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Biotechnology Progress Jun 2024Demand for monoclonal antibodies (mAbs) is rapidly increasing. To achieve higher productivity, there have been improvements to cell lines, operating modes, media, and...
Demand for monoclonal antibodies (mAbs) is rapidly increasing. To achieve higher productivity, there have been improvements to cell lines, operating modes, media, and cultivation conditions. Representative mathematical models are needed to narrow down the growing number of process alternatives. Previous studies have proposed mechanistic models to depict cell metabolic shifts (e.g., lactate production to consumption). However, the impacts of variations of some operating conditions have not yet been fully incorporated in such models. This paper offers a new mechanistic model considering variations in dissolved oxygen and glutamine depletion on cell metabolism applied to a novel Chinese hamster ovary (CHO) cell line. Expressions for the specific rates of lactate production, glutamine consumption, and mAb production were formulated for stirred and shaken-tank reactors. A deeper understanding of lactate metabolic shifts was obtained under different combinations of experimental conditions. Lactate consumption was more pronounced in conditions with higher DO and low glutamine concentrations. The model offers mechanistic insights that are useful for designing advanced operation strategies. It can be used in design space generation and process optimization for better productivity and product quality.
PubMed: 38924316
DOI: 10.1002/btpr.3486 -
Acta Physiologica (Oxford, England) Jun 2024Thermal sensitivity of cellular metabolism is crucial for animal physiology and survival under climate change. Despite recent efforts, effects of multigenerational...
AIM
Thermal sensitivity of cellular metabolism is crucial for animal physiology and survival under climate change. Despite recent efforts, effects of multigenerational exposure to temperature on the metabolic functioning remain poorly understood. We aimed at determining whether multigenerational exposure to temperature modulate the mitochondrial respiratory response of Medaka fish.
METHODS
We conducted a multigenerational exposure with Medaka fish reared multiple generations at 20 and 30°C (COLD and WARM fish, respectively). We then measured the oxygen consumption of tail muscle at two assay temperatures (20 and 30°C). Mitochondrial function was determined as the respiration supporting ATP synthesis (OXPHOS) and the respiration required to offset proton leak (LEAK(Omy)) in a full factorial design (COLD-20°C; COLD-30°C; WARM-20°C; WARM-30°C).
RESULTS
We found that higher OXPHOS and LEAK fluxes at 30°C compared to 20°C assay temperature. At each assay temperature, WARM fish had lower tissue oxygen fluxes than COLD fish. Interestingly, we did not find significant differences in respiratory flux when mitochondria were assessed at the rearing temperature of the fish (i.e., COLD-20°C vs. WARM -30°C).
CONCLUSION
The lower OXPHOS and LEAK capacities in warm fish are likely the result of the multigenerational exposure to warm temperature. This is consistent with a modulatory response of mitochondrial capacity to compensate for potential detrimental effects of warming on metabolism. Finally, the absence of significant differences in respiratory fluxes between COLD-20°C and WARM-30°C fish likely reflects an optimal respiration flux when organisms adapt to their thermal conditions.
PubMed: 38924292
DOI: 10.1111/apha.14194 -
Advanced Materials (Deerfield Beach,... Jun 2024Catalysts play a crucial role in water electrolysis by reducing the energy barriers for hydrogen and oxygen evolution reactions (HER and OER). Research aims to enhance... (Review)
Review
Catalysts play a crucial role in water electrolysis by reducing the energy barriers for hydrogen and oxygen evolution reactions (HER and OER). Research aims to enhance the intrinsic activities of potential catalysts through material selection, microstructure design, and various engineering techniques. However, the energy consumption of catalysts has often been overlooked due to the intricate interplay among catalyst microstructure, dimensionality, catalyst-electrolyte-gas dynamics, surface chemistry, electron transport within electrodes, and electron transfer among electrode components. Efficient catalyst development for high-current-density applications is essential to meet the increasing demand for green hydrogen. This involves transforming catalysts with high intrinsic activities into electrodes capable of sustaining high current densities. This review focuses on current improvement strategies of mass exchange, charge transfer, and reducing electrode resistance to decrease energy consumption. It aims to bridge the gap between laboratory-developed, highly efficient catalysts and industrial applications regarding catalyst structural design, surface chemistry, and catalyst-electrode interplay, outlining the development roadmap of hierarchically structured electrode-based water electrolysis for minimizing energy loss in electrocatalysts for water splitting. This article is protected by copyright. All rights reserved.
PubMed: 38923073
DOI: 10.1002/adma.202404658 -
Pediatric Obesity Jun 2024The identification of predictive parameters of the success of multidisciplinary weight loss interventions (MWLI) appears essential to optimize obesity management. The...
BACKGROUND
The identification of predictive parameters of the success of multidisciplinary weight loss interventions (MWLI) appears essential to optimize obesity management. The association between baseline cardiorespiratory fitness (CRF) and changes in anthropometric parameters and body composition during MWLI remains underexplored in adolescents with obesity.
OBJECTIVES
To assess whether baseline CRF was associated with the effectiveness of a 16-week MWLI measured through improved body mass, body mass index (BMI) and body composition (percentage of total fat mass (FM) as the main criterion).
METHODS
Cardiorespiratory fitness and body composition were respectively measured by peak oxygen consumption (VO) during maximal exercise tests and dual-photon x-ray absorptiometry (DXA), before (T0) and after (T1) a 16-week MWLI in 165 adolescents (aged 13.3 ± 1.38 years, 61.2% female, BMI 35.11 ± 5.16 kg/m).
RESULTS
Reductions in BMI and total FM percentage between T0 and T1 were greater in subjects with a baseline VO ≥ 3rd quartile compared to the first quartile (p < 0.001) and the interquartile range (p < 0.05 and p < 0.001, respectively). Baseline VO and VO at the first ventilator threshold were positively correlated with the reductions in body mass, BMI and total and visceral FM percentages and with the increase in lean mass (LM) percentage between T0 and T1 after adjustment for age and gender (p < 0.001).
CONCLUSION
Initial CRF is associated with the success of MWLI in adolescents with obesity. Improving their aerobic fitness before starting a MWLI might be a promising strategy to optimize its benefits.
PubMed: 38922794
DOI: 10.1111/ijpo.13147 -
Sports (Basel, Switzerland) Jun 2024Due to little available research on elite CrossFit athletes, the present investigation was undertaken to provide knowledge about their physical and physiological...
Due to little available research on elite CrossFit athletes, the present investigation was undertaken to provide knowledge about their physical and physiological characteristics. Nineteen international level CrossFit athletes (8 men; 11 women) were tested for maximum oxygen consumption (V˙Omax), Wingate, squat 1 repetition maximum (1RM), countermovement jump (CMJ), lower body force-velocity, and body composition (DXA). To provide perspective, the results were compared to sixteen elite-level Alpinists (8 men; 8 women). There was no significant difference in absolute nor relative V˙Omax between the CrossFit and Alpinist men ( = 0.335 and = 0.279, respectively). The CrossFit women showed similar absolute but higher relative V˙Omax than the Alpinist women ( = 0.055 and = 0.005, respectively). Mean anaerobic power was higher in both CrossFit men and women ( = 0.021 and = 0.008, respectively). There were no significant differences in squat 1RM and CMJ for both men and women ( > 0.05). Both CrossFit men and women showed lesser lower body force production ( = 0.043 and = 0.034, respectively) but higher power ( = 0.009 and = 0.003, respectively). The CrossFit men and women had a lower fat mass ( = 0.018 and = 0.002, respectively) and fat percentage ( = 0.027 and < 0.001, respectively). These observations show that elite CrossFit athletes possess physical and physiological characteristics comparable to world-class Alpinists.
PubMed: 38921856
DOI: 10.3390/sports12060162 -
Journal of Nanobiotechnology Jun 2024Premature ovarian insufficiency (POI) is an important cause of female infertility and seriously impacts the physical and psychological health of patients. Human...
BACKGROUND
Premature ovarian insufficiency (POI) is an important cause of female infertility and seriously impacts the physical and psychological health of patients. Human umbilical cord mesenchymal stem cell-derived exosomes (HucMSCs-Exs, H-Exs) have exhibited protective effects on ovarian function with unclear mechanisms.
METHODS
A comprehensive analysis of the Gene Expression Omnibus (GEO) database were used to identify POI-associated circRNAs and miRNAs. The relationship between HucMSC-derived exosomal circBRCA1/miR-642a-5p/FOXO1 axis and POI was examined by RT-qPCR, Western blotting, reactive oxygen species (ROS) staining, senescence-associated β-gal (SA-β-gal) staining, JC-1 staining, TEM, oxygen consumption rate (OCR) measurements and ATP assay in vivo and in vitro. RT-qPCR detected the expression of circBRCA1 in GCs and serum of patients with normal ovarian reserve function (n = 50) and patients with POI (n = 50); then, the correlation of circBRCA1 with ovarian reserve function indexes was analyzed.
RESULTS
Herein, we found that circBRCA1 was decreased in the serum and ovarian granulosa cells (GCs) of patients with POI and was associated with decreased ovarian reserve. H-Exs improved the disorder of the estrous cycles and reproductive hormone levels, reduced the number of atretic follicles, and alleviated the apoptosis and senescence of GCs in rats with POI. Moreover, H-Exs mitigated mitochondrial damage and reversed the reduced circBRCA1 expression induced by oxidative stress in GCs. Mechanistically, FTO served as an eraser to increase the stability and expression of circBRCA1 by mediating the mA demethylation of circBRCA1, and exosomal circBRCA1 sponged miR-642a-5p to block its interaction with FOXO1. CircBRCA1 insufficiency aggravated mitochondrial dysfunction, mimicking FTO or FOXO1 depletion effects, which was counteracted by miR-642a-5p inhibition.
CONCLUSION
H-Exs secreted circBRCA1 regulated by mA modification, directly sponged miR-642a-5p to upregulate FOXO1, resisted oxidative stress injuries in GCs and protected ovarian function in rats with POI. Exosomal circBRCA1 supplementation may be a general prospect for the prevention and treatment of POI.
Topics: Female; Granulosa Cells; Oxidative Stress; MicroRNAs; Animals; Exosomes; Rats; RNA, Circular; Humans; Primary Ovarian Insufficiency; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Forkhead Box Protein O1; Rats, Sprague-Dawley; Mesenchymal Stem Cells; Adult
PubMed: 38918838
DOI: 10.1186/s12951-024-02583-5 -
Journal of Nanobiotechnology Jun 2024Breast cancer ranks second as the most common malignancy globally, after lung cancer. Among the various subtypes of breast cancer, HER2 positive breast cancer (HER2...
INTRODUCTION
Breast cancer ranks second as the most common malignancy globally, after lung cancer. Among the various subtypes of breast cancer, HER2 positive breast cancer (HER2 BC)poses a particularly challenging prognosis due to its heightened invasiveness and metastatic potential. The objective of this study was to construct a composite piezoelectric nanoparticle based on poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) for imaging and treatment of HER2 BC.
METHOD
By reshaping the crystal structure of P(VDF-TrFE) piezoelectric nanoparticles, improving hydrophilicity, and incorporating imaging capabilities, we developed piezoelectric composite nanoparticles (PGd@tNBs) that integrate imaging and therapeutic functions. The in vitro characterization encompassed the assessment of piezoelectric properties, hydrophilicity, imaging performance, and therapeutic efficacy of these particles. The targeting and therapeutic effectiveness of PGd@tNBs particles were further validated in the SK-BR3 cell line and subsequently confirmed in HER2-positive tumor-bearing mice.
RESULTS
The nanoparticle demonstrated excellent biocompatibility and impressive multimodal imaging performance. Magnetic resonance imaging (MRI) observations revealed significant accumulation of PGd@tNBs particles in the HER2 positive tumor, exhibiting superior contrast-enhanced ultrasound performance compared to traditional ultrasound contrast agents, and small animal in vivo imaging showed that PGd@tNBs particles were primarily excreted through respiration and urinary metabolism. Piezoforce Microscopy characterization highlighted the outstanding piezoelectric properties of PGd@tNBs particles. Upon targeted binding to HER2-BC, ultrasound stimulation influenced the cell membrane potential, leading to reversible electroporation. This, in turn, affected the balance of calcium ions inside and outside the cells and the mitochondrial membrane potential. Following ingestion by cells, PGd@tNBs, when exposed to ultrasound, triggered the generation of reactive oxygen species (ROS), resulting in the consumption of glutathione and superoxide dismutase and achieving sonodynamic therapy. Notably, repeated ultrasound stimulation, post PGd@tNBs particles binding and entry into cells, increased ROS production and elevated the apoptosis rate by approximately 45%.
CONCLUSION
In conclusion, the PGd@tNBs particles developed exhibit outstanding imaging and therapeutic efficacy, holding potential for precise diagnosis and personalized treatment of HER2 BC.
Topics: Animals; Female; Breast Neoplasms; Humans; Mice; Cell Line, Tumor; Receptor, ErbB-2; Nanoparticles; Magnetic Resonance Imaging; Ultrasonic Therapy; Mice, Nude; Mice, Inbred BALB C; Contrast Media; Apoptosis
PubMed: 38918812
DOI: 10.1186/s12951-024-02639-6 -
Cell Biochemistry and Biophysics Jun 2024Toll-like receptors 3 (TLR3) are innate immune receptors expressed on a wide range of cell types, including glial cells. Inflammatory responses altered by hyperglycemia...
Toll-like receptors 3 (TLR3) are innate immune receptors expressed on a wide range of cell types, including glial cells. Inflammatory responses altered by hyperglycemia highlight the need to explore the molecular underpinnings of these changes in cellular models. Therefore, here we estimated TLR3-mediated response of astrocytes cultured at normal (NG, 5 mM) and high (HG, 22.5 mM) glucose concentrations for 48 h before stimulation with polyinosinic:polycytidylic acid Poly(I:C) (PIC) for 6 h. Seahorse Extracellular Flux Analyzer (Seahorse XFp) was used to estimate the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Although adaptation to HG affected ECAR and OCR, the stimulation of cells with PIC had no effect on ECAR. PIC reduced maximal OCR, but this effect disappeared upon adaptation to HG. PIC-stimulated release of cytokines IL-1β, IL-10 was reduced, and that of IL-6 and iNOS was increased in the HG model. Adaptation to HG reduced PIC-stimulated synthesis of COX-derived oxylipins measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Adaptation to HG did not alter PIC-stimulated p38 activity, ERK mitogen-activated protein kinase, STAT3 and ROS production. Metformin exhibited anti-inflammatory activity, reducing PIC-stimulated synthesis of cytokines and oxylipins. Cell adaptation to high glucose concentration altered the sensitivity of astrocytes to TLR3 receptor activation, and the hypoglycemic drug metformin may exert anti-inflammatory effects under these conditions.
PubMed: 38918312
DOI: 10.1007/s12013-024-01380-z -
European Journal of Applied Physiology Jun 2024To measure oxygen demand, uptake, and deficits in competitive cross-country skiers during outdoor roller skiing at different competition durations, ranging from the...
PURPOSE
To measure oxygen demand, uptake, and deficits in competitive cross-country skiers during outdoor roller skiing at different competition durations, ranging from the endurance domain to the sprint domain.
METHODS
Ten competitive cross-country skiers (6 males; O 78 ± 3 and 4 females; O 62 ± 3 mL∙kg∙min) raced time trials consisting of 1, 2, and 4 laps in a 1.6 km racecourse in a randomized order with 35 min recovery in-between. Oxygen uptake was measured using a wearable metabolic system while oxygen demand was estimated from kinematic data (GPS and IMU) and an athlete-specific model of skiing economy. Skiing economy and O was established on a separate test day using six submaximal constant-load trials at different speeds and inclines, and one maximal-effort trial on a roller-skiing treadmill.
RESULTS
Average oxygen demand was 112 ± 8%, 103 ± 7% and 98 ± 7% of O during the 1 (3:37 ± 0:20 m:ss), 2 (7:36 ± 0:38 m:ss) and 4 (15:43 ± 1:26 m:ss) lap time trials, respectively, and appeared to follow an inverse relationship with time-trial duration. Average oxygen uptake was unaffected by race length (86 ± 5%, 86 ± 5%, and 86 ± 7% of O, respectively). Accumulated oxygen deficit at the end of each time trial was 85 ± 13, 106 ± 32 and 158 ± 62 mL∙kg, while oxygen deficits per work bout was 23 ± 3, 18 ± 3 and 16 ± 3 mL∙kg for the 1, 2, and 4-lap time trials, respectively.
CONCLUSION
Elite cross-country skiers adjust their pacing strategies from attaining relatively small oxygen deficits per work bout in the endurance domain, to larger deficits in the sprint domain. This indicates a shift in strategy from prioritizing stable work-economy and rate-of-recovery in the endurance domain, to maximizing power output in the sprint domain.
PubMed: 38918220
DOI: 10.1007/s00421-024-05531-1 -
Reproduction (Cambridge, England) Jun 2024L-Carnitine (LC) is known to play key roles in lipid metabolism and antioxidative activity, implicating enhanced cryotolerance of bovine blastocysts. However,...
L-Carnitine (LC) is known to play key roles in lipid metabolism and antioxidative activity, implicating enhanced cryotolerance of bovine blastocysts. However, sustainability of LC supplementation during culture period on preimplantation development beyond the blastocyst stage has not been investigated so far. Therefore, all embryos were cultured under fatty acid free conditions, one group with LC (LC-Embryos) and the control group without LC (Control) supplementation. Transfer to recipients was conducted on day 6. Elongation-stage embryos were recovered on day 14; metrics of embryo recollection, developmental rates to early elongation-stage as well as mean embryo length did not differ between the groups. Gene expression analysis via NGS revealed 341 genes to be differentially regulated between elongation-stage embryos derived from LC supplementation compared to controls. These played mainly a role in molecular functions and biological processes like oxidoreductase activity, ATP dependent activity, cellular stress and respiration. Pathways like oxidative phosphorylation and thermogenesis, ECM receptor signaling, PI3K-Akt and focal adhesion were affected by differentially regulated genes. Moreover, all DEGs located on the mitochondria were significantly downregulated in the LC-Embryos, being in line with lower mitochondrial copy number and mtDNA integrity compared to the control group. Finally, we uncovered alterations of the bioenergetic profile on day 7 as a consequence of LC supplementation for the first time, revealing significantly higher oxygen consumption rates, ATP linked respiration and spare capacity for LC-embryos. Conclusively, we uncovered direct effects of LC supplementation during the culture period on the bioenergetic profile going along with sustainable effects on mtDNA copy numbers and transcriptome profile of bovine day 14 embryos.
PubMed: 38917030
DOI: 10.1530/REP-24-0004