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Purpose: To compare vertebroplasty (VP) and kyphoplasty (KP) with a titanium implantable vertebral augmentation device (TIVAD) in symptomatic subsequent vertebral compression fracture (SVCF) incidence among osteoporotic vertebral compression fracture (OVCF) patients stratified by age and sex., Methods: This retrospective cohort study involved OVCF patients aged ≥ 50, who underwent KP with TIVAD or VP in our hospital from 2014 to 2019. Subgroup analysis was conducted to evaluate the efficacy of KP with TIVAD and VP in patients stratified by age and sex., Results: The study included 472 patients (VP group: 303; TIVAD group: 169). SVCF incidence rates were 15.2% for VP group and 14.8% for TIVAD group (P = 0.87). In subgroup analysis, TIVAD group showed significantly lower SVCF incidence than VP group in women aged 50-70 (2.1% vs 14.3%; P = 0.03) and had significantly higher SVCF incidence than VP group in women aged > 70 (24.2% vs 13.1%; P = 0.02). In men, adjacent SVCF incidence was significantly lower in TIVAD group than VP group (0% vs 14.1%; P = 0.03)., Conclusion: Compared to VP, TIVAD is associated with lower symptomatic SVCF rate in men and younger women aged 50-70 but not in older women aged > 70. Age and gender may influence SVCF incidence., Level of Evidence: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding., Competing Interests: Declarations. Conflict of interest: The authors have no conflict of interest and financial support to disclose., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background/Objectives: Spinal conditions, such as fractures and herniated intervertebral discs (HIVDs), are often challenging to diagnose due to overlapping clinical symptoms and the difficulty in assessing their functional impact. Accurate differentiation between these conditions is crucial for effective treatment, particularly in the context of preoperative anesthesia evaluation, where understanding the underlying condition can influence anesthesia planning and pain management. Methods and Materials: This study presents a Support Vector Machine (SVM) model designed to distinguish between spinal fractures and HIVDs using key clinical predictors, including age, gender, preoperative Visual Analog Scale (VAS) pain scores, and the number of spinal fractures. A retrospective analysis was conducted on a dataset of 199 patients diagnosed with these conditions. The SVM model, using a radial basis function (RBF) kernel, classified the conditions based on the selected predictors. Model performance was evaluated using precision, recall, accuracy, and the Kappa index, with Leave-One-Out (LOO) cross-validation applied to ensure robust results. Results: The SVM model achieved a precision of 92.1% for fracture cases and 91.2% for HIVDs, with recall rates of 98.1% for fractures and 70.5% for HIVDs. The overall accuracy was 92%, and the Kappa index was 0.76, indicating substantial agreement. The analysis revealed that age and VAS pain scores were the most critical predictors for accurately diagnosing these conditions. Conclusions: These results highlight the potential of the SVM model with an RBF kernel to reliably differentiate between spinal fractures and HIVDs using routine clinical data. Future work could enhance model performance by incorporating additional clinical parameters relevant to preoperative anesthesia evaluation.

Scorpions are an ancient and charismatic group of arthropods with medical importance, but a high-quality reference genome for this group is still lacking. Here we perform whole-genome sequencing of Mesobuthus przewalskii, a desert scorpion endemic to the Taklimakan Desert. We combine PacBio HiFi sequencing and Hi-C chromosome conformation capturing to generate chromosomal-level, haplotype-resolved, and fully annotated genome assembly for this medically important scorpion. The assembly consists of two haplotypes (1052.01 Mbp and 1055.19 Mbp, respectively) reaching chromosome-level contiguity and >98% BUSCO completeness. Sequences were anchored in 13 chromosomes with a contig N50 of 34.44 Mbp and scaffold N50 of 81.43 Mbp. Several key genome features and the mitochondrial genome assembly were also provided. This genome represents the fifth but the most complete assembly for the order Scorpiones., (© The Author(s) 2024. Published by Oxford University Press on behalf of The American Genetic Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

During the COVID-19 pandemic, the use of lateral flow assays (LFAs) expanded significantly, offering testing beyond traditional health care. Their appeal lies in the ease of use, affordability, and quick results. However, LFAs often have lower sensitivity and specificity compared with ELISA and PCR tests. Efforts to improve LFAs have increased detection times and complexity, limiting their use in large-scale point-of-care settings. To address this, we propose a novel approach using probes that generate multiple signals to enhance the sensitivity and selectivity. This concept also allows multiplexed LFAs to detect multiple analytes concurrently. We developed a trimodal probe that integrates fluorescence, color, and magnetism into a single nanohybrid. The strong plasmonic absorption and high fluorescence of Au nanoparticles and polymer dots enable qualitative and semiquantitative diagnosis, while the magnetic signal facilitates accurate quantitative measurements. As proof-of-concept targets, we selected CYFRA 21-1 and CA15-3, biomarkers for lung and breast cancer, respectively. This trimodal LFA demonstrated a remarkable detection limit of 0.26 ng/mL for CYFRA 21-1 and 2.8 U/mL for CA15-3. To the best of our knowledge, this is the first platform of a trimodal LFA with multiplexing ability. The platform's accuracy and reliability were validated using clinical serum samples, showing excellent consistency with electrochemiluminescence immunoassay results. This universal concept can be applied to other targets, paving the way for the next-generation LFAs.

Hydrogen sulfide (H 2 S) is one of the three most crucial gaseous messengers in the body. The discovery of H 2 S donors, coupled with its endogenous synthesis capability, has sparked hope for the treatment of hematologic malignancies. In the last decade, the investigation into the impact of H 2 S has expanded, particularly within the fields of cardiovascular function, inflammation, infection, and neuromodulation. Hematologic malignancies refer to a diverse group of cancers originating from abnormal proliferation and differentiation of blood-forming cells, including leukemia, lymphoma, and myeloma. In this review, we delve deeply into the complex interrelation between H 2 S and hematologic malignancies. In addition, we comprehensively elucidate the intricate molecular mechanisms by which both H 2 S and its donors intricately modulate the progression of tumor growth. Furthermore, we systematically examine their impact on pivotal aspects, encompassing the proliferation, invasion, and migration capacities of hematologic malignancies. Therefore, this review may contribute novel insights to our understanding of the prospective therapeutic significance of H 2 S and its donors within the realm of hematologic malignancies., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

3-dB couplers, which are commonly used in photonic integrated circuits for on-chip information processing, precision measurement, and quantum computing, face challenges in achieving robust performance due to their limited 3-dB bandwidths and sensitivity to fabrication errors. To address this, we introduce topological physics to nanophotonics, developing a framework for topological 3-dB couplers. These couplers exhibit broad working wavelength range and robustness against fabrication dimensional errors. By leveraging valley-Hall topology and mirror symmetry, the photonic-crystal-slab couplers achieve ideal 3-dB splitting characterized by a wavelength-insensitive scattering matrix. Tolerance analysis confirms the superiority on broad bandwidth of 48 nm and robust splitting against dimensional errors of 20 nm. We further propose a topological interferometer for on-chip distance measurement, which also exhibits robustness against dimensional errors. This extension of topological principles to the fields of interferometers, may open up new possibilities for constructing robust wavelength division multiplexing, temperature-drift-insensitive sensing, and optical coherence tomography applications., (© 2024. The Author(s).)

Background: Spontaneous intracerebral hemorrhage (ICH) accounts for up to 20% of all strokes and results in 40% mortality at 30 days. Although conservative medical management is still the standard treatment for ICH patients with small hematoma, patients with residual hematoma ≤15 mL after surgery are associated with better functional outcomes and survival rates. This study reported our clinical experience with using Robotic Stereotactic Assistance (ROSA) as a safe and effective approach for stereotactic ICH aspiration and intra-clot catheter placement., Methods: A retrospective analysis was conducted of patients with spontaneous ICH who underwent ROSA-guided ICH aspiration surgery. ROSA-guided ICH surgical techniques, an aspiration and intra-clot catheter placement protocol, and a specific operative workflow (pre-operative protocol, intraoperative procedure and postoperative management) were employed to aspirate ICH using the ROSA One Brain, and appropriate follow-up care was provided., Results: From September 14, 2021 to May 4, 2022, a total of 7 patients were included in the study. Based on our workflow design, ROSA-guided stereotactic ICH aspiration effectively aspirated more than 50% of hematoma volume (or more than 30 mL for massive hematomas), thereby reducing the residual hematoma to less than 15 mL. The mean operative time of entire surgical procedure was 1.3 ± 0.3 h, with very little perioperative blood loss and no perioperative complications. No patients required catheter replacement and all patients' functional status improved., Conclusions: Within our clinical practice ROSA-guided ICH aspiration, using our established protocol and workflow, was safe and effective for reducing hematoma volume, with positive functional outcomes., Competing Interests: Declaration of competing interest Dr. Abel Huang holds ownership in ClearMind, a company focused on developing minimally invasive devices for treating intracerebral hemorrhage (ICH). While ClearMind has developed various ICH treatment devices, it is pertinent to clarify that none of their equipment was utilized in our ROSA-guided ICH aspiration procedure detailed in this study. Thus, there exists no direct conflict of interest regarding the equipment employed in this specific investigation. In addition, the remaining authors declare no conflicts of interest., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

This study aimed to translate and validate the traditional Chinese version of the Community Integration Questionnaire-Revised (TC-CIQ-R) in patients with traumatic brain injury (TBI). We included participants aged ≥20 years and diagnosed as having TBI for ≥6 months from neurosurgical clinics. The 18-item TC-CIQ-R, Participation Measure - 3 Domains, 4 Dimensions (PM-3D4D), Extended Glasgow Outcome Scale (GOSE), and Taiwanese Quality of Life After Brain Injury (TQOLIBRI) were completed. The sample included 180 TBI survivors (54% male, mean age 47 years) of whom 87% sustained a mild TBI. Exploratory factor analysis extracted four factors - home integration, social integration, productivity, and electronic social networking - which explained 63.03% of the variation, after discarding the tenth item with a factor loading of 0.25. For criterion-related validity, the TC-CIQ-R was significantly correlated with the PM-3D4D; convergent validity was exhibited by demonstrating the associations between the TC-CIQ-R and TQOLIBRI. Known-group validity testing revealed significant differences in the subdomain and total scores of the TC-CIQ-R between participants with a mean GOSE score of ≤6 and >7 (all P  < 0.001). The TC-CIQ-R exhibited acceptable Cronbach's α values (0.68-0.88). We suggest the 17-item TC-CIQ-R as a valid tool for rehabilitation professionals, useful for both clinical practice and research in assessing community integration levels following TBI., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Ion implanters have extensively been employed to simulate the irradiation effects of neutrons on relevant nuclear materials. In this study, a 50 kV hydrogen-helium mixed ion beam implanter was developed to generate H2+ and He+ ion beams, with a beam current of 20 µA, while keeping the impurity ion content below 2%. The ions are generated by an antenna-type 2.45 GHz electron cyclotron resonance ion source, and the hydrogen-to-helium ion beam ratio was controlled using two gas mass flow controllers to ensure long time stability of the beam current. As a result, the H2+/He+ ratio, beam size, and homogeneity of the beam spot can be maintained at a stable level. The beam line consisted of four Wien filters, a movable dual-slit plate, and an accelerator tube. The experimental results demonstrated successful transport of more than 20 µA of H2+ and He+ ion beams onto the target, with a beam axis deviation of less than 0.5 mm., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Social interaction enables the smooth progression of our daily lives. Mounting evidence from recent hyperscanning neuroimaging studies indicates that key components of social behavior can be evaluated using inter-brain oscillations and connectivity. However, mapping out inter-brain networks and developing neurocognitive theories that explain how humans co-create and share information during social interaction remains challenging. In this study, we developed a jigsaw puzzle-solving game with hyperscanning electroencephalography (EEG) signals recorded to investigate inter-brain activities during social interactions involving cooperation and competition. Participants were recruited and paired into dyads to participate in the multiplayer jigsaw puzzle game with 32-channel EEG signals recorded. The corresponding event-related potentials (ERPs), brain oscillations, and inter-brain functional connectivity were analyzed. The results showed different ERP morphologies of P3 patterns in competitive and cooperative contexts, and brain oscillations in the low-frequency band may be an indicator of social cognitive activities. Furthermore, increased inter-brain functional connectivity in the delta, theta, alpha, and beta frequency bands was observed in the competition mode compared to the cooperation mode. By presenting comparable and valid hyperscanning EEG results alongside those of previous studies using traditional paradigms, this study demonstrates the potential of utilizing hyperscanning techniques in real-life game-playing scenarios to quantitatively assess social cognitive interactions involving cooperation and competition. Our approach offers a promising platform with potential applications in the flexible assessment of psychiatric disorders related to social functioning.

Previous studies have reported a role of alterations in the brain's inhibitory control mechanism in addiction. Mounting evidence from neuroimaging studies indicates that its key components can be evaluated with brain oscillations and connectivity during inhibitory control. In this study, we developed an internet-related stop-signal task with electroencephalography (EEG) signal recorded to investigate inhibitory control. Healthy controls and participants with Internet addiction were recruited to participate in the internet-related stop-signal task with 19-channel EEG signal recording, and the corresponding event-related potentials and spectral perturbations were analyzed. Brain effective connections were also evaluated using direct directed transfer function. The results showed that, relative to the healthy controls, participants with Internet addiction had increased Stop-P3 during inhibitory control, suggesting that they have an altered neural mechanism in impulsive control. Furthermore, participants with Internet addiction showed increased low-frequency synchronization and decreased alpha and beta desynchronization in the middle and right frontal regions compared to healthy controls. Aberrant brain effective connectivity was also observed, with increased occipital-parietal and intra-occipital connections, as well as decreased frontal-paracentral connection in participants with Internet addiction. These results suggest that physiological signals are essential in future implementations of cognitive assessment of Internet addiction to further investigate the underlying mechanisms and effective biomarkers.

This study aims to investigate the factors that influence the willingness of highway construction enterprises in China to adopt intelligent construction technology. Based on the existing literature, a TOSE framework was proposed, and four dimensions and 15 hypothesized influencing factors were identified through expert interviews. By using a combination of PLS-SEM and ANN, 513 survey data were analyzed to determine the linear and non-linear relationships of the influencing factors on the willingness to adopt. The results showed that all 14 hypothesized factors had varying degrees of positive or negative effects on the willingness to adopt, except for organizational culture, which was found to have no significant impact. Specifically, technology cost was found to be the most influential negative factor, while market demand and organizational structure were the most influential positive factors. The findings of this study have important reference value for decision makers and participants in highway construction enterprises, as well as other construction companies when considering the adoption of smart construction technologies. The originality of this research lies in the novel application of the TOSE framework to investigate smart construction technology adoption, and the combined use of PLS-SEM and ANN to examine both linear and nonlinear relationships between variables for the first time., (© 2023. The Author(s).)

The development of the Internet has changed people's lives and has resulted in a new type of addictive behavior. In the past decade, Internet game addiction has been identified as a mental illness. Considering internet game addiction as the only cause of mental illness is limited in its view, as internet games, social platforms and other internet multimedia are also widely used. Thus, other internet-related behaviors, that maybe addictive, should also be included. Previous neuroimaging studies have reported a role of alteration in brain's inhibitory control mechanism in addiction. However, the results are still diverse with inconsistent findings. In this study, we used an Internet-related stop signal task with EEG signals recorded to study the relationship between internet addiction through brain oscillations and functional connectivity. We also compared the differences in the brain connectivity between addicted and non-addicted participants using phase lag index. We found that the brain connectivity in participants addicted to the internet is significantly greater than that of nonaddicted users.Clinical Relevance- In this study, we assessed brain functional networks of participants with Internet Gaming Disorder and internet addiction.

Background: The use of nanodiamonds (NDs) and fluorescent nanodiamonds (FNDs) as nonallergenic biocompatible additives in incomplete Freund's adjuvant (IFA) to elicit immune responses in vivo was investigated. Methods: C57BL/6 mice were immunized with chicken egg ovalbumin (OVA) in IFA and also OVA-conjugated NDs (or OVA-conjugated FNDs) in IFA to produce antibodies. OVA-expressing E.G7 lymphoma cells and OVA-negative EL4 cells were inoculated in mice to induce tumor formation. Results: The new formulation significantly enhanced immune responses and thus disease resistance. It exhibited specific therapeutic activities, effectively inhibiting the growth of E.G7 tumor cells in mice over 35 days. Conclusion: The high biocompatibility and multiple functionalities of NDs/FNDs render them applicable as active and trackable vaccine adjuvants and antitumor agents.

Autism spectrum disorder requires early detection and treatment. Thus, we developed a method to obtain reliable neurophysiological biomarkers to assist in diagnosing autism. This method includes a simple but typical jigsaw puzzle that allows participants to play and interact with each other. While playing this game, brain signals of the participants were observed and analyzed. The patients with autism were found to have differences in the time range of some event-related potential, such as P300 and N400. Altered patterns of function connectivity were also found in delta frequency bands in the patients while interacting with other people. Working around patients' capabilities, the jigsaw puzzle game was designed as easy to complete; this caused fewer mismatch conditions. The result suggested that these patterns are promising neurophysiological biomarker to assist doctors in social cognitive assessment in autism.Clinical Relevance-This study demonstrated the possibility of using hyperscanning technique for social cognitive assessment of autism spectrum disorder.

Background: Cognitive impairment is common in patients with traumatic brain injury (TBI). Studies that have examined the effectiveness of neurofeedback (NFB) on cognitive function following TBI have had poor study designs and small sample sizes., Objectives: This randomized controlled trial assessed the effects of low-resolution tomography Z-score NFB (LZNFB) and theta/beta NFB on cognitive impairment, return to productive activity, and quality of life in patients with TBI., Methods: We randomly assigned 87 patients with TBI with cognitive impairment to LZNFB, theta/beta NFB, or usual care (UC) groups. Patients in both NFB groups received weekly 60-minute treatment for 10 weeks, and those in the control group received UC and telephone interviews for 10 weeks. The primary outcome was cognitive function as measured by performance on cognitive tasks; the secondary outcomes included productive activity and quality of life based on the Community Integration Questionnaire-revised (CIQ-R) and the Quality of Life after Brain Injury (QOLIBRI), respectively, at baseline and immediately after the last intervention., Results: The LZNFB group exhibited significantly greater improvements in immediate recall, delayed recall, recognition memory, and selective attention compared with the UC group; the theta/beta NFB group exhibited improvements in only immediate memory and selective attention ( P < .05). The total CIQ-R scores of the LZNFB group after treatment were significantly improved than those of the UC group were., Conclusion: Consecutive LZNFB achieved therapeutic effects in memory, attention, and productive activity, whereas theta/beta NFB improved memory and attention in patients with TBI.This trial was prospectively registered at ClinicalTrial.gov (registration number: NCT03515317; https://clinicaltrials.gov/ct2/show/NCT03515317).

Glioblastoma multiforme (GBM) is a highly heterogeneous disease with a mesenchymal subtype tending to exhibit more aggressive and multitherapy-resistant features. Glioblastoma stem-cells derived from mesenchymal cells are reliant on iron supply, accumulated with high reactive oxygen species (ROS), and susceptible to ferroptosis. Temozolomide (TMZ) treatment is the mainstay drug for GBM despite the rapid development of resistance in mesenchymal GBM. The main interconnection between mesenchymal features, TMZ resistance, and ferroptosis are poorly understood. Herein, we demonstrated that a subunit of NADPH oxidase, CYBB, orchestrated mesenchymal shift and promoted TMZ resistance by modulating the anti-ferroptosis circuitry Nrf2/SOD2 axis. Public transcriptomic data re-analysis found that CYBB and SOD2 were highly upregulated in the mesenchymal subtype of GBM. Accordingly, our GBM cohort confirmed a high expression of CYBB in the GBM tumor and was associated with mesenchymal features and poor clinical outcome. An in vitro study demonstrated that TMZ-resistant GBM cells displayed mesenchymal and stemness features while remaining resilient to erastin-mediated ferroptosis by activating the CYBB/Nrf2/SOD2 axis. The CYBB maintained a high ROS state to sustain the mesenchymal phenotype, TMZ resistance, and reduced erastin sensitivity. Mechanistically, CYBB interacted with Nrf2 and consequently regulated SOD2 transcription. Compensatory antioxidant SOD2 essentially protected against the deleterious effect of high ROS while attenuating ferroptosis in TMZ-resistant cells. An animal study highlighted the protective role of SOD2 to mitigate erastin-triggered ferroptosis and tolerate oxidative stress burden in mice harboring TMZ-resistant GBM cell xenografts. Therefore, CYBB captured ferroptosis resilience in mesenchymal GBM. The downstream compensatory activity of CYBB via the Nrf2/SOD2 axis is exploitable through erastin-induced ferroptosis to overcome TMZ resistance.

Proinflammatory cytokines, reactive oxygen species and imbalance of neurotransmitters are involved in the pathophysiology of angiotensin II-induced hypertension. The hypothalamic paraventricular nucleus (PVN) plays a vital role in hypertension. Evidences show that microglia are activated and release proinflammatory cytokines in angiocardiopathy. We hypothesized that angiotensin II induces PVN microglial activation, and the activated PVN microglia release proinflammatory cytokines and cause oxidative stress through nuclear factor-kappa B (NF-κB) pathway, which contributes to sympathetic overactivity and hypertension. Male Sprague-Dawley rats (weight 275-300 g) were infused with angiotensin II to induce hypertension. Then, rats were treated with bilateral PVN infusion of microglial activation inhibitor minocycline, NF-κB activation inhibitor pyrrolidine dithiocarbamate or vehicle for 4 weeks. When compared to control groups, angiotensin II-induced hypertensive rats had higher mean arterial pressure, PVN proinflammatory cytokines, and imbalance of neurotransmitters, accompanied with PVN activated microglia. These rats also had more PVN gp91 phox (source of reactive oxygen species production), and NF-κB p65. Bilateral PVN infusion of minocycline or pyrrolidine dithiocarbamate partly or completely ameliorated these changes. This study indicates that angiotensin II-induced hypertensive rats have more activated microglia in PVN, and activated PVN microglia release proinflammatory cytokines and result in oxidative stress, which contributes to sympathoexcitation and hypertensive response. Suppression of activated PVN microglia by minocycline or pyrrolidine dithiocarbamate attenuates inflammation and oxidative stress, and improves angiotensin II-induced hypertension, which indicates that activated microglia promote hypertension through activated NF-κB. The findings may offer hypertension new strategies.

As an indigenous breed, the Tibetan chicken is found in highland regions and shows physiological adaptations to high altitude; however, the genetic changes that determine these adaptations remain elusive. We assumed that the microevolution of the Tibetan chicken occurred from lowland to highland regions with a continuous elevation range. In this study, we analyzed the genome of 188 chickens from lowland areas to the high-altitude regions of the Tibetan plateau with four altitudinal levels. Phylogenetic analysis revealed that Tibetan chickens are significantly different from other altitude chicken populations. Reconstruction of the demographic history showed that the migration and admixture events of the Tibetan chicken occurred at different times. The genome of the Tibetan chicken was also used to analyze positive selection pressure that is associated with high-altitude adaptation, revealing the well-known candidate gene that participates in oxygen binding ( HBAD ), as well as other novel potential genes (e.g., HRG and ANK2 ) that are related to blood coagulation and cardiovascular efficiency. Our study provides novel insights regarding the evolutionary history and microevolution mechanisms of the high-altitude adaptation in the Tibetan chicken., Competing Interests: The authors declare that they have no conflict of interest., (© 2022 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)

Background: It has been shown that activated microglia in brain releasing proinflammatory cytokines (PICs) contribute to the progression of cardiovascular diseases. In this study, we tested the hypothesis that microglial activation in hypothalamic paraventricular nucleus (PVN), induced by high-salt diet, increases the oxidative stress via releasing PICs and promotes sympathoexcitation and development of hypertension., Methods: High-salt diet was given to male Dahl salt-sensitive rats to induce hypertension. Those rats were bilaterally implanted with cannula for PVN infusion of minocycline, a selective microglial activation blocker, or artificial cerebrospinal fluid for 4 weeks., Results: High-salt diet elevated mean arterial pressure of Dahl salt-sensitive rats. Meanwhile, elevations of renal sympathetic nerve activity and central prostaglandin E2, as well as increase of plasma norepinephrine, were observed in those hypertensive rats. Tumor necrosis factor-α, interleukin-1β (IL-1β), and IL-6 increased in the PVN of those rats, associated with a significant activation of microglia and prominent disruption of redox balance, which was demonstrated by higher superoxide and NAD(P)H oxidase 2 (NOX-2) and NAD(P)H oxidase 4 (NOX-4), and lower Cu/Zn superoxide dismutase in PVN. PVN infusion of minocycline attenuated all hypertension-related alterations described above., Conclusion: This study indicates that high salt leads to microglial activation within PVN of hypertensive rats, and those activated PVN microglia release PICs and trigger the production of reactive oxygen species, which contributes to sympathoexcitation and development of hypertension. Blockade of PVN microglial activation inhibits inflammation and oxidative stress, therefore attenuating the development of hypertension induced by high-salt diet., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Glioblastoma multiforme (GBM) is the most malignant glioma, with a 30-60% epidermal growth factor receptor (EGFR) mutation. This mutation is associated with unrestricted cell growth and increases the possibility of cancer invasion. Patients with EGFR-mutated GBM often develop resistance to the available treatment modalities and higher recurrence rates. The drug resistance observed is associated with multiple genetic or epigenetic factors. The ubiquitin-specific protease 6 N-terminal-like protein (USP6NL) is a GTPase-activating protein that functions as a deubiquitinating enzyme and regulates endocytosis and signal transduction. It is highly expressed in many cancer types and may promote the growth and proliferation of cancer cells. We hypothesized that USP6NL affects GBM chemoresistance and tumorigenesis, and that its inhibition may be a novel therapeutic strategy for GBM treatment. The USP6NL level, together with EGFR expression in human GBM tissue samples and cell lines associated with therapy resistance, tumor growth, and cancer invasion, were investigated. Its pivotal roles and potential mechanism in modulating tumor growth, and the key mechanism associated with therapy resistance of GBM cells, were studied, both in vitro and in vivo. Herein, we found that deubiquitinase USP6NL and growth factor receptor EGFR were strongly associated with the oncogenicity and resistance of GBM, both in vitro and in vivo, toward temozolomide, as evidenced by enhanced migration, invasion, and acquisition of a highly invasive and drug-resistant phenotype by the GBM cells. Furthermore, abrogation of USP6NL reversed the properties of GBM cells and resensitized them toward temozolomide by enhancing autophagy and reducing the DNA damage repair response. Our results provide novel insights into the probable mechanism through which USP6NL/EGFR signaling might suppress the anticancer therapeutic response, induce cancer invasiveness, and facilitate reduced sensitivity to temozolomide treatment in GBM in an autolysosome-dependent manner. Therefore, controlling the USP6NL may offer an alternative, but efficient, therapeutic strategy for targeting and eradicating otherwise resistant and recurrent phenotypes of aggressive GBM cells.

Purpose: We performed a mediation analysis to investigate how mental fatigue mediates the relationship between cognitive functions and the return to productive activity following TBI., Methods: One hundred and one people (≥20 years) with first-time TBI more than 3 months who completed a series of cognitive tasks followed by Chinese versions of the Mental Fatigue Scale and Community Integration Questionnaire-Revised. Mediation analysis was used to test our hypotheses., Results: Recognition memory and information processing speed were the only cognitive functions correlated with mental fatigue (B = -0.56 and -0.37, P = .04 and < 0.001) and the return to productive activity (B = 0.69 and 0.19, both P < .001) after controlling for confounders. Mental fatigue partially mediated the associations of recognition memory and information processing speed with the return to productive activity (B = 0.15 and 0.08, P = .001 and < 0.001, proportion of mediation = 22% and 46%) after the adjustment of confounders., Conclusions: The findings suggest that mental fatigue can partially mediate the relationship between cognitive deficits and return to productive activity. Mental fatigue can be considered a crucial, treatable mediator of the adverse effects of cognitive impairment upon return to productive activity following TBI.

Objective: The use of robotics in spinal surgery has gained popularity because of its promising accuracy and safety. ROSA is a commonly used surgical robot system for spinal surgery. The aim of this study was to compare outcomes between robot-guided and freehand fluoroscopy-guided instrumentation in minimally invasive surgery (MIS)-transforaminal lumbar interbody fusion (TLIF)., Methods: This retrospective consecutive series reviewed 224 patients who underwent MIS-TLIF from March 2019 to April 2020 at a single institution. All patients were diagnosed with degenerative pathologies. Of those, 75 patients underwent robot-guided MIS-TLIF, and 149 patients underwent freehand fluoroscopy-guided MIS-TLIF. The incidences of pedicle breach, intraoperative outcomes, postoperative outcomes, and short-term pain control were compared., Results: The patients who underwent robot-guided surgery had a lower incidence of pedicle breach (0.27% vs 1.75%, p = 0.04) and less operative blood loss (313.7 ± 214.1 mL vs 431.6 ± 529.8 mL, p = 0.019). Nonsignificant differences were observed in operative duration (280.7 ± 98.1 minutes vs 251.4 ± 112.0 minutes, p = 0.056), hospital stay (6.6 ± 3.4 days vs 7.3 ± 4.4 days, p = 0.19), complications (intraoperative, 1.3% vs 1.3%, p = 0.45; postoperative surgery-related, 4.0% vs 4.0%, p = 0.99), and short-term pain control (postoperative day 1, 2.1 ± 1.2 vs 1.8 ± 1.2, p = 0.144; postoperative day 30, 1.2 ± 0.5 vs 1.3 ± 0.7, p = 0.610). A shorter operative duration for 4-level spinal surgery was found in the robot-guided surgery group (388.7 ± 107.3 minutes vs 544.0 ± 128.5 minutes, p = 0.047)., Conclusions: This retrospective review revealed that patients who underwent robot-guided MIS-TLIF experienced less operative blood loss. They also benefited from a shorter operative duration with higher-level (> 3 levels) spinal surgery. The postoperative outcomes were similar for both robot-guided and freehand fluoroscopy-guided procedures.

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, with a median duration of survival of approximately 14 months after diagnosis. High resistance to chemotherapy remains a major problem. Previously, BTK has been shown to be involved in the intracellular signal transduction including Akt/mTOR signaling and be critical for tumorigenesis. Thus, we aim to evaluate the effect of BTK and mTOR inhibition in GBM. We evaluated the viability of GBM cell lines after treatment with acalabrutinib and/or rapamycin through a SRB staining assay. We then evaluated the effect of both drugs on GBM stem cell-like phenotypes through various in vitro assay. Furthermore, we incubated HUVEC cells with tumorsphere conditioned media and observed their angiogenesis potential, with or without treatment. Finally, we conducted an in vivo study to confirm our in vitro findings and analyzed the effect of this combination on xenograft mice models. Drug combination assay demonstrated a synergistic relationship between acalabrutinib and rapamycin. CSCs phenotypes, including tumorsphere and colony formation with the associated expression of markers of pluripotency are inhibited by either acalabrutinib or rapamycin singly and these effects are enhanced upon combining acalabrutinib and rapamycin. We showed that the angiogenesis capabilities of HUVEC cells are significantly reduced after treatment with acalabrutinib and/or rapamycin. Xenograft tumors treated with both drugs showed significant volume reduction with minimal toxicity. Samples taken from the combined treatment group demonstrated an increased Desmin/CD31 and col IV/vessel ratio, suggesting an increased rate of vascular normalization. Our results demonstrate that BTK-mTOR inhibition disrupts the population of GBM-CSCs and contributes to normalizing GBM vascularization and thus, may serve as a basis for developing therapeutic strategies for chemoresistant/radioresistant GBM.

The negatively charged nitrogen-vacancy center in fluorescent nanodiamonds (FNDs) is a point defect with unique magneto-optical properties. It emits far-red fluorescence at ∼700 nm, and its intensity can be magnetically modulated with a depth of more than 10% at a field strength of 30 mT. We have closely examined this property and illustrated its practical use in biomedicine by applying a periodic, time-varying magnetic field to FNDs deposited on a surface or dispersed in a solution with a lock-in detection method. We achieved selective and sensitive detection of 100 nm FNDs on a nitrocellulose membrane at a particle density of 0.04 ng/mm 2 (or ∼2 × 10 4 particles/mm 2 ) and in an aqueous solution with a particle concentration of 1 ng/mL (or ∼1 fM) in 10 s as the detection limits. The utility and versatility of the technique were demonstrated with an application to background-free detection of FNDs as reporters for FND-based lateral flow immunoassays as well as selective quantification of FNDs in tissue digests for in vivo studies.

Abstract: BACKGROUND: Reports regarding prevalence of post-traumatic brain injury (TBI) cognitive deficits were inconsistent. We aimed to synthesize the prevalence of cognitive deficits after TBI in the acute, subacute, and chronic phases. METHODS: PubMed, EMBASE, and ProQuest Dissertations and Theses A&I databases were searched from the inception to April 27, 2020. Studies with prospective, retrospective, and cross-sectional designs reporting the prevalence of cognitive deficits after TBI in adults were included. RESULTS: A total of 15 articles were included for prevalence estimation. The pooled prevalence of memory and attention deficits after mild TBI was 31% and 20% in the acute phase and 26% and 18% in the subacute phase, respectively, and 49% and 54% in the subacute phase and 21% and 50% in the chronic phase after moderate-to-severe TBI. The overall prevalence of information processing speed deficits after mild TBI in the acute and subacute phases was 21% and 17%, respectively, and 57% in the chronic phase after moderate-to-severe TBI. The overall prevalence of executive dysfunction in the subacute and chronic phases was 48% and 38%, respectively, after moderate-to-severe TBI. CONCLUSION: Cognitive deficits are prevalent in the acute to chronic phases after TBI. Healthcare providers should design effective intervention targeting cognitive impairment after TBI as early as possible., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 American Association of Neuroscience Nurses.)

Background : Glioblastoma (GB) is one of the most common (~30%) and lethal cancers of the central nervous system. Although new therapies are emerging, chemoresistance to treatment is one of the major challenges in cancer treatment. Brain cytoplasmic 200 (BC200) RNA, also known as BCYRN1, is a long noncoding RNA (lncRNA) that has recently emerged as one of the crucial members of the lncRNA family. BC200 atypical expression is observed in many human cancers. BC200 expression is higher in invasive cancers than in benign tumors. However, the clinical significance of BC200 and its effect on GB multiforme is still unexplored and remains unclear. Methods : BC200 expression in GB patients and cell lines were investigated through RT-qPCR, immunoblotting, and immunohistochemistry analysis. The biological importance of BC200 was investigated in vitro and in vivo through knockdown and overexpression. Bioinformatic analysis was performed to determine miRNAs associated with BC200 RNA. Results : Our findings revealed that in GB patients, BC200 RNA expression was higher in blood and tumor tissues than in normal tissues. BC200 RNA expression have a statistically significant difference between the IDH1 and P53 status. Moreover, the BC200 RNA expression was higher than both p53, a prognostic marker of glioma, and Ki-67, a reliable indicator of tumor cell proliferation activity. Overexpression and silencing of BC200 RNA both in vitro and in vivo significantly modulated the proliferation, self-renewal, pluripotency, and temozolomide (TMZ) chemo-resistance of GB cells. It was found that the expressions of BC200 were up-regulated and that of miR-218-5p were down-regulated in GB tissues and cells. miR-218-5p inhibited the expression of BC200. Conclusions : This study is the first to show that the molecular mechanism of BC200 promotes GB oncogenicity and TMZ resistance through miR-218-5p expression modulation. Thus, the noncoding RNA BC200/miR-218-5p signaling circuit is a potential clinical biomarker or therapeutic target for GB.

A higher propensity of developing brain metastasis exists in triple-negative breast cancer (TNBC). Upon comparing the metastatic patterns of all breast cancer subtypes, patients with TNBC exhibited increased risks of the brain being the initial metastatic site, early brain metastasis development, and shortest brain metastasis-related survival. Notably, the development of brain metastasis differs from that at other sites owing to the brain-unique microvasculature (blood brain barrier (BBB)) and intracerebral microenvironment. Studies of brain metastases from TNBC have revealed the poorest treatment response, mostly because of the relatively backward strategies to target vast disease heterogeneity and poor brain efficacy. Moreover, TNBC is highly associated with the existence of cancer stem cells (CSCs), which contribute to circulating cancer cell survival before BBB extravasation, evasion from immune surveillance, and plasticity in adaptation to the brain-specific microenvironment. We summarized recent literature regarding molecules and pathways and reviewed the effects of CSC biology during the formation of brain metastasis in TNBC. Along with the concept of individualized cancer therapy, certain strategies, namely the patient-derived xenograft model to overcome the lack of treatment-relevant TNBC classification and techniques in BBB disruption to enhance brain efficacy has been proposed in the hope of achieving treatment success.

Objectives: To compare the prevalence of sleep disturbances in older adults with traumatic brain injury (TBI) with that of age- and gender-matched controls and to determine the risk factors for post-TBI sleep disturbances and the effects of post-TBI disturbances on quality of life (QOL)., Design: Cross-sectional case-comparison study., Participants: Eighty older adults (aged ≥65 years) with first-time TBI more than 3 months since injury and 80 older adults controls without TBI who completed sleep and health-related QOL questionnaires., Results: Older adults with TBI showed a higher prevalence of obstructive sleep apnea (OSA), insomnia, and daytime sleepiness than older adult controls. Being male, having higher levels of depression and pain, and the presence of insomnia were significantly correlated with the risks of OSA, insomnia, and daytime sleepiness following TBI, respectively. Both OSA and insomnia were significantly correlated with low QOL in older adults with TBI., Conclusions: Sleep disturbances are highly prevalent in older adults with TBI. Gender differences, depression severity, and pain level are correlated with the occurrence of post-TBI sleep disturbances. Both OSA and insomnia are regarded as major contributors to low QOL in older people with TBI. Interventions targeted at post-TBI sleep disturbances may improve QOL of older adults.

The performance of a lab-scale integrated anoxic and aerobic inverse fluidized bed bioreactors (IFBBR) for biological nutrient removal from synthetic municipal wastewater was studied at chemical oxygen demand (COD) loading rates of 0.34-2.10 kg COD/(m 3 -d) and nitrogen loading rates of 0.035-0.213 kg N/(m 3 -d). Total COD removal efficiencies of >84% were achieved, concomitantly with complete nitrification. The overall nitrogen removal efficiencies were >75%. Low biomass yields of 0.030-0.101 g VSS/g COD were achieved. Compared with other FBBR systems, the energy consumption for this IFBBR system was an average 59% less at organic loading rates (OLRs) of 1.02 and 2.10 kg COD/(m 3 -d). Bacterial community structures of attached and suspended biomass revealed that the dominant phyla were Proteobacteria, Bacteroidetes, and Epsilonbacteraeota, etc. The relative abundance of ammonia-oxidizing bacteria (AOBs) and nitrite-oxidizing bacteria (NOBs) in the aerobic attached biomass were 0.451% and 0.110%, respectively. COD mass balance in the anoxic zone was closed by consideration of sulfate reduction, which was confirmed by the presence of genus Chlorobium (sulfate-reducing bacteria) in the anoxic attached biofilm with a relative abundance of 0.32%., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The amorphous indium gallium oxide thin film transistor was fabricated using a cosputtering method. Two samples with different gate dielectric layers were used as follows: sample A with a SiO 2 dielectric layer; and sample B with an Al 2 O 3 dielectric layer. The influence of the gate dielectrics on the electric and photo performance has been investigated. Atomic layer deposition deposited the dense film with low interface trapping density and effectively increased drain current. Therefore, sample B exhibited optimal parameters, with an I on / I off ratio of 7.39 × 10 7 , the subthreshold swing of 0.096 V dec -1 , and μ FE of 5.36 cm 2 V -1 s -1 . For ultraviolet (UV) detection, the UV-to-visible rejection ratio of the device was 3 × 10 5 , and the photoresponsivity was 0.38 A W -1 at the V GS of -5 V., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Semiconducting 2D siloxene nanosheets of thickness 1.7 nm and band gap of 2.54 eV are synthesized using simple chemical route. Strong photoluminescence is observed in the as-synthesized nanosheets due to presence of oxygen atoms. The photoluminescence behaviour of siloxene nanosheets is investigated by controlling temperature, excitation and pH of the solution to understand the optical response and stability of the material. The as-synthesized sample heated with temperature 200 °C shows a blue shift of 90 nm compared to the sample synthesized at room temperature. The low temperature luminescence measurements of as-synthesized samples dried at different temperatures viz. 27, 100 and 200 °C. It is seen that the luminescence intensity is increasing with decreasing temperature for the sample dried at room temperature. However, after heating the sample at 100 °C, the luminescence intensity is not only increased but also red-shifted up to 52 nm. The photocurrent has been measured for the device structure of ITO/PEDOT: PSS/Siloxene/Al with different film thicknesses to optimize the photocurrent and the maximum percentage change in photo power gain. The maximum photopower gain of 2693% is observed for the film thickness of 600 nm., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Glioblastoma (GBM), a malignant grade IV tumor, is the most malignant brain tumor due to its hyper-proliferative and apoptosis-evading characteristics. The signal transducer and activators of transcription (STAT) family genes, including STAT3 and STAT5A , have been indicated to play important roles in GBM progression. Increasing number of reports suggest that garcinol, a polyisoprenylated benzophenone and major bioactive component of Garcinia indica contains potent anti-cancer activities., Material and Methods: The present study investigated the anti-GBM effects of garcinol, focusing on the STAT3/STAT5A activation, using a combination of bioinformatics, in vitro, and ex vivo assays., Results: Our bioinformatics analysis of The Cancer Genome Atlas (TCGA)-GBM cohort ( n = 173) showed that STAT3 and STAT5A are preferentially elevated in primary and recurrent GBM, compared to non-tumor brain tissues, and is significantly correlated with reduced overall survival. In support, our immunohistochemical staining of a GBM cohort ( n = 45) showed an estimated 5.3-fold ( p < 0.001) elevation in STAT3 and STAT5A protein expression in primary and recurrent GBM versus the non-tumor group. In vitro, garcinol treatment significantly suppressed the proliferative, invasive, and migratory potential of U87MG or GBM8401 cells, dose-dependently. In addition, garcinol anticancer effect significantly attenuated the GBM stem cell-like phenotypes, as reflected by diminished ability of U87MG or GBM8401 to form colonies and tumorspheres and suppressed expression of OCT4 and SOX2. Furthermore, analysis on GBM transcriptome revealed an inverse correlation between the level of STAT3/5A and hsa-miR-181d. Garcinol-mediated anti-GBM effects were associated with an increased hsa-miR-181d/ STAT3 and hsa-miR-181d/5A ratio. The results were further verified in vivo using U87MG mouse xenograft model where administration of garcinol significantly inhibited tumor growth., Conclusions: We present evidence of anti-GBM efficacy of garcinol mediated by enhancing the hsa-miR-181d/STAT3 and hsa-miR-181d/5A ratios in GBM cells. Our findings suggest a potential new therapeutic agent for combating aggressive GBM.

Objective: To investigate the incidence and constituent ratio of odontogenic tumors or odontogenic cysts in School and Hospital of Stomatology, Jilin University and to provide the reference for the clinical treatment. Methods: According to the WHO 2017 histological classification criteria, the pathological data of 4181 patients diagnosed as odontogenic tumors or odontogenic cysts in the Department of Pathology, Jilin University Stomatological Hospital from January 1961 to December 2017 were collected. Statistical analysis of the pathological types, gender, age and location of various tumors and cysts was conducted. Results: Of 4 181 cases, 1 055 were tumors and 3 126 were cysts. Among odontogenic tumors, benign tumors accounted for 96.11% (1 014/1 055), and malignant tumors accounted for 3.89% (41/1 055). The most common pathological type of odontogenic tumors was ameloblastoma [53.27% (562/1 055)], followed by cemento-ossifying fibroma [21.23% (224/1 055)] and odontoma [12.99% (137/1 055)]. The male-female ratio was 1∶1.04. The high-risk ages were 10-39. Maxilla-mandible ratio was 1∶2.85.As for cysts, radicular cysts [50.45% (1 577/3 126)] was the most common pathological type, followed by odontogenic keratocyst [25.59% (800/3 126)] and dentigerous cysts [21.56% (674/3 126)]. The male-female ratio was 1.37∶1. The high-risk ages were 20-49. Maxilla-mandible ratio was 1.37∶1. Conclusions: There was no gender preference for odontogenic tumors in Jilin Province area in the 57 years. The majority tumors occurred in the radicular. The most common pathological type was ameloblastoma. As for odontogenic cysts, males showed a higher incidence and the majority cysts occurred in the maxilla. The most common pathological type was radicular cysts.

Background: Ovatodiolide (Ova), a major bioactive diterpenoid isolate of Anisomeles indica has drawn considerable attention lately as an effective anticancer agent with several published works demonstrating its tumor-inhibitory activity in various cancer types., Purpose: In this study, we examined the modulatory effect of Ova on the oncogenicity, proliferation, and cancer stem cell-like traits of glioblastoma (GBM) cells, as well as investigated the underlying molecular mechanism for the anticancer activity of Ova in GBM cell lines, U-87MG and GBM8401., Methods: The antiproliferative, apoptotic, and stemness-attenuating effects of Ova were evaluated using the sulforhodamine B (SRB) colorimetric assay, western blot and fluorescent immunocytochemistry. Cell apoptosis was analyzed based on variation in the expression levels of Bcl-2 family of regulator proteins Bax, Bak, Bcl-2 and Bcl-xL., Results: Ova induced the apoptosis of the U-87MG and GBM8401 cells, as well as effectively inhibited the proliferation and motility of the GBM cell lines in a dose- and time-dependent manner. Ova-induced apoptosis correlated with increased Bax/Bcl-2 ratio, while inhibition of tumor cell migration and colony formation was associated with reduced Slug, Vimentin, NCadherin and β-catenin protein expression and increased E-Cadherin. In addition, exposure to Ova inhibited tumorsphere formation, elicited downregulation of CD44, CD133, Sox2, and Oct4, as well as correlated with dysregulation of the JAK2-STAT3 signaling pathway. Furthermore, we showed for the first time to the best of our knowledge that Ova potentiate the chemotherapeutic effect of Temozolomide., Conclusion: Taken together, our findings demonstrate the anticancer potential of Ova in GBM and its efficacy in the treatment of GBM as monotherapy and in combination with Temozolomide., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Background: The tumor microenvironment (TME) plays a crucial role in virtually every aspect of tumorigenesis of glioblastoma multiforme (GBM). A dysfunctional TME promotes drug resistance, disease recurrence, and distant metastasis. Recent evidence indicates that exosomes released by stromal cells within the TME may promote oncogenic phenotypes via transferring signaling molecules such as cytokines, proteins, and microRNAs., Results: In this study, clinical GBM samples were collected and analyzed. We found that GBM-associated macrophages (GAMs) secreted exosomes which were enriched with oncomiR-21. Coculture of GAMs (and GAM-derived exosomes) and GBM cell lines increased GBM cells' resistance against temozolomide (TMZ) by upregulating the prosurvival gene programmed cell death protein 4 (PDCD4) and stemness markers SRY (sex determining region y)-box 2 (Sox2), signal transducer and activator of transcription 3 (STAT3), Nestin, and miR-21-5p and increasing the M2 cytokines interleukin 6 (IL-6) and transforming growth factor beta 1(TGF-β1) secreted by GBM cells, promoting the M2 polarization of GAMs. Subsequently, pacritinib treatment suppressed GBM tumorigenesis and stemness; more importantly, pacritinib-treated GBM cells showed a markedly reduced ability to secret M2 cytokines and reduced miR-21-enriched exosomes secreted by GAMs. Pacritinib-mediated effects were accompanied by a reduction of oncomiR miR-21-5p, by which the tumor suppressor PDCD4 was targeted. We subsequently established patient-derived xenograft (PDX) models where mice bore patient GBM and GAMs. Treatment with pacritinib and the combination of pacritinib and TMZ appeared to significantly reduce the tumorigenesis of GBM/GAM PDX mice as well as overcome TMZ resistance and M2 polarization of GAMs., Conclusion: In summation, we showed the potential of pacritinib alone or in combination with TMZ to suppress GBM tumorigenesis via modulating STAT3/miR-21/PDCD4 signaling. Further investigations are warranted for adopting pacritinib for the treatment of TMZ-resistant GBM in clinical settings.

In this study, amorphous indium gallium oxide thin-film transistors (IGO TFTs) were fabricated by co-sputtering. Three samples with different deposition powers of the In₂O₃ target, namely, sample A with 50 W deposition power, sample B with 60 W deposition power, and sample C with 70 W deposition power, were investigated. The device performance revealed that oxygen vacancies are strongly dependent on indium content. However, when the deposition power of the In₂O₃ target increased, the number of oxygen vacancies, which act as charge carriers to improve the device performance, increased. The best performance was recorded at a threshold voltage of 1.1 V, on-off current ratio of 4.5 × 10⁶, and subthreshold swing of 3.82 V/dec in sample B. Meanwhile, the optical properties of sample B included a responsivity of 0.16 A/W and excellent ultraviolet-to-visible rejection ratio of 8 × 10⁴. IGO TFTs may act as photodetectors according to the results obtained for optical properties.

The defect-enhanced resistive switching behavior of Cr-doped ZnO films was investigated in this study, and evidence that the switching effect can be attributed to defects was found. X-ray photoelectron spectroscopy demonstrated the existence of oxygen vacancies in the ZnO-based films, and the concentration of oxygen vacancies in the Cr-doped ZnO film was larger than that in the undoped ZnO film, which can be attributed to Cr doping. We concluded that the defects in Cr-doped ZnO were due to the Cr dopant, leading to excellent performance of Cr-doped ZnO films. In particular, depth-profiling analysis of the X-ray photoelectron spectra demonstrated that the resistive switching effects corresponded to variations in the concentration of the defects. The results confirmed that oxygen vacancies are crucial for the entire class of resistive switching effects in Cr-doped ZnO films. In particular, the Cr-doped ZnO films not only show bipolar resistive switching behavior but also excellent reliability and stability, which should be beneficial for next-generation memory device applications., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Glioblastoma (GBM), a malignant form of glioma, is characterized by resistance to therapy and poor prognosis. Accumulating evidence shows that the initiation, propagation, and recurrence of GBM is attributable to the presence of GBM stem cells (GBM-CSCs)., Experimental Approach: Herein, we investigated the effect of 4-Acetylantroquinonol B (4-AAQB), a bioactive isolate of Antrodia cinnamomea , on GBM cell viability, oncogenic, and CSCs-like activities., Results: We observed that aberrant expression of catenin is characteristic of GBM, compared to other glioma types ( p = 0.0001, log-rank test = 475.2), and correlates with poor prognosis of GBM patients. Lower grade glioma and glioblastoma patients ( n = 1152) with low catenin expression had 25% and 21.5% better overall survival than those with high catenin expression at the 5 and 10-year time-points, respectively ( p = 3.57e-11, log-rank test = 43.8). Immunohistochemistry demonstrated that compared with adjacent non-tumor brain tissue, primary and recurrent GBM exhibited enhanced catenin expression (~10-fold, p < 0.001). Western blot analysis showed that 4-AAQB significantly downregulated β-catenin and dysregulated the catenin/LEF1/Stat3 signaling axis in U87MG and DBTRG-05MG cells, dose-dependently. 4-AAQB⁻induced downregulation of catenin positively correlated with reduced Sox2 and Oct4 nuclear expression in the cells. Furthermore, 4-AAQB markedly reduced the viability of U87MG and DBTRG-05MG cells with 48 h IC 50 of 9.2 M and 12.5 M, respectively, effectively inhibited the nuclear catenin, limited the migration and invasion of GBM cells, with concurrent downregulation of catenin, vimentin, and slug; similarly, colony and tumorsphere formation was significantly attenuated with reduced expression of c-Myc and KLF4 proteins., Conclusions: Summarily, we show for the first time that 4-AAQB suppresses the tumor-promoting catenin/LEF1/Stat3 signaling, and inhibited CSCs-induced oncogenic activities in GBM in vitro, with in vivo validation; thus projecting 4-AAQB as a potent therapeutic agent for anti-GBM target therapy., Competing Interests: The authors declare that there are no potential conflict of interest.

To construct CRISPR/Cas9 vectors for the editing of SmPAL1 in the phenylpropane metabolic pathway of Salvia miltiorrhiza, CIRSPR/Cas9 target sites of SmPAL1 were designed by online software. Its target efficiencies were detected in vitro by enzyme digestion and sequences with highly efficiency were constructed into CRISPR/Cas9 vectors. Three possible CRISPR target sequences (SmPAL1-g1, SmPAL1-g2, SmPAL1-g3) were designed and the enzyme digestion efficiencies were 53.3%, 76.6% and 10.0%. SmPAL1-g1 and SmPAL1-g2 were constructed into vector VK005-03 named as VK005-03-g1 and VK005-03-g2. The results of sequencing showed that the two CRISPR/Cas target sequences were all constructed into VK005-03. Here we first laid the foundation for the study of SmPAL1 and provided an effective strategy for the screening of sgRNA., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

This study employed cell recycling, batch adaptation, cell mating and high-throughput screening to select adapted Spathaspora passalidarum strains with improved fermentative ability. The most promising candidate YK208-E11 (E11) showed a 3-fold increase in specific fermentation rate compared to the parental strain and an ethanol yield greater than 0.45 g/g substrate while co-utilizing cellobiose, glucose and xylose. Further characterization showed that strain E11 also makes 40% less biomass compared to the parental strain when cultivated in rich media under aerobic conditions. A tetrazolium agar overlay assay in the presence of respiration inhibitors, including rotenone, antimycin A, KCN and salicylhydroxamic acid elucidated the nature of the mutational events. Results indicated that E11 has a deficiency in its respiration system that could contribute to its low cell yield. Strain E11 was subjected to whole genome sequencing and an ∼11 kb deletion was identified; the open reading frames absent in strain E11 code for proteins with predicted functions in respiration, cell division and the actin cytoskeleton, and may contribute to the observed physiology of the adapted strain. Results of the tetrazolium overlay also suggest that cultivation on xylose affects the respiration capacity in the wild-type strain, which could account for its faster fermentation of xylose as compared to glucose. These results support our previous finding that S. passalidarum has highly unusual physiological responses to xylose under oxygen limitation.

Glioblastoma multiforme (GBM) is a highly malignant type of brain tumor found in humans. GBM cells reproduce quickly, and the median survival time for patients after therapy is approximately 1 year with a high relapse rate. Current therapies and diagnostic tools for GBM are limited; therefore, we searched for a more favorable therapeutic target or marker protein for both therapy and diagnosis. We used mass spectrometry (MS) analysis to identify GBM-associated marker proteins from human plasma and GBM cell cultures. Additional plasma and 52 brain tissues obtained from patients with gliomas were used to validate the association rate of serum amyloid A1 (SAA1) in different grades of gliomas and its distribution in tumors. Microarray database analysis further validated the coefficient of SAA1 levels in gliomas. The cellular mechanisms of SAA1 in GBM proliferation and infiltration were investigated in vitro. We analyzed the correlation between SAA1 and patients' medication requirement to demonstrate the clinical effects of SAA1 in GBM. SAA1 was identified from MS analysis, and its level was revealed to be correlated with the disease grade, clinical severity, and survival rate of patients with gliomas. In vitro cultures, including GBM cells and normal astrocytes, revealed that SAA1 promotes cell migration and invasion through integrin αVβ3 to activate the Erk signaling pathway. Magnetic resonance imaging and tumor region-specific microarray analysis identified a correlation between SAA1 and GBM cell infiltration in patients. In summary, our results demonstrate that SAA1 in combination with integrin αV and β3 can serve as an indicator of high glioblastoma risk. We also identified the cellular mechanisms of SAA1 contributing to GBM progression, which can serve as the basis for future GBM therapy., (© 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

Ca2+-binding human S100A1 protein is a type of S100 protein. S100A1 is a significant mediator during inflammation when Ca2+ binds to its EF-hand motifs. Receptors for advanced glycation end products (RAGE) correspond to 5 domains: the cytoplasmic, transmembrane, C2, C1, and V domains. The V domain of RAGE is one of the most important target proteins for S100A1. It binds to the hydrophobic surface and triggers signaling transduction cascades that induce cell growth, cell proliferation, and tumorigenesis. We used nuclear magnetic resonance (NMR) spectroscopy to characterize the interaction between S100A1 and the RAGE V domain. We found that S100B could interact with S100A1 via NMR 1H-15N HSQC titrations. We used the HADDOCK program to generate the following two binary complexes based on the NMR titration results: S100A1-RAGE V domain and S100A1-S100B. After overlapping these two complex structures, we found that S100B plays a crucial role in blocking the interaction site between RAGE V domain and S100A1. A cell proliferation assay WST-1 also supported our results. This report could potentially be useful for new protein development for cancer treatment.