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.

Structural mutations of small single copy (SSC) region in the plastid genomes of five Cistanche species and inter-species identification.

BACKGROUND: Cistanche is an important genus of Orobanchaceae, with critical medicinal, economic, and desertification control values. However, the phylogenetic relationships of Cistanche genus remained obscure. To date, no effective molecular markers have been reported to discriminate effectively the Cistanche closely related species reported here. In this study, we obtained and characterized the plastomes of four Cistanche species from China, to clarify the phylogenetic relationship within the genus, and to develop molecular markers for species discrimination.  RESULTS: Four Cistanche species (Cistanche deserticola, Cistanche salsa, Cistanche tubulosa and Cistanche sinensis), were deep-sequenced with Illumina. Their plastomes were assembled using SPAdes and annotated using CPGAVAS2. The plastic genomes were analyzed in detail, finding that all showed the conserved quadripartite structure (LSC-IR-SSC-IR) and with full sizes ranging from 75 to 111 Kbp. We observed a significant contraction of small single copy region (SSC, ranging from 0.4-29 Kbp) and expansion of inverted repeat region (IR, ranging from 6-30 Kbp), with C. deserticola and C. salsa showing the smallest SSCs with only one gene (rpl32). Compared with other Orobanchaceae species, Cistanche species showed extremely high rates of gene loss and pseudogenization, as reported for other parasitic Orobanchaceae species. Furthermore, analysis of sequence divergence on protein-coding genes showed the three genes (rpl22, clpP and ycf2) had undergone positive selection in the Cistanche species under study. In addition, by comparison of all available Cistanche plastomes we found 25 highly divergent intergenic spacer (IGS) regions that were used to predict two DNA barcode markers (Cis-mk01 and Cis-mk02 based on IGS region trnR-ACG-trnN-GUU) and eleven specific DNA barcode markers using Ecoprimer software. Experimental validation showed 100% species discrimination success rate with both type of markers. CONCLUSION: Our findings have shown that Cistanche species are an ideal model to investigate the structure variation, gene loss and pseudogenization during the process of plastome evolution in parasitic species, providing new insights into the evolutionary relationships among the Cistanche species. In addition, the developed DNA barcodes markers allow the proper species identification, ensuring the effective and safe use of Cistanche species as medicinal products.

Protective effect and mechanism of baicalin on lung inflammatory injury in BALB/cJ mice induced by PM2.5.

The public health harms caused by fine particulate matter (PM2.5) have become a global focus, with PM2.5 exposure recognized as a critical risk factor for global morbidity and mortality. Chronic inflammation is the common pathophysiological feature of respiratory diseases induced by PM2.5 and is the most critical cause of all these diseases. However, presently there is a lack of effective preventive and therapeutic approaches for inflammatory lung injuries caused by PM2.5 exposure. Baicalin is a herb-derived effective flavonoid compound with multiple health benefits. This study established a murine lung inflammatory injury model via inhalation of PM2.5 aerosols. The data showed that after baicalin intervention, lung injury pathological score of baicalin (4.16 ± 0.54, 3.33 ± 0.76, 4.00 ± 0.45) and claricid (3.00 ± 0.78) treatments were markedly lower than PM2.5-treated mice (6.17 ± 0.31), and pathological damage was alleviated. Compared to the PM2.5 group, the spleen and lung indexes in the baicalin and claricid groups were significantly reduced. The inflammatory cytokines of TNF-α, IL-18, and IL-1ß in serum, alveolar lavage fluid, and lung tissue were significantly decreased in the baicalin and claricid groups. The expressions of inflammatory pathway-related genes and proteins HMGB1, NLRP3, ASC, and caspase-1 were up-regulated in the PM2.5 group. The expressions of these genes and proteins were significantly decreased following baicalin treatment. The lung function indicators showed that the MV (65.94 ± 8.19 mL), sRaw (1.79 ± 0.08 cm H2O.s), and FRC (0.52 ± 0.01 mL) in the PM2.5 group were higher than in the control and baicalin groups, and respiratory function was improved by baicalin. PM2.5 exposure markedly altered the bacterial composition at the genus level. The dominant flora relative abundances of uncultured_bacterium_f_Muribaculaceae, Streptococcus, and Lactobacillus, were decreased from the control group (9.20%, 8.53%, 6.21%) to PM2.5 group (6.26%, 5.49%, 4.77%), respectively. Following baicalin intervention, the relative abundances were 9.72%, 6.65%, and 3.57%, respectively. Therefore, baicalin could potentially prevent and improve mice lung inflammatory injury induced by PM2.5 exposure. Baicalin might provide a protective role by balancing oropharyngeal microbiota and affecting the expression of the HMGB1/Caspase1 pathway.

Neuroinflammation in the central nervous system: Symphony of glial cells.

Neuroinflammation in the central nervous system (CNS) is an important subject of neuroimmunological research. Emerging evidence suggests that neuroinflammation is a key player in various neurological disorders, including neurodegenerative diseases and CNS injury. Neuroinflammation is a complex and well-orchestrated process by various groups of glial cells in CNS and peripheral immune cells. The cross-talks between various groups of glial cells in CNS neuroinflammation is an extremely complex and dynamic process which resembles a well-orchestrated symphony. However, the understanding of how glial cells interact with each other to shape the distinctive immune responses of the CNS remains limited. In this review, we will discuss the joint actions of glial cells in three phases of neuroinflammation, including initiation, progression, and prognosis, the three movements of the symphony, as the role of each type of glial cells in neuroinflammation depends on the nature of inflammatory cues and specific course of diseases. This perspective of glial cells in neuroinflammation might provide helpful clues to the development of the early diagnosis and therapeutic intervention of the various CNS diseases.

NG2 glia regulate brain innate immunity via TGF-ß2/TGFBR2 axis.

BACKGROUND: Brain innate immunity is vital for maintaining normal brain functions. Immune homeostatic imbalances play pivotal roles in the pathogenesis of neurological diseases including Parkinson's disease (PD). However, the molecular and cellular mechanisms underlying the regulation of brain innate immunity and their significance in PD pathogenesis are still largely unknown. METHODS: Cre-inducible diphtheria toxin receptor (iDTR) and diphtheria toxin-mediated cell ablation was performed to investigate the impact of neuron-glial antigen 2 (NG2) glia on the brain innate immunity. RNA sequencing analysis was carried out to identify differentially expressed genes in mouse brain with ablated NG2 glia and lipopolysaccharide (LPS) challenge. Neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice were used to evaluate neuroinflammatory response in the presence or absence of NG2 glia. The survival of dopaminergic neurons or glial cell activation was evaluated by immunohistochemistry. Co-cultures of NG2 glia and microglia were used to examine the influence of NG2 glia to microglial activation. RESULTS: We show that NG2 glia are required for the maintenance of immune homeostasis in the brain via transforming growth factor-ß2 (TGF-ß2)-TGF-ß type II receptor (TGFBR2)-CX3C chemokine receptor 1 (CX3CR1) signaling, which suppresses the activation of microglia. We demonstrate that mice with ablated NG2 glia display a profound downregulation of the expression of microglia-specific signature genes and remarkable inflammatory response in the brain following exposure to endotoxin lipopolysaccharides. Gain- or loss-of-function studies show that NG2 glia-derived TGF-ß2 and its receptor TGFBR2 in microglia are key regulators of the CX3CR1-modulated immune response. Furthermore, deficiency of NG2 glia contributes to neuroinflammation and nigral dopaminergic neuron loss in MPTP-induced mouse PD model. CONCLUSIONS: These findings suggest that NG2 glia play a critical role in modulation of neuroinflammation and provide a compelling rationale for the development of new therapeutics for neurological disorders.

Prenatal BPA exposure disrupts male reproductive functions by interfering with DNA methylation and GDNF expression in the testes of male offspring rats.

BPA is a ubiquitous environmental endocrine-disrupting chemical, and maternal exposure to BPA is associated with impaired male reproductive functions; however, the mechanisms remain to be elucidated. Glial cell line-derived neurotrophic factor (GDNF) plays an important role in maintaining normal spermatogenesis and fertility. However, the effect of prenatal BPA exposure on GDNF expression and its mechanism in the testis has not been reported. In this study, pregnant Sprague-Dawley rats were respectively exposed to 0, 0.05, 0.5, 5, and 50 mg/kg/day BPA via oral gavage from gestational day (GD) 5 to GD 19, with 6 pregnant rats in each group. ELISA, histochemistry, real-time PCR, western blot, and methylation-specific PCR (MSP) were used to detect the sex hormone levels, testicular histopathology, mRNA and protein expression of DNA methyltransferases (DNMTs) and GDNF, and the promoter methylation of Gdnf in the testes of male offspring at postnatal day (PND) 21 and PND 56. Prenatal BPA exposure increased body weight; decreased sperm counts and serum levels of testosterone (T), follicle-stimulating hormone (FSH), and luteinizing hormone (LH); and induced testicular histological damage, which indicated the damage of male reproductive function. Prenatal BPA exposure also upregulated Dnmt1 in 5 mg/kg group and Dnmt3b in 0.5 mg/kg group, but down-regulated Dnmt1 in 50 mg/kg group at PND 21. At PND 56, Dnmt1 was significantly increased in 0.05 mg/kg group but decreased in 0.5, 5, and 50 mg/kg groups, Dnmt3a was decreased, and Dnmt3b was markedly increased in 0.05 and 0.5 mg/kg groups but decreased in 5 and 50 mg/kg groups. The mRNA and protein expression levels of Gdnf were decreased markedly in 0.5 and 50 mg/kg groups at PND 21. And the methylation level of Gdnf promoter was significantly increased in 0.5 mg/kg group, but decreased in 5 and 50 mg/kg groups at PND 21. In conclusion, our study indicates that prenatal BPA exposure disrupts male reproductive functions, interferes with the expression of DNMTs, and decreases Gdnf expression in the testes of male offspring. Gdnf expression may be regulated by DNA methylation; however, the detailed mechanism needs to be further investigated.

Characterization of the mitochondrial genome of Chlorolobion braunii ITBB-AG6, an azolla-associated green alga isolated from sanitary sewage.

Sphaeropleales have the characteristics of rapid growth, high oil content, and efficient removal rates of nitrogen and phosphorus in sewage waters, and is potentially valuable in biodiesel production and environmental remediation. In this study, we isolated a strain of Sphaeropleales, Chlorolobion braunii strain ITBB-AG6 from an azolla community in a sewage pond. Its mitochondrial genome contains 110,124 bp and harbors at least 40 genes, including 15 protein-coding genes, 20 tRNA genes, and three rRNA genes. The protein-coding genes include two for ATP synthases, seven for NAD(P)H-quinone oxidoreductases (nad), three for cytochrome c oxidase subunits (coxs), and one for cytochrome b (cob). Transfer RNA genes for 18 amino acids were identified, in which the tRNA genes for leucine and serine are doubled, but the tRNA genes for threonine and valine are not annotated. Phylogenetic analysis using the mitochondrial genomes of seven families of Sphaeropleales indicated that ITBB-AG6 is closely related to Monoraphidium neglectum, and falls in the family Selenastraceae with 100% bootstrap support. Two species in the family Neochloridaceae are separated by a species in Hydrodictyaceae, indicating a polyphyletic nature. These findings revealed the complicated phylogenetic relationships of the Sphaeropleales and the necessity of genome sequences in the taxonomy of microalgae.

Cholecystokinin neurons in mouse suprachiasmatic nucleus regulate the robustness of circadian clock.

The suprachiasmatic nucleus (SCN) can generate robust circadian behaviors in mammals under different environments, but the underlying neural mechanisms remained unclear. Here, we showed that the activities of cholecystokinin (CCK) neurons in the mouse SCN preceded the onset of behavioral activities under different photoperiods. CCK-neuron-deficient mice displayed shortened free-running periods, failed to compress their activities under a long photoperiod, and developed rapid splitting or became arrhythmic under constant light. Furthermore, unlike vasoactive intestinal polypeptide (VIP) neurons, CCK neurons are not directly light sensitive, but their activation can elicit phase advance and counter light-induced phase delay mediated by VIP neurons. Under long photoperiods, the impact of CCK neurons on SCN dominates over that of VIP neurons. Finally, we found that the slow-responding CCK neurons control the rate of recovery during jet lag. Together, our results demonstrated that SCN CCK neurons are crucial for the robustness and plasticity of the mammalian circadian clock.

Comparative effectiveness of ustekinumab vs. vedolizumab for anti-TNF-naïve or anti-TNF-exposed Crohn's disease: a multicenter cohort study.

Background: Ustekinumab and vedolizumab are both effective for treating Crohn's disease (CD). However, no head-to-head trials have been conducted thus far. We aimed to compare the effectiveness of ustekinumab and vedolizumab in CD patients either naïve or exposed to tumor necrosis factor-alpha inhibitors (TNFi). Methods: Patients treated with vedolizumab or ustekinumab for luminal CD were included from six centers in China from May 2020 to July 2023. Steroid-free remission, clinical remission, objective response, and remission at Weeks 26 and 52 were evaluated in a retrospective multicenter propensity score-weighted cohort. Findings: A total of 536 patients were included (386 ustekinumab, and 150 vedolizumab). After adjustment, ustekinumab showed higher rates of clinical remission (56.4% vs. 47.8%, P = 0.005), steroid-free remission (55.4% vs. 46.1%, P = 0.003), and objective response (67.8% vs. 42.7%, P < 0.001) than vedolizumab at Week 26. At Week 52, ustekinumab exhibited significantly higher rates of clinical remission (65.8% vs. 37.5%, P < 0.001), steroid-free remission (65.8% vs. 37.5%, P < 0.001), objective response (66.7% vs. 23.8%, P < 0.001), and objective remission (31.4% vs. 12.7%, P < 0.001). Subgroup analyses revealed that ustekinumab had higher rates of clinical remission, steroid-free remission, and objective response at Weeks 26 and 52, and objective remission at Week 52 in TNFi-exposed patients, while ustekinumab showed higher rates of objective response at Weeks 26 and 52 and clinical remission, steroid-free remission and objective remission at Week 52 in TNFi-naïve patients. Adverse event rates were similar between the groups (4.9% ustekinumab vs. 6.7% vedolizumab, P = 0.423). Interpretation: Ustekinumab showed superior clinical and objective outcomes compared to vedolizumab, with comparable safety outcomes. The therapeutic superiority was observed in both short-term and long-term phases in TNFi-exposed patients, and the long-term phase in TNFi-naïve patients. Funding: National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, Key Research Projects of the Sixth Affiliated Hospital, Sun Yat-sen University, the program of Guangdong Provincial Clinical Research Center for Digestive Diseases, and National Key Clinical Discipline.

Expert Consensus on Pathological Diagnosis of Intrahepatic Cholangiocarcinoma (2022 version).

Intrahepatic cholangiocarcinoma (iCCA) can originate from the large bile duct group (segment bile ducts and area bile ducts), small bile duct group (septal bile ducts and interlobular bile ducts), and terminal bile duct group (bile ductules and canals of Hering) of the intrahepatic biliary tree, which can be histopathological corresponding to large duct type iCCA, small duct type iCCA and iCCA with ductal plate malformation pattern, and cholangiolocarcinoma, respectively. The challenge in pathological diagnosis of above subtypes of iCCA falls in the distinction of cellular morphologies, tissue structures, growth patterns, invasive behaviors, immunophenotypes, molecular mutations, and surgical prognoses. For these reasons, this expert consensus provides nine recommendations as a reference for standardizing and refining the diagnosis of pathological subtypes of iCCA, mainly based on the 5th edition of the World Health Organization Classification of Tumours of the Digestive System.

Endoscopic Far-Lateral Supracerebellar Infratentorial Approach for Petroclival Region Meningioma: Surgical Technique and Clinical Experience.

BACKGROUND: The management of petroclival region meningioma remains the ultimate achievement in neurosurgery, because of the formidable technical challenges involved. OBJECTIVE: To describe the technique and feasibility of the purely endoscopic far-lateral supracerebellar infratentorial approach (EF-SCITA) for the treatment of petroclival region meningiomas. METHODS: We reviewed the clinical data of 10 consecutive cases of petroclival region meningiomas treated with the EF-SCITA from August 2018 to August 2020. The clinical outcomes were analyzed. The patient was placed in the lateral position, and then, a "C" shaped incision and craniotomy with exposed sigmoid and transverse sinuses were performed. With the endoscopic holder, endoscopic procedures were performed using standard 2-hand microsurgical techniques. Whether the tentorium or Meckel cave was handled depended on the tumor extension. RESULTS: The mean diameter was 45 × 25 mm. Dizziness and headache were the main symptoms. All 10 patients achieved gross total or subtotal resection (Petroclival Meningioma Grade I-III) with good neurological outcomes. The EF-SCITA provides satisfactory, direct exposure to the petroclival region. Cranial nerve deficits are the main postoperative complications. Two patients had a trochlear nerve injury, 3 patients had transient facial paralysis, and 2 patients had oculomotor paralysis (1 total and 1 incomplete), but both of them recovered during the follow-up period. One patient experienced an ipsilateral superior cerebellar artery infarction, and another patient had transient hemiparesis. CONCLUSION: The EF-SCITA is effective for most petroclival region meningiomas, except for the cavernous sinus type. This approach simplifies craniotomy procedures, omits burdensome petrosectomy, and avoids crossing posterior neurovascular structures.

Endoscopic Midline and Paramedian Supracerebellar Infratentorial Approaches to Pineal Region Tumors: A Clinical Study and Approach Comparison.

OBJECTIVE: This study was to analyze the advantages and disadvantages of endoscopic midline and paramedian supracerebellar infratentorial approaches (EM-SCITA and EPM-SCITA) for pineal region tumors. METHODS: We retrospectively analyzed the clinical data of 58 patients who underwent EM-SCITA and EPM-SCITA for pineal region tumors. Among them, 23 patients were treated with EM-SCITA, and 35 with EPM-SCITA. The patients were followed up for 6-84 months with magnetic resonance imaging and Karnofsky Performance Status scores. RESULTS: The average age of the patients was 37.98 years, and there were 16 women (27.6%). The average maximum diameter of the tumors was 2.92 cm. Gross total resection was achieved in 46 patients (79.31%). There were 45 patients (77.6%) whose Karnofsky Performance Status score was >70 at the final follow-up. There was no significant difference among the above items between EM-SCITA and EPM-SCITA. However, EM-SCITA required a longer craniotomy and closure time, with a larger bone and dural flap, with more bridging veins sacrificed. EPM-SCITA simplified the opening of the quadrigeminal cistern, and it was beneficial to expose the contralateral wall of the third ventricle. The longer and angled path limited the exposure of the anterior third ventricle and the ipsilateral wall of the third ventricle. CONCLUSIONS: Both approaches had remarkable clinical effects. The anatomy of EM-SCITA was easy to understand and has a larger operating space; it is suitable for neurosurgical beginners. In contrast, EPM-SCITA has limited operation space, an intricate anatomy, and is suitable for experienced operators. The occurrence of postoperative hydrocephalus should be alerted by EPM-SCITA.

Magnetic Resonance/Infrared Dual-Modal Imaging-Guided Synergistic Photothermal/Photodynamic Therapy Nanoplatform Based on Cu1.96S-Gd@FA for Precision Cancer Theranostics.

Developing new nanoplatforms for dynamically and quantitatively visualizing drug accumulation and targeting within tumors is crucial for precision cancer theranostic. However, achieving efficient tumor therapy via synergistic photothermal/photodynamic therapy (PTT/PDT) using a single excitation light source, remains a challenge. In this work, we designed Gd-surface functionalized copper sulfide nanoparticles that were modified with folic acid (FA) (Cu1.96S-Gd@FA) to overcome the above limitations and promote PTT/PDT therapeutics. Here, Cu1.96S-Gd nanoparticles were synthesized via a coprecipitation method. All samples exhibited high longitudinal relaxivity (up to 12.9 mM-1 s-1) and strong photothermal conversion efficiency (50.6%). Furthermore, the Gd ions promoted electron-hole segregation, inducing the Cu1.96S-Gd nanoparticles to generate more reactive oxygen species (ROS) than pure Cu1.96S nanoparticles. The Cu1.96S-Gd@FA enabled the targeting of folate receptor (FR) and promoted cellular uptake, consequently enhancing oncotherapy efficacy. Compared to non-targeted Cu1.96S-Gd, a higher signal enhancement for magnetic resonance (MR) imaging in vivo by Cu1.96S-Gd@FA was recorded. Given photothermal ability, the nanoparticles also could be visualized in infrared (IR) imaging. Furthermore, the nanoparticles exhibited biodegradation behavior and achieved good drug elimination performance via renal clearance. Our strategy, integrating Cu1.96S-Gd@FA nanoparticles, MR/IR dual-modal imaging, and PTT/PDT into one nanoplatform, demonstrated great potential for anti-breast cancer therapy by effectively targeting FR overexpressed breast cancer cells.

Single-neuron projectome of mouse prefrontal cortex.

Prefrontal cortex (PFC) is the cognitive center that integrates and regulates global brain activity. However, the whole-brain organization of PFC axon projections remains poorly understood. Using single-neuron reconstruction of 6,357 mouse PFC projection neurons, we identified 64 projectome-defined subtypes. Each of four previously known major cortico-cortical subnetworks was targeted by a distinct group of PFC subtypes defined by their first-order axon collaterals. Further analysis unraveled topographic rules of soma distribution within PFC, first-order collateral branch point-dependent target selection and terminal arbor distribution-dependent target subdivision. Furthermore, we obtained a high-precision hierarchical map within PFC and three distinct functionally related PFC modules, each enriched with internal recurrent connectivity. Finally, we showed that each transcriptome subtype corresponds to multiple projectome subtypes found in different PFC subregions. Thus, whole-brain single-neuron projectome analysis reveals organization principles of axon projections within and outside PFC and provides the essential basis for elucidating neuronal connectivity underlying diverse PFC functions.

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.

Nuclear isoform of FGF13 regulates post-natal neurogenesis in the hippocampus through an epigenomic mechanism.

The hippocampus is one of two niches in the mammalian brain with persistent neurogenesis into adulthood. The neurogenic capacity of hippocampal neural stem cells (NSCs) declines with age, but the molecular mechanisms of this process remain unknown. In this study, we find that fibroblast growth factor 13 (FGF13) is essential for the post-natal neurogenesis in mouse hippocampus, and FGF13 deficiency impairs learning and memory. In particular, we find that FGF13A, the nuclear isoform of FGF13, is involved in the maintenance of NSCs and the suppression of neuronal differentiation during post-natal hippocampal development. Furthermore, we find that FGF13A interacts with ARID1B, a unit of Brahma-associated factor chromatin remodeling complex, and suppresses the expression of neuron differentiation-associated genes through chromatin modification. Our results suggest that FGF13A is an important regulator for maintaining the self-renewal and neurogenic capacity of NSCs in post-natal hippocampus, revealing an epigenomic regulatory function of FGFs in neurogenesis.

Extensive gene loss in the plastome of holoparasitic plant Cistanche tubulosa (Orobanchaceae).

Extensive photosynthetic gene loss and rapid evolutionary rate occur in the plastomes of parasitic plants. The holoparasitic plant Cistanche tubulosa of Orobanchaceae is an important medicinal resources that are distributed in arid areas. In this study, the complete plastome of C. tubulosa has been sequenced, assembled and analyzed. The total plastome of C. tubulosa was 75,375 bp in length, consisting of a pair of inverted repeats (IRs, 6,593 bp), a large single-copy region (LSC, 32,470 bp) and a small single-copy region (SSC, 29,719 bp). It contained 24 intact protein coding genes, nine pseudogenes, and 44 missing genes. In addition, all the protein-coding genes, which were related to photosynthesis and energy production, were pseudogenised or lost. Four rRNA genes and 24 tRNA genes were intact meanwhile five tRNA genes were missing. Phylogenetic tree indicated that C. tubulosa was closely related to C. phelypaea. Our results may improve understanding of the plastome organization, classification, and evolution of parasitic plants.

Theoretical study of the mechanism of the N-heterocyclic carbene-catalyzed cyclotetramerization of acrylates.

A theoretical study of the N-heterocyclic carbene (NHC)-catalyzed cyclotetramerization of acrylates forming trisubstituted cyclopentenones indicates a mechanism through a key deoxy-Breslow intermediate generated from one molecule of NHC and two molecules of methyl acrylate (MA). Pathways involving different proton-transfer (α or ß) and the role of a tert-butoxide ( (t) BuO(-)) group were investigated.

Ebf2 is required for development of dopamine neurons in the midbrain periaqueductal gray matter of mouse.

Dopaminergic (DA) neurons in the midbrain ventral periaqueductal gray matter (PAG) play critical roles in various physiological and pathophysiological processes including sleep-wake rhyme, antinociception, and drug addiction. However, the molecular mechanisms underlying their development are poorly understood. Here, we showed that PAG DA neurons arose as early as E15.5 in mouse embryos. During the prenatal period, the majority of PAG DA neurons was distributed in the intermediate and caudal regions of the PAG. In the postnatal brain, ∼50% of PAG DA neurons were preferentially located in the caudal portion of the PAG. Moreover, transcription factor early B-cell factor 2 (Ebf2) was transiently expressed in a subset of DA neurons in embryonic ventral mesencephalon. Functional analysis revealed that loss of Ebf2 in vivo caused a marked reduction in the number of DA neurons in the midbrain PAG but not in the substantia nigra and ventral tegmental area. Thus, Ebf2 is identified as a novel and important regulator selectively required for midbrain PAG DA neuron development.

Identification of a Vav2-dependent mechanism for GDNF/Ret control of mesolimbic DAT trafficking.

Dopamine (DA) homeostasis is essential for a variety of brain activities. Dopamine transporter (DAT)-mediated DA reuptake is one of the most critical mechanisms for normal DA homeostasis. However, the molecular mechanisms underlying the regulation of DAT activity in the brain remain poorly understood. Here we show that the Rho-family guanine nucleotide exchange factor protein Vav2 is required for DAT cell surface expression and transporter activity modulated by glial cell line-derived neurotrophic factor (GDNF) and its cognate receptor Ret. Mice deficient in either Vav2 or Ret displayed elevated DAT activity, which was accompanied by an increase in intracellular DA selectively in the nucleus accumbens. Vav2(-/-) mice exposed to cocaine showed reduced DAT activity and diminished behavioral cocaine response. Our data demonstrate that Vav2 is a determinant of DAT trafficking in vivo and contributes to the maintenance of DA homeostasis in limbic DA neuron terminals.