Grape Seed Proanthocyanidins Improve the Quality of Fresh and Cryopreserved Semen in Bulls.

Oxidative stress leads to a decrease in semen quality during semen cryopreservation and fresh semen production. Grape seed proanthocyanidins (GSPs) are endowed with well-recognized antioxidant, anti-inflammatory, anti-cancer, and anti-aging activities. Therefore, the objective of this experiment was to explore the effects of GSPs on the quality of fresh and cryopreserved semen to provide a basis for GSPs as a new dietary additive and semen diluent additive for males' reproduction. Fresh semen from three healthy bulls aged 3 to 5 years old were gathered and mixed with semen diluents dissolved with 0 µg/mL, 30 µg/mL, 40 µg/mL, 50 µg/mL, and 60 µg/mL GSPs respectively. The motility, physiological structures (acrosome integrity, membrane integrity, mitochondrial activity), and antioxidant capacity of frozen-thawed sperm were measured after storage in liquid nitrogen for 7 days (d). Bulls were fed with 20 mg/kg body weight (BW) GSPs in their diet for 60 days; the weight of the bull is about 600 kg. Then, the reproductive performance and antioxidant indexes of bulls were measured before and after feeding. The results demonstrated that GSPs supplementation significantly increased sperm motility, physiological structures, GSH-Px, and CAT enzyme activities and significantly decreased MDA content in sperm during semen cryopreservation. The optimal concentration of GSPs was 40 µg/mL (p < 0.05). After 20 mg/kg (body weight) GSP supplementation, sperm motility was significantly heightened (p < 0.05), the sperm deformity rate was significantly reduced (p < 0.05), and antioxidant enzyme activities (such as SOD, CAT, and GSH-Px) were significantly enhanced (p < 0.05), and the production of MDA was significantly suppressed (p < 0.05) in serum compared with that before feeding. In conclusion, these results reveal that a certain concentration of GSPs has a good protective effect on sperm damage caused by semen cryopreservation and the reproductive performance reduction caused by stress in bulls, which may be attributed to the antioxidant function of GSPs. In summary, GSPs are a useful cryoprotective adjuvant and dietary additive for bull sperm quality.

Endoscopic far-lateral supracerebellar infratentorial approach for resection of dumbbell-shaped trigeminal schwannoma: surgical techniques and preliminary results.

BACKGROUND: Trigeminal schwannomas (TSs) are mostly benign tumors. However, dumbbell-shaped TSs are most challenging for surgeons and pose a high surgical risk. OBJECTIVE: We describe the technique of the purely endoscopic far-lateral supracerebellar infratentorial approach (EFL-SCITA) for removing dumbbell-shaped TSs and further discuss the feasibility of this approach and our experience. METHODS: EFL-SCITA was performed for resection of 5 TSs between January 2020 and March 2023. The entire procedure was performed endoscopically with the goal of total tumor resection. During the operation, the tumor was exposed in close proximity and multiple angles under the endoscope, and the peri-tumor nerves were carefully identified and protected, especially the normal trigeminal fiber bundles around the tumor. RESULTS: All the tumors of 5 patients involved the middle and posterior cranial fossa, of which total removal was achieved in 2 patients and near-total removal in 3 patients. The most common preoperative symptoms were relieved after surgery. Two patients had postoperative mild facial paralysis (House-Brackmann grade II), and 1 patient had abducens palsy; both recovered during the follow-up period. Two patients experienced new postoperative facial hypesthesia, and 1 experienced mastication weakness, which did not recover. There was no tumor recurrence or residual tumor growth during the follow-up period in any of the patients. CONCLUSION: EFL-SCITA is a new and effective alternative for the surgical treatment of TSs. For dumbbell-shaped TSs, this approach provides sufficient surgical field exposure and freedom of operation.

Lnc-TRTMFS promotes milk fat synthesis via the miR-132x/RAI14/mTOR pathway in BMECs.

As an important index to evaluate the quality of milk, milk fat content directly determines the nutrition and flavor of milk. Recently, growing evidence has suggested that long noncoding RNAs (lncRNAs) play important roles in bovine lactation, but little is known about the roles of lncRNAs in milk fat synthesis, particularly the underlying molecular processes. Therefore, the purpose of this study was to explore the regulatory mechanism of lncRNAs in milk fat synthesis. Based on our previous lncRNA-seq data and bioinformatics analysis, we found that Lnc-TRTMFS (transcripts related to milk fat synthesis) was upregulated in the lactation period compared to the dry period. In this study, we found that knockdown of Lnc-TRTMFS significantly inhibited milk fat synthesis, resulting in a smaller amount of lipid droplets and lower cellular triacylglycerol levels, and significantly decreased the expression of genes related to adipogenesis. In contrast, overexpression of Lnc-TRTMFS significantly promoted milk fat synthesis in bovine mammary epithelial cells (BMECs). In addition, Bibiserv2 analysis showed that Lnc-TRTMFS could act as a molecular sponge for miR-132x, and retinoic acid induced protein 14 (RAI14) was a potential target of miR-132x, which was further confirmed by dual-luciferase reporter assays, quantitative reverse transcription PCR, and western blots. We also found that miR-132x significantly inhibited milk fat synthesis. Finally, rescue experiments showed that Lnc-TRTMFS could weaken the inhibitory effect of miR-132x on milk fat synthesis and rescue the expression of RAI14. Taken together, these results revealed that Lnc-TRTMFS regulated milk fat synthesis in BMECs via the miR-132x/RAI14/mTOR pathway.

Milk fat is an important index to evaluate the quality of milk. The content of milk fat directly determines the quality and flavor of milk. Studies have shown that milk components can change with the expression of specific genes and noncoding RNA that regulate it in different lactation periods. In this study, after the interference and overexpression of Lnc-TRTMFS on milk fat metabolism in bovine mammany epithelial cells, we found that Lnc-TRTMFS could positively regulate milk fat synthesis in bovine mammary epithelial cells. The ceRNA network of Lnc-TRTMFS-miR-132x-RAI14 was constructed by software prediction and double fluorescein report test, and the salvage effect of Lnc-TRTMFS on milk fat synthesis was confirmed by salvage test. Most importantly, we found that Lnc-TRTMFS and miR-132x can regulate milk fat by regulating the mTOR pathway by regulating RAI14.

Leaf Extract of Perilla frutescens (L.) Britt Promotes Adipocyte Browning via the p38 MAPK Pathway and PI3K-AKT Pathway.

The leaf of Perilla frutescens (L.) Britt (PF) has been reported to negatively affect adipocyte formation, inhibit body-fat formation, and lower body weight. However, its effect on adipocyte browning remains unknown. Thus, the mechanism of PF in promoting adipocyte browning was investigated. The ingredients of PF were acquired from the online database and filtered with oral bioavailability and drug-likeness criteria. The browning-related target genes were obtained from the Gene Card database. A Venn diagram was employed to obtain the overlapped genes that may play a part in PF promoting adipocyte browning, and an enrichment was analysis conducted based on these overlapped genes. A total of 17 active ingredients of PF were filtered, which may regulate intracellular receptor-signaling pathways, the activation of protein kinase activity, and other pathways through 56 targets. In vitro validation showed that PF promotes mitochondrial biogenesis and upregulates brite adipocyte-related gene expression. The browning effect of PF can be mediated by the p38 MAPK pathway as well as PI3K-AKT pathway. The study revealed that PF could promote adipocyte browning through multitargets and multipathways. An in vitro study validated that the browning effect of PF can be mediated by both the P38 MAPK pathway and the PI3K-AKT pathway.

Rab32 promotes glioblastoma migration and invasion via regulation of ERK/Drp1-mediated mitochondrial fission.

The highly widespread and infiltrative nature of glioblastoma multiforme (GBM) makes complete surgical resection hard, causing high recurrence rate and poor patients' prognosis. However, the mechanism underlying GBM migration and invasion is still unclear. In this study, we investigated the role of a Ras-related protein Rab32 on GBM and uncovered its underlying molecular and subcellular mechanisms that contributed to GBM aggressiveness. The correlation of Rab32 expression with patient prognosis and tumor grade was investigated by public dataset analysis and clinical specimen validation. The effect of Rab32 on migration and invasion of GBM had been evaluated using wound healing assay, cell invasion assay, as well as protein analysis upon Rab32 manipulations. Mitochondrial dynamics of cells upon Rab32 alterations were detected by immunofluorescence staining and western blotting. Both the subcutaneous and intracranial xenograft tumor model were utilized to evaluate the effect of Rab32 on GBM in vivo. The expression level of Rab32 is significantly elevated in the GBM, especially in the most malignant mesenchymal subtype, and is positively correlated with tumor pathological grade and poor prognosis. Knockdown of Rab32 attenuated the capability of GBM's migration and invasion. It also suppressed the expression levels of invasion-related proteins (MMP2 and MMP9) as well as mesenchymal transition markers (N-cadherin, vimentin). Interestingly, Rab32 transported Drp1 to mitochondrial from the cytoplasm and modulated mitochondrial fission in an ERK1/2 signaling-dependent manner. Furthermore, silencing of Rab32 in vivo suppressed tumor malignancy via ERK/Drp1 axis. Rab32 regulates ERK1/2/Drp1-dependent mitochondrial fission and causes mesenchymal transition, promoting migration and invasion of GBM. It serves as a novel therapeutic target for GBM, especially for the most malignant mesenchymal subtype. Schematic of Rab32 promotes GBM aggressiveness via regulation of ERK/Drp1-mediated mitochondrial fission. Rab32 transports Drp1 from the cytoplasm to the mitochondria and recruits ERK1/2 to activate the ser616 site of Drp1, which in turn mediates mitochondrial fission and promotes mesenchymal transition, migration and invasion of GBM.

Multi-omics analysis of N6-methyladenosine reader IGF2BP3 as a promising biomarker in pan-cancer.

Background: Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) has been reported to exhibit an oncogenic effect as an RNA-binding protein (RBP) by promoting tumor cell proliferation, migration and invasion in several tumor types. However, a pan-cancer analysis of IGF2BP3 is not currently available, and the exact roles of IGF2BP3 in prognosis and immunology in cancer patients remain enigmatic. The main aim of this study was to provide visualization of the systemic prognostic landscape of IGF2BP3 in pan-cancer and to uncover the potential relationship between IGF2BP3 expression in the tumor microenvironment and immune infiltration profile. Methods: Raw data on IGF2BP3 expression were obtained from GTEx, CCLE, TCGA, and HPA data portals. We have investigated the expression patterns, diagnostic and prognostic significance, mutation landscapes, functional analysis, and functional states of IGF2BP3 utilizing multiple databases, including HPA, TISIDB, cBioPortal, GeneMANIA, GESA, and CancerSEA. Moreover, the relationship of IGF2BP3 expression with immune infiltrates, TMB, MSI and immune-related genes was evaluated in pan-cancer. IGF2BP3 with drug sensitivity analysis was performed from the CellMiner database. Furthermore, the expression of IGF2BP3 in different grades of glioma was detected by immunohistochemical staining and western blot. Results: We found that IGF2BP3 was ubiquitously highly expressed in pan-cancer and significantly correlated with diagnosis, prognosis, TMB, MSI, and drug sensitivity in various types of cancer. Besides, IGF2BP3 was involved in many cancer pathways and varied in different immune and molecular subtypes of cancers. Additionally, IGF2BP3 is critically associated with genetic markers of immunomodulators in various cancers. Finally, we validated that IGF2BP3 protein expression was significantly higher in glioma than in normal tissue, especially in GBM. Conclusions: IGF2BP3 may be a potential molecular biomarker for diagnosis and prognosis in pan-cancer, especially for glioma. It could become a novel therapeutic target for various cancers.

Endoscopic resection of thalamic lesions via supracerebellar infratentorial approach: a case series and technical note.

The deep location of the thalamus and the complex neural circuits in the surrounding area make surgery extremely challenging. Feasibility and advisability of using a supracerebellar infratentorial approach (SCITA) for endoscopic resection of thalamic lesions remains to be further evaluated. Fifteen patients who underwent endoscopic resection of thalamic via SCITA from 2014 to 2021 were retrospectively collected. We analyzed preoperative tumor-related variables and surgical procedures in detail, as well as postoperative outcomes. Lesions mainly located in the posterior and/or medial part of the thalamus, and some of them expanded downward, or backward. The mean size of them was 30 × 24 mm. Five of the nine patients with preoperative hydrocephalus underwent cerebrospinal fluid shunts to relieve increased intracranial pressure. Among the 15 patients, 4 were glioblastoma, 3 were pilocytic astrocytoma, and the rest included 1 case of anaplastic astrocytoma, melanoma, polymorphous low-grade neuroepithelial tumor of the young, rosette-forming glioneuronal tumor, inflammatory lesion, diffuse midline glioma, and cavernous hemangioma. The majority of patients (10/15) achieved gross total resection, which has become more pronounced since paramedian SCITA was used in place of the midline approach in 2020 (6/8). Three patients had unresolved or new onset of clinical symptoms after surgery, resulting in a decreased KPS score at discharge. Neuro-endoscopic techniques can ameliorate many of the shortcomings of the SCITA. With the accumulation of experience and technological progress, more deficiencies of this approach may be improved, enabling safe and effective resection of posterior and/or medial part thalamic lesions.

Endoscopic transcortical expanded transforaminal transvenous transchoroidal approach to third ventricle lesion resection using an endoport.

OBJECTIVE: To investigate the clinical experience and application value of endoscopic resection of lesions in and around the third ventricle using a transcortical expanded transforaminal transvenous transchoroidal approach with an endoport. METHODS: Clinical data and follow-up results of seven patients who underwent the removal of lesions in the third ventricle and its adjacent area with an endoport-guided endoscopic system from January 2018 to December 2020 in the Department of Neurosurgery, Zhongshan Hospital Affiliated to Fudan University, were analyzed retrospectively. Two other patients from the Affiliated Pediatric Hospital of Fudan University and the Affiliated Hospital of Guizhou Medical University, respectively, were included in the analysis. RESULTS: A total of nine cases of third ventricle tumors were included in the study, including six women and three men, with an average age of 37.8 years (4-84 years old) and a follow-up time of 6-44 months. These nine tumor cases included two pilocytic astrocytomas, one diffuse midline glioma (H3 K27-altered), two craniopharyngiomas, two choroid plexus (CP) papillomas, one germinoma, and one pineal parenchymal tumor of intermediate differentiation. Total resection was completed in eight cases, with one near-total resection. There were no complications related to the surgical approach, such as epilepsy, aphasia, or hemiplegia. CONCLUSIONS: The endoscope transcortical expanded transforaminal transvenous transchoroidal approach using an endoport can safely and effectively remove third ventricle lesions. This approach can reach a wide area, from the anterior to the posterior third ventricle.

Neuronavigation-Guided Transcortical-Transventricular Endoport-Assisted Endoscopic Resection for Thalamic Lesions: Preliminary Experience.

BACKGROUND: Surgery for thalamic lesions is generally challenging because they are deep-seated lesions surrounded by vital neurovascular structures. Whether neuronavigation-guided transcortical-transventricular endoport-assisted endoscopic resection for thalamic lesions is feasible remains to be further evaluated. METHODS: A retrospective review of 8 who patients received neuronavigation-guided transcortical-transventricular endoport-assisted endoscopic resection for thalamic lesions was performed. Preoperative and tumor-related variables and postoperative outcomes were analyzed. RESULTS: All lesions were located in the medial part of the thalamus, and most of them expanded forward, downward, or backward. Median size of lesions was 31 mm (range, 16-52 mm). Final pathology results confirmed that 1 case was a cavernous malformation, 3 were pilocytic astrocytomas, and 4 were glioblastomas. None of the patients had postoperative seizures. Gross total resection and long-term postoperative survival were achieved in all patients with benign lesions, while near-total resection (>90%) was achieved in 3 of 4 patients (75%) with glioblastoma, and subtotal resection (<90%) was achieved in 1 patient (25%). Among patients with glioblastoma, 1 patient remained free of recurrence at 16 months of follow-up; the other 3 patients had worse Karnofsky performance scale scores after surgery and died within 6 months. CONCLUSIONS: Combining the advantages of neuronavigation, endoscopy, and endoport techniques via the middle frontal gyrus approach can safely and effectively remove benign lesions in the medial part of the thalamus. This procedure can also be performed in well-selected cases of glioblastoma and likely confers a survival advantage for this rapidly and universally fatal disease.

Neurological Adverse Events Associated With Esketamine: A Disproportionality Analysis for Signal Detection Leveraging the FDA Adverse Event Reporting System.

Esketamine was approved for the treatment of treatment-resistant depression in 2019. After the approval of esketamine, numerous concerns have been raised regarding its long-term safety and tolerability. A previous systematic pharmacovigilance study on esketamine-related adverse events (AEs) was published in 2020; however, it has not been updated 2 years later. The primary aim of this study was to detect and characterize neurological safety signals of esketamine to partially update the knowledge in this field using the FDA pharmacovigilance database. Reporting odds ratio (ROR) was calculated for esketamine-related neurological AEs from 2019 to 2021 with a signal considered when the lower limit of the 95% confidence interval (CI) of ROR (ROR025) exceeded one. Severe and non-severe cases were compared using an independent samples t-test or chi-squared (χ2) test, and a rating scale was used to prioritize the signals. The database contained 720 cases of esketamine-associated neurological AEs, with 21 signals detected, ranging from a ROR025 of 1.05 (disturbance in attention) to 204.00 (sedation). 16 latest neurological AEs emerged in the second year of marketing approval of esketamine, with eight signals detected. The associations between esketamine and nervous system disorders persisted when stratifying by sex, age, and reporter type, whereas the spectrum of neurological AEs differed in stratification regimens. Esketamine dosage, antidepressant polypharmacy, or co-prescription with benzodiazepines affected AEs severity (t = 2.41, p = 0.017; χ2 = 6.75, p = 0.009; and χ2 = 4.10, p = 0.043; respectively), while age and sex did not (p = 0.053 and p = 0.397, respectively). Three signals were categorized as moderate clinical priority [i.e., sedation, dizziness, and dysgeusia (priority points 7, 5, and 5, respectively)], showing the same early failure type profiles. Notably, seven detected disproportionality signals were not previously detected in clinical trials. Although the majority of results were in line with those obtained in the previous study, there were discrepancies in the spectrum of neurological AEs and the effects of several risk factors on AEs severity among the two studies that should be recognized and managed early in clinical treatments.

The Research Progress of Antiangiogenic Therapy, Immune Therapy and Tumor Microenvironment.

Anti-angiogenesis therapy, a promising strategy against cancer progression, is limited by drug-resistance, which could be attributed to changes within the tumor microenvironment. Studies have increasingly shown that combining anti-angiogenesis drugs with immunotherapy synergistically inhibits tumor growth and progression. Combination of anti-angiogenesis therapy and immunotherapy are well-established therapeutic options among solid tumors, such as non-small cell lung cancer, hepatic cell carcinoma, and renal cell carcinoma. However, this combination has achieved an unsatisfactory effect among some tumors, such as breast cancer, glioblastoma, and pancreatic ductal adenocarcinoma. Therefore, resistance to anti-angiogenesis agents, as well as a lack of biomarkers, remains a challenge. In this review, the current anti-angiogenesis therapies and corresponding drug-resistance, the relationship between tumor microenvironment and immunotherapy, and the latest progress on the combination of both therapeutic modalities are discussed. The aim of this review is to discuss whether the combination of anti-angiogenesis therapy and immunotherapy can exert synergistic antitumor effects, which can provide a basis to exploring new targets and developing more advanced strategies.

Functional Characterization of a Cucumber (Cucumis sativus L.) Vacuolar Invertase, CsVI1, Involved in Hexose Accumulation and Response to Low Temperature Stress.

Cucumber (Cucumis sativus L.), an important vegetable plant species, is susceptible to low temperature stress especially during the seedling stage. Vacuolar invertase (VI) plays important roles in plant responses to abiotic stress. However, the molecular and biochemical mechanisms of VI function in cucumber, have not yet been completely understood and VI responses to low temperature stress and it functions in cold tolerance in cucumber seedlings are also in need of exploration. The present study found that hexose accumulation in the roots of cucumber seedlings under low temperature stress is closely related to the observed enhancement of invertase activity. Our genome-wide search for the vacuolar invertase (VI) genes in cucumber identified the candidate VI-encoding gene CsVI1. Expression profiling of CsVI1 showed that it was mainly expressed in the young roots of cucumber seedlings. In addition, transcriptional analysis indicated that CsVI1 expression could respond to low temperature stress. Recombinant CsVI1 proteins purified from Pichia pastoris and Nicotiana benthamiana leaves could hydrolyze sucrose into hexoses. Further, overexpression of CsVI1 in cucumber plants could increase their hexose contents and improve their low temperature tolerance. Lastly, a putative cucumber invertase inhibitor was found could form a complex with CsVI1. In summary, these results confirmed that CsVI1 functions as an acid invertase involved in hexose accumulation and responds to low temperature stress in cucumber seedlings.

A Fructan Exohydrolase from Maize Degrades Both Inulin and Levan and Co-Exists with 1-Kestotriose in Maize.

Enzymes with fructan exohydrolase (FEH) activity are present not only in fructan-synthesizing species but also in non-fructan plants. This has led to speculation about their functions in non-fructan species. Here, a cell wall invertase-related Zm-6&1-FEH2 with no "classical" invertase motif was identified in maize. Following heterologous expression in Pichia pastoris and in Nicotiana benthamiana leaves, the enzyme activity of recombinant Zm-6&1-FEH2 displays substrate specificity with respect to inulin and levan. Subcellular localization showed Zm-6&1-FEH2 exclusively localized in the apoplast, and its expression profile was strongly dependent on plant development and in response to drought and abscisic acid. Furthermore, formation of 1-kestotriose, an oligofructan, was detected in vivo and in vitro and could be hydrolyzed by Zm-6&1-FEH2. In summary, these results support that Zm-6&1-FEH2 enzyme from maize can degrade both inulin-type and levan-type fructans, and the implications of the co-existence of Zm-6&1-FEH2 and 1-kestotriose are discussed.

Quantitative proteomics revealed the molecular characteristics of distinct types of granulated somatotroph adenomas.

PURPOSE: Somatotroph adenomas are obviously heterogeneous in clinical characteristics, imaging performance, pathological diagnosis and therapeutic effect. The heterogeneity of the tumors, especially for SG and DG type adenomas, have attracted great interest in identifying the specific pathological markers and therapeutic targets of them. However, previous analyses of the molecular characteristics of the subtypes of somatotroph adenomas were performed at genomic and transcriptome level. The proteomic differences between the two subtypes of somatotroph adenomas are still unknown. METHODS: Tumor samples were surgically removed from 10 sporadic pituitary somatotroph adenoma patients and grouped according to the pathological type. Tandem mass tag (TMT)-based quantitative proteomic analysis was employed to analyze the proteomic differences between SG and DG tumors. RESULTS: In total, 228 differentially expressed proteins were identified between SG adenomas and DG adenomas. They were enriched mainly in extracellular matrix (ECM)-receptor interaction, leukocyte transendothelial migration, arrhythmogenic right ventricular cardiomyopathy and DNA replication pathways. Protein-protein interaction (PPI) network analysis indicated that Cadherin-1 and Catenin beta-1 were the most important key proteins in the differences between SG and DG adenomas. Immunohistochemistry (IHC) confirmed the expression levels of the key proteins. CONCLUSIONS: This study provides large-scale proteome molecular characteristics of distinct granulation subtypes of somatotroph adenomas. Compared with DG adenomas, The differential protein of SG adenomas mostly enrich in invasive and proliferative functions and pathways at the proteomic level. Cadherin-1 and Catenin beta-1 play key roles in the different biological characteristics of the two tumor subtypes.

Is MVD the effective treatment for poorly controlled hypertension?

BACKGROUND: Studies have shown that microvascular decompression (MVD) surgery could improve the clinical symptoms of hemifacial spasm (HFS) and decrease the blood pressure (BP) in patients with refractory hypertension. More positive long-term results are required to establish MVD as a treatment option for high blood pressure (HBP) and to refine the patient selection criteria. METHODS: From October 2015 to September 2018, based on patient selection for cases with both HFS and poorly controlled HBP of nervous origin, MVD surgeries were performed on 12 patients aiming for better BP control. The patients were followed-up for at least 2 years. The surgical outcomes and associated factors were analyzed. RESULTS: With respect to neurovascular compression (NVC) of facial nerve, the intra-operative findings concurred with pre-operative radiological findings except that in one case. Intra-operatively ipsilateral cranial nerve (CN) IX-X root exit zone (REZ) and rostral ventrolateral medulla (RVLM) NVCs were confirmed and concordant with pre-operative radiological findings in all 12 cases. 9 Of the 12 cases were completely free of facial spasm after surgery. 2 patients achieved partial relief. 1 patient still suffered from frequent facial spasm. 10 out of 12 patients achieved BP lowering after surgery. The BP of those 10 patients stayed at a relatively stable scale over the follow-up period. Although statistical significance was not obtained, for patients who are operated on the left side and those who have only 1 offensive artery, the surgery might lead to better BP control. CONCLUSIONS: MVD is a safe and effective treatment for hypertension due to central nervous system (CNS) NVC in patients with both HBP and HFS. Further studies are required to examine long-term outcomes and establish criteria for patient selection.

Apoplastic maize fructan exohydrolase Zm-6-FEH displays substrate specificity for levan and is induced by exposure to levan-producing bacteria.

Fructan exohydrolases (FEHs) are structurally related to cell wall invertases. While the latter are ubiquitous in higher plants, the role of FEHs in non-fructan species has remained enigmatic. To explore possible roles of FEHs in maize, a full length putative Zm-6-FEH-encoding cDNA was cloned displaying high sequence similarity with cell wall invertases. For functional characterization, Zm-6-FEH protein was expressed in Picha pastoris and in Nicotiana benthamiana leaves. Enzyme activity of recombinant Zm-6-FEH protein showed a strong preference for levan as substrate. Expression profiling in maize seedlings revealed higher transcript amounts in the more mature leaf parts as compared to the growth zone at the base of the leaf, in good correlation with FEH enzyme activities. Subcellular localization analysis indicated Zm-6-FEH location in the apoplast. Noteworthy, incubation of leaf discs with levan and co-incubation with high levan-producing bacteria selectively up-regulated transcript levels of Zm-6-FEH, accompanied by an increase of 6-FEH enzyme activity. In summary, the results indicate that Zm-6-FEH, a novel fructan exohydrolase of a non-fructan species, may have a role in plant defense against levan-producing bacteria.

GPR64 promotes cAMP pathway in tumor aggressiveness in sparsely granulated growth hormone cell adenomas.

PURPOSE: There is an increasing agreement that acromegaly caused by growth hormone (GH) cell adenoma has two distinct subtypes: densely granulated (DG) and sparsely granulated (SG). We hypothesized that differential molecular signatures may explain their behavior. METHODS: Total transcriptome sequencing was performed on ten DG and seven SG adenomas. The differentially expressed RNAs were identified by bioinformatic analyses, and a candidate RNA was verified by quantitative real-time PCR. Immunohistochemical staining was also performed to detect the protein expression of the candidate. Clinical parameters were correlated with protein expression. Subsequently, cell proliferation, colony formation, and cell cycle progression were analyzed after knockdown of the candidate in pituitary GH3 cells. Activation of the cAMP pathway was assessed by ELISA and Western blot. RESULTS: We confirmed that there were obvious differentially expressed genes between the subtypes. Through gene profiling, we discovered that an orphan adhesion G protein-coupled receptor, GPR64, was overexpressed in more aggressive SG adenomas. Noticeably, GPR64 knockdown significantly inhibited the proliferation of GH3 tumor cells and decreased colony formation. The knockdown also induced cell cycle arrest in GH3 tumor cells. Further studies revealed that GPR64 knockdown decreased cAMP levels and the ratios of p-CREB/CREB, indicating that it suppressed the cAMP/CREB pathway. CONCLUSIONS: Our results indicated that GPR64 may promote aggressiveness in SG-type GH cell adenomas and that it is a key factor regulating the cAMP pathway to promote aggressiveness of GH cell adenomas.

Serum phosphate: Does it more closely reflect the true state of acromegaly?

An increased serum phosphate (P) level is common in acromegaly patients, however, the relationships among P, growth hormone (GH), insulin-like growth factor 1 (IGF-1) and disease status remain unknown. To reveal these relationships, we examined the association of P with comprehensive clinical data. We measured the serum P, calcium, GH, oral glucose tolerance test-GH (OGTT-GH), IGF-1, and insulin-like growth factor binding protein-3 (IGBP-3) levels in 103 acromegaly patients. SAGIT® was used to assess the disease status comprehensively. Spearman's rank correlation coefficient was obtained to evaluate the associations among the above parameters. Stepwise multiple linear regression analysis was performed to investigate factors independently associated factors with the SAGIT scores. The area under the receiver operating characteristic curve (AUCROC) was used to evaluate the efficacy of the percentage change in the serum phosphate level in predicting remission in patients with postoperatively discordant GH and IGF-1 levels. Hyperphosphatemia was found in 68.9% of patients at baseline. The serum P level was higher in the non-remission group, but no correlation was found between hyperphosphatemia and remission. We revealed a significant correlation between the P level and SAGIT® score in patients both preoperatively (r = 0.659, p = 0.000) and 1-year postoperatively without remission patients (r = 0.534, p = 0.027). All biochemical levels decreased significantly postoperatively, and the GH and OGTT-GH levels achieved early stability (1 month); however, the P, IGF-1 and IGBP-3 levels showed a gradual decline. A percentage change in P of -8.12% is recommended as a cut-off value for predicting remission in patients with postoperatively discordant GH and IGF-1 levels. As a metabolic product which affected by the GH/IGF-1 axis, serum P appears to more closely reflect the comprehensive disease status in acromegaly. When the GH and IGF-1 levels are discordant during follow-up, perioperative change in the P level may be a potential predictor of remission.

AMR monitoring in microvascular decompression for hemifacial spasm: 115 cases report.

In MVD operations assisted by AMR monitoring, the reliability and validity of decompression can be evaluated by observing whether AMR disappears. Although intraoperative AMR monitoring has been used widely, debate exists over its reliability and positive contribution. In this series, 115 cases of HFS treated with MVD operations with AMR monitoring were enrolled. All MVD procedures were performed via a suboccipital retrosigmoid approach. Microscope and endoscope were used alternately as was needed. Medtronic Nim-eclipse system was used for intra-operative AMR monitoring. The zygomatic branch of the facial nerve was stimulated and AMRs were recorded form the mentalis muscle. In 112 of the 115 cases, AMR was recorded during operation. In the 112 cases with typical AMR, AMR disappeared in 105 cases. Among the 105 cases, 79 achieved immediate cure after operation, 21 were spasm-free within 6-month follow-up, and the symptom of 5 cases persisted at 6-month follow-up. Among the 7 cases whose AMR did not disappear at the end of operation, 2 cases achieved immediate cure and 2 cases achieved delayed relief. For those cases with electrophysiological relief, the overall relief rate was 95.2% (100/105); for those with persistent AMR, the overall relief rate was 57.1% (4/7, P < 0.05). In conclusion, AMR monitoring provide valuable information to MVD operation for HFS. The use and investigation of AMR will undoubtedly contribute to the understanding and curing of HFS.

The Purely Endoscopic Supracerebellar Infratentorial Approach for Resecting Pineal Region Tumors with Preservation of Cerebellomesencephalic Vein: Technical Note and Preliminary Clinical Outcomes.

BACKGROUND: The cerebellomesencephalic vein (CMV) was frequently sacrificed in surgery approached via the supracerebellar infratentorial (SCIT) route for resecting pineal region tumors, which resulted in potential risk of neurologic deficit. Preserving the CMV in the SCIT approach could enhance the safety and effectiveness of this natural corridor surgery. The aim of this article was to identify the probability and safety of preserving the CMV through the application of neuroendoscopy in the SCIT approach. METHODS: Clinical data of patients who underwent pineal region tumor resection through a purely endoscopic SCIT approach were retrospectively analyzed, focusing on surgical techniques and clinical outcomes. RESULTS: The study included 8 patients with pineal region tumors. The CMV was preserved intact in all patients. Total tumor removal was achieved in 7 of 8 patients. In 1 patient with 2 tumors in the pineal region and roof of the third ventricle, the tumor in the pineal region was resected completely, followed by subsequent chemotherapy combined with radiotherapy, after which the other tumor disappeared totally. All patients recovered normally with uneventful postoperative outcomes. CONCLUSIONS: The advantage of close observation and panoramic view provided by neuroendoscopy combined with meticulous manipulation improved the ability to preserve the CMV in resecting pineal region tumors via the SCIT approach. The neuroendoscopic technique enhances the safety and efficacy of the SCIT approach.