Chlamydomonas mutants lacking chloroplast TRIOSE PHOSPHATE TRANSPORTER3 are metabolically compromised and light sensitive.

Modulation of photoassimilate export from the chloroplast is essential for controlling the distribution of fixed carbon in the cell and maintaining optimum photosynthetic rates. In this study, we identified chloroplast TRIOSE PHOSPHATE/PHOSPHATE TRANSLOCATOR 2 (CreTPT2) and CreTPT3 in the green alga Chlamydomonas (Chlamydomonas reinhardtii), which exhibit similar substrate specificities but whose encoding genes are differentially expressed over the diurnal cycle. We focused mostly on CreTPT3 because of its high level of expression and the severe phenotype exhibited by tpt3 relative to tpt2 mutants. Null mutants for CreTPT3 had a pleiotropic phenotype that affected growth, photosynthetic activities, metabolite profiles, carbon partitioning, and organelle-specific accumulation of H2O2. These analyses demonstrated that CreTPT3 is a dominant conduit on the chloroplast envelope for the transport of photoassimilates. In addition, CreTPT3 can serve as a safety valve that moves excess reductant out of the chloroplast and appears to be essential for preventing cells from experiencing oxidative stress and accumulating reactive oxygen species, even under low/moderate light intensities. Finally, our studies indicate subfunctionalization of the TRIOSE PHOSPHATE/PHOSPHATE TRANSLOCATOR (CreTPT) transporters and suggest that there are differences in managing the export of photoassimilates from the chloroplasts of Chlamydomonas and vascular plants.

Sodium-glucose cotransporter 2 inhibitors, inflammation, and heart failure: a two-sample Mendelian randomization study.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are increasingly recognized for their role in reducing the risk and improving the prognosis of heart failure (HF). However, the precise mechanisms involved remain to be fully delineated. Evidence points to their potential anti-inflammatory pathway in mitigating the risk of HF. METHODS: A two-sample, two-step Mendelian Randomization (MR) approach was employed to assess the correlation between SGLT-2 inhibition and HF, along with the mediating effects of inflammatory biomarkers in this relationship. MR is an analytical methodology that leverages single nucleotide polymorphisms as instrumental variables to infer potential causal inferences between exposures and outcomes within observational data frameworks. Genetic variants correlated with the expression of the SLC5A2 gene and glycated hemoglobin levels (HbA1c) were selected using datasets from the Genotype-Tissue Expression project and the eQTLGen consortium. The Genome-wide association study (GWAS) data for 92 inflammatory biomarkers were obtained from two datasets, which included 14,824 and 575,531 individuals of European ancestry, respectively. GWAS data for HF was derived from a meta-analysis that combined 26 cohorts, including 47,309 HF cases and 930,014 controls. Odds ratios (ORs) and 95% confidence interval (CI) for HF were calculated per 1 unit change of HbA1c. RESULTS: Genetically predicted SGLT-2 inhibition was associated with a reduced risk of HF (OR 0.42 [95% CI 0.30-0.59], P < 0.0001). Of the 92 inflammatory biomarkers studied, two inflammatory biomarkers (C-X-C motif chemokine ligand 10 [CXCL10] and leukemia inhibitory factor) were associated with both SGLT-2 inhibition and HF. Multivariable MR analysis revealed that CXCL10 was the primary inflammatory cytokine related to HF (MIP = 0.861, MACE = 0.224, FDR-adjusted P = 0.0844). The effect of SGLT-2 inhibition on HF was mediated by CXCL10 by 17.85% of the total effect (95% CI [3.03%-32.68%], P = 0.0183). CONCLUSIONS: This study provides genetic evidence supporting the anti-inflammatory effects of SGLT-2 inhibitors and their beneficial impact in reducing the risk of HF. CXCL10 emerged as a potential mediator, offering a novel intervention pathway for HF treatment.

Dual substitution of host lattice ions to enhance the luminescence properties of Zn2TiO4:Cr3+ phosphor.

Near-infrared light sources have potential applications in many fields. Cr3+ is a good luminescence centre to prepare near-infrared phosphors. Improving the performance of existing near-infrared luminescent materials has indeed attracted great interest from researchers. The luminescence properties of Zn2TiO4:Cr3+ were improved by crystal field engineering strategies. Zn2+-Ti4+ was partially replaced using a Li+-Nb5+ ion pair based on the Zn2TiO4:Cr3+ phosphors. Luminescence Cr3+-activated luminescent materials are sensitive to changes in the local crystal structure and crystal field environment. Doping of Li+-Nb5+ increased the luminescence intensity up to 2.7 times that of the undoped sample. Also, the thermal stability of the phosphor was greatly increased by the replacement of Li+-Nb5+.

High-density lipoprotein cholesterol modifies the association between blood lead and uric acid: results from NHANES 2005-2016.

BACKGROUND: The association between blood lead (PbB) and uric acid (SUA) remains unclear in US adults without a high level of lead exposure. Additionally, the effects of high-density lipoprotein cholesterol (HDL-C) modifying this association are still unclear. Therefore, this study aims to assess the effect of modification of high-density lipoprotein cholesterol on the association between PbB and SUA. METHOD: This research analyzed National Health and Nutrition Examination Survey (NHANES) data from 2005 to 2016. Through several screenings, 18,578 participants over the age of 20 were eligible for the analysis. Multivariable linear regression was used to evaluate the association between PbB and SUA. By having stratified participants based on the HDL-C intake category (low HDL-C intake < 50 mg/dl; high HDL-C intake ≥ 50 mg/dl), effect modification by HDL-C was assessed through a likelihood ratio test between PbB and SUA. RESULT: Multivariable linear regression indicated that PbB positively affects SUA (ß = 0.19, 95% CI 0.16-0.22). The relationship between PbB and SUA was different in the low and high HDL-C intake group (ß 0.12 95% Cl 0.08-0.16 vs. ß 0.26 95% Cl 0.22 ~ - 0.30). Furthermore, high-density lipoprotein cholesterol significantly modified the relationship between PbB and SUA in all models which indicates that the interaction of lead exposure and HDL-C is more dangerous than the sum of the individual effects. CONCLUSIONS: Our study shows that high-density lipoprotein cholesterol and blood lead have an interactive effect on increasing uric acid, which may have great importance for clinical medication.

A novel Mn4+ -activated far-red Sr2 MgWO6 phosphor: synthesis, luminescence enhancement, and application prospect.

A novel far-red emitting phosphor Sr2 MgWO6 : Mn4+ was fabricated using high-temperature solid-state reaction. X-ray diffraction patterns, scanning electron microscopy images, and photoluminescence excitation and photoluminescence spectra for this phosphor were analyzed in detail. The analysis revealed that its emission ranged from 600 to 800 nm and peaked at 699 nm, which was attributed to the 2 Eg →4 A2g transition of Mn4+ under 314 nm excitation. Moreover, we introduced rare-earth Yb3+ ions into the Sr2 MgWO6 :Mn4+ to improve its far-red emitting intensity. The photoluminescence (PL) intensity of the Yb3+ co-doped phosphor was three times higher than that of the single-doped phosphor. Therefore charge compensation is an efficient approach to improving PL intensity. The phosphor emitted a far-red light that resembled the pigments essential for plant growth in terms of the absorption spectrum. Therefore, the obtained phosphor, Sr2 MgWO6 :0.006Mn4+ ,0.2Yb3+ , had the potential to be a new type of far-red luminescent powder for indoor plant growth LEDs.

Bearing Fault-Detection Method Based on Improved Grey Wolf Algorithm to Optimize Parameters of Multistable Stochastic Resonance.

In an effort to overcome the problem that the traditional stochastic resonance system cannot adjust the structural parameters adaptively in bearing fault-signal detection, this article proposes an adaptive-parameter bearing fault-detection method. First of all, the four strategies of Sobol sequence initialization, exponential convergence factor, adaptive position update, and Cauchy-Gaussian hybrid variation are used to improve the basic grey wolf optimization algorithm, which effectively improves the optimization performance of the algorithm. Then, based on the multistable stochastic resonance model, the structure parameters of the multistable stochastic resonance are optimized through improving the grey wolf algorithm, so as to enhance the fault signal and realize the effective detection of the bearing fault signal. Finally, the proposed bearing fault-detection method is used to analyze and diagnose two open-source bearing data sets, and comparative experiments are conducted with the optimization results of other improved algorithms. Meanwhile, the method proposed in this paper is used to diagnose the fault of the bearing in the lifting device of a single-crystal furnace. The experimental results show that the fault frequency of the inner ring of the first bearing data set diagnosed using the proposed method was 158 Hz, and the fault frequency of the outer ring of the second bearing data set diagnosed using the proposed method was 162 Hz. The fault-diagnosis results of the two bearings were equal to the results derived from the theory. Compared with the optimization results of other improved algorithms, the proposed method has a faster convergence speed and a higher output signal-to-noise ratio. At the same time, the fault frequency of the bearing of the lifting device of the single-crystal furnace was effectively diagnosed as 35 Hz, and the bearing fault signal was effectively detected.

The impact of needle location on clinical outcome of radiofrequency rhizotomy for trigeminal neuralgia.

BACKGROUND: Radiofrequency thermocoagulation trigeminal rhizotomy (RT-TR) through the foramen ovale is a minimally invasive treatment for trigeminal neuralgia. Navigation of magnetic resonance imaging (MRI) and CT fusion imaging is a well-established method for cannulation of the Gasserian ganglion. In this study, we use the inline measurements from fusion image to analyze the anatomical parameters between the actual and simulation trajectories and compare the short- and intermediate-term outcomes according to determinable factors. METHODS: The study included thirty-six idiopathic neuralgia patients who had undergone RT-TR with MRI and CT fusion image as a primary modality or repeated procedures. RESULTS: Among thirty-six treated patients, the inline length of the trigeminal cistern was longer for the simulated trajectory (8.4 ± 2.4 versus 6.5 ± 2.8 mm; p < 0.05), and the predominant structure at risk extrapolated from the inline trajectory was the brainstem, which signified a more medially directed route, in contrast with the equal weighting of temporal lobe and brainstem for the actual trajectory. The preoperative visual analogue scale (VAS) was 9.3 ± 1.0, which decreased to 2.5 ± 2.6 and 2.9 ± 3.1 at first (mean, 3 months) and second (mean, 14 months) postoperative follow-up, respectively. The postoperative VAS scores at the two follow-ups were not statistically significant without a covariate analysis. After adjustment for covariate risk factors, the second follow-up sustained therapeutic benefit was evident in patients with no prior history of related treatment, an ablation temperature greater than 70 °C, and needle location within or adjacent to the trigeminal cistern. CONCLUSIONS: This preliminary study demonstrated that the needle location between cistern and ganglion also plays a significant role in better intermediate-term results.

Bleeding risks with novel oral anticoagulants especially rivaroxaban versus aspirin: a meta-analysis.

BACKGROUND: This pairwise meta-analysis determines the difference in bleeding risks associated with the use of novel oral anticoagulants (NOACs) and aspirin. METHODS: PubMed, the Cochrane Library database, clinicaltrial.gov , and related studies were searched for randomized control trials (RCTs) comparing NOAC and aspirin published between January 1, 2000 and May 10, 2021. The primary endpoint was intracranial hemorrhage (ICH). RESULTS: Eleven studies involving 57,645 patients were included. Compared to aspirin, rivaroxaban (5 mg/day) had a similar risk of ICH, major bleeding, and fatal bleeding; rivaroxaban (10 mg/day) had higher risks of gastrointestinal hemorrhage (OR: 1.41; 95% CI: 1.03-1.94; P = 0.032; I2 = 0%) and a similar risk of ICH, major bleeding, and fatal bleeding; and rivaroxaban (15-20 mg/day) had higher risks of ICH (OR: 3.21; 95% CI: 1.36-7.60; P = 0.008; I2 = 0%), major bleeding (OR: 2.64; 95% CI: 1.68-4.16; P < 0.001; I2 = 0%), and fatal bleeding (OR: 2.26; 95% CI: 1.25-4.08; P = 0.007; I2 = 0%) and a similar risk of gastrointestinal hemorrhage. Bleeding outcomes between other NOACs (apixaban and dabigatran etexilate) and aspirin were not different. CONCLUSIONS: The bleeding risks associated with NOACs depend on drug type and dosage. For ≥15 mg/day of rivaroxaban, the risk of ICH was significantly higher than that with aspirin. However, further studies comparing dabigatran etexilate and apixaban versus aspirin are warranted to draw a definite conclusion.

Pituitary adenomas in older adults (≥ 65 years): 90-day outcomes and readmissions: a 10-year endoscopic endonasal surgical experience.

INTRODUCTION: Longer lifespan and newer imaging protocols have led to more older adults being diagnosed with pituitary adenomas. Herein, we describe outcomes of patients ≥ 65 years undergoing endoscopic adenoma removal. To address selection criteria, we also assess a conservatively managed cohort. METHODS: A retrospective analysis of 90-day outcomes of patients undergoing endoscopic pituitary adenomectomy from 2010 to 2019 by a neurosurgical/ENT team was performed. Tumor subtype, cavernous sinus invasion, extent of resection/early remission, endocrinology outcomes, complications, re-operations and readmissions were analyzed. A comparator cohort ≥ 65 years undergoing clinical surveillance without surgery was also analyzed. RESULTS: Of 468 patients operated on for pituitary adenoma, 123 (26%) were ≥ 65 years (range 65-93 years); 106 (86.2%) had endocrine-inactive adenomas; 18 (14.6%) had prior surgery. Of 106 patients with endocrine-inactive adenomas, GTR was achieved in 70/106 (66%). Of 17 patients with endocrine-active adenomas, early biochemical remission was: Cushing's 6/8; acromegaly 1/4; prolactinomas 1/5. Gland function recovery occurred in 28/58 (48.3%) patients with various degrees of preoperative hypopituitarism. New anterior hypopituitarism occurred in 3/110 (2.4%) patients; permanent DI in none. Major complications in 123 patients were: CSF leak 2 (1.6%), meningitis 1 (0.8%), vision decline 1 (0.8%). There were no vascular injuries, operative hematomas, anosmia, deaths, MIs, or thromboembolic events. Median length of stay was 2 days. Readmissions occurred in 14/123 (11.3%) patients, 57% for delayed hyponatremia. Intra-cohort analysis by age (65-69, 70-74, 75-79, ≥ 80 years) revealed no outcome differences. Cavernous sinus invasion (OR 7.7, CI 1.37-44.8; p = 0.02) and redo-surgery (OR 8.5, CI 1.7-42.8; p = 0.009) were negative predictors for GTR/NTR. Of 105 patients evaluated for presumed pituitary adenoma beginning in 2015, 72 (69%) underwent surgery, 8 (7%) had prolactinomas treated with cabergoline and 25 (24%) continue clinical surveillance without surgery, including two on new hormone replacement. CONCLUSION: This study suggests that elderly patients carefully selected for endoscopic adenoma removal can have excellent short-term outcomes including high resection rates, low complication rates and short length of stay. Our experience supports a multidisciplinary approach and the concept of pituitary centers of excellence. Based on our observations, approximately 25% of elderly patients with pituitary adenomas referred for possible surgery can be monitored closely without surgery.

Reduced vacuolar ß-1,3-glucan synthesis affects carbohydrate metabolism as well as plastid homeostasis and structure in Phaeodactylum tricornutum.

The ß-1,3-glucan chrysolaminarin is the main storage polysaccharide of diatoms. In contrast to plants and green algae, diatoms and most other algal groups do not accumulate storage polysaccharides in their plastids. The diatom Phaeodactylum tricornutum possesses only a single gene encoding a putative ß-1,3-glucan synthase (PtBGS). Here, we characterize this enzyme by expressing GFP fusion proteins in P. tricornutum and by creating and investigating corresponding gene silencing mutants. We demonstrate that PtBGS is a vacuolar protein located in the tonoplast. Metabolite analyses of two mutant strains with reduced amounts of PtBGS reveal a reduction in their chrysolaminarin content and an increase of soluble sugars and lipids. This indicates that carbohydrates are shunted into alternative pathways when chrysolaminarin production is impaired. The mutant strains show reduced growth and lower photosynthetic capacities, while possessing higher photoprotective abilities than WT cells. Interestingly, a strong reduction in PtBGS expression also results in aberrations of the usually very regular thylakoid membrane patterns, including increased thylakoid thickness, reduced numbers of thylakoids per plastid, and increased numbers of lamellae per thylakoid stack. Our data demonstrate the complex intertwinement of carbohydrate storage in the vacuoles with carbohydrate metabolism, photosynthetic homeostasis, and plastid morphology.

Characterization and Optimization of Chitosan-Coated Polybutylcyanoacrylate Nanoparticles for the Transfection-Guided Neural Differentiation of Mouse Induced Pluripotent Stem Cells.

Gene transfection is a valuable tool for analyzing gene regulation and function, and providing an avenue for the genetic engineering of cells for therapeutic purposes. Though efficient, the potential concerns over viral vectors for gene transfection has led to research in non-viral alternatives. Cationic polyplexes such as those synthesized from chitosan offer distinct advantages such as enhanced polyplex stability, cellular uptake, endo-lysosomal escape, and release, but are limited by the poor solubility and viscosity of chitosan. In this study, the easily synthesized biocompatible and biodegradable polymeric polysorbate 80 polybutylcyanoacrylate nanoparticles (PS80 PBCA NP) are utilized as the backbone for surface modification with chitosan, in order to address the synthetic issues faced when using chitosan alone as a carrier. Plasmid DNA (pDNA) containing the brain-derived neurotrophic factor (BDNF) gene coupled to a hypoxia-responsive element and the cytomegalovirus promotor gene was selected as the genetic cargo for the in vitro transfection-guided neural-lineage specification of mouse induced pluripotent stem cells (iPSCs), which were assessed by immunofluorescence staining. The chitosan-coated PS80 PBCA NP/BDNF pDNA polyplex measured 163.8 ± 1.8 nm and zeta potential measured -34.8 ± 1.8 mV with 0.01% (w/v) high molecular weight chitosan (HMWC); the pDNA loading efficiency reached 90% at a nanoparticle to pDNA weight ratio of 15, which also corresponded to enhanced polyplex stability on the DNA stability assay. The HMWC-PS80 PBCA NP/BDNF pDNA polyplex was non-toxic to mouse iPSCs for up to 80 µg/mL (weight ratio = 40) and enhanced the expression of BDNF when compared with PS80 PBCA NP/BDNF pDNA polyplex. Evidence for neural-lineage specification of mouse iPSCs was observed by an increased expression of nestin, neurofilament heavy polypeptide, and beta III tubulin, and the effects appeared superior when transfection was performed with the chitosan-coated formulation. This study illustrates the versatility of the PS80 PBCA NP and that surface decoration with chitosan enabled this delivery platform to be used for the transfection-guided differentiation of mouse iPSCs.

The mitochondrial alternative oxidase from Chlamydomonas reinhardtii enables survival in high light.

Photosynthetic organisms often experience extreme light conditions that can cause hyper-reduction of the chloroplast electron transport chain, resulting in oxidative damage. Accumulating evidence suggests that mitochondrial respiration and chloroplast photosynthesis are coupled when cells are absorbing high levels of excitation energy. This coupling helps protect the cells from hyper-reduction of photosynthetic electron carriers and diminishes the production of reactive oxygen species (ROS). To examine this cooperative protection, here we characterized Chlamydomonas reinhardtii mutants lacking the mitochondrial alternative terminal respiratory oxidases, CrAOX1 and CrAOX2. Using fluorescent fusion proteins, we experimentally demonstrated that both enzymes localize to mitochondria. We also observed that the mutant strains were more sensitive than WT cells to high light under mixotrophic and photoautotrophic conditions, with the aox1 strain being more sensitive than aox2 Additionally, the lack of CrAOX1 increased ROS accumulation, especially in very high light, and damaged the photosynthetic machinery, ultimately resulting in cell death. These findings indicate that the Chlamydomonas AOX proteins can participate in acclimation of C. reinhardtii cells to excess absorbed light energy. They suggest that when photosynthetic electron carriers are highly reduced, a chloroplast-mitochondria coupling allows safe dissipation of photosynthetically derived electrons via the reduction of O2 through AOX (especially AOX1)-dependent mitochondrial respiration.

Factors affecting long-term mortality rate after diagnosis of syringomyelia in disabled spinal cord injury patients: a population-based study.

STUDY DESIGN: A retrospective, population-based study. OBJECTIVES: To identify factors affecting long-term mortality and medical resources use in disabled spinal cord injury (SCI) patients after syringomyelia diagnosis. SETTING: A National Health Insurance Research Database containing 10,374 patients with SCI. METHODS: Data recorded between 1997 and 2012 for 376 disabled SCI patients with syringomyelia and 376 characteristics-matched disabled SCI patients without syringomyelia were collected. The index date was the date of syringomyelia diagnosis. Cox proportional hazards regression model was used to investigate the factors affecting 10-year mortality in these patients. Medical resources use was compared for 1 year before and after index date. RESULTS: The survival rate at 10-year follow-up after syringomyelia diagnosis was estimated at 68.6%. The 10-year survival rate was comparable between the two groups. Age ≥ 60 (adjusted hazard ratios (aHR) 4.21, 95% confidence interval (CI) 2.97 to 5.96) and < 30 years (aHR 0.25, 95% CI 0.10 to 0.62), spinal cord or spinal canal operations within 1 year after the index date (aHR 1.84, 95% CI 1.19 to 2.84), history of pneumonia (aHR 1.55, 95% CI 1.07 to 2.26), and history of coronary heart disease (CHD) (aHR 1.85, 95% CI 1.18 to 2.89) were significantly associated with long-term mortality. Outpatient prescription costs were higher during 1 year after the diagnosis than those of 1 year before the diagnosis. CONCLUSION: Age, spinal operations, history of pneumonia, and history of CHD are associated with 10-year mortality in disabled SCI patients with syringomyelia.

Minimally invasive surgical treatment of intracranial meningiomas in elderly patients (≥ 65 years): outcomes, readmissions, and tumor control.

OBJECTIVE: Increased lifespan has led to more elderly patients being diagnosed with meningiomas. In this study, the authors sought to analyze and compare patients ≥ 65 years old with those < 65 years old who underwent minimally invasive surgery for meningioma. To address surgical selection criteria, the authors also assessed a cohort of patients managed without surgery. METHODS: In a retrospective analysis, consecutive patients with meningiomas who underwent minimally invasive (endonasal, supraorbital, minipterional, transfalcine, or retromastoid) and conventional surgical treatment approaches during the period from 2008 to 2019 were dichotomized into those ≥ 65 and those < 65 years old to compare resection rates, endoscopy use, complications, and length of hospital stay (LOS). A comparator meningioma cohort of patients ≥ 65 years old who were observed without surgery during the period from 2015 to 2019 was also analyzed. RESULTS: Of 291 patients (median age 60 years, 71.5% females, mean follow-up 36 months) undergoing meningioma resection, 118 (40.5%) were aged ≥ 65 years and underwent 126 surgeries, including 20% redo operations, as follows: age 65-69 years, 46 operations; 70-74 years, 40 operations; 75-79 years, 17 operations; and ≥ 80 years, 23 operations. During 2015-2019, of 98 patients referred for meningioma, 67 (68%) had surgery, 1 (1%) had radiosurgery, and 31 (32%) were observed. In the 11-year surgical cohort, comparing 173 patients < 65 years versus 118 patients ≥ 65 years old, there were no significant differences in tumor location, size, or outcomes. Of 126 cases of surgery in 118 elderly patients, the approach was a minimally invasive approach to skull base meningioma (SBM) in 64 cases (51%) as follows: endonasal 18, supraorbital 28, minipterional 6, and retrosigmoid 12. Endoscope-assisted surgery was performed in 59.5% of patients. A conventional approach to SBM was performed in 15 cases (12%) (endoscope-assisted 13.3%), and convexity craniotomy for non-skull base meningioma (NSBM) in 47 cases (37%) (endoscope-assisted 17%). In these three cohorts (minimally invasive SBM, conventional SBM, and NSBM), the gross-total/near-total resection rates were 59.5%, 60%, and 91.5%, respectively, and an improved or stable Karnofsky Performance Status score occurred in 88.6%, 86.7%, and 87.2% of cases, respectively. For these 118 elderly patients, the median LOS was 3 days, and major complications occurred in 10 patients (8%) as follows: stroke 4%, vision decline 3%, systemic complications 0.7%, and wound infection or death 0. Eighty-three percent of patients were discharged home, and readmissions occurred in 5 patients (4%). Meningioma recurrence occurred in 4 patients (3%) and progression in 11 (9%). Multivariate regression analysis showed no significance of American Society of Anesthesiologists physical status score, comorbidities, or age subgroups on outcomes; patients aged ≥ 80 years showed a trend of longer hospitalization. CONCLUSIONS: This analysis suggests that elderly patients with meningiomas, when carefully selected, generally have excellent surgical outcomes and tumor control. When applied appropriately, use of minimally invasive approaches and endoscopy may be helpful in achieving maximal safe resection, reducing complications, and promoting short hospitalizations. Notably, one-third of our elderly meningioma patients referred for possible surgery from 2015 to 2019 were managed nonoperatively.

The Effects of Orientin on Proliferation and Apoptosis of T24 Human Bladder Carcinoma Cells Occurs Through the Inhibition of Nuclear Factor-kappaB and the Hedgehog Signaling Pathway.

BACKGROUND Orientin is a flavone isolated from medicinal plants used in traditional Chinese medicine (TCM), which suppresses the growth of cancer cells in vitro. The effects of orientin in bladder cancer cells remains unknown. This study aimed to investigate the effect of orientin on proliferation and apoptosis of T24 human transitional cell bladder carcinoma cells in vitro in the presence of an agonist and an inhibitor of nuclear factor-kappaB (NF-kappaB). MATERIAL AND METHODS T24 cells were cultured and divided into four study groups: an untreated control group; a group treated with 100 µM orientin; a group treated with 100 µM orientin with NF-kappaB agonist, phorbol 12-myristate 13-acetate (PMA); and a group treated with 100 µM orientin and the NF-kappaB inhibitor, IkappaBalpha. The MTT assay was performed to assess cell viability, and flow cytometry evaluated the cell cycle. The expression of proteins in the Hedgehog signaling pathway and inflammatory cytokines were determined by Western blot and enzyme-linked immunosorbent assay (ELISA). RESULTS Orientin inhibited the proliferation of T24 cells, caused cell cycle arrest, reduced cell viability, and inhibited the expression of inflammatory mediators. Treatment of T24 cells with orientin inhibited the expression of NF-kappaB and components of the Hedgehog signaling pathway, and the NF-kappaB agonist, PMA, reversed these effects. CONCLUSIONS Treatment of T24 human bladder carcinoma cells in vitro with orientin inhibited cell proliferation and promoted cell apoptosis by suppressing the Hedgehog signaling pathway and NF-kappaB.

Foramen ovale cannulation guided by intraoperative computed tomography with magnetic resonance image fusion plays a role in improving the long-term outcome of percutaneous radiofrequency trigeminal rhizotomy.

BACKGROUND: Percutaneous radiofrequency trigeminal rhizotomy (RF-TR) is a well-established treatment for patients suffering from trigeminal neuralgia (TN) as a primary modality or for those refractory to medical treatment. However, few existing studies have identified intraoperative parameter or navigation technique that can be used to predict the rates of short-term or long-term pain relief. In this study, we analyzed patient characteristics, intraoperative parameters and technical factors, and postoperative changes in relation to immediate and long-term pain relief. METHOD: This study included a total 252 patients in which 340 RF-TR were performed under the guidance of intraoperative computed tomography (iCT) alone or with magnetic resonance image (MRI) and iCT fusion imaging. RESULT: The immediate pain relief of RF-TR with iCT alone and iCT with MR image guidance with or without cerebrospinal fluid (CSF) outflow were all above 90.4%. The 2-year pain relief rate of RF-TR using iCT alone and iCT with MR images guidance with or without CSF outflow were 47.8%, 39.8%, 71.7%, and 53.9% respectively. Significant factors for 2-year pain relief were CSF outflow, iCT with MR image fusion, non-recurrent TN, and presence of postoperative facial numbness. CONCLUSION: This preliminary study demonstrated foramen ovale cannulation under the aid of iCT with MR image guidance could improve 2-year pain relief.

Comparison between Polybutylcyanoacrylate Nanoparticles with Either Surface-Adsorbed or Encapsulated Brain-Derived Neurotrophic Factor on the Neural Differentiation of iPSCs.

The brain-derived neurotrophic factor (BDNF) is vital in the neural differentiation of neural stem/progenitor cells, and together may have therapeutic potential for neural regeneration. In this study, a multiplexed polybutylcyanoacrylate nanoparticle (PBCA NP) delivery platform was constructed, incorporating either surface-adsorbed or encapsulated BDNF for the induction of neural differentiation in induced pleuripotent stem cells (iPSCs), where tween 80 (T80) and superparamagnetic iron oxide (SPIO) were added for central nervous system (CNS) targeting and magnetic resonance (MR) image tracking, respectively. Both methods by which the BDNF was carried resulted in loading efficiencies greater than 95%. The nanoparticle-mediated delivery of BDNF resulted in neural differentiation of iPSCs detected on immunofluorescence staining as early as 7 days, with enhanced differentiation efficiency by 1.3-fold compared to the control on flow cytometry; the delivery system of surface-adsorbed BDNF gave rise to cells that had the best neural development than the encapsulated formulation. T80-coating disrupted the in vitro blood⁻brain barrier model with a corresponding 1.5- to two-fold increase in permeability. SPIO-loaded PBCA NPs exhibited a concentration-dependent, rapid decay in signal intensity on the phantom MR experiment. This study demonstrates the versatility of the PBCA NP, and the surface-adsorption of BDNF is the preferred method of delivery for the differentiation of iPSCs.

Percutaneous dorsal root ganglion block for treating lumbar compression fracture-related pain.

BACKGROUND: The pain of acute compression fracture in the lumbar spine may be refractory to conservative treatment, and surgery is not an optimal choice for the elderly or infirm individuals. Moreover, even vertebroplasty can cause many side effects such as chemical leak, adjacent segment instability, and residual pain. Percutaneous dorsal root ganglion block (PDRGB) possibly is an alternative therapeutic option. In this study, we evaluated the efficacy of pain relief and the rate of adjacent level compression fracture in patients with acute compression fracture of the lumbar spine. METHODS: We retrospectively reviewed 40 patients with lumbar compression fracture from 2013 to 2015. The patients were treated with navigation-assisted CT-guided PDRGB with steroid at the pathological level and at the adjacent level above and below. Therapeutic response was evaluated using the Numerical Rating Scale (NRS); and an optimal, acceptable, and unfavorable outcome were analyzed. RESULTS: Among the 40 patients treated, initial pain relief on the first day was dramatic, and the average NRS did not change significantly up to the first-year follow-up. The highest percentage of a good outcome, at 90% (37.5% with an optimal outcome, 52.5% with an acceptable outcome), was reported at 1 week postoperatively. The percentage of optimal outcomes increased even at the 1-year follow-up. No adjacent compression fracture was found in the group treated with PDRGB alone at the 1-year follow-up. CONCLUSIONS: PDRGB is a simple, safe, and minimally invasive procedure that showed immediate and prolonged improvement of pain in lumbar osteoporotic compression fracture patients who failed conservative treatment or had residual pain after vertebroplasty. However, continuous medication for osteoporosis was still required.

Methylcrotonyl-CoA Carboxylase Regulates Triacylglycerol Accumulation in the Model Diatom Phaeodactylum tricornutum.

The model marine diatom Phaeodactylum tricornutum can accumulate high levels of triacylglycerols (TAGs) under nitrogen depletion and has attracted increasing attention as a potential system for biofuel production. However, the molecular mechanisms involved in TAG accumulation in diatoms are largely unknown. Here, we employed a label-free quantitative proteomics approach to estimate differences in protein abundance before and after TAG accumulation. We identified a total of 1193 proteins, 258 of which were significantly altered during TAG accumulation. Data analysis revealed major changes in proteins involved in branched-chain amino acid (BCAA) catabolic processes, glycolysis, and lipid metabolic processes. Subsequent quantitative RT-PCR and protein gel blot analysis confirmed that four genes associated with BCAA degradation were significantly upregulated at both the mRNA and protein levels during TAG accumulation. The most significantly upregulated gene, encoding the ß-subunit of methylcrotonyl-CoA carboxylase (MCC2), was selected for further functional studies. Inhibition of MCC2 expression by RNA interference disturbed the flux of carbon (mainly in the form of leucine) toward BCAA degradation, resulting in decreased TAG accumulation. MCC2 inhibition also gave rise to incomplete utilization of nitrogen, thus lowering biomass during the stationary growth phase. These findings help elucidate the molecular and metabolic mechanisms leading to increased lipid production in diatoms.

ABCG2 deficiency in skin impairs re-epithelialization in cutaneous wound healing.

The ATP-binding cassette transporter ABCG2 is expressed in the interfollicular epidermis and mediates the side-population phenotype in skin cells. However, the role of ABCG2 in skin is unclear. Increased expression levels of ABCG2 were found at the basal layer of transitional epidermis adjacent to cutaneous wounds in human patients, indicating that ABCG2 may be involved in regulating the wound healing process. To investigate the role of ABCG2 in cutaneous wound healing, full-thickness skin wounds were created in ABCG2 knockout (ABCG2-KO) and wild-type mice. The healing process was analysed and revealed that ABCG2 deficiency in skin results in delays in wound closure and impairments in re-epithelialization, as evidenced by reductions in both suprabasal differentiation and in p63-expressing keratinocytes migrating from transitional epidermis to epithelial tongues. The reduction in p63-expressing cells may be due to elevated levels of reactive oxygen species in ABCG2-KO epidermis, which can cause DNA damage and lead to proliferation arrest. To determine whether ABCG2 deficiency affects the potency of epidermal stem/progenitor cells (EPCs), transplantation studies were carried out, which demonstrated that ABCG2-KO EPCs display higher levels of γH2AX and lose the capacity to differentiate into suprabasal keratinocytes. A competitive repopulation assay confirmed that ABCG2 expression is critical for the proper expansion and differentiation of EPCs in cutaneous wounds. As EPCs are known to contribute to the healing of larger wounds, the current findings imply a functional role for ABCG2 in the expansion and differentiation of p63-expressing EPCs. Thus, ABCG2 deficiency in skin impairs re-epithelialization in cutaneous wound healing.