Treatment of Refractory Status Epilepticus With Continuous Intravenous Anesthetic Drugs: A Systematic Review.

Importance: Multiple continuous intravenous anesthetic drugs (CIVADs) are available for the treatment of refractory status epilepticus (RSE). There is a paucity of data comparing the different types of CIVADs used for RSE. Objective: To systematically review and compare outcome measures associated with the initial CIVAD choice in RSE in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Evidence Review: Data sources included English and non-English articles using Embase, MEDLINE, PubMed, and Web of Science (January 1994-June 2023) as well as manual search. Study selection included peer-reviewed studies of 5 or more patients and at least 1 patient older than 12 years with status epilepticus refractory to a benzodiazepine and at least 1 standard antiseizure medication, treated with continuously infused midazolam, ketamine, propofol, pentobarbital, or thiopental. Independent extraction of articles was performed using prespecified data items. The association between outcome variables and CIVAD was examined with an analysis of variance or χ2 test where appropriate. Binary logistic regressions were used to examine the association between outcome variables and CIVAD with etiology, change in mortality over time, electroencephalography (EEG) monitoring (continuous vs intermittent), and treatment goal (seizure vs burst suppression) included as covariates. Risk of bias was addressed by listing the population and type of each study. Findings: A total of 66 studies with 1637 patients were included. Significant differences among CIVAD groups in short-term failure, hypotension, and CIVAD substitution during treatment were observed. Non-epilepsy-related RSE (vs epilepsy-related RSE) was associated with a higher rate of CIVAD substitution (60 of 120 [50.0%] vs 11 of 43 [25.6%]; odds ratio [OR], 3.11; 95% CI, 1.44-7.11; P = .006) and mortality (98 of 227 [43.2%] vs 7 of 63 [11.1%]; OR, 17.0; 95% CI, 4.71-109.35; P < .001). Seizure suppression was associated with mortality (OR, 7.72; 95% CI, 1.77-39.23; P = .005), but only a small subgroup was available for analysis (seizure suppression: 17 of 22 [77.3%] from 3 publications vs burst suppression: 25 of 98 [25.5%] from 12 publications). CIVAD choice and EEG type were not predictors of mortality. Earlier publication year was associated with mortality, although the observation was no longer statistically significant after adjusting SEs for clustering. Conclusions and Relevance: Epilepsy-related RSE was associated with lower mortality compared with other RSE etiologies. A trend of decreasing mortality over time was observed, which may suggest an effect of advances in neurocritical care. The overall data are heterogeneous, which limits definitive conclusions on the choice of optimal initial CIVAD in RSE treatment.

Exposure of Danio rerio to environmental sulfamethoxazole may contribute to neurobehavioral abnormalities via gut microbiome disturbance.

The neurotoxic effects and mechanisms of low-dose and long-term sulfamethoxazole (SMZ) exposure remain unknown. This study exposed zebrafish to environmental SMZ concentrations and observed behavioral outcomes. SMZ exposure increased hyperactivity and altered the transcript levels of 17 genes associated with neurological function. It impaired intestinal function by reducing the number of intestinal goblet cells and lipid content. Metabolomic results indicated that the contents of several lipids and amino acids in the gut were altered, which might affect the expression levels of neurological function-related genes. Metagenomic results demonstrated that SMZ exposure substantially altered the composition of the gut microbiome. Zebrafish receiving a transplanted fecal microbiome from the SMZ group were also found to exhibit abnormal behavior, suggesting that the gut microbiome is an important target for SMZ exposure-induced neurobehavioral abnormalities. Multi-omics correlation analysis revealed that gut micrometabolic function was related to differential gut metabolite levels, which may affect neurological function through the gut-brain-axis. Reduced abundance of Lefsonia and Microbacterium was strongly correlated with intestinal metabolic function and may be the key bacterial genera in neurobehavioral changes. This study confirms for the first time that SMZ-induced neurotoxicity in zebrafish is closely mediated by alterations in the gut microbiome.

Effects of Innervation on Angiogenesis and Osteogenesis in Bone and Dental Tissue Engineering.

The repair and regeneration of critical-sized bone defects remain an urgent challenge. Bone tissue engineering represents an exciting solution for regeneration of large bone defects. Recently, the importance of innervation in tissue-engineered bone regeneration has been increasingly recognized. The cross talk between nerve and bone provides important clues for bone repair and regeneration. Furthermore, the promotion of angiogenesis by innervation can accelerate new bone formation. However, the mechanisms involved in the promotion of vascular and bone regeneration by the nervous system have not yet been established. In addition, simultaneous neurogenesis and vascularization in bone tissue engineering have not been fully investigated. This article represents the first review on the effects of innervation in enhancing angiogenesis and osteogenesis in bone and dental tissue engineering. Cutting-edge research on the effects of innervation through biomaterials on bone and dental tissue repairs is reviewed. The effects of various nerve-related factors and cells on bone regeneration are discussed. Finally, novel clinical applications of innervation for bone, dental, and craniofacial tissue regeneration are also examined.

Sterically Hindered Tetradentate [Pt(O

Described here are sterically hindered tetradentate [Pt(O^N^C^N)] emitters (Pt-1, Pt-2, and Pt-3) developed for stable and high-performance green phosphorescent organic light-emitting diodes (OLEDs). These Pt(II) emitters exhibit strong saturated green phosphorescence (λmax = 517-531 nm) in toluene and mCP thin films with emission quantum yields as high as 0.97, radiative rate constants (kr) as high as 4.4-5.3 × 105 s-1 and reduced excimer emission, and with a preferential horizontally oriented transition dipole ratio of up to 84%. Theoretical calculations show that p-(hetero)arene substituents at the periphery of the ligand scaffolds in Pt-1, Pt-2, and Pt-3 can i) enhance the spin-orbit coupling (SOC) between the lower singlet excited states and the T1 state, and S0→Sn (n = 1 or 2) transition dipole moment, and ii) introducing additional SOC activity and the bright 1ILCT[π(carbazole)→π*(N^C^N)] excited state (Pt-2 and Pt-3), which are the main contributors to the increased kr values. Utilizing these tetradentate Pt(II) emitters, green phosphorescent OLEDs are fabricated with narrow-band electroluminescence (FWHM down to 36 nm), high external quantum efficiency, current efficiency up to 27.6% and 98.7 cd A-1, and an unprecedented device lifetime (LT95) of up to 9270 h at 1000 cd m-2 under laboratory conditions.

Smart Dental Materials Intelligently Responding to Oral pH to Combat Caries: A Literature Review.

Smart dental materials are designed to intelligently respond to physiological changes and local environmental stimuli to protect the teeth and promote oral health. Dental plaque, or biofilms, can substantially reduce the local pH, causing demineralization that can then progress to tooth caries. Progress has been made recently in developing smart dental materials that possess antibacterial and remineralizing capabilities in response to local oral pH in order to suppress caries, promote mineralization, and protect tooth structures. This article reviews cutting-edge research on smart dental materials, their novel microstructural and chemical designs, physical and biological properties, antibiofilm and remineralizing capabilities, and mechanisms of being smart to respond to pH. In addition, this article discusses exciting and new developments, methods to further improve the smart materials, and potential clinical applications.

Early environmental exposure to oxytetracycline in Danio rerio may contribute to neurobehavioral abnormalities in adult zebrafish.

The common antibiotic oxytetracycline (OTC) is nowadays commonly found in natural aquatic environments. However, the underlying mechanisms of low-dose OTC exposure and its neurotoxic effects on aquatic animals remain unknown. In this study, we exposed zebrafish larvae to environmental concentrations of OTC in early life and performed neurobehavioral, 16S rRNA gene sequencing, and transcriptomic analyses. OTC exposure resulted in hyperactivity of larvae and a significant reduction in the number of neurons in the midbrain. The expression levels of 15 genes related to neural function changed. Additionally, the composition of 65 genera of the gut microbiota of larvae was altered, which may be one of the reasons for the abnormal neural development. We further studied the long-term outcomes among adult fish long after cessation of OTC exposure. OTC treatment caused adult fish to be depressive and impulsive, symbolizing bipolar disorder. Adult fish exposed to OTC had significantly fewer neurons and their gut bacteria composition did not recover 104 days after terminating OTC exposure. Finally, we analyzed the correlation between the gut microbiota of larvae, genes related to neural function, and metabolites of adult fish brain tissue. The results showed that the abundance of several members of the biome in larvae was related to the transcription levels of genes related to neural function, which were related to the metabolic levels in the adult brain. In conclusion, our study showed that early-life exposure to environmental concentrations of OTC can lead to persistent neurobehavioral abnormalities until adulthood through dysbiosis in the gut microbiota.

Development and application of a new biological nano-selenium fermentation broth based on Bacillus subtilis SE201412.

In order to improve the functionality and additional value of agricultural products, this study developing nano-selenium fermentation broth and established a new application strategy of bio-nano-selenium by screening and identifying selenium-rich microorganisms. We isolated a new strain from tobacco waste and named it Bacillus subtilis SE201412 (GenBank accession no. OP854680), which could aerobically grow under the condition of 66,000 mg L-1 selenite concentration, and could convert 99.19% of selenite into biological nano-selenium (BioSeNPs) within 18 h. Using strain SE201412, we industrially produced the different concentrations of fermentation broth containing 5000-3000 mg L-1 pure selenium for commercial use. The synthesized selenium nanoparticles (SeNPs) were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). TEM and SEM results showed that SeNPs were distributed outside cells. NTA assay of fermentation broth indicated that the nanoparticles were spherical with an average particle size of 126 ± 0.5 nm. Toxicity test revealed that the median lethal dose (LD50) of the fermentation broth to mice was 2710 mg kg-1, indicating its low toxicity and high safety. In addition, we applied BioSeNP fermentation broth to rice and wheat through field experiments. The results showed that the application of fermentation broth significantly increased the total selenium content and organic selenium percentage in rice and wheat grains. Our findings provide valuable reference for the development of BioSeNPs with extensive application prospects.

Effects of electroacupuncture on gait and proliferation and differentiation of muscle satellite cell in rats with acute blunt trauma of gastrocnemius muscle / 中国针灸

OBJECTIVE@#To observe the effects of electroacupuncture on threshold of pain, gait, proliferation and differentiation of muscle satellite cell in rats with acute blunt trauma of gastrocnemius muscle, and to explore the possible mechanism of electroacupuncture in promoting the repair of acute injury of skeletal muscle.@*METHODS@#A total of 48 SD rats were randomly divided into a blank group (6 rats), a model group (24 rats) and an electroacupuncture group (18 rats). In the model group and the electroacupuncture group, the model of acute blunt trauma of gastrocnemius muscle was established by self-made impactor. In the electroacupuncture group, electroacupuncture was applied at "Chengshan" (BL 57) and "Yanglingquan" (GB 34) on the right side, with disperse-dense wave, in frequency of 2 Hz/100 Hz, once a day, 30 min each time. Electroacupuncture intervention was performed for 3, 7 and 14 days according to the sampling time. On the 1st, 3rd, 7th and 14th days after modeling, the mechanical withdrawal pain threshold of hindfoot was detected by Von Frey method; the standing time and the maximum contact area of the right hindfoot were recorded by Cat Walk XTTM animal gait analysis instrument; the morphology of the right gastrocnemius muscle and the number of inflammatory cells were observed by HE staining; the positive expression of paired box gene 7 (Pax7) and myogenic differentiation (MyoD) of the right gastrocnemius muscle was detected by immunofluorescence.@*RESULTS@#After modeling, the muscle fiber rupture and massive infiltration of red blood cells and inflammatory cells were observed in the right gastrocnemius muscle; after electroacupuncture intervention, the morphology of muscle fiber was intact and the infiltration of inflammatory cells was improved. Compared with the blank group, in the model group, the differences of mechanical withdrawal pain threshold between the left and right foot were increased (P<0.05), the standing time was shortened and the maximum contact area of the right hindfoot was decreased (P<0.05), the number of inflammatory cells and the positive expression of Pax7 and MyoD of the right gastrocnemius muscle were increased (P<0.05) on the 1st, 3rd, 7th and 14th days after modeling. Compared with the model group, in the electroacupuncture group, the differences of mechanical withdrawal pain threshold were decreased (P<0.05), the standing time was prolonged (P<0.05), the number of inflammatory cells of right gastrocnemius muscle was decreased (P<0.05) on the 7th and 14th days after modeling; the maximum contact area of the right hindfoot was increased (P<0.05), the positive expression of MyoD of the right gastrocnemius muscle was increased (P<0.05) on the 3rd, 7th and 14th days after modeling; the positive expression of Pax7 of the right gastrocnemius muscle was increased (P<0.05) on the 3rd day after modeling.@*CONCLUSION@#Electroacupuncture can effectively improve the pain threshold and gait in rats with acute blunt trauma of gastrocnemius muscle, and promote the repair of skeletal muscle injury, the mechanism may be related to the up-regulation of Pax7 and MyoD, so as to promoting the proliferation and differentiation of muscle satellite cell.

Effect of Electroacupuncture at Proximal and Distal Acupoints on Pain-inducing Substances， Macrophages and Related Inflammatory Factors in Myofascial Pain Syndrome Model Rats / 中医杂志

ObjectiveTo explore the possible peripheral analgesic mechanism of electroacupuncture （EA） at promimal and distal acupoints in treatment of myofascial pain syndrome （MPS）. MethodsTwenty-four SD rats were randomly divided into blank group， model group， proximal group， and distal group， with six rats in each group. MPS model was prepared by “strike combined with centrifugal exercise” in all groups except for the blank group. After modeling， the rats in the proximal group received EA at the local myofascial trigger points （MTrPs）， namely the Ashi points， with dilatational waves of frequency of 2/100 HZ and voltage of 2-4 V， current intensity depending on a slight trembling of the left lower limbs， once a day， 15min each time，for 14 days. The rats in the distal group received EA at “Yanglingquan” （GB 34） and “Yinlingquan” （SP 9）， with the same operations as the proximal group. The rats in the blank group and the model group were only grasped and hedged， without other interventions. After intervention， the paw withdrawl mechanical threshold （PWMT） was measured， and variability between the left and right hind paws was calculated. Musculoskeletal ultrasound imaging and electromyography monitoring were performed on the left lower extremity vastus medialis. The morphological changes of vastus medialis muscle of the left lower extremity were observed by HE staining. The positive expression of substance P （SP）， calcitonin gene-related peptide （CGRP）， CD68 and CD206 in muscle tissue was detected by immunohistochemistry. Abdominal aortic serum interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， and interleukin-8 （interleukin-8） were detected by ELISA. ResultsCompared to those in the blank group， the fibers of the vastus medial muscle of the rats in the model group were broken and distorted with thickness in variation， and the myofascia was broken， with fibrillation potential， enlarged muscle cells， inward moved nucleus， and widened muscle space； the variability of PWMT between the left and right hind paws significantly increased， as well as the levels of SP， CGRP， CD68， and CD206 in the vastus medialis muscle （P＜0.01）， and the serum IL-8 and TNF-αlevels were significantly elevated （P＜0.05 or P＜0.01）. Compared to those in the model group， the muscle fibers in the proximal and distal group were complete in shape and arranged in an orderly manner， with continued non-broken myofascia， regular shape of muscle cells， and significantly reduced level of IL-8 （P＜0.01）； the amplitude and frequency of spontaneous discharge in the proximal group significantly decreased， as well as the variability of PWMT between the left and right hind paws， and the levels of SP， CGRP， and CD68 in the vastus medialis muscle， while the CD206 level increased significantly （P＜0.05 or P＜0.01 ）； there was complex discharges in the distal group， with significantly decreased level of CD68 in the vastus medialis muscle and increased level of CD206 （P＜0.01）. Compared to the proximal group， the level of IL-8 in the distal group was significantly higher （P＜0.05）. ConclusionsEA at proximal acupoints can significantly improve the pain threshold and local muscle tissue morpho-logy in rats， and its mechanism may be related to reducing the levels of pain-causing substances and related inflammatory factors and promoting the polarization of macrophages. The analgesic effect of EA at distal acupoints is not obvious， and the mechanism is still unclear.

Effects of Metformin Delivery via Biomaterials on Bone and Dental Tissue Engineering.

Bone tissue engineering is a promising approach that uses seed-cell-scaffold drug delivery systems to reconstruct bone defects caused by trauma, tumors, or other diseases (e.g., periodontitis). Metformin, a widely used medication for type II diabetes, has the ability to enhance osteogenesis and angiogenesis by promoting cell migration and differentiation. Metformin promotes osteogenic differentiation, mineralization, and bone defect regeneration via activation of the AMP-activated kinase (AMPK) signaling pathway. Bone tissue engineering depends highly on vascular networks for adequate oxygen and nutrition supply. Metformin also enhances vascular differentiation via the AMPK/mechanistic target of the rapamycin kinase (mTOR)/NLR family pyrin domain containing the 3 (NLRP3) inflammasome signaling axis. This is the first review article on the effects of metformin on stem cells and bone tissue engineering. In this paper, we review the cutting-edge research on the effects of metformin on bone tissue engineering. This includes metformin delivery via tissue engineering scaffolds, metformin-induced enhancement of various types of stem cells, and metformin-induced promotion of osteogenesis, angiogenesis, and its regulatory pathways. In addition, the dental, craniofacial, and orthopedic applications of metformin in bone repair and regeneration are also discussed.

Association of long-term effects of low-level sulfamethoxazole with ovarian lipid and amino acid metabolism, sex hormone levels, and oocyte maturity in zebrafish.

Sulfamethoxazole (SMZ) is an important antibiotic used to prevent and treat infections in both clinical settings and animal husbandry. High levels of SMZ may exhibit endocrine toxicity. Environmental SMZ enters the human body via food and water; however, the toxicity of environmental doses of SMZ and its effects on reproductive health are unknown. In the present study, zebrafish were exposed to low concentrations of SMZ (1000 and 5000 ng/L) from 2 h post-fertilization to 120 d post-fertilization. Consequently, the proportion of mature oocytes in adult female zebrafish ovarian tissue increased by 98.2 %, indicating that SMZ promotes ovarian maturation. Metabolomics analysis revealed significant changes in ovarian lipid and amino acid levels after SMZ treatment. An enzyme-linked immunoassay used to detect sex hormones in the ovaries showed that SMZ exposure significantly increased the levels of estradiol, a follicle-stimulating hormone, and of luteinizing hormone. Furthermore, an association analysis showed that most of the differentially expressed metabolites in the ovary were strongly correlated with the levels of sex hormones secreted by the pituitary gland. Therefore, significantly increased transcript levels of gonadotropin-releasing hormone (GnRH) and follicle-stimulating hormone detected in brain tissue suggested that SMZ may exhibit ovarian toxicity via the hypothalamus. In vitro experiments were performed to demonstrate that SMZ targets neurons in the hypothalamus. Exposure to SMZ significantly increased the GnRH content in GnRH neurons. Finally, molecular docking simulations indicated the potential interaction of SMZ with G protein-coupled receptor 54; this molecular binding can activate, synthesize, and release GnRH in neurons. In conclusion, long-term environmental exposure to SMZ may induce ovarian toxicity by affecting the hypothalamus-pituitary-gonad axis.

Longitudinal analysis of exposure to a low concentration of oxytetracycline on the zebrafish gut microbiome.

Oxytetracycline, a widely produced and administered antibiotic, is uncontrollably released in low concentrations in various types of environments. However, the impact of exposure to such low concentrations of antibiotics on the host remains poorly understood. In this study, we exposed zebrafish to a low concentration (5,000 ng/L) of oxytetracycline for 1 month, collected samples longitudinally (Baseline, and Days 3, 6, 9, 12, 24, and 30), and elucidated the impact of exposure on microbial composition, antibiotic resistance genes, mobile genetic elements, and phospholipid metabolism pathway through comparison of the sequenced data with respective sequence databases. We identified Pseudomonas aeruginosa, a well-known pathogen, to be significantly positively associated with the duration of oxytetracycline exposure (Adjusted P = 5.829e-03). Several tetracycline resistance genes (e.g., tetE) not only showed significantly higher abundance in the exposed samples but were also positively associated with the duration of exposure (Adjusted P = 1.114e-02). Furthermore, in the exposed group, the relative abundance of genes involved in phospholipid metabolism had also decreased. Lastly, we characterized the impact of exposure on zebrafish intestinal structure and found that the goblet cell counts were decreased (~82%) after exposure. Overall, our results show that a low concentration of oxytetracycline can increase the abundance of pathogenic bacteria and lower the abundance of key metabolic pathways in the zebrafish gut microbiome that can render them prone to bacterial infections and health-associated complications.

Stable Tetradentate Gold(III)-TADF Emitters with Close to Unity Quantum Yield and Radiative Decay Rate Constant of up to 2 × 106 s-1 : High-Efficiency Green OLEDs with Operational Lifetime (LT90 ) Longer than 1800 h at 1000 cd m-2.

High maximum external quantum efficiency (EQEmax ), small efficiency roll-offs, and long operational lifetime at practical luminances are three crucial parameters for commercialization of organic light-emitting diodes (OLEDs). To simultaneously achieve these goals, it is desirable to have the radiative decay rate constant (kr ) as large as possible, which, for a thermally activated delayed fluorescent (TADF) emitter, requires both a large S1 →S0 radiative decay rate constant (kr S ) and a small singlet-triplet energy gap (ΔEST ). Here, the design of a class of tetradentate gold(III) TADF complexes for narrowing the ΔEST while keeping the kr S large is reported. The as-synthesized complexes display green emission with close to unity emission quantum yields, and kr approaching 2 × 106 s-1 in thin films. The vacuum-deposited green OLEDs based on 1 and 4 demonstrate maximum EQEs of up to 24 and 27% with efficiency roll-offs of 5.5 and 2.2% at 1000 cd m-2 , respectively; the EQEs maintain high at 10 000 cd m-2 (19% (1) and 24% (4)). A long LT90 device lifetime of 1820 h at 1000 cd m-2 for complex 1 is achieved, which is one of the longest device lifetimes of TADF-OLEDs reported in the literature.

Genome-Resolved Characterization of Structure and Potential Functions of the Zebrafish Stool Microbiome.

Zebrafish have been used as a model organism for more than 50 years and are considered an excellent model for studying host-microbiome interactions. However, this largely depends on our understanding of the zebrafish gut microbiome itself. Despite advances in sequencing and data analysis methods, the zebrafish gut microbiome remains highly understudied. This study performed the de novo metagenome assembly and recovery of the metagenome-assembled genomes (MAGs) through genome binning (and refinement) of the contigs assembled from the zebrafish stool. The results indicate that majority of the MAGs had excellent quality i.e. high completeness (≥90%) and low contamination levels (≤5%). MAGs mainly belong to the taxa that are known to be members of the core zebrafish stool microbiome, including the phylum Proteobacteria, Fusobacteriota, and Actinobacteriota. However, most of the MAGs remained unclassified at the species level and reflected previously unexplored microbial taxa and their potential novelty. These MAGs also contained genes with predicted functions associated with diverse metabolic pathways that included carbohydrate, amino acid, and lipid metabolism pathways. Lastly, we performed a comparative analysis of Paucibacter MAGs and reference genomes that highlighted the presence of novel Paucibacter species and enriched metabolic potential in the recovered MAGs.

Enabling Real-Time Quality-of-Service and Fine-Grained Aggregation for Wireless TSN.

Wireless Time-Sensitive Networking (WTSN) has emerged as a promising technology for Industrial Internet of Things (IIoT) applications. To meet the latency requirements of WTSN, wireless local area network (WLAN) such as IEEE 802.11 protocol with the time division multiple access (TDMA) mechanism is shown to be a practical solution. In this paper, we propose the RT-WiFiQA protocol with two novel schemes to improve the latency and reliability performance: real-time quality of service (RT-QoS) and fine-grained aggregation (FGA) for TDMA-based 802.11 systems. The RT-QoS is designed to guarantee the quality-of-service requirements of different traffic and to support the FGA mechanism. The FGA mechanism aggregates frames for different stations to reduce the physical layer transmission overhead. The trade-off between the reliability and FGA packet size is analyzed with numerical results. Specifically, we derive a critical threshold such that the FGA can achieve higher reliability when the aggregated packet size is smaller than the critical threshold. Otherwise, the non-aggregation scheme outperforms the FGA scheme. Extensive experiments are conducted on the commercial off-the-shelf 802.11 interface. The experiment results show that compared with the existing TDMA-based 802.11 system, the developed RT-WiFiQA protocol can achieve deterministic bounded real-time latency and greatly improves the reliability performance.

Identifying gene network patterns and associated cellular immune responses in children with or without nut allergy.

BACKGROUND: Although evidence suggests that the immune system plays a key role in the pathophysiology of nut allergy, the precise immunological mechanisms of nut allergy have not been systematically investigated. The aim of the present study was to identify gene network patterns and associated cellular immune responses in children with or without nut allergy. METHODS: Transcriptome profiling of whole blood cells was compared between children with and without nut allergy. Three genes were selected to be validated on a larger cohort of samples (n = 86) by reverse transcription-polymerase chain reactions (RT-qPCR). The composition of immune cells was inferred from the transcriptomic data using the CIBERSORTx algorithm. A co-expression network was constructed employing weighted gene co-expression network analysis (WGCNA) on the top 5000 most variable transcripts. The modules were interrogated with pathway analysis tools (InnateDB) and correlated with clinical phenotypes and cellular immune responses. RESULTS: Proportions of neutrophils were positively correlated and CD4+ T-cells and regulatory T-cells (Tregs) were negatively correlated with modules of nut allergy. We also identified 2 upregulated genes, namely Interferon Induced With Helicase C Domain 1 (IFIH1), DNA damage-regulated autophagy modulator 1 (DRAM1) and a downregulated gene Zinc Finger Protein 512B (ZNF512B) as hub genes for nut allergy. Further pathway analysis showed enrichment of type 1 interferon signalling in nut allergy. CONCLUSIONS: Our findings suggest that upregulation of type 1 interferon signalling and neutrophil responses and downregulation of CD4+ T-cells and Tregs are features of the pathogenesis of nut allergy.

Prenatal environmental antibiotics and fetal and postnatal growth: A biomonitoring-based prospective study in Eastern China.

Thus far, the effect of environmental antibiotics exposure to offspring's growth remains unclear. Here we aimed to evaluate whether and to what extent environmental antibiotics exposure is associated with fetal and postnatal growth. A total of 735 pregnant women and their full-term offspring from the Shanghai Obesity Birth Cohort were involved in the study. Maternal urine specimen was collected during the third trimester, and urinary concentration of fifteen environmental antibiotics was measured by liquid chromatography-tandem mass spectrometry and enzymatic method. Children were followed at birth, 12, 24 and 60 months, and growth parameters of the weight and height of children were recorded. Linear regression model was applied, and it was found that maternal veterinary antibiotic (VA) concentration was negatively associated with birth weight and ponderal index [per natural-logarithm (ln)-unit: adjusted ß (95% confidence interval, CI) = - 42.1 (- 74.0, - 10.3) for birth weight, -0.11 (- 0.19, - 0.02) for birth weight z-score, and - 0.03 (- 0.05, - 0.002) for ponderal index]. Regarding specific VA, each ln-unit increment of florfenicol concentrations was likely to be associate with 39.7 g (95%CI: - 69.3, - 10.1) reduced birth weight, 0.10 (95%CI: - 0.18, - 0.02) reduced birth weight z-score, and 0.02 g/cm3 (95%CI: - 0.04, - 0.00) reduced ponderal index. Ciprofloxacin, a preferred-as-veterinary antibiotic, showed a similar dose-response relationship with neonatal anthropometric parameters to florfenicol. However, these adverse effects diminished as children grew up to 12-, 24- and 60-month-old. Larger prospective cohort studies and animal experiments are warranted to verify the hypothesis that environmental antibiotics exposure in early life, even at low doses, may cause fetal growth restriction.

Changes in Meibum Lipid Composition With Ocular Demodex Infestation.

Purpose: The purpose of this study was to understand the impact of Demodex infection in the lipid component of meibum in patients. Methods: The meibum samples were collected from four groups of subjects: (1) Demodex-negative with non-MGD (D-M-; n = 10); (2) Demodex-positive with non-MGD (D+M-; n = 10); (3) Demodex-negative with MGD (D-M+; n = 10); and (4) Demodex-positive with MGD (D+M+; n = 10). A liquid chromatography-mass spectrometry (LC-MS) system consisting of ultra-performance liquid chromatography and a Q Exactive high-resolution mass spectrometer was used for lipids separation and detection. Results: Compared with the D-M- group, the D+M- group had lower levels of phosphatidylcholines (PCs) and lysophosphatidylcholines (LPCs) and higher levels of phosphatidylethanolamines (PEs). Compared with the D-M+ group, the levels of sphingomyelins (SMs) and PCs in the D+M+ group were decreased, whereas the levels of (O-acyl)-ω-hydroxy fatty acids (OAHFAs), ceramides (CERs), LPCs, and diacylglycerols (DGs) were significantly increased. Triacylglycerols (TGs), DGs, CERs, and OAHFAs were decreased in D-M+ group, whereas levels of PEs, phosphatidylinositols, and phosphatidylglycerols were increased in meibum obtained from the D-M+ group compared with those in the D-M- group. TGs, SMs, CERs, and PEs were decreased in the D+M+ group, whereas levels of LPCs, LPEs, PCs, and PEs were increased in meibum from the D-M+ group compared with those in the D+M- group. Conclusions: To the best of our knowledge, this is the first study to assess the changes in meibum from patients with ocular Demodex infestation. The significant increase of OAHFAs in the Demodex-positive group suggest that OAHFAs may be associated with the progress of ocular Demodex infections. Translational Relevance: OAHFAs could be a potential new therapeutic target for ocular Demodex infestation.

Hyperkeratinization and Proinflammatory Cytokine Expression in Meibomian Glands Induced by Staphylococcus aureus.

Purpose: This exploratory study aimed to investigate the morphological and pathological alterations of the meibomian gland (MG) with the Staphylococcus aureus crude extracts (SACEs) treatment. Methods: Mouse MG explants were cultured and differentiated with or without SACEs for 48 hours. Explant's viability and cell death were determined by thiazolyl blue tetrazolium bromide (MTT) assay and TUNEL assay. MG morphology was observed by Hematoxylin and Eosin staining. Lipid droplet production was detected by Nile Red staining and LipidTox immunostaining. The pro-inflammatory cytokines were detected by ELISA. The relative gene and protein expression in MG explants was determined via quantitative RT-PCR, immunostaining, and immunoblotting. The components of the SACEs were analyzed by immunoblotting and silver staining. Results: Our findings demonstrated that the SACEs treatment induced overexpression of keratin 1 (Krt1) in the ducts and acini of MG explants, accompanied by a decrease in viability and an increase in cell death in explants. Furthermore, the SACEs treatment dose-dependently increased the levels of TNF-α, IL-1ß, and IL-6 in MG explants. The SACEs treatment induced activation of the nuclear factor kappa B (NF-κB) and AIM2 (absent in melanoma 2)/ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) inflammasome signaling pathway in explants. Further investigation showed expression of the key adipogenesis-related molecule peroxisome proliferator-activated receptor γ was decreased after SACEs treatment. However, no change was found in the lipid synthesis of MG explants after treatment with the SACEs. Staphylococcal enterotoxins B (SEB) was detected in the SACEs. SEB induced the overexpression of Krt1 and IL-1ß in ducts and acini of MG explants. Conclusions: Our findings confirm that Staphylococcus aureus induced hyperkeratinization and pro-inflammatory cytokines expression in MG explants ducts and acini. These effects might be mediated by SEB. Activation of the NF-κB and AIM2/ASC signaling pathway is involved in this process.