The phosphate starvation response regulator PHR2 antagonizes arbuscule maintenance in Medicago.

Phosphate starvation response (PHR) transcription factors play essential roles in regulating phosphate uptake in plants through binding to the P1BS cis-element in the promoter of phosphate starvation response genes. Recently, PHRs were also shown to positively regulate arbuscular mycorrhizal colonization in rice and lotus by controlling the expression of many symbiotic genes. However, their role in arbuscule development has remained unclear. In Medicago, we previously showed that arbuscule degradation is controlled by two SPX proteins that are highly expressed in arbuscule-containing cells. Since SPX proteins bind to PHRs and repress their activity in a phosphate-dependent manner, we investigated whether arbuscule maintenance is also regulated by PHR. Here, we show that PHR2 is a major regulator of the phosphate starvation response in Medicago. Knockout of phr2 showed reduced phosphate starvation response, symbiotic gene expression, and fungal colonization levels. However, the arbuscules that formed showed less degradation, suggesting a negative role for PHR2 in arbuscule maintenance. This was supported by the observation that overexpression of PHR2 led to enhanced degradation of arbuscules. Although many arbuscule-induced genes contain P1BS elements in their promoters, we found that the P1BS cis-elements in the promoter of the symbiotic phosphate transporter PT4 are not required for arbuscule-containing cell expression. Since both PHR2 and SPX1/3 negatively affect arbuscule maintenance, our results indicate that they control arbuscule maintenance partly via different mechanisms. While PHR2 potentiates symbiotic gene expression and colonization, its activity in arbuscule-containing cells needs to be tightly controlled to maintain a successful symbiosis in Medicago.

The association between metabolic dysfunction-associated steatotic liver disease, cardiovascular and cerebrovascular diseases and the thickness of carotid plaque.

BACKGROUND: The relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and atherosclerosis has been controversial, which has become a hit of recent research. The study aimed to explore the association between MASLD, cardiovascular and cerebrovascular diseases (CCVD), and the thickness of carotid plaque which was assessed by ultrasound. METHODS: From September 2018 to June 2019, 3543 patients were enrolled. We asked participants to complete questionnaires to obtain information. All patients underwent liver ultrasound and bilateral carotid ultrasound to obtain carotid intima-media thickness (IMT) and maximum carotid plaque thickness (CPT). Hepatic steatosis was quantified during examination according to Hamaguchi's ultrasonographic score, from 0 to 6 points. A score < 2 was defined as without fatty liver, and a score ≥ 2 was defined as fatty liver. Information about blood lipids was collected based on the medical records. RESULTS: We found common risk factors for CCVD events, MASLD, and atherosclerosis. There was a significant correlation between MASLD and carotid plaque, but not with CPT. No association was found between MASLD and CCVD events. CPT and IMT were thicker in CCVD patients than in non-CCVD patients. No significant difference was found between IMT and CPT in MASLD patients and non-MASLD patients. CCVD was independently and consistently associated with higher IMT, and free fatty acid (FFA). CONCLUSIONS: According to our results, we recommend carotid ultrasound examination of the patients when FFA is increased, regardless of the presence of risk factors and MASLD. Due to the distribution of CPT of both CCVD and MASLD patients in the CPT 2-4 mm group, contrast-enhanced ultrasound is necessary to assess the vulnerability of the plaque when CPT ≥ 2 mm. Timely treatment of vulnerable plaques may reduce the incidence of future CCVD events.

Expression of Phospholipase D Family Member 6 in Bovine Testes and Its Molecular Characteristics.

Spermatogonial stem cells (SSCs) are the only primitive spermatogonial cells in males that can naturally transmit genetic information to their offspring and replicate throughout their lives. Phospholipase D family member 6 (PLD6) has recently been found to be a surface marker for SSCs in mice and boars; however, it has not been validated in cattle. The results of reversed transcription-polymerase chain reaction (RT-PCR) and quantitative real-time PCR (qRT-PCR) found that the relative expression of the PLD6 gene in the testicular tissues of two-year-old Simmental calves was significantly higher than that of six-month-old calves. Immunofluorescent staining further verified the expression of PLD6 protein in bovine spermatogenic cells like germ cell marker DEAD box helicase 4 (DDX4, also known as VASA). Based on multiple bioinformatic databases, PLD6 is a conservative protein which has high homology with mouse Q5SWZ9 protein. It is closely involved in the normal functioning of the reproductive system. Molecular dynamics simulation analyzed the binding of PLD6 as a phospholipase to cardiolipin (CL), and the PLD6-CL complex showed high stability. The protein interaction network analysis showed that there is a significant relationship between PLD6 and piwi-interacting RNA (piRNA) binding protein. PLD6 acts as an endonuclease and participates in piRNA production. In addition, PLD6 in bovine and mouse testes has a similar expression pattern with the spermatogonium-related genes VASA and piwi like RNA-mediated gene silencing 2 (PIWIL2). In conclusion, these analyses imply that PLD6 has a relatively high expression in bovine testes and could be used as a biomarker for spermatogenic cells including SSCs.

COVID-19 contact tracking by group activity trajectory recovery over camera networks.

Contact tracking plays an important role in the epidemiological investigation of COVID-19, which can effectively reduce the spread of the epidemic. As an excellent alternative method for contact tracking, mobile phone location-based methods are widely used for locating and tracking contacts. However, current inaccurate positioning algorithms that are widely used in contact tracking lead to the inaccurate follow-up of contacts. Aiming to achieve accurate contact tracking for the COVID-19 contact group, we extend the analysis of the GPS data to combine GPS data with video surveillance data and address a novel task named group activity trajectory recovery. Meanwhile, a new dataset called GATR-GPS is constructed to simulate a realistic scenario of COVID-19 contact tracking, and a coordinated optimization algorithm with a spatio-temporal constraint table is further proposed to realize efficient trajectory recovery of pedestrian trajectories. Extensive experiments on the novel collected dataset and commonly used two existing person re-identification datasets are performed, and the results evidently demonstrate that our method achieves competitive results compared to the state-of-the-art methods.

Survivable potential of germ cells after trehalose cryopreservation of bovine testicular tissues.

Germplasm preservation of livestock or endangered animals and expansion of germline stem cells are important. The purpose of this study is to investigate whether supplementation of trehalose to the freezing medium (FM) reduces tissular damage and improves the quality of testicular cells in the cryopreserved bovine testicular tissues. We herein established an optimized protocol for the cryopreservation of bovine testicular tissues, and the isolation as well as culture of bovine germ cells containing spermatogonial stem cells (SSCs) from these tissues. The results showed that FM containing 10% dimethyl sulfoxide (Me2SO/DMSO), 10% knockout serum replacement (KSR) and 20% trehalose (FM5) combined with the uncontrolled slow freezing (USF) procedures has the optimized cryoprotective effect on bovine testicular tissues. The FM5 + USF protocol reduced the cell apoptosis, maintained high cell viability, supported the structural integrity and seminiferous epithelial cohesion similar to that in the fresh tissues. Viable germ cells containing SSCs were effectively isolated from these tissues and they maintained germline marker expressions in the co-testicular cells and co-mouse embryonic fibroblasts (MEF) feeder culture systems respectively, during the short-term culture. Additionally, upregulated transcriptions of spermatogenic differentiation marker C-KIT and meiotic marker SYCP3 were detected in these cells after retinoic acid-induced differentiation. Together, FM5 + USF is suitable for the cryopreservation of bovine testicular tissues, with benefits of reducing the apoptosis, maintaining the cell viability, supporting the testicular structure integrity, and sustaining the survival and differentiation potential of bovine germ cells containing SSCs.

Culture bovine prospermatogonia with 2i medium.

Germplasm cryopreservation and expansion of gonocytes/prospermatogonia or spermatogonial stem cells (SSCs) are important; however, it's difficult in cattle. Since inhibitors of Mek1/2 and Gsk3ß (2i) can enhance pluripotency maintenance, effects of 2i-based medium on the cultivation of bovine prospermatogonia from the cryopreserved tissues were examined. The testicular tissues of newborn bulls were well cryopreserved. High mRNA levels of prospermatogonium/SSC markers (PLZF, GFRα-1) and pluripotency markers (Oct4/Pouf5, Sox2, Nanog) were detected and the PLZF+ /GFRα-1+ prospermatogonia were consistently identified immunohistochemically in the seminiferous cords. Using differential plating and Percoll-based centrifugation, 41.59% prospermatogonia were enriched and they proliferated robustly in 2i medium. The 2i medium boosted mRNA abundances of Pouf5, Sox2, Nanog, GFRα-1, PLZF, anti-apoptosis gene Bcl2, LIF receptor gene LIFR and enhanced PLZF protein expression, but suppressed mRNA expressions of spermatogonial differentiation marker c-kit and pro-apoptotic gene Bax, in the cultured prospermatogonia. It also alleviated H2 O2 -induced apoptosis of the enriched cells and decreased histone H3 lysine (K9) trimethylation (H3K9me3) and its methylase Suv39h1/2 mRNA level in the cultured seminiferous cords. Overall, 2i medium improves the cultivation of bovine prospermatogonia isolated from the cryopreserved testes, by inhibiting Suv39h1/2-mediated H3K9me3 through Mek1/2 and Gsk3ß signalling, evidencing successful cryopreservation and expansion of bovine germplasm.

Cryopreservation of calf testicular tissues with knockout serum replacement.

To enrich bovine gonocytes from cryopreserved testicular tissues, the cryoprotection effects of the freezing media containing knockout serum replacement (KSR) were examined. Using Minimum essential medium (MEM) + 10% dimethyl sulfoxide (Me2SO) as the basic medium, calf testicular tissues were cryopreserved in media containing 0, 5, 10, 20, 40, 90% KSR and 5% fetal bovine serum (FBS) respectively. Morphologically, the seminiferous cords and interstitium were well preserved in all groups. The gonocytes were all glial cell line-derived neurotrophic factor (GDNF) family receptor α-1 (GFRα-1) positive. The recovery rates in all KSR groups were higher than that of the 10% Me2SO group, while comparable to the 5% FBS group. The enriched gonocytes expressed gonocyte marker GFRα-1 typically. Collectively, supplementation of 5-10% KSR can achieve comparable cryoprotective effects with using 5% FBS, which is useful in future study due to its defined formulation that is more consistent in quality and stable in supply.

hUMSCs Transplantation Regulates AMPK/NR4A1 Signaling Axis to Inhibit Ovarian Fibrosis in POI Rats.

BACKGROUND: The mechanism of human Umbilical Cord Mesenchymal Stem Cells (hUMSCs) transplantation to improve ovarian function in the rats with Premature Ovarian Insufficiency (POI) is still unclear. The aim of this study is to investigate the signal axis mechanism that is involved in the ovarian function recovery of POI rats following hUMSCs transplantation. METHODS: The rat model with POI was established by intraperitoneal injection of cisplatin. The hUMSCs were transplanted by caudal vein injection into POI rats. Hematoxylin-eosin (H&E) staining was performed to examine the morphology of rat ovarian tissue. Masson staining, Sirus red staining and immunofluorescence were used to observe the fibrosis extent of ovarian tissue. The levels of serum sex hormones and the expression of fibrosis related markers in ovarian tissues were measured by enzyme-linked immunosorbent assay (ELISA). The expression of NR4A1, Phospho-NR4A1 and AMP-activated protein kinase (AMPK) signaling in rat ovarian tissues was measured by immunohistochemistry and immunofluorescence. The role of AMPK/NR4A1 signaling axis in the regulation of ovarian function recovery in POI rats following hUMSCs transplantation was further investigated by adenovirus and siRNA intervention in isolated stromal cells. RESULTS: The results showed that the hUMSCs transplantation significantly inhibited ovarian tissue fibrosis and restored the ovarian function in POI rats. The level of NR4A1 and AMPK expression in ovarian tissue of POI rats after hUMSCs transplantation was significantly increased compared with the control group. In the cultured ovarian stromal cells, the similar results were obtained on the expression of NR4A1 and its regulation on fibrosis related molecular markers in Cisplatin (CDDP) damaged stromal cells following hUMSCs supernatant treatment. Both hUMSCs supernatant treatment and the addition of AMPK inhibitors increased NR4A1 expression in stromal cells. And after NR4A1 molecular intervention, fibrosis-related indicators in stromal cells changed. The data suggests that the AMPK/NR4A1 signaling axis is involved in the ovarian function changes in POI rats following hUMSCs transplantation. CONCLUSION: The data from this study indicate that the inhibition of tissue fibrosis and recovery of ovarian function is regulated by AMPK/NR4A1 signaling axis in POI rats following hUMSCs transplantation.

BP-Net: Boundary and perfusion feature guided dual-modality ultrasound video analysis network for fibrous cap integrity assessment.

Ultrasonography is one of the main imaging methods for monitoring and diagnosing atherosclerosis due to its non-invasiveness and low-cost. Automatic differentiation of carotid plaque fibrous cap integrity by using multi-modal ultrasound videos has significant diagnostic and prognostic value for cardiovascular and cerebrovascular disease patients. However, the task faces several challenges, including high variation in plaque location and shape, the absence of analysis mechanism focusing on fibrous cap, the lack of effective mechanism to capture the relevance among multi-modal data for feature fusion and selection, etc. To overcome these challenges, we propose a new target boundary and perfusion feature guided video analysis network (BP-Net) based on conventional B-mode ultrasound and contrast-enhanced ultrasound videos for assessing the integrity of fibrous cap. Based on our previously proposed plaque auto-tracking network, in our BP-Net, we further introduce the plaque edge attention module and reverse mechanism to focus the dual video analysis on the fiber cap of plaques. Moreover, to fully explore the rich information on the fibrous cap and inside/outside of the plaque, we propose a feature fusion module for B-mode and contrast video to filter out the most valuable features for fibrous cap integrity assessment. Finally, multi-head convolution attention is proposed and embedded into transformer-based network, which captures semantic features and global context information to obtain accurate evaluation of fibrous caps integrity. The experimental results demonstrate that the proposed method has high accuracy and generalizability with an accuracy of 92.35% and an AUC of 0.935, which outperforms than the state-of-the-art deep learning based methods. A series of comprehensive ablation studies suggest the effectiveness of each proposed component and show great potential in clinical application.

Naïve-like conversion of bovine induced pluripotent stem cells from Sertoli cells.

Feeder cells are essential to derive pluripotent stem cells (PSCs). Mouse embryonic fibroblasts (MEF) are widely used as feeder to generate and culture embryonic stem cells (ESCs) and induced PSCs (iPSCs) in many species. However it may not be suitable for livestock ESCs/iPSCs due to interspecies difference. Previously we derived bovine iPSCs from bovine Sertoli cells using MEF feeder. Here we compared the effects of MEF feeder and bovine embryonic fibroblasts (BEF) feeder on the maintenance of bovine iPSC pluripotency and morphology as well their contributions to the naïve-like conversion, based on a naïve medium (NM). The results showed successful conversion of the primed bovine iPSCs to naïve-like state within 3-4 days both on MEF feeder and BEF feeder in NM (termed as MNM and BNM respectively). These naïve-like iPSCs showed normal karyotype. There were more iPSC colonies under BNM condition than MNM condition. Epigenetically, histone modification H3K4 was upregulated, while H3K27 was downregulated in the naïve-like iPSCs. We further analyzed the naïve markers and differentiation potential both in vitro and in vivo of these cells, which were all reserved throughout the maintenance. Together, bovine naïve-like iPSCs can be generated both on MEF and BEF feeder in NM condition. The BNM condition is able to sustain the pluripotency and differentiation potential of the naïve-like bovine iPSCs, and improve the conversion efficiency.

Prevalence of syphilis among people living with HIV and its implication for enhanced coinfection monitoring and management in China: A meta-analysis.

Background: People living with HIV (PLWH) are at an increased risk of syphilis infection. The objectives of this study were to assess the overall prevalence of syphilis among PLWH in China and identify factors associated with syphilis infection among PLWH. Methods: We searched Medline, Embase, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), Wan-fang Data, and Chinese Biomedical Literature Database (CBM) to identify studies that reported the prevalence of syphilis among PLWH in China and were published in English or Chinese from January 1, 1990, to May 31, 2022. The reference lists of retrieved articles and relevant reviews were also checked to identify additional studies. A random-effect model was fitted to calculate the pooled syphilis prevalence among PLWH. Subgroup analyses, meta-regression analyses and sensitivity analyses were conducted to determine the potential source of heterogeneity. Results: Of the 1,599 articles screened, 29 studies involving 34,740 participants were eligible for inclusion in this meta-analysis. The overall prevalence of syphilis among PLWH in China was 19.9% [95% confidence interval (CI): 15.4-24.8%, I 2 = 98.9%]. Subgroup analysis showed that the pooled prevalence of syphilis among men who have sex with men (MSM) with HIV (21.9%, 95% CI: 17.2-26.9%) was much higher than that among heterosexuals (10.3%, 95% CI: 5.2-16.8%); there was regional diversity in the prevalence of syphilis, the highest in northern China (31.7%, 95% CI: 17.9-47.4%), followed by central-southern China (26.7%, 95% CI: 11.4-45.7%), and the lowest in northwestern China (15.0%, 95% CI: 6.9-25.4%); the syphilis prevalence among PLWH decreased as CD4 + T cell count increased (19.6% in CD4 + T cell < 200 vs. 8.7% in ≥ 500) and was higher among non-antiretroviral therapy (non-ART) HIV-infected patients (21.0%, 95% CI: 9.9-35.0%) than that among ART ones (16.1%, 95% CI: 3.9-34.3%). Conclusions: Our study showed a significantly high prevalence of syphilis among PLWH in China, particularly among MSM with HIV. Developing national guidelines for the integrated screening, monitoring, and management of HIV and syphilis as well as syphilis diagnosis and treatment training programs for physicians at designated HIV treatment hospitals is urgent and crucial to combat HIV and syphilis coinfection in China.

Current Evidence and Future Directions of Berberine Intervention in Depression.

A major type of serious mood disorder, depression is currently a widespread and easily overlooked psychological illness. With the low side effects of natural products in the treatment of diseases becoming the pursuit of new antidepressants, natural Chinese medicine products have been paid more and more attention for their unique efficacy in improving depression. In a view from the current study, the positive antidepressant effects of berberine are encouraging. There is a lot of work that needs to be done to accurately elucidate the efficacy and mechanism of berberine in depression. In this review, the relevant literature reports on the treatment of depression and anxiety by berberine are updated, and the potential pharmacological mechanism of berberine in relieving depression has also been discussed.

Schisandrin A and B affect the proliferation and differentiation of neural stem cells.

Schisandrin A and B (Sch A and B) are the important components of Asian dietary supplement and phytomedicine Schisandra chinensis (S. chinensis). They can enhance adult neurogenesis in vivo; however, these effects still need to be verified. Here NE-4 C neural stem cells (NSCs) were employed as the in vitro model and treated with Sch A and B at 0.1 µg/mL. EdU (5-Ethynyl-2'-deoxyuridine) labeling showed that both Sch A and B treatments enhanced NSC proliferation. Real-time PCR analysis showed the mRNA abundances of telomerase gene Tert and cell cycle gene Cyclin D1 were significantly up-regulated after the treatments. During the neurosphere induction, Sch B enhanced the neurosphere formation and neuronal differentiation, and increased the neurosphere semidiameters. Detection of the neuron differentiation marker Mapt indicates that both Sch A and B, especially Sch B, benefits the induced neuronal differentiation. Sch B treatment also enhanced mRNA expressions of the neurosphere-specific adhesion molecule Cdh2 and Wnt pathway-related genes including Mmp9, Cyclin D1 and ß-catenin. Together, Sch A especially Sch B, promotes the proliferation, affects the survival, differentiation and neurogenesis of NSCs, which is consistent with their in vivo effects. This study provides further clue on the potential neuropharmacological effects of S. chinensis.

Response of Fusarium pseudograminearum to Biocontrol Agent Bacillus velezensis YB-185 by Phenotypic and Transcriptome Analysis.

The use of biological control agents (BCAs) is a promising alternative control measure for Fusarium crown rot (FCR) of wheat caused by Fusarium pseudograminearum. A bacterial strain, YB-185, was isolated from the soil of wheat plants with FCR and identified as Bacillus velezensis. YB-185 exhibited strong inhibition of F. pseudograminearum mycelial growth and conidial germination in culture. Seed treatment with YB-185 in greenhouse and field resulted in reductions in disease by 66.1% and 57.6%, respectively, along with increased grain yield. Microscopy of infected root tissues confirmed that YB-185 reduced root invasion by F. pseudograminearum. RNA-seq of F. pseudograminearum during co-cultivation with B. velezensis YB-185 revealed 5086 differentially expressed genes (DEGs) compared to the control. Down-regulated DEGs included genes for glucan synthesis, fatty acid synthesis, mechanosensitive ion channels, superoxide dismutase, peroxiredoxin, thioredoxin, and plant-cell-wall-degrading enzymes, whereas up-regulated DEGs included genes for chitin synthesis, ergosterol synthesis, glutathione S-transferase, catalase, and ABC transporters. In addition, fungal cell apoptosis increased significantly, as indicated by TUNEL staining, and the scavenging rate of 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt radical cation (ABTS·+) in the fungus significantly decreased. Thus, F. pseudograminearum may be trying to maintain normal cell functions by increasing cell wall and membrane synthesis, antioxidant and anti-stress responses, detoxification of bacterial antimicrobial compounds, and transportation of damaging compounds from its cells. However, cell death and free radical accumulation still occurred, indicating that the responses were insufficient to prevent cell damage. Bacillus velezensis YB-185 is a promising BCA against FCR that acts by directly damaging F. pseudograminearum, thus reducing its ability to colonize roots and produce symptoms.

Automatic multi-plaque tracking and segmentation in ultrasonic videos.

Carotid plaque tracking and segmentation in ultrasound videos is the premise for subsequent plaque property evaluation and treatment plan development. However, the task is quite challenging, as it needs to address the problems of poor image quality, plaque shape variations among frames, the existence of multiple plaques, etc. To overcome these challenges, we propose a new automatic multi-plaque tracking and segmentation (AMPTS) framework. AMPTS consists of three modules. The first module is a multi-object detector, in which a Dual Attention U-Net is proposed to detect multiple plaques and vessels simultaneously. The second module is a set of single-object trackers that can utilize the previous tracking results efficiently and achieve stable tracking of the current target by using channel attention and a ranking strategy. To make the first module and the second module work together, a parallel tracking module based on a simplified 'tracking-by-detection' mechanism is proposed to solve the challenge of tracking object variation. Extensive experiments are conducted to compare the proposed method with several state-of-the-art deep learning based methods. The experimental results demonstrate that the proposed method has high accuracy and generalizability with a Dice similarity coefficient of 0.83 which is 0.16, 0.06 and 0.27 greater than MAST (Lai et al., 2020), Track R-CNN (Voigtlaender et al., 2019) and VSD (Yang et al., 2019) respectively and has made significant improvements on seven other indicators. In the additional Testing set 2, our method achieved a Dice similarity coefficient of 0.80, an accuracy of 0.79, a precision of 0.91, a Recall 0.70, a F1 score of 0.79, an AP@0.5 of 0.92, an AP@0.7 of 0.74, and an expected average overlap of 0.79. Numerous ablation studies suggest the effectiveness of each proposed component and the great potential for multiple carotid plaques tracking and segmentation in clinical practice.

Effective isolation of Sertoli cells from New Zealand rabbit testis.

OBJECTIVE: Sertoli cells (SCs) are important sustentacular cells in the seminiferous tubules of the testis. Isolation and identification of SCs are the premise for studying their functions. Since New Zealand rabbit is a stable strain which is widely used for biomedical research and animal farming, this study aimed to develop a simple and effective protocol for SC isolation in New Zealand rabbits. MATERIALS AND METHODS: The SCs of three 30-day-old New Zealand rabbits were isolated by incubation with enzymatic digestion I (Dulbecco's modified Eagle medium supplemented with 1 mg/ml collagenase IV and 50 µg/ml DNase I) and digestion II (digestion I + 1 mg/ml hyaluronidase + 1 mg/ml trypsin), as well as differential plating. The cells were enriched and identified by using immunocytochemical staining and reverse transcription polymerase chain reaction analysis. RESULTS: Homogeneous cells were obtained. They presented the typical large cell body and an irregular pyramidal shape after differential plating and passaging. These cells expressed mRNA of the SC marker sex-determining region Y-box 9 (SOX9) instead of the Leydig cell marker StAR. Immunocytochemically, they are positive of SOX9, GATA binding protein 4, and androgen-binding protein. CONCLUSION: The SCs were enriched from the testicular tissues of prepubertal New Zealand rabbits by a simple and effective protocol, which provides a basis for further theoretical researches and practical applications.

Contrast-enhanced ultrasound perfusion patterns and serum lipid signatures of vulnerable carotid artery plaque in predicting stroke: A cohort study of carotid stenosis in Chinese patients.

BACKGROUND: Early identification of vulnerable plaques at risk of rupture could help prevent cerebral ischemic stroke in patients with carotid artery disease. OBJECTIVE: To investigate the correlation between contrast-enhanced ultrasound (CEUS) perfusion patterns and serum lipid signatures of carotid artery plaques with the degree of carotid stenosis. METHODS: A total of 80 patients with carotid artery plaques who underwent CEUS were included. All patients underwent CEUS, computed tomography angiography or digital subtraction angiography, and serum lipid testing. RESULTS: The contrast agent enhancement levels and the CEUS perfusion patterns in the plaques were associated with the degree of carotid stenosis (P < 0.05). Serum free fatty acid (FFA) was associated with the contrast agent enhancement levels (P < 0.05), but did not correlate with the degree of stenosis (P > 0.05). There was no significant difference in total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides with respect to contrast agent enhancement levels (P > 0.05) or the degree of stenosis (P > 0.05). CONCLUSION: A high level of CEUS perfusion and increased serum FFA levels are indicative of vulnerable carotid plaques, which may be useful for the prediction of stroke in patients with carotid artery disease.

hUMSC transplantation restores ovarian function in POI rats by inhibiting autophagy of theca-interstitial cells via the AMPK/mTOR signaling pathway.

BACKGROUND: Previous studies of primary ovarian insufficiency (POI) have focused on granulosa cells (GCs) and ignored the role of theca-interstitial cells (TICs). This study aims to explore the mechanism of the protective effects of human umbilical cord-derived mesenchymal stem cells (hUMSCs) on ovarian function in POI rats by regulating autophagy of TICs. METHODS: The POI model was established in rats treated with cisplatin (CDDP). The hUMSCs were transplanted into POI rats by tail vein. Enzyme-linked immunosorbent assay (ELISA) analysis, hematoxylin and eosin (HE) staining, and immunohistochemistry were used to measure the protective effects of hUMSCs. The molecular mechanisms of injury and repairment of TICs were assessed by immunofluorescence, transmission electron microscope (TEM), flow cytometry (FCM), western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: In vivo, hUMSC transplantation restored the ovarian function and alleviated the apoptosis of TICs in POI rats. In vitro, hUMSCs reduced the autophagy levels of TICs by reducing oxidative stress and regulating AMPK/mTOR signaling pathway, thereby alleviating the apoptosis of TICs. CONCLUSION: This study indicates that hUMSCs protected ovarian function in POI by regulating autophagy signaling pathway AMPK/mTOR.

Schisandrin A and B enhance the dentate gyrus neurogenesis in mouse hippocampus.

Schisandrin A and B (Sch A and B) are the main effective components of Schisandra chinensis (S. chinensis), which is traditionally used to enhance mental and intellectual functions in eastern Asia. Previously, we reported Sch A and B remarkably affect adult neurogenesis in the subventricular zone of mouse lateral ventricle. Since the neurogenesis in the hippocampal dentate gyrus (DG) is more important to learning, memory and cognition, here we further examined their effects on the adult DG neurogenesis. Phosphohistone H3 (PHH3) immunostaining showed that Sch B significantly enhanced the cell proliferation in the DG. Glial fibrillary acidic protein (GFAP, mostly labels astrocytes and some stem cells) staining was used to further identify the proliferating cell type. Dramatically, increases of GFAP+ cells in both Sch A and B treated groups were observed. What's more, the total numbers of the mature neurons labeled by neuron-specific nuclear protein (NeuN) were also increased in both Sch A and B treated groups compared with the controls. Together, Sch A and B enhance the adult DG neurogenesis by increasing astrocytes/stem cells and improving the survival and maturation of DG neurons. Our study shed a new light on the neuropharmacological functions of the herbal medicine S. chinensis.

Decreased abundance of GDNF mRNA transcript in the immature Sertoli cells of cattle in response to protein kinase inhibitor staurosporine.

Sertoli cells (SC) have important functions in spermatogenesis by regulating development of spermatogenic cells. Glial cell line-derived neurotrophic factor (GDNF) are produced by SC. Although the effects of GDNF on spermatogenesis have been well studied, the understanding of how GDNF is synthesized is still limited, especially in food animal producing species. Because protein kinase (PK) has varied functions in multiple cellular processes and the PK pathway modulates SC functions, the objective of the present study was to determine whether PK modulates the abundance of GDNF protein in SC of cattle. To conduct this study, immature SC were enriched from cryopreserved testicular tissues of 1-day-old bulls. These cells had a marked proliferation capacity. Results from immunostaining analysis indicated that there was a sustained abundance of SC mRNA marker protein transcripts and marker proteins: androgen bind protein (ABP), GATA4 and VIMENTIN. There was subsequent characterization of SC treated with the PK inhibitor staurosporine for 0, 1 or 2 h. Results from real-time-PCR and Western blot analyses indicated the treatment (2 h) resulted in a decrease in Gdnf mRNA transcript and GDNF protein. Additionally, the staurosporine treatment resulted in an increase in the abundance of anti-apoptosis Bcl2 and decrease in pro-apoptosis Bax mRNA transcripts. Furthermore, results of the TUNEL assay indicated there was a decrease in apoptosis in the staurosprine-treated SC. Collectively, results indicate the PK signaling is involved in regulation of GDNF protein abundance in the immature SC and the survival of these cells in cattle.