Background
Obstetric critical illness is an important factor that leads to an increase in maternal mortality. Early warning assessment can effectively reduce maternal and neonatal mortality and ...morbidity. However, there are multiple early warning systems, and the effect and applicability of each system in China still need to be explored.
Objectives
To elaborate on the application, effectiveness and challenges of the existing early warning systems for high‐risk obstetric women in China and to provide a reference for clinical practice.
Design
A scoping review guided by the Arksey and O'Malley framework and reported using the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis for scoping review (PRISMA‐ScR) guidelines.
Eligibility criteria
We included original studies related to early warning and excluded those that were guidelines, consensus and reviews. The included studies were published in Chinese or English by Chinese scholars as of June 2021.
Data sources
CNKI, Wanfang, VIP, Cochrane, CINAHL, Embase, PubMed and Web of Science databases were searched systematically, and the reference sections of the included papers were snowballed.
Results
In total, 598 articles were identified. These articles were further refined using keyword searches and exclusion criteria, and 17 articles met the inclusion criteria. We extracted data related to each study's population, methods and results. Early warning tools, outcome indices, effects and challenges are discussed.
Conclusions
Although all studies have shown that early warning systems have good application effects, the use of early warning systems in China is still limited, with poor regional management and poor sensitivity for specific obstetric women. Future research needs to develop more targeted early warning tools for high‐risk obstetric women and address the current challenges in clinical applications.
Background
Glioma stem‐like cells (GSCs) are greatly responsible for the progression of glioma. Long noncoding RNAs (lncRNAs) play an important role in glioma tumor progression. This study aims to ...explore the role and underlying mechanism of lncRNA SNHG9 in regulating GSC cell growth.
Methods
GSCs were obtained from glioma cells (U87 and U251) and referred to as GSC‐87 and GSC‐251, respectively. The interactions between miR‐326 and SNHG9 or SOX9 were analyzed using luciferase reporter assay. Cell growth of GSCs was evaluated by EdU assay and sphere formation assay.
Results
SNHG9 expression was significantly higher in GSC‐87 and GSC‐251 cells than in U87 and U251 cells. SNHG9 overexpression promoted GSC cell growth, whereas SNHG9 knockdown inhibited GSC cell growth. Mechanistically, SNHG9 acted as a competitive endogenous RNA of miR‐326 to elevate the expression of SOX9, a direct target of miR‐326. Moreover, transfection with miR‐326 inhibitor counteracted SNHG9 knockdown‐mediated inhibition of GSC cell growth.
Conclusions
SNHG9 facilitates growth of GSCs via the miR‐326/SOX9 axis. This study provides a promising therapeutic target for glioma treatment.
LncRNA SNHG9 functions as a ceRNA of miR‐326 to elevate expression of SOX9, and thereby promotes cell proliferation of glioma stem cells (GSCs). Our findings suggest that SNHG9 may be a promising therapeutic target for the treatment of glioma.
spore powder, valued for its nutritional and medicinal properties, contains polysaccharides crucial for its efficacy. However, the complex structural nature of these polysaccharides necessitates ...further investigation to fully realize their potential. This study aimed to investigate the effects of acid heat treatment on
spore polysaccharides (GLSPs) to enhance their properties and application in antitumor activity. The GLSP was obtained via acid heat treatment, concentration, and centrifugal separation. This process led to a notable reduction in polysaccharide molecular weight, increasing water solubility and bioavailability. Analytical techniques including NMR spectroscopy and methylation analysis revealed a polysaccharide composition comprising four distinct monosaccharides, with molecular weights of 3291 Da (Mw) and 3216 Da (Mn). Six different linkage modes were identified, with a molar ratio of 1:5:2:3:4:3. In vivo experiments demonstrated the GLSP's significant inhibitory effect on the growth of four tumor models (sarcoma S180, Lewis lung cancer, liver cancer H22, and colon cancer C26) in mice, with no observed toxicity. These findings suggest the GLSP's potential as an antitumor therapeutic agent for clinical use.
Phosphoglycerate mutase 1 (PGAM1) plays a pivotal role in cancer metabolism and tumor progression via its metabolic activity and interaction with other proteins like α-smooth muscle actin (ACTA2). ...Allosteric regulation is considered to be an innovative strategy to discover a highly selective and potent inhibitor targeting PGAM1. Here, we identified a novel PGAM1 allosteric inhibitor, HKB99, via structure-based optimization. HKB99 acted to allosterically block conformational change of PGAM1 during catalytic process and PGAM1-ACTA2 interaction. HKB99 suppressed tumor growth and metastasis and overcame erlotinib resistance in non-small-cell lung cancer (NSCLC). Mechanistically, HKB99 enhanced the oxidative stress and altered multiple signaling pathways including the activation of JNK/c-Jun and suppression of AKT and ERK. Collectively, the study highlights the potential of PGAM1 as a therapeutic target in NSCLC and reveals a distinct mechanism by which HKB99 inhibits both metabolic activity and nonmetabolic function of PGAM1 by allosteric regulation.
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•A PGAM1 allosteric inhibitor HKB99 is developed via structure-based optimization•HKB99 modulates PGAM1 both in its catalytic process and ACTA2 interaction•HKB99 suppresses NSCLC growth and metastasis through allosteric PGAM1 regulation•PGAM1 is a potential therapeutic target in NSCLC
PGAM1 plays a critical role in cancer cell metabolism. Huang et al. discovered a novel PGAM1 inhibitor HKB99, which allosterically blocks the structure of PGAM1, impacting both its catalytic activity and ACTA2 interaction. HKB99 significantly inhibits NSCLC tumor growth and metastasis in vivo by impacting both PGAM1’s metabolic activity and nonmetabolic function.
Abstract
Objectives
Gastrointestinal stromal tumors (GISTs) carrying different KIT exon 11 (KIT-11) mutations exhibit varying prognoses and responses to Imatinib. Herein, we aimed to determine ...whether computed tomography (CT) radiomics can accurately stratify KIT-11 mutation genotypes to benefit Imatinib therapy and GISTs monitoring.
Methods
Overall, 1143 GISTs from 3 independent centers were separated into a training cohort (TC) or validation cohort (VC). In addition, the KIT-11 mutation genotype was classified into 4 categories: no KIT-11 mutation (K11-NM), point mutations or duplications (K11-PM/D), KIT-11 557/558 deletions (K11-557/558D), and KIT-11 deletion without codons 557/558 involvement (K11-D). Subsequently, radiomic signatures (RS) were generated based on the arterial phase of contrast CT, which were then developed as KIT-11 mutation predictors using 1408 quantitative image features and LASSO regression analysis, with further evaluation of its predictive capability.
Results
The TC AUCs for K11-NM, K11-PM/D, K11-557/558D, and K11-D ranged from 0.848 (95% CI 0.812–0.884), 0.759 (95% CI 0.722–0.797), 0.956 (95% CI 0.938–0.974), and 0.876 (95% CI 0.844–0.908), whereas the VC AUCs ranged from 0.723 (95% CI 0.660–0.786), 0.688 (95% CI 0.643–0.732), 0.870 (95% CI 0.824–0.918), and 0.830 (95% CI 0.780–0.878). Macro-weighted AUCs for the KIT-11 mutant genotype ranged from 0.838 (95% CI 0.820–0.855) in the TC to 0.758 (95% CI 0.758–0.784) in VC. TC had an overall accuracy of 0.694 (95%CI 0.660–0.729) for RS-based predictions of the KIT-11 mutant genotype, whereas VC had an accuracy of 0.637 (95%CI 0.595–0.679).
Conclusions
CT radiomics signature exhibited good predictive performance in estimating the KIT-11 mutation genotype, especially in prediction of K11-557/558D genotype. RS-based classification of K11-NM, K11-557/558D, and K11-D patients may be an indication for choice of Imatinib therapy.
Drought is a cyclical phenomenon in natural environments. During dehydration, stomatal closure is mainly regulated by abscisic acid (ABA) dynamics that limit transpiration in seed plants, but ...following rehydration, the mechanism of gas exchange recovery is still not clear. In this study, leaf water potential (ψleaf), stomatal conductance (gs), leaf hydraulic conductance (Kleaf), foliar ABA level, ethylene emission rate in response to dehydration and rehydration were investigated in four Caragana species with isohydric (Caragana spinosa and C. pruinosa) and anisohydric (C. intermedia and C. microphylla) traits. Two isohydric species with ABA‐induced stomatal closure exhibited more sensitive gs and Kleaf to decreasing ψleaf than two anisohydric species which exhibited a switch from ABA to water potential‐driven stomatal closure during dehydration. Following rehydration, the recovery of gas exchange was not associated with a decrease in ABA level but was strongly limited by the degradation of the ethylene emission rate in all species. Furthermore, two anisohydric species with low drought‐induced ethylene production exhibited more rapid recovery in gas exchange upon rehydration. Our results indicated that ethylene is a key factor regulating the drought‐recovery ability in terms of gas exchange, which may shape species adaptation to drought and potential species distribution.
Drought is a cyclical phenomenon in natural environments. During dehydration, stomatal closure is mainly regulated by abscisic acid (ABA) dynamics that limit transpiration in seed plants, but the mechanisms of gas exchange recovery are still not clear following rehydration. The results in this study indicate that ethylene is a key factor regulating the drought‐recovery ability in terms of gas exchange, which may shape species adaptation to drought and potential species distribution.
Herpes simplex virus type 1 strain 129 (H129) has represented a promising anterograde neuronal circuit tracing tool, which complements the existing retrograde tracers. However, the current H129 ...derived tracers are multisynaptic, neither bright enough to label the details of neurons nor capable of determining direct projection targets as monosynaptic tracer.
Based on the bacterial artificial chromosome of H129, we have generated a serial of recombinant viruses for neuronal circuit tracing. Among them, H129-G4 was obtained by inserting binary tandemly connected GFP cassettes into the H129 genome, and H129-ΔTK-tdT was obtained by deleting the thymidine kinase (TK) gene and adding tdTomato coding gene to the H129 genome. Then the obtained viral tracers were tested in vitro and in vivo for the tracing capacity.
H129-G4 is capable of transmitting through multiple synapses, labeling the neurons by green florescent protein, and visualizing the morphological details of the labeled neurons. H129-ΔTK-tdT neither replicates nor spreads in neurons alone, but transmits to and labels the postsynaptic neurons with tdTomato in the presence of complementary expressed TK from a helper virus. H129-ΔTK-tdT is also capable to map the direct projectome of the specific neuron type in the given brain regions in Cre transgenic mice. In the tested brain regions where circuits are well known, the H129-ΔTK-tdT tracing patterns are consistent with the previous results.
With the assistance of the helper virus complimentarily expressing TK, H129-ΔTK-tdT replicates in the initially infected neuron, transmits anterogradely through one synapse, and labeled the postsynaptic neurons with tdTomato. The H129-ΔTK-tdT anterograde monosynaptic tracing system offers a useful tool for mapping the direct output in neuronal circuitry. H129-G4 is an anterograde multisynaptic tracer with a labeling signal strong enough to display the details of neuron morphology.
Pd-phosphinooxazoline (Pd-PHOX)-catalyzed asymmetric hydroalkylation of 1,3-dienes with azlactones was successfully developed for the first time, affording various enantioenriched α-quaternary ...α-amino acid derivatives bearing contiguous quaternary and tertiary stereogenic centers in good yields with exclusive regioselectivity and excellent stereoselective control (up to 92% yield, >20:1 dr, and >99% ee). The scale-up catalytic asymmetric hydroalkylation was performed well without loss of reactivity and stereoselectivities, which exhibited great potential application. The synthetic utility of the current methodology was demonstrated through product transformations to access other biologically important compounds such as chiral β-amino alcohol and α-quaternary cyclic α-amino acid derivatives.
Summary
A recent study indicated that Lectin‐type oxidized LDL receptor‐1 (LOX‐1) was a distinct surface marker for human polymorphisms myeloid‐derived suppressor cells (PMN‐MDSC). The present study ...was aimed to investigate the existence LOX‐1 PMN‐MDSC in hepatocellular carcinoma (HCC) patients. One hundred and twenty‐seven HCC patients, 10 patients with mild active chronic hepatitis B, 10 liver cirrhosis due to hepatitis B, 10 liver dysplastic node with hepatitis B and 50 health control were included. LOX‐1+ CD15+ PMN‐MDSC were significantly elevated in HCC patients compared with healthy control and patients with benign diseases. LOX‐1+ CD15+ PMN‐MDSC in circulation were positively associated with those in HCC tissues. LOX‐1+ CD15+ PMN‐MDSCs significantly reduced proliferation and IFN‐γ production of T cells with a dosage dependent manner with LOX‐1− CD15+ PMNs reached negative results. The suppression on T cell proliferation and IFN‐γ production was reversed by ROS inhibitor and Arginase inhibitor. ROS level and activity of arginase of LOX‐1 +CD15+ PMN were higher in LOX‐1+ CD15+ PMN‐MDSCs than LOX‐1− CD15+ PMNs, as well as the expression of the NADPH oxidase NOX2 and arginase I. RNA sequence revealed that LOX‐1+ CD15+ PMN‐MDSCs displayed significantly higher expression of spliced X‐box ‐binding protein 1 (sXBP1), an endoplasmic reticulum (ER) stress marker. ER stress inducer induced LOX‐1 expression and suppressive function for CD15+ PMN from health donor. For HCC patients, LOX‐1+ CD15+ PMN‐MDSCs were positively related to overall survival. Above all, LOX‐1+ CD15+ PMN‐MDSC were elevated in HCC patients and suppressed T cell proliferation through ROS/Arg I pathway induced by ER stress. They presented positive association with the prognosis of HCC patients.
A recent study indicated that lectin‐type oxidized LDL receptor‐1 (LOX‐1) was a distinct surface marker for human polymorphonuclear myeloid‐derived suppressor cells (PMN‐MDSC). The present study found that LOX‐1+ CD15+ PMN‐MDSC were elevated in hepatocellular carcinoma (HCC) patients and suppressed T‐cell proliferation through ROS/Arg I pathway induced by ER stress. They presented a positive association with the prognosis of HCC patients.
Induced pluripotent stem cells (iPSCs) are reprogrammed somatic cells that gained self‐renewal and differentiation capacity similar to embryonic stem cells. Taking the precious opportunity of the ...TianZhou‐1 spacecraft mission, we studied the effect of space microgravity (µg) on the self‐renewal capacity of iPSCs. Murine iPSCs carrying pluripotency reporter Oct4‐GFP were used. The Oct4‐EGFP‐iPSCs clones were loaded into the bioreactor and exposed to μg in outer space for 14 days. The control experiment was performed in identical device but on the ground in earth gravity (1 g). iPSCs clones were compact and highly expressed Oct4 before launch. In μg condition, cells in iPSC clones spread out more rapidly than those in ground 1 g condition during the first 3 days after launch. However, in 1 g condition, as the cell density increases, the Oct4‐GFP signal dropped significantly during the following 3 days. Interestingly, in μg condition, iPSCs originated from the spread‐out clones during the first 3 days appeared to cluster together and reform colonies that activated strong Oct4 expression. On the other hand, iPSC clones in 1 g condition were not able to recover Oct4 expression after overgrown. Our study for the first time performed real‐time imaging on the proliferation process of iPSCs in space and found that in μg condition, cell behaviour appeared to be more dynamic than on the ground.
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