CD36 deletion prevents white matter injury by modulating microglia polarization through the Traf5-MAPK signal pathway.

BACKGROUND: White matter injury (WMI) represents a significant etiological factor contributing to neurological impairment subsequent to Traumatic Brain Injury (TBI). CD36 receptors are recognized as pivotal participants in the pathogenesis of neurological disorders, including stroke and spinal cord injury. Furthermore, dynamic fluctuations in the phenotypic polarization of microglial cells have been intimately associated with the regenerative processes within the injured tissue following TBI. Nevertheless, there is a paucity of research addressing the impact of CD36 receptors on WMI and microglial polarization. This investigation aims to elucidate the functional role and mechanistic underpinnings of CD36 in modulating microglial polarization and WMI following TBI. METHODS: TBI models were induced in murine subjects via controlled cortical impact (CCI). The spatiotemporal patterns of CD36 expression were examined through quantitative polymerase chain reaction (qPCR), Western blot analysis, and immunofluorescence staining. The extent of white matter injury was assessed via transmission electron microscopy, Luxol Fast Blue (LFB) staining, and immunofluorescence staining. Transcriptome sequencing was employed to dissect the molecular mechanisms underlying CD36 down-regulation and its influence on white matter damage. Microglial polarization status was ascertained using qPCR, Western blot analysis, and immunofluorescence staining. In vitro, a Transwell co-culture system was employed to investigate the impact of CD36-dependent microglial polarization on oligodendrocytes subjected to oxygen-glucose deprivation (OGD). RESULTS: Western blot and qPCR analyses revealed that CD36 expression reached its zenith at 7 days post-TBI and remained sustained at this level thereafter. Immunofluorescence staining exhibited robust CD36 expression in astrocytes and microglia following TBI. Genetic deletion of CD36 ameliorated TBI-induced white matter injury, as evidenced by a reduced SMI-32/MBP ratio and G-ratio. Transcriptome sequencing unveiled differentially expressed genes enriched in processes linked to microglial activation, regulation of neuroinflammation, and the TNF signaling pathway. Additionally, bioinformatics analysis pinpointed the Traf5-p38 axis as a critical signaling pathway. In vivo and in vitro experiments indicated that inhibition of the CD36-Traf5-MAPK axis curtailed microglial polarization toward the pro-inflammatory phenotype. In a Transwell co-culture system, BV2 cells treated with LPS + IFN-γ exacerbated the damage of post-OGD oligodendrocytes, which could be rectified through CD36 knockdown in BV2 cells. CONCLUSIONS: This study illuminates that the suppression of CD36 mitigates WMI by constraining microglial polarization towards the pro-inflammatory phenotype through the down-regulation of the Traf5-MAPK signaling pathway. Our findings present a potential therapeutic strategy for averting neuroinflammatory responses and ensuing WMI damage resulting from TBI.

Neutrophil extracellular traps facilitate sympathetic hyperactivity by polarizing microglia toward M1 phenotype after traumatic brain injury.

Traumatic brain injury (TBI), particularly diffuse axonal injury (DAI), often results in sympathetic hyperactivity, which can exacerbate the prognosis of TBI patients. A key component of this process is the role of neutrophils in causing neuroinflammation after TBI by forming neutrophil extracellular traps (NETs), but the connection between NETs and sympathetic excitation following TBI remains unclear. Utilizing a DAI rat model, the current investigation examined the role of NETs and the HMGB1/JNK/AP1 signaling pathway in this process. The findings revealed that sympathetic excitability intensifies and peaks 3 days post-injury, a pattern mirrored by the activation of microglia, and the escalated NETs and HMGB1 levels. Subsequent in vitro exploration validated that HMGB1 fosters microglial activation via the JNK/AP1 pathway. Moreover, in vivo experimentation revealed that the application of anti-HMGB1 and AP1 inhibitors can mitigate microglial M1 polarization post-DAI, effectively curtailing sympathetic hyperactivity. Therefore, this research elucidates that post-TBI, NETs within the PVN may precipitate sympathetic hyperactivity by stimulating M1 microglial polarization through the HMGB1/JNK/AP1 pathway.

Trends in Adherence to Recommended Physical Activity and Its Association with Mortality and Disease Progression among US Adults with Chronic Kidney Disease.

INTRODUCTION: This study aimed to examine the trends in adherence to the Physical Activity Guidelines (PAG) for aerobic activity and sedentary time and their effects on mortality and disease progression among US adults with chronic kidney disease (CKD). METHODS: We studied individuals from the National Health and Nutrition Examination Survey 2007-08 to 2017-18 with a mortality file in 2015. Multivariate regression models were used to evaluate the association between adherence to PAG and sedentary time with mortality, estimated glomerular filtration rate (eGFR), and urine albumin-to-creatinine ratio. RESULTS: For the CKD population, adherence rate increased from 48.2% in 2007-08 to 55.0% in 2017-18, and sedentary time peaked in 2013-14 (7.5 h/day) and then decreased afterward. There was no difference in the trends across the non-CKD and CKD population. For the CKD population, adherence to the PAG was significantly associated with all-cause mortality (HR, 0.49; 95% CI: 0.38-0.63), malignant neoplasm mortality (HR, 0.30; 95% CI: 0.17-0.52), and albumin-creatinine ratio (OR, -0.27; 95% CI: -0.39 to -0.15). Sedentary time was significantly associated with all-cause mortality (HR, 1.12; 95% CI: 1.08-1.15), heart disease mortality (HR, 1.13; 95% CI: 1.08-1.19), and eGFR (OR, -0.49; 95% CI: -0.72 to -0.26). CONCLUSIONS: Favorable trends were observed in adherence to the PAG and sedentary time. Adherence to the PAG and reduction in sedentary time reduced all-cause and cause-specific mortality and prevented disease progression differently. Efforts are needed to decrease sedentary time rather than adhering to the PAG for aerobic activity alone.

The emerging roles of circular RNAs in CNS injuries.

With high morbidity and mortality worldwide, injuries to the central nervous system (CNS) usually result in devastating consequences. However, the underlying mechanisms have not been fully understood and current therapies are still limited. Circular RNA (circRNA) is a novel type of endogenous noncoding RNAs, characterized by covalently closed annular structure. It is gradually recognized that circRNAs are involved in multiple biological processes, such as acting as microRNA sponges or scaffolds during the assembly of protein complex and modulating the transcription of certain genes. Interestingly, circRNAs have been found to be highly expressed in the CNS, which indicates their neurospecificity. Several circRNAs have already been discovered to be associated with multiple pathophysiological processes following neurological diseases. Currently, the molecular roles of circRNAs in CNS injuries have gained increasing attention, leading to uninterrupted relevant researches. Herein, we presented a review of current studies on the role of circRNAs in CNS injuries. The therapeutic potency of circRNAs in CNS injuries was also analyzed.

Peak Neutrophil-to-Lymphocyte Ratio Correlates with Clinical Outcomes in Patients with Severe Traumatic Brain Injury.

BACKGROUND: Studies suggested that the neutrophil-to-lymphocyte ratio (NLR) was associated with unfavorable outcomes in different diseases such as intracerebral hemorrhage, cardiovascular problem, cancer, and severe traumatic brain injury (sTBI). We aimed to evaluate the relationship between peak NLR and 1-year outcomes in patients with sTBI. METHODS: We retrospectively reviewed the clinical data of patients with sTBI who were treated in our department between January 2013 and January 2017. NLRs between day 1 and day 12 after admission as well as other related indicators were collected. The relationship between peak NLR and 1-year outcomes was analyzed. Factors associated with larger peak NLR were also explored. RESULTS: A total of 316 patients were included, and 81.3% (257/316) experienced unfavorable outcomes. Peak NLR was identified as an independent predictor for unfavorable outcomes after sTBI in multivariable logistic regression analysis (odds ratio, 1.086; 95% confidence interval, 1.037-1.137; P < 0.001). Its predictive value was confirmed by receiver operating characteristic analysis (area under curve = 0.775; P < 0.001). The day 1 NLR as well as admission Glasgow Coma Scale score was independently correlated with increased peak NLR. CONCLUSION: Peak NLR was associated with the clinical prognosis after sTBI and was a promising predictor for 1-year outcomes.

Berberine and chlorogenic acid-assembled nanoparticles for highly efficient inhibition of multidrug-resistant Staphylococcus aureus.

Due to the bacteria resistant to various first-line antibiotics, it is urgent to develop efficient antibiotic alternatives and formulate multidimensional strategies. Herein, supramolecular Chinese medicine nanoparticles are synthesized by self-assembly of berberine (BBR) and chlorogenic acid (CGA), which exhibit higher inhibitory effect against Staphylococcus aureus and multidrug-resistant Staphylococcus aureus (MRSA) than ampicillin, oxacillin, BBR, CGA, as well as mixture of BBR and CGA (minimum inhibitory concentration, MIC = 1.5 µM). The inhibition by BBR/CGA nanoparticles (2.5 µM) reaches 99.06 % for MRSA, which is significantly higher than ampicillin (29.03 %). The nanoparticles with 1/2 MIC can also synergistically restore the antimicrobial activity of ampicillin against MRSA. Moreover, in vivo therapeutic outcome in the murine skin wound infection model suggests that the nanoparticles are able to promote wound healing. This study provides new insights in the application of Chinese medicines self-assembly for MRSA inhibition, as well as solutions for potential persistent clinical infections and drug deficiencies.

Simultaneous adsorption and biodegradation of oxytetracycline in wastewater by Mycolicibacterium sp. immobilized on magnetic biochar.

Due to the adverse effects of long-term oxytetracycline (OTC) residues in aquatic environments, an effective treatment is urgently needed. Immobilized microbial technology has been widely explored in the treatment of various organic pollutants in aquatic environments with its excellent environmental adaptability. Nevertheless, studies on its application in the removal of antibiotics are relatively scarce and not in sufficient depth. Only a few studies have further investigated the final fate of antibiotics in the immobilized bacteria system. In this study, a novel kind of OTC-degrading bacteria Mycolicibacterium sp. was immobilized on straw biochar and magnetic biochar, respectively. Magnetic biochar was proved to be a more satisfactory immobilization carrier due to its superior property and the advantage of easy recycling. Compared with free bacteria, immobilized bacteria had stronger environmental adaptability under different OTC concentrations, pH, and heavy metal ions. After 5 cycles, immobilized bacteria could still remove 71.8% of OTC, indicating that it had a stable recyclability. Besides, OTC in real swine wastewater was completely removed by immobilized bacteria within 2 days. The results of FTIR showed that bacteria were successfully immobilized on biochar and O-H, N-H, and C-N groups might be involved in the removal of OTC. The fate analysis indicated that OTC was removed by simultaneous adsorption and biodegradation, while biodegradation (92.8%) played a dominant role in the immobilized bacteria system. Meanwhile, the amount of adsorbed OTC (7.20%) was rather small, which could effectively decrease the secondary pollution of OTC. At last, new degradation pathways of OTC were proposed. This study provides an eco-friendly and effective approach to remedy OTC pollution in wastewater.

Structure-performance correlation guided cerium-based metal-organic frameworks: Superior adsorbents for fluoride removal in water.

Fluoride in the hydrosphere exceeds the standard, which could be critically hazardous to human health and the natural environment. The adsorption method is a mature and effective way to remove pollutants in water, including fluoride. In this study, we synthesized three kinds of cerium-based metal-organic frameworks (Ce-MOFs) with different structures and properties by modulating the organic ligands (i.e., trimesic acid (BTC), 1,2,4,5-benzenetetracarboxylic acid (PMA), and terephthalic acid (BDC)) via the solvothermal method. The adsorption kinetics of Ce-MOFs on fluoride well fit the pseudo second order model, and their adsorption isotherms also conform to Langmuir isothermal model. The thermodynamic study reveals that the adsorption process is a spontaneous endothermic reaction. The maximum saturated adsorption capacities of Ce-BTC, Ce-PMA, and Ce-BDC are 70.7, 159.6, and 139.5 mg g-1, respectively. Ce-MOFs have stable and excellent adsorption capacity at pH = 3-9. Coexisting anions (Cl-, SO42-, and NO3-) do not affect the performance of Ce-MOFs for fluoride removal. Moreover, Ce-MOFs also show their broad prospect as superior fluoride adsorbents because of their excellent performance and reusability in real water samples. Organic ligands have a remarkable influence on the defluoridation performance of Ce-MOFs. This work will provide a feasible idea for designing MOFs as superiors adsorbents for defluoridation.

Trends in adherence to recommended physical activity and its effects on cardiometabolic markers in US adults with pre-diabetes.

INTRODUCTION: This study aimed to examine the trends in adherence to Physical Activity Guidelines for Americans (PAG) as well as the association between them and cardiometabolic risk factors among US adults with pre-diabetes. RESEARCH DESIGN AND METHODS: This study included 6734 participants who were diagnosed with pre-diabetes from the National Health and Nutrition Examination Survey 2007-2008 to 2017-2018. The logistic regression model and linear regression model were used to test the trends in adherence to PAG. The multivariable linear regression model was used to examine the association between adherence to PAG and cardiometabolic risk factors. RESULTS: The rate of adherence to the PAG for aerobic physical activity was not significantly changed (64.1% in 2007-2008 to 66.4% in 2017-2018, p=0.599). The sedentary time changed significantly (5.6, 6.8, and 6.0 hours in 2007-2008, 2013-2014, and 2017-2018, respectively; p<0.001). Adherence to the PAG was significantly associated with levels of waist circumference, body mass index (BMI), high-density lipoprotein cholesterol (HDL-C), triglycerides, insulin, 2-hour postload plasma glucose, and measurements of insulin resistance (homeostatic model assessment for insulin resistance (HOMA-IR)) and ß-cell function (homeostasis model assessment of ß-cell function (HOMA-ß)). There was a significant relationship between sedentary time and levels of waist circumference, BMI, HDL-C, insulin, 2-hour postload glucose, HOMA-IR, and HOMA-ß. The associations of adherence to the PAG and sedentary time with the levels of systolic and diastolic blood pressures and hemoglobin A1c were not significant. CONCLUSIONS: Adherence to PAG for aerobic activity did not change significantly among US adults with pre-diabetes. The time spent on sedentary behavior peaked in 2013-2014 and then decreased afterward. Adhering to the PAG for aerobic activity and reducing sedentary time significantly improved cardiometabolic health among adults with pre-diabetes.

Methyladenosine Modification in RNAs: From Regulatory Roles to Therapeutic Implications in Cancer.

Methyladenosine modifications are the most abundant RNA modifications, including N6-methyladenosine (m6A), N1-methyladenosine (m1A), and 2'-O-methyladenosine (m6Am). As reversible epigenetic modifications, methyladenosine modifications in eukaryotic RNAs are not invariable. Drastic alterations of m6A are found in a variety of diseases, including cancers. Dynamic changes of m6A modification induced by abnormal methyltransferase, demethylases, and readers can regulate cancer progression via interfering with the splicing, localization, translation, and stability of mRNAs. Meanwhile, m6A, m1A, and m6Am modifications also exert regulatory effects on noncoding RNAs in cancer progression. In this paper, we reviewed recent findings concerning the underlying biomechanism of methyladenosine modifications in oncogenesis and metastasis and discussed the therapeutic potential of methyladenosine modifications in cancer treatments.

The Alteration of M6A-Tagged Transcript Profiles in the Retina of Rats After Traumatic Optic Neuropathy.

Messager RNA (mRNA) can be modified in a variety of ways, among which the modification of N6-methyladenosine (m6A) is one of the most common ones. Recent studies have found that the m6A modification in mRNA could functionally regulate the splicing, localization, translation, and stability of mRNA, which might be closely related to multiple diseases. However, the roles of m6A modification in traumatic optic neuropathy (TON) are unknown. Herein, we detected the expression of m6A-related genes via quantitative real-time PCR (qRT-PCR) and performed methylated RNA immunoprecipitation sequencing (MeRIP-seq) as well as RNA-sequencing to analyze the alteration profiles of m6A modification after TON. The results showed that the expression of m6A-related genes (METTL3, WTAP, FTO, and ALKBH5) were all upregulated after TON. In all, 2,810 m6A peaks were differentially upregulated and 689 m6A peaks were downregulated. In addition, the hypermethylated and hypomethylated profiles of mRNA transcripts were also identified. To sum up, our study revealed the differentially expressed m6A modification in the early stage of TON, which may provide novel insights into the mechanism and treatment of TON.

NETs Lead to Sympathetic Hyperactivity After Traumatic Brain Injury Through the LL37-Hippo/MST1 Pathway.

Background: Paroxysmal sympathetic hyperactivity (PSH) is one of the important reasons for the high mortality and morbidity of traumatic brain injury (TBI). We aim to explore the role of the neutrophil extracellular traps (NETs) in the pathogenesis of sympathetic hyperexcitability after TBI and the underlying mechanisms, providing evidence for clinical treatment. Methods: Enzyme-linked immunosorbent assay was used to assess the plasma metanephrine and normetanephrine levels which represented the variation of the sympathetic system after TBI with rat diffuse axonal injury (DAI) model. NETs in the paraventricular nucleus (PVN) and circulating blood were examined using immunofluorescence and flow cytometry. Neutrophils-microglia co-culture system was established to further explore the effect of NETs on PSH and its mechanisms. Results: After TBI, metanephrine and normetanephrine levels began to increase at 9 h and peaked at 72 h. After the injury, the level of NETs kept increasing at 24 and 72 h in the PVN. A positive correlation was found between the concentration of the PVN NETs and blood catecholamine. Flow cytometry of peripheral blood cells revealed that NETs level in the injury group was higher than that in the control group. Immunofluorescence results confirmed the presence of NETs in the PVN after TBI. The positive result of immunoprecipitation suggested a correlation effect between LL37 and P2 × 7. Peptidyl arginine deiminase-4 (PAD4) inhibitor could inhibit the expression levels of MST1, YAP, and IL-1ß. The hippo/MST1 pathway inhibitor could inhibit the expression levels of YAP and IL-1ß. Conclusion: NETs formation in the PVN might be associated with sympathetic hyperactivity after TBI, which might relate to the activation of microglia cells and increased secretion of IL-1ß via the hippo/MST1 pathway.

Management of a Steel Bar Injury Penetrating the Head and Neck: A Case Report and Review of the Literature.

BACKGROUND: Nonmissile penetrating injuries to the head and neck caused by a steel bar are rare, and a standard management strategy is lacking. CASE DESCRIPTION: A 42-year-old woman sustained a steel bar injury with penetration of the head and neck. Computed tomography and three-dimensional reconstruction were performed for preoperative evaluation. Digital subtraction angiography was performed to confirm potential vascular injury. The steel bar was successfully removed through an open surgical procedure by a multidisciplinary team. CONCLUSIONS: Relevant literature regarding nonmissile penetrating injuries involving a steel bar was reviewed to propose appropriate management strategies. Comprehensive imaging evaluation and prompt surgery by a multidisciplinary team contributed to the successful removal of the steel bar.