Activation of GPER-1 Attenuates Traumatic Brain Injury-Induced Neurological Impairments in Mice.

This study aimed to investigate the effects of G1-activated G protein-coupled estrogen receptor 1 (GPER1) on neurological impairments and neuroinflammation in traumatic brain injury (TBI) mice. The controlled cortical impingement (CCI) method was used to establish the TBI model. The mice were subjected to ovariectomy (OVX) for two weeks prior to modeling. GPER1 agonist G1 was administered by intracerebroventricular injection. Brain tissue water content was detected by wet/dry method, and blood-brain barrier damage was detected by Evans blue extravasation. The neurological impairments in mice were evaluated by open field test, Y-maze test, nest-building test, object location memory test and novel object recognition test. Ionized calcium-binding adapter molecule 1 (Iba1) staining was used to indicate the activation of microglia. Expression of M1/M2-type microglia markers and inflammatory factors were evaluated by ELISA and qRT-PCR. The G1 administration significantly reduced cerebral edema and Evans blue extravasation at injury ipsilateral cortex and basal ganglia in TBI mice. Activation of GPER1 by G1 improved the anxiety behavior and the cognitive dysfunction of mice induced by TBI. G1 administration significantly decreased Iba1-positive staining cells and the mRNA levels of CD86, macrophage cationic peptide 1 (Mcp-1), nitric oxide synthase 2 (Nos2), interleukin 1 beta (IL-1ß), and macrophage inflammatory protein-2 (MIP-2), while increased the mRNA levels of interleukin 10 (IL-10), arginase1 (Arg-1) and CD206. Activation of GPER1 through G1 administration has the potential to ameliorate cognitive dysfunction induced by TBI in mice. It may also inhibit the activation of M1 microglia in cortical tissue resulting from TBI, while promoting the activation of M2 microglia and contributing to the regulation of inflammatory responses.

Clinical outcomes of solitary fibrous tumors and hemangiopericytomas and risk factors related to recurrence and survival based on the 2021 WHO classification of central nervous system tumors.

OBJECTIVE: The authors aimed to explore the clinical outcomes and risk factors related to recurrence of and survival from solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) that were reclassified according to the 2021 WHO classification of central nervous system (CNS) tumors. METHODS: The authors retrospectively collected and analyzed the clinical and pathological data of SFTs and HPCs recorded from January 2007 to December 2021. Two neuropathologists reassessed pathological slides and regraded specimens on the basis of the 2021 WHO classification. The prognostic factors related to progression-free survival (PFS) and overall survival (OS) were statistically assessed with univariate and multivariate Cox regression analyses. RESULTS: A total of 146 patients (74 men and 72 women, mean ± SD [range] age 46.1 ± 14.3 [3-78] years) were reviewed, and 86, 35, and 25 patients were reclassified as having grade 1, 2, and 3 SFTs on the basis of the 2021 WHO classification, respectively. The median PFS and OS of the patients with WHO grade 1 SFT were 105 months and 199 months after initial diagnosis; for patients with WHO grade 2 SFT, 77 months and 145 months; and for patients with WHO grade 3 SFT, 44 months and 112 months, respectively. Of the entire cohort, 61 patients experienced local recurrence and 31 died, of whom 27 (87.1%) died of SFT and relevant complications. Ten patients had extracranial metastasis. In multivariate Cox regression analysis, subtotal resection (STR) (HR 4.648, 95% CI 2.601-8.304, p < 0.001), tumor located in the parasagittal or parafalx region (HR 2.105, 95% CI 1.099-4.033, p = 0.025), tumor in the vertebrae (HR 3.352, 95% CI 1.228-9.148, p = 0.018), WHO grade 2 SFT (HR 2.579, 95% CI 1.343-4.953, p = 0.004), and WHO grade 3 SFT (HR 5.814, 95% CI 2.887-11.712, p < 0.001) were significantly associated with shortened PFS, whereas STR (HR 3.217, 95% CI 1.435-7.210, p = 0.005) and WHO grade 3 SFT (HR 3.433, 95% CI 1.324-8.901, p = 0.011) were significantly associated with shortened OS. In univariate analyses, patients who received adjuvant radiotherapy (RT) after STR had longer PFS than patients who did not receive RT. CONCLUSIONS: The 2021 WHO classification of CNS tumors better predicted malignancy with different pathological grades, and in particular WHO grade 3 SFT had worse prognosis. Gross-total resection (GTR) can significantly prolong PFS and OS and should serve as the most important treatment method. Adjuvant RT was helpful for patients who underwent STR but not for patients who underwent GTR.

Direct Seawater Electrolysis: From Catalyst Design to Device Applications.

Direct seawater electrolysis (DSE) for hydrogen production, using earth-abundant seawater as the feedstock and renewable electricity as the driving source, paves a new opportunity for flexible energy conversion/storage and smooths the volatility of renewable energy. Unfortunately, the complex environments of seawater impose significant challenges on the design of DSE catalysts, and the practical performance of many current DSE catalysts remains unsatisfactory on the device level. However, many studies predominantly concentrate on the development of electrocatalysts for DSE without giving due consideration to the specific devices. To mitigate this gap, the most recent progress (mainly published within the year 2020-2023) of DSE electrocatalysts and devices are systematically evaluated. By discussing key bottlenecks, corresponding mitigation strategies, and various device designs and applications, the tremendous challenges in addressing the trade-off among activity, stability, and selectivity for DSE electrocatalysts by a single shot are emphasized. In addition, the rational design of the DSE electrocatalysts needs to align with the specific device configuration, which is more effective than attempting to comprehensively enhance all catalytic parameters. This work, featuring the first review of this kind to consider rational catalyst design in the framework of DSE devices, will facilitate practical DSE development.

Knowledge structure and hotspots research of glioma immunotherapy: a bibliometric analysis.

Background: Glioma is the most common primary brain tumor. Traditional treatments for glioma include surgical resection, radiotherapy, chemotherapy, and bevacizumab therapy, but their efficacies are limited. Immunotherapy provides a new direction for glioma treatment. This study aimed to summarize the knowledge structure and research hotspots of glioma immunotherapy through a bibliometric analysis. Method: Publications pertaining to glioma immunotherapy published during the period from 1st January 1990 to 27th March 2023 were downloaded from the Web of Science Core Collection (WoSCC). Bibliometric analysis and visualization were performed using the CiteSpace, VOSviewer, Online Analysis Platform of Literature Metrology, and R software. The hotspots and prospects of glioma immunotherapy research were illustrated via analyzing the countries, institutions, journals, authors, citations and keywords of eligible publications. Results: A total of 1,929 publications pertaining to glioma immunotherapy in 502 journals were identified as of 27th March 2023, involving 9,505 authors from 1,988 institutions in 62 countries. Among them were 1,285 articles and 644 reviews. Most of publications were produced by the United States. JOURNAL OF NEURO-ONCOLOGY published the majority of publications pertaining to glioma immunotherapy. Among the authors, Lim M contributed the largest number of publications. Through analyzing keyword bursts and co-cited references, immune-checkpoint inhibitors (ICIs) were identified as the research focus and hotspot. Conclusion: Using a bibliometric analysis, this study provided the knowledge structure and research hotspots in glioma immunotherapy research during the past 33 years, with ICIs staying in the current and future hotspot. Our findings may direct the research of glioma immunotherapy in the future.

A Six-Surface System to Describe Anatomy of Anterior Clinoid Process and Its Application in Anterior Clinoidectomy and Resection of Paraclinoid Meningioma.

OBJECTIVE: The anterior clinoid process (ACP) is surrounded by nerves and vessels that, together, constitute an intricate anatomical structure with variations that challenges the performance of individualized anterior clinoidectomy in treating lesions with different extents of invasion. In the present study, we established a 6-surface system for the ACP based on anatomical landmarks and analyzed its value in guiding ACP drilling and resection of paraclinoid meningiomas. METHODS: Using the anatomical characteristics of 10 dry skull specimens, we set 9 anatomical landmarks to delineate the ACP into 6 surfaces. Guided by our 6-surface system and eggshell technique, 5 colored silicone-injected anatomical specimens were dissected via a frontotemporal craniotomy to perform anterior clinoidectomy. Next, 3 typical cases of paraclinoid meningioma were selected to determine the value of using our 6-surface system in tumor resection. RESULTS: Nine points (A-H and T) were proposed to delineate the ACP surface into frontal, temporal, optic nerve, internal carotid artery, cranial nerve III, and optic strut surfaces according to the adjacent tissues. Either intradurally or extradurally, the frontal and temporal surfaces could be identified and drilled into depth, followed by skeletonization of the optic nerve, cranial nerve III, internal carotid artery, and optic strut surfaces. After the residual bone was removed, the ACP was drilled off. In surgery of paraclinoid meningiomas, our 6-surface system provided great benefit in locating the dura, nerves, and vessels, thus, increasing the safety of opening the optic canal and relaxing the oculomotor or optic nerves and allowing for individualized ACP drilling for meningioma removal. CONCLUSIONS: Our 6-surface system adds much anatomical information to the classic Dolenc triangle and can help neurosurgeons, especially junior ones, to increase their understanding of the paraclinoid spatial structure and accomplish individualized surgical procedures with high safety and minimal invasiveness.

Metal Oxide-Supported Metal Catalysts for Electrocatalytic Oxygen Reduction Reaction: Characterization Methods, Modulation Strategies, and Recent Progress.

The sluggish kinetics of the oxygen reduction reaction (ORR) with complex multielectron transfer steps significantly limits the large-scale application of electrochemical energy devices, including metal-air batteries and fuel cells. Recent years witnessed the development of metal oxide-supported metal catalysts (MOSMCs), covering single atoms, clusters, and nanoparticles. As alternatives to conventional carbon-dispersed metal catalysts, MOSMCs are gaining increasing interest due to their unique electronic configuration and potentially high corrosion resistance. By engineering the metal oxide substrate, supported metal, and their interactions, MOSMCs can be facilely modulated. Significant progress has been made in advancing MOSMCs for ORR, and their further development warrants advanced characterization methods to better understand MOSMCs and precise modulation strategies to boost their functionalities. In this regard, a comprehensive review of MOSMCs for ORR is still lacking despite this fast-developing field. To eliminate this gap, advanced characterization methods are introduced for clarifying MOSMCs experimentally and theoretically, discuss critical methods of boosting their intrinsic activities and number of active sites, and systematically overview the status of MOSMCs based on different metal oxide substrates for ORR. By conveying methods, research status, critical challenges, and perspectives, this review will rationally promote the design of MOSMCs for electrochemical energy devices.

Unruptured anterior Inferior cerebellar artery aneurysm following stereotactic irradiation for vestibular schwannoma: Case report and literature review.

Background: The clinical features and therapeutic measures of vestibular schwannoma (VS) radiation-related aneurysm (RRA) have not been well described. We reported the first VS RRA case admitted for acute anterior inferior cerebella artery (AICA) ischemic symptoms. Literature was reviewed to present the research fruits about VS RRAs, and some therapeutic advices were given. Materials and methods: A 54-year-old woman who had undergone GKS 10 years previously for a right VS was admitted to our hospital in 2018 because of sudden onset of severe vertigo and vomiting, accompanied with unsteady gait. During tumor resection, a dissecting aneurysm arose from the main trunk of AICA was encountered accidently within the tumor. The aneurysm was successfully treated with direct clip ligation, sparing the parent vessel. Data about this case were combined with those of other 11 radiation-related AICA aneurysm cases retrieved from the current literature. The following parameters were evaluated: Age, Sex, Diagnostic method, Location of aneurysm, Age of radiotherapy (Years)/Latency, Rupture, x-ray dosage, Type of radiotherapy, History of surgical resection of VS, Aneurysm Type, Morphology, Number, Treatment, Operative complications, Sequela, Outcome. VS RRAs mainly occurred in women (75%) with a median age of 62.5 years and were mainly located on AICA. Ruptured aneurysms accounted for 75.0% of the total cases. This paper reported the first VS case admitted with acute AICA ischemic symptoms. Cases with sacciform-like, irregular and fusiform-shaped aneurysms accounted for 50.0%, 25.0% and 25.0% of the total, respectively. After surgical treatment, 75.0% patients recovered, except for 3 patients who developed new ischemic consequence. Conclusion: Patients should be informed of the risk of RRAs after receiving radiotherapy for VS. In these patients, RRAs should be suspected when subarachnoid hemorrhage or AICA ischemic symptoms occurred. Active intervention should be conducted considering the high instability and bleeding rate of VS RRAs.

P7C3-A20 Attenuates Microglial Inflammation and Brain Injury after ICH through Activating the NAD+/Sirt3 Pathway.

Intracerebral hemorrhage (ICH) is lethal but lacks effective therapies. Nicotinamide adenine dinucleotide (NAD+) is a central metabolite indispensable for a broader range of fundamental intracellular biological functions. Reduction of NAD+ usually occurs after acute brain insults, and supplementation of NAD+ has been proven neuroprotective. P7C3-A20 is a novel compound featuring its ability to facilitate the flux of NAD+. In this study, we sought to determine the potential therapeutic value of P7C3-A20 in ICH. In collagenase-induced ICH mouse models, we found that P7C3-A20 treatment could diminish lesion volume, reduce blood-brain barrier (BBB) damage, mitigate brain edema, attenuate neural apoptosis, and improve neurological outcomes after ICH. Further, RNA sequencing and subsequent experiments revealed that ICH-induced neuroinflammation and microglial proinflammatory activities were significantly suppressed following P7C3-A20 treatment. Mitochondrial damage is an important trigger of inflammatory response. We examined mitochondrial morphology and function and found that P7C3-A20 could attenuate OxyHb-induced impairment of mitochondrial dynamics and functions in vitro. Mechanistically, Sirt3, an NAD+-dependent deacetylase located in mitochondria, was then found to play a vital role in the protection of P7C3-A20 against mitochondrial damage and inflammatory response. In rescue experiments, P7C3-A20 failed to exert those protective effects in microglia-specific Sirt3 conditional knockout (CKO) mice. Finally, preclinical research revealed a correlation between the plasma NAD+ level and the neurological outcome in ICH patients. These results demonstrate that P7C3-A20 is a promising therapeutic agent for neuroinflammatory injury after ICH and exerts protective actions, at least partly, in a Sirt3-dependent manner.

The effect of postoperative early lumbar drainage on delayed fever after cerebellopontine angle tumour surgery: study protocol for a randomized controlled trial.

BACKGROUND: Postoperative fever is one of the common complications in neurosurgery, and intracranial aseptic inflammation and infection are important risk factors. Continuous drainage of cerebrospinal fluid (CSF) via lumbar drainage (LD) is often used in the treatment of postoperative intracranial infection or aseptic inflammation. Compared with the previously reported placement of LD after the onset of meningitis symptoms, we designed this randomized controlled trial (RCT) to evaluate the effectiveness and safety of early drainage (1st day postoperation) of CSF using the preset lumbar cistern to prevent delayed fever (fever occurred after the third day postoperation) or reduce its treatment time after cerebellopontine angle (CPA) tumour surgery. METHODS: Patients suffering from CPA tumours and who underwent resection of the tumour with an intraoperative dura opening time > 4 h are recruited for this study. The study is a 2-arm RCT to compare the early LD group and the no early LD group. Postoperative duration and rate of delayed fever and postoperative length of stay (LOS), as the main outcomes, will be compared in the two groups. DISCUSSION: Here, we present the study design of a prospective RCT to evaluate the safety and efficacy of using preoperative preset LD to treat or reduce postoperative delayed fever. TRIAL REGISTRATION: China Clinical Trial Registry ChiCTR2100049057. Registered on July 20, 2021.

A New Practical Method Based on MRI to Individually Localize the Transverse-Sigmoid Sinus Junction in Retrosigmoid Craniotomy: A Retrospective Before-After Study.

Background: Although the asterion has long been used as a skeletal surface marker of the transverse-sigmoid sinuses junction (TSSJ) point in the retrosigmoid approach, abundant evidence shows that the relationship between asterion and TSSJ point varies greatly. In recent years, new technologies have been developed, such as neuronavigation and three-dimensional volume rendering imaging, that can guide in exposing the TSSJ point individually. However, they are not only expensive but also difficult to apply in emergency surgery. Objective: To introduce a quick, practical, and low-cost new method for locating the TSSJ point precisely. Methods: In this retrospective before-after study, the test group located the TSSJ point with our new method during a 6-month period, while the control group used asterion as a surface landmark to estimate the TSSJ during the preceding 6 months. The primary outcome is the immediate exposure rate of the TSSJ point by the initial burr hole. Results: There were 60 patients in both control and test groups as no significant difference in the general clinical characteristics of both groups were observed. The new three-step method significantly increased the TSSJ exposure rate by initial burr hole compared with the control group (96.67% vs. 53.33%, P = 0.0002). Moreover, the total bone loss and craniotomy duration were significantly reduced by the new method. Incidence of sinus injury (10% vs. 6.6%), post-operation infection (3.33% vs. 3.33%), and CSF leakage (3.33% vs. 0%) were similar. Conclusions: The novel three-step approach accurately locates TSSJ points in retrosigmoid craniotomy, reduces bone defects, saves time, and does not increase the risk of sinus injury, infection, and CSF leakage.

Endoscopic endonasal resection of two rare cases of hemangiopericytomas invading the cavernous sinus and literature review.

Hemangiopericytomas (HPCs) invading the cavernous sinus (CS) are extremely rare invasive tumors that have a great propensity for local recurrence. To date, only eight cases have been reported in the literature. Owing to the abundant vascular supply of HPCs, intracavernous bleeding and important blood vessels and nerves passing through the CS, it is very difficult and challenging for neurosurgeons to completely resect HPCs. Here, we report two cases of HPCs invading the CS and introduce their clinical manifestations, imaging findings, surgical approaches and histopathological features in detail. We have implemented the surgery by the endoscopic transpterygoid transcavernous approach (ETPTCa) for the two patients, and one patient has undergone gross total resection (GTR) and another has undergone subtotal resection (STR) and postoperative stereotactic radiosurgery (SRS). The ETPTCa may serve as a viable option to facilitate HPCs resection. Radiotherapy is helpful in prolonging progression-free survival (PFS) following STR of the tumor.

Postoperative Early Lumbar Drainage Can Reduce the Duration of Fever or Infection in Patients with Complicated Intracranial Tumors after a Long Operation Time.

Background: Intracranial fever or infection is one of the common complications after craniotomy, especially for complicated intracranial tumors such as deep skull base tumors. Objective: We used early cerebrospinal fluid (CSF) drainage with a preplaced lumbar drainage (LD) tube after surgery and observed whether this procedure could reduce the rate and duration of fever or infection. Material and Methods: The authors conducted a retrospective study of 142 patients who underwent complicated intracranial tumor surgery with no less than four hours of dural opening at the Center of Neurosurgery of Tangdu Hospital. The LD group underwent preoperative LD placement, intraoperative CSF release and postoperative continuous drainage, but the control group received routine craniotomy without preoperative LD. The primary outcomes included the rate, duration, and hospital length of stay (LOS) for patients with fever or infection after surgery, as compared between the two groups. The second outcome included complications related to LD and the rate of postoperative CSF leakage. Results: There were 22 patients in the LD group and 23 patients in the control group who presented with delayed fever, which was supposed to be caused by intracranial infection or aseptic inflammation. The median duration of delayed fever in the LD group was obviously lower than that in the control group (7.762 ± 3.129 days vs 11.73 ± 5.239 days), and there was a statistically significant difference (P = 0.0046). In addition, there was a significant reduction in the median postoperative LOS (12 [8,10,15,21] days in the LD group vs 15 [9,13,20,28] days in the controls). Moreover, there was no significant difference in complications related to LD between the two groups. Three patients with brain herniation were observed in the LD group compared with one patient in the control group. All four patients had contemporary mild-to-moderate neurologic disorders after surgery or conservative treatment. Additionally, the rate of CSF leakage in the LD group was 5.41% (4/74), which was lower than that in the control group (8/68, [11.76%]), although there was no significant difference (P = 0.174). Conclusions: For patients receiving complicated intracranial lesions following a long operation time, postoperative early LD was beneficial for the treatment of patients with fever or infection. It not only reduced the duration of infection or fever in postoperative patients but also decreased the postoperative LOS. We should minimize the complications related to LD by careful and standardized LD and management processes, and ensure the effectiveness and safety of this treatment.

Surgical Strategies and Outcomes for Intracranial Chondromas: A Retrospective Study of 17 Cases and Systematic Review.

Objective: To improve the diagnosis and treatment of intracranial chondromas (ICDs) by discussing the clinical manifestations and imaging characteristics of ICDs, as well as surgical methods and treatment strategies. Methods: We retrospectively analyzed 17 patients diagnosed with ICDs who underwent microsurgery or endoscopic transsphenoidal surgery at the Tangdu Hospital of Air Force Military Medical University and the Mianyang Central Hospital from January 2010 to November 2021. Clinical manifestations, imaging examinations, surgical treatments, and prognosis of these patients were analyzed. Results: ICDs had often been misdiagnosed as craniopharyngioma, chordoma, schwannoma, cavernous hemangioma, pituitary adenoma, and meningioma before surgery. Of the 17 cases, gross total resection (GTR) was performed in 10 cases, subtotal resection (STR) in 5, and partial resection in 2. GTR of tumor was achieved in eight cases via the endoscopic endonasal transsphenoidal approach (EETA) or the extended endoscopic endonasal transsphenoidal approach (EEETA), and the remaining patients underwent craniotomies. Clinical symptoms were assessed 1 week after surgery, 10 cases were relieved at varying degrees, and four cases had no improvement. Postoperative complications included right-limb hemiparesis, diplopia, eyelid ptosis, pulmonary infection, subcutaneous hydrops, cerebrospinal-fluid leakage (CSFL), and intracranial infection (ICI). One patient received gamma knife treatment at 3 months after surgery, two patients died due to tumor progression, and the remaining patients had no tumor recurrence. Conclusions: ICDs lack typical imaging features and are often misdiagnosed. The EETA or EEETA helps improve the surgical outcomes and GTR rates of ICDs at different sites.

Application of Subperineural Resection Technique in Vestibular Schwannomas: Surgical Efficacy and Outcomes in 124 patients.

Objective: We aimed to explore the application and prospects of the subperineural resection technique for tumor separation and removal under the perineurium during surgery for vestibular schwannomas (VSs). Methods: This study retrospectively analyzed 124 patients with VSs who underwent surgery via a retrosigmoid approach from July 2015 to October 2020 in the Department of Neurosurgery, Tangdu Hospital, Air Force Military Medical University. The data will be discussed with regard to the following aspects: clinical features, surgical strategies, tumor resection extent, facial-acoustic function preservation, and postoperative complications. Results: Gross total resection (GTR) of the tumor was achieved in 104 patients, with a GTR rate of 83.9%, and subtotal resection (STR) of the tumor was achieved in 20 patients. There was no significant difference in facial and acoustic nerve functional preservation between GTR and STR, as well as in tumor resection between solid and cystic tumors. The retention rate reached 97.6% in terms of complete anatomical facial nerve preservation. Facial nerve function was assessed using the House-Brackmann (HB) grading score. Consequently, HB grades of I-II, III-IV, and V-VI were determined for 96 (77.4%), 25 (20.2%), and 3 (2.4%) cases, respectively, 1 week postoperatively and accounted for 110 cases (88.7%), 13 cases (10.5%), and 1 case (0.8%), respectively, at 6 months. Fifteen of 35 (42.9%) patients with serviceable hearing before the operation still had serviceable hearing at 6 months postoperatively. There were 5 cases of cerebellar or brainstem bleeding after the operation, and one patient died. Multivariate logistic regression analysis showed that older age (≥60 years, p = 0.011), large tumor (>3 cm, p = 0.004), and cystic tumor (p = 0.046) were independent risk factors associated with the extent of adhesion between the tumor and the brainstem and facial-acoustic nerve. Conclusion: We successfully applied the subperineural resection technique to a large series of patients with VSs and achieved satisfactory results. Accurate identification of the perineurium and subperineural resection of the tumor can effectively reduce the disturbance of the facial-acoustic nerve during the operation and provide an intuitive basis for judging the tumor boundary. The subperineural resection technique may be conducive to improving the rate of total tumor resection and facial-acoustic nerve functional preservation in the surgical treatment of VSs.

Wearable Motion Smartsensors Self-Powered by Core-Shell Au@Pt Methanol Fuel Cells.

A wearable self-powered sensor is a promising frontier in recent flexible electronic devices. In this work, a wearable fuel cell (FC)-type self-powering motion smartsensor has been fabricated, particularly in choosing methanol vapor as a target fuel for the first time. The core-shell structure of Pt@Au/N-rGO and the porous carbon network act as methanol oxidation and oxygen reduction reaction catalysts, with a highly conductive alkaline hydrogel as a solid-state electrolyte. As a result, a wearable FC for a self-powered sensing system demonstrates excellent sensing performance toward 2-20% (v/v) methanol vapor with a maximum power density of 2.26 µW cm-1 and good mechanical behaviors during the bending or twisting process. Significantly, this wearable FC device could power strain sensors of human motion, and real-time signals can be easily remotely detected via a cellphone. With attractive biocompatibility and self-powering performance, wearable FCs for a self-powering system would provide new opportunities for next-generation flexible smartsensing electronics and initiate a developed self-powering platform in future practical application of wearable smart monitoring.

Reconstruction of a Context-Specific Model Based on Genome-Scale Metabolic Simulation for Identification of Prochloraz Resistance Mechanisms in Penicillium digitatum.

Penicillium digitatum is the most destructive postharvest pathogen of citrus fruits, causing substantial economic losses. Prochloraz-resistant strains have emerged due to overuse of imidazole fungicides in agriculture. To study the prochloraz resistance mechanisms at the system level, a genome-scale metabolic model (GEM, iPD1512) of P. digitatum was reconstructed and constrained based on context-specific transcriptome data of the prochloraz-resistant strain, PdF6, from our previous work, a newly sequenced, context-specific transcriptome result of the major facilitator superfamily transporter-encoding gene mfs2 knockout mutant PdF6Δmfs2, and experimentally derived growth rate data. Through the model, iPD1512, the processes of prochloraz resistance in P. digitatum were well simulated. In detail, the growth rates of both wild-type and mutant P. digitatum under different prochloraz concentrations were simulated using constraint-based reconstruction and analysis. The growth rates of the mutant strains (sterol regulatory element-binding protein-encoding gene sreA knockout mutant PdF6ΔsreA and PdF6Δmfs2) were calculated and confirmed to be consistent with the simulation results. Furthermore, correlations between genes and prochloraz resistance were predicted and showed a great difference when compared with correlation results based on p-values from the hypothesis testing used by comparative transcriptomics. To sum up, in contrast to traditional transcriptome analysis, the GEM provides a systemic and dynamic drug resistance mechanism, which might help to detect some key upstream regulatory genes, but with small expression changes, and might provide more efficient targets to control prochloraz-resistant P. digitatum.

Aminoalcohol-Induced Activation of Organophosphorus Hydrolase (OPH) towards Diisopropylfluorophosphate (DFP).

Aminoalcohols have been addressed as activating buffers for alkaline phosphatase. However, there is no record on the buffer activation regarding organophosphorus hydrolase (OPH). Here we reported the activating effects of aminoalcohols on OPH-catalyzed hydrolysis of diisopropylfluorophosphate (DFP), an analog molecule of G-type warfare agents. The kinetic parametors kcat, Vmax and kcat/Km in the OPH reaction were remarkably increased in the buffers (pH 8.0, 25°C) containing aminoalcohols with C2 between nitrogen (N) and oxygen (O) in their structures, including triethanolamine (TEA), diethanolamine, monoethanolamine, 1-amino-2-propanol, 2-amino-2-methyl-1-propanol, and triisopropanolamine. In contrast, much lower or no rate-enhancing effects were observed in the adding of amines, alcohols, amine/alcohol mixtures, or 3-amino-1-propanol (C3 between N and O). The 300 mM TEA further increased DFP-degrading activities of OPH mutants F132Y and L140Y, the previously reported OPH mutants with desirable activities towards DFP. However, the treatment of ethylenediaminetetraacetate (EDTA) markedly abolished the TEA-induced activation of OPH. The product fluoride effectively inhibited OPH-catalyzed hydrolysis of DFP by a linear mixed inhibition (inhibition constant Ki ~ 3.21 mM), which was partially released by TEA adding at initial or later reaction stage. The obtained results indicate the activation of OPH by aminoalcohol buffers could be attributed to the reduction of fluoride inhibition, which would be beneficial to the hydrolase-based detoxification of organophosphofluoridate.

Efficacy and safety of stenting for elderly patients with severe and symptomatic carotid artery stenosis: a critical meta-analysis of randomized controlled trials.

OBJECTIVE: To investigate both short-term and long-term therapeutic efficacy and safety of carotid artery stenting (CAS) and carotid artery endarterectomy (CEA) for elderly patients with severe and symptomatic carotid artery stenosis. METHODS: PubMed, EMBASE, Cochrane Library, Clinical Trials Register Centers, and Google Scholar were comprehensively searched. After identifying relevant randomized controlled trials, methodological quality was assessed by using Cochrane tools of bias assessment. Meta-analysis was performed by RevMan software, and subgroup analyses according to different follow-up periods were also conducted. RESULTS: Sixteen articles of nine randomized controlled trials containing 6,984 patients were included. Compared with CEA, CAS was associated with high risks of stroke during periprocedural 30 days (risk ratio [RR]=1.47, 95% confidence interval [CI]: 1.15-1.88), 48 months (RR=1.37, 95% CI: 1.11-1.70), and >48 months (RR=1.76, 95% CI: 1.34-2.31). There was no significant difference in the aspects of death, disabling stroke, or death at any time between the groups. For other periprocedural complications, CAS decreased the risk of myocardial infarction (RR=0.44, 95% CI: 0.26-0.75), cranial nerve palsy (RR=0.09, 95% CI: 0.04-0.22) and hematoma (RR=0.31, 95% CI: 0.14-0.68) compared with CEA, while it increased the risk of bradycardia or hypotension (RR=8.45, 95% CI 2.91-24.58). CONCLUSION: Compared with CEA, CAS reduced hematoma, periprocedural myocardial infarction, and cranial nerve palsy, while it was associated with higher risks of both short-term and long-term nondisabling stroke. And they seemed to be equivalent in other outcome measures. As regards to its minimal invasion, it should be applied only in specific patients.

Separation and purification of γ-aminobutyric acid from fermentation broth by flocculation and chromatographic methodologies.

To date, the multifunctional γ-aminobutyric acid (GABA) is mainly produced by microbial fermentation in industry. The purpose of this study was to find an effective method for separation and purification of 31.2 g/L initial GABA from the fermentation broth of Enterococcus raffinosus TCCC11660. To remove the impurities from fermentation broth, flocculation pretreatment using chitosan and sodium alginate was first implemented to facilitate subsequent filtration. Ultrafiltration followed two discontinuous diafiltration steps to effectively remove proteins and macromolecular pigments, and the resulting permeate was further decolored by DA201-CII resin at a high decoloration ratio and GABA recovery. Subsequently, ion exchange chromatography (IEC) with Amberlite 200C resin and gradient elution were applied for GABA separation from glutamate and arginine. Finally, GABA crystals of 99.1% purity were prepared via warm ethanol precipitation twice. Overall, our results reveal that the successive process including flocculation, filtration, ultrafiltration, decoloration, IEC, and crystallization is promising for scale-up GABA extraction from fermentation broth.

A genetic variation map for chicken with 2.8 million single-nucleotide polymorphisms.

We describe a genetic variation map for the chicken genome containing 2.8 million single-nucleotide polymorphisms (SNPs). This map is based on a comparison of the sequences of three domestic chicken breeds (a broiler, a layer and a Chinese silkie) with that of their wild ancestor, red jungle fowl. Subsequent experiments indicate that at least 90% of the variant sites are true SNPs, and at least 70% are common SNPs that segregate in many domestic breeds. Mean nucleotide diversity is about five SNPs per kilobase for almost every possible comparison between red jungle fowl and domestic lines, between two different domestic lines, and within domestic lines--in contrast to the notion that domestic animals are highly inbred relative to their wild ancestors. In fact, most of the SNPs originated before domestication, and there is little evidence of selective sweeps for adaptive alleles on length scales greater than 100 kilobases.