Abnormal Swelling Research Articles

Phenylmercury stress induces root tip swelling through auxin homeostasis disruption

We previously reported that in Arabidopsis, the phytochelatin-mediated metal-detoxification machinery is also essential for organomercurial phenylmercury (PheHg) tolerance. PheHg treatment causes severe root growth inhibition in cad1-3, an Arabidopsis phytochelatin-deficient mutant, frequently accompanied by abnormal root tip swelling. Here, we examine morphological and physiological characteristics of PheHg-induced abnormal root tip swelling in comparison to Hg(II) stress and demonstrate that auxin homeostasis disorder in the root is associated with the PheHg-induced root tip swelling. Both Hg(II) and PheHg treatments severely inhibited root growth in cad1-3 and simultaneously induced the disappearance of starch-containing plastid amyloplasts in columella cells. However, further confocal imaging of the root tip revealed distinct effects of Hg(II) and PheHg toxicity on root cell morphology. PheHg treatment suppressed most major genes involved in auxin homeostasis, whereas these expression levels were up-regulated after 24 h of Hg(II) treatment. PheHg-triggered suppression of auxin transporters PIN1, PIN2, and PIN3 as GFP-fusion proteins was observed in the root tip, accompanied by an auxin reporter DR5rev::GFP signal reduction. Supplementation of indole-3-acetic acid (IAA) drastically canceled the PheHg-induced root swelling, however, Hg(II) toxicity was not mitigated by IAA. The presented results show that the collapse of auxin homeostasis especially in root tips is a cause for the abnormal root tip swelling under PheHg stress conditions.

Percutaneous Sclerotherapy of Cystic Lesions at Kenyatta National Hospital: Indications, Outcomes, Efficacy, and Complications

Background: Percutaneous sclerotherapy is a minimally invasive treatment for cystic lesions and has emerged as a preferred alternative to traditional surgical methods due to its faster recovery times and lower complication rates. A sclerosing agent is instilled into the lesion causing cyst wall inflammation and lesion shrinkage. It has a significant role in managing cystic lesions, with better health outcomes. Objectives: To evaluate the indications, outcomes, efficacy, and complications of percutaneous sclerotherapy in the management of cystic lesions. Methodology: The study was a prospective cross-sectional study involving patients with cystic lesions referred for percutaneous sclerotherapy. Data was collected, analyzed, and presented in percentages, graphs, tables. Technical and clinical success rates were calculated. Efficacy was analyzed using chi-square test. Results: 27 patients with cystic lesions were treated. Most were females (77.8%), and males (22.2%), with a male-to-female ratio of 1:3.5. The commonest indication was pain (26.1%), followed by pressure symptoms (22.7%) and abnormal swelling (20.5%). Most lesions were located in the liver (25.9%), followed by the kidney (18.5%). Majority had significant improvement in clinical symptoms and size reduction with p-values < 0.05. The technical success rate was 100% and the clinical success rate was 96.3%. Minor complications were encountered including mild pain (7.4%), catheter blockage, cyst abscess formation, catheter insertion site infection, and inflammatory cyst septations (each 3.7%). Conclusion: Percutaneous sclerotherapy is a safe, efficacious treatment of cystic lesions with a high technical and clinical success rate. It should be considered as a first line of treatment for cystic lesions.

Nynrin preserves hematopoietic stem cell function by inhibiting the mitochondrial permeability transition pore opening

Mitochondria are key regulators of hematopoietic stem cell (HSC) homeostasis. Our research identifies the transcription factor Nynrin as a crucial regulator of HSC maintenance by modulating mitochondrial function. Nynrin is highly expressed in HSCs under both steady-state and stress conditions. The knockout Nynrin diminishes HSC frequency, dormancy, and self-renewal, with increased mitochondrial dysfunction indicated by abnormal mPTP opening, mitochondrial swelling, and elevated ROS levels. These changes reduce HSC radiation tolerance and promote necrosis-like phenotypes. By contrast, Nynrin overexpression in HSCs diminishes irradiation (IR)-induced lethality. The deletion of Nynrin activates Ppif, leading to overexpression of cyclophilin D (CypD) and further mitochondrial dysfunction. Strategies such as Ppif haploinsufficiency or pharmacological inhibition of CypD significantly mitigate these effects, restoring HSC function in Nynrin-deficient mice. This study identifies Nynrin as a critical regulator of mitochondrial function in HSCs, highlighting potential therapeutic targets for preserving stem cell viability during cancer treatment.

Stress-related physiological responses and ultrastructural changes in Hypoxis hemerocallidea leaves exposed to cadmium and aluminium

Hypoxis hemerocallidea is a medicinal plant containing hypoxoside (a pharmacologically active phytosterol diglucoside). This study evaluated the elemental composition in leaves of H. hemerocallidea treated with cadmium (Cd) and aluminium (Al) using scanning electron microscopy (SEM) combined with energy-dispersive X-ray spectroscopy (EDX). The impact of Cd and Al on photosynthetic pigments and performance, antioxidant activities and ultrastructure were also assessed. Corms of H. hemerocallidea were micropropagated, rooted and then exposed to varying concentrations of Cd, Al, and Cd + Al for six weeks. The SEM/EDX analysis indicated a two-fold increase in carbon content across all treated plants compared to the control. No/little Cd was detected in the leaves compared to a progressive increase in Al concentration with increasing Al treatment levels. This indicted that Al is more readily translocated to the shoots compared to Cd. Plants treated with Cd exhibited a significant decrease in total chlorophyll content accompanied by reduced photosynthetic performance and lower relative electron transport rates. Cd and Al exposure led to higher carotenoid, superoxide dismutase and malondialdehyde levels, indicating oxidative stress. Cd-treated plants displayed increased amylase activity and decreased carbohydrates content. Ultrastructural alterations occurred with exposure to Cd and Al, including abnormal swelling or disintegration of chloroplasts and thylakoid degeneration. An increase in starch grains and a decrease in plastoglobuli were also noted. In conclusion, this investigation provides evidence that both Cd and higher concentrations of Al exert detrimental effects on the ultrastructure, metabolism and photosynthetic performance of H. hemerocallidea, contributing to reduced growth and biological activity when stressed.

Emergency Department Triage Chief Complaints Among Children Evaluated for Physical Abuse Concerns.

The aims of this study were to describe chief complaints provided at emergency department triage for young children ultimately given a diagnosed with injuries concerning for physical abuse and compare chief complaints by hospital child protection team assessment (abuse most likely, accident most likely, undetermined) among children younger than 2 years who were the subject of a report to child protective services. This is a retrospective review of children evaluated by the child protection team at an urban children's hospital over a 5-year period. Children younger than 2 years who were the subject of a report to child protective services for suspected physical abuse were included. Chief complaints noted in emergency department triage notes were categorized as follows: 1, medical sign or symptom; 2, accidental trauma incident; 3, identified injury; 4, concern for abuse; or 5, multiple unrelated complaints. Child protection team assessments were categorized as follows: 1, abuse most likely; 2, accident most likely; or 3, undetermined. We used descriptive statistics and tests of association (χ 2 , Fisher exact, Kruskal-Wallis). Median age of the 422 children included was 4.9 months. Child protection team assessment was abuse most likely in 44%, accident most likely in 23%, and undetermined in 34%. Chief complaints in the overall sample were 39% medical, 29% trauma incident, 16% injury, 10% abuse concern, and 6% multiple unrelated. When the abuse most likely and accident most likely groups were compared, medical chief complaints were more common in the former (47% vs 19%, P < 0.001), whereas trauma incident chief complaints were more common in the latter (19% vs 64%, P < 0.001). Most common medical complaints in the abuse most likely group were altered mental status, abnormal limb use, swelling, pain, apnea, and vomiting. Many children found to have injuries concerning for abuse (47%) present without mention of trauma, injury, or abuse concern as part of the chief complaint. Our findings suggest important topics to include in training physicians about recognition of abuse.

Brain Tumor Detection using Deep Learning

Abstract: A tumor is an abnormal swelling or growth that is caused by the division of the cells in the nervous system. A brain tumor is one of the most dangerous types of tumors. There are four different types of brain tumor. The treatment for brain tumors is determined by the type, grade, and locationof the tumor. If the tumor is not detected early, it can be fatal. MRI images are used to diagnose brain tumors. The accuracy of the results depends on the expertise and domain knowledge of the experts, and it is also a very time-consuming and costly process. In order to overcome these limitations, several deep learning algorithms for the detection of brain tumors have been proposed.

Abnormal swelling in water of carboxylic ion exchanger in the forms of ammonium and tetraethylammonium ions

A fibrous carboxylic ion exchanger, obtained by post-radiation grafting of polyacrylic acid to polypropylene fiber, in the ammonium form has an abnormally low swelling in water, corresponding to 10 moles of water per equivalent, and in the form of tetraethylammonium ion (NEt4+) – abnormally high 25 moles of water/eq. Considering that NH4+ is a hydrophilic particle and NEt4+ is hydrophobic, this fact seems paradoxical. The article attempts to explain this phenomenon using molecular modeling (ab initio calculations of the structure of hydrate complexes in the HF MO LCAO approximation with the 6-31G basis set) in combination with the Predominant Hydrates Model, which made it possible to calculate the theoretical water sorption isotherms of the ion exchanger and compare them with experimental data. The abnormally low swelling of the ion exchanger in the NH4+-form is caused by the formation of a strong bond between the carboxylate anion and ammonium with a significant degree of covalence due to the superposition of the Coulomb interaction of the ions and the formation of a hydrogen bond between them. The abnormally high swelling of NEt4+-forms is caused by the absence of a strong interaction between cations and carboxylate groups due to the impossibility of their convergence due to steric reasons. The high swelling of the ion exchanger is caused by the absence of blocking of the hydrophilic carboxylate groups of the ion exchanger by hydrogen bonds with the cation. The ion exchanger matrix does not contain a cross agent and does not create a spatial restriction for the high swelling of the ion exchanger.

Indications, Outcomes, Efficacy, and Complications of Percutaneous Sclerotherapy in the Management of Hemangiomas at Kenyatta National Hospital

Background The effective management of hemangiomas using percutaneous sclerotherapy optimizes desired clinical outcomes and minimizes the associated complications in affected patients. Intra-lesional sclerotherapy involves injecting a sclerosing agent (such as bleomycin and sodium tetradecyl sulfate) into a lesion or the interstitial space around the lesion, causing endothelial injury, thrombosis, inflammation, scarring, and shrinkage of the lesion. Extensive literature suggests that sclerotherapy has a role in the management of hemangiomas, as demonstrated by better health outcomes and improved quality of life among affected patients. Objectives To evaluate the indications, outcomes, efficacy, and complications of percutaneous intra-lesional sclerotherapy in the management of hemangiomas. Materials and methods The study was a prospective cross-sectional study, conducted at a level 6 National Referral Hospital Interventional Radiology Unit. Patients with hemangiomas referred for intralesional sclerotherapy were treated. Data including the indications of intra-lesional sclerotherapy, short-term outcomes, complications were collected, analyzed, and presented in percentages, graphs, pie charts, tables. Technical and clinical success rates were calculated. The efficacy of intralesional sclerotherapy was analyzed using chi-square test. Results A total of 20 patients with hemangiomas were treated. There were 11 females comprising 55% and 9 males comprising 45% with a male to female ratio of 1:1.2. The commonest indication for referral was pain (21.6%), followed by abnormal swelling (18.9%). Most lesions were located in the liver comprising 25%. Other locations included the hand, cheek, lower lip, lower extremities (calf, distal leg, foot, and thigh), lumbar region, posterior thoracic back region and abdomen mesenteric region. Majority of the patients had significant improvement of clinical symptoms with a p-value &lt;0.05. Similarly, there was a statistically significant reduction in the sizes of the lesions treated with a p-value of &lt;0.05. The technical success rate was 100% and the overall clinical success rate was 90%. Mild pain (10%), mild edema (10%) and skin discoloration (5%) were the commonest minor complications encountered, with no major complications. Conclusion Percutaneous intralesional sclerotherapy is a safe and efficacious treatment of hemangiomas with a high technical and clinical success rate. It should be considered as a first line of treatment for the hemangiomas.

10252-COT-27 TWO CASES OF OVARIAN HYPERSTIMULATION SYNDROME IN A YOUNG FEMALE PATIENTS WITH GLIOMA WHO UNDERWENT OOCYTE CRYOPRESERVATION.

Abstract Young women with malignant gliomas may wish to have their oocytes preserved prior to the start of chemotherapy in order to maintain fertility. In such cases, fertility drugs make it possible to mature and retrieve multiple oocytes in the ovaries. However, the ovaries may overreact and mature many oocytes at once, resulting in adverse symptoms such as abnormal swelling of the ovaries, abdominal discomfort and pain, nausea and vomiting, abdominal distention, fluid retention (edema), and difficulty breathing. This is called ovarian hyperstimulation syndrome (OHSS), in which excessive secretion of estradiol associated with multiple follicle development leads to excessive production of VEGF, which rapidly increases the vascular permeability of systemic organs, resulting in a fluid shift into the third space, which is thought to cause ascites and pulmonary edema. In severe cases, intravascular dehydration and decreased circulating plasma volume can cause hypotension and oliguria, and the increased coagulation capacity associated with hemoconcentration can cause serious thrombotic complications. The severity of OHSS is classified into three levels: mild, moderate, and severe, based on four findings: subjective symptoms, the amount of pleural effusion, the degree of ovarian enlargement (ovarian diameter), and blood test findings. Early detection and appropriate management are essential. We have had two cases of OHSS, one of which was moderate and resolved successfully, while the other became severe, and we had to postpone the start of radiotherapy for a week longer than planned. Severe OHSS is a medical complication that neurosurgeons rarely encounter, and we report this case with a literature review.

VdTps2 modulates plant colonization and symptom development in Verticillium dahliae.

The trehalose biosynthesis pathway is a potential target for antifungal drugs development. Trehalose phosphate synthase/phosphatase (TPS/TPP) are widely conserved components of trehalose biosynthesis in fungi. However, the role of trehalose biosynthesis in the vascular plant pathogenic fungus Verticillium dahliae remains unclear. Here, we investigated the functions of the TPS complex, including VdTps1, VdTps2, and VdTps3 in V. dahliae. Unlike VdTps2, deletion of VdTps1 or VdTps3 did not alter any phenotypes compared with the wild-type strain. In contrast, the ΔVdTps2 strain showed severely depressed radial growth due to the abnormal swelling of the hyphal tips. Further, deletion of VdTps2 increased microsclerotia formation, melanin biosynthesis, and resistance to cell wall perturbation and high-temperature stress. Virulence assays and quantification of fungal biomass revealed that deletion of VdTps2 delayed disease symptom development as evident by the reduced virulence and decreased biomass of the ΔVdTps2 strain in plant stem tissue following inoculation. Additionally, increases in penetration peg formation observed in the ΔVdTps2 strain in the present of H2O2 suggested that VdTps2 suppresses initial colonization. Our results also revealed the role of VdTps2 as a regulator of autophagy. Together, these results indicate that VdTps2 contributes to plant colonization and disease development.

Solvent-exchange triggered hydrogen bond activation strategy toward self-adaptive strong and tough organohydrogel artificial muscle

Hydrogel actuators have aroused tremendous interests in various fields such as artificial muscles, biomedicine and wearable devices. However, hydrogel actuators face persistent challenges due to their intrinsic weak and hydrophilic networks, which result in brittle and weak mechanical properties after swelling. Here, we proposed a solvent-exchange hydrogen bond activation strategy to fabricate a highly strong and tough self-adaptive organohydrogel actuators (SOA). The glycerol releasing and water retention triggers abnormal swelling of SOA due to the cross-linking of tannic acid (TA) and polyvinyl alcohol (PVA) nanofibrillar network. After the hydrogen bond activation between PVA and TA, SOA shows a denser and porous nanofibrillar network with high tensile strength (5.4 ± 0.2 MPa), high fracture energy (134.9 ± 7.6 kJ/m2), and high toughness (18.5 ± 0.7 MJ/m3). Owing to its good processibility, an anisotropic multi-filament twisted fiber actuator that exhibits ultra-high modulus (83.5 ± 2.6 MPa) and humidity-sensitive actuation performance was developed. The proposed solvent-exchange strategy shows great potential for the rational design and fabrication of bionic strong and tough artificial muscles.

Clinical outcomes of periodontal regenerative therapy with carbonate apatite granules for treatments of intrabony defects, Class II and Class III furcation involvements: A 9-month prospective pilot clinical study

IntroductionCarbonated apatite (CO3Ap) has unique properties as an alloplastic bone substitute and has been reported the safety and efficacy for bone regeneration. However, no previous studies reported the clinical application of CO3Ap for periodontal regeneration therapy. The aim of this study was to evaluate the safety and efficacy of periodontal regeneration with CO3Ap in treating intrabony defects, Class II and Class III furcation involvement (FI). MethodsA single-arm and single-center prospective pilot clinical study was performed to verify the safety and efficacy of CO3Ap in patients with periodontitis. A total of four patients with seven teeth, including three deep intrabony defects, two Class II FI, and two Class III FI, were treated with CO3Ap. The clinical parameters, including probing pocket depth (PPD), clinical attachment level (CAL), bleeding on probing (BOP), tooth mobility (Mo), Plaque index (PI), and Gingival index (GI) were evaluated at baseline, 6 months, and 9 months after the surgery. Radiographic analysis was conducted on images of dental X-ray and cone beam computed tomography (CBCT) at baseline and 9 months post-surgery. ResultsThe postoperative healing in all cases was uneventful, with no abnormal bleeding, pain, or swelling. The mean PPD reduction and CAL gain were 5.0 ± 1.0 mm, 4.5 ± 0.7 mm, 1.5 ± 0.7 mm, and 4.7 ± 1.2 mm, 4.5 ± 0.7 mm, 0.0 mm for intrabony defect, Class II and Class III FI, respectively. According to radiographic analysis, linear bone height in intrabony defects and vertical subclassification of FI in Class II FI were improved. ConclusionsThe clinical application of CO3Ap for the treatment of intrabony defects and Class II FI could be effective for periodontal regeneration, although its efficacy in treating Class III FI might be limited. Despite the limitations of this study, the findings in this study suggested that CO3Ap has the potential to be a promising bone graft substitute for periodontal regeneration.

Clock genes regulate skeletal muscle energy metabolism through NAMPT/NAD+/SIRT1 following heavy-load exercise.

The biological clock is an invisible "clock" in the organism, which can regulate behavior, physiology, and biochemical reactions. However, the relationship between clock genes and energy metabolism in postexercise skeletal muscle is not well known. The purpose of this study was to determine the mechanisms through which peripheral clock genes regulate energy metabolism in skeletal muscle. We analyzed the rhythm of mRNA expression of the clock genes Bmal1 and Clock in skeletal muscle following heavy-load exercise and measured related indicators of mitochondrial structure and function. We obtained the following experimental results. First, heavy-load exercise induced loss of circadian rhythm of Bmal1 between ZT0 and ZT24, and the circadian rhythm of Clock was not restored between ZT0 and ZT72. Second, analysis of mitochondrial morphology in group E showed abnormal swelling and ridge structure damage at ZT0, which recovered somewhat at ZT24 and ZT48, and the damage had essentially disappeared by ZT72. Third, the expression of NAMPT/NAD+/SIRT1 signaling axis proteins in group E was abnormal at ZT0, the content of NAMPT and the activity of SIRT1 significantly increased, and the content of NAD+ significantly decreased. Fourth, the expression of BMAL1 and PGC-1α in group E significantly increased, whereas the ATP and ADP content, as well as the activities of COXII and COXIV, were significantly changed. Finally, the colocalization of BMAL1 and SIRT1 in group E was significantly upregulated at ZT0. These results suggest that the skeletal muscle clock gene Bmal1 may regulate the energy metabolism level of skeletal muscle after exercise through the NAMPT/NAD+/SIRT1 signaling pathway.

Abnormal Thigh Swelling after Anterior Cruciate Ligament Reconstruction with Tourniquet

Background: Anterior cruciate ligament (ACL) reconstruction surgery is a common orthopedic procedure. Minimally invasive surgeries and arthroscopy are becoming more common, and tourniquets are utilized in these procedures to reduce bleeding and allow for improved tissue visualization.&#x0D; Case Report: In this paper, we report a 32-year-old man who underwent the right knee ACL reconstruction using a tourniquet following trauma. He developed thigh swelling at the tourniquet site after surgery. Right thigh ultrasound and magnetic resonance imaging (MRI) indicated extensive interstitial edema in all compartments without collection, hematoma, or hemorrhage. The patient was treated with dexamethasone and Lasix for four days. Rehabilitation activities included exercises to improve range of motion (ROM), strength exercises, and a home workout routine. Two weeks after discharge, the swelling decreased by about 80%.&#x0D; Conclusion: We believe that using a tourniquet during the reconstruction surgery may be responsible for the extensive edema in the limb. However, despite several diagnostic methods, we could not explain the reason for the edema in the limb following surgery.

Isothermal reduction kinetics and microstructure evolution of various vanadium titanomagnetite pellets in direct reduction

Vanadium titanomagnetite (VTM) pellets is an important charge for utilizing VTM through the rotary kiln-electric furnace process, and its reduction characteristic is essential to industrial production. This paper investigated the reduction behaviors and mechanism of three types of fired VTM pellets, i.e. PA, PB and PC with 13.02%, 11.70% and 5.25% TiO2, respectively. Under the optimal conditions, which were reduced at 1423 K for 150, 120 and 100 min, respectively, they obtained more than 90% reduction degree. During reduction, PA exhibited excellent resistance to volume swelling and great morphology, while PB and PC displayed abnormal swelling and structural damage. Kinetic and microstructure studies indicated that the reduction of PA, which consisted of titanohematite and pseudobrookite, was controlled by the random nucleation and subsequent growth of metallic iron, whereas that of PB and PC, which mainly contained titanohematite, was controlled by intrinsic chemical reactions. Iron- and titanium-bearing oxides were reduced to metallic iron via two routes: titanohematite → titanomagnetite → wustite → metallic iron and pseudobrookite → metallic iron. These various compositions and grain sizes of iron- and titanium-bearing oxides led to different generation rates and morphologies of metallic iron, directly affecting the reduction characteristics and macroscopic performance of VTM pellets.

Atlanto‐occipital subluxation in an adult Thoroughbred gelding

SummaryA 13‐year‐old gelding was referred to the University of Liverpool Equine Hospital for further investigation of ataxia and neck pain following a suspected traumatic incident in the field 5 days prior. The following case report documents the clinical presentation, ultrasonographic, radiographic and computed tomographic (CT) findings of a right lateral atlanto‐occipital (AO) subluxation. In brief, clinical presentation included abnormal head carriage, ataxia and cranial cervical swelling with associated neck pain. Radiography showed lateral deviation of the poll and subluxation of the right AO joint with significant widening of the left AO joint. CT was undertaken standing which confirmed lateral luxation of the right occipital condyle in relation to the right articular process of the AO joint such that the right articular process of the atlas was located medial to the right occipital condyle. The gelding was subjected to euthanasia and post‐mortem the subluxation was resolved with a closed traction procedure. This case initiates discussion of diagnosis, management and outcome for this uncommon injury. The use of CT in this case gives previously undocumented detail on the nature of the subluxation and assisted in the management and post‐mortem closed reduction procedure.

Abscisic Acid Inhibits Cortical Microtubules Reorganization and Enhances Ultraviolet-B Tolerance in Arabidopsis thaliana.

Ultraviolet-B (UV-B) radiation is one of the important environmental factors limiting plant growth. Both abscisic acid (ABA) and microtubules have been previously reported to be involved in plant response to UV-B. However, whether there is a potential link between ABA and microtubules and the consequent signal transduction mechanism underlying plant response to UV-B radiation remains largely unclear. Here, by using sad2-2 mutant plants (sensitive to ABA and drought) and exogenous application of ABA, we saw that ABA strengthens the adaptive response to UV-B stress in Arabidopsis thaliana (A. thaliana). The abnormal swelling root tips of ABA-deficient aba3 mutants demonstrated that ABA deficiency aggravated the growth retardation imposed by UV-B radiation. In addition, the cortical microtubule arrays of the transition zones of the roots were examined in the aba3 and sad2-2 mutants with or without UV-B radiation. The observation revealed that UV-B remodels cortical microtubules, and high endogenous ABA can stabilize the microtubules and reduce their UV-B-induced reorganization. To further confirm the role of ABA on microtubule arrays, root growth and cortical microtubules were evaluated after exogenous ABA, taxol, and oryzalin feeding. The results suggested that ABA can promote root elongation by stabilizing the transverse cortical microtubules under UV-B stress conditions. We thus uncovered an important role of ABA, which bridges UV-B and plants' adaptive response by remodeling the rearrangement of the cortical microtubules.

Amyloid-β accumulation in human astrocytes induces mitochondrial disruption and changed energy metabolism

BackgroundAstrocytes play a central role in maintaining brain energy metabolism, but are also tightly connected to the pathogenesis of Alzheimer’s disease (AD). Our previous studies demonstrate that inflammatory astrocytes accumulate large amounts of aggregated amyloid-beta (Aβ). However, in which way these Aβ deposits influence their energy production remain unclear.MethodsThe aim of the present study was to investigate how Aβ pathology in astrocytes affects their mitochondria functionality and overall energy metabolism. For this purpose, human induced pluripotent cell (hiPSC)-derived astrocytes were exposed to sonicated Aβ42 fibrils for 7 days and analyzed over time using different experimental approaches.ResultsOur results show that to maintain stable energy production, the astrocytes initially increased their mitochondrial fusion, but eventually the Aβ-mediated stress led to abnormal mitochondrial swelling and excessive fission. Moreover, we detected increased levels of phosphorylated DRP-1 in the Aβ-exposed astrocytes, which co-localized with lipid droplets. Analysis of ATP levels, when blocking certain stages of the energy pathways, indicated a metabolic shift to peroxisomal-based fatty acid β-oxidation and glycolysis.ConclusionsTaken together, our data conclude that Aβ pathology profoundly affects human astrocytes and changes their entire energy metabolism, which could result in disturbed brain homeostasis and aggravated disease progression.

Transcriptome profiling reveals the underlying mechanism of grape post-harvest pathogen Penicillium olsonii against the metabolites of Bacillus velezensis.

Pathogen infection influences the post-harvest shelf life of grape berries. In a preliminary study, metabolites produced by Bacillus velezensis significantly inhibited the growth of the grape postharvest pathogen Penicillium olsonii. To investigate the mechanism of interaction between B. velezensis and P. olsonii, a draft genome was generated for P. olsonii WHG5 using the Illumina NovaSeq platform, and the transcriptomic changes in WHG5 were analyzed in response to the exposure to B. velezensis metabolites (10% v/v). The expression levels of genes associated with sporulation, including GCY1, brlA, and abaA, were down-regulated compared with those of the control. In addition, spore deformation and abnormal swelling of the conidiophore were observed. The expression of crucial enzymes, including fructose 2,6-bisphosphate and mannitol-2-dehydrogenase, was down-regulated, indicating that the glycolytic pathway of WHG5 was adversely affected by B. velezensis metabolites. The KEGG pathway enrichment analysis revealed that glutathione metabolism and the antioxidant enzyme system were involved in the response to B. velezensis metabolites. The down-regulation of the pathogenesis-related genes, PG1 and POT1, suggested that B. velezensis metabolites decreased the pathogenicity of P. olsonii. B. velezensis metabolites disrupted the homeostasis of reactive oxygen species in P. olsonii by affecting glucose metabolism, resulting in spore deformation and disruption of growth. In addition, the expression of key pathogenesis-related genes was down-regulated, thereby reducing the pathogenicity of P. olsonii. This study provides insights into the responses of P. olsonii to B. velezensis metabolites and identifies potential target genes that may be useful in biocontrol strategies for the suppression of post-harvest spoilage in grapes.

Lymphatic endothelial cell RXRα is critical for 9-cis-retinoic acid-mediated lymphangiogenesis and prevention of secondary lymphedema.

Secondary lymphedema is a debilitating disease characterized by abnormal soft tissue swelling and caused by lymphatic system dysfunction. Despite a high prevalence of secondary lymphedema after cancer treatments, current management is supportive and there are no approved therapeutic agents that can thwart disease progression. We have previously demonstrated that 9-cis-retinoic acid (9-cisRA) has the potential to be repurposed for lymphedema as it mitigates disease by promoting lymphangiogenesis at the site of lymphatic injury. Although the efficacy of 9-cisRA has been demonstrated in previous studies, the mechanism of action is not completely understood. In this study, we demonstrate that when RXRα is specifically deleted in lymphatic endothelial cells, 9-cisRA fails to induce lymphangiogenesis in vitro and prevent pathologic progression of postsurgical lymphedema in vivo. These findings demonstrate that downstream nuclear receptor RXRα plays a critical role in the therapeutic efficacy of 9-cisRA in postsurgical lymphedema.