Large-Scale Comparative Analyses of Tick Genomes Elucidate Their Genetic Diversity and Vector Capacities.

Among arthropod vectors, ticks transmit the most diverse human and animal pathogens, leading to an increasing number of new challenges worldwide. Here we sequenced and assembled high-quality genomes of six ixodid tick species and further resequenced 678 tick specimens to understand three key aspects of ticks: genetic diversity, population structure, and pathogen distribution. We explored the genetic basis common to ticks, including heme and hemoglobin digestion, iron metabolism, and reactive oxygen species, and unveiled for the first time that genetic structure and pathogen composition in different tick species are mainly shaped by ecological and geographic factors. We further identified species-specific determinants associated with different host ranges, life cycles, and distributions. The findings of this study are an invaluable resource for research and control of ticks and tick-borne diseases.

Genetic and phenotypic profiling of single living circulating tumor cells from patients with microfluidics.

Accurate prediction of the efficacy of immunotherapy for cancer patients through the characterization of both genetic and phenotypic heterogeneity in individual patient cells holds great promise in informing targeted treatments, and ultimately in improving care pathways and clinical outcomes. Here, we describe the nanoplatform for interrogating living cell host-gene and (micro-)environment (NICHE) relationships, that integrates micro- and nanofluidics to enable highly efficient capture of circulating tumor cells (CTCs) from blood samples. The platform uses a unique nanopore-enhanced electrodelivery system that efficiently and rapidly integrates stable multichannel fluorescence probes into living CTCs for in situ quantification of target gene expression, while on-chip coculturing of CTCs with immune cells allows for the real-time correlative quantification of their phenotypic heterogeneities in response to immune checkpoint inhibitors (ICI). The NICHE microfluidic device provides a unique ability to perform both gene expression and phenotypic analysis on the same single cells in situ, allowing us to generate a predictive index for screening patients who could benefit from ICI. This index, which simultaneously integrates the heterogeneity of single cellular responses for both gene expression and phenotype, was validated by clinically tracing 80 non-small cell lung cancer patients, demonstrating significantly higher AUC (area under the curve) (0.906) than current clinical reference for immunotherapy prediction.

EMX2 inhibits clear cell renal cell carcinoma progress via modulating Akt/FOXO3a pathway.

Empty spiracles homeobox 2 (EMX2) is initially identified as a key transcription factor that plays an essential role in the regulation of neuronal development and some brain disorders. Recently, several studies emphasized that EMX2 could as a tumor suppressor, but its role in human clear cell renal cell carcinoma (ccRCC) remains unclear. In the present study, we investigated the role and underlying mechanism of EMX2 in the regulation of ccRCC progress. Our results demonstrated that EMX2 expression was markedly decreased in ccRCC tissues and cell lines, and low EMX2 expression predicted the poor prognosis of ccRCC patients. In addition, forced expression of EMX2 significantly inhibited the cell growth, migration, and invasion in vitro, as well as ccRCC tumor growth in nude mice, via, at least in part, regulating Akt/FOXO3a pathway. In detail, EMX2 could attenuate the phosphorylation levels of Akt and FOXO3a, and increase FOXO3a expression without affecting total Akt expression in vivo and in vitro. Meanwhile, shRNA-mediated knockdown of FOXO3a expression could obviously attenuate the effects of EMX2 on cell growth, migration, invasion, and tumor growth. Furthermore, EMX2 could significantly attenuate the interaction between Akt and FOXO3a. Taken together, our results demonstrated that EMX2 could inhibit ccRCC progress through, at least in part, modulating Akt/FOXO3a signaling pathway, thus representing a novel role and underlying mechanism of EMX2 in the regulation of ccRCC progress.

LbCOPT1 is a copper transporter induced in Lycium barbarum mycorrhizal roots, which allows tobacco with improved growth and nutrient uptake.

KEY MESSAGE: Overexpressing the copper transporter LbCOPT1 leads to a notable increase in the abundance of mycorrhizal arbuscules that suggests the potential application of LbCOPT1 in breeding programs aimed at enhancing symbiotic nutrient uptake in Lycium barbarum L.

Scoparone attenuates glioma progression and improves the toxicity of temozolomide by suppressing RhoA/ROCK1 signaling.

BACKGROUND: Glioma, a type of malignant brain tumor, has become a challenging health issue globally in recent years. METHODS: In this study, we investigated the potential therapeutic role of scoparone in glioma and the underlying mechanism. Initially, transcriptome sequencing was conducted to identify genes that exhibited differential expression in glioma cells treated with scoparone compared to untreated cells. Subsequently, the impact of scoparone on the proliferation, migration, and invasion of glioma cells was assessed in vitro using a range of assays including cell viability, colony formation, wound healing, and transwell assays. Moreover, the apoptotic effects of scoparone on glioma cells were evaluated through flow cytometry and western blot analysis. Furthermore, we established a glioma xenograft mouse model to assess the in vivo antitumor activity of scoparone. Lastly, by integrating transcriptome analysis, we endeavored to unravel the molecular mechanisms underlying the observed antitumor effects of scoparone by examining the expression levels of RhoA/ROCK1 signaling pathway components using western blot analysis and qRT-PCR. RESULTS: Our transcriptome sequencing results revealed that scoparone significantly downregulated RhoA/ROCK1 signaling in glioma cells. Furthermore, scoparone treatment inhibited glioma cell proliferation, migration, and invasion, and promoted cell apoptosis in vitro. Moreover, scoparone reduced tumor growth and prolonged survival in a glioma xenograft mouse model, and improved the toxicity of temozolomide. Finally, our results showed that the antitumor effects of scoparone were mediated by the suppression of RhoA/ROCK1 signaling. CONCLUSION: Scoparone could be a promising therapeutic agent for glioma by suppressing RhoA/ROCK1 signaling. These findings pave the way for future research endeavors aimed at the development and optimization of scoparone-based therapeutic strategies.

The Ideal Proportion of the Auricle Exposure via a Morphometric Analysis in Asian Women.

BACKGROUND: Ears are an important aesthetic feature that is vital to the overall attractiveness of the face. Although there have been many studies on the aesthetics of the auricle, there is currently a lack of consensus on the ideal proportion of auricle exposure for Asian women in frontal view. OBJECTIVES: This study aimed to investigate ideal proportion of auricle exposure in Asian women. METHODS: An observational study was carried out on the photographs of 84 women on the list of the 100 most beautiful faces in Asia (published by TCC Asia in 2020). The proportion of the distance between the outer canthus and the outermost point of auricle to the distance between the inner canthus and the outermost point of auricle was calculated as the auricle exposure proportion. Evaluators were asked to rank a set of photographs of the volunteer with varying auricle exposure proportions from most attractive to least attractive. RESULTS: Measurements of the photographs of the 84 women showed a mean ear exposure proportion of 0.600. With 487 questionnaire responses received, the proportion of auricle exposure that the evaluators considered most attractive was 0.600. People with aesthetic experience considered 0.625 the most attractive proportion, while the general group considered 0.600 the most attractive. CONCLUSIONS: The ideal proportion of the auricle exposure for Asian women is in the range of 0.60-0.625, which may help surgeons reconstruct aesthetically pleasing ears. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Simulated microgravity attenuates skin wound healing by inhibiting dermal fibroblast migration via F-actin/YAP signaling pathway.

Skin and its cell components continuously subject to extrinsic and intrinsic mechanical forces and are mechanical sensitive. Disturbed mechanical homeostasis may lead to changes in skin functions. Gravity is the integral mechanical force on the earth, however, how gravity contributes to the maintenance of skin function and how microgravity in space affects the wound healing are poorly understood. Here, using microgravity analogs, we show that simulated microgravity (SMG) inhibits the healing of cutaneous wound and the accumulation of dermal fibroblasts in the wound bed. In vitro, SMG inhibits the migration of human foreskin fibroblast cells (HFF-1), and decreases the F-actin polymerization and YAP (yes-associated protein) activity. The SMG-inhibited migration can be recovered by activating YAP or F-actin polymerization using lysophosphatidic acid (LPA) or jasplakinolide (Jasp), suggesting the involvement of F-actin/YAP signaling pathway in this process. In SMG rats, LPA treatment improves the cutaneous healing with increased dermal fibroblasts in the wound bed. Together, our results demonstrate that SMG attenuates the cutaneous wound healing by inhibiting dermal fibroblast migration, and propose the crucial role of F-actin/YAP mechano-transduction in the maintenance of skin homeostasis under normal gravity, and YAP as a possible therapeutic target for the skin care of astronauts in space.

Fc Fragment of IgE Receptor Ig (FCER1G) acts as a key gene involved in cancer immune infiltration and tumour microenvironment.

Although recent studies have revealed the relationship between Fc Fragment of IgE Receptor Ig (FCER1G) and human tumours, there is still a lack of a more comprehensive pan-cancer analysis of FCER1G as an immune-related gene. In this study, we investigated the expression pattern and prognostic value of FCER1G based on multiple databases. Subsequently, we further explored the role of FCER1G in tumour proliferation and metastasis, as well as its genomic alterations and DNA methylation levels, we next assessed the association between FCER1G and the immune infiltrating cells of the tumour microenvironment in different cancers and verified it by immunohistochemical staining. The correlation between FCER1G and immune checkpoint genes expression and its predictive power in the immune checkpoint blockade treatment cohorts were used to evaluate the importance of FCER1G in immunotherapy. Enrichment analysis of FCER1G-associated partners was also performed. In addition, we substantiated the expression of FCER1G in specific cell types of different tumours using single-cell RNA sequencing data from different databases. Our research results showed that FCER1G is up-regulated in most tumour. Positive associations were found between FCER1G expression and tumour prognosis, proliferation, and metastasis, we also found that FCER1G is closely related to the tumour microenvironment and tumour immunity. Moreover, FCER1G-associated partners were enriched in pathways associated with neutrophils activation. Finally, we confirmed that FCER1G was mainly expressed in monocyte/macrophages of the tumour microenvironment. In conclusion, our findings provided a comprehensive understanding of FCER1G in oncogenesis and tumour immunology among various tumours and demonstrated its potential value in prognosis prediction and tumour immunotherapy.

Constructing Biomass-Based Ultrahigh-Rate Performance SnOy @C/SiOx Anode for LIBs via Disproportionation Effect.

To break the stereotype that silica can only be reduced via a magnesiothermic and aluminothermic method at low-temperature condition, the novel strategy for converting silica to SiOx using disproportionation effect of SnO generated via low-temperature pyrolysis coreduction reaction between SnO2 and rice husk is proposed, without any raw materials waste and environmental hazards. After the low-temperature pyrolysis reaction, SnOy @C/SiOx composites with unique structure (Sn/SnO2 dispersed on the surface and within pores of biochar as well as SiOx residing in the interior) are obtained due to the exclusive biological properties of rice husk. Such unique structural features render SnOy @C/SiOx composites with an excellent talent for repairing the damaged structure and the highly electrochemical storage ability (530.8 mAh g-1 at 10 A g-1 after 7500 cycles). Furthermore, assembled LiFePO4 ||SnOy -50@C/SiOx full cell displays a high discharge capacity of 463.7 mAh g-1 after 100 cycles at 0.2 A g-1 . The Li+ transport mechanism is revealed by density functional theory calculations. This work provides references and ideas for green, efficient, and high-value to reduce SiO2 , especially in biomass, which also avoids the waste of raw materials in the production process, and becomes an essential step in sustainable development.

Adaptive behaviors and vaccination on curbing COVID-19 transmission: Modeling simulations in eight countries.

Current persistent outbreak of COVID-19 is triggering a series of collective responses to avoid infection. To further clarify the impact mechanism of adaptive protection behavior and vaccination, we developed a new transmission model via a delay differential system, which parameterized the roles of adaptive behaviors and vaccination, and allowed to simulate the dynamic infection process among people. By validating the model with surveillance data during March 2020 and October 2021 in America, India, South Africa, Philippines, Brazil, UK, Spain and Germany, we quantified the protection effect of adaptive behaviors by different forms of activity function. The modeling results indicated that (1) the adaptive activity function can be used as a good indicator for fitting the intervention outcome, which exhibited short-term awareness in these countries, and it could reduce the total human infections by 3.68, 26.16, 15.23, 4.23, 7.26, 1.65, 5.51 and 7.07 times, compared with the reporting; (2) for complete prevention, the average proportions of people with immunity should be larger than 90%, 92%, 86%, 71%, 92%, 84%, 82% and 76% with adaptive protection behaviors, or 91%, 97%, 94%, 77%, 92%, 88%, 85% and 90% without protection behaviors; and (3) the required proportion of humans being vaccinated is a sub-linear decreasing function of vaccine efficiency, with small heterogeneity in different countries. This manuscript was submitted as part of a theme issue on "Modelling COVID-19 and Preparedness for Future Pandemics".

Comparative effects of vitamin and mineral supplements in the management of type 2 diabetes in primary care: A systematic review and network meta-analysis of randomized controlled trials.

Medical nutrition treatment can manage diabetes and slow or prevent its complications. The comparative effects of micronutrient supplements, however, have not yet been well established. We aimed at evaluating the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM) to inform clinical practice. Electronic and hand searches for randomized controlled trials (RCTs) were performed until June 1, 2022. We selected RCTs enrolling patients with T2DM who were treated with vitamin supplements, mineral supplements, or placebo/no treatment. Data were pooled via frequentist random-effects network meta-analyses. A total of 170 eligible trials and 14223 participants were included. Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively). Vitamin K supplements ranked best in reducing glycated hemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence. Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%). Niacin supplements ranked best in triglyceride reductions and increasing high-density lipoprotein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively). Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%). Our analyses indicated that micronutrient supplements, especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more efficacious in managing T2DM than other micronutrients. Considering the clinical importance of these findings, new research is needed to get better insight into this issue.

Transmission trends of the global COVID-19 pandemic with combined effects of adaptive behaviours and vaccination.

We developed a mechanism model which allows for simulating the novel coronavirus (COVID-19) transmission dynamics with the combined effects of human adaptive behaviours and vaccination, aiming at predicting the end time of COVID-19 infection in global scale. Based on the surveillance information (reported cases and vaccination data) between 22 January 2020 and 18 July 2022, we validated the model by Markov Chain Monte Carlo (MCMC) fitting method. We found that (1) if without adaptive behaviours, the epidemic could sweep the world in 2022 and 2023, causing 3.098 billion of human infections, which is 5.39 times of current number; (2) 645 million people could be avoided from infection due to vaccination; and (3) in current scenarios of protective behaviours and vaccination, infection cases would increase slowly, levelling off around 2023, and it would end completely in June 2025, causing 1.024 billion infections, with 12.5 million death. Our findings suggest that vaccination and the collective protection behaviour remain the key determinants against the global process of COVID-19 transmission.

Combined toxicity of erythromycin and roxithromycin and their removal by Chlorella pyrenoidosa.

The ecological effects of antibiotics in surface water have attracted increasing research attention. In this study, we investigated the combined ecotoxicity of erythromycin (ERY) and roxithromycin (ROX) on the microalgae, Chlorella pyrenoidosa, and the removal of ERY and ROX during the exposure. The calculated 96-h median effect concentration (EC50) values of ERY, ROX, and their mixture (2:1 w/w) were 7.37, 3.54, and 7.91 mg∙L-1, respectively. However, the predicted EC50 values of ERY+ROX mixture were 5.42 and 1.51 mg∙L-1, based on the concentration addition and independent action models, respectively. This demonstrated the combined toxicity of ERY+ ROX mixture showed an antagonistic effect on Chlorella pyrenoidosa. During the 14-d culture, low-concentration (EC10) treatments with ERY, ROX, and their mixture caused the growth inhibition rate to decrease during the first 12 d and increase slightly at 14 d. In contrast, high-concentration (EC50) treatments significantly inhibited microalgae growth (p < 0.05). Changes in the total chlorophyll contents, SOD and CAT activities, and MDA contents of microalgae suggested that individual treatments with ERY and ROX induced higher oxidative stress than combined treatments. After the 14-d culture time, residual Ery in low and high concentration Ery treatments were 17.75% and 74.43%, and the residual Rox were 76.54% and 87.99%, but the residuals were 8.03% and 73.53% in ERY+ ROX combined treatment. These indicated that antibiotic removal efficiency was higher in combined treatments than that in individual treatments, especially at low concentrations (EC10). Correlation analysis suggested that there was a significant negative correlation between the antibiotic removal efficiency of C. pyrenoidosa and their SOD activity and MDA content, and the enhanced antibiotic removal ability of microalgae benefited from increased cell growth and chlorophyll content. Findings in this study contribute to predicting ecological risk of coexisting antibiotics in aquatic environment, and to improving biological treatment technology of antibiotics in wastewater.

Arbuscular mycorrhizal fungi improve growth and tolerance of Platycladus orientalis under lead stress.

Platycladus orientalis is a significant woody plant for phytoremediation in heavy metals contaminated soils. The growth and tolerance of host plants under the lead (Pb) stress were enhanced by arbuscular mycorrhizal fungi (AMF). To evaluate the adjustment by AMF on growth and activity of antioxidant system of P. orientalis under Pb stress. The two-factor pot experiment was conducted with three AM fungal treatments (noninoculated, Rhizophagus irregularis, and Funneliformis mosseae) and four Pb levels (0, 500, 1000, and 2000 mg kg-1). AMF increased dry weight, phosphorus uptake, root vitality, and total chlorophyll content of P. orientalis in spite of Pb stress. Compared with nonmycorrhizal treatments, mycorrhizal P. orientalis had lower H2O2 and malondialdehyde (MDA) contents under Pb stress. AMF increased Pb uptake in roots and decreased the Pb translating to the shoots yet under Pb stress. Total glutathione and ascorbate in roots of P. orientalis were decreased by AMF inoculation. Mycorrhizal P. orientalis had higher superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and glutathione S-transferase (GST) activities in shoots and roots than nonmycorrhizal counterparts. Mycorrhizal P. orientalis under Pb stress showed higher expression of PoGST1 and PoGST2 in roots than that in CK treatments. Future studies will explore the function of induced tolerance genes by AMF of P. orientalis under Pb stress.

Arbuscular mycorrhizal fungi (AMF) decreased the reduced toxicity of lead to Platycladus orientalis under lead stress, including improving growth, root activity, photosynthesis, and antioxidant system activity, while reducing its oxidative damage. At the same time, lead inhibited the symbiosis between AMF and Platycladus orientalis.

Deep Temporal Artery Anatomy: Implications for Improving the Safety of Deep Temporal Injections.

BACKGROUND: Knowledge of the anatomy of the deep temporal artery (DTA) is critical to ensure safe filling of the deep temporal region. However, current treatment guidelines still focus on how to avoid the superficial temporal artery and the middle temporal vein, and an understanding of the safety of avoiding DTA injury is lacking. OBJECTIVE: The purpose of this study was to determine the positioning and course of the DTA to help clinicians safely perform the injection and filling in the temporal region. METHODS: Computed tomography (CT) scans and dissections of the skulls of 34 fresh frozen cadavers perfused with lead oxide were performed. Reconstruction and trajectory analysis of all DTA branches were performed using Mimics and MATLAB software. RESULTS: In this study, the DTA was identified in all samples, which originated from the maxillary artery of the external carotid artery system. According to image reconstruction and anatomical observations, the distribution of the anterior and posterior branches of the DTA had two different distribution patterns. The anatomical level of the DTA is located between the temporal muscle and the periosteal layer. Compared with observations in previous studies, the anterior branch of the DTA is slightly different, and we found that its course is closer to the frontal area in Asian specimens. CONCLUSION: The anatomical information on the DTA described in this study may help improve awareness of the safety of temporal injection by aesthetic physicians. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine Ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266. .

Positions of the Glabellar Arteries: Implications for Glabellar Injection.

BACKGROUND: Glabellar filler injection is linked to an increased risk of blindness. A thorough understanding of vascular changes in the glabellar area is critical for safety. The study's goal was to precisely determine the three-dimensional placements of the arteries in the glabellar area. METHODS: In 117 cadavers, the vascular structures in the glabellar area were examined. There were four segments (S1/S1'-S4/S4') and five points (P1-P5) specified. The number of identified arteries found in each section and at each position was tallied. Additionally, the depth of the underlying identified artery under each site was measured. RESULTS: One to three named arteries per glabellar segment were found. Each segment had at least one named artery, and the number of named arteries detected between S1/S1' and S4/S4' decreased. The chance of encountering identified arteries at the 5 designated locations, P1-P5, was 7/117 (6.0%), 6/117 (5.1%), 7/117 (6.0%), 6/117 (5.1%), and 16/117 (13.7%), respectively. At P1-P5, the major artery trunk was 1.8 ± 0.3 mm, 1.6 ± 0.3 mm, 1.4 ± 0.2 mm, 1.3 ± 0.3 mm, and 1.1 ± 0.2 mm below the skin. CONCLUSIONS: The site of the glabellar arteries was clearly shown in this investigation; these arteries were met at a rate of 14% from P1 to P5. We demonstrated that a single entry site through the glabella via cannula could readily keep the needle deep enough for safe glabellar filler injection. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Knockdown of MTHFD2 inhibits proliferation and migration of nasopharyngeal carcinoma cells through the ERK signaling pathway.

PURPOSE: Folate-mediated one-carbon metabolism (FOCM) plays a vital role in supporting cancer cells hyperproliferation. Malignant cells, including nasopharyngeal carcinoma (NPC) cells, are characterized by rapid proliferation and thus need large numbers of nucleotides and nutrients generated from FOCM. However, the mechanism and key genes involved in FOCM playing a vital role in NPC progression are still unclear. This study aimed to find out the key gene, and its functions in NPC and explore the potential mechanism. METHODS: Bioinformatics analysis based on TCGA and GSEA database were performed to screen the key FOCM related gene in HNSCC. The effects of MTHFD2 on cell proliferation, apoptosis and migration were conducted through MTHFD2 knockdown cell lines in vitro experiments. Cell proliferation was explored by CCK8 assay and colony formation assay. Cell apoptosis was tested through flow cytometry. Transwell migration assay was performed to study the cell migration. The potential pathway was explored by RNA-seq and the ERK inhibitor SCH772984 and the ERK activator tBHQ were applied to verify the effect of MTHFD2 in NPC via the ERK pathway. Finally, xenograft tumor model was used to explore the tumorigenicity of NPC cells in vivo and IHC was performed to study the expression of related proteins. RESULTS: MTHFD2 was highly expressed in NPC and associated with a poor prognosis. MTHFD2 knockdown inhibited the proliferation, migration and induced apoptosis of NPC cells in vitro. In consistent with cellular results, knockdown of MTHFD2 suppressed the tumorigenicity of NPC cells in vivo. MAPK pathway was enriched among DEGs between MTHFD2 knockdown cells and control cells. And the level of p-ERK1/2 and p-p38 MAPK was decreased in MTHFD2 knockdown cells and xenograft tumors of MTHFD2 knockdown cells. Furthermore, the application of the selective ERK inhibitor SCH772984 and the ERK activator tBHQ confirmed that MTHFD2-knockdown inhibited the proliferation and migration of NPC cells via the ERK signaling pathway. CONCLUSION: MTHFD2 was up-regulated in NPC tissues and its high expression was linked to a poor prognosis. Knockdown of MTHFD2 inhibited proliferation and migration of NPC cells through the ERK signaling pathway, which may provide new clues and targets for the treatment of NPC.

Hypoxia-induced MIF induces dysregulation of lipid metabolism in Hep2 laryngocarcinoma through the IL-6/JAK-STAT pathway.

PURPOSE: Hypoxia is a common feature of laryngocarcinoma. Alterations in lipid metabolism are an important metabolic rewiring phenomenon for malignant cells to maintain their rapid proliferation in the hypoxic microenvironment, which makes most cancers, including laryngocarcinoma, difficult to cure. However, the mechanisms involved in lipid metabolism in laryngocarcinoma is still unclear. This study aimed to clarify the changes in lipid metabolism of laryngocarcinoma cells under hypoxic conditions and explore the related mechanisms. METHODS: Hep2 cells were incubated in a normoxic or hypoxic environment (5% CO2 and 1% O2) at 37 °C for 24 h. CCK-8 cell viability assay and colony formation assay were performed to detect cells proliferation. And lipid metabolic indices including TG and NEFA were determined by kits. The mechanism involved in the regulation of lipid metabolism was explored by RNA-seq and bioinformatic analysis. The MIF inhibitor ISO-1 and JAK inhibitor XL019 were used to verify the mechanism. Finally, a tumour xenograft model was applied to further verify these results in vivo. RESULTS: Hypoxia promoted cell proliferation and increased the levels of TG and NEFA in Hep2 cells. Three genes, MIF, ENO2, and LDHA, that were screened by the intersection of hypoxia gene sets and fatty gene sets and were verified by qPCR. The MIF levels were elevated when cells were exposed to hypoxia. Through GSEA and RNA-seq analysis, the JAK/STAT pathway was screened. Hypoxia increased MIF levels and activated the IL-6/JAK/STAT pathway. The MIF inhibitor ISO-1inhibited cell proliferation under hypoxia and reversed the change in TG levels and IL-6 levels. And ISO-1 reversed the expression pattern of the screened genes in the JAK/STAT pathway. Finally, a tumour xenograft model further verified these results in vivo. CONCLUSION: Hypoxia induced reprogramming of lipid metabolism in laryngocarcinoma cells through the MIF/IL-6/JAK-STAT pathway. This study revealed one mechanism that allows laryngocarcinoma cells to adapt to the hypoxic tumour microenvironment. Therefore, a drug targeting the MIF/IL-6/JAK-STAT pathway might be a promising therapeutic option for the treatment of laryngocarcinoma.

7,8-Dihydroxyflavone protects retinal ganglion cells against chronic intermittent hypoxia-induced oxidative stress damage via activation of the BDNF/TrkB signaling pathway.

PURPOSE: Chronic intermittent hypoxia (CIH) plays a key role in the complications of obstructive sleep apnea (OSA), which is strongly associated with retinal and optic nerve diseases. Additionally, the brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling pathway plays an important protective role in neuronal injury. In the present study, we investigated the role of 7,8-dihydroxyflavone (7,8-DHF) in regulating CIH-induced injury in mice retinas and rat primary retinal ganglion cells (RGCs). METHODS: C57BL/6 mice and in vitro primary RGCs were exposed to CIH or normoxia and treated with or without 7,8-DHF. The mice eyeballs or cultured cells were then taken for histochemistry, immunofluorescence or biochemistry, and the protein expression of the BDNF/TrkB signaling pathway analysis. RESULTS: Our results showed that CIH induced oxidative stress (OS) in in vivo and in vitro models and inhibited the conversion of BDNF precursor (pro-BDNF) to a mature form of BDNF, which increased neuronal cell apoptosis. 7,8-DHF reduced the production of reactive oxygen species (ROS) caused by CIH and effectively activated TrkB signals and downstream protein kinase B (Akt) and extracellular signal-regulated kinase (Erk) survival signaling pathways, which upregulated the expression of mature BDNF. ANA-12 (a TrkB specific inhibitor) blocked the protective effect of 7,8-DHF. CONCLUSION: In short, the activation of the BDNF/TrkB signaling pathway alleviated CIH-induced oxidative stress damage of the optic nerve and retinal ganglion cells. 7,8-DHF may serve as a promising agent for OSA related neuropathy.

Acoustic Multi-Parameter Early Warning Method for Transformer DC Bias State.

The acoustic signal in the operation of a power transformer contains a lot of transformer operation state information, which is of great significance to the detection of DC bias state. In this paper, three typical parameters used for DC bias state detection are selected by comparing the acoustic variation of a 500 kV Jingting transformer substation No. 2 transformer with that of the core model built in the laboratory; then, acoustic samples of the 162 EHV normal state transformers are collected, and the distribution regularity of three typical parameters in normal state is given. Finally, according to the distribution regularity, clear warning threshold of typical parameters are given, and the DC bias cases from the 500 kV Jingting transformer substation are used to verify the effectiveness of the threshold.