: Dysbiosis of SCFAs-producing bacteria and SCFAs in AIS patients increased the subsequent risk for poor functional outcomes, indicating that SCFAs could be potential prognostic markers and therapeutic targets for stroke.

Insights on seed abortion (endosperm and embryo development failure) from the transcriptome analysis of the wild type plant species Paeonia lutea.

Paeonia lutea is a wild peony (an endangered flowering plant species) found in China. Seed abortion (endosperm and embryo development failure) is linked to several endangered plant species. Therefore, it is of interest to complete a comparative analysis of transcriptome between the normal active seeds (Population A) and the endangered abortion seeds (Population H). Data from GO assignments of differentially expressed genes (DEGs) shows that "metabolic process", "binding", "cellular process", "catalytic activity", "cell" and "cell part" are commonly prevalent in these popuations. DEGs between the populations are found to be connected with metabolic pathways, biosynthesis of secondary metabolites, purine metabolism and ribosome. We used quantitative RT-PCR to validate 16 DEGs associated with these populations. It is found that histone genes and proline-rich extensin genes are predominant in the common groups. Histone genes (H2A, H2B, H3, H4 and linker histone H1) show 3 to 4 folds log2FC higher expession in population A than in population H in stage I unlike in stage II and III. Increased activity of proline-rich extensin genes in population A than in population H corresponding to seed abortion in the later population is implied. These preliminary data from the transcriptome analysis of the wild type plant species Paeonia lutea provide valuable insights on seed abortion.

Differences in Pathological Composition Among Large Artery Occlusion Cerebral Thrombi, Valvular Heart Disease Atrial Thrombi and Carotid Endarterectomy Plaques.

Background and Purpose: Acute ischemic stroke (AIS) with large artery occlusion (LAO) may lead to severe disability or death if not promptly treated. To determine the source of cerebral artery occlusion thrombosis, we studied the pathological components of cerebral artery thrombosis with different etiological classifications to guide clinical formulation of preventive treatment. Materials and Methods: Eighty-eight thrombi from AIS patients with LAO, 12 atrial thrombi from patients with valvular heart disease (VHD), and 11 plaques obtained by carotid endarterectomy (CEA) from patients with carotid artery stenosis were included in this retrospective study. The hematoxylin and eosin-stained specimens were quantitatively analyzed for erythrocytes, white blood cells (WBCs) and fibrin; platelets were shown by immunohistochemistry for CD31. Results: The thrombi of VHD showed the highest percentage of fibrin, followed by those of cardioembolism (CE) and stroke of undetermined etiology (SUE), and these values were higher than those of the other groups. Plaques obtained by CEA showed the highest erythrocyte number, followed by the large artery atherosclerosis (LAA) thrombi, and showed significantly noticeable differences between other stroke subtypes. The proportions of fibrin and erythrocytes in the thrombi of CE and SUE were most similar to those in the thrombi of VHD, and the LAA thrombi were the closest to those obtained by CEA. CE thrombi and CEA plaques had a higher percentage of WBCs than thrombi of other stroke thrombus subtypes and VHD. Conclusions: CE and most cryptogenic thrombi may originate from the heart, and the formation of carotid atherosclerotic plaques may be related to atherosclerotic cerebral embolism. Inflammation may be involved in their formation.

Male Sterility is linked to the Flavonoid Biosynthesis Pathways in Prunus mira.

Sterility plays an important role in plant adaptation and evolution and has contributed to the development of high yielding crop hybrids. We used the widely targeted metabolomics profiling to survey the metabolites and biological pathways associated with male sterility in Prunus mira by comparing flowers from fertile and sterile trees. Male sterile flowers displayed abnormal stamen, uncolored anthers, and distorted and shrunken pollen grains with an apparent lack of turgidity. We report 566 metabolites in six flower samples and 140 differentially accumulated metabolites (DAMs) between both flower types. Most of the DAMs belong to the phenyl propanoid biosynthesis pathway, particularly flavonoid, flavone and flavonol biosynthesis pathways, implying that alterations in these key pathways link to male sterility in P. mira. The known link between low levels of flavonoid metabolites, weak expression levels of several structural genes from the phenyl propanoid biosynthesis pathway and hyper accumulation of reactive oxygen species were highlighted for understanding the underlying mechanism leading to the abnormal or aborted pollen grains observed in the sterile flowers. Data on the molecular mechanism of male sterility in Prunus mira will facilitate further in-depth investigations on this important agronomic and ecological trait.

Dynamic Changes and Prognostic Value of Gut Microbiota-Dependent Trimethylamine-N-Oxide in Acute Ischemic Stroke.

Background: Acute ischemic stroke (AIS) is an atherothrombotic disease. Trimethylamine-N-oxide (TMAO), a gut microbiota-dependent metabolite, has been shown to be proatherogenic and prothrombotic. However, the involvement of TMAO in AIS remains unclear. This study aimed to observe the dynamic changes of TMAO in AIS patients and identify the prognostic value of TMAO for major ischemic events and unfavorable functional outcomes. Methods: This study included 204 AIS patients and 108 healthy controls. Blood samples for TMAO analyses were drawn at admission, 2 and 7 days of admission. Logistic regression models and receiver operating characteristic curves were established to identify associations between TMAO levels and major ischemic events (ischemic stroke, myocardial infarction, or death from an ischemic vascular event), as well as unfavorable functional outcomes (modified Rankin Scale score ≥3), at 90 days and 12 months. Results: TMAO levels showed no significant changes before and within 24 h of AIS treatment (at admission) but decreased significantly thereafter. Elevated log2-transformed baseline TMAO levels were associated with increased risks of 90-day [odds ratio (OR), 2.62; 95% confidence interval (CI), 1.55-4.45; p < 0.001] and 12-month (OR, 3.59; 95% CI, 2.12-6.09; p < 0.001) major ischemic events, as well as 90-day (OR, 2.89; 95% CI, 1.46-5.71; p = 0.002) and 12-month (OR, 2.58; 95% CI, 1.50-4.46; p = 0.001) unfavorable functional outcomes, after adjustments for confounding factors. The areas under curve of baseline TMAO levels for predicting 90-day and 12-month major ischemic events were 0.72 (95% CI, 0.61-0.83; p < 0.001) and 0.76 (95% CI, 0.66-0.85; p < 0.001). Baseline TMAO levels improved the prognostic accuracy of conventional risk factors, National Institutes of Health Stroke Scale (NIHSS) score and N-terminal B-type natriuretic peptide (NT-proBNP) level. Conclusions: TMAO levels decreased with time since stroke onset. Elevated TMAO levels at an earlier period portended poor stroke outcomes, broadening the potential clinical utility of TMAO as an independent prognostic marker and therapeutic target.

Dry storage improves the vase quality of cut peony by increasing water uptake efficiency through aquaporins regulation.

Proper storage prolongs peony market supply. Here, we determined the changes in fresh weight and expression of four aquaporin genes under dry storage (DS) and wet storage (WS). It has showed that after harvesting, the fresh weight change was accompanied with flower opening. After both short- and long-term of storage, the water uptake efficiency in DS group was greater during the first few vase days, providing a direct material basis of DS improved vase quality. The gene expression results showed that PlPIP1;3 and PlTIP2;1 were mainly expressed in petals, whereas PlNIP1;2-like and PlSIP2;1 were mainly expressed in the green tissues. In addition, the expression of PlTIP2;1 in the petals was consistent with the flower opening process, indicating that it may play a major role in facilitating water uptake. During cold storage, the expression of PlPIP1;3 and PlTIP2;1 was higher or more rapidly induced in the DS group, and thus we deduced that they play important roles in improving the vase quality of DS. Furthermore, the expression of PlNIP1;2-like in the early stage of the DS group was more stable than in WS, which may also be partially responsible for the vase quality improvement. In contrast, PlSIP2;1 may not be involved, since no significant change was observed between the DS and WS group. In short, the expression of PlPIP1;3 and PlTIP2;1 in the DS group during storage may improve water uptake efficiency during the vase period and then improving the vase quality of cut peony.

Transcriptomic and metabolomic profiling provide novel insights into fruit development and flesh coloration in Prunus mira Koehne, a special wild peach species.

BACKGROUND: Flesh color is one of the most important traits for the commercial value of peach fruit. To unravel the underlying regulatory network in Prunus mira, we performed an integrated analysis of the transcriptome and metabolome of 3 fruit types with various flesh pigmentations (milk-white, yellow and blood) at 3 developmental stages (pit-hardening, cell enlargement and fruit ripening). RESULTS: Transcriptome analysis showed that an intense transcriptional adjustment is required for the transition from the pit-hardening to the cell enlargement stage. In contrast, few genes were differentially expressed (DEGs) from the cell enlargement to the fruit ripening stage and importantly, the 3 fruits displayed diverse transcriptional activities, indicating that difference in fruit flesh pigmentations mainly occurred during the ripening stage. We further investigated the DEGs between pairs of fruit types during the ripening stage and identified 563 DEGs representing the 'core transcriptome' associated with major differentiations between the 3 fruit types, including flesh pigmentation. Meanwhile, we analyzed the metabolome, particularly, at the ripening stage and uncovered 40 differential metabolites ('core metabolome') between the 3 fruit types including 5 anthocyanins, which may be the key molecules associated with flesh coloration. Finally, we constructed the regulatory network depicting the interactions between anthocyanins and important transcripts involved in fruit flesh coloration. CONCLUSIONS: The major metabolites and transcripts involved in fruit flesh coloration in P. mira were unraveled in this study providing valuable information which will undoubtedly assist in breeding towards improved fruit quality in peach.

Identification of Potential Metabolites Mediating Bird's Selective Feeding on Prunus mira Flowers.

In peach orchards, birds severely damage flowers during blossom season, decreasing the fruit yield potential. However, the wild peach species Prunus mira shows intraspecific variations of bird damage, indicating that some of the wild trees have developed strategies to avert bird foraging. Motivated by this observation, we formulated the present study to identify the potential flower metabolites mediating the bird's selective feeding behavior in P. mira flowers. The birds' preferred (FG) and avoided (BFT) flowers were collected from wild P. mira trees at three different locations, and their metabolite contents were detected, quantified, and compared. The widely-targeted metabolomics approach was employed to detect a diverse set of 603 compounds, predominantly, organic acids, amino acid derivatives, nucleotide and its derivatives, and flavones. By quantitatively comparing the metabolite contents between FG and BFT, three candidate metabolites, including Eriodictiol 6-C-hexoside 8-C-hexoside-O-hexoside, Luteolin O-hexosyl-O-hexosyl-O-hexoside, and Salvianolic acid A, were differentially accumulated and showed the same pattern across the three sampling locations. Distinctly, Salvianolic acid A was abundantly accumulated in FG but absent in BFT, implying that it may be the potential metabolite attracting birds in some P. mira flowers. Overall, this study sheds light on the diversity of the floral metabolome in P. mira and suggests that the bird's selective feeding behavior may be mediated by variations in floral metabolite contents.