Transcutaneous auricular vagus nerve stimulation for epilepsy.

BACKGROUND: Several studies have suggested that transcutaneous vagus nerve stimulation (tVNS) may be effective for the treatment of epilepsy. However, auricular acupoint therapy (including auricular acupuncture and auricular point-sticking therapy), a method of stimulating the vagus nerve, has been poorly reviewed. This systematic review is the first to categorize auricular acupoint therapy as transcutaneous auricular vagus nerve stimulation (taVNS), aiming to assess the efficacy of taVNS in patients with epilepsy (PWE), and to analyse the results of animal experiments on the antiepileptic effects of taVNS. METHODS: We searched MEDLINE, EMBASE, Web of Science, Scopus, and various Chinese databases from their inception to June 10, 2023 and found nine clinical studies (including a total of 788 PWE) and eight preclinical studies. We performed a meta-analysis and systematic review of these articles to assess the efficacy of taVNS in PWE and the association between taVNS and electroencephalogram (EEG) changes. We also analysed the effects on epileptic behaviour, latency of the first seizure, and seizure frequency in epileptic animals. The PRISMA 2020 checklist provided by the EQUATOR Network was used in this study. RESULTS: taVNS had a higher response rate in PWE than the control treatment (OR = 2.94, 95 % CI = 1.94 - 4.46, P < 0.05). The analysis showed that the taVNS group showed wider EEG changes than the control group (OR = 2.17, 95 % CI 1.03 to 4.58, P < 0.05). The preclinical studies analysis revealed significant differences in epileptic behaviour (SMD = -4.78, 95 % CI -5.86 to -3.71, P < 0.05) and seizure frequency (SMD = -5.06, 95 % CI -5.96 to -4.15, P < 0.05) between the taVNS and control groups. No statistical difference was found in the latency of the first seizure between the two groups (SMD =13.54; 95 % CI 7.76 to 19.33, P < 0.05). CONCLUSION: Based on the available data, PWE may benefit from the use of taVNS. taVNS is an effective procedure for improving epileptic behaviour in animal models.

Analysis of Body Mass Index and Clinicopathological Factors in Patients with Papillary Thyroid Carcinoma.

Objective: To analyze the correlation between body mass index (BMI) and clinicopathological factors of papillary thyroid cancer (PTC). Methods: The clinical data of patients with PCT who were hospitalized in the Department of Thyroid Surgery of the Affiliated Hospital of Guizhou Medical University from March 2023 to September 2023 were retrospectively collected, including age, gender, height, weight, BMI, v-raf murine sarcoma viral oncogene homolog B (BRAF) gene mutation, tumor size, multifocus, Hashimoto's thyroiditis, lymph node metastasis and other clinicopathological factors. According to the World Health Organization (WHO) definition for Asian population, BMI≥25kg/m2 was obese group, 23≤BMI≤24.9kg/m2 was overweight group, 18.5≤BMI≤22.9kg/m2 was normal weight group, and BMI≤18.5kg/m2 was low weight group. The clinicopathological factors of overweight and obese patients with PTC were analyzed. Results: A total of 164 PTC patients were included, with an average BMI of (24.44±3.57) kg/m2. Age of overweight and obese PTC patients (Z=1.978, p=0.083); Gender of overweight and obese PTC patients (χ2 value: 11.570, p=0.004); Tumor size in overweight and obese PTC patients (Z=0.894, p=0.411); BRAF gene mutation in overweight and obese PTC patients (χ2 value: 1.452, p =0.623); Multifocal lesions were found in overweight and obese patients (χ2 value: 1.653, p =0.201). Hashimoto's thyroiditis was found in overweight and obese PTC patients (χ2 value: 1.147, p=0.298). Overweight and obese patients with PTC had lymph node metastasis (χ2 value: 1.690, p =0.251). Conclusion: Overweight and obesity in PTC patients are correlated with male, but not with age, tumor size, BRAF mutation, multifocality, Hashimoto's thyroiditis and lymph node metastasis.

Rasch analysis of the pre-sleep arousal scale in patients with acute insomnia disorder.

BACKGROUND: Hyperarousal plays an essential role in the initiation and maintenance of insomnia, highlighting the need for a tool that measure the hyperarousal state during the early course of insomnia. Pre-sleep Arousal Scale (PSAS) is a self-report questionnaire to evaluate subjective pre-sleep arousal of insomnia. The aim of this study was to examine the psychometric properties of the PSAS among patients with acute insomnia disorder (AID) using Rasch analysis. METHODS: Totally 170 patients with AID from 31 public hospitals in China were recruited and completed the test. The psychometric properties of the PSAS were tested using Rasch analysis by Winsteps v5.4.1.0, including unidimensionality, local item independence, item fit, category diagnostics, reliability, item-person maps and differential item functioning (DIF) by age and gender. RESULTS: According to Rasch analysis, somatic and cognitive subscales were unidimensional and basically demonstrated good item-fit statistics. 4-point Likert scale may be more appropriate for PSAS. All items have a good reliability and separation. No gender and age bias were detected for the scale. However, the person arousal level is not well matched to item difficulty. CONCLUSION: The present study further reveals appropriate psychometric properties of the PSAS in patients with AID and provides suggestions for refinements and supplements to the PSAS.

A Novel Strategy for Fabrication of Polyamide 66/Nanohydroxyapatite Composite Bone Repair Scaffolds by Low-Temperature Three-Dimensional Printing.

Due to the decomposition temperature of Polyamide 66 (PA66) in the environment is close to its thermoforming temperature, it is difficult to construct porous scaffolds of PA66/nanohydroxyapatite (PA66/HAp) by fused deposition modeling (FDM) three-dimensional (3D) printing. In this study, we demonstrated for the first time a method for 3D printing PA66/HAp composites at room temperature, prepared PA66/HAp printing ink using a mixed solvent of formic acid/dichloromethane (FA/DCM), and constructed a series of composite scaffolds with varying HAp content. This printing system can print composite materials with a high HAp content of 60 wt %, which is close to the mineral content in natural bone. The physicochemical evaluation presented that the hydroxyapatite was uniformly distributed within the PA66 matrix, and the PA66/HAp composite scaffold with 30 wt % HAp content exhibited optimal mechanical properties and printability. The results of in vitro cell culture experiments indicated that the incorporation of HAp into the PA66 matrix significantly improved the cell adhesion, proliferation, and osteogenic differentiation of bone marrow stromal cells (BMSCs) cultured on the scaffold. In vivo animal experiments suggested that the PA66/HAp composite material with 30 wt % HAp content had the best structural maintenance and osteogenic performance. The three-dimensional PA66/HAp composite scaffold prepared by low temperature printing in the current study holds great potential for the repair of large-area bone defects.

Is cognitive behavioral therapy for insomnia (CBTI) more cost-effective? New-perspective on economic evaluations: a systematic review and meta-analysis.

STUDY OBJECTIVES: To investigate the cost-effectiveness of cognitive behavioral therapy for insomnia (CBTI), with an additional focus on digital cognitive behavioral therapy for insomnia (dCBTI) in adults with insomnia. METHODS: We searched eight electronic databases for economic evaluations of CBTI: PubMed, Scopus, Web of Science, psycINFO, Cochrane, Library, CINAHL, ProQuest and National Health Service Economic Evaluation Database. Meta-analyses were performed to investigate the effects and costs between CBTI and control groups (no treatment, other treatments included hygiene education and treatment as usual). Subgroup analyses for dCBTI were conducted. RESULTS: Twelve randomized controlled trails studies between 2004 and 2023 were included in our systematic review and meta-analyses. The incremental cost-utility ratios and incremental cost-effectiveness ratios showed that the CBTI and dCBTI groups were more cost-effective than controls, from healthcare perspective and societal perspective, respectively. Compared to controls, CBTI demonstrated significantly better efficacy within 12 months. Healthcare costs were significantly higher in the CBTI groups compared to the controls within 6 months but there was no difference at 12 months. Additionally, dCBTI was associated with significantly lower presenteeism costs compared to controls at 6 months. CONCLUSIONS: Our findings suggest that CBTI is more cost-effective than other treatments or no treatment for adults with insomnia. It may bring more economic benefits in the long-term, especially in long-lasting efficacy and costs reduction. In addition, dCBTI is one of the cost-effective options for insomnia.

Depletion of protective microbiota promotes the incidence of fruit disease.

Plant-associated microbiomes play important roles in plant health and productivity. However, despite fruits being directly linked to plant productivity, little is known about the microbiomes of fruits and their potential association with fruit health. Here, by integrating 16S rRNA gene, ITS high-throughput sequencing data, and microbiological culturable approaches, we reported that roots and fruits (pods) of peanut, a typical plant that bears fruits underground, recruit different bacterial and fungal communities independently of cropping conditions and that the incidence of pod disease under monocropping conditions is attributed to the depletion of Bacillus genus and enrichment of Aspergillus genus in geocarposphere. On this basis, we constructed a synthetic community (SynCom) consisting of three Bacillus strains from geocarposphere soil under rotation conditions with high culturable abundance. Comparative transcriptome, microbiome profiling, and plant phytohormone signaling analysis reveal that the SynCom exhibited more effective Aspergillus growth inhibition and pod disease control than individual strain, which was underpinned by a combination of molecular mechanisms related to fungal cell proliferation interference, mycotoxins biosynthesis impairment, and jasmonic acid-mediated plant immunity activation. Overall, our results reveal the filter effect of plant organs on the microbiome and that depletion of key protective microbial community promotes the fruit disease incidence.

Histology and transcriptomic analysis reveal the inflammation and affected pathways under 2-methylisoborneol (2-MIB) exposure on grass carp.

2-Methylisoborneol (2-MIB) is a common and widely distributed off-flavor compound in water. However, the toxic mechanisms of 2-MIB on aquatic organisms remain largely unexplored. In this study, grass carp larvae were exposed to different concentrations (0, 5, and 20 µg L-1) of 2-MIB for 96 h. The accumulation of 2-MIB in the dorsal muscle was measured. Histological analysis, ultrastructure observations, and transcriptomic sequencing were conducted on the liver tissues. The results showed that 2-MIB accumulated significantly in the fish muscle, with the accumulation increasing as the exposure concentration increased through gas chromatography-mass spectrometry (GC-MS) detection. Histological and ultrastructure observations indicated that 2-MIB caused concentration-dependent inflammatory infiltration and mitochondrial damage in the liver. Transcriptomic analysis revealed lipid metabolism disorders induced by exposure to 2-MIB in grass carp. Additionally, 5 µg L-1 2-MIB affected the neurodevelopment and cardiovascular system of grass carp larvae through extracellular matrix (ECM)-receptor interaction and focal adhesion pathway. Furthermore, several pathways related to the digestive system were significantly enriched, implying that 2-MIB may impact pancreatic secretion function, protein digestion and absorption processes. These findings provide new insights into the potential toxicological mechanisms of 2-MIB.

A new loach species of the genus Oreonectes (Teleostei, Cypriniformes, Nemacheilidae) from Guangxi, China.

A new loach species, Oreonectesandongensissp. nov. is described from the Guangxi Zhuang Autonomous Region, China. The new species can be differentiated from other members of the genus by combinations of characters: a developed posterior chamber of the swim bladder, 13-14 branched caudal-fin rays, 8-16 lateral-line pores, body width 12-15% of standard length (SL), interorbital width 42-47% of head length (HL), and caudal peduncle length 11-16% of SL. Bayesian inference phylogenetic analysis based on mitochondrial Cyt b provided strong support for validity of O.andongensissp. nov. (uncorrected p-distance 6.0-7.5%).

STING-dependent trained immunity contributes to host defense against Clostridium perfringens infection via mTOR signaling.

Clostridium perfringens (C. perfringens) infection is recognized as one of the most challenging issues threatening food safety and perplexing agricultural development. To date, the molecular mechanisms of the interactions between C. perfringens and the host remain poorly understood. Here, we show that stimulator of interferon genes (STING)-dependent trained immunity protected against C. perfringens infection through mTOR signaling. Heat-killed Candida albicans (HKCA) training elicited elevated TNF-α and IL-6 production after LPS restimulation in mouse peritoneal macrophages (PM). Although HKCA-trained PM produced decreased levels of TNF-α and IL-6, the importance of trained immunity was demonstrated by the fact that HKCA training resulted in enhanced bacterial phagocytic ability and clearance in vivo and in vitro during C. perfringens infection. Interestingly, HKCA training resulted in the activation of STING signaling. We further demonstrate that STING agonist DMXAA is a strong inducer of trained immunity and conferred host resistance to C. perfringens infection in PM. Importantly, corresponding to higher bacterial burden, reduction in cytokine secretion, phagocytosis, and bacterial killing were shown in the absence of STING after HKCA training. Meanwhile, the high expression levels of AKT/mTOR/HIF1α were indeed accompanied by an activated STING signaling under HKCA or DMXAA training. Moreover, inhibiting mTOR signaling with rapamycin dampened the trained response to LPS and C. perfringens challenge in wild-type (WT) PM after HKCA training. Furthermore, STING­deficient PM presented decreased levels of mTOR signaling-related proteins. Altogether, these results support STING involvement in trained immunity which protects against C. perfringens infection via mTOR signaling.

CD9 shapes glucocorticoid sensitivity in pediatric B-cell precursor acute lymphoblastic leukemia.

Resistance to glucocorticoids (GCs), the common agents for remission induction in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), poses a significant therapeutic hurdle. Therefore, dissecting the mechanisms shaping GC resistance could lead to new treatment modalities. Here, we showed that CD9- BCP-ALL cells were preferentially resistant to prednisone and dexamethasone over other standard cytotoxic agents. Concordantly, we identified significantly more poor responders to the prednisone prephase among BCP-ALL patients with a CD9- phenotype, especially for those with adverse presenting features including older age, higher white cell count and BCR-ABL1. Furthermore, gain- and loss-of-function experiments dictated a definitive functional linkage between CD9 expression and GC susceptibility, as demonstrated by the reversal and acquisition of relative GC resistance in CD9low and CD9high BCP-ALL cells, respectively. Despite physical binding to the GC receptor NR3C1, CD9 did not alter its expression, phosphorylation or nuclear translocation but potentiated the induction of GC-responsive genes in GCresistant cells. Importantly, the MEK inhibitor trametinib exhibited higher synergy with GCs against CD9- than CD9+ lymphoblasts to reverse drug resistance in vitro and in vivo. Collectively, our results elucidate a previously unrecognized regulatory function of CD9 in GC sensitivity, and inform new strategies for management of children with resistant BCP-ALL.

The role of afforestation with diverse woody species in enhancing and restructuring the soil microenvironment in polymetallic coal gangue dumps.

To elucidate the effects of long-term (20 years) afforestation with different woody plant species on the soil microenvironment in coal gangue polymetallic contaminated areas. This study analyzed the soil physicochemical properties, soil enzyme activities, soil ionophore, bacterial community structure, soil metabolite, and their interaction relationships at different vertical depths. Urease, sucrase, and acid phosphatase activities in the shallow soil layers increased by 4.70-7.45, 3.83-7.64, and 3.27-4.85 times, respectively, after the restoration by the four arboreal plant species compared to the plant-free control soil. Additionally, it reduced the content of available elements in the soil and alleviated the toxicity stress for Cd, Ni, Co, Cr, As, Fe, Cu, U, and Pb. After the long-term restoration of arboreal plants, the richness and Shannon indices of soil bacteria significantly increased by 4.77-23.81% and 2.93-7.93%, respectively, broadening the bacterial ecological niche. The bacterial community structure shaped by different arboreal plants exhibited high similarity, but the community similarity decreased with increasing vertical depth. Soils Zn, U, Sr, S, P, Mg, K, Fe, Cu, Ca, Ba, and pH were identified as important influencing factors for the community structure of Sphingomonas, Pseudarthrobacter, Nocardioides, and Thiobacillus. The metabolites such as sucrose, raffinose, L-valine, D-fructose 2, 6-bisphosphate, and oxoglutaric acid were found to have the greatest effect on the bacterial community in the rhizosphere soils for arboreal plants. The results of the study demonstrated that long-term planting for woody plants in gangue dumps could regulate microbial abundance and symbiotic patterns through the accumulation of rhizosphere metabolites in the soil, increase soil enzyme activity, reduce heavy metal levels, and improve the soil environment in coal gangue dumps.

Association between eicosapentaenoic acid consumption and the risk of depressive symptoms in US adults: Analyses from NHANES 2005-2018.

BACKGROUND: This study examines the relationship between eicosapentaenoic acid (EPA) intake from food and depression. EPA, an Omega-3 fatty acid commonly found in fish and seafood, has garnered attention for its potential role in depression prevention and treatment. METHODS: We selected 30,976 participants from the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2018. Depressive symptoms were diagnosed using the Patient Health Questionnaire (PHQ-9). EPA intake was assessed through dietary evaluation. Logistic regression and restricted cubic spline regression (RCS) were employed to assess the correlation between EPA and depressive symptom. RESULTS: The prevalence of depressive symptoms was 7.3 %. Participants with depressive symptoms exhibited lower EPA intake from food compared to non-depressed individuals. This negative association with depressive symptoms persisted even after accounting for various potential influencing factors (e.g., age, gender, body mass index, total energy intake, comorbidities). Notably, EPA demonstrated a nonlinear association with depressive symptoms, particularly in females. CONCLUSIONS: This study emphasizes a significant negative correlation between EPA consumption and depressive symptoms, particularly in females. This suggests that maintaining a rich EPA diet may play a role in depression prevention and treatment.

One-Step Prepared Multifunctional Polyacrylonitrile/MIL-100(Fe) Membrane with High-Density Porous Fibers for Efficient Dye/Oil Wastewater Remediation.

With environmental pollution becoming more serious, developing efficient treatment technologies for all kinds of organic wastewater has become the focus of current research. In this work, the coaxial electrospinning technology was used to one-step fabricate a porous and underwater superoleophobic polyacrylonitrile nanofibrous membrane with an Fe-based metal-organic framework (MIL-100(Fe)). Benefiting from the synergistic effect of two jets, the nanofibers are smaller and denser, which prompt the exposure of more nanomaterial additives (MIL-100(Fe)). The BET surface area increased to 202.888 m2/g, and the membranes demonstrated outstanding underwater superoleophobicity. Moreover, compared with traditional blended matrix membranes by the single-axis method, separation of the modifier and membrane matrix material by coaxial methods also maintained excellent mechanical properties, which enhanced Young's modulus 3.4 times (∼1.34 MPa). As a result, facing soluble dyes, the porous C-PAN/MIL-100(Fe) membrane can demonstrate outstanding and fast adsorptive property (the Qm of MB and CR reached 44.71 and 88.74 mg g-1, respectively). For oily emulsion, the hydrophilic and oleophobic nanofibrous reticular surface provided excellent separation performance (flux: 1124.0-1549.3 L m-2 h-1, R > 98%). Moreover, the porous and underwater superoleophobic C-PAN/MIL-100(Fe)-0.5 membrane can synchronously purify the dye/oil mixture emulsions by one-step filtration. Based on the above performance, we believe that the modified nanofibrous membrane prepared by one-step coaxial electrospinning technology can promote more studies of the development of membrane preparation technology in the field of oily wastewater treatment.

The Effect of Contrast-enhanced Ultrasound via Vessels and Surgical Drains Guidance Percutaneous Catheter Drainage in the Treatment of Pyogenic Liver Abscess.

BACKGROUND: Pyogenic liver abscess (PLA) is a purulent disease caused by microbial contamination of liver parenchyma and includes amoebic liver abscess, fungal liver abscess, and the most common bacterial liver abscess. OBJECTIVE: Explore the efficacy of contrast-enhanced ultrasound (CEUS) via vessels and surgical drain guidance percutaneous catheter drainage (PCD) in the treatment of pyogenic liver abscesses (PLA). MATERIALS AND METHODS: A total of 86 PLA patients who underwent PCD treatment in our hospital from May 2018 to February 2023 were retrospectively selected. Of them, 41 patients were treated under intravenous CEUS guidance (Control group), and 45 patients were treated under CEUS via vessels and surgical drain guidance (study group). Perioperative characteristics, treatment effectiveness, and incidence of complications were analyzed and compared between groups. RESULTS AND DISCUSSION: The duration of surgery, drainage, white blood cell recovery, body temperature recovery, and hospitalization in the study group were longer than those in the control group (P<0.05). The total effective rate of the study group (95.56%) was higher than that of the control group (80.49%) (P<0.05). The incidence of complications in the study group (4.44%) was lower than that in the control group (19.51%) (P<0.05). CONCLUSION: Compared with intravenous CEUS alone, treatment under CEUS via vessels and surgical drains-guided PCD was associated with shorter surgical time, faster recovery, better treatment effect, lower risk of complications, and ensured treatment safety in PLA patients.

The Implication of Diabetes-Specialized Nurses in Aiming for the Better Treatment and Management of Patients with Diabetes Mellitus: A Brief Narrative Review.

Diabetes mellitus (DM) is regarded as one of the most critical public health challenges of the 21st century. It has evolved into a burgeoning epidemic since the last century, and today ranks among the major causes of mortality worldwide. Diabetes specialist nurses (DSNs) are central to good patient care and outcomes including confident self-care management. Evidence shows that DSNs are cost-effective, improve clinical outcomes, and reduce length of stay in hospital. In this brief narrative review, we aim to describe the roles of DSNs and their contribution in the treatment and management of patients with DM. This narrative review describes the importance of DSNs in healthcare practice, in the inpatient and outpatient departments, in the pediatrics department, in managing diabetic foot ulcers, in the treatment and management of gestational diabetes, in prescribing medications for DM and in diabetes self-management education on glycosylated hemoglobin, and cardiovascular risk factors. To conclude, DSNs have a crucial role in the treatment and management of patients with DM and its complications. DSNs have a great impact on diabetes therapy, and hence implementation of DSNs and nurse-led diabetic clinics might be beneficial for the health care system. Finally, having DSNs might significantly contribute to good healthcare practice and support. Even though DSNs are not available in several regions around the globe, and even though this post is still new to several health care institutions, the presence of DSNs recognized and certified by the various healthcare systems would be very useful.

Endothelial ELABELA improves post-ischemic angiogenesis by upregulating VEGFR2 expression.

BACKGROUND: Post-ischemic angiogenesis is critical for perfusion recovery and tissue repair. ELABELA (ELA) plays an essential role in embryonic heart development and vasculogenesis. However, the mechanism of ELA on post-ischemic angiogenesis is poorly characterized. METHODS: We first assessed ELA expression after hind limb ischemia (HLI) in mice. We then established a HLI model in tamoxifen-inducible endothelial-ELA-specific knockout mice (ELAECKO) and assessed the rate of perfusion recovery, capillary density, and VEGFR2 pathway. Knockdown of ELA with lentivirus or siRNA and exogenous addition of ELA peptides were employed to analyze the effects of ELA on angiogenic capacity and VEGFR2 pathway in endothelial cells in vitro. The serum levels of ELA in healthy people and patients with type 2 diabetes mellitus (T2DM) and diabetic foot ulcer (DFU) were detected by a commercial ELISA kit. RESULTS: In murine HLI models, ELA was significantly up-regulated in the ischemic hindlimb. Endothelial-specific deletion of ELA impaired perfusion recovery and angiogenesis. In physiologic conditions, no significant difference in VEGFR2 expression was found between ELAECKO mice and ELAWT mice. After ischemia, the expression of VEGFR2, p-VEGFR2, and p-AKT was significantly lower in ELAECKO mice than in ELAWT mice. In cellular experiments, the knockdown of ELA inhibited endothelial cell proliferation and tube formation, and the addition of ELA peptides promoted proliferation and tube formation. Mechanistically, ELA upregulated the expression of VEGFR2, p-VEGFR2, and p-AKT in endothelial cells under hypoxic conditions. In clinical investigations, DFU patients had significantly lower serum levels of ELA compared to T2DM patients. CONCLUSION: Our results indicated that endothelial ELA is a positive regulator of post-ischemic angiogenesis via upregulating VEGFR2 expression. Targeting ELA may be a potential therapeutic option for peripheral arterial diseases.

A pan-cancer analysis of the prognosis and immune infiltration of eEF1A2 and its potential function in thyroid carcinoma.

Purpose: Eukaryotic translation elongation factor 1α2 (eEF1A2) promotes tumour progression in various cancers. We performed a pan-cancer analysis of eEF1A2 and explored its role in thyroid carcinoma (THCA). Methods: Databases from The Cancer Genome Atlas (TCGA), the University of Alabama at Birmingham Cancer data analysis Portal (UALCAN), and the Human Protein Atlas (HPA) were used to investigate the differential expression of eEF1A2 in pan-cancer. The pathological stage, prognostic characteristics, tumour microenvironment (TME), tumour mutational burden (TMB), and microsatellite instability (MSI) were analysed in diverse tumours with different expression levels of eEF1A2. The expression levels in papillary thyroid carcinoma (PTC) and its specific role in cell proliferation, migration, invasion, and cell glycolysis in PTC cells were verified by quantitative real time polymerase chain reaction (qRT-PCR), immunohistochemistry, cell counting kit-8, colony formation, wound healing, Transwell assay, and lactate acid and glucose assays.Results:eEF1A2 was differentially expressed in various malignant tumour tissues compared to control tissues and was associated with poor pathological stage and prognosis in most types of tumours. Moreover, eEF1A2 expression closely correlated with the infiltration of immunosuppressive cells, TMB, and MSI in some tumour types. Expression of eEF1A2 in PTC is higher than the para-carcinoma, and eEF1A2 downregulation suppressed TPC-1 and BCPAP cell proliferation, migration, invasion, and glycolysis. Conclusion: Our study suggests that the expression of eEF1A2 is related to the prognosis and immune infiltration of some tumours and may be a predictor of prognosis and immunotherapy. eEF1A2 could promote malignant behaviour of PTC cells.

Revealing the diversity of endogenous peptides and parent proteins in human colostrum and mature milk through peptidomics analysis.

Endogenous peptides and their parent proteins are important nutritional components with diverse biological functions. The objective of this study was to analyze and compare endogenous peptides and parent proteins found in human colostrum (HC) and human mature milk (HM) using a 4D label-free technique. In total, 5162 and 940 endogenous peptides derived from 258 parent proteins were identified in human milk by database (DB) search and de novo, respectively. Among these peptides, 2446 differentially expressed endogenous peptides with various bioactivities were identified. The Gene Ontology analysis unveiled the cellular components, biological processes, and molecular functions associated with these parent proteins. Metabolic pathway analysis suggested that neutrophil extracellular trap formation had the greatest significance with 24 parent proteins. These findings will offer a fresh perspective on the development of infant formula powder, highlighting the potential for incorporating these changes to enhance its nutritional composition and benefits.

Effect of the defoliant tribufos on the reproductive ability of Japanese quail (Coturnix japonica).

As a cotton defoliator, tribufos (S,S,S-tributyl phosphorotrithioate) is widespread in the environment. It can cause neurotoxicity in chickens, reproductive toxicity in rats, and can also cause headaches and nausea in humans. However, little is known about its impact on the reproduction of birds. Here, by analyzing the differences in reproductive indexs and histopathological characteristics, we investigated the chronic effects of 32 mg a.i./kg, 160 mg a.i./kg and 800 mg a.i./kg tribufos treatment on the reproductive ability of Japanese quail (Coturnix japonica). The results indicated that 32 mg a.i./kg and 160 mg a.i./kg tribufos treatment significantly reduced the food intake of quails, significantly increased the broken egg rate, and had adverse effects on gonads and liver tissue. The 160 mg a.i./kg tribufos treatment also significantly reduced the average egg production. Moreover, 800 mg a.i./kg treatment had significant negative effects on feed intake (FI), body weight (BW), eggshell thickness, egg production (EP), fertilization rate, hatchability and progeny 14-d survival rate, and it also significantly increased the broken egg rate. In addition, tribufos exposure caused lesions in quail gonads and liver tissue. Overall, our results revealed that tribufos had adverse effects on the reproductive ability of Japanese quail, especially at high concentrations.

The Potential Transcriptomic and Metabolomic Mechanisms of ATO and ATRA in Treatment of FLT3-ITD Acute Myeloid Leukemia.

BACKGROUND: Acute myeloid leukemia (AML) with Fms-like tyrosine kinase 3 gene internal tandem duplication (FLT3-ITD) mutations has a poor prognosis. The combination of arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) has a synergistic killing effect on leukemia cells with FLT3-ITD mutation. However, the mechanism, especially the changes of gene expression and metabolic activity remain unclear. Here we explore the transcriptome and metabolomics changes of FLT3-ITD AML cells treated with ATO/ATRA. METHODS: RNA-seq was used to identify differential expressed genes (DEGs), and ultra-high performance liquid chromatography-quadrupole electrostatic field orbital trap mass spectrometry (UHPLC-QE-MS) nontargeted metabolomics method was used to screen out the differential metabolites in FLT3-ITD mutant cell lines treated with ATRA and ATO. KEGG pathway database was utilized for pathway exploration and Seahorse XF24 was used to detect extracellular acidification rate (ECAR). Metabolic polymerase chain reaction (PCR) array and real-time quantitative PCR (RT-qPCR) were used to detect mRNA levels of key metabolic genes of glycolysis and fatty acid after drug treatment. RESULTS: A total of 3873 DEGs were identified and enriched in 281 Gene Ontology (GO) terms, among which 210 were related to biological processes, 43 were related to cellular components, and 28 were related to molecular functions. Besides, 1794 and 927 differential metabolites were screened in positive and negative ion mode separately, and 59 different metabolic pathways were involved, including alanine-aspartate-glutamate metabolic pathway, arginine, and proline metabolic pathway, glycerophospholipid metabolic pathways, etc. According to KEGG Pathway analysis of transcriptome combined with metabolome, glycolysis/gluconeogenesis pathway and fatty acid metabolism pathway were significantly founded enriched. ATRA + ATO may inhibit the glycolysis of FLT3-ITD AML cells by inhibiting FLT3 and its downstream AKT/HK2-VDAC1 signaling pathway. CONCLUSIONS: The gene transcription profile and metabolites of FLT3-ITD mutant cells changes significantly after treatment, which might be related to the anti-FLT3-ITD AML effect. The screened DEGs, differential metabolites pathway are helpful in studying the mechanism of anti-leukemia effects and drug targets.