Vitamin D accelerates the subdural hematoma clearance through improving the meningeal lymphatic vessel function.

Subdural hematoma (SDH) drains into the extracranial lymphatic system through the meningeal lymphatic vessels (mLVs) but the formation of SDH impairs mLVs. Because vitamin D (Vit D) can protect the endothelial cells, we hypothesized that Vit D may enhance the SDH clearance. SDH was induced in Sprague-Dawley rats and treated with Vit D or vehicle. Hematoma volume in each group was measured by H&E staining and hemoglobin quantification. Evans blue (EB) quantification and red blood cells injection were used to evaluated the drainage of mLVs. Western blot analysis and immunofluorescence were conducted to assess the expression of lymphatic protein markers. We also examined the inflammatory factors levels in subdural space by ELISA. Vit D treatment significantly reduced SDH volume and improved the drainage of SDH to cervical lymph nodes. The structure of mLVs in SDH rats were protected by Vit D, and the expressions of LYVE1, PROX1, FOXC2, and VE-cadherin were increased after Vit D treatment. The TNF-α, IL-6, and IL-8 levels were reduced in Vit D group. In vitro, Vit D also increased the VE-cadherin expression levels under inflammation. Vit D protects the structure of mLVs and enhances the absorption of SDH, partly by the anti-inflammatory effect of Vit D.

luxS contributes to intramacrophage survival of Streptococcus agalactiae by positively affecting the expression of fruRKI operon.

The LuxS quorum sensing system is a widespread system employed by many bacteria for cell-to-cell communication. The luxS gene has been demonstrated to play a crucial role in intramacrophage survival of piscine Streptococcus agalactiae, but the underlying mechanism remains largely unknown. In this study, transcriptome analysis, followed by the luxS gene deletion and subsequent functional studies, confirmed that impaired bacterial survival inside macrophages due to the inactivation of luxS was associated with reduced transcription of the fruRKI operon, encoding the fructose-specific phosphotransferase system. Further, luxS was determined not to enhance the transcription of fruRKI operon by binding its promoter, but to upregulate the expression of this operon via affecting the binding ability of catabolite control protein A (CcpA) to the catabolite responsive element (cre) in the promoter of fruRKI. Collectively, our study identifies a novel and previously unappreciated role for luxS in bacterial intracellular survival, which may give a more thorough understanding of the immune evasion mechanism in S. agalactiae.

Preparation of Fe/Ni-MOFs for the Adsorption of Ciprofloxacin from Wastewater.

This work studies the use of Fe/Ni-MOFs for the removal of ciprofloxacin (CIP) in wastewater. Fe/Ni-MOFs are prepared by the solvothermal method and characterized by X-ray diffraction (XRD), a scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FT-IR), and a thermal gravimetric analyzer (TG). Under the conditions of the concentration of 50 ppm, a mass of 30 mg, and a temperature of 30 °C, the maximum adsorption capacity of ciprofloxacin removal within 5 h was 232.1 mg/g. The maximum removal rate was 94.8% when 40 mg of the Fe/Ni-MOFs was added to the solution of 10 ppm ciprofloxacin. According to the pseudo-second-order (PSO) kinetic model, the R2 values were all greater than 0.99, which proved that the adsorption theory of ciprofloxacin by Fe/Ni-MOFs was consistent with the practice. The adsorption results were mainly affected by solution pH and static electricity, as well as other factors. The Freundlich isotherm model characterized the adsorption of ciprofloxacin by Fe/Ni-MOFs as multilayer adsorption. The above results indicated that Fe/Ni-MOFs were effective in the practical application of ciprofloxacin removal.

Production and characterization of polyclonal and monoclonal antibodies of lamprey pore-forming protein.

In the most primitive jawless vertebrate lamprey, the complement-dependent cytotoxicity regulated by variable lymphocyte receptors (VLRs) plays an important role in the adaptive immunity. Our previous studies have shown that the lamprey pore-forming protein (LPFP) acted as the terminal effector of VLR to lyse and kill the target cells. Here, the recombinant GST-LPFP protein was expressed and purified in prokaryotic expression system, and then used as the immunogen to produce mouse monoclonal antibody and rabbit polyclonal antibody. With these antibodies, we proved that LPFP existed as homodimers in the lamprey serum, and could be recruited to the membrane of target cells after stimulation. In conclusion, the antibodies we produced could specifically recognize the LPFP protein, which could be the useful tools to further study the pore-forming mechanism of LPFP.

The inflammatory cellular feature in the peripheral blood of chronic subdural hematoma patients.

BACKGROUND: Chronic subdural hematoma (CSDH) is a common neurosurgical disease with an increasing incidence. The absorption route of CSDH is not clear. Whether inflammatory factors enter the peripheral blood and cause systemic reactions is unknown. METHODS: We screened 105 CSDH patients and 105 control individuals. Their clinical characteristics and blood routine results were collected and compared. The blood routine changes of CSDH patients before and after treatment were compared. Age-stratified analysis was performed due to age may affect the inflammatory markers. RESULTS: The white blood cell count, absolute neutrophil count, neutrophil percentage, neutrophil-lymphocyte count ratio (NLR), and platelet to lymphocyte count ratio (PLR) of CSDH patients before treatment were within the normal range, while were significantly higher than the control individuals (p < 0.001). The absolute lymphocyte count and lymphocyte percentage of control individuals were higher than those of patients (p < 0.001). The inflammatory cells in patients of different age groups were similar. After the patient was cured, the white blood cell count, the absolute value and percentage of neutrophils decreased (p < 0.05), while the number of monocytes increased. CONCLUSIONS: CSDH caused slight systemic inflammatory responses in the peripheral blood, implying that there is a non-hematologic route for the absorption of hematoma.

Dexamethasone enhances the efficacy of atorvastatin in inhibiting excessively inflammation-induced abnormal angiogenesis by regulating macrophages.

BACKGROUND: We have recently showed that atorvastatin (ATO) combined with low dose of dexamethasone (DEX) was more efficacious in treating patients with chronic subdural haematoma (CSDH) than ATO monotherapy. This study was designed to investigate the underlying mechanisms of the improved efficacy of this combined therapy. METHODS: Mass spectrometry was performed to quantitatively detect drugs in haematoma fluids and serum samples from CSDH patients and also in cultured macrophages after treatment with either ATO alone or in combination with DEX. The differentiation and apoptosis of macrophages were evaluated using flow cytometry. The expression of cytokines, chemokines and angiogenesis-related proteins was evaluated using proteome profile arrays, immunoblots and ELISA, respectively. RESULTS: ATO was detected in haematoma fluids and serum samples, whose levels were increased significantly in samples collected from patients treated with both ATO and DEX. ATO was also increased in cultured macrophages treated with ATO and DEX. The numbers of M1-polarized macrophages were higher than the M2 phenotype in the haematoma fluids of patients. Cultured macrophages treated with ATO and DEX had reduced numbers of M1-polarized macrophages, increased numbers of M2-polarized macrophages as compared to monotherapies, and decreased rate of apoptosis induced by high-dose DEX. DEX enhanced the anti-inflammatory and anti-angiogenic activity of ATO by suppressing VEGFA and other inflammatory angiogenic factors. Consistent with the finding, patients responded well to the drug treatments had lower serum levels of VEGFA. CONCLUSIONS: We have shown for the first time that ATO given orally was detected in CSDH haematoma fluids. DEX enhances the anti-inflammatory and anti-angiogenic effects of ATO, primarily by increasing the presence of ATO in haematoma and macrophages and by regulating the functions of macrophages.

Low-dimensional material based wearable sensors.

Wearable sensors are believed to be the most important part of the Internet of Things. In order to meet the application requirements, low-dimensional materials such as graphene and carbon nanotubes have been attempted to constitute wearable sensors with high performance. Our discussions in this review include the different low-dimensional material based sensors which are employed in wearable applications. Low-dimensional materials based wearable sensors for detecting various physical quantities in surroundings, including temperature sensor, pressure or strain sensor and humidity sensor, is introduced. The primary objective of this paper is to provide a comprehensive review of research status and future development direction of low-dimensional materials based wearable sensors. Challenges for developing commercially low-dimensional namomaterials based wearable sensors are highlighted as well.

Role of luxS in immune evasion and pathogenicity of piscine Streptococcus agalactiae is not dependent on autoinducer-2.

luxS-mediated autoinducer 2 (AI-2)-dependent quorum sensing (QS) has been demonstrated to affect many bacterial phenotypes, including virulence. Streptococcus agalactiae harbors a functional luxS gene required for the biosynthesis of AI-2. In this study, we investigated the regulation effect and mechanism of the luxS/AI-2 QS system in the pathogenicity of the piscine S. agalactiae strain GD201008-001. We found that inactivation of luxS caused a marked decrease in biofilm formation, hemolytic activity, antiphagocytosis and intracellular survival of S. agalactiae. Except for hemolytic activity, the altered phenotypes due to the luxS deletion were AI-2-independent. Further investigation indicated that high levels of the proinflammatory cytokines IL-1ß and IL-6 could be induced in macrophages co-incubated with the luxS deletion mutant and synthetic AI-2, single or combined. Also, the results of tilapia infection showed that inactivation of luxS significantly decreased the virulence of S. agalactiae but upregulated the expression of cytokines in spleens and brains. Increased proinflammatory effects of the luxS mutant were restored in the luxS complemented strain but could not be restored by AI-2 addition. All the findings suggest that luxS is involved in virulence-associated phenotypes and immunological evasion of S. agalactiae, and furthermore, this involvement is mostly AI-2-independent. This study will provide valuable insights into our understanding of the role of the LuxS/AI-2 QS system in the pathogenesis of S. agalactiae.

Interaction mechanism between multi-layered MoS2 and H2O2 for self-generation of reactive oxygen species.

Elucidating the generation mechanism of reactive oxygen species (ROS) is essential for advanced oxidation processes with respect to environmental and biological sciences. Herein, self-generation of ROS such as hydroxyl radicals (·OH), superoxide radicals (O2•-) and singlet oxygen (1O2) from the interaction between multi-layered flowerlike MoS2 nanosheets and H2O2 is presented. The results demonstrate that H2O2 can exfoliate multi-layered MoS2 into quantum dots and promote a 2H to 1 T phase change accompanied by the dissolution of MoS2 to produce H+, MoO42- and SO42-. Electron spin resonance (ESR) spectroscopy confirm the production of ·OH, superoxide radicals O2•- and 1O2 in the MoS2/H2O2 system. The calculation data based on density functional theory (DFT) indicate that the 1 T-MoS2 can lower the free energy profiles for stepwise catalytic decomposition of H2O2 to produce ROS as compared to 2H-MoS2.

Laser Ranging-Assisted Binocular Visual Sensor Tracking System.

Aimed at improving the low measurement accuracy of the binocular vision sensor along the optical axis in the process of target tracking, we proposed a method for auxiliary correction using a laser-ranging sensor in this paper. In the process of system measurement, limited to the mechanical performance of the two-dimensional turntable, the measurement value of a laser-ranging sensor is lagged. In this paper, the lag information is updated directly to solve the time delay. Moreover, in order to give full play to the advantages of binocular vision sensors and laser-ranging sensors in target tracking, federated filtering is used to improve the information utilization and measurement accuracy and to solve the estimated correlation. The experimental results show that the real-time and measurement accuracy of the laser ranging-assisted binocular visual-tracking system is improved by the direct update algorithm and the federal filtering algorithm. The results of this paper are significant for binocular vision sensors and laser-ranging sensors in engineering applications involving target tracking systems.

Multi-Physical Models of Bending Characteristics on the Double-Clamped Beam Switch for Flexible Electronic Devices Application.

In this paper, multi-physical models of bending characteristics, including the static, dynamic and microwave models, are firstly proposed for the double-clamped beam switch based on flexible substrate. Both simulated and experimental verification have been carried out to prove that the changing regularity of the driving voltage and time of the switch is inversely proportional with the increase in the bending curvature of the flexible substrate. The microwave performance of the switch at the ON state is found to get worse with the increase in the bending curvature. The measured results indicate that when the bending curvature increases from 0 m-1 to 28.6 m-1, the measured driving voltage decreases from 90.0 V to 72.6 V with the error of 5.9% compared with the calculated results. The measured driving time decreases from 52.4 µs to 35.6 µs with the error of 16.7% compared with the calculated results. When the substrate bending curvature increases from 0 m-1 to 28.6 m-1, the measured reflection loss S11 of the switch gradually deteriorates from -27.1 dB to -22.0 dB with the error of 1.3 dB corresponding to the calculated results at 10 GHz. All the simulated and experimental results are consistent with the theoretical calculated results.

The three branches of the unfolded protein response exhibit differential significance in breast cancer growth and stemness.

The unfolded protein response (UPR) is widely activated in cancers. The mammalian UPR encompasses three signaling branches, namely inositol-requiring enzyme-1α (IRE1α), protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) and activating transcription factor 6α (ATF6α). The functional significance of each branch in tumorigenesis is incompletely understood, especially in cancer stem cells (CSCs). Here, we report that inhibition and silencing of the three UPR sensors has differential effects on breast cancer growth and the CSC population. The levels of PERK and ATF6α strongly correlate with the expression of sex determining region Y (SRY)-box 2 (SOX2), a pluripotency regulator, in human breast cancer tissues. UPR activation is also elevated in the CSC-enriched mammospheres. Inhibition of the UPR sensors or excess ER stress markedly reduces the formation and maintenance of mammospheres, suggesting that an appropriate level of UPR activation is critical for the CSC survival. Mechanistically, transcription factors from UPR and pluripotency pathways interact and reciprocally influence each other. A transcription modulator, CCAAT-enhancer-binding protein delta (C/EBPδ), interacts with pluripotency regulator, SOX2, and UPR transcription factors, thus likely serving as a link to coordinate UPR and pluripotency maintenance in CSCs. Our findings demonstrate that UPR is critical for both cancer growth and pluripotency, and highlight the differential role and complexity of the three UPR branches in tumorigenesis.

Solution-assisted ultrafast transfer of graphene-based thin films for solar cells and humidity sensors.

Vacuum filtration enables the fabrication of large-area graphene-based membranes (GBMs), possessing a smoother surface than that by spray, spin coating or drop casting. However, due to the strong interaction with substrates, the separation of thin GBMs from the filter is problematic. Conventional stamping separation/transfer of graphene oxide (GO) thin films requires another substrate and pressing for >10 h, which may damage the delicate structure of the transfer substrates. Other methods require GO to be reduced on filters before separation, thus limiting the reduction methods. Inspired by a coagulation bath that enables rapid formation of ultrastrong GO fibers, we present an ultrafast (<1 min) and solution-assisted strategy to fabricate smooth and freestanding GO films. The diverse interfacial energy of hydrogen bonds also demonstrates another reason for the successful separation. The film thickness ranges from 45 nm to several micrometers. When used as a composite of counter electrodes in dye sensitized solar cells, it showed higher (8.58%) power conversion efficiency than its spin-(7.71%) and spray-coated (8.07%) counterparts. It also showed promising performance in capacitive humidity sensors. The capacitance varied by three orders of magnitude in the range of the relative humidity of 15%-95%. Therefore the strategy realizes an ultrafast and high-quality film production which is suitable for various applications.

Integrated physio-biochemical and transcriptomic analysis reveals the joint toxicity mechanisms of two typical antidepressants fluoxetine and sertraline on Microcystis aeruginosa.

Selective serotonin reuptake inhibitor (SSRI) antidepressants are of increasing concern worldwide due to their ubiquitous occurrence and detrimental effects on aquatic organisms. However, little is known regarding their effects on the dominant bloom-forming cyanobacterium, Microcystis aeruginosa. Here, we investigated the individual and joint effects of two typical SSRIs fluoxetine (FLX) and sertraline (SER) on M. aeruginosa at physio-biochemical and molecular levels. Results showed that FLX and SER had strong growth inhibitory effects on M. aeruginosa with the 96-h median effect concentrations (EC50s) of 362 and 225 µg/L, respectively. Besides, the mixtures showed an additive effect on microalgal growth. Meanwhile, both individual SSRIs and their mixtures can inhibit photosynthetic pigment synthesis, cause oxidative damage, destroy cell membrane, and promote microcystin-leucine-arginine (MC-LR) synthesis and release. Moreover, the mixtures enhanced the damage to photosynthesis, antioxidant system, and cell membrane and facilitated MC-LR synthesis and release compared to individuals. Furthermore, transcriptomic analysis revealed that the dysregulation of the key genes related to transport, photosystem, protein synthesis, and non-ribosomal peptide structures was the fundamental molecular mechanism underlying the physio-biochemical responses of M. aeruginosa. These findings provide a better understanding of the toxicity mechanisms of SSRIs to microalgae and their risks to aquatic ecosystems.

Microelectromechanical system for in situ quantitative testing of tension-compression asymmetry in nanostructures.

Tension-compression asymmetry is a topic of current interest in nanostructures, especially in strain engineering. Herein, we report a novel on-chip microelectromechanical system (MEMS) that can realize in situ quantitative mechanical testing of nanostructures under tension-compression functions. The mechanical properties of three kinds of nanostructures fabricated by focused ion beam (FIB) techniques were systematically investigated with the presented on-chip testing system. The results declare that both Pt nanopillars and C nanowires exhibit plastic deformation behavior under tension testing, with average Young's moduli of 70.06 GPa and 58.32 GPa, respectively. However, the mechanical deformation mechanisms of the two nanostructures changed in compression tests. The Pt nanopillar exhibited in-plane buckling behavior, while the C nanowire displayed 3D twisting behavior with a maximum strain of 25.47%, which is far greater than the tensile strain. Moreover, asymmetric behavior was also observed in the C nanospring during five loading-unloading tension-compression deformation tests. This work provides a novel insight into the asymmetric mechanical properties of nanostructures, with potential applications in nanotechnology research.

Susceptibility to Hepatotoxic Drug-Induced Liver Injury Increased After Traumatic Brain Injury in Mice.

The early stages of brain injury can induce acute liver injury, which can be recovered in the short term. Continued medication treatment during hospitalization for brain injury alleviates the prognosis and contributes to a high incidence of drug-induced liver injury (DILI). We hypothesize that there is an interaction between changes in the hepatic environment after brain injury and liver injury produced by intensive drug administration, leading to an upregulation of the organism's sensitivity to DILI. In this study, mice models of TBI were established by controlled cortical impact (CCI) and models of DILI were constructed by acetaminophen (APAP). All mice were divided into four groups: Sham, TBI, APAP, and TBI+APAP, and related liver injury indicators in liver and serum were detected by Western blot, Quantitative real-time PCR (qRT-PCR), and immunohistochemical staining. The results suggested that liver injury induced in the early stages of brain injury recovered in 3 days, but this state could still significantly aggravate DILI, represented by higher liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]), oxidative stress (increase in malondialdehyde [MDA] concentration and deregulation of glutathione [GSH] and superoxide dismutase [SOD] activities), inflammatory response (activation of the HMGB1/TLR4/NF-κB signaling pathway, and increased messenger RNA [mRNA] and protein levels of pro-inflammatory cytokines including tumor necrosis factor alpha [TNF-α], interleukin [IL]-6, and IL-1ß), and apoptosis (TUNEL assay, upregulation of Bax protein and deregulation of Bcl-2 protein). In summary, our results suggested that TBI is a potential susceptibility factor for DILI and exacerbates DILI.

Chinese Neurosurgical Randomized Controlled Trials: Dynamics in Trial Implementation and Completion.

BACKGROUND AND OBJECTIVES: The focus on evidence-based neurosurgery has led to a considerable amount of neurosurgical evidence based on randomized controlled trials (RCTs) being published. Nevertheless, there has been no systematic appraisal of China's contribution to RCTs. Information about the changes in characteristics of Chinese neurosurgical RCTs before and during the COVID-19 pandemic is limited. This study aims to perform a detailed examination and comprehensive analysis of the characteristics of Chinese neurosurgical RCTs and to examine the differences before and during the COVID-19 pandemic. METHODS: We conducted a comprehensive database search including PubMed, Web of Science, Embase, and Cochrane Library up to March 2023, with a criterion of inclusion based on an impact factor above 0. We subsequently examined the design and quality parameters of the included RCTs and assessed the differences before and during the COVID-19 pandemic (based on follow-up ending before or after January 2020). Moreover, we investigated potential factors that may affect the quality and developmental trends of neurosurgical RCTs in China. RESULTS: The main focus of the 91 neurosurgical RCTs was vascular disease (47.3%) and trauma (18.7%). Over half of the trials used Consolidated Standards of Reporting Trial diagrams (69.2%), and the majority compared nonsurgical treatments (63.7%). Larger trials tended to have better quality scores, but those with significant efficacy were less likely to have power calculations. Over time, there was an increase in the use of Consolidated Standards of Reporting Trial diagrams and well-specified outcomes. The COVID-19 pandemic may have hindered the completion of neurosurgical RCTs in China, but it has had little impact on the design and quality so far. CONCLUSION: Chinese neurosurgeons have made significant progress in advancing neurosurgical RCTs despite challenges. However, shortcomings in sample size and power calculation need attention. Improving the rigor, rationality, and completeness of neurosurgical RCT design is crucial.

Cognitive impairment in Chinese traumatic brain injury patients: from challenge to future perspectives.

Traumatic Brain Injury (TBI) is a prevalent form of neurological damage that may induce varying degrees of cognitive dysfunction in patients, consequently impacting their quality of life and social functioning. This article provides a mini review of the epidemiology in Chinese TBI patients and etiology of cognitive impairment. It analyzes the risk factors of cognitive impairment, discusses current management strategies for cognitive dysfunction in Chinese TBI patients, and summarizes the strengths and limitations of primary testing tools for TBI-related cognitive functions. Furthermore, the article offers a prospective analysis of future challenges and opportunities. Its objective is to contribute as a reference for the prevention and management of cognitive dysfunction in Chinese TBI patients.

Delayed Administration of an Angiotensin II Type 2 Receptor Agonist Promotes Functional Recovery of the Brain and Heart After Traumatic Brain Injury.

Cardiac injury is a common complication following traumatic brain injury (TBI) that can lead to poor clinical outcomes. Angiotensin II type 2 receptor (AT2R) activation exerts protective roles in the brain and heart, yet its potential impact on TBI or TBI-induced cardiac deficits remains elusive. The goal of this study was to investigate the influence of AT2R activation on recovery after TBI-induced cognitive and cardiac injury using the selective nonpeptide AT2R agonist compound 21 (C21). TBI was induced by cortical impact injury in male adult C57BL/6J mice, and the mice received C21 (0.03 mg/kg, intraperitoneally) starting from 24 h after TBI and continuing once daily. C21 facilitated cognitive function recovery until 1 month after TBI. C21 alleviated blood-brain barrier leakage and brain edema and inhibited the expression of proinflammatory cytokines in the brain after 3 consecutive days of treatment. C21 improved cerebral blood flow after 1 month, although the lesion volume was not affected. C21 also reduced the expression of proinflammatory cytokines in the heart after a 3-day consecutive treatment. Meanwhile, C21 benefited cardiac function, as identified by increased left ventricular ejection fraction 1 month after TBI. In addition, C21 alleviated TBI-induced cardiac hypertrophy and fibrosis; however, blood pressure was not affected. Our results demonstrate that AT2R activation ameliorates TBI-induced neurological and cardiac deficits.

Metabolomic machine learning predictor for diagnosis and prognosis of gastric cancer.

Gastric cancer (GC) represents a significant burden of cancer-related mortality worldwide, underscoring an urgent need for the development of early detection strategies and precise postoperative interventions. However, the identification of non-invasive biomarkers for early diagnosis and patient risk stratification remains underexplored. Here, we conduct a targeted metabolomics analysis of 702 plasma samples from multi-center participants to elucidate the GC metabolic reprogramming. Our machine learning analysis reveals a 10-metabolite GC diagnostic model, which is validated in an external test set with a sensitivity of 0.905, outperforming conventional methods leveraging cancer protein markers (sensitivity < 0.40). Additionally, our machine learning-derived prognostic model demonstrates superior performance to traditional models utilizing clinical parameters and effectively stratifies patients into different risk groups to guide precision interventions. Collectively, our findings reveal the metabolic landscape of GC and identify two distinct biomarker panels that enable early detection and prognosis prediction respectively, thus facilitating precision medicine in GC.