Evaluation of genetic response of mesenchymal stem cells to nanosecond pulsed electric fields by whole transcriptome sequencing.

BACKGROUND: Mesenchymal stem cells (MSCs) modulated by various exogenous signals have been applied extensively in regenerative medicine research. Notably, nanosecond pulsed electric fields (nsPEFs), characterized by short duration and high strength, significantly influence cell phenotypes and regulate MSCs differentiation via multiple pathways. Consequently, we used transcriptomics to study changes in messenger RNA (mRNA), long noncoding RNA (lncRNA), microRNA (miRNA), and circular RNA expression during nsPEFs application. AIM: To explore gene expression profiles and potential transcriptional regulatory mechanisms in MSCs pretreated with nsPEFs. METHODS: The impact of nsPEFs on the MSCs transcriptome was investigated through whole transcriptome sequencing. MSCs were pretreated with 5-pulse nsPEFs (100 ns at 10 kV/cm, 1 Hz), followed by total RNA isolation. Each transcript was normalized by fragments per kilobase per million. Fold change and difference significance were applied to screen the differentially expressed genes (DEGs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to elucidate gene functions, complemented by quantitative polymerase chain reaction verification. RESULTS: In total, 263 DEGs were discovered, with 92 upregulated and 171 downregulated. DEGs were predominantly enriched in epithelial cell proliferation, osteoblast differentiation, mesenchymal cell differentiation, nuclear division, and wound healing. Regarding cellular components, DEGs are primarily involved in condensed chromosome, chromosomal region, actin cytoskeleton, and kinetochore. From aspect of molecular functions, DEGs are mainly involved in glycosaminoglycan binding, integrin binding, nuclear steroid receptor activity, cytoskeletal motor activity, and steroid binding. Quantitative real-time polymerase chain reaction confirmed targeted transcript regulation. CONCLUSION: Our systematic investigation of the wide-ranging transcriptional pattern modulated by nsPEFs revealed the differential expression of 263 mRNAs, 2 miRNAs, and 65 lncRNAs. Our study demonstrates that nsPEFs may affect stem cells through several signaling pathways, which are involved in vesicular transport, calcium ion transport, cytoskeleton, and cell differentiation.

Clinical characteristics and prognosis in 12 children with SARS-CoV-2 Omicron variant infection-associated acute necrotizing encephalopathy / 中国当代儿科杂志

OBJECTIVES@#To study the clinical characteristics and prognosis of SARS-CoV-2 Omicron variant infection-associated acute necrotizing encephalopathy (ANE) in children .@*METHODS@#A retrospective analysis was conducted on the medical data of 12 children with SARS-CoV-2 Omicron variant infection-associated ANE who were admitted to the Pediatric Intensive Care Unit, Qingdao Women and Children's Hospital from December 18 to 29, 2022. The children were divided into two groups based on outcomes: death group (7 cases) and survival group (5 cases). The clinical manifestations and auxiliary examination results were compared between the two groups.@*RESULTS@#The median age of the 12 patients was 30 months, with a male-to-female ratio of 1:1. All patients presented with persistent high fever, with a median highest body temperature of 41℃. The median time from fever onset to seizure or consciousness disturbance was 18 hours. The death group had a higher proportion of neurogenic shock, coagulation dysfunction, as well as elevated lactate, D-dimer, interleukin-6, interleukin--8, and interleukin-10 levels compared to the survival group (P<0.05).@*CONCLUSIONS@#Children with SARS-CoV-2 Omicron variant infection-associated with ANE commonly present with persistent high fever, rapidly progressing disease, and have a high likelihood of developing consciousness disorders and multiorgan dysfunction within a short period. The occurrence of neurogenic shock, coagulation dysfunction, and significantly elevated cytokine levels suggests an increased risk of mortality.

corilagin protects non-alcoholic fatty liver disease in mice induced by high fat and high sugar diet via regulating AMPK-autophagy signaling / 中国药理学通报

Aim To explore the effects of corilagin on non-alcoholic fatty liver disease induced by high-fat and high-sugar diet in mice via regulating AMPK-autophagy signaling. Methods Healthy 8-week-old male C57BL/6J mice were randomly divided into control group, model group and corilagin group. The mice of model group and corilagin group were fed with a high-fat and high-sugar diet for four weeks at the age of eight weeks. The corilagin group mice were also intraperitoneally injected with corilagin (20 mg • k g

Different responses of banana classical AGP genes and cell wall AGP components to low-temperature between chilling sensitive and tolerant cultivars.

KEY MESSAGE: Seventeen classical MaAGPs and 9 MbAGPs were identified and analyzed. MaAGP1/2/6/9/16/17, the antigens of JIM13 and LM2 antibodies are likely to be involved in banana chilling tolerance. Classical arabinogalactan proteins (AGPs) belong to glycosylphosphatidylinositol-anchored proteins, which are proved to be involved in signaling and cell wall metabolism upon stresses. However, rare information is available on the roles of classical AGPs in low temperature (LT) tolerance. Cultivation of banana in tropical and subtropical region is seriously threatened by LT stress. In the present study, 17 classical MaAGPs and nine MbAGPs in banana A and B genome were identified and characterized, respectively. Great diversity was present among different classical MaAGP/MbAGP members while five members (AGP3/6/11/13/14) showed 100% identity between these two gene families. We further investigated different responses of classical AGPs to LT between a chilling sensitive (CS) and tolerant (CT) banana cultivars. In addition, different changes in the temporal and spatial distribution of cell wall AGP components under LTs between these two cultivars were compared using immunofluorescence labeling. Seven classical MbAGPs were upregulated by LT(s) in the CT cultivar. Classical MaAGP4/6 was induced by LT(s) in both cultivars while MaAGP1/2/9/16/17 only in the CT cultivar. Moreover, these genes showed significantly higher transcription abundance in the CT cultivar than the CS one under LT(s) except classical MaAGP4. Similar results were observed with the epitopes of JIM13 and LM2 antibodies. The antigens of these antibodies and classical MaAGP1/2/6/9/16/17 might be related to LT tolerance of banana. These results provide additional information about plant classical AGPs and their involvement in LT tolerance, as well as their potential as candidate genes to be targeted when breeding CT banana.

A novel grey power-Markov model for the prediction of China's electricity consumption.

Forecasting the electricity consumption has always played an important role in the management of power system management, which requires higher forecasting technology. Therefore, based on the principle of "new information priority", combined with rolling mechanism and Markov theory, a novel grey power-Markov prediction model with time-varying parameters (RGPMM(λ,1,1)) is designed, which overcomes the inherent defects of fixed structure and poor adaptability to the changes of original data. In addition, in order to prove the validity and applicability of the prediction model, we have used the model to predict China's total electricity consumption, and have compared it with the prediction results by a series of benchmark models. The result shows that the can better adapt to the characteristics of electricity consumption data, and it also shows the advantages of the proposed forecasting model. In this paper, the proposed forecasting model is used to predict China's total electricity consumption in the next six years from 2018 to 2023, so as to provide certain reference value for power system management and distribution.

Erratum: Yuan, W., et al. Genome-Wide Identification of Banana Csl Gene Family and Their Different Responses to Low Temperature between Chilling-Sensitive and Tolerant Cultivars. Plants 2021, 10, 122.

The authors wish to make the following corrections to this paper [...].

Genome-Wide Identification of Banana Csl Gene Family and Their Different Responses to Low Temperature between Chilling-Sensitive and Tolerant Cultivars.

The cell wall plays an important role in responses to various stresses. The cellulose synthase-like gene (Csl) family has been reported to be involved in the biosynthesis of the hemicellulose backbone. However, little information is available on their involvement in plant tolerance to low-temperature (LT) stress. In this study, a total of 42 Csls were identified in Musa acuminata and clustered into six subfamilies (CslA, CslC, CslD, CslE, CslG, and CslH) according to phylogenetic relationships. The genomic features of MaCsl genes were characterized to identify gene structures, conserved motifs and the distribution among chromosomes. A phylogenetic tree was constructed to show the diversity in these genes. Different changes in hemicellulose content between chilling-tolerant and chilling-sensitive banana cultivars under LT were observed, suggesting that certain types of hemicellulose are involved in LT stress tolerance in banana. Thus, the expression patterns of MaCsl genes in both cultivars after LT treatment were investigated by RNA sequencing (RNA-Seq) technique followed by quantitative real-time PCR (qPCR) validation. The results indicated that MaCslA4/12, MaCslD4 and MaCslE2 are promising candidates determining the chilling tolerance of banana. Our results provide the first genome-wide characterization of the MaCsls in banana, and open the door for further functional studies.

Changes in Homogalacturonan Metabolism in Banana Peel during Fruit Development and Ripening.

Though numerous studies have focused on the cell wall disassembly of bananas during the ripening process, the modification of homogalacturonan (HG) during fruit development remains exclusive. To better understand the role of HGs in controlling banana fruit growth and ripening, RNA-Seq, qPCR, immunofluorescence labeling, and biochemical methods were employed to reveal their dynamic changes in banana peels during these processes. Most HG-modifying genes in banana peels showed a decline in expression during fruit development. Four polygalacturonase and three pectin acetylesterases showing higher expression levels at later developmental stages than earlier ones might be related to fruit expansion. Six out of the 10 top genes in the Core Enrichment Gene Set were HG degradation genes, and all were upregulated after softening, paralleled to the significant increase in HG degradation enzyme activities, decline in peel firmness, and the epitope levels of 2F4, CCRC-M38, JIM7, and LM18 antibodies. Most differentially expressed alpha-1,4-galacturonosyltransferases were upregulated by ethylene treatment, suggesting active HG biosynthesis during the fruit softening process. The epitope level of the CCRC-M38 antibody was positively correlated to the firmness of banana peel during fruit development and ripening. These results have provided new insights into the role of cell wall HGs in fruit development and ripening.

Regulatory Mechanism of Traditional Chinese Medicine in Mitochondrial Quality Control for Diabetic Cardiomyopathy： A Review / 中国实验方剂学杂志

Diabetic cardiomyopathy occurs in diabetic patients and is different from hypertensive heart disease， coronary atherosclerotic heart disease， and other cardiac abnormalities. The main clinical symptoms are systolic and diastolic cardiac dysfunction， myocardial fibrosis， congestive heart failure， and angina pectoris. As one of the main complications of diabetes， its incidence and fatality rates have been on the rise year by year. However， modern medicine still fails to figure out its pathogenesis and no specific drug is available， which has seriously affected the survival and quality of life of patients. Cardiomyocytes contain a large number of mitochondria， which participate in cardiac energy metabolism and other biological activities and occupy an important position in the development of diabetic cardiomyopathy. Mitochondrial quality control mainly involves mitochondrial oxidative stress， mitochondrial dynamics， mitochondrial autophagy， and intracellular calcium regulation， which is an important condition for stabilizing the normal mitochondrial structure and exerting normal mitochondrial functions. In recent years， the efficacy of traditional Chinese medicine in intervening in mitochondrial quality control through multiple angles， pathways， and targets to affect the structure and function of myocardial mitochondria and significantly improve the clinical symptoms of patients with diabetic cardiomyopathy has attracted wide attention from scholars. Therefore， this paper reviewed the experimental studies and/or clinical observations concerning the treatment of diabetic cardiomyopathy with effective compounds of Chinese herbs and/or Chinese herbal compounds in the past ten years to further explain the pathogenesis of diabetic cardiomyopathy， clarify the regulatory mechanism of traditional Chinese medicine in mitochondrial quality control， and summarize the scientific connotations and shortcomings of traditional Chinese medicine in the treatment of diabetic cardiomyopathy， hoping to provide certain ideas and methods for further clinical application of traditional Chinese medicine in the treatment of diabetic cardiomyopathy.

Acceleration of Carbon Fixation in Chilling-Sensitive Banana under Mild and Moderate Chilling Stresses.

Banana is one of the most important food and fruit crops in the world and its growth is ceasing at 10-17 °C. However, the mechanisms determining the tolerance of banana to mild (>15 °C) and moderate chilling (10-15 °C) are elusive. Furthermore, the biochemical controls over the photosynthesis in tropical plant species at low temperatures above 10 °C is not well understood. The purpose of this research was to reveal the response of chilling-sensitive banana to mild (16 °C) and moderate chilling stress (10 °C) at the molecular (transcripts, proteins) and physiological levels. The results showed different transcriptome responses between mild and moderate chilling stresses, especially in pathways of plant hormone signal transduction, ABC transporters, ubiquinone, and other terpenoid-quinone biosynthesis. Interestingly, functions related to carbon fixation were assigned preferentially to upregulated genes/proteins, while photosynthesis and photosynthesis-antenna proteins were downregulated at 10 °C, as revealed by both digital gene expression and proteomic analysis. These results were confirmed by qPCR and immunofluorescence labeling methods. Conclusion: Banana responded to the mild chilling stress dramatically at the molecular level. To compensate for the decreased photosynthesis efficiency caused by mild and moderate chilling stresses, banana accelerated its carbon fixation, mainly through upregulation of phosphoenolpyruvate carboxylases.

Nanosecond pulsed electric fields enhance mesenchymal stem cells differentiation via DNMT1-regulated OCT4/NANOG gene expression.

BACKGROUND: Multiple strategies have been proposed to promote the differentiation potential of mesenchymal stem cells (MSCs), which is the fundamental property in tissue formation and regeneration. However, these strategies are relatively inefficient that limit the application. In this study, we reported a novel and efficient strategy, nanosecond pulsed electric fields (nsPEFs) stimulation, which can enhance the trilineage differentiation potential of MSCs, and further explained the mechanism behind. METHODS: We used histological staining to screen out the nsPEFs parameters that promoted the trilineage differentiation potential of MSCs, and further proved the effect of nsPEFs by detecting the functional genes. In order to explore the corresponding mechanism, we examined the expression of pluripotency genes and the methylation status of their promoters. Finally, we targeted the DNA methyltransferase which was affected by nsPEFs. RESULTS: The trilineage differentiation of bone marrow-derived MSCs was significantly enhanced in vitro by simply pre-treating with 5 pulses of nsPEFs stimulation (energy levels as 10 ns, 20 kV/cm; 100 ns, 10 kV/cm), due to that the nsPEFs demethylated the promoters of stem cell pluripotency genes OCT4 and NANOG through instantaneous downregulation of DNA methylation transferase 1 (DNMT1), thereby increasing the expression of OCT4 and NANOG for up to 3 days, and created a treatment window period of stem cells. CONCLUSIONS: In summary, nsPEFs can enhance MSCs differentiation via the epigenetic regulation and could be a safe and effective strategy for future stem cell application.

Nanosecond pulsed electric fields enhanced chondrogenic potential of mesenchymal stem cells via JNK/CREB-STAT3 signaling pathway.

BACKGROUND: Nanosecond pulsed electric fields (nsPEFs) can produce more significant biological effects than traditional electric fields and have thus attracted rising attention in developing medical applications based on short pulse duration and high field strength, such as effective cancer therapy. However, little is known about their effects on the differentiation of stem cells. Furthermore, mechanisms of electric fields on chondrogenic differentiation of mesenchymal stem cells (MSCs) remain elusive, and effects of electric fields on cartilage regeneration need to be verified in vivo. Here, we aimed to study the effects of nsPEFs on chondrogenic differentiation of MSCs in vitro and in vivo and further to explore the mechanisms behind the phenomenon. METHODS: The effects of nsPEF-preconditioning on chondrogenic differentiation of mesenchymal stem cells (MSCs) in vitro were evaluated using cell viability, gene expression, glycosaminoglycan (sGAG) content, and histological staining, as well as in vivo cartilage regeneration in osteochondral defects of rats. Signaling pathways were investigated with protein expression and gene expression, respectively. RESULTS: nsPEF-preconditioning with proper parameters (10 ns at 20 kV/cm, 100 ns at 10 kV/cm) significantly potentiated chondrogenic differentiation capacity of MSCs with upregulated cartilaginous gene expression and increased matrix deposition through activation of C-Jun NH2-terminal kinase (JNK) and cAMP-response element binding protein (CREB), followed by activation of downstream signal transducer and activator of transcription (STAT3). Implantation of nsPEF-preconditioned MSCs significantly enhanced cartilage regeneration in vivo, compared with implantation of non-nsPEF-preconditioned MSCs. CONCLUSION: This study demonstrates a unique approach of nsPEF treatment to potentiate the chondrogenic ability of MSCs through activation of JNK/CREB-STAT3 that could have translational potential for MSC-based cartilage regeneration.

Intermedin in Paraventricular Nucleus Attenuates Sympathoexcitation and Decreases TLR4-Mediated Sympathetic Activation via Adrenomedullin Receptors in Rats with Obesity-Related Hypertension / 神经科学通报·英文版

Intermedin/adrenomedullin-2 (IMD/AM2), a member of the calcitonin gene-related peptide/AM family, plays an important role in protecting the cardiovascular system. However, its role in the enhanced sympathoexcitation in obesity-related hypertension is unknown. In this study, we investigated the effects of IMD in the paraventricular nucleus (PVN) of the hypothalamus on sympathetic nerve activity (SNA), and lipopolysaccharide (LPS)-induced sympathetic activation in obesity-related hypertensive (OH) rats induced by a high-fat diet for 12 weeks. Acute experiments were performed under anesthesia. The dynamic alterations of sympathetic outflow were evaluated as changes in renal SNA and mean arterial pressure (MAP) in response to specific drugs. Male rats were fed a control diet (12% kcal as fat) or a high-fat diet (42% kcal as fat) for 12 weeks to induce OH. The results showed that IMD protein in the PVN was downregulated, but Toll-like receptor 4 (TLR4) and plasma norepinephrine (NE, indicating sympathetic hyperactivity) levels, and systolic blood pressure were increased in OH rats. LPS (0.5 µg/50 nL)-induced enhancement of renal SNA and MAP was greater in OH rats than in obese or control rats. Bilateral PVN microinjection of IMD (50 pmol) caused greater decreases in renal SNA and MAP in OH rats than in control rats, and inhibited LPS-induced sympathetic activation, and these were effectively prevented in OH rats by pretreatment with the AM receptor antagonist AM22-52. The mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) inhibitor U0126 in the PVN partially reversed the LPS-induced enhancement of SNA. However, IMD in the PVN decreased the LPS-induced ERK activation, which was also effectively prevented by AM22-52. Chronic IMD administration resulted in significant reductions in the plasma NE level and blood pressure in OH rats. Moreover, IMD lowered the TLR4 protein expression and ERK activation in the PVN, and decreased the LPS-induced sympathetic overactivity. These results indicate that IMD in the PVN attenuates SNA and hypertension, and decreases the ERK activation implicated in the LPS-induced enhancement of SNA in OH rats, and this is mediated by AM receptors.

Improvement of Core Competitiveness of the Hospital through Construction of the Information Integration Platform / 医学信息学杂志

Taking the Fourth Affiliated Hospital of China Medical University as an example,the information integration platform of the hospital is constructed in accordance with the national data and information interaction standard and HL7 standard.The paper introduces the idea for selecting platform products,and technical route and effect of platform construction,and provides guarantee for sustainable development of the hospital,in order to greatly improve core competitiveness of the hospital.

Extension of Medical Services of Hospitals under the Support of the Mobile APP Follow-up System / 医学信息学杂志

The paper introduces the extension of medical services of hospitals under the support of the mobile APP follow-up system and its system architecture and functions,and indicates that this system can be applied to promote the communication between doctors and patients,reduce the contradiction between doctors and patients,improve the quality of medical services,reduce the workload of medical care personnel,assist regional medical construction.

Plasma brain natriuretic peptide and endothelin-1 levels in artial septal defect patients with pulmonary hypertension at altitude / 中华胸心血管外科杂志

Objective To explore the change of Brain natriuretic peptide(BNP) and endothelin-1 (ET-1) levels in artial septal defect(ASD) patients and the relationship among BNP,ET-1 and pulmonary pressure.Methods 105 final diagnosed ASD patients were divide into non-pulmonary hypertension group (nPH group) and pulmonary hypertension group(PH group),and the PH group were divided into two subgroup:slight PH group,moderate and sever PH group.According to the altitude of habitation,105 ASD patients also were divided into 3 groups:＜ 2 500 m group,2 501-3 500 m group and ＞ 3 500 m group.Plasma BNP were measured by radioimmunity method and ET-1 were measured by ELISA.The data analysis used single factor analysis and Fisher least singnificant difference t test.Results Both the plasma BNP levels (152.34 ± 40.61) pg/ml and ET-1 level (137.69 ± 37.17) pg/ml of the ASD-PH group were significantly higher than those [BNP (126.70 ± 32.27) pg/ml,ET-1 (92.92 ± 32.3) pg/ml] of ASD-nPH group.There were strong difference in plasma BNP levels and ET-1 levels among different degree PH groups(F =6.782,P ＜ 0.05 ; F =8.475,P ＜ 0.05).Statistical difference were also shown in BNP(F =6.846,P ＜ 0.05) and ET-1 (F =9.327,P ＜ 0.05) levels by compared difference altitude groups.The BNP levels are positively correlated with mean pulmonary artery pressure (r =0.326,P ＜ 0.05),size of defect (r=0.301,P＜0.05) and the altitude of habitation (r =0.252,P＜0.05).Conclusion Plasma BNPand ET-1 levelsof ASD-PH group significantly higher than those of ASD-nPH group.By the increasing of the altitude and PH degree,the plasma BNP and ET-1 levels are increasing,which suggest that BNP and ET-1 play an important role on the proceeding and development of the PH and hypoxia promoted secretion of BNP and ET-1.