Visualization of metabolite distribution based on matrix-assisted laser desorption/ionization-mass spectrometry imaging of tea seedlings (Camellia sinensis).

Tea seedlings (Camellia sinensis) have a well-developed root system with a strong taproot and lateral roots. Compared with ordinary cuttings, tea has stronger vitality and environmental adaptability, thus facilitating the promotion of good varieties. However, there is less of detailed research on the rooting and germination process of tea seeds. In this study, matrix-assisted laser desorption ionization time-of-flight-mass spectrometry was used to conduct non-targeted spatial mass spectrometry imaging of the main organs during growth of tea seedlings. A total of 1234 compounds were identified, which could be divided into 24 classes. Among them, theanine, as the most prominent nitrogen compound, was synthesized rapidly at the early stage of embryo germination, accounting for >90% of the total free amino acids in the radicle, and it was then transferred to each meristem region through the mesocolumnar sheath, indicating that theanine-based nitrogen flow plays a decisive role in organ formation during the development of tea seedlings. Nutrients stored in the cotyledon were rapidly hydrolyzed to dextrin and 3-phosphoglyceraldehyde at the early stages of germination, and subsequently converted to other forms that provided carbon and energy for development, such as raffinose and d-galactose (glucose), which were mainly distributed in the growing zones of the root apex and the apical meristems of the stem. This study provides a new perspective on the synthesis and metabolism of substances during the development of tea seedlings and contributes to a better understanding of the biological characteristics of tea varieties.

Arterial stiffness is associated with new-onset chronic kidney disease.

Background: A potential independent association between arterial stiffness (AS) and the development of new-onset chronic kidney disease (CKD) has not been thoroughly examined. Patients and methods: A total of 6929 participants were collected from the Kailuan study. All participants were free of CKD at the baseline. The participants were divided into four groups based on their brachial-ankle pulse wave velocity (baPWV) values. Cox regression models were used to analyze the relationship between baPWV values and the risk of new-onset CKD. Results: Over the course of a 10.06-year follow-up period, a total of 962 cases of new-onset CKD were documented. Cox proportional hazards analyses showed that a higher baPWV quartile was linked to an increased risk of new-onset CKD. Conclusions: Brachial-ankle pulse wave velocity has a strong correlation with the development of new-onset CKD. Therefore, baPWV can be considered an innovative indicator for predicting the occurrence of new-onset CKD.

Designing electrolytes with high solubility of sulfides/disulfides for high-energy-density and low-cost K-Na/S batteries.

Alkaline metal sulfur (AMS) batteries offer a promising solution for grid-level energy storage due to their low cost and long cycle life. However, the formation of solid compounds such as M2S2 and M2S (M = Na, K) during cycling limits their performance. Here we unveil intermediate-temperature K-Na/S batteries utilizing advanced electrolytes that dissolve all polysulfides and sulfides (K2Sx, x = 1-8), significantly enhancing reaction kinetics, specific capacity, and energy density. These batteries achieve near-theoretical capacity (1655 mAh g-1 sulfur) at 75 °C with a 1 M sulfur concentration. At a 4 M sulfur concentration, they deliver 830 mAh g-1 at 2 mA cm-2, retaining 71% capacity after 1000 cycles. This new K-Na/S battery with specific energy of 150-250 Wh kg-1 only employs earth-abundant elements, making it attractive for long-duration energy storage.

Blood MALT1 serves as a potential biomarker reflecting the response and survival of immune­checkpoint­inhibitor therapy in advanced hepatocellular carcinoma.

Treatment modalities involving an immune-checkpoint-inhibitor (ICI) have emerged as therapeutic options in advanced hepatocellular carcinoma (HCC). Nonetheless, auxiliary biomarkers are required to evaluate their efficacy. The present study aimed to assess the potential of blood mucosa-associated lymphoid tissue 1 (MALT1) in reflecting clinical response and prognosis in patients with advanced HCC who received ICI therapy. Peripheral blood was collected from 51 patients with advanced HCC who were about to receive ICI or ICI-based treatment. Blood MALT1 levels were determined using reverse transcription-quantitative PCR, and the blood MALT1 levels in 50 healthy controls (HCs) were also assessed. Besides, the treatment response and survival data were collected. The Wilcoxon rank-sum test was used for comparison analysis and the Spearman's rank correlation coefficient test was used for correlation analysis. The prognostic value of MALT1 was determined by Kaplan-Meier curve analysis with the log-rank test. Univariate and multivariate Cox regression models were used to identify factors associated with progression-free survival (PFS) and overall survival (OS). The results demonstrated that blood MALT1 levels were significantly increased in patients with advanced HCC compared with that in HCs (P<0.001). Blood MALT1 levels were increased in patients with portal vein invasion (vs. without portal vein invasion; P=0.010), extrahepatic disease (vs. without extrahepatic disease; P=0.026) and α-fetoprotein (AFP) ≥200 ng/ml (vs. AFP <200 ng/ml; P=0.040). After 4 cycles of ICI therapy, the objective response rate (ORR) and disease control rate (DCR) was 29.4 and 68.6%, respectively. Blood MALT1 levels were also significantly and negatively associated with the ORR (P=0.043) and DCR (P=0.004). Furthermore, PFS and OS were shortened in patients with high blood MALT1 levels (cut-off by the median) compared to those with low blood MALT1 levels. After adjusting using multivariate Cox regression models, high blood MALT1 levels were demonstrated to be a significant independent risk factor for shortened PFS [hazard ratio (HR)=2.419; P=0.009] and OS (HR=2.706, P=0.018) in patients with advanced HCC who received ICI therapy. In summary, blood MALT1 levels serve as a potential biomarker to reflect treatment response and survival in patients with advanced HCC who receive ICI therapy.

Triglyceride-glucose index predicts major adverse cardiovascular events in patients with chronic kidney disease.

BACKGROUND AND PURPOSE: Triglyceride-glucose (TyG) index has been regarded as a reliable surrogate marker of insulin resistance for predicting cardiovascular outcomes. The current study aimed to explore the associations between TyG index with major adverse cardiovascular events (MACE) in patients with chronic kidney disease (CKD). METHODS/PATIENTS: 13,517 patients with chronic kidney disease (CKD) from the Kailuan study were included. Patients were divided into quartiles according to the TyG index. The outcomes were MACE, including acute myocardial infarction (AMI) and ischemic stroke (IS). The association between TyG index and the risk of MACE was analyzed by Cox regression models. RESULTS: During 13.87-year follow-up, a total 1356 MACEs occurred. Multivariable Cox proportional-hazards analyses showed that a higher TyG index quartile was associated with an elevated risk of MACE. CONCLUSIONS: TyG index is significantly related to MACE in patients with CKD. TyG index can be regarded as a novel predictor of MACE for patients with CKD.

γ-Glutamyl-transpeptidase CsGGT2 functions as light-activated theanine hydrolase in tea plant (Camellia sinensis L.).

Theanine is an important secondary metabolite endowing tea with umami taste and health effects. It is essential to explore the metabolic pathway and regulatory mechanism of theanine to improve tea quality. Here, we demonstrated that the expression patterns of CsGGT2 (γ-glutamyl-transpeptidase), participated in theanine synthesis in vitro in our previous research, are significantly different in the aboveground and underground tissues of tea plants and regulated by light. Light up-regulated the expression of CsHY5, directly binding to the promoter of CsGGT2 and acting as an activator of CsGGT2, with a negative correlation with theanine accumulation. The enzyme activity assays and transient expression in Nicotiana benthamiana showed that CsGGT2, acting as bifunctional protein, synthesize and degrade theanine in vitro and in planta. The results of enzyme kinetics, Surface plasmon resonance (SPR) assays and targeted gene-silencing assays showed that CsGGT2 had a higher substrate affinity of theanine than that of ethylamine, and performed a higher theanine degradation catalytic efficiency. Therefore, light mediates the degradation of theanine in different tissues by regulating the expression of the theanine hydrolase CsGGT2 in tea plants, and these results provide new insights into the degradation of theanine mediated by light in tea plants.

Comparison of Two Diagnostic Assays for the Detection of Serum Neutralizing Antibody to Porcine Epidemic Diarrhea Virus.

Lactogenic immunity is important for the protection of piglets against many pathogens including porcine epidemic diarrhea virus. Circulating neutralizing antibodies levels in sow sera may help determine if a detectable immune response could confer protection to piglets. Neutralizing antibodies can be detected through various diagnostic assays. This study evaluated the diagnostic characteristics of two neutralizing antibody assays for porcine epidemic diarrhea virus neutralizing antibodies in serum of challenged gilts. Four treatment groups, control, non-vaccinated, vaccinated prior to challenge, and vaccinated following challenge, were comprised of 20 gilts. Serum sample were collected from each gilt prior to and following challenge with porcine epidemic diarrhea virus. Samples were evaluated for the presence of neutralizing antibodies via a fluorescent focus neutralization assay and a high-throughput neutralization assay. Diagnostic sensitivity and specificity for the fluorescent focus neutralization and high-throughput neutralization assays for this study were optimized at a cutoff of a dilution of 80 and 80% fluorescent reduction respectively and demonstrated moderate agreement based off the kappa statistic. The focus fluorescent neutralization and high-throughput neutralization assays can be used to monitor the status of neutralizing antibodies within animals or a population of animals. The high-throughput assay has advantages over the focus fluorescent assay in that it has a higher specificity at the indicated cut-off and the nature of the results allows for more discrimination between individual results.

Surface positive-charged modification of inorganic fillers to optimize lithium ion conductive pathways in composite polymer electrolytes for lithium-metal batteries.

The incorporation of inorganic fillers into composite polymer electrolytes (CPEs) is a common strategy to improve ionic conductivity. However, the high surface energy of inorganic fillers typically aggravates poor interfacial contact with polymer chains. Herein, we develop a surface positive-charge modification strategy for enhancing the intermolecular interaction of poly(ethylene oxide) (PEO) electrolytes with inorganic fillers and optimizing lithium ion (Li+) conductive pathways in CPEs. The SiO2 nanoparticles are coated with a polydopamine adhesive layer and then functionalized with a branched polyethyleneimine positively charged functional layer. Such surface modification not only effectively induces more amorphous structure into the PEO matrix but also promotes the dissociation of lithium salts and activates more free Li+ in the PEO to accelerate Li+ transport. The CPEs achieved a superior ionic conductivity of 6.12 × 10-5 S cm-1 at 30 °C. In addition, the modified fillers could induce the formation of a lithium fluoride (LiF)-rich solid-state interphase and correspondingly achieve excellent compatibility with Li metal. The Li symmetric battery using the as-prepared CPEs delivered stable Li plating/stripping performances over 3960 h under 0.2 mA cm-2. The resulting LiFePO4|Li battery has an excellent capacity retention of 92.8 % after 260 cycles at 0.5C and 60 °C.

Insight into derivative Weibull mixture model in describing simulated distributed activation energy model and distillers dried grains with solubles pyrolysis processes.

The kinetics of biomass pyrolysis is fundamental for exploring its mechanisms and optimizing its processes, which is helpful for designing its systems. The derivative Weibull mixture model was proposed for kinetic description of the simulated distribution energy model (DAEM) processes and distillers dried grains with solubles (DDGS) pyrolysis processes. The conversion rate data of these processes at different heating rates could be accurately described by the derivative Weibull mixture model. Moreover, the proposed model could effectively smooth the noises contained in the experimental conversion rate data of DDGS pyrolysis. The derivative Weibull mixture model separated DDGS pyrolysis reactions into several individual processes, and provided some data required for further isoconversional kinetic analysis. The predicted curves from the derivative Weibull mixture model allowed us to obtain the effective activation energies of DDGS pyrolysis, which varied significantly from 170 to 330 kJ mol-1 in the conversion range between 0.1 and 0.9.

Cementless bipolar hemiarthroplasty compared with proximal femoral nail anti-rotation of unstable intertrochanteric fractures in senile patients with osteoporosis: a retrospective study.

BACKGROUND: Implant design for the correction of osteoporotic unstable intertrochanteric fractures in elderly patients is a controversial issue. Our study aims to compare the efficacy of PFNA and cementless bipolar hemiarthroplasty (CBH) in treating osteoporotic unstable intertrochanteric fractures in the elderly. METHODS: We retrospectively assessed 70 elderly patients, aged > 70 years old, with intertrochanteric fractures (AO/OTA 31-A2 fractures) from 2014 to 2019. Among them, 34 patients received PFNA and 36 patients received CBH, accompanied with 2-year follow-ups. Additionally, the efficacy difference between the two implants was compared. RESULTS: Both groups had similar general variables like age, gender, fracture site, degree of osteoporosis, fracture classification, ASA score, basic diseases, preoperative preparation time, anesthesia mode, amount of postoperative blood loss, hospital length of stay, along with postoperative blood transfusions and postoperative complications (P > 0.05). Conversely, significant differences were observed among intraoperative variables (amount of blood loss, amount of blood transfusions, operative time, number of intraoperative fluoroscopy), postoperative variables (weight-bearing time out of bed), and Harris hip function score within 12 months of operation (P < 0.05). CONCLUSIONS: CBH showed no obvious advantage over PFNA in the perioperative period in elderly patients with osteoporotic unstable intertrochanteric fractures. However, the joint replacement allowed for earlier ambulation after the operation and rapid recovery of the hip joint function.

Catalpol protects mouse ATDC5 chondrocytes against interleukin-1ß-induced catabolism.

Catalpol is a natural product with promising anti-inflammatory effects, however, its effects on chondrocytes and osteoarthritis (OA) have not been well investigated. OA is a painful and debilitating joint disease that affects people worldwide. Traditional Chinese Medicine has been sought to treat OA, including the Rehmannia extract, Catalpol. Here, we examined the effects of Catalpol, a plant derivative used in traditional Chinese medicine, on ATDC5 chondrocytes originating from mouse teratocarcinoma cells stimulated with interleukin-1ß (IL-1ß) to mimic the OA cellular environment. Catalpol significantly reduced matrix metalloproteinase-1, -3, -13 (MMP-1, -3, -13), a disintegrin and metalloproteinase with thrombospondin motifs -4, -5 (ADAMTS-4, -5) against IL-1ß, demonstrating a likely anti-cartilage degradation activity. We also found that Catalpol exerted a significant anti-oxidative stress effect by downregulating the production of inducible nitric oxide synthase (iNOS), nitric oxide (NO), reactive oxygen species (ROS), and malondialdehyde (MDA). Catalpol treatment significantly reduced the levels of several key inflammatory factors, including Prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1). We further demonstrate that the effects of Catalpol were mediated by the nuclear factor -κB (NF-κB) pathway via downregulation of the phosphorylation of inhibitor of nuclear factor κB-α (IκBα). This was confirmed by measuring p38 and p65 protein levels as well as the luciferase activity of NF-κB. Altogether, we demonstrate the potential of Catalpol as a novel treatment agent against cartilage matrix degradation, oxidative stress, and inflammation in OA.

Divergent Response Strategies of CsABF Facing Abiotic Stress in Tea Plant: Perspectives From Drought-Tolerance Studies.

In plants, the bZIP family plays vital roles in various biological processes, including seed maturation, flower development, light signal transduction, pathogen defense, and various stress responses. Tea, as a popular beverage, is widely cultivated and has withstood a degree of environmental adversity. Currently, knowledge of the bZIP gene family in tea plants remains very limited. In this study, a total of 76 CsbZIP genes in tea plant were identified for the whole genome. Phylogenetic analysis with Arabidopsis counterparts revealed that CsbZIP proteins clustered into 13 subgroups, among which 13 ABFs related to the ABA signaling transduction pathway were further identified by conserved motif alignment and named CsABF1-13, these belonged to the A and S subgroups of CsbZIP and had close evolutionary relationships, possessing uniform or similar motif compositions. Transcriptome analysis revealed the expression profiles of CsABF genes in different tissues (bud, young leaf, mature leaf, old leaf, stem, root, flower, and fruit) and under diverse environmental stresses (drought, salt, chilling, and MeJA). Several CsABF genes with relatively low tissue expression, including CsABF1, CsABF5, CsABF9, and CsABF10, showed strong expression induction in stress response. Thirteen CsABF genes, were examined by qRT-PCR in two tea plant cultivars, drought-tolerant "Taicha 12" and drought-sensitive "Fuyun 6", under exogenous ABA and drought stress. Furthermore, CsABF2, CsABF8, and CsABF11, were screened out as key transcription factors regulating drought tolerance of tea cultivars. Subsequently, some potential target genes regulated by CsABFs were screened by co-expression network and enrichment analysis. This study update CsbZIP gene family and provides a global survey of the ABF gene family in tea plant. The resolution of the molecular mechanism of drought resistance in different varieties could be helpful for improving stress resistance in tea plant via genetic engineering.

In Situ Formed Lithiophilic LixNbyO in a Carbon Nanofiber Network for Dendrite-Free Li-Metal Anodes.

Lithium metal is considered as a strongly attractive anode candidate for the high-energy-storage field, but its dreadful dendrite growth has haunted its commercialization progress. Herein, we develop a lithiophilic Nb2O5-embedded three-dimensional (3D) carbon nanofiber network (Nb2O5-CNF) as a scaffold to preload molten Li for the fabrication of dendrite-free composite anode. The in situ lithiation reaction between molten Li and Nb2O5 nanocrystals results in the formation of nanosize LixNbyO nanoparticles, which can serve as preferred sites that regulate nucleation/growth behavior of Li during the plating process. Besides, due to its high structural stability and abundant internal inner space, the 3D CNF network can function as a reservoir to confine the dimensional expansion of "hostless Li". The resulting Li composite anodes exhibit enlarged active areas and reduced interfacial energy barriers, delivering a prolonged cycling of 1000 h with an ultralow hysteresis of 52 mV and dendrite-free morphology in a symmetric cell (1.0 mA cm-2). Coupled with the LiFePO4 cathode, the Li@Nb2O5-CNF anode sustains a reversible capacity of 163 mAh g-1 with an excellent capacity retention of 93.0% after 370 cycles at 0.5C. This all-around strategy of lithiophilic sites coupled with a 3D conductive nanofiber matrix may shed light on promising applications of high-capacity and dendrite-free Li-metal batteries.

Homogenously dispersed ultrasmall niobium(V) oxide nanoparticles enabling improved ionic conductivity and interfacial compatibility of composite polymer electrolyte.

Composite polymer electrolytes (CPEs) decorated with ceramic fillers have emerged as appealing structures that exhibit coalesced merits of both inorganic and polymer solid electrolytes, but are currently challenged by the particle agglomeration that weakens ionic conductivity and electrochemical performances. Herein, a facile solvothermal method is proposed to fabricate the ultrasmall niobium(V) oxide (Nb2O5) nanoparticle of average size being less than 3 nm, enabling the composite polymer electrolyte with homogenous dispersity (nano-CPE). Owning to the superior dispersity of ultrasmall Nb2O5 nanoparticles, the polymer chains can be effectively disordered to enhance the local segmental motion through the physical interruption. Moreover, strong Lewis acid-based interactions between Nb2O5 nanoparticles and lithium salts are formed, resulting in accelerating the dissociation of lithium salt and releasing more free charge carriers. Therefore, the 3D connected Li+ fast pathways along the amorphous region between the Nb2O5 nanoparticles and polymer chains are constructed, ensuring the improved ionic conductivity. In addition, the homogenous Li deposition can also be simultaneously achieved through the intimate interfacial contact, which can efficiently suppress the growth of lithium dendrite in the metal anode. The fabricated nano-CPE presents a high ionic conductivity of 6.6 × 10-5 S/cm at room temperature and wide anti-oxidative potential of 5.1 V. The lithium symmetric battery using nano-CPE delivers a decent lithium plating/stripping performance for 200 h at 0.5 mA/cm2. The solid-sate LiFePO4 battery achieves long stable cycling performances (151mAh/g and 140 mAh/g after 230 cycles at 0.5C and 1.0C, respectively). This work may offer a facile and efficient synthesized method of highly dispersed ultrasmall nanoparticles for advancing the CPE with improved ionic conductivity, interfacial contact and cell performances.

Isoflurane preconditioning effects on brain damage induced by electromagnetic pulse radiation through epigenetic modification of BDNF gene transcription.

BACKGROUND: The effects of electromagnetic pulse (EMP) radiation on cognitive impairment have attracted much attention, but the mechanism is still unclear. Regulation of brain-derived neurotrophic factor (BDNF) gene expression has been found to promote memory formation and neuronal survival. Isoflurane preconditioning (IP) was reported to have a neuroprotective effect. In this study, we verified the protective effect of IP against brain injury induced by EMP exposure and examined the relation of this effect with BDNF gene regulation. METHODS: Twenty-four hours before EMP exposure, rats were pretreated with 2% inhaled isoflurane for 30 minutes. At 24 hours after EMP injury, the Morris water maze test was carried out. Meanwhile, the other rats were executed and their brain tissues were used for Nissl staining, qRT-PCR, western blot and chromatin immunoprecipitation. RESULTS: The Morris water maze results showed that 2% IP improved the spatial learning and memory ability of the rats. The Nissl staining results showed 2% of IP alleviated neuronal damage. Also, we detected the mRNA and protein expression of BDNF, and 2% IP significantly increased the expression of BDNF. We also found the expression level of histone deacetylase 2 (HDAC2) was increased and that EMP exposure significantly decreased H3 acetylation, while 2% IP reversed these phenomena, individually, BDNF transcription was activated, and neurogenesis after EMP exposure was alleviated. CONCLUSIONS: Our results suggested that 2% of IP alleviates cognitive impairment induced by EMP exposure in rats. Also, the sustained elevated level of BDNF gene transcription may be an essential mechanism for stimulating neurogenesis because of the increased level of HDAC2-dependent H3 acetylation.

Derlin-1 Promotes the Progression of Human Hepatocellular Carcinoma via the Activation of AKT Pathway.

INTRODUCTION: Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. In the present research, we explored a new oncogene, derlin-1 (DERL1), and studied its role and mechanism in human HCC. METHODS: We assessed the expression and prognosis value of DERL1 in human HCC by using GEPIA dataset analysis and immunohistochemistry. To elucidate the specific function of DERL1, we suppressed its expression in two HCC cell lines, HuH7 and Hep3B, and overexpressed DERL1 in Hep3B cells. Cell proliferation and migration was detected by CCK8 and transwell assays. Cell flow cytometry was used to evaluate cell apoptosis. RESULTS: Our results demonstrated that DERL1 was highly expressed in HCC samples (n = 369) than in normal samples (n = 160). Similar results were obtained in 60 clinical samples that we collected from the local hospital. The high expression rate of DERL1 reached 78.3% (47/60). DERL1 overexpression samples were concentrated in patients with tumor diameters >5cm or lymph node metastases. Thus, we speculated that DERL1 operated as a tumor promotor in HCC, and its expression might be proposed as a predictor for tumor metastasis of human HCC. Interference of DERL1 markedly blocked cell proliferation and migration, and induced the apoptosis of HCC cells in vitro. Phosphorylation of Akt was significantly inhibited in cells transfected with DERL1 siRNA compared to their control cells in HuH7 and Hep3B cell lines. The opposite result was observed in the DERL1 overexpression cells. CONCLUSION: Our findings prove that DERL1 promotes tumor progression via AKT pathway and provide a new potential target for the clinical treatment and diagnosis of human HCC.

Detection of porcine epidemic diarrhea virus-neutralizing antibody using high-throughput imaging cytometry.

Porcine epidemic diarrhea virus (PEDV) is an emerging porcine coronavirus that causes a tremendous economic burden on the swine industry. The assessment of PEDV-neutralizing antibody levels provides a valuable tool to assess and predict herd immunity. We evaluated the performance of a PEDV imaging cytometry-based high-throughput neutralization test (HTNT) and compared the HTNT to a fluorescent focus neutralization (FFN) assay using serum samples from pigs of known PEDV infection status (n = 159). Estimates of diagnostic sensitivity and specificity for HTNT and FFN assays derived from receiver-operator characteristic (ROC) curve analyses showed that both PEDV FFN and HTNT provided excellent diagnostic performance. However, in the laboratory, imaging cytometry provided an objective and semi-automated approach that removed human subjectivity from the testing process and reduced the read-time of a 96-well plate to < 4 min. In addition, imaging cytometry facilitated the rapid collection and long-term storage of test images and data for further evaluation or client consultation. For PEDV and other pathogens, imaging cytometry could provide distinct advantages over classic virus neutralization or FFN assays for the detection and quantitation of neutralizing antibody.

Isoflurane preconditioning ameliorates electromagnetic pulse-induced neural damage by shifting microglia polarization toward anti-inflammatory phenotype via upregulation of SOCS1.

With the speedy technological advances during the past few decades, human exposure to the electromagnetic field (EMF) has become increasingly common. Exposure to EMF may induce neural injuries and dysfunction of various organs, likely involving neuroinflammation and activation of microglial cells. Isoflurane preconditioning (IP) is shown to provide neuroprotection in various neurological diseases by inhibiting excessive neuroinflammatory responses. Brain samples harvested from rats exposed to electromagnetic pulse (EMP) with or without IP were subjected to qPCR, Western blot assay, and immunohistochemistry to determine the expression of pro-inflammatory/anti-inflammatory microglia markers and a variety of pro- and anti-inflammatory mediators. Suppressor of cytokine signaling 1 (SOCS1) siRNA was used in cultured N9 microglia cells to examine the roles of SOCS1 in the effect of IP. In both in vivo and in vitro experiments, EMP-exposed microglia were predominantly pro-inflammatory microglia, accompanied by increased expression of pro-inflammatory cytokines and chemokines, and activation of TLR4 pathway, leading to neuronal death. IP reversed the changes induced by EMP and switched the activated microglia to an anti-inflammatory phenotype. SOCS1 siRNA abolished the beneficial effects of IP. IP ameliorates EMP-induced neural injuries by shifting microglia polarization from pro-inflammatory to anti-inflammatory phenotype via upregulation of SOCS1.

MARCH8 is associated with poor prognosis in non-small cell lung cancers patients.

MARCH8 belongs to a family of membrane-associated RING-CH (MARCH) ubiquitin ligases. The functions of MARCH8 have been thoroughly investigated but its mechanism of action remains unknown. In this study, we detected the expression of MARCH8 protein in NSCLC samples and identified MARCH8 mRNA expression through a TCGA database. In addition, we analyzed the correlation between MARCH8 and the clinical characteristics of NSCLC patients and their prognosis.(www.kmplot.com). The roles of MARCH8 in proliferation, migration, and metastasis were further explored through ectopic expression analysis and western blot analysis; its mechanism of expressionwas also explored. We discovered that MARCH8 was downregulated in NSCLC tissues compared to adjacent normal lung tissues. Overexpression of MARCH8 inhibited NSCLC cell proliferation and metastasis via the PI3K and mTOR signaling pathways; this also increased apoptosis of A549 and H1299 cells. Our results indicated that MARCH8 plays crucial roles in NSCLC against carcinogenesis and progression; therefore, MARCH8 might be a predictive factor and an attractive therapeutic target for NSCLC patients.