Histological Features of Uterine Myometrial Dysfunction: Possible Involvement of Localized Inflammation.

OBJECTIVE: The latest perspective suggests that elevated levels of inflammation and cytokines are implicated in atonic postpartum hemorrhage. Lipopolysaccharide (LPS) has been widely used to induce inflammation in animal models. Therefore, this study aimed to induce uterine inflammation using LPS to investigate whether local inflammation triggers dysfunction and atrophy in the myometrium, as well as the potential underlying molecular mechanisms involved. METHODS: In vivo, an animal model was established by intraperitoneal injection of 300 µg/ kg LPS in rats on gestational day 21. Hematoxylin-eosin (H&E) staining and Masson staining were employed to determine morphological changes in the rat uterine smooth muscle. Enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory cytokines. Immunohistochemistry, tissue fluorescence, and Western blotting were conducted to assess the expression levels of the uterine contraction-related proteins Toll-like receptor 4 (TLR4) and the nuclear factor kappa-B (NF-κB) signaling pathway. In vitro, human uterine smooth muscle cells (HUtSMCs) were exposed to 2 µg/mL LPS to further elucidate the involvement of the TLR4/NF-κB signaling pathway in LPS-mediated inflammation. RESULTS: In this study, LPS induced uterine myometrial dysfunction in rats, leading to a disorganized arrangement, a significant increase in collagen fiber deposition, and widespread infiltration of inflammatory cells. In both in vivo animal models and in vitro HUtSMCs, LPS elevated IL-6, IL-1ß, and TNF-α levels while concurrently suppressing the expression of connexin 43 (Cx43) and oxytocin receptor (OXTR). Mechanistically, the LPS-treated group exhibited TLR4 activation, and the phosphorylation levels of p65 and IκBα were notably increased. CONCLUSION: LPS triggered the TLR4/NF-κB signaling pathway, inducing an inflammatory response in the myometrium and leading to uterine myometrial dysfunction and uterine atony.

Multilayer network analysis of dynamic network reconfiguration in patients with moderate-to-severe obstructive sleep apnea and its association with neurocognitive function.

BACKGROUND: Brain functional network disruption and neurocognitive dysfunction have been reported in obstructive sleep apnea (OSA) patients. Nevertheless, most research studies static networks, while brain evolution continues dynamically. PURPOSE: To investigate the characteristics of dynamical networks in moderate-to-severe OSA patients using multilayer network analysis of dynamic networks and compare their association with neurocognitive function. METHODS: Twenty-seven moderate-to-severe OSA patients and twenty-five matched healthy controls (HCs) who completed the examination of the Epworth sleepiness scale (ESS), neurocognitive function, polysomnography, and functional magnetic resonance imaging (fMRI) were prospectively included. The dynamic variations of resting-state functional networks in both groups were described via network switching rate. Switching rates and their correlation with clinical parameters were analyzed. RESULTS: At the global level, network switching rates were notably lower in the OSA group than in the HCs group (p = 0.002). More specifically, the differences include the default mode network (DMN), auditory network, and ventral attention network at the subnetwork level, and the right rolandic operculum, left middle temporal gyrus, and right precentral gyrus at the nodal level. Furthermore, these altered switching rates have a close correlation with ESS, sleep parameters, and neurocognitive function. CONCLUSION: Patients with moderate-to-severe OSA showed lower network switching rates, especially in the DMN, auditory network, and ventral attention network. The disruption of dynamic functional networks may be a potentially crucial mechanism of neurocognitive dysfunction in moderate-to-severe OSA patients.

LncRNA HCG27 Promotes Glucose Uptake Ability of HUVECs by MiR-378a-3p/MAPK1 Pathway.

OBJECTIVE: Gestational diabetes mellitus (GDM) is the most common metabolic disorder during pregnancy. LncRNA HLA complex group 27 (HCG27) plays a crucial role in various metabolic diseases. However, the relationship between lncRNA HCG27 and GDM is not clear. This study aimed to verify a competing endogenous RNA (ceRNA) interaction regulation axis of miR-378a-3p/mitogen-activated protein kinase 1 (MAPK1) regulated by HCG27 in GDM. METHODS: LncRNA HCG27 and miR-378a-3p were detected by RT-qPCR. The expression of MAPK1 in umbilical vein endothelial cells (HUVECs) was detected by RT-qPCR and that in the placenta by Western blotting. To explore the relationship among lncRNA HCG27, miR-378a-3p, MAPK1 and the glucose uptake ability of HUVECs, vector HCG27, si-HCG27, miR-378a-3p mimic and inhibitor were transfected to achieve overexpression and inhibition of HCG27 or miR-378a-3p. The interaction between miR-378a-3p and lncRNA HCG27 or MAPK1 was confirmed by the dual-luciferase reporter assay. Besides, glucose consumption by HUVECs was detected by the glucose assay kit. RESULTS: HCG27 expression was significantly decreased in both the placenta and primary umbilical vein endothelial cells, while the expression of miR-378a-3p was significantly increased in GDM tissues, and the expression of MAPK1 was decreased in GDM tissues. This ceRNA interaction regulation axis was proved to affect the glucose uptake function of HUVECs. The transfection of si-HCG27 could significantly reduce the expression of the MAPK1 protein. If the MAPK1 overexpression plasmid was transfected simultaneously with si-HCG27 transfection, the reduced glucose uptake in HUVECs resulting from the decrease in lncRNA HCG27 was reversed. MiR-378a-3p mimic can significantly reduce the mRNA expression of MAPK1 in HUVECs, whereas miR-378a-3p inhibitor can significantly increase the mRNA expression of MAPK1. The inhibition of miR-378a-3p could restore the decreased glucose uptake of HUVECs treated with si-HCG27. Besides, overexpression of lncRNA HCG27 could restore the glucose uptake ability of the palmitic acid-induced insulin resistance model of HUVECs to normal. CONCLUSION: LncRNA HCG27 promotes glucose uptake of HUVECs by miR-378a-3p/MAPK1 pathway, which may provide potential therapeutic targets for GDM. Besides, the fetal umbilical cord blood and umbilical vein endothelial cells collected from pregnant women with GDM after delivery could be used to detect the presence of adverse molecular markers of metabolic memory, so as to provide guidance for predicting the risk of cardiovascular diseases and health screening of offspring.

Differential and correlational tractography as tract-based biomarkers in mild traumatic brain injury: A longitudinal MRI study.

We evaluated the fiber bundles in mild traumatic brain injury (mTBI) patients using differential and correlational tractography in a longitudinal analysis. Diffusion MRI data were acquired in 34 mTBI patients at 7 days (acute stage) and 3 months or longer (chronic stage) after mTBI. Trail Making Test A (TMT-A) and Digital Symbol Substitution Test changes were used to evaluate the cognitive performance. Longitudinal correlational tractography showed decreased anisotropy in the corpus callosum during the chronic mTBI stage. The changes in anisotropy in the corpus callosum were significantly correlated with the changes in TMT-A (false discovery rate [FDR] = 0.000094). Individual longitudinal differential tractography found that anisotropy decreased in the corpus callosum in 30 mTBI patients. Group cross-sectional differential tractography found that anisotropy increased (FDR = 0.02) in white matter in the acute mTBI patients, while no changes occurred in the chronic mTBI patients. Our study confirms the feasibility of using correlational and differential tractography as tract-based monitoring biomarkers to evaluate the disease progress of mTBI, and indicates that normalized quantitative anisotropy could be used as a biomarker to monitor the injury and/or repairs of white matter in individual mTBI patients.

Genes Associated with Altered Brain Structure and Function in Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) has been widely reported to cause abnormalities in brain structure and function, but the genetic mechanisms behind these changes remain largely unexplored. Our research aims to investigate the relationship between sleep characteristics, cognitive impairments, genetic factors, and brain structure and function in OSA. Using structural and resting-state functional magnetic resonance imaging data, we compared cortical morphology and spontaneous brain activity between 28 patients with moderate-to-severe OSA and 34 healthy controls (HCs) utilizing voxel-based morphology (VBM) and the amplitude of low-frequency fluctuations (ALFF) analyses. In conjunction with the Allen Human Brain Atlas, we used transcriptome-neuroimaging spatial correlation analyses to investigate gene expression patterns associated with changes in gray matter volume (GMV) and ALFF in OSA. Compared to the HCs, the OSA group exhibited increased ALFF values in the left hippocampus (t = 5.294), amygdala (t = 4.176), caudate (t = 4.659), cerebellum (t = 5.896), and decreased ALFF values in the left precuneus (t = -4.776). VBM analysis revealed increased GMV in the right inferior parietal lobe (t = 5.158) in OSA. Additionally, functional enrichment analysis revealed that genes associated with both ALFF and GMV cross-sampling were enriched in gated channel activity and synaptic transmission, glutamatergic synapse, and neuron.

Voicing the story behind the cover.

In this selection, we celebrate the art of science by highlighting some of the submitted cover images from the past year. In this collection, our authors share the stories behind their inspiration for how to portray their science to captivate a broader audience.

Effectiveness of six-step complex decongestive therapy for treating upper limb lymphedema after breast cancer surgery.

BACKGROUND: Complex decongestive therapy (CDT) is currently recommended as the standard treatment for lymphedema. CDT is a four-step detumescence therapy that can effectively treat upper limb lymphedema after breast cancer surgery, and is considered non-invasive, painless and without side effects. AIM: To determine the effectiveness of a six-step CDT involving a foam granule bandage for the treatment of upper extremity lymphedema pressure after breast cancer surgical intervention. METHODS: The study included 100 patients with upper extremity lymphedema after breast cancer surgery. The surgical methods were mastectomy plus axillary lymph node dissection and breast preservation plus sentinel lymph node biopsy. The study population was further divided into the experimental group and control group with 50 cases in each group. The control group was given conventional CDT (four-step method), which included skin care, freehand lymphatic drainage, foam granule pressurized bandage, and functional exercise. In the experimental group, a six-step CDT method was applied that involved a foam particle bandage combined with air wave pressure therapy in addition to the four steps of conventional CDT. Patients in both groups were given one course of treatment daily (20 times), and the changes in body moisture and subjective symptoms were measured before and after treatment, preoperatively and 20 times after treatment. RESULTS: No statistically significant differences in 50-Hz bioelectrical impedance and extracellular moisture ratio were observed between the two groups before treatment, suggesting comparability of the baseline data. After treatment, the 50-Hz bioelectrical impedance of the experimental group was significantly higher than that in the control group, and the extracellular moisture ratio was significantly lower than that in the control group. A comparison of the differences between the two groups before and after treatment indicated that the treatment effect in the experimental group was better than that in the control group. After 20 treatments, according to subjective evaluations, the tightness and swelling of the limbs in the experimental group were significantly reduced as compared with those in the control group. CONCLUSION: The six-step CDT method can effectively reduce lymphedema, promote lymphatic circulation, and alleviate the subjective symptoms of patients, and thereby improve the quality of life and treatment compliance among patients.

An ex vivo system to study cellular dynamics underlying mouse peri-implantation development.

Upon implantation, mammalian embryos undergo major morphogenesis and key developmental processes such as body axis specification and gastrulation. However, limited accessibility obscures the study of these crucial processes. Here, we develop an ex vivo Matrigel-collagen-based culture to recapitulate mouse development from E4.5 to E6.0. Our system not only recapitulates embryonic growth, axis initiation, and overall 3D architecture in 49% of the cases, but its compatibility with light-sheet microscopy also enables the study of cellular dynamics through automatic cell segmentation. We find that, upon implantation, release of the increasing tension in the polar trophectoderm is necessary for its constriction and invagination. The resulting extra-embryonic ectoderm plays a key role in growth, morphogenesis, and patterning of the neighboring epiblast, which subsequently gives rise to all embryonic tissues. This 3D ex vivo system thus offers unprecedented access to peri-implantation development for in toto monitoring, measurement, and spatiotemporally controlled perturbation, revealing a mechano-chemical interplay between extra-embryonic and embryonic tissues.

R2* value derived from multi-echo Dixon technique can aid discrimination between benign and malignant focal liver lesions.

BACKGROUND: R2* estimation reflects the paramagnetism of the tumor tissue, which may be used to differentiate between benign and malignant liver lesions when contrast agents are contraindicated. AIM: To investigate whether R2* derived from multi-echo Dixon imaging can aid differentiating benign from malignant focal liver lesions (FLLs) and the impact of 2D region of interest (2D-ROI) and volume of interest (VOI) on the outcomes. METHODS: We retrospectively enrolled 73 patients with 108 benign or malignant FLLs. All patients underwent conventional abdominal magnetic resonance imaging and multi-echo Dixon imaging. Two radiologists independently measured the mean R2* values of lesions using 2D-ROI and VOI approaches. The Bland-Altman plot was used to determine the interobserver agreement between R2* measurements. Intraclass correlation coefficient (ICC) was used to determine the reliability between the two readers. Mean R2* values were compared between benign and malignant FFLs using the nonparametric Mann-Whitney test. Receiver operating characteristic curve analysis was used to determine the diagnostic performance of R2* in differentiation between benign and malignant FFLs. We compared the diagnostic performance of R2* measured by 2D-ROI and VOI approaches. RESULTS: This study included 30 benign and 78 malignant FLLs. The interobserver reproducibility of R2* measurements was excellent for the 2D-ROI (ICC = 0.994) and VOI (ICC = 0.998) methods. Bland-Altman analysis also demonstrated excellent agreement. Mean R2* was significantly higher for malignant than benign FFLs as measured by 2D-ROI (P < 0.001) and VOI (P < 0.001). The area under the curve (AUC) of R2* measured by 2D-ROI was 0.884 at a cut-off of 25.2/s, with a sensitivity of 84.6% and specificity of 80.0% for differentiating benign from malignant FFLs. R2* measured by VOI yielded an AUC of 0.875 at a cut-off of 26.7/s in distinguishing benign from malignant FFLs, with a sensitivity of 85.9% and specificity of 76.7%. The AUCs of R2* were not significantly different between the 2D-ROI and VOI methods. CONCLUSION: R2* derived from multi-echo Dixon imaging whether by 2D-ROI or VOI can aid in differentiation between benign and malignant FLLs.

Detection and Classification of Breast Lesions With Readout-Segmented Diffusion-Weighted Imaging in a Large Chinese Cohort.

Objectives: To evaluate the performance of readout-segmented echo-planar imaging DWI (rs-EPI DWI) in detecting and characterizing breast cancers in a large Chinese cohort with comparison to dynamic contrast-enhanced MRI (DCE-MRI). Methods: The institutional review board approved this retrospective study with waived written informed consent. A total of 520 women (mean age, 43.1- ± 10.5-years) were included from July 2013 to October 2019. First, the ability of rs-EPI DWI in detecting breast lesions identified by DCE-MRI was evaluated. The lesion conspicuity of rs-EPI-DWI and DCE-MRI was compared using the Wilcoxon signed rank test. With pathology as a reference, the performance of rs-EPI DWI and DCE-MRI in distinguishing breast cancers was evaluated and compared using the Chi-square test. Results: Of 520 women, 327/520 (62.9%) patients had 423 lesions confirmed by pathology with 203 benign and 220 malignant lesions. The rs-EPI DWI can detect 90.8% (659/726) (reader 1) and 90.6% (663/732) (reader 2) of lesions identified by DCE-MRI. The lesion visibility was superior for DCE-MRI than rs-EPI-DWI (all p < 0.05). With pathology as a reference, the sensitivities and specificities of rs-EPI DWI in diagnosing breast cancers were 95.9% (211/220) and 85.7% (174/203) for reader 1 and 97.7% (215/220) and 86.2% (175/203) for reader 2. No significant differences were found for the performance of DCE-MRI and rs-EPI DWI in discriminating breast cancers (all p > 0.05). Conclusions: Although with an inferior lesion visibility, rs-EPI DWI can detect about 90% of breast lesions identified by DCE-MRI and has comparable diagnostic capacity to that of DCE-MRI in identifying breast cancer.

[Effect of psoralen on rat osteoblasts injuries induced by TCP wear particles in vitro and its mechanism].

Objective: To investigate the effect and mechanism of psoralen on calvarial osteoblasts injuries caused by tricalcium phosphate (TCP) wear particles in vitro.Methods: Primary osteoblasts were obtained from the calvaria of neonatal SD rat by the series of digestion and were identified with ALP staining. Calvarial osteoblasts were treated with TCP wear particles for 48 h to establish the in vitro model of osteoblasts injuries. The rat osteoblasts were randomly divided into control group, TCP wear particles (0.1 mg/ml) group, psoralen treated (at the concentrations of 10-7, 10-6, 10-5 mol/L) groups. WST assay and the flow cytometry were used to detect the cell viability of osteoblasts and apoptosis, respectively. Chemical colorimetry was performed to examine ALP activity of osteobalsts. When the osteoblasts were treated for 14 day, mineral nodules formation was observed with alizarin red S staining. Western blot was applied to examine protein expressions of glucose regulated protein78/94(GRP78/94), inositol dependent enzyme 1 alpha (IREα), spliced X-box binding protein 1 (XBP1s) and phosphorylated c-Jun N-terminal kinase (p-JNK) in calvarial osteoblasts. Results: Compared with control group, the cell viability of osteoblasts, ALP activity and mineral nodules formation in TCP group were decreased significantly (P＜0.05), while the percentage of apoptosis and protein expressions of GRP78/94, IRE1α, XBP1 and p-JNK were obviously increased in calvarial osteoblasts (P＜0.05). Compared with TCP group, the injuries of calvarial osteoblasts and cell apoptosis in psoralen treated groups were obviously decreased (P＜0.05), and the expression levels of GRP78/94, IRE1α, XBP1 and p-JNK were down-regulated remarkably (P＜0.05). Conclusion: Psoralen prevents osteoblasts injuries caused by TCP wear particles through IRE1α-XBP1s-JNK signaling pathway activation.

Salvianolic acid B decreases interleukin-1ß-induced colitis recurrence in mice.

BACKGROUND: Degree of mucosal recovery is an important indicator for evaluating the therapeutic effects of drugs in treatment of inflammatory bowel disease (IBD). Increasing evidences has proved that tight junction (TJ) barrier dysfunction is one of the pathological mechanisms of IBD. The aim of this study was to observe whether enhancement of TJ can decrease colitis recurrence. METHODS: Eighty C57BL/6 mice were randomly divided into four groups including normal group, colitis group, sulfasalazine (SASP) treated group, and traditional Chinese drug salvianolic acid B (Sal B) treated group. Colitis was established in mice by free drinking water containing dextran sulfate sodium, after treatments by SASP and Sal B, recombinant human interleukin-1ß (IL-1ß) was injected intraperitoneally to induce colitis recurrence. RESULTS: Compared with sham control, cell apoptosis in colitis group was increased from 100.85 ±â€Š3.46% to 162.89 ±â€Š11.45% (P = 0.0038), and TJ dysfunction marker myosin light chain kinase (MLCK) was also significantly increased from 99.70 ±â€Š9.29% to 296.23 ±â€Š30.78% (P = 0.0025). The increased cell apoptosis was reversed by both SASP (125.99 ±â€Š8.45% vs. 162.89 ±â€Š11.45%, P = 0.0059) and Sal B (104.27 ±â€Š6.09% vs. 162.89 ±â€Š11.45%, P = 0.0044). High MLCK expression in colitis group was reversed by Sal B (182.44 ±â€Š89.42% vs. 296.23 ±â€Š30.78%, P = 0.0028) but not influenced by SASP (285.23 ±â€Š41.04% vs. 296.23 ±â€Š30.78%, P > 0.05). The recurrence rate induced by recombinant human IL-1ß in Sal B-treated group was significantly lower than that in SASP-treated group. CONCLUSIONS: These results suggested a link between intestinal mucosal barrier dysfunction, especially TJ barrier dysfunction, and colitis recurrence. The TJ barrier dysfunction in remission stage of colitis increased the colitis recurrence. This study might provide potential treatment strategies for IBD recurrence.

Symmetry Breaking in the Mammalian Embryo.

We present an overview of symmetry breaking in early mammalian development as a continuous process from compaction to specification of the body axes. While earlier studies have focused on individual symmetry-breaking events, recent advances enable us to explore progressive symmetry breaking during early mammalian development. Although we primarily discuss embryonic development of the mouse, as it is the best-studied mammalian model system to date, we also highlight the shared and distinct aspects between different mammalian species. Finally, we discuss how insights gained from studying mammalian development can be generalized in light of self-organization principles. With this review, we hope to highlight new perspectives in studying symmetry breaking and self-organization in multicellular systems.

Evaluating steady-state and time-resolved fluorescence as a tool to study the behavior of asphaltene in toluene.

A combination of steady-state fluorescence, fluorescence lifetime measurements and the determination of time-resolved emission spectra were employed to characterize asphaltene toluene solutions. Lifetime measurements were shown to be insensitive to the source of asphaltene or the alkane solvent from which asphaltene was precipitated. This insensitivity suggests that either the composition of Athabasca and Cold Lake asphaltene is very similar or that the fluorescence behavior is dominated by the same sub-set of fluorophores for the different samples. These results highlight the limitations in using fluorescence to characterize asphaltene solutions. Different dependencies were observed for the average lifetimes with the asphaltene concentration when measured at two different emission wavelengths (420 nm and 520 nm). This result suggests that different fluorophores underwent diverse interactions with other asphaltene molecules as the asphaltene concentration was raised, suggesting that models for asphaltene aggregation need to include molecular diversity.

Effect of terbium(III) on the binding of aromatic guests with sodium taurocholate aggregates.

The effect of binding Tb(3+) to sodium taurocholate aggregates containing polyaromatic hydrocarbon guests was examined using pyrene and 1-ethylnaphthalene as guests that bind to the primary aggregate, and 1-naphthyl-1-ethanol as a secondary aggregate guest. Time-resolved fluorescence quenching studies were used to study the binding site properties, while laser flash photolysis quenching studies provided information on the dynamics of the guest-aggregate system. Both the primary and secondary aggregate binding sites became more compact in the presence of bound Tb(3+), while only the primary aggregate became more accessible to anionic molecules. The binding dynamics for the guest-primary aggregate system became faster when Tb(3+) was bound to the aggregate. In contrast, for the guest-secondary aggregate the presence of Tb(3+) resulted in a small decrease in the dissociation rate constant. The influence of bound Tb(3+) on the primary and secondary bile salt aggregates is significantly different, which affects how these aggregates can be used as supramolecular host systems to modify guest reactivity.