Sustainable treatment of aquaculture water employing fungi-microalgae consortium: Nutrients removal enhancement, bacterial communities optimization, emerging contaminants elimination, and mechanism analysis.

Fungi-microalgae consortium (FMC) has emerged as a promising system for advanced wastewater treatment due to its high biomass yield and environmental sustainability. This study aimed to investigate the nutrients removal, bacterial community shift, emerging contaminants elimination, and treatment mechanism of a FMC composed of Cordyceps militaris and Navicula seminulum for aquaculture pond water treatment. The fungi and microalgae were cultured and employed either alone or in combination to evaluate the treatment performance. The results demonstrated that the FMC could improve water quality more significantly by reducing nutrient pollutants and optimizing the bacterial community structures. Furthermore, it exhibited stronger positive correlation between the enrichment of functional bacteria for water quality improvement and pollutants removal performance than the single-species treatments. Moreover, the FMC outperformed other groups in eliminating emerging contaminants such as heavy metals, antibiotics, and pathogenic Vibrios. Superiorly, the FMC also showed excellent symbiotic interactions and cooperative mechanisms for pollutants removal. The results collectively corroborated the feasibility and sustainability of using C. militaris and N. seminulum for treating aquaculture water, and the FMC would produce more mutualistic benefits and synergistic effects than single-species treatments.

LncRNA in periodontal tissue-derived cells on osteogenic differentiation in the periodontitis field.

OBJECTIVE: Periodontitis can lead to the destruction of periodontal tissues and potentially tooth loss. Numerous periodontal tissue-derived cells display osteogenic differentiation potential. The presence of differentially expressed long non-coding RNAs (lncRNAs) in these cells indicate their ability to regulate the process of osteogenic differentiation. We aim to elucidate the various lncRNA-mediated regulatory mechanisms in the osteogenic differentiation of periodontal tissue-derived cells in the field of periodontitis at epigenetic modification, transcriptional, and post-transcriptional levels. SUBJECTS AND METHODS: We systematically searched the PubMed, Web of Science, and ScienceDirect databases to identify relevant literature in the field of periodontitis discussing the role of lncRNAs in regulating osteogenic differentiation of periodontal tissue-derived cells. The identified literature was subsequently summarized for comprehensive review. RESULTS: In this review, we have comprehensively summarized the regulatory mechanisms of lncRNAs in the osteogenic differentiation of periodontal tissue-derived cells in the field of periodontitis and discussed how these lncRNAs provide novel perspectives for understanding the pathogenesis and progression of periodontitis. CONCLUSION: These results indicate the pivotal role of lncRNAs as regulators in the osteogenic differentiation of periodontal tissue-derived cells, providing a solid basis for future investigations on the role of lncRNAs in the periodontitis field.

Analytical and Functional Similarity of Aflibercept Biosimilar ABP 938 with Aflibercept Reference Product.

INTRODUCTION: ABP 938 is being developed as a biosimilar candidate to aflibercept reference product (RP), a biologic used for certain angiogenic eye disorders. This study was designed to provide a comparative analytical assessment of the structural and functional attributes of ABP 938 and aflibercept RP sourced from the United States (US) and the European Union (EU). METHODS: Structural and functional characterization studies were performed using state-of-the-art analytical techniques that were appropriate to assess relevant quality attributes and capable of detecting qualitative and quantitative differences in primary structure, higher-order structure and biophysical properties, product-related substances and impurities, general properties, and biological activities. RESULTS: ABP 938 had the same amino acid sequence and exhibited similar secondary and tertiary structures, and biological activity as aflibercept RP. There were minor differences in a small number of biochemical attributes which are not expected to impact clinical performance. In addition, aflibercept RP sourced from the US and EU were analytically similar. CONCLUSIONS: ABP 938 was structurally and functionally similar to aflibercept RP. Since aflibercept RP sourced from the US and EU were analytically similar, this allows for the development of a scientific bridge such that a single-source RP can be used in nonclinical and clinical studies.

Eylea^® (aflibercept) is a biologic medication approved for the treatment of patients with certain eye diseases that can result in low vision or blindness. Biosimilars are biologic medications that are highly similar to an existing approved biologic medication, often called a reference product. Biosimilars have the potential to reduce medication costs despite having no clinically significant differences in quality, efficacy, and safety from their reference products. ABP 938 is currently being developed as a biosimilar to aflibercept reference product. We have conducted similarity studies to compare multiple batches of ABP 938 and aflibercept reference product sourced from both the United States and the European Union, using state-of-the-art analytical methods. The results demonstrated that ABP 938 had the same amino acid sequence and similar structural and biological activities as aflibercept reference product. Before biosimilars can be used as medicines, studies such as this one are required by the Food and Drug Administration and other regulatory authorities to ensure that biosimilars are as safe and effective as their reference products.

Comparative pharmacokinetics of polymyxin B in critically ill elderly patients with extensively drug-resistant gram-negative bacteria infections.

Introduction: Elderly patients are more prone to develop acute kidney injury during infections and polymyxin B (PMB)-associated nephrotoxicity than young patients. The differential response to PMB between the elderly and young critically ill patients is unknown. We aimed to assess PMB exposure in elderly patients compared with young critically ill patients, and to determine the covariates of PMB pharmacokinetics in critically ill patients. Methods: Seventeen elderly patients (age ≥ 65 years) and six young critically ill patients (age < 65 years) were enrolled. Six to eight blood samples were collected during the 12 h intervals after at least six doses of intravenous PMB in each patient. PMB plasma concentrations were quantified by high-performance liquid chromatography-tandem mass spectrometry. The primary outcome was PMB exposure as assessed by the area under the concentration-time curve over 24 h at steady state (AUCss, 0-24 h). Results and Discussion: The elderly group had lower total body weight (TBW) and higher Charlson comorbidity scores than young group. Neither AUCss, 0-24 h nor normalized AUCss, 0-24 h (adjusting AUC for the daily dose in mg/kg of TBW) was significantly different between the elderly group and young group. The half-life time was longer in the elderly patients than in young patients (11.21 vs 6.56 h respectively, p = 0.003). Age and TBW were the covariates of half-life time (r = 0.415, p = 0.049 and r = -0.489, p = 0.018, respectively). TBW was the covariate of clearance (r = 0.527, p = 0.010) and AUCss, 0-24 h (r = -0.414, p = 0.049). Patients with AUCss, 0-24 h ≥ 100 mg·h/L had higher baseline serum creatinine levels and lower TBW than patients with AUCss, 0-24 h < 50 mg·h/L or patients with AUCss, 0-24 h 50-100 mg·h/L. The PMB exposures were comparable in elderly and young critically ill patients. High baseline serum creatinine levels and low TBW was associated with PMB overdose. Trial registration: ChiCTR2300073896 retrospectively registered on 25 July 2023.

New Horizons of Covalent Complex of Plant-Derived Recombinant Human Lactoferrin (OsrhLF) Combined with Different Polyphenols: Formation, Physicochemical Properties, and Gastrointestinal Fate.

Four typical dietary polyphenols ((-)-epigallocatechin gallate (EGCG), quinic acid (QA), caffeic acid (CA), and ferulic acid (FA)) were covalently prepared with rice recombinant human lactoferrin (OsrhLF) and bovine lactoferrin (bLF), and their structure and physicochemical properties were investigated, different lycopene emulsions were made by ultrasonic emulsification to analyze gastrointestinal fate. The results indicated that the covalent modification polyphenols changed the secondary/tertiary structure of LF, significantly improving the surface hydrophilicity, thermal stability, and antioxidant activity of LF. Compared with the bLF group, the OsrhLF group was more hydrophilic and the thermal denaturation temperature of the OsrhLF-CA reached 104.4 °C. LF-polyphenol emulsions significantly enhanced the photochemical stability and bioavailability of lycopene and achieved effective encapsulation and protection of lycopene compared to free lycopene, and the OsrhLF-EGCG reached 58.94% lycopene bioavailability. In short, OsrhLF does not differ much from bLF in terms of physicochemical properties and has a strong potential in the field of dietary supplements.

A novel short-type peptidoglycan recognition protein with unique polysaccharide recognition specificity in sea cucumber, Apostichopus japonicus.

Pattern recognition receptors (PRRs) are the first line of immune defense in invertebrates against pathogen infection; they recognize pathogens and transmit signals to downstream immune pathways. Among these, peptidoglycan recognition proteins (PGRPs) are an important family in invertebrates that generally comprise of complicated isoforms. A comprehensive understanding of PGRPs in evolutionarily and economically important marine invertebrates, such as the sea cucumber, Apostichopus japonicus, is crucial. Previous studies have identified two PGRPs in sea cucumber, AjPGRP-S and AjPGRP-S1, and another novel short-type PGRP, AjPGRP-S3, was additionally identified here. The full-length cDNA sequence of AjPGRP-S3 was obtained here by PCR-RACE, followed by which showed its gene expression analyses by in situ hybridization that showed it to be relatively highly expressed in coelomocytes and tube feet. Based on an analysis of the recombinant protein, rAjPGRP-S3, a board-spectrum pathogen recognition ability was noted that covered diverse Gram-negative and -positive bacteria, and fungi. Moreover, according to the results of yeast two-hybridization, it was suggested that rAJPGRP-S3 interacted with multiple immune-related factors, including proteins involved in the complement system, extracellular matrix, vesicle trafficking, and antioxidant system. These findings prove the important functions of AjPGRP-S3 in the transduction of pathogen signals to downstream immune effectors and help explore the functional differences in the AjPGRP isoforms.

The signaling pathways involved in non-coding RNA regulation during osteogenic differentiation of periodontal tissue-derived cells in the field of periodontitis.

Periodontitis is a prevalent oral disease caused by chronic inflammation of the periodontal tissues surrounding the teeth, which can lead to bone loss, tooth loosening, and even tooth loss. This inflammation has a negative impact on the osteogenic differentiation capacity of periodontal tissue-derived cells. Non-coding RNAs (ncRNAs) are a class of RNA molecules that do not encode proteins but can regulate various physiological processes. In this review, we summarized the critical signaling pathways that ncRNAs modulate in osteogenic differentiation of periodontal tissue-derived cells, such as the Wnt, BMP/Smad, NF-κB, and PI3-K/Akt/mTOR pathways. This comprehensive exploration of ncRNA-mediated modulation offers fresh and promising insights for prospective approaches in the management of periodontitis and the advancement of periodontal regeneration therapies.

Effect of chewing gum on orthodontic pain in patients receiving fixed orthodontic treatment: a systematic review and meta-analysis.

OBJECTIVES: The objective of this systematic review and meta-analysis was to evaluate the effect of chewing gum on orthodontic pain and to determine the rate of bracket breakage associated with fixed orthodontic appliances. METHODS: This review and its reporting were performed according to the Cochrane Handbook for Systematic Reviews of Interventions and the PRISMA guidelines. Six electronic databases were searched up to March 16, 2023, to identify relevant studies that met the inclusion and exclusion criteria. Furthermore, grey literature resources were searched. The Cochrane Collaboration Risk of Bias tool 2 was used to assess the quality of the included studies. Meta-analysis was conducted using RevMan, and sensitivity analysis and publication bias analysis were performed using STATA software. GRADE tool was used to evaluate the certainty of evidence. RESULTS: Fifteen studies with 2116 participants were ultimately included in this review, and 14 studies were included in the meta-analysis. Compared with the blank group, chewing gum had a significant pain relieving effect at all times after fixation of the initial archwire (P ≤ 0.05). No significant difference was found between the chewing gum group and the analgesics group at any timepoints (P > 0.05). Only four studies evaluated the rate of bracket breakage and revealed that chewing gum did not increase the rate of bracket breakage. The sensitivity analysis showed that there was no significant difference in the pooled outcomes after the included studies were removed one at times, and Egger analysis revealed no significant publication bias in included studies (P > 0.05). CONCLUSIONS: Chewing gum is a non-invasive, low-cost and convenient method that has a significant effect on relieving orthodontic pain and has no effect on the rate of bracket breakage. Therefore, chewing gum can be recommended as a suitable substitute for analgesics to reduce orthodontic pain.

The Biological Significance Of AFF4: Promoting Transcription Elongation, Osteogenic Differentiation and Tumor Progression.

As a member of the AF4/FMR2 (AFF) family, AFF4 is a scaffold protein in the superelongation complex (SEC). In this mini-view, we discuss the role of AFF4 as a transcription elongation factor that mediates HIV activation and replication and stem cell osteogenic differentiation. AFF4 also promotes the progression of head and neck squamous cell carcinoma, leukemia, breast cancer, bladder cancer and other malignant tumors. The biological function of AFF4 is largely achieved through SEC assembly, regulates SRY-box transcription factor 2 (SOX2), MYC, estrogen receptor alpha (ESR1), inhibitor of differentiation 1 (ID1), c-Jun and noncanonical nuclear factor-κB (NF-κB) transcription and combines with fusion in sarcoma (FUS), unique regulatory cyclins (CycT1), or mixed lineage leukemia (MLL). We explore the prospects of using AFF4 as a therapeutic in Acquired immunodeficiency syndrome (AIDS) and malignant tumors and its potential as a stemness regulator.

Temporal stability and assembly mechanisms of gut microbiota in sea cucumbers response to nanoplastics treatment.

Aquaculture provides essential food for humans, and the health of farmed species is particularly important for the aquaculture industry. Aquaculture environment could be a sink of plastic debris (PDs) due to the enclosed character and heavy use of plastics. Gut microbiota of aquaculture species could respond to the exogenous pollutants and regulate the health of hosts. Here, variations in gut microbiota of Apostichopus japonicus induced by the ingested nanoplastics (NPs) were investigated by a lab experiment. We selected a NPs concentration gradient of 100 mg/kg and 500 mg/kg to simulate microplastic pollution to A. japonicus, and the significant differences in gut microbiota composition after 21 days of NP exposure were evaluated. According to the high-throughput sequencing from time series samples, a decrease of diversity in gut microbiota of A. japonicus with dietary NPs was observed. In addition, the gut microbiota compositions of sea cucumbers with and without NPs exposure were also distinct, expressing as enrichment of Bacteroidota while reducement of Proteobacteria under NPs stresses. Combined the results of network analysis, the less complexity and stability of gut microbiota in sea cucumbers with dietary NPs were proved. Based on the neutral community model, the ingested NPs elevated the contribution of stochastic processes for the gut microbiota assembly in sea cucumbers. Our study showed that substantial variations in gut microbiota of A. japonicus under NPs stresses, and also explored the underlying mechanisms regulating these changes. This research would offer new meaningful insights into the toxicity of NPs on sea cucumbers, contributing a solid fundament to improve the health of sea cucumbers under NPs stresses.

Succession and assembly mechanisms of seawater prokaryotic communities along an extremely wide salinity gradient.

Salinity is an important environmental factor in microbial ecology for affecting the microbial communities in diverse environments. Understanding the salinity adaptation mechanisms of a microbial community is a significant issue, while most previous studies only covered a narrow salinity range. Here, variations in seawater prokaryotic communities during the whole salt drying progression (salinity from 3% to 25%) were investigated. According to high-throughput sequencing results, the diversity, composition, and function of seawater prokaryotic communities varied significantly along the salinity gradient, expressing as decreased diversity, enrichment of some halophilic archaea, and powerful nitrate reduction in samples with high salt concentrations. More importantly, a sudden and dramatic alteration of prokaryotic communities was observed when salinity reached 16%, which was recognized as the change point. Combined with the results of network analysis, we found the increasing of complexity but decreasing of stability in prokaryotic communities when salinity exceeded the change point. Moreover, prokaryotic communities became more deterministic when salinity exceeded the change point due to the niche adaptation of halophilic species. Our study showed that substantial variations in seawater prokaryotic communities along an extremely wide salinity gradient, and also explored the underlying mechanisms regulating these changes.

Automatic three-dimensional nasal and pharyngeal airway subregions identification via Vision Transformer.

OBJECTIVES: Upper airway assessment requires a fully-automated segmentation system for complete or sub-regional identification. This study aimed to develop a novel Deep Learning (DL) model for accurate segmentation of the upper airway and achieve entire and subregional identification. METHODS: Fifty cone-beam computed tomography (CBCT) scans, including 24,502 slices, were labelled as the ground truth by one orthodontist and two otorhinolaryngologists. A novel model, a lightweight multitask network based on the Swin Transformer and U-Net, was built for automatic segmentation of the entire upper airway and subregions. Segmentation performance was evaluated using Precision, Recall, Dice similarity coefficient (DSC) and Intersection over union (IoU). The clinical implications of the precision errors were quantitatively analysed, and comparisons between the AI model and Dolphin software were conducted. RESULTS: Our model achieved good performance with a precision of 85.88-94.25%, recall of 93.74-98.44%, DSC of 90.95-96.29%, IoU of 83.68-92.85% in the overall and subregions of three-dimensional (3D) upper airway, and a precision of 91.22-97.51%, recall of 90.70-97.62%, DSC of 90.92-97.55%, and IoU of 83.41-95.29% in the subregions of two-dimensional (2D) crosssections. Discrepancies in volume and area caused by precision errors did not affect clinical outcomes. Both our AI model and the Dolphin software provided clinically acceptable consistency for pharyngeal airway assessments. CONCLUSION: The novel DL model not only achieved segmentation of the entire upper airway, including the nasal cavity and subregion identification, but also performed exceptionally well, making it well suited for 3D upper airway assessment from the nasal cavity to the hypopharynx, especially for intricate structures. CLINICAL SIGNIFICANCE: This system provides insights into the aetiology, risk, severity, treatment effect, and prognosis of dentoskeletal deformities and obstructive sleep apnea. It achieves rapid assessment of the entire upper airway and its subregions, making airway management-an integral part of orthodontic treatment, orthognathic surgery, and ENT surgery-easier.

Global, regional, and national time trends in mortality for stroke, 1990-2019: An age-period-cohort analysis for the global burden of disease 2019 study and implications for stroke prevention.

BACKGROUND: Despite the fact that stroke is the second leading cause of death globally, a comprehensive and comparable assessment of mortality, and epidemiologic trends has not been conducted for most regions.We estimated the global and regional burden of stroke from 1990 to 2019 using data from the 2019 Global Study of Diseases, Injuries, and Risk Factors. METHODS: For the period between 1990 and 2019, we used an age-period-cohort model to calculate the annual percentage changes in mortality (net drifts), local drifts, and period and cohort relative risks (period/cohort effects). Meanwhile, to quantify the temporal trends in stroke age-standardised mortality rate (ASMR), Average annual percentage changes (AAPCs) were determined by sex, area. With the potential to uncover disparities and treatment gaps in stroke care, this approach enables the examination and differentiation of age, period, and cohort effects in mortality trends. FINDINGS: Global stroke deaths in 2019 were 6,552,725 (95% UI 5,995,200 to 7,015,139). Between 1990 and 2019, the ASMR declined globally by 36.43% (95% UI -41.65 to -31.2), with decreases in all SDI quintiles. The net drift in stroke mortality from 1990 to 2019 varied from -2.83% per year (95% confidence interval [CI]:-3.39 to -2.77) in countries with a high Socio-demographic Index (SDI) to -1.21% per year (95% CI: -1.26 to -1.16) in countries with a low SDI. During the past 30 years, favorable mortality reductions were generally found in high-SDI countries (net drift = -3.1% [95% CI: -3.4 to -2.8] per year) and high-middle SDI countries (-2.8% [-3.0 to -2.6]). However, 31 of 204 countries had either increasing trends (net drifts≥0.0%) or stagnated reductions (≥ - 0.5%) in mortality. The relative risk of mortality generally showed improving trends over time and in successively younger birth cohorts among high and high-middle SDI countries, with the exceptions of Kuwait, Ukraine, Kazakhstan, Guam, RussianFederation, Lithuania, Turkey, Montenegro, Serbia, Bosnia and Herzegovin, and Bulgaria. INTERPRETATION: Notwithstanding mortality from stroke has increased globally over the past 30 years, adverse period and cohort effects have been found in many countries, calling into question the adequacy of healthcare for stroke patients of all ages. These lapses have a significant impact on the likelihood of achieving the Sustainable Development Goal (SDG) targets on mortality from age 60+ and NCDs.

Minocycline protects against microgliopathy in a Csf1r haplo-insufficient mouse model of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP).

BACKGROUND: Mutations in colony-stimulating factor 1 receptor (CSF1R) are known to cause adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), which has been recently demonstrated as a primary microgliopathy characterized by cognitive impairment. Although the molecular mechanism underlying CSF1R-mediated microgliopathy remains unclear, therapeutic strategies have generally targeted modulation of microglial function. In particular, the microglial inhibitor, minocycline, has been shown to attenuate learning and memory deficits in several neurodegenerative diseases. The objectives of this study were to investigate the pathogenic mechanisms underlying ALSP and to explore the therapeutic effects of minocycline in an in vivo model of ALSP. We hypothesized that inhibiting microglial activation via minocycline could reverse the behavior and pathological defects in ALSP model mice. METHODS: We generated a Csf1r haploinsufficiency mouse model of ALSP using CRISPR/Cas9 genome editing and conducted electrophysiological recordings of long-term potentiation (LTP) and behavioral tests to validate the recapitulation of clinical ALSP characteristics in 8- to 11-month-old mice. RNA-sequencing was used to explore enriched gene expression in the molecular pathogenesis of ALSP. Microglial activation was assessed by immunofluorescent detection of Iba1 and CD68 in brain sections of male ALSP mice and pro-inflammatory activation and phagocytosis were assessed in Csf1r+/- microglia. Therapeutic effects were assessed by behavioral tests, histological analysis, and morphological examination after four weeks of intraperitoneal injection with minocycline or vehicle control in Csf1r+/- mice and wild-type control littermates. RESULTS: We found that synaptic function was reduced in LTP recordings of neurons in the hippocampal CA1 region, while behavioral tests showed impaired spatial and cognitive memory specifically in male Csf1r+/- mice. Increased activation, pro-inflammatory cytokine production, and enhanced phagocytic capacity were also observed in Csf1r+/- microglia. Treatment with minocycline could suppress the activation of Csf1r+/- microglia both in vitro and in vivo. Notably, the behavioral and pathological deficits in Csf1r+/- mice were partially rescued by minocycline administration, potentially due to inhibition of microglial inflammation and phagocytosis in Csf1r+/- mice. CONCLUSIONS: Our study shows that CSF1R deficiency results in aberrant microglial activation, characterized by a pro-inflammatory phenotype and enhanced phagocytosis of myelin. Our results also indicate that microglial inhibition by minocycline can ameliorate behavioral impairment and ALSP pathogenesis in CSF1R-deficient male mice, suggesting a potential therapeutic target for CSF1R-related leukoencephalopathy. Collectively, these data support that minocycline confers protective effects against CSF1R-related microgliopathy in male ALSP model mice.

Cognitive impairment of MRL mice is related to NMDA receptor-mediated inflammatory response and production of adhesion molecules in MRL/lpr mice-derived micro-vascular endothelial cells.

Systemic lupus erythematosus (SLE) is a chronic recurrent autoimmune disease affecting almost all organs. This study was conducted to investigate cognitive impairment of SLE mice (MRL/lpr mice), and explore associated pathological mechanism. Behavior tests (open-field test, elevated plus-maze test, forced swimming test, sucrose preference test, and Morris water maze test) were conducted in MRL/MPJ and MRL/lpr mice. ELISA test was performed to determine levels of antibodies (anti-dsDNA, anti-RPA, anti-ACA, and anti-NR2a/b) and inflammatory factors [tumour necrosis factor a (TNF-a), interleukin (IL)-6, IL-8, and IL-10]. Micro-vascular endothelial cells (MVECs) were isolated, identified, and divided into MVECs (NC), anti-NR2a/2b, memantine, glycine, dexamethasone, and IL-1b groups. Cell proliferation was measured using cell counting kit-8 (CCK-8) assay, and Western blotting was applied to evaluate ELAM-1, VCAM-1, ICAM-1, IKBa, p-IKBa expression. MRL/lpr mice demonstrated lower locomotion/exploration ability, higher anxiety, obvious depression symptoms, lower learning/memory capability compared with MRL/MPJ mice. MRL/lpr mice demonstrated high levels of anti-NR2a/b antibody and auto-antibodies. NMDA receptor antagonist (memantine) significantly increased, and NMDA receptor agonist (glycine) significantly decreased MVECs proliferation compared with NC group ( p < 0.05). Memantine significantly reduced and glycine predominantly enhanced TNF-a, IL-6, IL-8, and IL-10 levels compared with NC group ( p < 0.05). NMDA receptor antagonist and agonist modulated adhesion molecules expression in MVECs. ELAM-1, VCAM-1, and ICAM-1 expressions were significantly down-modulated in memantine group, and remarkably up-modulated in glycine group compared with NC group ( p < 0.05). NMDA receptor antagonist and agonist regulated phosphorylation of p-IKBa. The above effects of memantine evenly equaled to dexamethasone, and glycine evenly equaled to IL-1b. In conclusion, cognitive impairment of MRL mice might be associated with NMDA receptor-mediated inflammatory response and production of adhesion molecules in MRL/lpr mice-derived MVECs.

Adverse effects of polystyrene nanoplastics on sea cucumber Apostichopus japonicus and their association with gut microbiota dysbiosis.

The mariculture environment is a sink of microplastics (MPs) due to its enclosed nature and mass use of plastics. Nanoplastics (NPs) are MPs with a diameter <1 µm that have a more toxic effect on aquatic organisms than other MPs. However, little is known about the underlying mechanisms of NP toxicity on mariculture species. Here, we performed a multi-omics investigation to explore gut microbiota dysbiosis and associated health problems induced by NPs in juvenile sea cucumber Apostichopus japonicus, a commercially and ecologically important marine invertebrate. We observed significant differences in gut microbiota composition after 21 days of NP exposure. Ingestion of NPs significantly increased core gut microbes, especially Rhodobacteraceae and Flavobacteriaceae families. Additionally, gut gene expression profiles were altered by NPs, especially those related to neurological diseases and movement disorders. Correlation and network analyses indicated close relationships between transcriptome changes and gut microbiota variation. Furthermore, NPs induced oxidative stress in sea cucumber intestines, which may be associated with intraspecies variation in Rhodobacteraceae in the gut microbiota. The results suggested that NPs were harmful to the health of sea cucumbers, and they highlighted the importance of the gut microbiota in the responses to NP toxicity in marine invertebrates.

Identification of immunological bioprocesses involved in peri-implantitis using weighted gene co-expression network analysis.

BACKGROUND: Peri-implantitis is an irreversible infectious disease that occurs with high incidence. Exploring the immune responses of peri-implantitis is key to developing targeted treatment strategies. However, there is limited research on the immune response of peri-implantitis. METHODS: This study performed a weighted gene co-expression network analysis to identify the peri-implantitis related gene network and conducted a functional enrichment analysis of the gene network. Thereafter, the candidate hub genes were selected by constructing a protein-protein interaction network and drawing an upset plot. The hub genes were identified through their significant associations with disease condition and validated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. Using the gene set variation analysis, the hub genes were further used to explore infiltrating immunocytes and immune factors in peri-implantitis. Finally, the immunocytes and immune factor related hub genes were intersected to obtain the therapeutic target, which was validated using histological staining. RESULTS: The peri-implantitis related gene network was enriched in innate and adaptive immune response. Subsequently, interleukin (IL)1B, IL10, ITGAM, ITGB1, STAT3, and TLR4 were identified as hub genes. Plasmacytoid dendritic cells, macrophages, myeloid-derived suppressor cells, natural killer T cells, and immature B cells were positively and significantly related to the hub genes IL1B, TLR4, ITGAM, and ITGB1 (correlation coefficient > 0.80). While immune factors CXCL10, IL6, and CXCL12 and hub genes IL10 and IL1B held the highest degree in the immune factors network. IL1B may be a promising therapeutic target. CONCLUSION: This study provides new insights into the hub genes, immunocytes, and immune factors underlying peri-implantitis immunological bioprocess.

FAM3 Family as Prognostic Factors for Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Although head and neck squamous cell carcinoma (HNSCC) is a common malignancy, the molecular biology landscape underlying its occurrence and development remains poorly understood. The family with sequence similarity (FAM) 3 family of proteins includes four family members, namely FAM3A, FAM3B, FAM3C and FAM3D. In particular, FAM3C has been previously reported to be closely associated with various human malignancies. METHODS: Combining analyses using The Cancer Genome Atlas, Gene Expression Profiling Interactive Analysis, Tumor Immune Estimation Resource and MethSurv databases, coupled with the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes bioinformatics tools, the possible biological function and key pathways regulated by the FAM3 family in HNSCC were probed. RESULTS: High FAM3A expression was found to increase HNSCC mitochondrial biosynthesis and energy metabolism, inhibit immune cell infiltration in the HNSCC tumor microenvironment, and be associated with poor prognosis. By contrast, lower expression levels of FAM3B in HNSCC were associated with a poorer prognosis in patients with HNSCC. This was most likely due to the finding that FAM3B can inhibit the development of HNSCC by increasing immune cell infiltration, inhibiting epithelial-mesenchymal transition (EMT) and the cytochrome P450 pathway. FAM3C was overexpressed in oral squamous cell carcinoma (OSCC) and associated with increased OSCC cell stemness, immune escape and EMT. In the present study, FAM3C expression was associated with poor prognosis for patients with HNSCC by suppressing tumor immune cell infiltration. FAM3C expression was also positively correlated with the expression of epithelial and mesenchymal markers such as E-cadherin, N-cadherin, Vimentin and ZO-1, which may promote the partial EMT status in HNSCC and greatly increase its malignancy. FAM3D is a maintenance factor of the epithelial phenotype in HNSCC that can inhibit the progression of EMT, promote tumor immune cell infiltration and inhibit HNSCC progression. In addition, methylation levels of the FAM3 gene family were correlated with the overall survival rate of HNSCC. CONCLUSION: The FAM3 family may be applied as a biomarker and potential therapeutic target for HNSCC.