High intensity interval training vs. moderate intensity continuous training on aerobic capacity and functional capacity in patients with heart failure: a systematic review and meta-analysis.

Background: Exercise training is commonly employed as a efficacious supplementary treatment for individuals suffering from heart failure, but the optimal exercise regimen is still controversial. The objective of the review was to compare the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on the exercise capacity, cardiac function, quality of life (QoL) and heart rate among patients with heart failure with reduced ejection fraction. Methods: A systematic search was performed using the following eight databases from their inception to July 5, 2023: PubMed, Web of Science, Embase, Cochrane Library, Clinical Trials, China Knowledge Network, Wan fang Data, and the China Biology Medicine databases. The meta-analysis results were presented as mean difference (MD) and 95% confidence interval (CI). The Cochrane Risk of Bias tool was used for the included studies. The Grading of Recommendations Assessment, Development, and Evaluations was used to assess the certainty of evidence. Results: Thirteen randomized controlled trials were included in the study. The results showed that HIIT had a significant positive effect on peak oxygen uptake (MD = 1.78, 95% CI for 0.80-2.76), left ventricular ejection fraction (MD = 3.13, 95% CI for 1.25-5.02), six-minute walk test (MD = 28.13, 95% CI for 14.56-41.70), and Minnesota Living with Heart Failure Questionnaire (MD = -4.45, 95% CI for -6.25 to -2.64) compared to MICT. However, there were no statistically significant differences observed in resting heart rate and peak heart rate. Conclusions: HIIT significantly improves peak oxygen uptake, left ventricular ejection fraction, six-minute walk test, and Minnesota Living with Heart Failure Questionnaire in patients with heart failure with reduced ejection fraction. Additionally, HIIT exhibits greater effectiveness in improving peak oxygen uptake among patients with lower body mass index. Systematic Review Registration: https://www.doi.org/10.37766/inplasy2023.7.0100, identifier (INPLASY2023.7.0100).

Multicenter study of seasonal and regional airborne allergens in Chinese preschoolers with allergic rhinitis.

This study is nationwide multicenter epidemiological research, aimed at investigating the distribution changes and seasonal patterns of various airborne allergens among preschool children with allergic rhinitis (AR) in different regions of China, and analyzing the clinical correlation between sensitization to various airborne allergens and AR symptoms in children. Information on children was collected through standard questionnaires, and total IgE (tIgE) and specific IgE (sIgE) for 11 inhalant allergens were tested. The results showed that dust mites are the primary allergens for preschool AR children (39%). Among pollen allergens, Amb a had the highest positivity rate (8.1%), followed by Art v (7.8%). The sensitization rates for two mites peaked in May (46.9% and 40.6%). Art v peaked in August (21.5%), while Amb a had peaks in May (12.7%) and August (17.8%). The sensitization peaks for various tree pollens mainly occurred in August. In the Eastern monsoon region, the sensitization rate to mites was significantly higher than in the Northwest arid and semi-arid regions; whereas, for pollen allergens, the sensitization rates to Amb a, Pla a, Pin a, Pop d, and Bet v were significantly higher in the Northwest arid and semi-arid regions than in the Eastern monsoon region. The correlation among various tree pollens, specifically between Pla a, Pin r, Pop d, and Bet v was strong (0.63 ~ 0.79), with a cross-overlapping percentage of 53.9%. Children with multiple pollen sensitizations had higher cumulative nasal symptom scores than those negative for pollen (P < 0.01). Children with only pollen sensitization had higher cumulative rhinitis symptom scores than the all-negative group (P < 0.0001) and the mite-only sensitization group [P < 0.05], while the mite-only sensitization group also had higher scores than the all-negative group [P < 0.05], and the group sensitized to both pollen and mites had lower scores than the pollen-only group [P < 0.05]. This study indicates that sensitization to mites and grass pollens exhibits significant regional differences, with grass pollen allergies primarily occurring in autumn, sensitization to pollens in general exhibits a pronounced seasonal pattern. Moreover, pollen sensitization aggravates nasal and ocular symptoms in AR children.

The impact of water storage capacity on plant dynamics in arid environments: A stoichiometric modeling approach.

Plants in arid environments have evolved many strategies to resist drought. Among them, the developed water storage tissue is an essential characteristic of xerophytes. To clarify the role of water storage capacity in plant performance, we originally formulate a stoichiometric model to describe the interaction between plants and water with explicit water storage. Via an ecological reproductive index, we explore the effects of precipitation and water storage capacity on plant dynamics. The model possesses saddle-node bifurcation and forward or backward bifurcation, and the latter may lead to the emergence of alternative stable states between a stable survival state and a stable extinction state. Numerical simulations illustrate the persistence and resilience of plants regulated by soil conditions, precipitation and water storage capacity. Our findings contribute to the botanical theory in the perspectives of environmental change and plant water storage traits.

Precipitation governing vegetation patterns in an arid or semi-arid environment.

In an arid or semi-arid environment, precipitation plays a vital role in vegetation growth. Recent researches reveal that the response of vegetation growth to precipitation has a lag effect. To explore the mechanism behind the lag phenomenon, we propose and investigate a water-vegetation model with spatiotemporal nonlocal effects. It is shown that the temporal kernel function does not affect Turing bifurcation. For better understanding the influences of lag effect and nonlocal competition on the vegetation pattern formation, we choose some special kernel functions and obtain some insightful results: (i) Time delay does not trigger the vegetation pattern formation, but can postpone the evolution of vegetation. In addition, in the absence of diffusion, time delay can induce the occurrence of stability switches, while in the presence of diffusion, spatially nonhomogeneous time-periodic solutions may emerge, but there are no stability switches; (ii) The spatial nonlocal interaction may trigger the pattern onset for small diffusion ratio of water and vegetation, and can change the number and size of isolated vegetation patches for large diffusion ratio. (iii) The interaction between time delay and spatial nonlocal competition may induce the emergence of traveling wave patterns, so that the vegetation remains periodic in space, but is oscillating in time. These results demonstrate that precipitation can significantly affect the growth and spatial distribution of vegetation.

Molecular and cellular regulation of thermogenic fat.

Thermogenic fat, consisting of brown and beige adipocytes, dissipates energy in the form of heat, in contrast to the characteristics of white adipocytes that store energy. Increasing energy expenditure by activating brown adipocytes or inducing beige adipocytes is a potential therapeutic strategy for treating obesity and type 2 diabetes. Thus, a better understanding of the underlying mechanisms of thermogenesis provides novel therapeutic interventions for metabolic diseases. In this review, we summarize the recent advances in the molecular regulation of thermogenesis, focusing on transcription factors, epigenetic regulators, metabolites, and non-coding RNAs. We further discuss the intercellular and inter-organ crosstalk that regulate thermogenesis, considering the heterogeneity and complex tissue microenvironment of thermogenic fat.

Whole-Genome Methylation Sequencing of Large Yellow Croaker (Larimichthys crocea) Liver Under Hypoxia and Acidification Stress.

Large yellow croaker (Larimichthys crocea) is an important aquaculture species in China. This study analysed whole-genome methylation differences in liver tissues of young fish under different hypoxic and acidification conditions. Differentially methylated regions (DMRs) and differentially methylated genes (DMGs) were identified. Gene ontology (GO) and Kyoto encyclopaedia of genes and genomes (KEGG) enrichment analyses of DMGs were conducted to explore the mechanism of coping with hypoxic acidification. The main methylation type was CG, accounting for > 70% of total methylation, significantly higher than CHG and CHH methylation types. GO enrichment analysis of DMGs revealed strong enrichment of nervous system development, cell periphery, plasma membrane, cell junction organisation, cell junction, signalling receptor activity, molecular sensor activity, cell-linked tissue junction organisation, cell-cell adhesion and nervous system development. KEGG enrichment analysis of DMR-related genes identified cell adhesion molecules, cortisol synthesis and secretion and aldosterone synthesis and secretion as the three key pathways regulating the physiological responses to hypoxia and acidification. Long-term hypoxic and acidification stress affected the immune system, nervous system and stress responses of large yellow croaker. Whole-genome sequencing analysis of exposed tissues was used to investigate changes that occur in L. crocea in response to hypoxic and acidic conditions at the DNA methylation level. The findings contribute to our comprehensive understanding of functional methylation in large yellow croaker and will support future research on the response mechanisms of this species under different environmental pressures.

Myeloperoxidase PET Imaging Tracks Intracellular and Extracellular Treatment Changes in Experimental Myocardial Infarction.

Myeloperoxidase (MPO) is a highly oxidative, pro-inflammatory enzyme involved in post-myocardial infarction (MI) injury and is a potential therapeutic target. While multiple MPO inhibitors have been developed, the lack of an imaging reporter to select appropriate patients and assess therapeutic efficacy has hampered clinical development. Thus, a translational imaging method to detect MPO activity non-invasively would help to better understand the role MPO plays in MI and facilitate novel therapy development and clinical validation. Interestingly, many MPO inhibitors affect both intracellular and extracellular MPO, but previous MPO imaging methods can only report extracellular MPO activity. In this study, we found that an MPO-specific PET imaging agent (18F-MAPP) can cross cell membranes to report intracellular MPO activity. We showed that 18F-MAPP can track the treatment effect of an MPO inhibitor (PF-2999) at different doses in experimental MI. The imaging results were corroborated by ex vivo autoradiography and gamma counting data. Furthermore, extracellular and intracellular MPO activity assays revealed that 18F-MAPP imaging can report the changes induced by PF-2999 on both intracellular and extracellular MPO activities. These findings support 18F-MAPP as a translational candidate to noninvasively report MPO activity and accelerate drug development against MPO and other related inflammatory targets.

Transcriptomic Analysis of Large Yellow Croaker (Larimichthys crocea) during Early Development under Hypoxia and Acidification Stress.

Fishes live in aquatic environments and several aquatic environmental factors have undergone recent alterations. The molecular mechanisms underlying fish responses to hypoxia and acidification stress have become a serious concern in recent years. This study revealed that hypoxia and acidification stress suppressed the growth of body length and height of the large yellow croaker (Larimichthys crocea). Subsequent transcriptome analyses of L. crocea juveniles under hypoxia, acidification, and hypoxia-acidification stress led to the identification of 5897 differentially expressed genes (DEGs) in the five groups. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that several DEGs were enriched in the 'protein digestion and absorption' pathway. Enrichment analysis revealed that this pathway was closely related to hypoxia and acidification stress in the five groups, and we found that genes of the collagen family may play a key role in this pathway. The zf-C2H2 transcription factor may play an important role in the hypoxia and acidification stress response, and novel genes were additionally identified. The results provide new clues for further research on the molecular mechanisms underlying hypoxia-acidification tolerance in L. crocea and provides a basic understanding of the potential combined effects of reduced pH and dissolved oxygen on Sciaenidae fishes.

The Effects of High-Intensity Interval Training on Exercise Capacity and Prognosis in Heart Failure and Coronary Artery Disease: A Systematic Review and Meta-Analysis.

Objective: The purpose of this study is to compare the effects of high-intensity interval training (HIIT) versus moderate-intensity continuous training (MICT) on exercise capacity and several prognostic markers in patients with coronary artery disease (CAD) and heart failure (HF). Methods: This systematic review is registered on the INPLASY website (number: INPLASY202080112). We conducted a comprehensive search in eight databases of literature before September 13, 2019. Trials comparing HIIT and MICT in participants with CAD or HF aged 52-78 years were included. Exercise capacity (peak oxygen consumption (peak VO2)) and prognostic markers, such as the anaerobic threshold (AT), minute ventilation/carbon dioxide production (VE/VCO2) slope, left ventricular ejection fraction (LVEF), and prognostic value of the predicted VO2 max per cent (the predicted VO2 peak (%)) were examined. Results: A total of 15 studies were included comprising 664 patients, 50% of which were male, with an average age of 60.3 ± 13.2 years. For patients with CAD, HIIT significantly improved peak VO2 values (95% CI 0.7 to 2.11) compared with MICT, but peak VO2 values in patients with HF did not seem to change. For training lasting less than eight weeks, HIIT significantly improved peak VO2 values (95% CI 0.70 to 2.10), while HIIT lasting 12 weeks or longer resulted in a modestly increased peak VO2 value (95% CI 0.31 to 5.31). High-intensity interval training significantly increased the AT when compared with MICT (95% CI 0.50 to 1.48). High-intensity interval training also caused a moderate increase in LVEF (95% CI 0.55 to 5.71) but did not have a significant effect on the VE/VCO2 slope (95% CI -2.32 to 0.98) or the predicted VO2 peak (95% CI -2.54 to 9.59) compared with MICT. Conclusions: High-intensity interval training is an effective therapy for improving peak VO2 values in patients with CAD. High-intensity interval training in the early stage (eight weeks or fewer) is superior to MICT. Finally, HIIT significantly improved prognostic markers, including the AT and LVEF in patients with CAD and HF.

Myeloperoxidase exerts anti-tumor activity in glioma after radiotherapy.

BACKGROUND: Host immune response is a critical component in tumorigenesis and immune escape. Radiation is widely used for glioblastoma (GBM) and can induce marked tissue inflammation and substantially alter host immune response. However, the role of myeloperoxidase (MPO), a key enzyme in inflammation and host immune response, in tumorigenesis after radiotherapy is unclear. In this study, we aimed to determine how post-radiation MPO activity influences GBM and outcome. METHODS: We injected C57BL/6J or MPO-knockout mice with 005 mouse GBM stem cells intracranially. To observe MPO's effects on post-radiation tumor progression, we then irradiated the head with 10 Gy unfractionated and treated the mice with a specific MPO inhibitor, 4-aminobenzoic acid hydrazide (ABAH), or vehicle as control. We performed semi-quantitative longitudinal molecular MRI, enzymatic assays and flow cytometry to assess changes in inflammatory response and tumor size, and tracked survival. We also performed cell culture experiments in murine and human GBM cells to determine the effect of MPO on these cells. RESULTS: Brain irradiation increased the number of monocytes/macrophages and neutrophils, and boosted MPO activity by ten-fold in the glioma microenvironment. However, MPO inhibition dampened radiation-induced inflammation, demonstrating decreased MPO-specific signal on molecular MRI and attenuated neutrophil and inflammatory monocyte/macrophage recruitment to the glioma. Compared to saline-treated mice, both ABAH-treated and MPO-knockout mice had accelerated tumor growth and reduced survival. We further confirmed that MPO decreased tumor cell viability and proliferation in cell cultures. CONCLUSION: Local radiation to the brain initiated an acute systemic inflammatory response with increased MPO-carrying cells both in the periphery and the GBM, resulting in increased MPO activity in the tumor microenvironment. Inhibition or absence of MPO activity increased tumor growth and decreased host survival, revealing that elevated MPO activity after radiation has an anti-tumor role.

[Effects of hypoxia and acidification stress on ion regulation and gill structure of juvenile Larimichthys crocea.] / ä½Žæ°§åŠé ¸åŒ–èƒè¿«å¯¹å¤§é»„é±¼å¹¼é±¼ç¦»å­è°ƒèŠ‚ä¸Žé³ƒç»„ç»‡ç»“æž„çš„å½±å“.

To investigate the ion regulation of large yellow croaker (Larimichthys crocea) under hypoxia and acidification stresses, we investigated the effects of hypoxia (dissolved oxygen DO 3.5 mg·L-1, pH 8.1), acidification (DO 7.0 mg·L-1, pH 7.35) and combined stresses of hypoxia and acidification (DO 3.5 mg·L-1, pH 7.35) on gill tissue structure and physiological indices related to ion regulation of juvenile L. croaker. The results showed that, under hypoxia stress, gill Na+/K+-ATPase activity, serum Na+, Ca2+ and Cl- contents of juvenile L. croaker decreased first and then increased. Under acidification stress, gill Ca2+-ATPase activity, serum Na+ and Ca2+ contents of juvenile L. croaker increased first and then decreased. Under the combined stresses of hypoxia and acidification, Na+/K+-ATPase activity and Na+, K+ and Ca2+ contents increased first and then decreased, while Ca2+-ATPase activity and Cl- content decreased first and then increased. The results of gill histology showed that hypoxia and acidification stresses led to the detachment of gill epithelial cells, and the combined stresses of hypoxia and acidification led to proliferation, hypertrophy and swelling of gill epithelial cells. Comprehensive analysis showed that hypoxia and acidification stress affected the activities of major ion regulatory enzymes in juvenile L. croaker and caused different degrees of damage to gill tissue, resulting in imbalanced ion regulation in juvenile L. croaker.

miR-223-3p inhibits the progression of atherosclerosis via down-regulating the activation of MEK1/ERK1/2 in macrophages.

BACKGROUND: microRNAs (miRNAs) have drawn more attention to the progression of atherosclerosis (AS), due to their noticeable inflammation function in cardiovascular disease. Macrophages play a crucial role in disrupting atherosclerotic plaque, thereby we explored the involvement of miR-223-3p in the inflammatory response in macrophages. METHODS: RT-qPCR was used to analyze the miR-223-3p levels in carotid arteries and serum of AS patients. ROC curve was used to assess the diagnostic value of miR-223-3p. Movat staining was applied to evaluate the morphological differences. FISH was used to identify the expression of miR-223-3p in macrophages of atherosclerotic lesions. Bioinformatic analysis was performed. Double-immunofluorescence and western blot were performed to assess the inflammatory cytokine secretion and p-ERK1/2. C16-PAF was injected into the culture medium of the miR-223-3p mimic/NC-transfected macrophages with ox-LDL. RESULTS: MiR-223-3p was up-regulated in AS patients and was associated with a higher overall survival rate. MiR-223-3p was co-localized with CD68+ macrophages in vulnerable atherosclerotic lesions. MiR-223-3p mimics decreased atherosclerotic lesions, macrophages numbers whereas increased SMCs numbers in the lesions. The TNF-a immune-positive areas were reduced by miR-223-3p mimics. MAP2K1 was negatively associated with miR-223-3p. MiR-223-3p mimics reduced the inflammation and the MEK1/ERK1/2 signaling pathway in vivo and in vitro. C16-PAF reversed the effects of miR-223-3p mimics on inflammation and ERK1/2 signaling pathway. CONCLUSIONS: MiR-223-3p negatively regulates inflammatory responses by the MEK1/ERK1/2 signaling pathway. Our study provides new insight into how miR-223-3p protects against atherosclerosis, representing a broader therapeutic prospect for treating atherosclerosis by miR-223-3p.

Spatiotemporal patterns of a diffusive prey-predator model with spatial memory and pregnancy period in an intimidatory environment.

Spatial memory and predator-induced fear have recently been considered in modeling population dynamics of animals independently. This paper is the first to integrate both aspects in a prey-predator model with pregnancy cycle to investigate the direct and indirect effects of predation on the spatial distribution of prey. We extensively study Turing instability and Hopf bifurcation. When the prey population has slow memory-based diffusion, the model is easier to generate Turing patterns. While when the prey population has fast memory-based diffusion, the model can exhibit rich dynamics. Specifically, (1) for the model with spatial memory delay only, the prey population with long term memory shows a spatially nonhomogeneous periodic distribution; (2) for the model with pregnancy delay only, the prey population with long pregnancy cycles shows a spatially homogeneous (or nonhomogeneous) periodic distribution, and (3) for the model with both the two time delays, more interesting spatiotemporal dynamics can be observed for long memory delay and (or) long pregnancy cycles. Our findings indicate that both spatial memory and pregnancy cycle play significant roles in the pattern formation of prey-predator interactions.

Molecular immuno-imaging improves tumor detection in head and neck cancer.

Detection and accurate delineation of tumor is important for the management of head and neck squamous cell carcinoma (HNSCC) but is challenging with current imaging techniques. In this study, we evaluated whether molecular immuno-imaging targeting myeloperoxidase (MPO) activity, an oxidative enzyme secreted by many myeloid innate immune cells, would be superior in detecting tumor extent compared to conventional contrast agent (DTPA-Gd) in a carcinogen-induced immunocompetent HNSCC murine model and corroborated in human surgical specimens. In C57BL/6 mice given 4-nitroquinoline-N-oxide (4-NQO), there was increased MPO activity in the head and neck region as detected by luminol bioluminescence compared to that of the control group. On magnetic resonance imaging, the mean enhancing volume detected by the MPO-targeting agent (MPO-Gd) was higher than that by the conventional agent DTPA-Gd. The tumor volume detected by MPO-Gd strongly correlated with tumor size on histology, and higher MPO-Gd signal corresponded to larger tumor size found by imaging and histology. On the contrary, the tumor volume detected by DTPA-Gd did not correlate as well with tumor size on histology. Importantly, MPO-Gd imaging detected areas not visualized with DTPA-Gd imaging that were confirmed histopathologically to represent early tumor. In human specimens, MPO was similarly associated with tumors, especially at the tumor margins. Thus, molecular immuno-imaging targeting MPO not only detects oxidative immune response in HNSCC, but can better detect and delineate tumor extent than nonselective imaging agents. Thus, our findings revealed that MPO imaging could improve tumor resection as well as be a useful imaging biomarker for tumor progression, and potentially improve clinical management of HNSCC once translated.

D-Mannose Slows Glioma Growth by Modulating Myeloperoxidase Activity.

Host immune response in the tumor microenvironment plays key roles in tumorigenesis. We hypothesized that D-mannose, a simple sugar with anti-inflammatory properties, could decrease oxidative stress and slow glioma progression. Using a glioma stem cell model in immunocompetent mice, we induced gliomas in the brain and tracked MPO activity in vivo with and without D-mannose treatment. As expected, we found that D-mannose treatment decreased the number of MPO+ cells and slowed glioma progression compared to PBS-treated control animals with gliomas. Unexpectedly, instead of decreasing MPO activity, D-mannose increased MPO activity in vivo, revealing that D-mannose boosted the MPO activity per MPO+ cell. On the other hand, D-glucose had no effect on MPO activity. To better understand this effect, we examined the effect of D-mannose on bone marrow-derived myeloid cells. We found that D-mannose modulated MPO activity via two mechanisms: directly via N-glycosylation of MPO, which boosted the MPO activity of each molecule, and indirectly by increasing H2O2 production, the main substrate for MPO. This increased host immune response acted to reduce tumor size, suggesting that increasing MPO activity such as through D-mannose administration may be a potential new therapeutic direction for glioma treatment.

d-mannose suppresses oxidative response and blocks phagocytosis in experimental neuroinflammation.

Inflammation drives the pathology of many neurological diseases. d-mannose has been found to exert an antiinflammatory effect in peripheral diseases, but its effects on neuroinflammation and inflammatory cells in the central nervous system have not been studied. We aimed to determine the effects of d-mannose on key macrophage/microglial functions-oxidative stress and phagocytosis. In murine experimental autoimmune encephalomyelitis (EAE), we found d-mannose improved EAE symptoms compared to phosphate-buffered saline (PBS)-control mice, while other monosaccharides did not. Multiagent molecular MRI performed to assess oxidative stress (targeting myeloperoxidase [MPO] using MPO-bis-5-hydroxytryptamide diethylenetriaminepentaacetate gadolinium [Gd]) and phagocytosis (using cross-linked iron oxide [CLIO] nanoparticles) in vivo revealed that d-mannose-treated mice had smaller total MPO-Gd+ areas than those of PBS-control mice, consistent with decreased MPO-mediated oxidative stress. Interestingly, d-mannose-treated mice exhibited markedly smaller CLIO+ areas and much less T2 shortening effect in the CLIO+ lesions compared to PBS-control mice, revealing that d-mannose partially blocked phagocytosis. In vitro experiments with different monosaccharides further confirmed that only d-mannose treatment blocked macrophage phagocytosis in a dose-dependent manner. As phagocytosis of myelin debris has been known to increase inflammation, decreasing phagocytosis could result in decreased activation of proinflammatory macrophages. Indeed, compared to PBS-control EAE mice, d-mannose-treated EAE mice exhibited significantly fewer infiltrating macrophages/activated microglia, among which proinflammatory macrophages/microglia were greatly reduced while antiinflammatory macrophages/microglia increased. By uncovering that d-mannose diminishes the proinflammatory response and boosts the antiinflammatory response, our findings suggest that d-mannose, an over-the-counter supplement with a high safety profile, may be a low-cost treatment option for neuroinflammatory diseases such as multiple sclerosis.

Recapitulative haematopoietic development of human pluripotent stem cells in the absence of exogenous haematopoietic cytokines.

To improve the recapitulative quality of human pluripotent stem cell (hPSC) differentiation, we removed exogenous haematopoietic cytokines from the defined differentiation system. Here, we show that endogenous stimuli and VEGF are sufficient to induce robust hPSC-derived haematopoiesis, intensive generation of haematopoietic progenitors, maturation of blood cells and the emergence of definitive precursor cells including those that phenotypically identical to early human embryonic haematopoietic stem cells (HSCs). Moreover, the cytokine-free system produces significantly higher numbers of haematopoietic progenitors compared to the published protocols. The removal of cytokines revealed a broad developmental potential of the early blood cells, stabilized the hPSC-derived definitive precursors and led to spontaneous activation of inflammatory signalling. Our cytokine-free protocol is simple, efficient, reproducible and applicable for embryonic stem cells (ESCs) and induced PSCs. The spectrum of recapitulative features of the novel protocol makes the cytokine-free differentiation a preferred model for studying the early human haematopoietic development.

Highly Efficient Activatable MRI Probe to Sense Myeloperoxidase Activity.

Myeloperoxidase (MPO) is a key component of innate immunity but can damage tissues when secreted abnormally. We developed a new generation of a highly efficient MPO-activatable MRI probe (heMAMP) to report MPO activity. heMAMP has improved Gd stability compared to bis-5-HT-Gd-DTPA (MPO-Gd) and demonstrates no significant cytotoxicity. Importantly, heMAMP is more efficiently activated by MPO compared to MPO-Gd, 5HT-DOTA(Gd), and 5HT-DOTAGA-Gd. Molecular docking simulations revealed that heMAMP has increased rigidity via hydrogen bonding intramolecularly and improved binding affinity to the active site of MPO. In animals with subcutaneous inflammation, activated heMAMP showed a 2-3-fold increased contrast-to-noise ratio (CNR) compared to activated MPO-Gd and 4-10 times higher CNR compared to conventional DOTA-Gd. This increased efficacy was further confirmed in a model of unstable atherosclerotic plaque where heMAMP demonstrated a comparable signal increase and responsiveness to MPO inhibition at a 3-fold lower dosage compared to MPO-Gd, further underscoring heMAMP as a potential translational candidate.

A systematic review of clinical efficacy of frozen-thawed embryos and fresh embryos in in-vitro fertilization cycles.

BACKGROUND: Frozen-thawed embryo (FTE) and fresh embryo (FE) transfer are two common strategies in vitro fertilization (IVF), while the results and findings still vary among studies. METHODS: We searched multiple databases for relevant studies comparing the clinical effects of FTE and FE. Meta-analyses were conducted with Review Manager 5.0 to assess the efficacy among included articles. We also analyzed the risk of bias for the reports. RESULTS: Nine studies eventually met the inclusion criteria from 2010 to 2018, and 11396 patients were included. The meta-analyses indicated no significant difference in biochemical pregnancy, clinical pregnancy and ongoing pregnancy rates. Meanwhile, the implantation rate and live birth rate in frozen-thawed embryos were much higher than those of fresh embryo. The birth weight in the frozen-thawed ET group was greater than that of the FE group, and the low birth weight rate in FTE was lower than FE group. CONCLUSION: Our findings suggested a trend toward favouring frozen-thawed FTE might be a preferred transfer strategy for patients with IVF.

Establishment of an induced pluripotent stem cell line SPHi001-A from a systemic lupus erythematosus patient combined with preeclampsia and psoriasis.

Systemic lupus erythematosus (SLE) is a heterogeneous, autoimmune disease that can affect multiple organs and systems such as skin, joints, kidneys, hematologic system or central nervous system. Women of childbearing age are the predominate population affected by SLE. In this study, we generated an iPS cell line from a 30-year-old female who was pregnant with a gestational age of 27 weeks and diagnosed with severe preeclampsia, SLE and psoriasis. This patient-specific iPSC line will be useful to create the specific disease model of systemic lupus erythematosus to elucidate the pathological mechanisms and develop drug screening.