COVID-19 Vaccination in Pregnancy: Pilot Study of Plasma MicroRNAs Associated with Inflammatory Cytokines after COVID-19 mRNA Vaccination.

BACKGROUND: The impact of mRNA COVID-19 vaccines on the immunological profiles of pregnant women remains a crucial area of study. This research aims to explore the specific immunological changes triggered by these vaccines in this demographic. METHODS: In a focused investigation, we examined the effects of mRNA COVID-19 vaccination on microRNA expression in pregnant women. Key microRNAs, including miR-451a, miR-23a-3p, and miR-21-5p, were analyzed for expression changes post-vaccination. Additionally, we assessed variations in S1RBD IgG levels and specific cytokines to gauge the broader immunological response. RESULTS: Post-vaccination, significant expression shifts in the targeted microRNAs were observed. Alongside these changes, we noted alterations in S1RBD IgG and various cytokines, indicating an adapted inflammatory response. Notably, these immunological markers displayed no direct correlation with S1RBD IgG concentrations, suggesting a complex interaction between the vaccine and the immune system in pregnant women. CONCLUSIONS: Our pilot study provides valuable insights into the nuanced effects of the mRNA COVID-19 vaccine on immune dynamics in pregnant women, particularly emphasizing the role of microRNAs. The findings illuminate the intricate interplay between vaccines, microRNAs, and immune responses, enhancing our understanding of these relationships in the context of pregnancy. This research contributes significantly to the growing body of knowledge regarding mRNA COVID-19 vaccines and their specific impact on maternal immunology, offering a foundation for further studies in this vital area.

Bronchobiliary fistula after traumatic liver rupture: a case report.

INTRODUCTION: Bronchobiliary fistulas are rare and difficult to treat. Peacock first reported this entity in 1850 while treating a patient with hepatic encopresis. CASE PRESENTATION: A 67-year-old Chinese male patient presented to the outpatient clinic with a complaint of coughing up phlegm with chest tightness for 4 days with symptoms of intermittent bilirubin sputum with a sputum volume of about 500 ml per day but no symptoms of abdominal pain or jaundice and no yellow urine or steatorrhea. The examination revealed cyanosis of the lips and mouth, barrel chest, low breath sounds on the right side, and a large number of wet rales heard in both lungs. The imaging investigations were suggestive of bronchobiliary fistula. Therefore, the patient was operated on and discharged with no perioperative complications. CONCLUSION: Bronchobiliary fistula should be considered diagnostically in patients with known liver disease who also experience trauma or medical treatment and cough up bile-colored sputum, regardless of the presence of concurrent infections, and in conjunction with radiological expertise to identify it. Here, we report a case of bronchobiliary fistula and a brief review of the literature on it.

The N6-methyladenosine Epitranscriptomic Landscape of Lung Adenocarcinoma.

Comprehensive m6A epitranscriptome profiling of primary tumors remains largely uncharted. Here, we profiled the m6A epitranscriptome of 10 non-neoplastic lung (NL) tissues and 51 lung adenocarcinoma (LUAD) tumors, integrating the corresponding transcriptome, proteome and extensive clinical annotations. We identified distinct clusters and genes that were exclusively linked to disease progression through m6A modifications. In comparison with NL tissues, we identified 430 transcripts to be hypo-methylated and 222 to be hyper-methylated in tumors. Among these genes, EML4 emerged as a novel metastatic driver, displaying significant hyper-methylation in tumors. m6A modification promoted the translation of EML4, leading to its widespread overexpression in primary tumors. Functionally, EML4 modulated cytoskeleton dynamics through interacting with ARPC1A, enhancing lamellipodia formation, cellular motility, local invasion, and metastasis. Clinically, high EML4 protein abundance correlated with features of metastasis. METTL3 small molecule inhibitor markedly diminished both EML4 m6A and protein abundance, and efficiently suppressed lung metastases in vivo.

Formyl Peptide Receptor 1 Inhibits Reparative Angiogenesis and Aggravates Neuroretinal Dysfunction in Ischemic Retinopathy.

PURPOSE: Ischemic retinopathy is the major cause of vision-threatening conditions. Inflammation plays an important role in the pathogenesis of ischemic retinopathy. Formyl peptide receptor 1 (FPR1) has been reported to be implicated in the regulation of inflammatory disorders. However, the role of FPR1 in the progression of ischemic retinal injury has not been fully explained. METHODS: The activation of FPR1 was measured by real-time PCR and western blotting in the retina of OIR. The effect of FPR1 on the expression of inflammatory cytokines and relevant pro-angiogenic factors was assessed between wild-type and FPR1-deficiency OIR mice. The impact of FPR1 on retinal angiogenesis was evaluated through quantifying retinal vaso-obliteration and neovascularization between FPR1+/+ and FPR1-/- OIR mice. At last, the neuronal effect of FPR1 on the ischemic retina was investigated by ERG between wild-type and FPR1-deficient OIR mice. RESULTS: The expression of FPR1 significantly increased in the retina of OIR. Furthermore, FPR1 deficiency downregulated pro-inflammatory and pro-angiogenic factors. Ablation of FPR1 suppressed the retinal pathological neovascularization and promoted reparative revascularization, ultimately improving retinal neural function after ischemic injury. CONCLUSION: In ischemic retinopathy, FPR1 aggravates inflammation and inhibits reparative angiogenesis to exacerbate neuronal dysfunction.

A Bacillus velezensis strain isolated from oats with disease-preventing and growth-promoting properties.

Endophytes have been shown to promote plant growth and health. In the present study, a Bacillus velezensis CH1 (CH1) strain was isolated and identified from high-quality oats, which was capable of producing indole-3-acetic acid (IAA) and strong biofilms, and capabilities in the nitrogen-fixing and iron carriers. CH1 has a 3920 kb chromosome with 47.3% GC content and 3776 code genes. Compared genome analysis showed that the largest proportion of the COG database was metabolism-related (44.79%), and 1135 out of 1508 genes were associated with the function "biosynthesis, transport, and catabolism of secondary metabolites." Furthermore, thirteen gene clusters had been identified in CH1, which were responsible for the synthesis of fifteen secondary metabolites that exhibit antifungal and antibacterial properties. Additionally, the strain harbors genes involved in plant growth promotion, such as seven putative genes for IAA production, spermidine and polyamine synthase genes, along with multiple membrane-associated genes. The enrichment of these functions was strong evidence of the antimicrobial properties of strain CH1, which has the potential to be a biofertilizer for promoting oat growth and disease resistance.

High-Entropy Transition Metal Phosphorus Trichalcogenides for Rapid Sodium Ion Diffusion.

High-entropy strategies are regarded as a powerful means to enhance performance in energy storage fields. The improved properties are invariably ascribed to entropy stabilization or synergistic cocktail effect. Therefore, the manifested properties in such multicomponent materials are usually unpredictable. Elucidating the precise correlations between atomic structures and properties remains a challenge in high-entropy materials (HEMs). Herein, atomic-resolution scanning transmission electron microscopy annular dark field (STEM-ADF) imaging and four dimensions (4D)-STEM are combined to directly visualize atomic-scale structural and electric information in high-entropy FeMnNiVZnPS3. Aperiodic stacking is found in FeMnNiVZnPS3 accompanied by high-density strain soliton boundaries (SSBs). Theoretical calculation suggests that the formation of such structures is attributed to the imbalanced stress of distinct metal-sulfur bonds in FeMnNiVZnPS3. Interestingly, the electric field concentrates along the two sides of SSBs and gradually diminishes toward the two-dimensional (2D) plane to generate a unique electric field gradient, strongly promoting the ion-diffusion rate. Accordingly, high-entropy FeMnNiVZnPS3 demonstrates superior ion-diffusion coefficients of 10-9.7-10-8.3 cm2 s-1 and high-rate performance (311.5 mAh g-1 at 30 A g-1). This work provides an alternative way for the atomic-scale understanding and design of sophisticated HEMs, paving the way for property engineering in multi-component materials.

CoCo-ST: Comparing and Contrasting Spatial Transcriptomics data sets using graph contrastive learning.

Traditional feature dimension reduction methods have been widely used to uncover biological patterns or structures within individual spatial transcriptomics data. However, these methods are designed to yield feature representations that emphasize patterns or structures with dominant high variance, such as the normal tissue spatial pattern in a precancer setting. Consequently, they may inadvertently overlook patterns of interest that are potentially masked by these high-variance structures. Herein we present our graph contrastive feature representation method called CoCo-ST (Comparing and Contrasting Spatial Transcriptomics) to overcome this limitation. By incorporating a background data set representing normal tissue, this approach enhances the identification of interesting patterns in a target data set representing precancerous tissue. Simultaneously, it mitigates the influence of dominant common patterns shared by the background and target data sets. This enables discerning biologically relevant features crucial for capturing tissue-specific patterns, a capability we showcased through the analysis of serial mouse precancerous lung tissue samples.

Fluorescence-based reagent and spectrum-based optical reader for lactoferrin detection in tears: differentiating Sjögren's syndrome from non-Sjögren's dry eye syndrome.

Identification of an early biomarker and effective testing device to differentiate dry eye disease secondary to autoimmune disease (Sjögren's syndrome dry eye disease) from non-Sjögren's dry eye disease are prerequisites for appropriate treatment. We aimed to demonstrate the capacity of a new photo-detection device to evaluate tear lactoferrin levels as a tool for differentiating systemic conditions associated with dry eye disease. Patients with non-Sjögren's and Sjögren's syndrome dry eye disease (n = 54 and n = 52, respectively) and controls (n = 11) were enrolled. All participants completed the Ocular Surface Disease Index questionnaire. Tear collection was performed with Schirmer test, and tear break-up time was examined using a slit lamp. Tear lactoferrin was evaluated using our newly developed photo-detection device. The average lactoferrin concentration was significantly lower in samples from patients with non-Sjögren's dry eye disease (0.337 ± 0.227 mg/mL, n = 54) and Sjögren's syndrome dry eye disease (0.087 ± 0.010 mg/mL, n = 52) than in control samples (1.272 ± 0.54 mg/mL, n = 11) (p < 0.0001). Further, lactoferrin levels were lower in patients with Sjögren's syndrome dry eye disease than in those with non-Sjögren's dry eye disease (p < 0.001). Our cost-effective, antibody-free, highly sensitive photo-detection device for evaluating tear lactoferrin levels can assist ophthalmologists in differentiating different types of dry eye diseases.

Integrated 68Ga-FAPI-04 PET/MR in Pancreatic Cancer: Prediction of Tumor Response and Tumor Resectability After Neoadjuvant Therapy.

PURPOSE: This study aimed to investigate the value of 68Ga-fibroblast activation protein inhibitor (FAPI) PET/MR semiquantitative parameters in the prediction of tumor response and resectability after neoadjuvant therapy in patients with pancreatic cancer. PATIENTS AND METHODS: This study was performed retrospectively in patients with borderline resectable or locally advanced pancreatic cancer who underwent 68Ga-FAPI PET/MRI from June 2020 to June 2022. The SUVmax, SUVmean, SUVpeak, uptake tumor volume (UTV), and total lesion FAP expression (TLF) of the primary tumor were recorded. The target-to-background ratios (TBRs) of the primary tumor to normal tissue muscle (TBRmuscle) and blood (TBRblood) were also calculated. In addition, the minimum apparent diffusion coefficient value of the tumor was measured. After 3-4 cycles of gemcitabine + nab-paclitaxel chemotherapy, patients were divided into responders and nonresponders groups according to RECIST criteria (v.1.1). They were also divided into resectable and unresectable groups according to the surgical outcome. The variables were compared separately between groups. RESULTS: A total of 18 patients who met the criteria were included in this study. The UTV and TLF were significantly higher in nonresponders than in responders (P < 0.05). The SUVmax, SUVmean, and TBRmuscle were significantly higher in unresectable patients than in resectable ones (P < 0.05). Receiver operating characteristic curve analysis identified UTV (area under the curve [AUC] = 0.840, P = 0.015) and TLF (AUC = 0.877, P = 0.007) as significant predictors for the response to gemcitabine + nab-paclitaxel chemotherapy, with cutoff values of 25.05 and 167.38, respectively. In addition, SUVmax (AUC = 0.838, P = 0.016), SUVmean (AUC = 0.812, P = 0.026), and TBRmuscle (AUC = 0.787, P = 0.041) were significant predictors of the resectability post-NCT, with cutoff values of 14.0, 6.0, and 13.9, respectively. According to logistic regression analysis, TLF was found to be significantly associated with tumor response (P = 0.032) and was an independent predictor of tumor response (P = 0.032). In addition, apparent diffusion coefficient value was an independent predictor of tumor resectability (P = 0.043). CONCLUSIONS: This pilot study demonstrates the value of 68Ga-FAPI PET/MR for the prediction of tumor response and resectability after neoadjuvant therapy. It may aid in individualized patient management by guiding the treatment regimens.

Identifying high-risk multiple myeloma patients: A novel approach using a clonal gene signature.

Multiple myeloma (MM) is a heterogeneous disease with a small subset of high-risk patients having poor prognoses. Identifying these patients is crucial for treatment management and strategic decisions. In this study, we developed a novel computational framework to define prognostic gene signatures by selecting genes with expression driven by clonal copy number alterations. We applied this framework to MM and developed a clonal gene signature (CGS) consisting of 22 genes and evaluated in five independent datasets. The CGS provided significant prognostic values after adjusting for well-established factors including cytogenetic abnormalities, International Staging System (ISS), and Revised ISS (R-ISS). Importantly, CGS demonstrated higher performance in identifying high-risk patients compared to the GEP70 and SKY92 signatures recommended for prognostic stratification of MM. CGS can further stratify patients into subgroups with significantly differential prognoses when applied to the high- and low-risk groups identified by GEP70 and SKY92. Additionally, CGS scores are significantly associated with patient response to dexamethasone, a commonly used treatment for MM. In summary, we proposed a computational framework that requires only gene expression data to identify CGSs for prognosis prediction. CGS provides a useful biomarker for improving prognostic stratification in MM, especially for identifying the highest-risk patients.

Doubly robust estimation and sensitivity analysis for marginal structural quantile models.

The marginal structure quantile model (MSQM) provides a unique lens to understand the causal effect of a time-varying treatment on the full distribution of potential outcomes. Under the semiparametric framework, we derive the efficiency influence function for the MSQM, from which a new doubly robust estimator is proposed for point estimation and inference. We show that the doubly robust estimator is consistent if either of the models associated with treatment assignment or the potential outcome distributions is correctly specified, and is semiparametric efficient if both models are correct. To implement the doubly robust MSQM estimator, we propose to solve a smoothed estimating equation to facilitate efficient computation of the point and variance estimates. In addition, we develop a confounding function approach to investigate the sensitivity of several MSQM estimators when the sequential ignorability assumption is violated. Extensive simulations are conducted to examine the finite-sample performance characteristics of the proposed methods. We apply the proposed methods to the Yale New Haven Health System Electronic Health Record data to study the effect of antihypertensive medications to patients with severe hypertension and assess the robustness of the findings to unmeasured baseline and time-varying confounding.

High Fatty Acid-Binding Protein 4 Expression Associated with Favorable Clinical Characteristics and Prognosis in Papillary Thyroid Carcinoma.

Fatty acid-binding protein 4 (FABP4), a fatty acid transporter that coordinates lipid metabolism, is reported to exert a tumorigenic role in certain cancers. We investigated the effects of FABP4 in the carcinogenesis of thyroid cancer. Bioinformatics data about FABP4 in thyroid cancer were collected from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Sixteen paired papillary thyroid cancer (PTC) tissues from Taipei Medical University (TMU) were gathered, and commercial thyroid cancer complementary (c)DNA and tissue arrays were purchased to measure FABP4 messenger (m)RNA and protein levels. By analyzing data from the GEO and TCGA, we showed that FABP4 mRNA was reduced in PTC and follicular thyroid carcinoma (FTC). In addition, a lower FABP4 mRNA level in PTC was associated with poor clinical parameters and outcomes in the TCGA database. Moreover, FABP4 transcripts and proteins were downregulated in PTC and FTC, and its mRNA expression was associated with PTC staging in clinical specimens. In the TCGA database and TMU cohort, FABP4 mRNA levels were associated with thyroglobulin (r = 0.511 and r = 0.656, respectively), thyroid peroxidase (r = 0.612 and r = 0.909, respectively), and sodium iodide symporter (r = 0.485 and r = 0.637, respectively) transcripts. In conclusion, FABP4 mRNA and protein levels were reduced in PTC and FTC, and may be used as a potential indicator for thyroid cancer evolution in clinical settings. Further, well-designed research to dissect the molecular mechanism of FABP4 in modulating thyroid carcinogenesis is needed.

Isochlorogenic acid A ameliorated lead-induced anxiety-like behaviors in mice by inhibiting ferroptosis-mediated neuroinflammation via the BDNF/Nrf2/GPX4 pathways.

Lead (Pb) is a common environmental neurotoxicant that causes behavioral impairments in both rodents and humans. Isochlorogenic acid A (ICAA), a phenolic acid found in a variety of natural sources such as tea, fruits, vegetables, coffee, plant-based food products, and various medicinal plants, exerts multiple effects, including protective effects on the lungs, livers, and intestines. The objective of this study was to investigate the potential neuroprotective effects of ICAA against Pb-induced neurotoxicity in ICR mice. The results indicate that ICAA attenuates Pb-induced anxiety-like behaviors. ICAA reduced neuroinflammation, ferroptosis, and oxidative stress caused by Pb. ICAA successfully mitigated the Pb-induced deficits in the cholinergic system in the brain through the reduction of ACH levels and the enhancement of AChE and BChE activities. ICAA significantly reduced the levels of ferrous iron and MDA in the brain and prevented decreases in GSH, SOD, and GPx activity. Immunofluorescence analysis demonstrated that ICAA attenuated ferroptosis and upregulated GPx4 expression in the context of Pb-induced nerve damage. Additionally, ICAA downregulated TNF-α and IL-6 expression while concurrently enhancing the activations of Nrf2, HO-1, NQO1, BDNF, and CREB in the brains of mice. The inhibition of BDNF, Nrf2 and GPx4 reversed the protective effects of ICAA on Pb-induced ferroptosis in nerve cells. In general, ICAA ameliorates Pb-induced neuroinflammation, ferroptosis, oxidative stress, and anxiety-like behaviors through the activation of the BDNF/Nrf2/GPx4 pathways.

The evolution of lung adenocarcinoma precursors is associated with chromosomal instability and transition from innate to adaptive immune response/evasion.

Studying lung adenocarcinoma (LUAD) early carcinogenesis is challenging, primarily due to the lack of LUAD precursors specimens. We amassed multi-omics data from 213 LUAD and LUAD precursors to identify molecular features underlying LUAD precancer evolution. We observed progressively increasing mutations, chromosomal aberrations, whole genome doubling and genomic instability from precancer to invasive LUAD, indicating aggravating chromosomal instability (CIN). Telomere shortening, a crucial genomic alteration linked to CIN, emerged at precancer stage. Moreover, later-stage lesions demonstrated increasing cancer stemness and decreasing alveolar identity, suggesting epithelial de-differentiation during early LUAD carcinogenesis. The innate immune cells progressively diminished from precancer to invasive LUAD, concomitant with a gradual recruitment of adaptive immune cells (except CD8+ and gamma-delta T cells that decreased in later stages) and upregulation of numerous immune checkpoints, suggesting LUAD precancer evolution is associated with a shift from innate to adaptive immune response and immune evasion mediated by various mechanisms.

Superhalide-Anion-Motivator Reforming-Enabled Bipolar Manipulation toward Longevous Energy-Type Zn||Chalcogen Batteries.

Neutrophilic superhalide-anion-triggered chalcogen conversion-based Zn batteries, despite latent high-energy merit, usually suffer from a short lifespan caused by dendrite growth and shuttle effect. Here, a superhalide-anion-motivator reforming strategy is initiated to simultaneously manipulate the anode interface and Se conversion intermediates, realizing a bipolar regulation toward longevous energy-type Zn batteries. With ZnF2 chaotropic additives, the original large-radii superhalide zincate anion species in ionic liquid (IL) electrolytes are split into small F-containing species, boosting the formation of robust solid electrolyte interphases (SEI) for Zn dendrite inhibition. Simultaneously, ion radius reduced multiple F-containing Se conversion intermediates form, enhancing the interion interaction of charged products to suppress the shuttle effect. Consequently, Zn||Se batteries deliver a ca. 20-fold prolonged lifespan (2000 cycles) at 1 A g-1 and high energy/power density of 416.7 Wh kgSe-1/1.89 kW kgSe-1, outperforming those in F-free counterparts. Pouch cells with distinct plateaus and durable cyclability further substantiate the practicality of this design.

Joint multi-omics discriminant analysis with consistent representation learning using PANDA.

Integrative multi-omics analysis provides deeper insight and enables better and more realistic modeling of the underlying biology and causes of diseases than does single omics analysis. Although several integrative multi-omics analysis methods have been proposed and demonstrated promising results in integrating distinct omics datasets, inconsistent distribution of the different omics data, which is caused by technology variations, poses a challenge for paired integrative multi-omics methods. In addition, the existing discriminant analysis-based integrative methods do not effectively exploit correlation and consistent discriminant structures, necessitating a compromise between correlation and discrimination in using these methods. Herein we present PAN-omics Discriminant Analysis (PANDA), a joint discriminant analysis method that seeks omics-specific discriminant common spaces by jointly learning consistent discriminant latent representations for each omics. PANDA jointly maximizes between-class and minimizes within-class omics variations in a common space and simultaneously models the relationships among omics at the consistency representation and cross-omics correlation levels, overcoming the need for compromise between discrimination and correlation as with the existing integrative multi-omics methods. Because of the consistency representation learning incorporated into the objective function of PANDA, this method seeks a common discriminant space to minimize the differences in distributions among omics, can lead to a more robust latent representations than other methods, and is against the inconsistency of the different omics. We compared PANDA to 10 other state-of-the-art multi-omics data integration methods using both simulated and real-world multi-omics datasets and found that PANDA consistently outperformed them while providing meaningful discriminant latent representations. PANDA is implemented using both R and MATLAB, with codes available at https://github.com/WuLabMDA/PANDA.

Stabilizing Zn/electrolyte Interphasial Chemistry by a Sustained-Release Drug Inspired Indium-Chelated Resin Protective Layer for High-Areal-Capacity Zn//V2O5 Batteries.

For zinc-metal batteries, the instable chemistry at Zn/electrolyte interphasial region results in severe hydrogen evolution reaction (HER) and dendrite growth, significantly impairing Zn anode reversibility. Moreover, an often-overlooked aspect is this instability can be further exacerbated by the interaction with dissolved cathode species in full batteries. Here, inspired by sustained-release drug technology, an indium-chelated resin protective layer (Chelex-In), incorporating a sustained-release mechanism for indium, is developed on Zn surface, stabilizing the anode/electrolyte interphase to ensure reversible Zn plating/stripping performance throughout the entire lifespan of Zn//V2O5 batteries. The sustained-release indium onto Zn electrode promotes a persistent anticatalytic effect against HER and fosters uniform heterogeneous Zn nucleation. Meanwhile, on the electrolyte side, the residual resin matrix with immobilized iminodiacetates anions can also repel detrimental anions (SO4 2- and polyoxovanadate ions dissolved from V2O5 cathode) outside the electric double layer. This dual synergetic regulation on both electrode and electrolyte sides culminates a more stable interphasial environment, effectively enhancing Zn anode reversibility in practical high-areal-capacity full battery systems. Consequently, the bio-inspired Chelex-In protective layer enables an ultralong lifespan of Zn anode over 2800 h, which is also successfully demonstrated in ultrahigh areal capacity Zn//V2O5 full batteries (4.79 mAh cm-2).

Deciphering metabolic heterogeneity in retinoblastoma unravels the role of monocarboxylate transporter 1 in tumor progression.

BACKGROUND: Tumors exhibit metabolic heterogeneity, influencing cancer progression. However, understanding metabolic diversity in retinoblastoma (RB), the primary intraocular malignancy in children, remains limited. METHODS: The metabolic landscape of RB was constructed based on single-cell transcriptomic sequencing from 11 RB and 5 retina samples. Various analyses were conducted, including assessing overall metabolic activity, metabolic heterogeneity, and the correlation between hypoxia and metabolic pathways. Additionally, the expression pattern of the monocarboxylate transporter (MCT) family in different cell clusters was examined. Validation assays of MCT1 expression and function in RB cell lines were performed. The therapeutic potential of targeting MCT1 was evaluated using an orthotopic xenograft model. A cohort of 47 RB patients was analyzed to evaluate the relationship between MCT1 expression and tumor invasion. RESULTS: Distinct metabolic patterns in RB cells, notably increased glycolysis, were identified. This metabolic heterogeneity correlated closely with hypoxia. MCT1 emerged as the primary monocarboxylate transporter in RB cells. Disrupting MCT1 altered cell viability and energy metabolism. In vivo studies using the MCT1 inhibitor AZD3965 effectively suppressed RB tumor growth. Additionally, a correlation between MCT1 expression and optic nerve invasion in RB samples suggested prognostic implications. CONCLUSIONS: This study enhances our understanding of RB metabolic characteristics at the single-cell level, highlighting the significance of MCT1 in RB pathogenesis. Targeting MCT1 holds promise as a therapeutic strategy for combating RB, with potential prognostic implications.

Lead-induced liver fibrosis and inflammation in mice by the AMPK/MAPKs/NF-κB and STAT3/TGF-ß1/Smad2/3 pathways: the role of Isochlorogenic acid a.

Lead (Pb) is a nonessential heavy metal, which can cause many health problems. Isochlorogenic acid A (ICAA), a phenolic acid present in tea, fruits, vegetables, coffee, plant-based food products, and various medicinal plants, exerts multiple effects, including anti-oxidant, antiviral, anti-inflammatory and antifibrotic functions. Thus, the purpose of our study was to determine if ICAA could prevent Pb-induced hepatotoxicity in ICR mice. An evaluation was performed on oxidative stress, inflammation and fibrosis, and related signaling. The results indicate that ICAA attenuates Pb-induced abnormal liver function. ICAA reduced liver fibrosis, inflammation and oxidative stress caused by Pb. ICAA abated Pb-induced fibrosis and decreased inflammatory cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-alpha (TNF-α). ICAA abrogated reductions in activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Masson staining revealed that ICAA reduced collagen fiber deposition in Pb-induced fibrotic livers. Western blot and immunohistochemistry analyses showed ICAA increased phosphorylated AMP-activated protein kinase (p-AMPK) expression. ICAA also reduced the expression of collagen I, α-smooth muscle actin (α-SMA), phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated c-jun N-terminal kinase (p-JNK), p-p38, phosphorylated signal transducer and phosphorylated activator of transcription 3 (p-STAT3), transforming growth factor ß1 (TGF-ß1), and p-Smad2/3 in livers of mice. Overall, ICAA ameliorates Pb-induced hepatitis and fibrosis by inhibiting the AMPK/MAPKs/NF-κB and STAT3/TGF-ß1/Smad2/3 pathways.

Succession of tissue microbial community during oat developmental.

Investigating oat tissue microflora during its different developmental stages is necessary for understanding its growth and anti-disease mechanism. In this study, 16S rDNA and ITS (Internally Transcribed Spacer) high-throughput sequencing technology were used to explore the microflora diversity of oat tissue. Twenty-seven samples of leaves, stems, and roots from three developmental stages, namely the seedling stage (SS), jointing stage (JS), and maturity stage (MS), underwent sequencing analysis. The analysis showed that 6480 operational taxonomic units (OTUs) were identified in the examined samples, of which 1698 were fungal and 4782 were bacterial. Furthermore, 126 OTUs were shared by fungi, mainly Ascomycota, Basidiomycota, and Mucoromycota at the phylum level, and 39 OTUs were shared by bacteria, mainly Actinobacteriota and Proteobacteria at the phylum level. The microbial diversity of oat tissue in the three developmental stages showed differences, and the α-diversity of the bacteria and ß-diversity of the bacteria and fungi in the roots were higher than those of the stems and leaves. Among the bacteria species, Thiiopseudomonas, Rikenellaceae RC9 gut group, and Brevibacterium were predominant in the leaves, MND1 was predominant in the roots, and Lactobacillus was predominant in the stems. Moreover, Brevibacterium maintained a stable state at all growth stages. In the fungal species, Phomatospora was dominant in the leaves, Kondoa was dominant in the roots, and Pyrenophora was dominant in the stems. All species with a high abundance were related to the growth process of oats and antagonistic bacteria. Furthermore, connection modules were denser in bacterial than in fungal populations. The samples were treated with superoxide dismutase and peroxidase. There were 42 strains associated with SOD (Superoxide dismutase), 60 strains associated with POD (Peroxidase), and 38 strains in total, which much higher than fungi. The network analysis showed that bacteria might have more dense connection modules than fungi, The number of bacterial connections to enzymes were much higher than that of fungi. Furthermore, these results provide a basis for further mechanistic research.