Description and phylogenetic analysis of the complete mitochondrial genome in Eulaelaps silvestris provides new insights into the molecular classification of the family Haemogamasidae.

In this study, the mitochondrial genome of Eulaelaps silvestris, which parasitizes Apodemus chevrieri, was sequenced and assembled to fill the gap in understanding the molecular evolution of the genus Eulaelaps. The E. silvestris mitochondrial genome is a double-stranded DNA molecule with a length of 14 882 bp, with a distinct AT preference for base composition and a notably higher AT content than GC content. The arrangement between genes is relatively compact, with a total of 10 gene intergenic regions and 12 gene overlap regions. All protein-coding genes had a typical ATN initiation codon, and only 2 protein-coding genes had an incomplete termination codon T. Out of the 13 protein-coding genes, the 5 most frequently used codons ended in A/U, with only 1 codon ending in G/C had an relative synonymous codon usage value >1. Except for trnS1 and trnS2, which lacked the D arm, all other tRNAs were able to form a typical cloverleaf structure; and there were a total of 38 mismatches in the folding process of tRNA genes. Unlike the gene arrangement order of the arthropod hypothetical ancestor, the E. silvestris mitochondrial genome underwent fewer rearrangements, mainly near tRNA genes and control regions. Both the maximum likelihood tree and the Bayesian tree showed that the family Haemogamasidae is most closely related to the family Dermanyssidae. The results not only provide a theoretical basis for studying the phylogenetic relationships of the genus Eulaelaps, but also provide molecular evidence that the family Haemogamasidae does not belong to the subfamily Laelapidae.

The complete mitochondrial genome of Eulaelaps huzhuensis (Mesostigmata: Haemogamasidae).

Some mites of the family Haemogamasidae can transmit a variety of zoonotic diseases and have important public health and safety implications. Currently, however, little attention has been paid to molecular data of Haemogamasidae species, limiting our understanding of their evolutionary and phylogenetic relationships. In this study, the complete mitochondrial genome of Eulaelaps huzhuensis was determined for the first time, and its genomic information was analyzed in detail. The mitochondrial genome of E. huzhuensis is 14,872 bp in length with 37 genes and two control regions. The base composition showed a distinct AT preference. Twelve protein-coding genes have a typical ATN as the start codon, and three protein-coding genes have incomplete stop codons. During the folding of tRNA genes, a total of 30 mismatches occurred, and three tRNA genes had an atypical cloverleaf secondary structure. The order of the E. huzhuensis mitochondrial genome arrangement is a new type of rearrangement in Mesostigmata. The phylogenetic analysis confirmed that the family Haemogamasidae is a monophyletic branch and does not belong to a subfamily of the Laelapidae. Our results lay the foundation for subsequent studies on the phylogeny and evolutionary history of the family Haemogamasidae.

The MdBBX22-miR858-MdMYB9/11/12 module regulates proanthocyanidin biosynthesis in apple peel.

Proanthocyanidins (PAs) have antioxidant properties and are beneficial to human health. The fruit of apple (Malus × domestica Borkh.), especially the peel, is rich in various flavonoids, such as PAs, and thus is an important source of dietary antioxidants. Previous research on the regulation of PAs in apple has mainly focussed on the transcription level, whereas studies conducted at the post-transcriptional level are relatively rare. In this study, we investigated the function of mdm-miR858, a miRNA with multiple functions in plant development, in the peel of apple fruit. We showed that mdm-miR858 negatively regulated PA accumulation by targeting MdMYB9/11/12 in the peel. During fruit development, mdm-miR858 expression was negatively correlated with MdMYB9/11/12 expression and PA accumulation. A 5'-RACE experiment, GUS staining assays and transient luminescent assays indicated that mdm-miR858 cleaved and inhibited the expression of MdMYB9/11/12. Overexpression of mdm-miR858 in apple calli, tobacco and Arabidopsis reduced the accumulation of PAs induced by overexpression of MdMYB9/11/12. Furthermore, we found that MdBBX22 bound to the mdm-miR858 promoter and induced its expression. Overexpression of MdBBX22 induced the expression of mdm-miR858 to inhibit the accumulation of PAs in apple calli overexpressing MdMYB9/11/12. Under light stress, MdBBX22 induced mdm-miR858 expression to inhibit PA accumulation and thereby indirectly enhanced anthocyanin synthesis in the peel. The present results revealed that the MdBBX22-miR858-MdMYB9/11/12 module regulates PA accumulation in apple. The findings provide a reference for further studies of the regulatory mechanism of PA accumulation and the relationship between PAs and anthocyanins.

Empowering pro-environmental behavior in tourists through digital media: the influence of eco-guilt and empathy with nature.

In the digital economy era, leveraging digital media to foster tourists' pro-environmental behavioral intention (TPEBI) has become crucial in the field of sustainable tourism. While existing studies have mainly focused on the driving mechanism of TPEBI within physical tourism contexts, the correlation between digital media information sharing and TPEBI remains unclear. Our study employs the cognitive-affective-conative framework to construct a theoretical model, considering eco-guilt and empathy with nature as mediating variables. It aims to explore the influencing mechanism of destination environmental information sharing through digital media on TPEBI from a presence perspective. Thereby, two scenario experiments were designed: Study 1 examined the impact of different formats of destination environmental threat information presentation on digital media on the sense of presence, while Study 2 explored the influencing mechanism of presence on TPEBI based on the conclusions of Study 1. Results indicate that (1) vivid and visible presentation formats of destination environmental threat information on digital media enhance individuals' sense of presence; (2) sense of presence positively influences TPEBI; and (3) eco-guilt and empathy with nature mediate between presence and TPEBI. These findings not only contribute to theoretical and empirical research on digital media information sharing in sustainable tourism but also offer guidance for governments and tourism destinations to effectively stimulate TPEBI through digital media, achieve the sustainable development of destinations.

Corrigendum: TAT-HSP27 peptide improves neurologic deficits via reducing apoptosis after experimental subarachnoid hemorrhage.

[This corrects the article DOI: 10.3389/fncel.2022.878673.].

Aberrant DNA methylation in cervical carcinogenesis.

Persistent infection with high-risk types of human papillomavirus(HPV) is known to cause cervical cancer; however, additional genetic and epigenetic alterations are required for progression from precancerous disease to invasive cancer. DNA methylation is an early and frequent molecular alteration in cervical carcinogenesis. In this review, we summarize DNA methylation within the HPV genome and human genome and identify its clinical implications. Methylation of the HPV long control region (LCR) and L1 gene is common during cervical carcinogenesis and increases with the severity of the cervical neoplasm. The L1 gene of HPV16 and HPV18 is consistently hypermethylated in invasive cervical cancers and can potentially be used as a clinical marker of cancer progression. Moreover, promoters of tumor suppressor genes (TSGs) involved in many cellular pathways are methylated in cervical precursors and invasive cancers. Some are associated with squamous cell carcinomas, and others are associated with adenocarcinomas. Identification of methylated TSGs in Pap smear could be an adjuvant test in cervical cancer screening for triage of women with high-risk HPV, atypical squamous cells of undetermined significance, or low grade squamous intraepithelial lesion (LSIL). However, consistent panels must be validated for this approach to be translated to the clinic. Furthermore, reversion of methylated TSGs using demethylating drugs may be an alternative anticancer treatment, but demethylating drugs without toxic carcinogenic and mutagenic properties must be identified and validated.

GRADE Use in Evidence Syntheses Published in High-Impact-Factor Gynecology and Obstetrics Journals: A Methodological Survey.

Objective: To identify and describe the certainty of evidence of gynecology and obstetrics systematic reviews (SRs) using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Method: Database searches of SRs using GRADE, published between 1 January 2016 to 31 December 2020, in the 10 "gynecology and obstetrics" journals with the highest impact factor, according to the Journal Citation Report 2019. Selected studies included those SRs using the GRADE approach, used to determine the certainty of evidence. Results: Out of 952 SRs, ninety-six SRs of randomized control trials (RCTs) and/or nonrandomized studies (NRSs) used GRADE. Sixty-seven SRs (7.04%) rated the certainty of evidence for specific outcomes. In total, we identified 946 certainty of evidence outcome ratings (n = 614 RCT ratings), ranging from very-low (42.28%) to low (28.44%), moderate (17.65%), and high (11.63%). High and very low certainty of evidence ratings accounted for 2.16% and 71.60% in the SRs of NRSs, respectively, compared with 16.78% and 26.55% in the SRs of RCTs. In the SRs of RCTs and NRSs, certainty of evidence was mainly downgraded due to imprecision and bias risks. Conclusions: More attention needs to be paid to strengthening GRADE acceptance and building knowledge of GRADE methods in gynecology and obstetrics evidence synthesis.

Diet quality and survival after ovarian cancer: results from an ovarian cancer follow-up study (OOPS).

Background and aims: Owing to the limited studies and controversial evidence, the connection between diet quality and survival of patients with ovarian cancer (OC) has been indistinct. Our study intends to first investigate this topic based on Chinese diet quality scores. Methods: Our data come from an ovarian cancer follow-up study, which includes 796 patients with OC between 2015 and 2020. Three diet quality scores, including the Chinese Healthy Eating Index (CHEI), Dietary Balance Index (DBI), and Chinese Food Pagoda Score (CFPS), were calculated using a validated 111-item food frequency questionnaire. We used the Cox proportional hazards regression model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Potential multiplicative and additive interactions were also assessed. Results: With a median follow-up time of 37.17 months (interquartile: 24.73-50.17 months), we recorded 130 deaths. According to comparisons of the highest to lowest tertile of scores, the pre-diagnosis CHEI was linked to better overall survival (OS) in patients (HR = 0.56, 95% CI: 0.36, 0.88). A dose-response relationship between CHEI and OS was also observed (HR = 0.85, 95% CI: 0.71, 1.00, per 1 standard deviation increment). However, no evidence of significant associations between DBI and CFPS with OS was observed. Additionally, significant multiplicative and additive interactions were seen in the diet quality scores (CHEI and DBI) with the body mass index and the menopausal status. Conclusions: A high CHEI was associated with an improved OS for patients with OC, while DBI and CFPS were unrelated to OC survival.

Association between pre-diagnostic dietary antioxidant vitamin consumption and ovarian cancer survival: a prospective cohort study.

Background: Epidemiological evidence regarding the relationship between dietary antioxidant vitamin intake and ovarian cancer (OC) survival is not clear. Herein, we aimed to first evaluate this topic in a prospective cohort study in China. Methods: The present study included participants from the Ovarian Cancer Follow-Up Study, which was a hospital-based prospective cohort study including OC patients who were aged 18 to 79 years during 2015-2020. The information on the intake of antioxidant vitamins, consisting of vitamin A, retinol, α-carotene, ß-carotene, vitamin C, and vitamin E, and other diet information was obtained through a 111-item food frequency questionnaire. Deaths were recorded until March 31, 2021. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival were evaluated using Cox proportional hazards models. Results: There were 130 (18.49%) deaths among 703 OC patients during a median 37.19 months follow-up. In the multivariable-adjusted model, the highest tertile of dietary vitamin C (HR = 0.43, 95% CI = 0.25-0.75, P for trend <0.05) and ß-carotene intake (HR = 0.52, 95% CI = 0.31-0.87, P for trend <0.05) was inversely associated with the overall survival of OC when compared with the lowest tertile group. Retinol, vitamin A, vitamin E, and α-carotene consumption showed no association with OC survival. Of note is that the multiplicative interaction was identified between vitamin C intake and residual lesions in OC survival (P for interaction <0.05). Conclusion: Our findings indicate that pre-diagnostic higher vitamin C and ß-carotene intake was associated with improved OC survival.

Palmitoylation of MDH2 by ZDHHC18 activates mitochondrial respiration and accelerates ovarian cancer growth.

Epithelial ovarian cancer (EOC) exhibits strong dependency on the tricarboxylic acid (TCA) cycle and oxidative phosphorylation to fuel anabolic process. Here, we show that malate dehydrogenase 2 (MDH2), a key enzyme of the TCA cycle, is palmitoylated at cysteine 138 (C138) residue, resulting in increased activity of MDH2. We next identify that ZDHHC18 acts as a palmitoyltransferase of MDH2. Glutamine deprivation enhances MDH2 palmitoylation by increasing the binding between ZDHHC18 and MDH2. MDH2 silencing represses mitochondrial respiration as well as ovarian cancer cell proliferation both in vitro and in vivo. Intriguingly, re-expression of wild-type MDH2, but not its palmitoylation-deficient C138S mutant, sustains mitochondrial respiration and restores the growth as well as clonogenic capability of ovarian cancer cells. Notably, MDH2 palmitoylation level is elevated in clinical cancer samples from patients with high-grade serous ovarian cancer. These observations suggest that MDH2 palmitoylation catalyzed by ZDHHC18 sustains mitochondrial respiration and promotes the malignancy of ovarian cancer, yielding possibilities of targeting ZDHHC18-mediated MDH2 palmitoylation in the treatment of EOC.

Relationship between different forms of dietary choline and ovarian cancer survival: findings from the ovarian cancer follow-up study, a prospective cohort study.

Background: Choline has important and diverse functions in both cellular maintenance and growth. However, the relationships between the prediagnosis of the different forms of dietary choline intake and ovarian cancer (OC) survival are relatively unknown. This study is the first to investigate this topic based on the Ovarian Cancer Follow-Up Study, a prospective cohort study conducted in China. Methods: In the present study, 635 new cases of ovarian cancer between the ages of 18 and 79 were enrolled. A valid and reliable 111-item food frequency questionnaire was used to assess dietary choline intake. Deaths were ascertained until March 31, 2021, via medical records and active follow-up. Multivariable-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: During a median follow-up of 37.2 months (interquartile: 24.7-50.2 months), 114 deaths were identified. Higher lipid-soluble choline intake was significantly associated with better overall survival for patients with OC (Tertile 3 vs. Tertile 1: HR = 0.56; 95% CI: 0.34, 0.92; P trend = 0.02) in the fully adjusted model. Similar associations were observed for phosphatidylcholine intake (Tertile 3 vs. Tertile 1: HR = 0.55; 95% CI: 0.33, 0.91; P trend = 0.02). However, no associations were found between total water-soluble choline (free choline, phosphocholine, and glycerophosphocholine), sphingomyelin, and betaine intake and OC survival. Significant additive interactions between higher fat-soluble choline intake and positive expression of estrogen receptor and Wilms tumor-1 as well as higher phosphatidylcholine intake and positive expression of estrogen receptor and Wilms tumor-1 on OC survival were detected. Conclusions: Our findings indicate that prediagnosis, total lipid-soluble choline and phosphatidylcholine intake were associated with improved overall survival among OC patients.

TAT-HSP27 Peptide Improves Neurologic Deficits via Reducing Apoptosis After Experimental Subarachnoid Hemorrhage.

Cell apoptosis plays an important role in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Heat shock protein 27 (HSP27), a member of the small heat shock protein (HSP) family, is induced by various stress factors and exerts protective role on cells. However, the role of HSP27 in brain injury after SAH needs to be further clarified. Here, we reported that HSP27 level of cerebrospinal fluid (CSF) is increased obviously at day 1 in patients with aneurysmal SAH (aSAH) and related to the grades of Hunt and Hess (HH), World Federation of Neurological Surgeons (WFNS), and Fisher score. In rat SAH model, HSP27 of CSF is first increased and then obviously declined; overexpression of HSP27, not knockdown of HSP27, attenuates SAH-induced neurological deficit and cell apoptosis in the basal cortex; and overexpression of HSP27 effectively suppresses SAH-elevated activation of mitogen-activated protein Kinase Kinase 4 (MKK4), the c-Jun N-terminal kinase (JNK), c-Jun, and caspase-3. In an in vitro hemolysate-damaged cortical neuron model, HSP2765-90 peptide effectively inhibits hemolysate-induced neuron death. Furthermore, TAT-HSP2765-90 peptide, a fusion peptide consisting of trans-activating regulatory protein (TAT) of HIV and HSP2765-90 peptide, effectively attenuates SAH-induced neurological deficit and cell apoptosis in the basal cortex of rats. Altogether, our results suggest that TAT-HSP27 peptide improves neurologic deficits via reducing apoptosis.

Expression profiling and regulation of genes related to silkworm posterior silk gland development and fibroin synthesis.

The posterior silk gland (PSG) is the most important suborgan responsible for the synthesis and secretion of silk core fibroin proteins in silkworm. Here, we performed genome-scale expression profiling analysis of silkworm PSG at the fourth molting (M4) and at day 1 (V1), day 3 (V3), day 5 (V5), and wandering stage (W) of the fifth instar by microarray analysis with 22 987 probes. We found that the five genes of silk proteins secreted from PSG including fibroin heavy (H) and light (L) chains, P25, seroin 1, and seroin 2 basically showed obvious up-regulation at V3 which lasted to V5, while slight down-regulation at W. The expression of translation-related genes including ribosomal proteins and translation initiation factors generally remained stable from M4 to V5, whereas it showed clear down-regulation at W. Clustering analysis of the 643 significantly differentially expressed transcripts revealed that 43 of the important genes including seroin 1 and sugar transporter protein had co-expression patterns which were consistent with the rate changes of fibroin synthesis and PSG growth. Pathway analysis disclosed that the genes in different clusters might have co-regulations and direct interactions. These genes were supposed to be involved in the fibroin synthesis and secretion. The differential expression of several hormone-related genes also suggested their functions on the regulation of PSG development and fibroin synthesis. 2D gel-based proteomics and phosphoproteomics profiling revealed that the phosphorylated proteins accounted for no more than one-sixth of the total proteins at each stage, which was much lower than the level in normal eukaryotic cells. Changes in the phosphorylation status and levels of several proteins such as actin-depolymerizing factor 1 and enolase might be deeply involved in fibroin secretion and tissue development. Shotgun proteomic profiling combined with label-free quantification analysis on the PSG at V3, V5, and W revealed that many small heat shock proteins (sHSP) were specially expressed at W, which was substantially consistent with the results from 2-DE analysis, and implied the close correlations of sHSP with the physiological states of PSG at W. A majority of significantly up-regulated proteins at V5 were related to ribosome pathway, which was different from the microarray results, implying that the translation-level regulation of ribosomal proteins might be critical for fibroin synthesis. In contrast, the ubiquitin-proteasome pathway related proteins appeared obviously up-regulated at W, suggesting that the programmed cell death process of PSG cells might be started before cocooning.

Gene expression profile analysis of tobacco leaf trichomes.

BACKGROUND: Leaf trichomes of Nicotiana tabacum are distinguished by their large size, high density, and superior secretion ability. They contribute to plant defense response against biotic and abiotic stress, and also influence leaf aroma and smoke flavor. However, there is limited genomic information about trichomes of this non-model plant species. RESULTS: We have characterized Nicotiana tabacum leaf trichome gene expression using two approaches. In the first, a trichome cDNA library was randomly sequenced, and 2831 unique genes were obtained. The most highly abundant transcript was ribulose bisphosphate carboxylase (RuBisCO). Among the related sequences, most encoded enzymes involved in primary metabolism. Secondary metabolism related genes, such as isoprenoid and flavonoid biosynthesis-related, were also identified. In the second approach, a cDNA microarray prepared from these 2831 clones was used to compare gene expression levels in trichome and leaf. There were 438 differentially expressed genes between trichome and leaves-minus-trichomes. Of these, 207 highly expressed genes in tobacco trichomes were enriched in second metabolic processes, defense responses, and the metabolism regulation categories. The expression of selected unigenes was confirmed by semi-quantitative RT-PCR analysis, some of which were specifically expressed in trichomes. CONCLUSION: The expression feature of leaf trichomes in Nicotiana tabacum indicates their metabolic activity and potential importance in stress resistance. Sequences predominantly expressed in trichomes will facilitate gene-mining and metabolism control of plant trichome.

[Epidemiological analysis of maternal death in Beijing from 1995 to 2010].

OBJECTIVE: To analysis the trend of maternal death time and explore the impact of the variety of death causes and birth place to maternal death time. METHODS: According to the data provided by Beijing Maternal and Children Health Hospital, the 372 death cases of pregnant and lying-in women from 1995 to 2010, a retrospective study was performed to analyze the death causes, maternal death time and the influencing factors. RESULTS: The MMR declined from 27.9 per 100 000 live births from 1995 to 2000 to 14.8 per 100 000 live births from 2006 to 2010, with a decline of 46.9%. Among the maternal death within 24 hours of delivery, 79.7% (106/133) died of obstetric hemorrhage, hypertensive disorder complicating pregnancy and amniotic fluid embolism. It took up 47.8% (64/134) from 1995 to 2000, reduced to 37.5% (45/120) from 2006 to 2010. At the same time, the maternal mortality ratio within 24 hours reduced from 40.2%(54/134) to 28.3% (34/120), the variation of death time was consistent with the causes of maternal mortality (χ² = 59.109, P < 0.05). Indirect obstetric causes increased significantly from 2006 to 2010, 53.2% (33/62) of pregnant women with heart disease, cerebrovascular disease and pulmonary embolism died in prenatal or more than 120 hours postnatal. Among the maternal death delved in hospital, 29.0% (29/100) died within 24 hours, 52 cases delved at home or in private clinics, 43 cases (82.6%) died within 24 h postnatal. There were significant differences between birth place and death time (χ² = 24.500, P < 0.05). CONCLUSION: Maternal death time changed from 24 hours of delivery to prenatal or postnatal a long time. The maternal mortality causes and hospital delivery is an important factor affecting maternal time.

MdBBX21, a B-Box Protein, Positively Regulates Light-Induced Anthocyanin Accumulation in Apple Peel.

The red coloration of apple (Malus × domestica Borkh.) is due to the accumulation of anthocyanins in the fruit peel. Light is essential for anthocyanin biosynthesis in apple. In this study, we performed a transcriptome sequencing (RNA-seq) analysis of apple fruit exposed to light after unbagging. The identified differentially expressed genes included MdBBX21, which is homologous to Arabidopsis BBX21, suggesting it may be involved in light-induced anthocyanin biosynthesis. Additionally, MdBBX21 was localized in the nucleus and its gene was expressed earlier than MdMYB1 in apple peel treated with light. Overexpressing MdBBX21 in Arabidopsis and apple calli under light increased anthocyanin accumulation. Dual-luciferase and yeast one-hybrid assays confirmed that MdBBX21 binds to the MdHY5, MdBBX20, and MdBBX22-1/2 promoters and induces expression. At the same time, MdHY5 can also activate the expression of MdBBX21. Furthermore, bimolecular fluorescence complementation and yeast two-hybrid assays demonstrated that MdBBX21 can interact with MdHY5. This interaction can significantly enhance MdMYB1 promoter activity. These findings clarify the molecular mechanism by which MdBBX21 positively regulates light-induced anthocyanin accumulation in apple.

Structural basis for high-pressure improvement in depolymerization of interfacial protein from RFRS meat batters in relation to their solubility.

High-pressure processing (HPP) can modify the construction of interfacial proteins (IPs) to improve the properties of reduced-fat and reduced-salt (RFRS) meat batters. In this study, the relationship between the construction of IPs and their solubility at fat droplet/water interface in RFRS meat batters with HPP treatments was investigated. When 200 MPa for 2 min was applied, the IPs exhibited the highest solubility due to a high concentration of absorbed myosin with the content of random coil 65.62%, but the particle diameter was in reverse. The microscopy revealed the depolymerization of IPs occurred at low pressure, while macromolecular aggregates were produced as the cross-linking of IPs to some degree at pressure ≥ 200 MPa. This phenomenon was supported by the result of SDS-PAGE and the sulfhydryl of IPs. In conclusion, the HPP induced solubility alteration of IPs was achieved by modifying their construction through adjusting the secondary structures and regulating bond interactions.

mdm-miR828 Participates in the Feedback Loop to Regulate Anthocyanin Accumulation in Apple Peel.

Anthocyanins are responsible for the red pigmentation in the peel of apple (Malus × domestica Borkh.) fruit. Relatively few studies have investigated anthocyanins at the posttranscriptional level. MicroRNAs play an important role in plant growth and development by regulating gene expression at the posttranscriptional level. In this study, mdm-miR828 showed a relatively low expression level during the rapid fruit coloration period. However, the mdm-miR828 expression level increased in the late fruit coloration stage. Overexpression of mdm-miR828 inhibited anthocyanin synthesis in apple and Arabidopsis. Dual-luciferase and yeast one-hybrid assays showed that MdMYB1 is capable of binding to the promoter of mdm-MIR828b to promote its expression. The results indicate that mdm-miR828 is involved in a feedback regulatory mechanism associated with anthocyanin accumulation in apple. In addition, mdm-miR828 is involved in the inhibition of anthocyanin accumulation in response to high temperature.

Negative Allosteric Modulator of mGluR1 Improves Long-Term Neurologic Deficits after Experimental Subarachnoid Hemorrhage.

Aneurysmal subarachnoid hemorrhage (SAH) causes permanent neurological sequelae, but the underlying mechanism needs to be further clarified. Here, we show that inhibition of metabotropic glutamate receptor 1 (mGluR1) with negative allosteric modulator JNJ16259685 improves long-term neurobehavioral outcomes in an endovascular perforation model of SAH. JNJ16259685 improves cerebrovascular dysfunction through attenuation of cerebral blood flow (CBF) reduction, cerebral vasoconstrictio, and microthrombosis formation in a rat SAH model. Moreover, JNJ16259685 reduces experimental SAH-induced long-term neuronal damage through alleviation of neuronal death and degeneration. Mechanically, JNJ16259685 maintains phosphorylation of endothelial NO synthase (eNOS) and vasodilator-stimulated phosphoprotein (VASP) and decreases apoptosis-related factors Bax, active caspase-9, and active caspase-3 following experimental SAH. Altogether, our results suggest JNJ16259685 improves long-term functional impairment through neurovascular protection.

Role of Neurotrophin 3 in spinal neuroplasticity in rats subjected to cord transection.

That neuroplasticity occurs in mammalian spinal cord is well known, though the underlying mechanism still awaits elucidation. This study evaluated the role of endogenous Neurotrophin-3 (NT-3) in the spinal neuroplasticity. Following cord transection at the junction between T9 and T10, the hindlimb locomotor functions of rats showed gradual but significant improvement from 7 to 28 days post-operation. Corresponding to this was a significant increase in the level of NT-3 in the cord segments caudal to injury site. Significantly, after NT-3-antibody administration, the spinal transected rats displayed poor hindlimb locomotor functions and a decrease in the number of neurons in spinal laminae VIII-IX. Whether NT-3-antibody was administered, corticospinal tract regeneration and somatosensory evoked potentials could not be detected. Our findings suggested that endogenous NT-3 could play an important role in spinal plasticity in adult spinal cords subjected to transection, possibly through a regulation of neuronal activity in the local circuitry.