Andrographolide sensitizes glioma to temozolomide by inhibiting DKK1 expression.

BACKGROUND: Temozolomide (TMZ) is the first-line chemotherapeutic drug for gliomas treatment. However, the clinical efficacy of TMZ in glioma patients was very limited. Therefore, it is urgently needed to discover a novel approach to increase the sensitivity of glioma cells to TMZ. METHODS: Western blot, immunohistochemical staining, and qRT-PCR assays were used to explore the mechanisms underlying TMZ promoting DKK1 expression and andrographolide (AND) inhibiting DKK1 expression. HPLC was used to detect the ability of andrographolide (AND) to penetrate the blood-brain barrier. MTT assay, bioluminescence images, magnetic resonance imaging (MRI) and H&E staining were employed to measure the proliferative activity of glioma cells and the growth of intracranial tumors. RESULTS: TMZ can promote DKK1 expression in glioma cells and brain tumors of an orthotopic model of glioma. DKK1 could promote glioma cell proliferation and tumor growth in an orthotopic model of glioma. Mechanistically, TMZ increased EGFR expression and subsequently induced the activation of its downstream MEK-ERK and PI3K-Akt pathways, thereby promoting DKK1 expression in glioma cells. Andrographolide inhibited TMZ-induced DKK1 expression through inactivating MEK-ERK and PI3K-Akt pathways. Andrographolide can cross the blood-brain barrier, the combination of TMZ and andrographolide not only improved the anti-tumor effects of TMZ but also showed a survival benefit in an orthotopic model of glioma. CONCLUSION: Andrographolide can enhance anti-tumor activity of TMZ against glioma by inhibiting DKK1 expression.

Somatic mutation phasing and haplotype extension using linked-reads in multiple myeloma.

Somatic mutation phasing informs our understanding of cancer-related events, like driver mutations. We generated linked-read whole genome sequencing data for 23 samples across disease stages from 14 multiple myeloma (MM) patients and systematically assigned somatic mutations to haplotypes using linked-reads. Here, we report the reconstructed cancer haplotypes and phase blocks from several MM samples and show how phase block length can be extended by integrating samples from the same individual. We also uncover phasing information in genes frequently mutated in MM, including DIS3, HIST1H1E, KRAS, NRAS, and TP53, phasing 79.4% of 20,705 high-confidence somatic mutations. In some cases, this enabled us to interpret clonal evolution models at higher resolution using pairs of phased somatic mutations. For example, our analysis of one patient suggested that two NRAS hotspot mutations occurred on the same haplotype but were independent events in different subclones. Given sufficient tumor purity and data quality, our framework illustrates how haplotype-aware analysis of somatic mutations in cancer can be beneficial for some cancer cases.

20S-O-Glc-DM treats left ventricular diastolic dysfunction by modulating cardiomyocyte mitochondrial quality and excess autophagy.

BACKGROUND: Left ventricular diastolic dysfunction (LVDD) is a manifestation of heart failure, with both its incidence and prevalence increasing annually. Currently, no pharmacological treatments are available for LVDD, highlighting the urgent need for new therapeutic discoveries. Ginsenosides are commonly used in cardiovascular therapy. Previous research has synthesized the ginsenoside precursor molecule, 20S-O-Glc-DM (C20DM), through biosynthesis. C20DM shows greater bioavailability, eco-friendliness, and cost-effectiveness compared to traditional ginsenosides, positioning it as a promising option for treating LVDD. PURPOSE: This study firstly documents the therapeutic activity of C20DM against LVDD and unveils its potential mechanisms of action. It provides a pharmacological basis for C20DM as a new cardiovascular therapeutic agent. METHODS: In this study, models of LVDD in mice and ISO-induced H9C2 cell damage were developed. Cell viability, ROS and Ca2+ levels, mitochondrial membrane potential, and proteins associated with mitochondrial biogenesis and autophagy were evaluated in the in vitro experiments. Animal experiments involved administering medication for 3 weeks to validate the therapeutic effects of C20DM and its impact on mitochondria and autophagy. RESULTS: Research has shown that C20DM is more effective than Metoprolol in treating LVDD, significantly lowering the E/A ratio, e'/a' ratio, and IVRT, and ameliorating myocardial inflammation and fibrosis. C20DM influences the activity of PGC-1α, downregulates PINK1 and Parkin, thereby enhancing mitochondrial quality control, and restoring mitochondrial oxidative respiration and membrane potential. Furthermore, C20DM reduces excessive autophagy in cardiomyocytes via the AMPK-mTOR-ULK1 pathway, diminishing cardiomyocyte hypertrophy and damage. CONCLUSIONS: Overall, our research indicates that C20DM has the potential to enhance LVDD through the regulation of mitochondrial quality control and cellular autophagy, making it a promising option for heart failure therapy.

Engineered Microfibers for Tissue Engineering.

Hydrogel microfibers are hydrogel materials engineered into fiber structures. Techniques such as wet spinning, microfluidic spinning, and 3D bioprinting are often used to prepare microfibers due to their ability to precisely control the size, morphology, and structure of the microfibers. Microfibers with different structural morphologies have different functions; they provide a flow-through culture environment for cells to improve viability, and can also be used to induce the differentiation of cells such as skeletal muscle and cardiac muscle cells to eventually form functional organs in vitro through special morphologies. This Review introduces recent advances in microfluidics, 3D bioprinting, and wet spinning in the preparation of microfibers, focusing on the materials and fabrication methods. The applications of microfibers in tissue engineering are highlighted by summarizing their contributions in engineering biomimetic blood vessels, vascularized tissues, bone, heart, pancreas, kidney, liver, and fat. Furthermore, applications of engineered fibers in tissue repair and drug screening are also discussed.

A class of geranylquinol-derived polycyclic meroterpenoids from Arnebia euchroma against heart failure by reducing excessive autophagy and apoptosis in cardiomyocytes.

Ten new B-ring aromatized 6/6/6-tricyclic dearomatized benzocogeijerene-based meroterpenoids with unusual methyl 1,2-shift or demethylation (2-9b), and two new geranylquinol derivatives (1 and 10), together with two known compounds (11 and 12), were isolated from the roots of Arnebia euchroma. Their structures were elucidated by extensive spectroscopic methods, X-ray diffraction crystallography, and ECD calculations. The plausible biosynthetic pathways including the unusual methyl 1,2-shfit and demethylation for B-ring aromatized 6/6/6-tricyclic meroterpenoids were discussed. Compounds 1, 2, 5, 6, 11, and 12 showed significant cardioprotective activities comparable to diltiazem against isoprenaline (ISO)-induced H9C2 cell damage in vitro. Compound 11 probably exerted heart-protective effect on ISO-induced H9C2 cells by modulating the PI3K-AKT-mTOR pathway, reducing excessive autophagy, and decreasing myocardial apoptosis.

Mesenchymal Stem Cells Injection Is More Effective Than Hyaluronic Acid Injection in the Treatment of Knee Osteoarthritis With Similar Safety: A Systematic Review and Meta-Analysis.

PURPOSE: To evaluate the efficacy and safety of intra-articular injection of mesenchymal stem cells (MSCs) versus hyaluronic acid (HA) in the treatment of knee osteoarthritis (KOA). METHODS: Eligible randomized controlled trials (RCTs) were identified through a search of PubMed, Embase, the Cochrane Library, Web of Science, SinoMed, and CNKI databases from inception to March 2024. For meta-analysis, data on clinical outcomes were measured using visual analog scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and data on cartilage repair were measured using the Whole-Organ Magnetic Resonance Imaging Score (WORMS); data on safety were evaluated by the incidence of adverse events. Two researchers independently read the included literature, extracted data and evaluated the quality, used the Cochrane risk bias assessment tool for bias risk assessment, and used RevMan5.3 software for meta-analysis. RESULTS: Ten RCTs involving 818 patients with KOA ranging from I to Ⅲ on the Kellgren-Lawrence grading scale were included in this meta-analysis. Meta-analysis results showed that at 12 months, the WOMAC total score (mean difference [MD] = -10.22, 95% confidence interval [CI]: -14.86 to -5.59, P < .0001, Z = 4.32), VAS score (MD = -1.31, 95% CI: -1.90 to -0.73, P < .0001, Z = 4.40); and WORMS score (MD = -26.01, 95% CI: -31.88 to -20.14, P < .001, Z = 8.69) of the MSCs group all decreased significantly (P < .05) compared with the HA control group and reached the minimal clinically important differences. Furthermore, there was no significant difference in the incidence of adverse events (relative risk = 1.54, 95% CI: 0.85-2.79, P = .16, I2 = 0) between the 2 groups (P > .05). CONCLUSIONS: Compared with HA, intra-articular injection of MSCs therapy appears to alleviate joint pain effectively, improving clinical function of KOA patients. These benefits are observed to last for at least 12 months without an increase in adverse events. Due to limited, varied, and lacking minimal clinically important differences results in existing literature, further research is needed. LEVEL OF EVIDENCE: Level I, meta-analysis of Level I studies.

20S-O-Glc-DM treats metabolic syndrome-induced heart failure through regulating gut flora.

Heart failure is a multifactorial disease, the percentage of patients with heart failure caused by metabolic syndrome is increasing year by year. The effect of gut flora dysbiosis on metabolic syndrome and heart failure has received widespread attention in recent years. Drugs to treat the condition urgently need to be discovered. C20DM, as a precursor compound of ginsenoside, is a small molecule compound obtained by biosynthetic means and is not available in natural products. In this project, we found that C20DM could improve the diversity of gut flora and elevate the expression of intestinal tight junction proteins-Occludin, Claudin, ZO-1, which inhibited the activity of the TLR4-MyD88-NF-kB pathway, and as a result, reduced myocardial inflammation and slowed down heart failure in metabolic syndrome mice. In conclusion, our study suggests that C20DM can treat heart failure by regulating gut flora, and it may be a candidate drug for treating metabolic syndrome-induced heart failure.

Comprehensive Analysis of Methylome and Transcriptome to Identify Potential Genes Regulating Porcine Testis Development.

DNA methylation plays a critical role in regulating gene expression during testicular development. However, few studies report on candidate genes related to the DNA methylation regulation of porcine testicular development. This study examined the differentially expressed genes (DEGs) and their methylation levels in testicular tissues from pigs at 60 days of age (60 d) and 180 days of age (180 d) using RNA-Seq and whole genome bisulfite sequencing (WGBS). It was determined that DNA methylation primarily occurs in the cytosine-guanine (CG) context, and the analysis identified 106,282 differentially methylated regions (DMRs) corresponding to 12,385 differentially methylated genes (DMGs). Further integrated analysis of RNA-Seq and WGBS data revealed 1083 DMGs negatively correlated with the expression of DEGs. GO analysis showed that these genes were significantly enriched in spermatogenesis, germ cell development, and spermatid differentiation. The screening of enriched genes revealed that hyper-methylation repressed ADAM30, ADAM3A, DPY19L2, H2BC1, MAK, RPL10L, SPATA16, and YBX2, while hypo-methylation elevated CACNA1I, CADM1, CTNNB1, JAM2, and PAFAH1B3 expression. Additionally, the methylation status of the key genes ADAM3A, ADAM30, YBX2, JAM2, PAFAH1B3, and CTNNB1 was detected by bisulfite sequencing PCR (BSP). This study offers insights into the epigenetic regulation mechanisms underlying porcine testicular development.

Isomer engineering for deep understanding of aggregation-induced photothermal enhancement in conjugated systems.

Organic photothermal materials based on conjugated structures have significant potential applications in areas such as biomedical diagnosis, therapy, and energy conversion. Improving their photothermal conversion efficiency through molecular design is critical to promote their practical applications. Especially in similar structures, understanding how the position of heteroatoms affects the conversion efficiency is highly desirable. Herein, we prepared two isomeric small D-A molecules with different sulfur atom positions (TBP-MPA and i-TBP-MPA), which display strong and broad absorption in the UV-visible region due to their strong intramolecular charge transfer characteristics. Compared to i-TBP-MPA, TBP-MPA demonstrates aggregation-induced photothermal enhancement (AIPE). Under simulated sunlight (1 kW m-2) irradiation, the stable temperature of TBP-MPA powder reached 60 °C, significantly higher than the 50 °C achieved by i-TBP-MPA. Experimental and theoretical results indicate that the S⋯N non-covalent interactions in TBP-MPA impart a more rigid conjugated framework to the molecule, inducing ordered molecular stacking during aggregation. This ordered stacking provides additional non-radiative transition channels between TBP-MPA molecules, enhancing their photothermal performance in the aggregated state. Under 1 sun irradiation, TBP-MPA achieved a water evaporation rate of 1.0 kg m-2 h-1, surpassing i-TBP-MPA's rate of 0.92 kg m-2 h-1.

Analysis of Medication Adherence Status and Influencing Factors in Adolescents with Major Depressive Episodes.

BACKGROUND: By analyzing the current status and influencing factors of medication adherence in adolescent patients with major depressive episode, this study aimed to provide more evidence on clinical medication treatment of such patients. METHODS: This was a retrospective study. A total of 218 adolescents with major depressive disorder (MDD) admitted to the mental health center of the First Affiliated Hospital of Guangxi Medical University from June 2022 to June 2023 were selected as the study subjects. The 8-item Morisky Medication Adherence Questionnaire (MAQ-8) was used to group the patients. All of the patients were collected in accordance with general sociological characteristics and disease characteristics. Conducted χ2 test, t-test, and binary logistic regression analysis. p values less than 0.05 indicated statistically significant differences. RESULTS: A total of 218 adolescents with MDD were included in this study. The average score of MAQ-8 was 4.44 ± 2.09, of which 139 (63.76%) with a score less than 6 were included in the medication non-adherence group. Six to eight points with 79 cases (36.24%) were included in the medication compliance group. Family economic status (odds ratio (OR) = 6.211, 95% confidence interval (CI) 2.761-13.974), family history (OR = 2.298, 95% CI 1.043-5.062), course of diseases (OR = 2.107, 95% CI 1.002-4.429), Beck Depression Inventory (BDI) score (OR = 2.303, 95% CI 1.043-5.084), drug side effects (OR = 7.139, 95% CI 3.257-15.647), attitude to treatment (OR = 2.583, 95% CI 1.221-5.466), and satisfaction with doctors (OR = 2.338, 95% CI 1.08-5.064) were the effect of medication adherence. CONCLUSION: Severe depression of adolescent patients with poor medication compliance, as well as influencing factors, including family economic conditions, family history, course of diseases, BDI score, and drug side effects, were clinically investigated to formulate corresponding measures and improve patients' medication adherence.

Dominant Malignant Clones Leverage Lineage Restricted Epigenomic Programs to Drive Ependymoma Development.

ZFTA-RELA is the most recurrent genetic alteration seen in pediatric supratentorial ependymoma (EPN) and is sufficient to initiate tumors in mice. Despite ZFTA-RELA's potent oncogenic potential, ZFTA-RELA gene fusions are observed exclusively in childhood EPN, with tumors located distinctly in the supratentorial region of the central nervous system (CNS). We hypothesized that specific chromatin modules accessible during brain development would render distinct cell lineage programs at direct risk of transformation by ZFTA-RELA. To this end, we performed combined single cell ATAC and RNA-seq analysis (scMultiome) of the developing mouse forebrain as compared to ZR-driven mouse and human EPN. We demonstrate that specific developmental lineage programs present in radial glial cells and regulated by Plagl family transcription factors are at risk of neoplastic transformation. Binding of this chromatin network by ZFTA-RELA or other PLAGL family motif targeting fusion proteins leads to persistent chromatin accessibility at oncogenic loci and oncogene expression. Cross-species analysis of mouse and human EPN reveals significant cell type heterogeneity mirroring incomplete neurogenic and gliogenic differentiation, with a small percentage of cycling intermediate progenitor-like cells that establish a putative tumor cell hierarchy. In vivo lineage tracing studies reveal single neoplastic clones that aggressively dominate tumor growth and establish the entire EPN cellular hierarchy. These findings unravel developmental epigenomic states critical for fusion oncoprotein driven transformation and elucidate how these states continue to shape tumor progression. HIGHLIGHTS: 1. Specific chromatin modules accessible during brain development render distinct cell lineage programs at risk of transformation by pediatric fusion oncoproteins.2. Cross-species single cell ATAC and RNA (scMultiome) of mouse and human ependymoma (EPN) reveals diverse patterns of lineage differentiation programs that restrain oncogenic transformation.3. Early intermediate progenitor-like EPN cells establish a tumor cell hierarchy that mirrors neural differentiation programs.4. ZFTA-RELA transformation is compatible with distinct developmental epigenetic states requiring precise 'goldilocks' levels of fusion oncoprotein expression.5. Dominant tumor clones establish the entire EPN cellular hierarchy that reflects normal gliogenic and neurogenic differentiation programs.

The impact of nimodipine combined with Ginkgo biloba extract on cognitive function and ADL scores in patients with Parkinson's disease: A retrospective study.

This study aims to explore the value of nimodipine combined with Ginkgo biloba extract in improving cognitive function and daily living abilities in patients with Parkinson's disease. Clinical data from 551 patients with Parkinson's disease admitted to the Neurology Department of the Affiliated Hospital of Beihua University from January 2022 to December 2022 were retrospectively collected. Cognitive function and daily living abilities were assessed in patients before treatment, and a reevaluation was conducted after 12 weeks of medication. Patients treated solely with nimodipine were categorized into the monotherapy group, while patients treated with nimodipine combined with Ginkgo biloba extract were included in the combination group. After 1:1 propensity score matching, a total of 83 pairs of patients were matched, and differences in relevant indicators between the 2 groups were compared. The total effective rate of treatment in the combination group was 90.36%, which was higher than the control group at 72.29% (P < .05). However, after treatment, the observation group showed higher Mini-Mental State Examination and activities of daily living scores compared to the control group (P < .05). The combined treatment of nimodipine and Ginkgo biloba extract in patients with Parkinson's disease has a significant effect and can effectively improve cognitive function and enhance daily living abilities.

Targeting DKK1 enhances the antitumor activity of paclitaxel and alleviates chemotherapy-induced peripheral neuropathy in breast cancer.

Chemotherapy in combination with immunotherapy has gradually shown substantial promise to increase T cell infiltration and antitumor efficacy. However, paclitaxel in combination with immune checkpoint inhibitor targeting PD-1/PD-L1 was only used to treat a small proportion of metastatic triple-negative breast cancer (TNBC), and the clinical outcomes was very limited. In addition, this regimen cannot prevent paclitaxel-induced peripheral neuropathy. Therefore, there was an urgent need for a novel target to enhance the antitumor activity of paclitaxel and alleviate chemotherapy-induced peripheral neuropathy in breast cancer. Here, we found that Dickkopf-1 (DKK1) expression was upregulated in multiply subtypes of human breast cancer specimens after paclitaxel-based chemotherapy. Mechanistic studies revealed that paclitaxel promoted DKK1 expression by inducing EGFR signaling in breast cancer cells, and the upregulation of DKK1 could hinder the therapeutic efficacy of paclitaxel by suppressing the infiltration and activity of CD8+ T cells in tumor microenvironment. Moreover, paclitaxel treatment in tumor-bearing mice also increased DKK1 expression through the activation of EGFR signaling in the primary sensory dorsal root ganglion (DRG) neurons, leading to the development of peripheral neuropathy, which is charactered by myelin damage in the sciatic nerve, neuropathic pain, and loss of cutaneous innervation in hindpaw skin. The addition of an anti-DKK1 antibody not only improved therapeutic efficacy of paclitaxel in two murine subtype models of breast cancer but also alleviated paclitaxel-induced peripheral neuropathy. Taken together, our findings providing a potential chemoimmunotherapy strategy with low neurotoxicity that can benefit multiple subtypes of breast cancer patients.

Histone serotonylation regulates ependymoma tumorigenesis.

Bidirectional communication between tumours and neurons has emerged as a key facet of the tumour microenvironment that drives malignancy1,2. Another hallmark feature of cancer is epigenomic dysregulation, in which alterations in gene expression influence cell states and interactions with the tumour microenvironment3. Ependymoma (EPN) is a paediatric brain tumour that relies on epigenomic remodelling to engender malignancy4,5; however, how these epigenetic mechanisms intersect with extrinsic neuronal signalling during EPN tumour progression is unknown. Here we show that the activity of serotonergic neurons regulates EPN tumorigenesis, and that serotonin itself also serves as an activating modification on histones. We found that inhibiting histone serotonylation blocks EPN tumorigenesis and regulates the expression of a core set of developmental transcription factors. High-throughput, in vivo screening of these transcription factors revealed that ETV5 promotes EPN tumorigenesis and functions by enhancing repressive chromatin states. Neuropeptide Y (NPY) is one of the genes repressed by ETV5, and its overexpression suppresses EPN tumour progression and tumour-associated network hyperactivity through synaptic remodelling. Collectively, this study identifies histone serotonylation as a key driver of EPN tumorigenesis, and also reveals how neuronal signalling, neuro-epigenomics and developmental programs are intertwined to drive malignancy in brain cancer.

Identification of immune- and oxidative stress-related signature genes as potential targets for mRNA vaccines for pancreatic cancer patients.

Adenocarcinoma of the pancreas (PAAD) is one of the deadliest malignant tumors, and messenger ribonucleic acid vaccines, which constitute the latest generation of vaccine technology, are expected to lead to new ideas for the treatment of pancreatic cancer. The Cancer Genome Atlas-PAAD and Genotype-Tissue Expression data were merged and analyzed. Weighted gene coexpression network analysis was used to identify gene modules associated with tumor mutational burden among the genes related to both immunity and oxidative stress. Differentially expressed immune-related oxidative stress genes were screened via univariate Cox regression analysis, and these genes were analyzed via nonnegative matrix factorization. After immune infiltration analysis, least absolute shrinkage and selection operator regression combined with Cox regression was used to construct the model, and the usefulness of the model was predicted based on the receiver operating characteristic curve and decision curve analysis curves after model construction. Finally, metabolic pathway enrichment was analyzed using gene set enrichment analysis combined with Kyoto Encyclopedia of Genes and Genomes and gene ontology biological process analyses. This model consisting of the ERAP2, mesenchymal-epithelial transition factor (MET), CXCL9, and angiotensinogen (AGT) genes can be used to help predict the prognosis of pancreatic cancer patients more accurately than existing models. ERAP2 is involved in immune activation and is important in cancer immune evasion. MET binds to hepatocyte growth factor, leading to the dimerization and phosphorylation of c-MET. This activates various signaling pathways, including MAPK and PI3K, to regulate the proliferation, invasion, and migration of cancer cells. CXCL9 overexpression is associated with a poor patient prognosis and reduces the number of CD8 + cytotoxic T lymphocytes in the PAAD tumor microenvironment. AGT is cleaved by the renin enzyme to produce angiotensin 1, and AGT-converting enzyme cleaves angiotensin 1 to produce angiotensin 2. Exposure to AGT-converting enzyme inhibitors after pancreatic cancer diagnosis is associated with improved survival. The 4 genes identified in the present study - ERAP2, MET, CXCL9, and AGT - are expected to serve as targets for messenger ribonucleic acid vaccine development and need to be further investigated in depth.

Evaluating the Impact of an Organic Trace Mineral mix on the Redox Homeostasis, Immunity, and Performance of Sows and their Offspring.

The objective of the study was to evaluate the effects of trace mineral supplementation in sows during gestation and lactation on the performance and health status of sows and their offspring. Sows (n = 30; Landrace × Yorkshire; avg parity = 3.9) were randomly allocated into two dietary treatments. Sows received a basal diet supplemented with 12 mg/kg Cu, 30 mg/kg Fe, 90 mg/kg Zn, 70 mg/kg Mn, 0.30 mg/kg Se, and 1.5 mg/kg I from an inorganic trace mineral source (ITM) or a blend of hydroxychloride and organic trace mineral source (HOTM) from day 1 of gestation until the end of the lactation period at day 21. Compared to the ITM, the HOTM supplementation increased (P < 0.05) both litter birth weight and individual piglet birth weight. Although not statistically significant, HOTM tended to increase (P = 0.069) the level of lactose in colostrum. HOTM increased (P < 0.05) the concentration of Mn and Se in the colostrum, milk, and serum of sows and/or piglets. Notably, the Zn concentration in the serum of sows was higher in sows supplemented with ITM compared to HOTM. Moreover, HOTM increased (P < 0.05) the activities of GPX and SOD in gestating sows and piglets, as well as increased (P < 0.05) cytokines (IL-1ß, TNF-α, and IL-10) in the serum of sows. The immunoglobulins (IgA, IgG, and IgM) also increased in sows and/or piglets at certain experimental time points. In conclusion, HOTM supplementation positively affected piglet development and improved the health status of sows and piglets potentially by regulating redox homeostasis and immunity.

Allergic fungal rhinosinusitis linked to other hyper-IgE syndromes through defective TH17 responses.

BACKGROUND: In a gene expression analysis comparing sinus mucosa samples from allergic fungal rhinosinusitis (AFRS) patients with samples from non-AFRS chronic rhinosinusitis with nasal polyp (CRSwNP) patients, the antimicrobial peptide (AMP) histatin 1 (HTN1) was found to be the most differentially downregulated gene in AFRS. OBJECTIVE: We sought to identify the molecular etiology of the downregulated expression of HTN1. METHODS: We used RT-PCR to compare the expression of AMPs and a fungistasis assay to evaluate the antifungal activity of sinus secretions. Using flow cytometry, we characterized the presence of TH17/TH22 cells and signal transducer and activator of transcription (STAT) signaling from AFRS patients, non-AFRS CRSwNP patients, and healthy controls. RESULTS: We confirmed decreased expression of AMPs in AFRS sinus mucosa with concordant decrease in antifungal activity in sinus secretions. IL-22 and IL-22-producing T cells were deficient within sinus mucosa of AFRS patients. In vitro studies demonstrated a defect in IL-6/STAT3 signaling critical for TH17/TH22 differentiation. Epithelial cells from AFRS patients could express AMPs when stimulated with exogenous IL-22/IL-17 and circulating TH17 cell abundance was normal. CONCLUSIONS: Similar to other hyper-IgE syndromes, but distinct from CRSwNP, AFRS patients express a defect in STAT3 activation limited to IL-6-dependent STAT3 phosphorylation that is critical for TH17/TH22 differentiation. This defect leads to a local deficiency of IL-17/IL-22 cytokines and deficient AMP expression within diseased sinus mucosa of AFRS patients. Our findings support evaluation of therapeutic approaches that enhance airway AMP production in AFRS.

Mapping and analyzing the spatiotemporal dynamics of forest aboveground biomass in the ChangZhuTan urban agglomeration using a time series of Landsat images and meteorological data from 2010 to 2020.

In the context of global warming, there is a substantial demand for accurate and cost-effective assessment and comprehensive understanding of forest above-ground biomass (AGB) dynamics. The timeliness and low cost of optical remote sensing data enable the mapping of large-scale forest AGB dynamics. However, mapping forest AGB with optical remote sensing data presents challenges primarily due to data uncertainty and the complex nature of the forest environment. Previous studies have demonstrated the potential of meteorological data in enhancing forest AGB mapping. To accurately capture the dynamics of forest AGB, we initially acquired Landsat datasets, digital elevation model (DEM), and meteorological datasets (temperature, humidity, and precipitation) from 2010 to 2020 in Changsha-Zhuzhou-Xiangtan urban agglomeration (CZT) located in Hunan Province, China. Spectral variables (SVs), including spectral bands and vegetation indices, were extracted from Landsat images, while meteorological variables (MVs) were derived from the monthly meteorological data using the Savitzky-Golay (S-G) filtering algorithm. Additionally, terrain variables (TVs) were also extracted from the DEM data. Three modelling models, multiple linear regression (MLR), K nearest neighbor (KNN) and random forest (RF), were developed for mapping the dynamics of forest AGB in CZT. The result revealed that MVs have the potential to improve forest AGB mapping. Integration of MVs into the models resulted in a significant reduction in root mean square error (RMSE) ranging from 32.85 % to 19.25 % compared to utilizing only SVs. However, minimal improvement was observed with the inclusion of TVs due to negligible topographic relief within the study area. An upward trend of forest AGB in CZT was observed during this period, which can be attributed to the effective implementation of government environmental protection policies. It is confirmed that the meteorological data has significant contribution to forest AGB mapping, thereby endorsing advancements in forest resource monitoring and management programs.

Correction: Deng et al. Therapeutic Potential of a Combination of Electroacupuncture and Human iPSC-Derived Small Extracellular Vesicles for Ischemic Stroke. Cells 2022, 11, 820.

The authors wish to make the following changes to their paper [...].