Search Results (2,241)

Background: Sweet potato (Ipomoea batatas (L.) Lam.) is widely cultivated as an important food crop. However, the molecular regulatory mechanisms affecting root tuber development are not well understood. Methods: The aim of this study was to systematically reveal the regulatory network of sweet potato root enlargement through transcriptomic and metabolomic analysis in different early stages of sweet potato root development, combined with phenotypic and anatomical observations. Results: Using RNA-seq, we found that the differential genes of the S1 vs. S2, S3 vs. S4, and S4 vs. S5 comparison groups were enriched in the phenylpropane biosynthesis pathway during five developmental stages and identified 67 differentially expressed transcription factors, including AP2, NAC, bHLH, MYB, and C2H2 families. Based on the metabolome, K-means cluster analysis showed that lipids, organic acids, organic oxides, and other substances accumulated differentially in different growth stages. Transcriptome, metabolome, and prophetypic data indicate that the S3-S4 stage is the key stage of root development of sweet potato. Weighted gene co-expression network analysis (WGCNA) showed that transcriptome differential genes were mainly enriched in fructose and mannose metabolism, pentose phosphate, selenium compound metabolism, glycolysis/gluconogenesis, carbon metabolism, and other pathways. The metabolites of different metabolites are mainly concentrated in amino sugar and nucleotide sugar metabolism, flavonoid biosynthesis, alkaloid biosynthesis, pantothenic acid, and coenzyme A biosynthesis. Based on WGCNA analysis of gene-metabolite correlation, 44 differential genes and 31 differential metabolites with high correlation were identified. Conclusions: This study revealed key gene and metabolite changes in early development of sweet potato root tuber and pointed out potential regulatory networks, providing new insights into sweet potato root tuber development and valuable reference for future genetic improvement. Full article

Candidemia and invasive candidiasis (IC) are causes of morbidity and mortality in healthcare settings, with notable differences between children and adults. Understanding the species distribution and antimicrobial susceptibility profiles of clinical isolates can guide empiric therapy in patients at risk of IC. This study investigated the incidence and antifungal susceptibility patterns of yeasts involved in IC in pediatric and adult patients from 2019 to 2023. The average incidence of IC was 0.715 per 1000 patients, increasing over the study period; infants had the highest incidence rates. Over half of the IC episodes occurred in intensive care units (ICUs). Non-albicans Candida (NAC) species represented the most frequently isolated species in adults and children (55.96% and 50.0%, respectively), with the prevalence of C. parapsilosis (26.45% and 14.7%, respectively), N. glabratus (14.97% and 8.82%, respectively) and C. tropicalis (4.36% and 2.94%, respectively). C. lusitaniae was identified in 14.7% of pediatric IC cases. In NAC species, antifungal resistance has also increased over the five years of the study: 69.12% were resistant to azoles and 7.35% were resistant to micafungin. Resistance was higher in pediatric patients. Our study highlights differences in IC characteristics between pediatric and adult populations and emphasizes the importance of targeted antifungal stewardship in ICU patients with NAC invasive infections. Full article

Chenopodium hircinum, the putative wild ancestor of quinoa, is a source of traits that could improve the tolerance of crop quinoa to high temperatures. However, seeds of C. hircinum have physiological dormancy (PD), which is an obstacle for plant propagation and use in breeding programs. We studied the intraspecific variability in morpho-anatomical traits of embryo covering structures and their association with PD. We also evaluated the effects of different dormancy-breaking treatments on PD alleviation and germination. Seeds were dispersed with a remnant perianth and a persistent pericarp that could be removed by scraping. The seed coat was formed by palisade cells impregnated with tannins, and the seed contained a thin layer of peripheral endosperm surrounding the embryo. In our investigation, the thickness of the pericarp (P) and/or seed coat (SC) varied among populations. Populations with higher P and/or SC thickness showed lower percentages of germination and water absorption. The combined dormancy-breaking treatment (bleach + perforated coverings + gibberellic acid) promoted dormancy release and increased germination. C. hircinum seeds showed non-deep physiological dormancy. Based on previous knowledge about quinoa, and our results, we conclude that embryo coverings, especially the seed coat, have an important role in dormancy control, imposing a mechanical restraint on radicle emergence. Full article

Background and Objectives: Sensation of the breast skin and nipple-areolar complex (NAC) is commonly assumed to be diminished or completely absent following nipple-sparing mastectomy (NSM) with implant- or expander-based reconstruction. The purpose of this cohort study was to evaluate breast skin and NAC long-term touch pressure sensibility, from 1 month to 1 year, after NSM followed by reconstruction with an implant or expander, and patient quality of life (QoL), hypothesizing that sensibility may diminish with a small progressive return throughout the postoperative period. Materials and Methods: This was achieved by performing sensation tests using Semmes-Weinstein monofilaments (SWM) in nine predefined points of the breast and NAC, a two-point discrimination test (TPD) in the four quadrants of the breast, and QoL assessment using the BREAST-Q. We evaluated 42 patients in Pauls Stradiņš Clinical University Hospital, with a total of 66 breasts, who underwent NSM between 2021 and 2023, performing the breast sensation tests before surgery and postoperatively at 1/3/6 months and 1 year. The BREAST-Q was administered to assess patient satisfaction and well-being. Results: Our results reflect a decline in breast skin and NAC sensation in the 1-month evaluation after NSM (mean: 4.67) when compared to the assessment before surgery (mean: 2.57), with a small progressive return reflected in the 3 months (mean: 3.79), 6 months (mean: 3.68), and 1-year evaluations (mean: 3.14). The following were the mean scores obtained from the BREAST-Q: Psychosocial Well-being (mean: 66), Sexual Well-being (mean: 50), Satisfaction with Breasts Pre-OP (mean: 58), satisfaction with breast reconstruction (mean: 52), Satisfaction with Implants, Satisfaction with nipple reconstruction, Physical Well-being Chest, Adverse effects of radiation, and Satisfaction with Information. Conclusions: This study confirms that sensibility diminishes after this procedure, as observed when comparing the sensation evaluation results before the operation with the 1-month evaluation, reflecting a small progressive return in the following months. Full article

Dengue virus (DENV) infection, prevalent in tropical and subtropical regions, can progress to dengue hemorrhagic fever (DHF), which increases mortality during secondary infections. DHF is characterized by endothelial damage and vascular leakage. Despite its severity, no specific antiviral treatments exist, and the viral factors responsible for endothelial damage remain unclear. This study examines the role of the DENV envelope protein domain III (EIII) in inducing endothelial apoptosis using a mouse model. Additionally, we aim to explore whether cell death-inducing pathways could serve as drug targets to ameliorate EIII-induced endothelial injury and hemorrhage. In vitro experiments using human endothelial HMEC-1 cells demonstrated that both recombinant EIII (rEIII) and DENV markedly induced caspase-3-mediated endothelial cell death, an effect that was attenuated by co-treatment with chondroitin sulfate B (CSB), N-acetyl cysteine (NAC), and the caspase-3 inhibitor z-DEVD-FMK. In vivo, sequential injections of rEIII and anti-platelet immunoglobulin in mice, designed to mimic the clinical phase of DHF with peak viremia followed by an increase in DENV-induced Ig, including autoantibodies, revealed that these dual treatments markedly triggered caspase-3-dependent apoptosis in vascular endothelial cells at hemorrhage sites. Treatments with z-DEVD-FMK effectively reduced DHF-like symptoms such as thrombocytopenia, hemorrhage, inflammation, hypercoagulation, and endothelial damage. Additionally, CSB and NAC alleviated hemorrhagic symptoms in the mice. These results suggest that targeting EIII, reactive oxygen species, and caspase-3-mediated apoptosis could offer potential therapeutic strategies for addressing EIII-induced hemorrhagic pathogenesis. Full article

Continuous flow technologies have become increasingly important for biocatalytic processes. In this study, we present the application and modelling of covalently immobilised N-acetylglucosamine 2-epimerase and N-acetylneuraminic acid lyase in packed bed reactors for the synthesis of N-acetylneuraminic acid. The immobilised enzymes were stable under continuous flow process conditions with half-life times of >28 d (epimerase immobilised on hexamethylamino methacrylate HA403/M) or 58 d (lyase immobilised on dimenthylamino methacrylate ECR8309M), suitable for continuous flow applications. Kinetic studies revealed Michaelis–Menten kinetic behaviour for both enzymes. The kinetic parameters and the inhibitions were analysed under continuous flow conditions and were integrated into a process model using Python. The model was validated by varying flow rates, the mass of immobilised enzymes and the reactor dimensions and shows a low error compared to the measured data. An error accuracy of 6% (epimerase) or 9% (lyase) was achieved. The product concentrations of the enzyme cascade at the end of the packed bed reactor can be predicted with an accuracy of 9% for the calculation of a large column (84.5 mL) or of 24% if several small columns (2.5 mL, 0.8 mL) are connected in series. The developed model has proved to be valid and will be used to optimise the process with respect to substrate concentrations, reactor dimensions and flow rate. Full article

The color of coffee fruits is influenced by several factors, including cultivar, ripening stage, and metabolite composition. However, the metabolic accumulation of pigments and the molecular mechanisms underlying peel coloration during the ripening process of Coffea arabica L. remain relatively understudied. In this study, UPLC-MS/MS-based metabolomics and RNA sequencing (RNA-seq)-based transcriptomics were integrated to investigate the accumulation of anthocyanins and carotenoids in the peel of Coffea arabica at different ripening stages: green peel (GP), green-yellow peel (GYRP), red peel (RP), and red-purple peel (RPP). This integration aimed at elucidating the molecular mechanisms associated with these changes. A total of ten anthocyanins, six carotenoids, and thirty-five xanthophylls were identified throughout the ripening process. The results demonstrated a gradual decrease in the total carotenoid content in the peel with fruit maturation, while anthocyanin content increased significantly. Notably, the accumulation of specific anthocyanins was closely associated with the transition of peel colors from green to red. Integrated metabolomics and transcriptomics analyses identified the GYRP stage as critical for this color transition. A weighted gene co-expression network analysis (WGCNA) revealed that enzyme-coding genes such as 3AT, BZ1, and lcyE, along with transcription factors including MYB, NAC, and bHLH, which interact with PHD and SET TR, may regulate the biosynthesis of anthocyanins and carotenoids, thereby influencing peel pigmentation. These findings provide valuable insights into the molecular mechanisms underlying the accumulation of anthocyanins and carotenoids in Coffea arabica peel during fruit maturation. Full article

NAC has mucolytic, antioxidant, and antimicrobial effects in living organisms. However, the therapeutic effects of NAC on clinical recovery among neonatal calves with respiratory diseases have not yet been studied. Our study represents the first investigation of the effects of NAC in neonatal calves with pneumonia. The objective of this work was to observe the effects of NAC in the treatment of neonatal pneumonia, including its ability to reduce the clinical score, shorten the duration of the treatment, and improve the overall health condition of neonatal calves. For this study, calves were divided into two groups: a treatment group that received NAC and amoxicillin with clavulanic acid, and a control group that received amoxicillin with clavulanic acid (antimicrobial only). The findings of this study indicate that NAC treatment significantly shortened the time to resolution (p < 0.001), compared to the results in the group without NAC treatment. Generally, NAC-supplemented therapy reduced the recovery time by more than 27 h (or slightly more than one day), compared to that in the antimicrobial-only group. Our study presents the first reported usage of NAC in therapy for respiratory disorders. Full article

A green, low-carbon concrete is a top way to recycle waste in construction. This study uses industrial solid waste slag powder (S95) and fly ash (FA) as binders to completely replace cement. This study used recycled coarse aggregate (RCA) instead of natural coarse aggregate (NCA). This is to prepare alkali-activated recycled concrete (AARC) with different cementitious material systems. Alkali-activated concrete (AAC) mixtures are modified for strength and performance based on the mechanical qualities and durability of AARC. Also, the time-varying effects of the environment on AARC properties are explored. The results show that with the performance enhancement of RCA, the mechanical performance of AARC is significantly improved. As RCA’s quality improves, so does AARC’s compressive strength. At a cementitious material content of 550 kg/m³, AARC’s 28d compressive strengths using I-, II-, and III-class RCA were reduced by 2.2%, 12.7%, and 21.8%, respectively. I-class AARC has characteristics similar to natural aggregate concrete (NAC) in terms of shrinkage, resistance to chloride penetration, carbonization, and frost resistance. AARC is a new type of green building material that uses industrial solid waste to prepare alkali-activated cementitious materials. It can effectively reduce the amount of cement and alleviate energy consumption. This is conducive to the reuse of resources, environmental protection, and sustainable development. Full article

Paulownia species not only have significant economic benefits but also show great potential in ecological conservation. However, they are highly susceptible to phytoplasma infections, causing Paulownia witches’ broom (PaWB), which severely restricts the development of the Paulownia industry. Salicylic acid (SA) plays a crucial role in plant disease resistance. However, there have been no reports on the effect of SA on PaWB. Due to the properties of SA, it may have potential in controlling PaWB. Based on the above speculation, the prevention and therapeutic effect of SA on PaWB and its effect on the PaWB-infected Paulownia transcriptome and proteome were studied in this work. The results indicated that 0.1 mmol/L was the optimal SA concentration for inhibiting the germination of Paulownia axillary buds. In terms of resistance physiological indicators, SA treatment significantly affected both Paulownia tomentosa infected (PTI) seedlings and Paulownia fortunei infected (PFI) seedlings, where the activities of peroxidase (POD) and superoxide dismutase (SOD) were enhanced. Malondialdehyde (MDA), O₂⁻, and H₂O₂, however, were significantly reduced. Specifically, after SA treatment, SOD activity increased by 28% in PFI and 25% in PTI, and POD activity significantly increased by 61% in PFI and 58% in PTI. Moreover, the MDA content decreased by 30% in PFI and 23% in PTI, the H₂O₂ content decreased by 26% in PFI and 19% in PTI, and the O₂⁻ content decreased by 21% in PFI and 19% in PTI. Transcriptomic analysis showed that there were significant upregulations of MYB, NAC, and bHLH and other transcription factors after SA treatment. Moreover, genes involved in PaWB-related defense responses such as RAX2 also showed significant differences. Furthermore, proteomic analysis indicated that after SA treatment, proteins involved in signal transduction, protein synthesis modification, and disease defense were differentially expressed. This work provides a research foundation for the prevention and treatment of PaWB and offers references for exploring anti-PaWB methods. Full article

Objective: The objective of this study was to determine the influence of sex and strain on striatal and nucleus accumbens dopamine neurochemistry and dopamine-related behavior due to a high-saturated-fat diet (HFD). Methods: Male and female C57B6/J (B6J) and Balb/cJ (Balb/c) mice were randomly assigned to a control-fat diet (CFD) containing 10% kcal fat/g or a mineral-matched HFD containing 60% kcal fat/g for 12 weeks. Results: Intraperitoneal glucose tolerance testing (IPGTT) and elevated plus maze experiments (EPM) confirmed that an HFD produced marked blunting of glucose clearance and increased anxiety-like behavior, respectively, in male and female B6J mice. Electrically evoked dopamine release in the striatum and reuptake in the nucleus accumbens (NAc), as measured by ex vivo fast scan cyclic voltammetry, was reduced for HFD-fed B6J females. Impairment in glucose metabolism explained HFD-induced changes in dopamine neurochemistry for B6J males and, to a lesser extent, Balb/c males. The relative expressions of protein markers associated with the activation of microglia, ionized calcium binding adaptor molecule (Iba1) and cluster of differentiation molecule 11b (CD11b) in the striatum were increased due to an HFD for B6J males but were unchanged or decreased amongst HFD-fed Balb/c mice. Conclusions: Our findings demonstrate that strain and sex influence the insulin- and microglia-dependent mechanisms of alterations to dopamine neurochemistry and associated behavior due to an HFD. Full article

A major reason for the failure of the immune system to detect tumor antigens (TAs) is the insufficient uptake, processing, and presentation of TAs by antigen-presenting cells (APCs). The immunogenicity of TAs in the individual patient can be markedly increased by the in situ targeting of tumor cells for robust uptake by APCs, without the need to identify and characterize the TAs. This is feasible by the intra-tumoral injection of α-gal micelles comprised of glycolipids presenting the carbohydrate-antigen “α-gal epitope” (Galα1-3Galβ1-4GlcNAc-R). Humans produce a natural antibody called “anti-Gal” (constituting ~1% of immunoglobulins), which binds to α-gal epitopes. Tumor-injected α-gal micelles spontaneously insert into tumor cell membranes, so that multiple α-gal epitopes are presented on tumor cells. Anti-Gal binding to these epitopes activates the complement system, resulting in the killing of tumor cells, and the recruitment of multiple APCs (dendritic cells and macrophages) into treated tumors by the chemotactic complement cleavage peptides C5a and C3a. In this process of converting the treated tumor into a personalized TA vaccine, the recruited APC phagocytose anti-Gal opsonized tumor cells and cell membranes, process the internalized TAs and transport them to regional lymph-nodes. TA peptides presented on APCs activate TA-specific T cells to proliferate and destroy the metastatic tumor cells presenting the TAs. Studies in anti-Gal-producing mice demonstrated the induction of effective protection against distant metastases of the highly tumorigenic B16 melanoma following injection of natural and synthetic α-gal micelles into primary tumors. This treatment was further found to synergize with checkpoint inhibitor therapy by the anti-PD1 antibody. Phase-1 clinical trials indicated that α-gal micelle immunotherapy is safe and can induce the infiltration of CD4+ and CD8+ T cells into untreated distant metastases. It is suggested that, in addition to converting treated metastases into an autologous TA vaccine, this treatment should be considered as a neoadjuvant therapy, administering α-gal micelles into primary tumors immediately following their detection. Such an immunotherapy will convert tumors into a personalized anti-TA vaccine for the period prior to their resection. Full article

Drought stress, as one of the most common environmental factors, seriously affects seed- ling establishment as well as plant growth and productivity. The growth of Toona ciliata is constrained by soil moisture deficit, and drought stress can reduce its productivity and limit its suitable growing environment. To explore the molecular mechanism of Toona ciliata responding to drought stress, leaves of two-year-old Toona ciliata seedlings were used as experimental materials for transcriptome sequencing and physiological index measurements. Under drought stress, the contents of Chl, MDA, POD, SP, SS, and RWC all change differently. We performed transcriptome sequencing, obtaining 4830 differential genes. The enrichment analysis indicates that the primary effects on the leaves of Toona ciliata under drought stress are related to photosynthesis and responses to plant hormone signal transduction. Transcription factor families associated with drought resistance include the NAC, WRKY, bZIP, bHLH, AP2-EREBP, C3H, GRAS, and FRAI transcription factor families. A weighted gene co-expression network analysis (WGCNA) analysis successfully identified 10 hub genes in response to drought stress in Toona ciliata leaves. Real-time quantitative PCR (RT-qPCR) validated the reliability of the transcriptomic data, and the analysis of its results showed a close correlation with the data obtained from RNA-seq. This study clarifies the transcriptional response of Toona ciliata to drought stress, contributing to the revelation of the molecular mechanisms of drought adaptation. Full article

Osteosarcoma is a primary malignant tumor found in the bones of children and adolescents. Unfortunately, many patients do not respond well to treatment and succumb to the illness. Therefore, it is necessary to discover novel bioactive compounds to overcome therapeutic limitations. Liriope platyphylla Wang et Tang is a well-known herb used in oriental medicine. Studies have shown that metabolic diseases can be clinically treated using the roots of L. platyphylla. Recent studies have demonstrated the anticarcinoma potential of root extracts; however, the exact mechanism remains unclear. The aim of this study was to examine the anti-osteosarcoma activity of a single compound extracted from the dried roots of L. platyphylla. We purified Spicatoside A (SpiA) from the dried roots of L. platyphylla. SpiA significantly inhibited the proliferation of human osteosarcoma MG63 cells in a dose- and time-dependent manner. SpiA also regulated the expression of various downstream proteins that mediate apoptosis (PARP, Bcl-2, and Bax), cell growth (cyclin D1, Cdk4, and Cdk6), angiogenesis (VEGF), and metastasis (MMP13). The Proteome Profiler Human Phospho-Kinase Array Kit showed that the AKT signaling protein was a target of SpiA in osteosarcoma cells. We also found that SpiA suppressed the constitutive activation of the PI3K-AKT-mTOR-p70S6K1 signaling pathway. We further validated the effects of SpiA on the AKT signaling pathway. SpiA induced autophagosome formation and suppressed necroptosis (a form of programmed cell death). SpiA increased the generation of reactive oxygen species (ROS) and led to the loss of mitochondrial membrane potential. N-acetylcysteine (NAC)-induced inhibition of ROS generation reduced SpiA-induced AKT inhibition, apoptotic cell death, and anti-metastatic effects by suppressing cell migration and invasion. Overall, these results highlight the anti-osteosarcoma effect of SpiA by inhibiting the AKT signaling pathway through ROS generation, suggesting that SpiA may be a promising compound for the treatment of human osteosarcoma. Full article

To assess the regulatory mechanisms involved in the transcriptomic response of Ginkgo biloba to water shock and rehydration, ginkgo seedlings were subjected to dehydration for 0, 3, 6, 12, and 24 h, followed by rehydration for 12 h (Re12 h). A total of 1388, 1802, 2267, 2667, and 3352 genes were upregulated, whereas 1604, 1839, 1934, 2435, and 3035 genes were downregulated, at 3, 6, 12, 24, and Re12 h, respectively, compared to 0 h. Two KEGG pathways—the plant pathogen interaction pathway and mitogen-activated protein kinase (MAPK) signaling pathway—were enriched under water shock but not under rehydration. Moreover, plant hormone signal transduction was enriched under both water shock and rehydration. Differentially expressed genes (DEGs) involved in the ABA signaling pathway (PYR/PYLs, PP2Cs, and SnRK2s) and major differentially expressed transcription factors (MYB, bHLH, AP2/ERF, NAC, WRKY, and bZIP TFs) were identified. qRT-PCR analysis further revealed GbWRKY3 as a negative regulator of the water shock response in G. biloba. The subcellular localization results revealed GbWRKY3 as a nuclear protein. These phenotype-related DEGs, pathways, and TFs provide valuable insight into the water shock and rehydration response in G. biloba. Full article