Activation Of Gene Expression Research Articles

Resistance of Pinus pinea to Bursaphelenchus xylophilus explained by the dynamic response of phytohormones, antioxidant activity, and stress-related gene expression

Key messageThe effects of MJ on pine trees are species-specific and trigger a resistant phenotype to the PWN. A more dynamic response of hormones and gene expression in Pinus pinea explains the high resistance to Bursaphelenchus xylophilus of this species.Knowledge on hormonal and genetic mechanisms of pine trees in response to the pinewood nematode (PWN; Bursaphelenchus xylophilus) is limited. To describe tree defence strategies against B. xylophilus, this study used the plant stress hormone methyl jasmonate (MJ) on four pine species with different susceptibility (Pinus pinaster < P. radiata ≈ P. sylvestris < P. pinea). Three-year-old trees were sprayed with MJ at 0, 25, and 50 mM, and 2 months later challenged with the PWN. Multiple samples were taken to assess nematode content, oxidative stress, secondary metabolites, phytohormone levels, and stress-related gene expression. Nematode infestation in trees correlated negatively with the water content of needles and phenolics of stems, and positively with the concentration of indole-3-carboxylic acid in stems. MJ spray reduced in a dose-dependent manner the nematode content in P. pinaster and P. sylvestris. The effects of MJ were species-specific, although a more pronounced impact was observed in the susceptible P. pinaster species, leading to a decrease of chlorophyll and water loss and to the upregulation of the gene involved in the biosynthesis of terpenoids (AFS). After MJ spray, increased levels of JA-Ile were observed in P. pinea only. Hormone profiling, predisposition to activate antioxidant response, and gene expression in P. pinea trees provide evidence of why this species is highly resistant to B. xylophilus. On the contrary, the lack of effective hormonal changes in P. pinaster explained the lack of defence responses to B. xylophilus of this susceptible species. This study is a first approach to explore biochemical, molecular, and hormonal interactions between Pinus species and the PWN, and presents unprecedented insights into alterations induced by exogenous MJ in regulating defence mechanisms in pine trees.

Digestive and absorptive capacity and digesta microbiota throughout the gastrointestinal tract of nursery pigs from parents with divergent estimated breeding value for feed conversion ratio

This study investigated digestive and absorptive function changes and microbiota adaptations during weaning in nursery pigs from parents with divergent estimated breeding values for feed conversion ratio (EBV_FCR). The research aimed to investigate whether these changes differed between two groups: pigs from high EBV_FCR (low efficiency, LE) parents and pigs from low EBV_FCR (high efficiency, HE) parents. Furthermore, digesta samples from duodenum, jejunum, ileum, colon, and cecum were collected from 56-day-old post-weaned pigs and subjected to microbiota analysis using 16S rRNA gene profiling. Enzyme activity kinetics and gene expression analyses of nutrient transporters in various segments of the digestive tract showed no significant differences between the two groups. Tight junction proteins gene expression also showed no significant differences in the jejunum between the two groups. Microbiota analysis revealed consistent dominance of Firmicutes in the jejunum and ileum, with Firmicutes and Bacteroidetes prevalent in the cecum and colon across both groups. However, significant differences were observed at the genus level. Lactobacillus was predominant in the small intestine of HE pigs, while the large intestine of LE pigs harbored higher levels of Prevotella, Streptococcus, and Blautia compared to HE pigs. These differences suggest potential functional differences that warrant further investigation.

Increased apoptosis in late-developing in vitro fertilized bovine blastocysts decreases successful pregnancy.

Pregnancy in cattle after embryo transfer (ET) is influenced by several factors, including embryo quality. Therefore, preparing high-quality embryos with the greatest developmental potential is essential for achieving a successful pregnancy after ET. Meanwhile, blastocysts produced by in vitro fertilization (IVF) procedure have different developmental speed during in vitro culture (IVC) and they exhibited different competence in the establishment of pregnancy. This study aimed to identify the comparative features of early-, mid-, and late-developing bovine IVF blastocysts, when they first appeared at Day 7, 8, and 9 during IVC, respectively. In addition, the correlations between their molecular features and pregnancy ability were analyzed. The results showed no difference in the morphological characteristics, including total cell count and diameter, between the Day 7, 8, and 9 blastocysts. However, the pregnancy rate post-ET was significantly different between the groups at 51.7%, 36.7%, and 17.8% for Day 7, 8, and 9 blastocysts, respectively. During early embryo development, late-developing blastocysts demonstrated a reduced cell count in the inner cell mass and decreased expression of the early embryo developmental genes (Oct4 and Sox2) compared with the early- and mid-developing blastocysts. In addition, the number of apoptotic cells and apoptosis-related gene expression (increased Bax and decreased Bcl2) gradually elevated from the Day 7 to Day 9 blastocysts. However, there was no difference in mitochondrial activity and mitochondria-relevant gene expression (Tfam and Cox1) between the groups. Correlation analysis identified a significantly negative correlation between the pregnancy rate and the blastocysts' degree of apoptosis, indicating that the low pregnancy ability of late-developing blastocysts was mainly caused by increased apoptosis. This study's results may contribute to the field of animal biotechnology by assisting in establishing an improved strategy for bovine ET with IVF embryos.

Overexpression of AtbZIP69 in transgenic wheat confers tolerance to nitrogen and drought stress.

AtbZIP69 overexpression in wheat significantly enhanced drought and low nitrogen tolerance by modulating ABA synthesis, antioxidant activity, nitrogen allocation, and transporter gene expression, boosting yield. In this study, we generated wheat plants with improved low nitrogen (LN) and drought tolerance by introducing AtbZIP69, a gene encoding a basic leucine zipper domain transcription factor, into the wheat cultivar Shi 4056. AtbZIP69 localized to the nucleus and activated transcription. A greenhouse study further revealed that, compared to wild type (WT) wheat, AtbZIP69 transgenic wheat exhibited significantly increased drought and LN stress tolerance. Under drought stress, the H2O2 concentration in transgenic lines decreased, whereas SOD activity and proline content increased, resulting in remarkably enhanced drought resistance. Furthermore, drought stress boosted the expression of critical abscisic acid (ABA) synthesis enzymes as well as the ABA content of transgenic plants, implying that this gene may improve wheat's drought resistance by promoting ABA production. Additionally, during a two-year field test, the yield and the number of spikes of transgenic wheat were significantly higher than those of WT wheat under LN conditions. Mechanistically, the overexpression of AtbZIP69 altered nitrogen distribution by allocating more nitrogen to grains under LN conditions. In addition, the expression of genes encoding nitrogen transporter proteins was higher in AtbZIP69 transgenic wheat than in WT wheat under LN conditions. These findings suggest that the insertion of AtbZIP69 opens up new opportunities for wheat stress resistance breeding.

A 3D-printed multi-compartment organ-on-chip platform with a tubing-free pump models communication with the lymph node.

Multi-organ-on-chip systems (MOOCs) have the potential to mimic communication between organ systems and reveal mechanisms of health and disease. However, many existing MOOCs are challenging for non-experts to implement due to complex tubing, electronics, or pump mechanisms. In addition, few MOOCs have incorporated immune organs such as the lymph node (LN), limiting their applicability to model critical events such as vaccination. Here we developed a 3D-printed, user-friendly device and companion tubing-free impeller pump with the capacity to co-culture two or more tissue samples, including a LN, under a recirculating common media. Native tissue structure and immune function were incorporated by maintaining slices of murine LN tissue ex vivo in 3D-printed mesh supports for at least 24 h. In a two-compartment model of a LN and an upstream injection site in mock tissue, vaccination of the multi-compartment chip was similar to in vivo vaccination in terms of locations of antigen accumulation and acute changes in activation markers and gene expression in the LN. We anticipate that in the future, this flexible platform will enable models of multi-organ immune responses throughout the body.

Promoting Angiogenesis/Osteogenesis by a New Copper/Magnesium Hydroxide Hybrid Nanoparticle: InVitro and InVivo Investigation.

In this study, a new hybrid nanoparticle composed of magnesium hydroxide and copper oxide (Mg(OH)2/CuO) with an optimized ratio of magnesium (Mg) to copper (Cu) was designed and incorporated into a 3D-printed scaffold made of polycaprolactone (PCL) and gelatin. These hybrid nanostructures (MCNs) were prepared using a green, solvent-free method. Their topography, surface morphology, and structural properties were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The fabricated 3D-printed PCL/Gelatin/MCN scaffolds were investigated invitro and invivo. Cell viability tests on murine calvarial preosteoblasts (MC3T3-E1) and human umbilical vein endothelial cells (HUVECs) demonstrated that the scaffolds could induce proper cell proliferation. Additionally, the angiogenic and osteogenic properties of the constructs were evaluated using alkaline phosphatase (ALP) activity, osteogenesis-related, and angiogenesis-related gene expression tests. The invivo study was conducted using a rat calvarial defect model, which confirmed the superior angiogenic and osteogenic properties of the PCL/gelatin/MCN scaffolds compared to PCL/Gelatin and PCL/Gelatin/Mg(OH)2 scaffolds. Overall, the PCL/Gelatin/MCN scaffolds showed promising potential for bone regeneration, particularly for critical-sized defects where proper angiogenesis is essential for tissue reconstruction.

Microbial community and functional shifts across agricultural and urban landscapes within a Lake Erie watershed.

The role of sediment microbial communities in regulating the loss and retention of nutrients in aquatic ecosystems has been increasingly recognised. However, in the Great Lakes, where nutrient mitigation focuses on harmful algal blooms, there are limited studies examining the fundamental role of water/sediment microbes in nutrient biogeochemical cycling. Little is understood in this regard considering the increase in anthropogenic pressure on in-stream biological processes impacting nutrient flux to lakes. In this study, metagenomic and metatranscriptomic approaches were used to investigate the microbial community and gene regulation. The study focused on nitrogen (N) metabolism in a nutrient-polluted watershed of Lake Erie in southwestern Ontario, Canada. Nutrients and microbial analyses of water and sediments were collected in 2020 and 2021 from Sturgeon Creek headwaters to the nearshore of Lake Erie. Results showed no significant shifts in community structure with nutrient concentrations or land use. Metabolically, active genes involved in denitrification (consisting of 32-53% of N metabolic transcripts) showed the highest expression within agricultural and wetland dominant locations. Based on active gene expression patterns, the urbanised location coinciding with peak nitrate (NO3-) concentrations showed the greatest potential for nitrous oxide (N2O) emission and nitrogen loss along this transect. In contrast to denitrification, direct nitrification (5-21% of N metabolic transcripts) increased two-fold approaching downstream and nearshore lake locations. Across this river-lake corridor, expression of key functional genes associated with N transformation showed strong correlation with the change in concentrations of aqueous NO3- and nitrite (NO2-) and the ratio of NO2-/NO3-. Our findings demonstrated a clear link between sediment microbial metabolism and overlying water chemistry in this lotic system. We suggest that future studies assessing nutrient mitigation consider sediment biogeochemical processes and N-metabolising bacteria, and their fundamental role and cooperative relationship with nutrient and hydrological dynamics of overlying waters.

Small Extracellular Vesicles Derived from Lipopolysaccharide-Treated Stem Cells from the Apical Papilla Modulate Macrophage Phenotypes and Inflammatory Interactions in Pulpal and Periodontal Tissues.

Inflammation significantly influences cellular communication in the oral environment, impacting tissue repair and regeneration. This study explores the role of small extracellular vesicles (sEVs) derived from lipopolysaccharide (LPS)-treated stem cells from the apical papilla (SCAP) in modulating macrophage polarization and osteoblast differentiation. SCAPs were treated with LPS for 24 h, and sEVs from untreated (SCAP-sEVs) and LPS-treated SCAP (LPS-SCAP-sEVs) were isolated via ultracentrifugation and characterized using transmission electron microscopy, Western blot, and Tunable Resistive Pulse Sensing. LPS-SCAP-sEVs exhibited characteristic exosome morphology (~100 nm diameter) and expressed vesicular markers (CD9, CD63, CD81, and HSP70). Functional analysis revealed that LPS-SCAP-sEVs promoted M1 macrophage polarization, as evidenced by the increased pro-inflammatory cytokines (IL-6 and IL-1β) and the reduced anti-inflammatory markers (IL-10 and CD206), while impairing the M2 phenotype. Additionally, LPS-SCAP-sEVs had a minimal impact on SCAP metabolic activity or osteogenic gene expression but significantly reduced mineralization capacity in osteogenic conditions. These findings suggest that sEVs mediate the inflammatory interplay between SCAP and macrophages, skewing macrophage polarization toward a pro-inflammatory state and hindering osteoblast differentiation. Understanding this sEV-driven communication axis provides novel insights into the cellular mechanisms underlying inflammation in oral tissues and highlights potential therapeutic targets for modulating extracellular vesicle activity during acute inflammatory episodes.

Pharmacological blockade of infection chronification modulates oxy-inflammation and prevents the activation of stress-induced premature senescence markers in schistosomiasis.

Chronic inflammation, oxidative stress, and DNA damage are observed in schistosomiasis and premature aging. However, the potential of these events to trigger stress-induced premature senescence (SIPS) throughout schistosomiasis progression remains overlooked, especially in response to the first-line pharmacological treatment. Thus, we investigated the relationship between oxidative stress and SIPS sentinel markers in untreated Schistosoma mansoni-infected mice and those receiving praziquantel (Pz)-based reference treatment. Swiss mice were randomized into 5 groups: uninfected (followed by 60- and 180-days post-infection), acutely (60 days) and chronically (180 days) infected untreated, and infected treated with Pz followed until 180 days. Our results indicated that infection chronification was accompanied by the worsening of hepatic granulomatous inflammation, increased number of granulomas, IL-4, TGF-β, reactive oxygen species (ROS) levels, fibrosis, hepatocytes DNA damage, upregulation in SA-β-gal activity, p16 and p21 gene expression, and hepatocytes proliferation down-regulation in the absence of telomeric shortening. These abnormalities were blocked by Pz treatment, which prevented infection chronification and the decline in hepatocytes proliferative potential, stimulating granulomatous inflammation resolution. Taken together, our findings provide the evidence that progressive fibrosis, sustained production of high ROS levels, marked DNA damage and decline in p16 and p21 expression are associated with hepatocytes replication attenuation in the chronic phase of S. mansoni infection. Thus, pharmacological blockade of infection and granulomatous inflammation is essential to prevent these premature senescence markers associated with hepatocytes replicative disorders, stimulating liver regeneration in schistosomiasis mansoni.

Breaking Left-Right Symmetry by the Interplay of Planar Cell Polarity, Calcium Signaling and Cilia.

The formation of the embryonic left-right axis is a fundamental process in animals, which subsequently conditions both the shape and the correct positioning of internal organs. During vertebrate early development, a transient structure, known as the left-right organizer, breaks the bilateral symmetry in a manner that is critically dependent on the activity of motile and immotile cilia or asymmetric cell migration. Extensive studies have partially elucidated the molecular pathways that initiate left-right asymmetric patterning and morphogenesis. Wnt/planar cell polarity signaling plays an important role in the biased orientation and rotational motion of motile cilia. The leftward fluid flow generated in the cavity of the left-right organizer is sensed by immotile cilia through complex mechanisms to trigger left-sided calcium signaling and lateralized gene expression pattern. Disrupted asymmetric positioning or impaired structure and function of cilia leads to randomized left-right axis determination, which is closely linked to laterality defects, particularly congenital heart disease. Despite of the formidable progress made in deciphering the critical contribution of cilia to establishing the left-right asymmetry, a strong challenge remains to understand how cilia generate and sense fluid flow to differentially activate gene expression across the left-right axis. This review analyzes mechanisms underlying the asymmetric morphogenesis and function of the left-right organizer in left-right axis formation. It also aims to identify important questions that are open for future investigations.

ZNF143 binds DNA and stimulates transcription initiation to activate and repress direct target genes.

Transcription factors bind to sequence motifs and act as activators or repressors. Transcription factors interface with a constellation of accessory cofactors to regulate distinct mechanistic steps to regulate transcription. We rapidly degraded the essential and pervasively expressed transcription factor ZNF143 to determine its function in the transcription cycle. ZNF143 facilitates RNA polymerase initiation and activates gene expression. ZNF143 binds the promoter of nearly all its activated target genes. ZNF143 also binds near the site of genic transcription initiation to directly repress a subset of genes. Although ZNF143 stimulates initiation at ZNF143-repressed genes (i.e. those that increase transcription upon ZNF143 depletion), the molecular context of binding leads to cis repression. ZNF143 competes with other more efficient activators for promoter access, physically occludes transcription initiation sites and promoter-proximal sequence elements, and acts as a molecular roadblock to RNA polymerases during early elongation. The term context specific is often invoked to describe transcription factors that have both activation and repression functions. We define the context and molecular mechanisms of ZNF143-mediated cis activation and repression.

Development of a spontaneous model of renal interstitial fibrosis in NOD/SCID mice: Aging-induced pathogenesis.

Renal interstitial fibrosis, a condition prevalent in aging humans and animals, is closely linked to the eventual development of renal failure. Establishing an animal model that exactly replicates the pathogenesis of renal interstitial fibrosis induced by natural aging in humans is crucial for advancing mechanistic studies and testing antifibrotic therapies. Implanted allogeneic or xenogeneic cells are cleared by the immune system when stem cell therapy is applied in nonimmunodeficient animal fibrosis models, affecting the effect of the intervention and making it difficult to demonstrate the survival, proliferation, differentiation, or secretion of the delivered autologous human-derived cells. This study effectively developed a model of spontaneous renal interstitial fibrosis linked to natural aging in 43-week-old NOD/SCID mice. Compared with those of 12- and 32-week-old mice, the kidneys of the model mice exhibited prominent fibrosis characteristics, accompanied by numerous fibrous septa and collagen deposition, increased COL1A1 expression, and decreased MMP9 expression. SA-β-gal activity and P21 gene expression levels increased, confirming renal cell senescence in the model mice. Additionally, an increase in α-SMA staining indicated an increase in epithelial-mesenchymal transition. More importantly, we observed TGF-β-SMAD3 pathway activation, mitochondrial dysfunction, decreased antioxidant capacity, oxidative stress, and an enhanced inflammatory response in the model group, consistent with renal interstitial fibrosis in elderly individuals. In this comprehensive investigation, we successfully developed a spontaneous mouse model of renal interstitial fibrosis and revealed the molecular pathways contributing to increased susceptibility to kidney injury and renal fibrosis in elderly individuals.

Protective effects of soybean peptides on H2O2-induced oxidative injury in IPEC-J2 cells

The purpose of the study was to demonstrate how soybean peptides (SBP) protect against H2O2 -induced injury in intestinal porcine epithelial cells (IPEC-J2). SBP were prepared by protease hydrolysis, in which the molecular weights of 95.76% SBP were smaller than 3 kDa. Cell experiment included four groups: Control group (IPEC-J2 cells were treated with HGDMEM), SBP group (100 μg/mL SBP incubation for 13 h), H2O2 treatment group (1 mM H2O2 treatment for 1 h), SBP + H2O2 group (100 μg/mL SBP pretreatment for 12 h followed by 1 mM H2O2 treatment for 1 h). This study showed that that treatment with single 1 mM H2O2 for 1 h significantly reduced cell viability to 52.99% (p &amp;lt; 0.05), up-regulated Bax and Caspase-3 gene expressions (p &amp;lt; 0.05), and down-regulated gene expressions of ZO-1, CAT, SOD1, HO-1 and Nrf2 (p &amp;lt; 0.05), compared with the control group. However, pretreatment with SBP followed by H2O2 inducement significantly increased cell viability to 72.99%, decreased cell apoptosis, increased SOD, CAT and GSH-Px activity (p &amp;lt; 0.05), down-regulated Bax and Caspase-3 gene expressions (p &amp;lt; 0.05), and up-regulated the gene expressions of ZO-1, Claudin-1, Occludin, catalase, glutathione GPX1, SOD1, HO-1, NQO1 and Nrf2, compared with the single H2O2–induced cells. According to the study, SBP pretreatment reduced H2O2-induced oxidative stress in cells and preserved the integrity of intestinal cells.

Green Synthesized Silver Nanoparticles Induced Accumulation of Biomass and Secondary Metabolites in Hairy Roots of Rehmannia glutinosa.

The hairy roots of Rehmannia glutinosa (Gaertn.) Libosch. ex Fisch. & C. A. Mey. are capable of producing active compounds such as iridoid glycoside, and phenylethanoid glycosides, which have potential applications in the pharmaceutical industry. Silver nanoparticles (AgNPs) have been used as novel elicitors in the induced cultivation of hairy roots, but there is a lack of research regarding their effects on R. glutinosa hairy roots. In the present study, silver nanoparticles (Pp-AgNPs) synthesized by the endophytic fungus Penicillium polandii PG21 were adopted to elicit hairy roots of R. glutinosa, to investigate their influences on the biomass, color, secondary metabolites, antioxidant activity, sucrose metabolism, and phytohormone-related gene expression. The results revealed that the dry weight and fresh weight of R. glutinosa hairy roots were both higher in the treated group than in the control group after addition of 2 mg/L Pp-AgNPs for 20 d. The content of verbascoside, total phenylethanol glycosides and total cycloartenoid in the treatment group reached the highest level at 20 d, which were 1.75, 1.51, 1.44 times more than those in the control group, respectively. Pp-AgNPs significantly stimulated the enzyme activities of catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD). The growth-promoting effect of Pp-AgNPs may be accomplished by increasing sucrose metabolism, and regulating the synthesis and signal transduction of gibberellin (GA) and indoleacetic acid (IAA). Moreover, expressed sequence tags-simple sequence repeat (EST-SSR)-based genetic diversity analyses indicated that there was little possibility of genetic variation among samples under different treatment conditions. In conclusion, the appropriate concentration of Pp-AgNPs can be used as an effective elicitor to improve the biomass and secondary metabolites content in R. glutinosa hairy roots.

Toxicity comparison of polylactic acid and polyethylene microplastics co-exposed with methylmercury on Daphnia magna

The prevalence of microplastics (MPs) in aquatic ecosystems has become a significant environmental concern due to their persistence and potential toxicity. Although bioplastics, such as polylactic acid (PLA), are promoted as eco-friendly alternatives to conventional plastics, their toxicity remains poorly understood. This study compares the toxicity and pollutant vector roles of polar PLA-derived bio-microplastics (bio-MPs) with apolar low-density polyethylene (LDPE) MPs, both individually and in combination with methylmercury (MeHg), in Daphnia magna. PLA bio-MPs, both alone and in combination with MeHg, significantly reduced survival rates and reproduction while inducing oxidative stress. Additionally, PLA bio-MPs increased Hg accumulation and negatively impacted acetylcholinesterase activity and vitellogenin gene expression compared to LDPE MPs. The findings of this study suggest that PLA bio-MPs, despite being in vivo biodegradable, may pose similar or even greater environmental risks than fossil fuel-based MPs, particularly due to their potential to enhance the bioaccumulation and toxicity of coexisting pollutants.

Unveiling the HSF1 Interaction Network: Key Regulators of Its Function in Cancer.

Heat shock factor 1 (HSF1) plays a central role in orchestrating the heat shock response (HSR), leading to the activation of multiple heat shock proteins (HSPs) genes and approximately thousands of other genes involved in various cellular functions. In cancer cells, HSPs play a particular role in coping with the accumulation of damaged proteins resulting from dysregulated translation and post-translational processes. This proteotoxic stress is a hallmark of cancer cells and causes constitutive activation of HSR. Beyond its role in the HSR, HSF1 regulates diverse processes critical for tumor cells, including proliferation, cell death, and drug resistance. Emerging evidence also highlights HSF1's involvement in remodeling the tumor immune microenvironment as well as in the maintenance of cancer stem cells. Consequently, HSF1 has emerged as an attractive therapeutic target, prompting the development of specific HSF1 inhibitors that have progressed to clinical trials. Importantly, HSF1 possesses a broad interactome, forming protein-protein interactions (PPIs) with components of signaling pathways, transcription factors, and chromatin regulators. Many of these interactors modulate HSF1's activity and HSF1-dependent gene expression and are well-recognized targets for cancer therapy. This review summarizes the current knowledge on HSF1 interactions with molecular chaperones, protein kinases, and other regulatory proteins. Understanding the key HSF1 interactions promoting cancer progression, along with identifying factors that disrupt these protein complexes, may offer valuable insights for developing innovative therapeutic strategies against cancer.

Application of glucose to prepare Aspergillus oryzae koji as an adjunct to prevent rancidity in cheese products.

Koji made using Aspergillus oryzae shows potential for application as a cheese adjunct; however, flavor defects resulting from volatile free fatty acid (FFA) accumulation should be avoided. Hence, a modified glucose-containing whey solid medium was used to culture A. oryzae AHU 7139, and the triacylglycerol (TG) lipase activity and lipase gene (tglA and mdlB) expression were compared with those of a culture using a conventional whey solid medium. The results showed that TG lipase activity and the expression of both lipase genes were reduced in the modified medium. Moreover, the expression level of farA, a positive transcription factor of the lipase genes, was also reduced. The cheese adjunct prepared by culturing the AHU 7139 strain in the modified medium lowered the FFA content in the cheese products, resulting in comparable FFA levels with those in the adjunct-free cheese. Thus, adding glucose is recommended to prepare the koji adjunct for cheesemaking.

Physiology and Metabolism Alterations in Flavonoid Accumulation During Buckwheat (Fagopyrum esculentum Moench.) Sprouting.

In this research, we investigated the physiological modifications, flavonoid metabolism, and antioxidant systems of two buckwheat (Fagopyrum esculentum Moench.) cultivars, Pintian and Suqiao, during germination. The results demonstrated an initial increase followed by a subsequent decline in the flavonoid content of the buckwheat sprouts throughout germination. On the third day of germination, the highest flavonoid concentrations were observed, with the Pintian and Suqiao varieties reaching 996.75 and 833.98 μg/g fresh weight, respectively. Both the activity and relative gene expression level of the flavonoid metabolizing enzyme showed a significant rise in 3-day-old buckwheat sprouts, which was strongly correlated with the flavonoid content. The correlation analysis revealed that the buckwheat sprouts accumulated flavonoids by enhancing the activities and gene expression levels of flavonoid synthases. The antioxidant capacity and the activities and gene expression profiles of the antioxidant enzymes in both buckwheat cultivars notably increased after three days of germination. The correlation analysis indicated a significant positive link between antioxidant capacity and the activity and gene expression levels of the antioxidant enzymes, flavonoid content, and total phenol content. This research demonstrated that germination treatment can significantly boost the accumulation of flavonoids and total phenols, thereby enhancing the antioxidant properties of buckwheat sprouts, despite variations among different buckwheat varieties.

Decreased prefrontal glutamatergic function is associated with a reduced astrocyte-related gene expression in treatment-resistant depression

Glutamatergic dysfunction is involved in the pathophysiology of treatment-resistant depression (TRD). However, few physiological studies have evaluated its pathophysiology in vivo in individuals with TRD. Transcranial magnetic stimulation-electroencephalography (TMS-EEG) techniques can assess intracortical facilitation (ICF), which reflects glutamatergic neurophysiological function in specific cortical regions. The objectives of this study were (1) to compare glutamatergic receptor-mediated function as indexed with ICF TMS-EEG in the dorsolateral prefrontal cortex (DLPFC) between participants with TRD and healthy controls (HCs) and (2) to explore the relationships between cell-specific gene expression levels and the group difference in glutamatergic neural propagation using virtual histology approach. Sixty participants with TRD and thirty HCs were examined with ICF TMS-EEG measure (80 single-pulse TMS and paired-pulse ICF) in the left DLPFC. Both sensor and source-level ICF measures were computed to compare them between the TRD and HC groups. Furthermore, we conducted spatial correlation analyses interregionally between ICF glutamatergic activity and cell-specific gene expression levels employing the Allen Human Brain Atlas dataset. DLPFC-ICF at the sensor level was not significantly different between the two groups, whereas DLPFC-ICF at the source level was reduced in the TRD group compared with the HC group (p = 0.026). Moreover, the reduced ICF signal propagation of TRD correlated with astrocyte-specific gene expression level (p < 0.0001). The glutamatergic neural activities indexed by ICF in the left DLPFC were decreased in participants with TRD. Additionally, a relative reduction in glutamatergic signal propagation originating from the DLPFC in TRD may be associated with astrocytic abnormality.

Bisphenol B Exposure Promotes Melanoma Progression via Dysregulation of Lipid Metabolism in C57BL/6J Mice.

The increasing incidence of cancer underscore the necessity of investigating contributors such as endocrine-disrupting chemicals (EDCs), including bisphenol A (BPA). Although BPA's risks are well-documented, comprehensive studies on its substitutes, such as bisphenol B (BPB), are limited. Dysregulated lipid metabolism is a hallmark of cancer progression. Our previous work demonstrated that BPA and bisphenol S (BPS) disrupt lipid metabolism via the peroxisome proliferator-activated receptor γ (PPARγ) pathway. We hence hypothesized that BPB might similarly perturb lipid metabolism and promote tumor growth. BPB's impact on lipid metabolism was investigated invitro and invivo using B16 melanoma cancer cells. Our findings indicate BPB exposure significantly increased lipid metabolism in B16 cells, enhancing cell proliferation and migration, and promoting tumor development in mice. Utilizing siRNA transfection or chemical inhibitor, we found that stearoyl-CoA desaturase-1 (SCD1), a key enzyme in lipid synthesis pathway, was required for BPB-induced lipid accumulation and cancer cell migration. Docking analysis revealed BPB may activate gene expression related to lipid metabolism and angiogenesis by interacting with PPARγ and hypoxia-inducible factor-1α (HIF-1α). This study illuminates BPB's potential role in advancing melanoma through lipid metabolism manipulation, highlighting the need for further research into the safety of BPA substitutes and their impact on cancer development.