Phenotypic and transcriptome profiling of spikes reveals the regulation of light regimens on spike growth and fertile floret number in wheat.

The spike growth phase is critical for the establishment of fertile floret (grain) numbers in wheat (Triticum aestivum L.). Then, how to shorten the spike growth phase and increase grain number synergistically? Here, we showed high-resolution analyses of floret primordia (FP) number, morphology and spike transcriptomes during the spike growth phase under three light regimens. The development of all FP in a spike could be divided into four distinct stages: differentiation (Stage I), differentiation and morphology development concurrently (Stage II), morphology development (Stage III), and polarization (Stage IV). Compared to the short photoperiod, the long photoperiod shortened spike growth and stimulated early flowering by shortening Stage III; however, this reduced assimilate accumulation, resulting in fertile floret loss. Interestingly, long photoperiod supplemented with red light shortened the time required to complete Stages I-II, then raised assimilates supply in the spike and promoted anther development before polarization initiation, thereby increasing fertile FP number during Stage III, and finally maintained fertile FP development during Stage IV until they became fertile florets via a predicted dynamic gene network. Our findings proposed a light regimen, critical stages and candidate regulators that achieved a shorter spike growth phase and a higher fertile floret number in wheat.

Low sucrose availability reduces basal spikelet fertility by inducing abscisic acid and jasmonic acid synthesis in wheat.

Within a spike of wheat, the central spikelets usually generate three to four fertile florets, while the basal spikelets generate zero to one fertile floret. The physiological and transcriptional mechanism behind the difference in fertility between the basal and central spikelets is unclear. This study reports a high temporal resolution investigation of transcriptomes, number and morphology of floret primordia, and physiological traits. The W6.5-W7.5 stage was regarded as the boundary to distinguish between fertile and abortive floret primordia; those floret primordia reaching the W6.5-W7.5 stage during the differentiation phase (3-9 d after terminal spikelet stage) usually developed into fertile florets in the next dimorphism phase (12-27 d after terminal spikelet stage), whereas the others aborted. The central spikelets had a greater number of fertile florets than the basal spikelets, which was associated with more floret primordia reaching the W6.5-W7.5 stage. Physiological and transcriptional results demonstrated that the central spikelets had a higher sucrose content and lower abscisic acid (ABA) and jasmonic acid (JA) accumulation than the basal spikelets due to down-regulation of genes involved in ABA and JA synthesis. Collectively, we propose a model in which ABA and JA accumulation is induced under limiting sucrose availability (basal spikelet) through the up-regulation of genes involved in ABA and JA synthesis; this leads to floret primordia in the basal spikelets failing to reach their fertile potential (W6.5-W7.5 stage) during the differentiation phase and then aborting. This fertility repression model may also regulate spikelet fertility in other cereal crops and potentially provides genetic resources to improve spikelet fertility.

Warming-Induced Stimulation of Soil N2O Emissions Counteracted by Elevated CO2 from Nine-Year Agroecosystem Temperature and Free Air Carbon Dioxide Enrichment.

Globally, agricultural soils account for approximately one-third of anthropogenic emissions of the potent greenhouse gas and stratospheric ozone-depleting substance nitrous oxide (N2O). Emissions of N2O from agricultural soils are affected by a number of global change factors, such as elevated air temperatures and elevated atmospheric carbon dioxide (CO2). Yet, a mechanistic understanding of how these climatic factors affect N2O emissions in agricultural soils remains largely unresolved. Here, we investigate the soil N2O emission pathway using a 15N tracing approach in a nine-year field experiment using a combined temperature and free air carbon dioxide enrichment (T-FACE). We show that the effect of CO2 enrichment completely counteracts warming-induced stimulation of both nitrification- and denitrification-derived N2O emissions. The elevated CO2 induced decrease in pH and labile organic nitrogen (N) masked the stimulation of organic carbon and N by warming. Unexpectedly, both elevated CO2 and warming had little effect on the abundances of the nitrifying and denitrifying genes. Overall, our study confirms the importance of multifactorial experiments to understand N2O emission pathways from agricultural soils under climate change. This better understanding is a prerequisite for more accurate models and the development of effective options to combat climate change.

Novel annual nitrogen management strategy improves crop yield and reduces greenhouse gas emissions in wheat-maize rotation systems under limited irrigation.

Excessive irrigation and nitrogen application have long seriously undermined agricultural sustainability in the North China Plain (NCP), leading to declining groundwater tables and intensified greenhouse gas (GHG) emissions. Developing low-input management practices that meet the growing food demand while reducing environmental costs is urgently needed. Here, we developed a novel nitrogen management strategy for a typical winter wheat-summer maize rotation system in the NCP under limited irrigation (wheat sowing irrigation only (W0) or sowing and jointing irrigation (W1)) and low nitrogen input (360 kg N ha-1, about 70 % of traditional annual nitrogen input). Novel nitrogen management strategy promoted efficient nitrogen fertilizer uptake and utilization by both crops via optimization of nitrogen fertilizer allocation between the two crops, i.e., increasing nitrogen inputs to wheat (from 180 to 240 kg N ha-1) while reducing nitrogen inputs to maize (from 180 to 120 kg N ha-1). Three-year field study demonstrated that integrated management practices combining novel nitrogen management strategy with limited irrigation increased annual yields and PFPN by 1.9-5.7 %, and reduced TGE by 55-68 kg CO2-eq ha-1 and GHGI by 2.2-10.3 %, without any additional cost. Our results provide agricultural operators and policymakers with practical and easy-to-scalable integrated management strategy, and offer key initiative to promote grain production in the NCP towards agriculture sustainable intensification with high productivity and efficiency, water conservation and emission reduction.

Dynamic gene regulatory networks improving spike fertility through regulation of floret primordia fate in wheat.

The developmental process of spike is critical for spike fertility through affecting floret primordia fate in wheat; however, the genetic regulation of this dynamic and complex developmental process remains unclear. Here, we conducted a high temporal-resolution analysis of spike transcriptomes and monitored the number and morphology of floret primordia within spike. The development of all floret primordia in a spike was clearly separated into three distinct phases: differentiation, pre-dimorphism and dimorphism. Notably, we identified that floret primordia with meiosis ability at the pre-dimorphism phase usually develop into fertile floret primordia in the next dimorphism phase. Compared to control, increasing plant space treatment achieved the maximum increasement range (i.e., 50%) in number of fertile florets by accelerating spike development. The process of spike fertility improvement was directed by a continuous and dynamic regulatory network involved in transcription factor and genes interaction. This was based on the coordination of genes related to heat shock protein and jasmonic acid biosynthesis during differentiation phase, and genes related to lignin, anthocyanin and chlorophyll biosynthesis during dimorphism phase. The multi-dimensional association with high temporal-resolution approach reported here allows rapid identification of genetic resource for future breeding studies to realise the maximum spike fertility potential in more cereal crops.

Association between host nitrogen absorption and root-associated microbial community in field-grown wheat.

Plant roots and rhizosphere soils assemble diverse microbial communities, and these root-associated microbiomes profoundly influence host development. Modern wheat has given rise to numerous cultivars for its wide range of ecological adaptations and commercial uses. Variations in nitrogen uptake by different wheat cultivars are widely observed in production practices. However, little is known about the composition and structure of the root-associated microbiota in different wheat cultivars, and it is not sure whether root-associated microbial communities are relevant in host nitrogen absorption. Therefore, there is an urgent need for systematic assessment of root-associated microbial communities and their association with host nitrogen absorption in field-grown wheat. Here, we investigated the root-associated microbial community composition, structure, and keystone taxa in wheat cultivars with different nitrogen absorption characteristics at different stages and their relationships with edaphic variables and host nitrogen uptake. Our results indicated that cultivar nitrogen absorption characteristics strongly interacted with bacterial and archaeal communities in the roots and edaphic physicochemical factors. The impact of host cultivar identity, developmental stage, and spatial niche on bacterial and archaeal community structure and network complexity increased progressively from rhizosphere soils to roots. The root microbial community had a significant direct effect on plant nitrogen absorption, while plant nitrogen absorption and soil temperature also significantly influenced root microbial community structure. The cultivar with higher nitrogen absorption at the jointing stage tended to cooperate with root microbial community to facilitate their own nitrogen absorption. Our work provides important information for further wheat microbiome manipulation to influence host nitrogen absorption. KEY POINTS: • Wheat cultivar and developmental stage affected microbiome structure and network. • The root microbial community strongly interacted with plant nitrogen absorption. • High nitrogen absorption cultivar tended to cooperate with root microbiome.

Association of vascular endothelial function and quality of life in patients with ischemia and non-obstructive coronary artery disease.

Improvements are required in the quality of life (QoL) of patients with ischemia and non-obstructive coronary artery disease (INOCA). Several patients with INOCA experience vascular endothelial dysfunction. However, the relationship between endothelial function and QoL remains unelucidated. This study aimed to initially investigate the relationship between endothelial function and QoL in patients with INOCA. This prospective observational study included 121 patients with INOCA (aged 31-85 years). Vascular endothelial function was assessed by flow-mediated dilatation (FMD) of the peripheral brachial artery. QoL was evaluated using the 36-Item Short-Form Health Survey (SF-36). Patients with INOCA were divided into two groups according to the median FMD change during the 1-year follow-up (group A, ≥ median FMD change cut-off; group B, < median FMD change cut-off). The median change in FMD was 0.92%. The mean baseline SF-36 scores were comparable between the two groups (53.95 ± 6.46 vs. 53.92 ± 4.29, p = 0.98). The QoL at follow-up was better in group A than in group B (56.61 ± 5.50 vs. 53.32 ± 5.58, p = 0.002). The change in FMD (r = 0.34, p < 0.01), rather than FMD at baseline (r = - 0.01, p = 0.89) or follow-up (r = 0.13, p = 0.15), was related to the follow-up SF-36 scores. FMD improvement was an independent predictor of increased QoL (odds ratio, 3.90; 95% confidence interval: 1.59-9.53, p = 0.003). Endothelial function change is associated with QoL, and patients with improved endothelial function have a better QoL than those without.

Superoxide Dismutase, BDNF, and Cognitive Improvement in Drug-Naive First-Episode Patients With Schizophrenia: A 12-Week Longitudinal Study.

OBJECTIVE: Cognitive improvement after antipsychotic agents in patients with schizophrenia (SCZ) appears to involve redox regulation through neurotrophins such as brain derived neurotropic factor (BDNF). This study examined whether cognitive improvement was associated with the increase in superoxide dismutase (SOD) and whether higher levels of BDNF could have a permissive role in allowing SOD to improve cognition. METHODS: We examined this hypothesis in 183 drug-naïve first-episode SCZ patients taking risperidone monotherapy for 12 weeks. We measured total copper-zinc SOD (CuZn-SOD), manganese SOD (Mn-SOD), and SOD activities and BDNF levels in these patients and compared their levels with 152 healthy controls. We assessed cognitive functioning and clinical symptoms at baseline and 12-week follow-up. RESULTS: After treatment with risperidone, CuZn-SOD activity was significantly increased, and BDNF levels were slightly increased. Increased CuZn-SOD activity was associated with the cognitive effectiveness of risperidone monotherapy. The BDNF levels and SOD activities were correlated at baseline but not after 12-week treatment. Furthermore, baseline CuZn-SOD activity positively correlated with improvement on the delayed memory subscale of the Repeatable Battery for the Assessment of Neuropsychological Status only in the high BDNF subgroup. CONCLUSIONS: Our longitudinal study suggests that risperidone can enhance SOD activity and that, in combination with higher baseline BDNF levels acting in a permissive role, can improve cognitive impairments in SCZ. Greater baseline CuZn-SOD activity also may have predictive value for cognitive improvement of delayed memory in SCZ patients receiving risperidone treatment.

Neuregulin-1 regulates the conversion of M1/M2 microglia phenotype via ErbB4-dependent inhibition of the NF-κB pathway.

BACKGROUND: The inflammatory response caused by microglia in the central nervous system plays an important role in Alzheimer's disease. Neuregulin-1 (NRG1) is a member of the neuregulin family and has been demonstrated to have anti-inflammatory properties. The relationship between NRG1, microglia phenotype and neuroinflammation remains unclear. MATERIALS AND METHODS: BV2 cells were used to examine the mechanism of NRG1 in regulating microglia polarization. Neuronal apoptosis, inflammatory factors TNF-α and iNOS, microglia polarization, ErbB4 and NF-κB p65 expression were assessed. RESULTS: We found that exogenous NRG1 treatment or overexpression improved microglial activity and reduced the secretion of the inflammatory factors TNF-α and iNOS in vitro. The expression of Bax in SH-SY5Y neuron cells incubated with medium collected from the NRG1 treatment group decreased. Additionally, our study showed that NRG1 treatment reduced the levels of the M1 microglia markers CD120 and iNOS and increased the levels of the M2 microglia markers CD206 and Arg-1. Furthermore, we observed that NRG1 treatment attenuated Aß-induced NF-κB activation and promoted the expression of p-ErbB4 and that knockdown of ErbB4 abrogated the effects of NRG1 on NF-κB, Bax levels and M2 microglial polarization. CONCLUSION: NRG1 inhibits the release of inflammatory factors in microglia and regulates the switching of the M1/M2 microglia phenotype, most likely via ErbB4-dependent inhibition of the NF-κB pathway.

Effect of nitrogen supply on stay-green sorghum in differing post-flowering water regimes.

MAIN CONCLUSION: The expression of stay-green (SG) characteristic in sorghum under water stress was related to N supply. SG genotype performed better than a non-stay-green (NSG) genotype at medium and high N levels. The differences in physiological parameters between SG and NSG genotypes were not significant at low N level and severe water stress. Grain sorghum [Sorghum bicolor (L.) Moench] with stay-green (SG) trait has the potential to produce more biomass and use soil water and nitrogen (N) more efficiently under post-flowering water stress. Previous studies were mostly conducted without N deficiency and more information is needed for interactions among soil N availability, SG genotype, and post-flowering water stress. In this study, the differences in leaf growth and senescence, shoot and root biomass, evapotranspiration (ET), water use efficiency (WUE), leaf photosynthetic responses, and nitrogen use efficiency (NUE) between a SG genotype (BTx642) and a non-stay-green (NSG) genotype (Tx7000) were examined. The two genotypes were grown at three N levels (Low, LN; Medium, MN; High, HN) and under three post-flowering water regimes (No water deficit, ND; Moderate water deficit, MD; Severe water deficit, SD). The genotypic difference was generally significant while it frequently interacted with N levels and water regimes. At medium and high N levels, SG genotype consistently had greater green leaf area, slower senescence rate, more shoot biomass and root biomass, and greater WUE and NUE than the NSG genotype under post-flowering drought. However, differences in several variables (e.g., leaf senescence, ET, WUE and NUE) between genotypes were not significant under SD at LN. At HN and MN, photosynthetic function of SG genotype was better maintained under drought. At LN, SG genotype maintained greater green leaf area but had lower photosynthetic activity than the NSG genotype. Nonetheless, adequate N supply is important for SG genotype under drought and greater root biomass may contribute to greater NUE in SG genotype.

Determination of Minimum Miscibility Pressure of CO2-Oil System: A Molecular Dynamics Study.

CO2 enhanced oil recovery (CO2-EOR) has become significantly crucial to the petroleum industry, in particular, CO2 miscible flooding can greatly improve the efficiency of EOR. Minimum miscibility pressure (MMP) is a vital factor affecting CO2 flooding, which determines the yield and economic benefit of oil recovery. Therefore, it is important to predict this property for a successful field development plan. In this study, a novel model based on molecular dynamics to determine MMP was developed. The model characterized a miscible state by calculating the ratio of CO2 and crude oil atoms that pass through the initial interface. The whole process was not affected by other external objective factors. We compared our model with several famous empirical correlations, and obtained satisfactory results-the relative errors were 8.53% and 13.71% for the two equations derived from our model. Furthermore, we found the MMPs predicted by different reference materials (i.e., CO2/crude oil) were approximately linear (R2 = 0.955). We also confirmed the linear relationship between MMP and reservoir temperature (TR). The correlation coefficient was about 0.15 MPa/K in the present study.

[Monitoring microwave ablation using ultrasound backscatter homodyned K imaging: Comparison of estimators].

The feasibility of ultrasound backscatter homodyned K model parametric imaging (termed homodyned K imaging) to monitor coagulation zone during microwave ablation was investigated. Two recent estimators for the homodyned K model parameter, RSK (the estimation method based on the signal-to-noise ratio, the skewness, and the kurtosis of the amplitude envelope of ultrasound) and XU (the estimation method based on the first moment of the intensity of ultrasound, X statistics and U statistics), were compared. Firstly, the ultrasound backscattered signals during the microwave ablation of porcine liver ex vivo were processed by the noise-assisted correlation algorithm, envelope detection, sliding window method, digital scan conversion and color mapping to obtain homodyned K imaging. Then 20 porcine livers' microwave ablation experiments ex vivo were used to evaluate the effect of homodyned K imaging in monitoring the coagulation zone. The results showed that the area under the receiver operating characteristic curve of the RSK method was 0.77 ± 0.06 (mean ± standard deviation), and that of the XU method was 0.83 ± 0.08 (mean ± standard deviation). The accuracy to monitor the coagulation zone was (86 ± 10)% (mean ± standard deviation) by the RSK method and (90 ± 8)% (mean ± standard deviation) by the XU method. Compared with the RSK method, the Bland-Altman consistency for the coagulation zone estimated by the XU method and that of actual porcine liver tissue was higher. The time for parameter estimation and imaging by the XU method was less than that by the RSK method. We conclude that ultrasound backscatter homodyned K imaging can be used to monitor coagulation zones during microwave ablation, and the XU method is better than the RSK method.

A temperature-dependent conformational shift in p38α MAPK substrate-binding region associated with changes in substrate phosphorylation profile.

Febrile-range hyperthermia worsens and hypothermia mitigates lung injury, and temperature dependence of lung injury is blunted by inhibitors of p38 mitogen-activated protein kinase (MAPK). Of the two predominant p38 isoforms, p38α is proinflammatory and p38ß is cytoprotective. Here, we analyzed the temperature dependence of p38 MAPK activation, substrate interaction, and tertiary structure. Incubating HeLa cells at 39.5 °C stimulated modest p38 activation, but did not alter tumor necrosis factor-α (TNFα)-induced p38 activation. In in vitro kinase assays containing activated p38α and MAPK-activated kinase-2 (MK2), MK2 phosphorylation was 14.5-fold greater at 39.5 °C than at 33 °C. By comparison, we observed only 3.1- and 1.9-fold differences for activating transcription factor-2 (ATF2) and signal transducer and activator of transcription-1α (STAT1α) and a 7.7-fold difference for p38ß phosphorylation of MK2. The temperature dependence of p38α:substrate binding affinity, as measured by surface plasmon resonance, paralleled substrate phosphorylation. Hydrogen-deuterium exchange MS (HDX-MS) of p38α performed at 33, 37, and 39.5 °C indicated temperature-dependent conformational changes in an α helix near the common docking and glutamate:aspartate substrate-binding domains at the known binding site for MK2. In contrast, HDX-MS analysis of p38ß did not detect significant temperature-dependent conformational changes in this region. We observed no conformational changes in the catalytic domain of either isoform and no corresponding temperature dependence in the C-terminal p38α-interacting region of MK2. Because MK2 participates in the pathogenesis of lung injury, the observed changes in the structure and function of proinflammatory p38α may contribute to the temperature dependence of acute lung injury.

Metal-Based Nanocatalyst for Combined Cancer Therapeutics.

As a classical nanocatalyst-based therapeutic modality, chemodynamic therapy (CDT) has received more and more attention. To improve the therapeutic efficacy of CDT, various metal-based nanocatalysts have been designed and constructed to catalyze the Fenton or Fenton-like reaction in the past few years. However, the therapeutic efficacy of certain CDT is still restricted by the tumor microenvironment, such as limited concentration of intracellular H2O2, inappropriate pH condition, as well as overexpressed glutathione (GSH). Therefore, many other therapeutic modalities, such as photodynamic therapy (PDT), photothermal therapy (PTT), starvation therapy, chemotherapy, and gas therapy, have been utilized to combine with CDT for increasing the tumor treatment performance. In this review, we summarized the development of combinatory therapeutic modalities based on CDT in recent years.

Suppressed ABA signal transduction in the spike promotes sucrose use in the stem and reduces grain number in wheat under water stress.

Water stress is a primary trigger for reducing grain number per spike in wheat during the reproductive period. However, under stress conditions, the responses of plant organs and the interactions between them at the molecular and physiological levels remain unclear. In this study, when water stress occurred at the young microspore stage, RNA-seq data indicated that the spike had 970 differentially expressed genes, while the stem, comprising the two internodes below the spike (TIS), had 382. Abscisic acid (ABA) signal transduction genes were down-regulated by water stress in both these tissues, although to a greater extent in the TIS than in the spike. A reduction in sucrose was observed, and was accompanied by increases in cell wall invertase (CWIN) and sucrose:sucrose 1-fructosyl-transferase (1-SST) activities. Hexose and fructan were increased in the TIS but decreased in the spike. ABA was increased in the spike and TIS, and showed significant positive correlation with CWIN and 1-SST activities in the TIS. Overall, our results suggest that water stress induces the conversion of sucrose to hexose by CWIN, and to fructan by 1-SST, due to increased down-regulation of ABA signal transduction related-genes in the TIS; this leads to deficient sucrose supply to the spike and a decrease in grain number.

Cardiac damage in patients with the severe type of coronavirus disease 2019 (COVID-19).

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a global pandemic. Studies showed COVID-19 affected not only the lung but also other organs. In this study, we aimed to explore the cardiac damage in patients with COVID-19. METHODS: We collected data of 100 patients diagnosed as severe type of COVID-19 from February 8 to April 10, 2020, including demographics, illness history, physical examination, laboratory test, and treatment. In-hospital mortality were observed. Cardiac damage was defined as plasma hypersensitive troponin I (hsTnI) over 34.2 pg/ml and/or N-terminal-pro brain natriuretic peptide (NTproBNP) above 450 pg/ml at the age < 50, above 900 pg/ml at the age < 75, or above 1800 pg/ml at the age ≥ 75. RESULTS: The median age of the patients was 62.0 years old. 69 (69.0%) had comorbidities, mainly presenting hypertension, diabetes, and cardiovascular disease. Fever (69 [69.0%]), cough (63 [63.0%]), chest distress (13 [13.0%]), and fatigue (12 [12.0%]) were the common initial symptoms. Cardiac damage occurred in 25 patients. In the subgroups, hsTnI was significantly higher in elder patients (≥ 60 years) than in the young (median [IQR], 5.2 [2.2-12.8] vs. 1.9 [1.9-6.2], p = 0.018) and was higher in men than in women (4.2 [1.9-12.8] vs. 2.9 [1.9-7.4], p = 0.018). The prevalence of increased NTproBNP was significantly higher in men than in women (32.1% vs. 9.1%, p = 0.006), but was similar between the elder and young patients (20.0% vs. 25.0%, p = 0.554). After multivariable analysis, male and hypertension were the risk factors of cardiac damage. The mortality was 4.0%. CONCLUSIONS: Cardiac damage exists in patients with the severe type of COVID-19, especially in male patients with hypertension. Clinicians should pay more attention to cardiac damage.

Influencing factors of vascular endothelial function in patients with non-obstructive coronary atherosclerosis: a 1-year observational study.

BACKGROUND: Endothelial dysfunction may play a key role in non-obstructive coronary artery atherosclerosis. Our study aimed to evaluate the vascular endothelial function and its influencing factors in patients with non-obstructive coronary artery atherosclerosis. METHODS: A total of 131 consecutive patients with non-obstructive coronary artery atherosclerosis were enrolled. Flow-mediated dilatation (FMD) was measured at baseline and 1-year follow-up. Endothelial progenitor cells (EPCs) were counted by staining the fasting venous blood with antibodies against CD34 and vascular endothelial growth factor receptor 2. RESULTS: Systolic blood pressure, pulse pressure and the levels of HbA1c in participants with baseline FMD < 6% (n = 65) were significantly higher than those with baseline FMD ≥ 6% (n = 66). Baseline FMD was negatively associated with EPC counts (r = - 0.199, P < 0.05) and systolic blood pressure (r = - 0.315, P < 0.01). The 1-year FMD was significantly increased compared to the baseline FMD [(9.31 ± 5.62) % vs (7.31 ± 5.26) %, P < 0.001]. Independent predictors of FMD improvement included elevated EPC counts (OR = 1.104, 95% CI: 1.047-1.165, P < 0.001) and decreased levels of serum creatinine (OR = 0.915, 95% CI: 0.843-0.993, P = 0.034). CONCLUSIONS: Family history of premature cardiovascular diseases, hypertension, elevated systolic pressure, and HbA1c > 6.5% are independent risk factors for endothelial dysfunction in non-obstructive atherosclerotic patients. Elevated peripheral blood EPC counts and decreased levels of serum creatinine are independent predictors of endothelial function improvement.

Exosomes secreted from osteocalcin-overexpressing endothelial progenitor cells promote endothelial cell angiogenesis.

Exosome secretion is an important paracrine way of endothelial progenitor cells (EPCs) to modulate resident endothelial cells. The osteocalcin (OCN)-expressing EPCs have been found to be increased in cardiovascular disease patients and are considered to be involved in the process of coronary atherosclerosis. Since OCN has been proven to prevent endothelial dysfunction, this study aimed to evaluate the effect of exosomes derived from OCN-overexpressed EPCs on endothelial cells. Exosomes derived from EPCs (Exos) and OCN-overexpressed EPCs (OCN-Exos) were isolated and incubated with rat aorta endothelial cells (RAOECs) with or without the inhibition of OCN receptor G protein-coupled receptor family C group 6 member A (GPRC6A). The effects of exosomes on the proliferation activity of endothelial cells were evaluated by CCK-8 assay, and the migration of endothelial cells was detected by wound healing assay. A tube formation assay was used to test the influence of exosomes on the angiogenesis performance of endothelial cells. Here, we presented that OCN was packed into Exos and was able to be transferred to the RAOECs via exosome incorporation, which was increased in OCN-Exos groups. Compared with Exos, OCN-Exos had better efficiency in promoting RAOEC proliferation and migration and tube formation. The promoting effects were impeded after the inhibition of GPRC6A expression in RAOECs. These data suggest that exosomes from OCN-overexpressed EPCs have a beneficial regulating effect on endothelial cells, which involved enhanced OCN-GPRC6A signaling.

Comparison of Ultrasound, Radiography, and Clinical Investigations in the Diagnosis of Early Rheumatoid Synovitis in Patients with Nonspecific Musculoskeletal Symptoms: A Multicenter Cross-Sectional Study.

BACKGROUND Early diagnosis and treatment of rheumatoid synovitis can reduce the progression of rheumatoid arthritis (RA). However, in the early stages of rheumatoid synovitis, patients may only have non-specific musculoskeletal symptoms, and plain film radiographs may not detect early synovial changes. The aim of this study was to compare the sensitivity and specificity of ultrasound with radiography, and clinical investigations in the detection of rheumatoid synovitis in patients presenting with nonspecific musculoskeletal symptoms. MATERIAL AND METHODS This was a non-randomized, cross-sectional, clinical study that included 189 patients who had nonspecific musculoskeletal symptoms. All patients underwent clinical investigations, postero-anterior and dorsal radiographic imaging, and bilateral grey-scale ultrasound examinations of the third and second metacarpophalangeal (MCP) joints, the third and the second proximal interphalangeal (PIP) joints, the second and the fifth metatarsophalangeal (MTP) joints, and the wrist. RESULTS There was no clear predictive value for detection of early synovitis by clinical investigations alone. Plain film radiography of patients only provided accurate information of joint erosions but less information for synovitis. Grey-scale ultrasound was more effective at detecting early synovitis compared with clinical investigations (p=0.00015; q=4.548) and compared with plain film radiography (p=0.0002; q=4.537), and quantified the synovial changes. The predictive values of plain film radiography and clinical investigations had 0.43 and 0.24 sensitivity and 0 specificity compared with ultrasound. CONCLUSIONS The findings of this study support the use of grey-scale ultrasound in the detection of early rheumatoid synovitis of the fingers and the wrist.

Inhibition of PTEN Attenuates Endoplasmic Reticulum Stress and Apoptosis via Activation of PI3K/AKT Pathway in Alzheimer's Disease.

Amyloid plaques and neurofibrillary tangles are pathologic hallmarks of Alzheimer's disease (AD). Endoplasmic reticulum (ER) stress has been implicated in the loss of neurons in AD. The phosphatase and tensin homolog deleted on chromosome ten (PTEN) plays an important role in regulating neuronal survival processes. However, the direct effects of the PTEN on ER stress and apoptosis in AD have not been elucidated. In this study, we demonstrate that the expression of PTEN and ER stress related proteins, GRP78 and CHOP, increased in APP/PS1 transgenic AD mice compared with WT mice. A PTEN inhibitor, dipotassium bisperoxo-(5-hydroxypyridine-2-carboxyl)-oxovanadate (bpv) could decrease apoptosis, induce AKT phosphorylation and inhibit the ER stress response proteins in hippocampus in APP/PS1 transgenic AD model mice. Furthermore, treatment with the specific PI3K inhibitor, LY294002, significantly blocked the anti-apoptotic effects of bpv in AD mice. The expression in GRP78, CHOP and apoptosis levels by bpv was reversed after PI3K inhibitor treatment. Taken together, our results indicate that the neuroprotective role of bpv involves the suppression of ER stress via the activation of the PI3K/AKT signalling pathways in APP/PS1 transgenic AD model mice.