Theoretical Validation of Non-Noble Cu Sites Integrated on SnO2 Nanoflowers for Enhanced Gas Sensing of Ethanethiol at Room Temperature.

Ethanethiol (EtSH), being highly toxic, flammable, and explosive, poses significant risks to human health and safety and is capable of causing fires and explosions. Room-temperature detection using chemiresistive gas sensors is essential for managing these risks. However, the gas-sensing performance of conventional metal-oxide sensing materials may be limited by their weak interaction with EtSH at room temperature. Herein, SnO2 nanoflowers assembled with non-noble Cu-site-enriched porous nanosheets were designed and prepared by an in situ self-template pyrolysis synthesis strategy to enable highly sensitive and selective room-temperature detection of EtSH. By regulating the number of non-noble Cu sites, these nanoflowers achieved efficient EtSH sensing with a Ra/Rg value of 11.0 at 50 ppb, ensuring high selectivity, reproducibility, and stability at room temperature. Moreover, a comparative analysis of the room-temperature gas-sensing performance of SnO2 nanoflowers with non-noble Fe- or Ni-site-enriched nanosheets highlights the benefits of non-noble Cu sites for EtSH detection. Density functional theory (DFT) analysis reveals that non-noble Cu sites have a unique affinity for EtSH, offering preferential binding over other gases and explaining the outstanding sensing performance of non-noble Cu-site-enriched nanosheet-assembled SnO2 nanoflowers. The structural and interface engineering of the sensing materials presented in this work provides a promising approach for offering efficient and durable gas sensors operable at room temperature.

Advances in mesenchymal stem cells therapy for tendinopathies.

Tendinopathies are chronic diseases of an unknown etiology and associated with inflammation. Mesenchymal stem cells (MSCs) have emerged as a viable therapeutic option to combat the pathological progression of tendinopathies, not only because of their potential for multidirectional differentiation and self-renewal, but also their excellent immunomodulatory properties. The immunomodulatory effects of MSCs are increasingly being recognized as playing a crucial role in the treatment of tendinopathies, with MSCs being pivotal in regulating the inflammatory microenvironment by modulating the immune response, ultimately contributing to improved tissue repair. This review will discuss the current knowledge regarding the application of MSCs in tendinopathy treatments through the modulation of the immune response.

Single-cell RNA sequencing reveals tumor heterogeneity within salivary gland pleomorphic adenoma: A preliminary study.

BACKGROUND: Salivary gland pleomorphic adenoma (SPA) is a common neoplasm of salivary glands that displays remarkable histological diversity. Previous studies have demonstrated the involvement of gene rearrangements and cytoskeleton-remodeling-related myoepithelial cells in SPA tumorigenesis. Cytoskeleton remodeling is necessary for epithelial-mesenchymal transition (EMT), a key process in tumor progression. However, the heterogeneity of tumor cells and cytoskeleton remodeling in SPA has not been extensively investigated. METHODS: An analysis of single-cell RNA sequencing (scRNA-seq) was performed on 27 810 cells from two donors with SPA. Bioinformatic tools were used to assess differentially expressed genes, cell trajectories, and intercellular communications. Immunohistochemistry and double immunofluorescence staining were used to demonstrate FOXC1 and MYLK expression in SPA tissues. RESULTS: Our analysis revealed five distinct cell subtypes within the tumor cells of SPA, indicating a high level of intra-lesional heterogeneity. Cytoskeleton-remodeling-related genes were highly enriched in subtype 3 of the tumor cells, which showed a close interaction with mesenchymal cells. We found that tumoral FOXC1 expression was closely related to MYLK expression in the tumor cells of SPA. CONCLUSION: Tumor cells enriched with cytoskeleton-remodeling-related genes play a crucial role in SPA development, and FOXC1 may partially regulate this process.

Electroacupuncture Zusanli (ST36) Relieves Somatic Pain in Colitis Rats by Inhibiting Dorsal Root Ganglion Sympathetic-Sensory Coupling and Neurogenic Inflammation.

Referred somatic pain triggered by hyperalgesia is common in patients with inflammatory bowel disease (IBD). It was reported that sprouting of sympathetic nerve fibers into the dorsal root ganglion (DGR) and neurogenic inflammation were related to neuropathic pain, the excitability of neurons, and afferents. The purpose of the study was to explore the potential and mechanism of electroacupuncture (EA) at Zusanli (ST36) for the intervention of colon inflammation and hyperalgesia. Sprague-Dawley (SD) was randomly divided into four groups, including control, model, EA, and sham-EA. Our results showed EA treatment significantly attenuated dextran sulfate sodium- (DSS-) induced colorectal lesions and inflammatory cytokine secretion, such as TNF-α, IL-1ß, PGE2, and IL-6. EA also inhibited mechanical and thermal pain hypersensitivities of colitis rats. Importantly, EA effectively abrogated the promotion effect of DSS on ipsilateral lumbar 6 (L6) DRG sympathetic-sensory coupling, manifested as the sprouting of tyrosine hydroxylase- (TH-) positive sympathetic fibers into sensory neurons and colocalization of and calcitonin gene-related peptide (CGRP). Furthermore, EA at Zusanli (ST36) activated neurogenic inflammation, characterized by decreased expression of substance P (SP), hyaluronic acid (HA), bradykinin (BK), and prostacyclin (PGI2) in colitis rat skin tissues corresponding to the L6 DRG. Mechanically, EA treatment reduced the activation of the TRPV1/CGRP, ERK, and TLR4 signaling pathways in L6 DRG of colitis rats. Taken together, we presumed that EA treatment improved colon inflammation and hyperalgesia, potentially by suppressing the sprouting of sympathetic nerve fibers into the L6 DGR and neurogenic inflammation via deactivating the TRPV1/CGRP, ERK, and TLR4 signaling pathways.

A high-quality genome of the dobsonfly Neoneuromus ignobilis reveals molecular convergences in aquatic insects.

Neoneuromus ignobilis is an archaic holometabolous aquatic predatory insect. However, a lack of genomic resources hinders the use of whole genome sequencing to explore their genetic basis and molecular mechanisms for adaptive evolution. Here, we provided a high-contiguity, chromosome-level genome assembly of N. ignobilis using high coverage Nanopore and PacBio reads with the Hi-C technique. The final assembly is 480.67 MB in size, containing 12 telomere-ended pseudochromosomes with only 17 gaps. We compared 42 hexapod species genomes including six independent lineages comprising 11 aquatic insects, and found convergent expansions of long wavelength-sensitive and blue-sensitive opsins, thermal stress response TRP channels, and sulfotransferases in aquatic insects, which may be related to their aquatic adaptation. We also detected strong nonrandom signals of convergent amino acid substitutions in aquatic insects. Collectively, our comparative genomic analysis revealed the evidence of molecular convergences in aquatic insects during both gene family evolution and convergent amino acid substitutions.

The mitochondrial genome of Chelonus formosanus (Hymenoptera: Braconidae) with novel gene orders and phylogenetic implications.

Chelonus formosanus Sonan is an important egg-larval parasitoid of noctuid moths and a potential candidate for understanding interactions between host and parasitoid mediated by polydnavirues (PDVs). We sequenced and annotated the mitochondrial genome of C. formosanus, which is 15,466 bp in length and possesses 38 mitochondrial genes. However, unlike most animal mitochondrial genomes, it contains one extra trnF gene. There are five transfer RNA (tRNA) rearrangement events compared with the ancestral gene order, which is a novel rearrangement type in Hymenoptera for all published mitogenomes so far. Phylogenetic trees supported C. formosanus from the subfamily Cheloninae was closely related to the subfamily Cardiochilinae and Microgastrinae.

Diagnostic efficacy of visual subtypes and low attenuation area based on HRCT in the diagnosis of COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease. Current gold standard criteria, pulmonary function tests (PFTs) may result in underdiagnosis of potential COPD patients. Therefore, we hypothesize that the combination of high-resolution computed tomography (HRCT) and clinical basic characteristics will enable the identification of more COPD patients. METHODS: A total of 284 patients with respiratory symptoms who were current or former smokers were included in the study, and were further divided into 5 groups of GOLD grade I-IV and non-COPD according to PFTs. All patients underwent inspiratory HRCT scanning and low attenuation area (LAA) was measured. Then they were divided into seven visual subtypes according to the Fleischner Society classification system. Non-parametric tests were used for exploring differences in basic characteristics and PFTs between different groups of enrolled patients and visual subtypes. Binary logistic regression was to find the influencing factors that affected the patients' outcome (non-COPD vs GOLD I-IV). The area under the receiver operating characteristic curve (AUC-ROC) was to explore the diagnostic efficacy of LAA, visual subtypes, and combined basic characteristics related to COPD for COPD diagnosis. Finally, based on the cut-off values of ROC analysis, exploring HRCT features in patients who do not meet the diagnostic criteria but clinically suspected COPD. RESULTS: With the worsening severity of COPD, the visual subtypes gradually progressed (p < 0.01). There was a significant difference in LAA between GOLD II-IV and non-COPD (p < 0.0001). The diagnostic efficacy of LAA, visual subtypes, and LAA combined with visual subtypes for COPD were 0.742, 0.682 and 0.730 respectively. The diagnostic efficacy increased to 0.923-0.943 when basic characteristics were added (all p < 0.001). Based on the cut-off value of ROC analysis, LAA greater than 5.6, worsening of visual subtypes, combined with positive basic characteristics can help identify some potential COPD patients. CONCLUSION: The heterogeneous phenotype of COPD requires a combination of multiple evaluation methods. The diagnostic efficacy of combining LAA, visual subtypes, and basic characteristics achieves good consistency with current diagnostic criteria.

Regulation of circular RNAs act as ceRNA in a hypoxic pulmonary hypertension rat model.

To explore potential critical genes and identify circular RNAs (circRNAs) that act as the competitive endogenous RNA (ceRNA) in a hypoxic pulmonary hypertension (HPH) rat model. Constructed rat model, and a bioinformatics method was used to analyse differentially expressed (DE) genes and construct a circRNA-miRNA-mRNA ceRNA regulatory network. Then, qRT-PCR was used to verify. The significant DEcircRNAs/DEmiRNAs/DEmRNAs was showed, and a ceRNA network with 8 DEcircRNAs, 9 DEmiRNAs and 46 DEmRNAs were constructed. The functional enrichment suggested the inflammatory response, NF-κB signalling, MAPK cascade and Toll-like receptor were associated with HPH. Further assessment confirmed that circ_002723, circ_008021, circ_016925 and circ_020581 could have a potential ceRNA mechanism by sponging miR-23a or miR-21 to control downstream target gene and be involved in the pathophysiology of HPH. The qRT-PCR validation results were consistent with the RNA-Seq results. This study revealed potentially important genes, pathways and ceRNA regulatory networks in HPH.

Succinate induces skeletal muscle fiber remodeling via SUNCR1 signaling.

The conversion of skeletal muscle fiber from fast twitch to slow-twitch is important for sustained and tonic contractile events, maintenance of energy homeostasis, and the alleviation of fatigue. Skeletal muscle remodeling is effectively induced by endurance or aerobic exercise, which also generates several tricarboxylic acid (TCA) cycle intermediates, including succinate. However, whether succinate regulates muscle fiber-type transitions remains unclear. Here, we found that dietary succinate supplementation increased endurance exercise ability, myosin heavy chain I expression, aerobic enzyme activity, oxygen consumption, and mitochondrial biogenesis in mouse skeletal muscle. By contrast, succinate decreased lactate dehydrogenase activity, lactate production, and myosin heavy chain IIb expression. Further, by using pharmacological or genetic loss-of-function models generated by phospholipase Cß antagonists, SUNCR1 global knockout, or SUNCR1 gastrocnemius-specific knockdown, we found that the effects of succinate on skeletal muscle fiber-type remodeling are mediated by SUNCR1 and its downstream calcium/NFAT signaling pathway. In summary, our results demonstrate succinate induces transition of skeletal muscle fiber via SUNCR1 signaling pathway. These findings suggest the potential beneficial use of succinate-based compounds in both athletic and sedentary populations.

Association between mode of delivery and postpartum depression: A systematic review and network meta-analysis.

BACKGROUND: Postpartum depression is one of the most common postpartum diseases, which has an important impact on the interaction between mother, infant, partner and family, as well as the long-term emotional and cognitive development of infants. However, there are still great disagreements on whether the delivery mode will affect the risk of postpartum depression. The purpose of this study is to explore whether the mode of delivery will affect the risk of postpartum depression through the comprehensive network meta-analysis of elective cesarean section, emergency cesarean section, instrumental vaginal delivery and spontaneous vaginal delivery. METHODS: We searched in three electronic databases: PubMed, EMBASE and Cochrane Library. RESULTS: This paper included 43 studies with a total sample size of 1,827,456 participants. Direct meta-analysis showed that the odds ratio of postpartum depression risk was 1.33 (95% confidence interval = [1.21, 1.46]) between cesarean section and vaginal delivery. The odds ratios of high Edinburgh Postpartum Depression Scale score between cesarean section and vaginal delivery in the three postpartum periods (within 2 weeks, within half a year and over half a year) were basically the same. There was no difference between cesarean section and vaginal delivery in the risk of severe postpartum depression at the Edinburgh Postpartum Depression Scale cut-off point ⩾13 (odds ratio = 1.07; 95% confidence interval = [0.99, 1.16]). Network meta-analysis showed that the risk of postpartum depression in the pairwise comparisons emergency cesarean section vs spontaneous vaginal delivery and elective cesarean section vs spontaneous vaginal delivery was odds ratio = 1.53 (95% confidence interval = [1.22, 1.91]) and 1.47 (95% confidence interval = [1.16, 1.86]). CONCLUSION: The mode of delivery has a significant effect on the occurrence of mild postpartum depression. Women who give birth by cesarean section, especially who give birth by emergency cesarean section, are at a higher risk of mild postpartum depression. We should carefully monitor the progress of postpartum mental disorders in women who delivered by cesarean section and make it possible for women to have a quick access to mental healthcare.

Synaptotagmin 1 regulates cortical granule exocytosis during mouse oocyte activation.

Synaptotagmin 1 (Syt1) is an abundant and important presynaptic vesicle protein that binds Ca2+ for the regulation of synaptic vesicle exocytosis. Our previous study reported its localization and function on spindle assembly in mouse oocyte meiotic maturation. The present study was designed to investigate the function of Syt1 during mouse oocyte activation and subsequent cortical granule exocytosis (CGE) using confocal microscopy, morpholinol-based knockdown and time-lapse live cell imaging. By employing live cell imaging, we first studied the dynamic process of CGE and calculated the time interval between [Ca2+]i rise and CGE after oocyte activation. We further showed that Syt1 was co-localized to cortical granules (CGs) at the oocyte cortex. After oocyte activation with SrCl2, the Syt1 distribution pattern was altered significantly, similar to the changes seen for the CGs. Knockdown of Syt1 inhibited [Ca2+]i oscillations, disrupted the F-actin distribution pattern and delayed the time of cortical reaction. In summary, as a synaptic vesicle protein and calcium sensor for exocytosis, Syt1 acts as an essential regulator in mouse oocyte activation events including the generation of Ca2+ signals and CGE.

Comparison on radiation effective dose and image quality of right coronary artery on prospective ECG-gated method between 320 row CT and 2nd generation (128-slice) dual source CT.

This retrospective study was to compare the image quality of right coronary artery (RCA) and effective radiation dose on prospective ECG-gated method between 320 row computed tomography (CT) and 2nd generation (128-slice) dual source CT. A total of 215 candidates underwent CT coronary angiography using prospective ECG-gated method, 120 patients enrolled in 320 row CT group, and 95 patients in dual source CT group. We divided RCA image quality scores as 1/2/3/4, which means excellent/good/adequate/not assessable and heart rates were considered, as well as the radiation dose. There is no statistically significant difference of RCA image quality of Score 1/2 between 320 row CT and 2nd generation dual source CT, but lower heart rate (<70/min) improved RCA image quality. Meanwhile, the 2nd generation dual source CT scan have significant lower radiation dose. For patients with high level heart rate variation, both prospective ECG-gated method of 320 row CT scan (Toshiba) and 2nd generation dual source CT scan (Siemens) basically provided good image quality on RCA. There is an advantage of effective radiation dose reduction in prospective ECG-gated method using the 2nd generation dual source CT scan. After the iodine contrast agent was injected into elbow vein, the threshold triggering method was used to carry out prospective gated scanning, and the acquired fault image was reconstructed by the standard post-processing software of each manufacturer. The radiation dose value is obtained through the dose report automatically generated after each scan.

Effect of Moringa oleifera supplementation on productive performance, colostrum composition and serum biochemical indexes of sow.

Moringa oleifera has been considered as a potential functional feed or food, since it contains multiple components beneficial to animal and human. However, little is known about the effects of Moringa oleifera supplementation on productive performances in sows. In the current study, the results showed that dietary Moringa oleifera significantly decreased the farrowing length and the number of stillborn (p < .05), while had an increasing trend in the number of live-born (0.05 < p < .10). Furthermore, 8% Moringa oleifera supplementation significantly elevated protein levels in the colostrum (p < .05); 4% Moringa oleifera lowed serum urea nitrogen of sows after 90 days of gestation (p < .05) and significantly decreased serum glucose on 10 days of lactation (p < .05). Both groups showed significant elevation in serum T-AOC activity (p < .05). The serum malondialdehyde (MDA) of sows declined significantly in 4% Moringa oleifera addition group (p < .05). 8% Moringa oleifera meal significantly elevated serum CAT activity after 60 days of gestation (p < .05), while decreased the serum MDA level and increased the serum GSH-Px activity of sows at 10 days of lactation (p < .05). Of piglets, both two dosages of Moringa oleifera supplementation essentially reduced the serum urea nitrogen (p < .05), and 4% Moringa oleifera meal increased serum total protein (p < .05). In addition, piglets that received 8% Moringa oleifera had the highest serum CAT and SOD activities among all groups (p < .05). The present study indicated that Moringa oleifera supplementation could enhance the reproduction performances, elevate protein levels in the colostrum and improve the serum antioxidant indices in both sows and piglets.

Plant MIR156 regulates intestinal growth in mammals by targeting the Wnt/ß-catenin pathway.

MicroRNAs (miRNAs) are important negative regulators of genes involved in physiological and pathological processes in plants and animals. Recent studies have shown that miRNAs might regulate gene expression among different species in a cross-kingdom manner. However, the specific roles of plant miRNAs in animals remain poorly understood and somewhat. Herein, we found that plant MIR156 regulates proliferation of intestinal cells both in vitro and in vivo. Continuous administration of a high plant miRNA diet or synthetic MIR156 elevated MIR156 levels and inhibited the Wnt/ß-catenin signaling pathway in mouse intestine. Bioinformatics predictions and luciferase reporter assays indicated that MIR156 targets Wnt10b. In vitro, MIR156 suppressed proliferation by downregulating the Wnt10b protein and upregulating ß-catenin phosphorylation in the porcine jejunum epithelial (IPEC-J2) cell line. Lithium chloride and an MIR156 inhibitor relieved this inhibition. This research is the first to demonstrate that plant MIR156 inhibits intestinal cell proliferation by targeting Wnt10b. More importantly, plant miRNAs may represent a new class of bioactive molecules that act as epigenetic regulators in humans and other animals.

Autophagy in pulmonary hypertension: Emerging roles and therapeutic implications.

Autophagy is an important mechanism for cellular self-digestion and basal homeostasis. This gene- and modulator-regulated pathway is conserved in cells. Recently, several studies have shown that autophagic dysfunction is associated with pulmonary hypertension (PH). However, the relationship between autophagy and PH remains controversial. In this review, we mainly introduce the effects of autophagy-related genes and some regulatory molecules on PH and the relationship between autophagy and PH under the conditions of hypoxia, monocrotaline injection, thromboembolic stress, oxidative stress, and other drugs and toxins. The effects of other autophagy-related drugs, such as chloroquine, 3-methyladenine, rapamycin, and other potential therapeutic drugs and targets, in PH are also described.

ß-Glucanase specific expression in the intestine of transgenic pigs.

Producing heterologous enzymes in the animal digestive tract to improve feed utilization rate is a new research strategy by transgenic technology. In this study, transgenic pigs specifically expressing ß-glucanase gene in the intestine were successfully produced by somatic cell nuclear transfer technology in order to improve digestibility of dietary ß-glucan and absorption of nutrients. The ß-glucanase activity in the intestinal juice of 4 transgenic pigs was found to be 8.59 ± 2.49 U/mL. The feeding trial results showed that the crude protein digestion of 4 transgenic pigs was significantly increased compared with that of the non-transgenic pigs. In order to investigate the inheritance of the transgene, 7 G1 transgenic pigs were successfully obtained. The ß-glucanase activity in the intestinal juice of 7 G1 transgenic pigs was found to be 2.35 ± 0.72 U/mL. The feeding trial results showed the crude protein digestion and crude fat digestion were significantly higher in 7 G1 transgenic pigs than in non-transgenic pigs. Taken together, our study demonstrated that the foreign ß-glucanase expressing in the intestine of the transgenic pigs could reduce the anti-nutritional effect of ß-glucans in feed. In addition, ß-glucanase gene could be inherited to the offsprings and maintain its physiological function. It is a promising approach to improve feed utilization by producing transgenic animals.

Modified balloon-stent kissing technique avoid side-branch compromise for simple true bifurcation lesions.

BACKGROUND: Coronary bifurcation remains one of the most challenging lesion subsets in interventinal cardiology. Provisional stenting (PS) is the dominate technique for bifurcation lesions, but the key problem is the deterioration of side branch. Balloon-stent kissing technique (BSKT) as a new systematic approach which is based on modified jailed balloon technique is applied to improve the procedure success. In our center, we proposed a modified balloon-stent kissing technique(M-BSKT), which routine usage of proximal optimizing technique (POT) after rewiring was added as an optimization step to BSKT. Thus, whether M-BSKT for addressing simple true coronary bifurcation lesions can provide more benefits in intra-operation effect and long term outcomes is still unknown. METHODS: A cohort of 120 consecutive patients underwent Percutaneous Coronary Intervention (PCI) with simple true coronary bifurcation lesions satisfied the criteria were included in this retrospective, single-center registry. To assemble a cohort with similar baseline characteristics, a 1:1 propensity-matched score was used. The primary outcomes were the rate of device and procedural success, the situation of side branch (SB) after main vessel (MV) inflation and the complications during intra-operative. The secondary outcomes were the clinical prognosis at 12 months such as rehospitalization for unstable angina and MACEs. RESULTS: Before propensity matching, there were no significant differences in primary and secondary outcomes between two groups. After propensity-matched was used, 68 patients with similar propensity scores were included. At immediate procedural, M-BSKT was associated with a lower risk of SB deterioration and the application of final kissing balloon inflation (FKBI)[P = 0.036]. For ACS patients, besides the significant differences of immediate SB deterioration [P = 0.014] and FKBI application [P = 0.033], the incidence of TIMI flow< 3 in the PS was statistically significant higher than M-BSKT [P= 0.042]. The prognosis at 12 months such as rehospitalization for unstable angina and MACEs were similar for two groups [P = 0.613]. CONCLUSION: These observations prove that the M-BSKT enables side branch to be better protected in simple true bifurcation lesions, by a narrow margin. It may improve the angiographic outcomes about side branch deterioration and final kissing balloon performing compared with PS, especially in ACS patients. However, long-term clinical outcomes did not differ between patients treated for M-BSKT and PS at 12 months.

MicroRNA-214-3p Regulates Hypoxia-Mediated Pulmonary Artery Smooth Muscle Cell Proliferation and Migration by Targeting ARHGEF12.

BACKGROUND miR-214-3p has been found to inhibit proliferation and migration in cancer cells. The objective of this study was to determine whether ARHGEF12 is involved in miR-214-3p-mediated suppression of proliferation and migration of pulmonary artery smooth muscle cells (PASMCs). MATERIAL AND METHODS PASMCs were cultured under normoxia or hypoxia. miR-214-3p mimics or inhibitors were transiently transfected into PASMCs. Proliferation, apoptosis, and migration of PASMCs were evaluated using MTT assay, flow cytometry, and Boyden chamber apparatus. Western blot analysis was used to examine expression of Rho guanine nucleotide exchange factor 12 (ARHGEF12), c-fos, c-jun, and caspase-3. Luciferase reporter assay was used to test the direct regulation of miR-214-3p on the 3'-untranslated region (UTR) of ARHGEF12. RESULTS miR-214-3p was significantly upregulated in hypoxia-treated PASMCs. Knockdown of miR-214-3p significantly attenuated hypoxia-induced proliferation and migration in PASMCs and promoted apoptosis, whereas this effect was aggravated by overexpression of miR-214-3p. In addition, dual-luciferase reporter assay demonstrated that ARHGEF12 is a direct target gene of miR-214-3p. The protein levels of ARHGEF12 were downregulated after knockdown of miR-214-3p in PASMCs. Rescue experiment results indicated that decreased proliferation of PASMCs resulted from knockdown of miR-214-3p were partially reversed by silencing of ARHGEF12 by siRNA. Furthermore, knockdown of miR-214-3p reduced expression of c-jun and c-fos, but increased expression of caspase-3 in PASMCs under hypoxia. CONCLUSIONS In conclusion, these results indicate that miR-214-3p acts as a novel regulator of hypoxia-induced proliferation and migration by directly targeting ARHGEF12 and dysregulating c-jun and c-fos in PASMCs, and may be a potential therapeutic target for treating pulmonary hypertension.

Exploration of long noncoding RNA in bovine milk exosomes and their stability during digestion in vitro.

Previous studies have demonstrated that bovine milk contains mRNA and microRNA that are largely encapsulated in milk-derived exosomes. However, little information is available about long noncoding RNAs (lncRNA) in bovine milk. Increasing evidence suggests that lncRNA are of particular interest given their key role in gene expression and development. We performed a comprehensive analysis of lncRNA in bovine milk exosomes by RNA sequencing. We used a validated human in vitro digestion model to investigate the stability of lncRNA encapsulated in bovine milk exosomes during the digestion process. We identified 3,475 novel lncRNA and 6 annotated lncRNA. The lncRNA shared characteristics with those of other mammals in terms of length, exon number, and open reading frames. However, lncRNA showed higher expression than mRNAs. We selected 12 lncRNA of high-expression abundance and identified them by PCR. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that lncRNA regulate immune function, osteoblastogenesis, neurodevelopment, reproduction, cell proliferation, and cell-cell communication. We also investigated the 12 lncRNA using quantitative real-time PCR to reveal their expression profiles in milk exosomes during different stages of lactation (colostrum 2 d, 30 d, 150 d, and 270 d); their resulting expression levels in milk exosomes showed variations across the stages. A digestion experiment showed that bovine milk exosome lncRNA was resistant to in vitro digestion with different digestive juices, including saliva, gastric juice, pancreatic juice, and bile juice. Taken together, these results show for the first time that cow milk contains lncRNA, and that their abundance varied at different stages of lactation. As expected, bovine milk exosomal lncRNA were stable during in vitro digestion. These findings provide a basis for further understanding of the physiological role of milk lncRNA.