Controlled atmosphere as cold chain support for extending postharvest life in cabbage.

Postharvest management of cabbage relies on high-intensity cooling to control postharvest physiology, minimising quality loss despite incurring significant energy and environmental costs. As an alternative, we hypothesised that controlled atmosphere (CA) could allow increased storage temperature by supporting physiological regulation, while maintaining quality and reducing energy demand. This study examined the effect CA (1.5 kPa CO2 and 6 kPa O2) at 5 or 10 °C on cabbage quality, with the aim of proposing a more sustainable and resilient supply chain. CA treatment was effective at reducing head respiration at higher temperature, with CA/10 °C treatment achieving lower respiration rates than Control/5 °C. Improved head colour retention and maintenance of stump quality were observed in cabbage under CA conditions. CA effects were seen also at a regulatory level; CA promoted an average of 25.4% reduction in abscisic acid accumulation potentially as part of a wider hypoxia stress response and was successful in decreasing expression of the senescence-coordinating transcription factor BoORE15. This finding was linked with a lower in downstream expression of pheophytinase and subtilisin protease. These results demonstrated that CA treatment fundamentally modified postharvest physiology in cabbage, which can be exploited to enable storage at warmer temperatures, contributing to supply chains with lower energy demand and its associated environmental benefits.

Relative uteroplacental insufficiency of labor.

Relative uteroplacental insufficiency of labor (RUPI-L) is a clinical condition that refers to alterations in the fetal oxygen "demand-supply" equation caused by the onset of regular uterine activity. The term RUPI-L indicates a condition of "relative" uteroplacental insufficiency which is relative to a specific stressful circumstance, such as the onset of regular uterine activity. RUPI-L may be more prevalent in fetuses in which the ratio between the fetal oxygen supply and demand is already slightly reduced, such as in cases of subclinical placental insufficiency, post-term pregnancies, gestational diabetes, and other similar conditions. Prior to the onset of regular uterine activity, fetuses with a RUPI-L may present with normal features on the cardiotocography. However, with the onset of uterine contractions, these fetuses start to manifest abnormal fetal heart rate patterns which reflect the attempt to maintain adequate perfusion to essential central organs during episodes of transient reduction in oxygenation. If labor is allowed to continue without an appropriate intervention, progressively more frequent, and stronger uterine contractions may result in a rapid deterioration of the fetal oxygenation leading to hypoxia and acidosis. In this Commentary, we introduce the term relative uteroplacental insufficiency of labor and highlight the pathophysiology, as well as the common features observed in the fetal heart rate tracing and clinical implications.

Integrated transcriptome and metabolome analysis reveals the molecular responses of Pardosa pseudoannulata to hypoxic environments.

Terrestrial organisms are likely to face hypoxic stress during natural disasters such as floods or landslides, which can lead to inevitable hypoxic conditions for those commonly residing within soil. Pardosa pseudoannulata often inhabits soil crevices and has been extensively studied, yet research on its response to hypoxic stress remains unclear. Therefore, we investigated the adaptive strategies of Pardosa pseudoannulata under hypoxic stress using metabolomics and transcriptomics approaches. The results indicated that under hypoxic stress, metabolites related to energy and antioxidants such as ATP, D-glucose 6-phosphate, flavin adenine dinucleotide (FAD), and reduced L-glutathione were significantly differentially expressed. Pathways such as the citric acid (TCA) cycle and oxidative phosphorylation were significantly enriched. Transcriptome analysis and related assessments also revealed a significant enrichment of pathways associated with energy metabolism, suggesting that Pardosa pseudoannulata primarily copes with hypoxic environments by modulating energy metabolism and antioxidant-related substances.

Effects of different nitric oxide synthases on pulmonary and systemic hemodynamics in hypoxic stress rat model.

BACKGROUND: Under hypoxia, exaggerated compensatory responses may lead to acute mountain sickness. The excessive vasodilatory effect of nitric oxide (NO) can lower the hypoxic pulmonary vasoconstriction (HPV) and peripheral blood pressure. While NO is catalyzed by various nitric oxide synthase (NOS) isoforms, the regulatory roles of these types in the hemodynamics of pulmonary and systemic circulation in living hypoxic animals remain unclear. Therefore, this study aims to investigate the regulatory effects of different NOS isoforms on pulmonary and systemic circulation in hypoxic rats by employing selective NOS inhibitors and continuously monitoring hemodynamic parameters of both pulmonary and systemic circulation. METHODS: Forty healthy male Sprague-Dawley (SD) rats were randomly divided into four groups: Control group (NG-nitro-D-arginine methyl ester, D-NAME), L-NAME group (non-selective NOS inhibitor, NG-nitro-L-arginine methyl ester), AG group (inducible NOS inhibitor group, aminoguanidine), and 7-NI group (neurological NOS inhibitor, 7-nitroindazole). Hemodynamic parameters of rats were monitored for 10 min after inhibitor administration and 5 min after induction of hypoxia [15% O2, 2200 m a. sl., 582 mmHg (76.5 kPa), Xining, China] using the real-time dynamic monitoring model for pulmonary and systemic circulation hemodynamics in vivo. Serum NO concentrations and blood gas analysis were measured. RESULTS: Under normoxia, mean arterial pressure and total peripheral vascular resistance were increased, and ascending aortic blood flow and serum NO concentration were decreased in the L-NAME and AG groups. During hypoxia, pulmonary arterial pressure and pulmonary vascular resistance were significantly increased in the L-NAME and AG groups. CONCLUSIONS: This compensatory mechanism activated by inducible NOS and endothelial NOS effectively counteracts the pulmonary hemodynamic changes induced by hypoxic stress. It plays a crucial role in alleviating hypoxia-induced pulmonary arterial hypertension.

Effect of low oxygen stress on the metabolic responses of tomato fruit cells.

Postharvest losses of fruits and vegetables can occur due to cell breakdown and browning during controlled atmosphere storage as a result of low oxygen (O2) stress. Therefore, the study was designed to better understand the underlying mechanisms of the response of isolated tomato fruit cells incubated at low O2 (hypoxic and anoxic) conditions as a model system. The O2 stress conditions used for the experiment were based on the results of the Michaelis-Menten constant (Km) of respiration. A total of 56 polar metabolites belonging mainly to different functional groups, including amino acids, organic acids, sugars and sugar alcohols, were identified using GC-MS. O2 stress stimulated the biosynthesis of most of the free amino acids while decreasing the synthesis of most of the organic acids (especially those linked to the tricarboxylic acid cycle), sugars (except for ribose) and other nitrogen-containing compounds. The down-regulation of these TCA cycle metabolites served to provide energy to ensure the survival of the cell. Increases in the sugar alcohol levels and induction of fermentative metabolism were observed under low O2 stress. By employing multivariate statistics, metabolites were identified that were essential to the oxygen stress response and establishing the correlation between metabolite abundance, oxygen levels, and incubation period were achievable. A higher correlation was observed between the O2 levels and most of the metabolites.

Hypoxic stress caused apoptosis of MDBK cells by p53/BCL6-mitochondrial apoptosis pathway.

Hypoxia is an important characteristic of Tibetan plateau environment. It can lead to apoptosis, but the mechanism of apoptosis caused by hypoxic stress needs further clarification. Here, cattle kidney cell MDBK were used as cell model. The effect of hypoxic stress on apoptosis and its molecular mechanism were explored. MDBK cells were treated with hypoxic stress, apoptosis and mitochondrial apoptotic pathway were significantly increased, and the expression of B-cell lymphoma 6 (BCL6) was significantly decreased. Overexpressing or inhibiting BCL6 demonstrated that BCL6 inhibited the apoptosis. And the increase of apoptosis controlled by hypoxic stress was blocked by BCL6 overexpressing. MDBK cells were treated with hypoxic stress, the expression and the nuclear localization of p53 were significantly increased. Overexpressing or inhibiting p53 demonstrated that hypoxic stress suppressed the expression of BCL6 through p53. Together, these results indicated that hypoxic stress induced the apoptosis of MDBK cells, and BCL6 was an important negative factor for this regulation process. In MDBK cells, hypoxic stress suppressed the expression of BCL6 through p53/BCL6-mitochondrial apoptotic pathway. This study enhanced current understanding of the molecular mechanisms underlying the regulation of apoptosis by hypoxic stress in MDBK cells.

Long-lasting adverse effects of short-term stress during the suckling-mastication transition period on masticatory function and intraoral sensation in rats.

Early-life stress affects brain development, eventually resulting in adverse behavioral and physical health consequences in adulthood. The present study assessed the hypothesis that short-term early-life stress during infancy before weaning, a period for the maturation of mastication and sleep, poses long-lasting adverse effects on masticatory function and intraoral sensations later in life.Rat pups were exposed to either maternal separation (MS) or intermittent hypoxia (IH-Infancy) for 6 h/day in the light/sleep phase from postnatal day (P)17 to P20 to generate "neglect" and "pediatric obstructive sleep apnea" models, respectively. The remaining rats were exposed to IH during P45-P48 (IH-Adult). Masticatory ability was evaluated based on the rats' ability to chew pellets and bite pasta throughout the growth period (P21-P70). Intraoral chemical and mechanical sensitivities were assessed using two-bottle preference drinking tests, and hind paw pain thresholds were measured in adulthood (after P60).No differences were found in body weight, grip force, and hind paw sensitivity in MS, IH-Infancy, and IH-Adult rats compared with naïve rats. Masticatory ability was lower in MS and IH-Infancy rats from P28 to P70 than in naïve rats. MS and IH-Infancy rats exhibited intraoral hypersensitivity to capsaicin and mechanical stimulations in adulthood. The IH-Adult rats did not display inferior masticatory ability or intraoral hypersensitivity.In conclusion, short-term early-life stress during the suckling-mastication transition period potentially causes a persistent decrease in masticatory ability and intraoral hypersensitivity in adulthood. The period is a "critical window" for the maturation of oral motor and sensory functions.

Integrated Transcriptomics and Metabolomics Reveal Changes in Cell Homeostasis and Energy Metabolism in Trachinotus ovatus in Response to Acute Hypoxic Stress.

Trachinotus ovatus is an economically important mariculture fish, and hypoxia has become a critical threat to this hypoxia-sensitive species. However, the molecular adaptation mechanism of T. ovatus liver to hypoxia remains unclear. In this study, we investigated the effects of acute hypoxic stress (1.5 ± 0.1 mg·L-1 for 6 h) and re-oxygenation (5.8 ± 0.3 mg·L-1 for 12 h) in T. ovatus liver at both the transcriptomic and metabolic levels to elucidate hypoxia adaptation mechanism. Integrated transcriptomics and metabolomics analyses identified 36 genes and seven metabolites as key molecules that were highly related to signal transduction, cell growth and death, carbohydrate metabolism, amino acid metabolism, and lipid metabolism, and all played key roles in hypoxia adaptation. Of these, the hub genes FOS and JUN were pivotal hypoxia adaptation biomarkers for regulating cell growth and death. During hypoxia, up-regulation of GADD45B and CDKN1A genes induced cell cycle arrest. Enhancing intrinsic and extrinsic pathways in combination with glutathione metabolism triggered apoptosis; meanwhile, anti-apoptosis mechanism was activated after hypoxia. Expression of genes related to glycolysis, gluconeogenesis, amino acid metabolism, fat mobilization, and fatty acid biosynthesis were up-regulated after acute hypoxic stress, promoting energy supply. After re-oxygenation for 12 h, continuous apoptosis favored cellular function and tissue repair. Shifting from anaerobic metabolism (glycolysis) during hypoxia to aerobic metabolism (fatty acid ß-oxidation and TCA cycle) after re-oxygenation was an important energy metabolism adaptation mechanism. Hypoxia 6 h was a critical period for metabolism alteration and cellular homeostasis, and re-oxygenation intervention should be implemented in a timely way. This study thoroughly examined the molecular response mechanism of T. ovatus under acute hypoxic stress, which contributes to the molecular breeding of hypoxia-tolerant cultivars.

Integrated transcriptomic and proteomic analysis reveals Guizhi-Fuling Wan inhibiting STAT3-EMT in ovarian cancer progression.

BACKGROUND: Ovarian cancer (OC) is the most lethal gynecological malignancy. Frequent peritoneal dissemination is the main cause of low survival rate. Guizhi-Fuling Wan (GZFL) is a classical traditional Chinese herbal formula that has been clinically used for treating ovarian cancer with good outcome. However, its therapeutic mechanism for treating OC has not been clearly elucidated. PURPOSE: We aim to elucidate the potential mechanisms of GZFL in treating OC with a focus on STAT3 signaling pathway. METHODS: In vivo efficacy of GZFL was assessed using an OC xenograft mouse model. Proteomics analysis in OC cells and RNA-seq analysis in mice tumors were performed to fully capture the translational and transcriptional signature of GZFL. Effects of GZFL on proliferation, spheroid formation and reactive oxygen species (ROS) were assessed using wildtype and STAT3 knockout OC cells in vitro. STAT3 activation and transcription activity, hypoxia and EMT-related protein expression were assessed to validate the biological activity of GZFL. RESULTS: GZFL suppresses tumor growth with a safety profile in mice, while prevents cell growth, spheroid formation and accumulates ROS in a STAT3-dependent manner in vitro. GZFL transcriptionally and translationally affects genes involved in inflammatory signaling, EMT, cell migration, and cellular hypoxic stress response. In depth molecular study confirmed that GZFL-induced cytotoxicity and EMT suppression in OC cells are directly corelated to inhibition of STAT3 activation and transcription activity. CONCLUSION: Our study provides the first evidence that GZFL inhibits OC progression through suppressing STAT3-EMT signaling. These results will further support its potential clinical use in OC.

Effects of sodium butyrate on growth performance, antioxidant status, inflammatory response and resistance to hypoxic stress in juvenile largemouth bass (Micropterus salmoides).

The aim of this study was to investigate the effects of sodium butyrate (SB) supplementation on growth performance, antioxidant enzyme activities, inflammatory factors, and hypoxic stress in largemouth bass (Micropterus salmoides). Diets were supplemented with different doses of SB at 0 (SB0), 0.5 (SB1), 1.0 (SB2) and 2.0 (SB3) g/kg. The hypoxic stress experiment was performed after 56 days of culture. The results showed that compared with the SB0 group, the final body weight, weight gain rate and protein deposition rate of the SB3 group were significantly increased (P<0.05), while FCR was significantly decreased (P<0.05). The contents of dry matter, crude lipids, and ash in the SB2 group were significantly higher than those in the SB0 group (P<0.05). The urea level was significantly decreased (P<0.05), and the glucose content was significantly increased (P<0.05) in the SB supplement group. Compared with the SB0 group, the SB2 group had significant reductions in the levels of serum triglyceride, cholesterol, elevated-density lipoprotein cholesterol, and low-density lipoprotein (P<0.05), and significant reductions in the levels of liver alkaline phosphatase and malondialdehyde (P<0.05). The total antioxidant capacity of the SB1 group was higher than that of other groups (P<0.05). Compared with the SB0 group, the mRNA expression of TLR22, MyD88, TGF-ß1, IL-1ß and IL-8 in the SB2 group significantly decreased (P<0.05). The cumulative mortality rate was significantly decreased in the SB2 and SB3 groups in comparison with that in the SB0 group after three hours of hypoxic stress (P<0.05). In a 56-day feeding trial, SB enhanced largemouth bass growth by increasing antioxidant enzyme activity and inhibiting TLR22-MyD88 signaling, therefore increasing cumulative mortality from hypoxic stress in largemouth bass.

The Multifaceted Effects of Short-Term Acute Hypoxia Stress: Insights into the Tolerance Mechanism of Propsilocerus akamusi (Diptera: Chironomidae).

Plenty of freshwater species, especially macroinvertebrates that are essential to the provision of numerous ecosystem functions, encounter higher mortality due to acute hypoxia. However, within the family Chironomidae, a wide range of tolerance to hypoxia/anoxia is displayed. Propsilocerus akamusi depends on this great tolerance to become a dominant species in eutrophic lakes. To further understand how P. akamusi responds to acute hypoxic stress, we used multi-omics analysis in combination with histomorphological characteristics and physiological indicators. Thus, we set up two groups-a control group (DO 8.4 mg/L) and a hypoxic group (DO 0.39 mg/L)-to evaluate enzyme activity and the transcriptome, metabolome, and histomorphological characteristics. With blue-black chromatin, cell tightness, cell membrane invagination, and the production of apoptotic vesicles, tissue cells displayed typical apoptotic features in the hypoxic group. Although lactate dehydrogenase (LDH), alcohol dehydrogenase (ADH), catalase (CAT), and Na+/K+ -ATPase (NKA) activities were dramatically enhanced under hypoxic stress, glycogen content, and superoxide dismutase (SOD) activities were significantly reduced compared to the control group. The combined analysis of the transcriptome and metabolome, which further demonstrated, in addition to carbohydrates, including glycogen, the involvement of energy metabolism pathways, including fatty acid, protein, trehalose, and glyoxylate cycles, provided additional support for the aforementioned findings. Lactate is the end product of glycogen degradation, and HIF-1 plays an important role in promoting glycogenolysis in acute hypoxic conditions. However, we discovered that the ethanol tested under hypoxic stress likely originates from the symbiodinium of P. akamusi. These results imply that some parameters related to energy metabolism, antioxidant enzyme activities, and histomorphological features may be used as biomarkers of eutrophic lakes in Chironomus riparius larvae. The study also provides a scientific reference for assessing toxicity and favoring policies to reduce their impact on the environment.

A comparative metabolomics analysis of domestic yak (Bos grunniens) milk with human breast milk.

Yaks are tough animals living in Tibet's hypoxic stress environment. However, the metabolite composition of yak milk and its role in hypoxic stress tolerance remains largely unexplored. The similarities and differences between yak and human milk in hypoxic stress tolerance are also unclear. This study explored yak colostrum (YC) and yak mature milk (YMM) using GC-MS, and 354 metabolites were identified in yak milk. A comparative metabolomic analysis of yak and human milk metabolites showed that over 70% of metabolites were species-specific. Yak milk relies mainly on essential amino acids- arginine and essential branched-chain amino acids (BCAAs): L-isoleucine, L-leucine, and L-valine tolerate hypoxic stress. To slow hypoxic stress, human breast milk relies primarily on the neuroprotective effects of non-essential amino acids or derivates, such as citrulline, sarcosine, and creatine. In addition, metabolites related to hypoxic stress were significantly enriched in YC than in YMM. These results reveal the unique metabolite composition of yak and human milk and provide practical information for applying yak and human milk to hypoxic stress tolerance.

Integrated transcriptomic and metabolomic analysis reveals the response of pearl oyster (Pinctada fucata martensii) to long-term hypoxia.

The frequency at which organisms are exposed to hypoxic conditions in aquatic environments is increasing due to coastal eutrophication and global warming. To reveal the effects of long-term hypoxic stress on metabolic changes of pearl oyster, commonly known as Pinctada (Pinctada fucata martensii), the present study performed the integrated analysis of transcriptomics and metabolomics to investigate the global changes of genes and metabolites following 25 days hypoxia challenge. Transcriptome analysis detected 1108 differentially expressed genes (DEGs) between the control group and the hypoxia group. The gene ontology (GO) analysis of DEGs revealed that they are significantly enriched in functions such as "microtubule-based process", "histone (H3-K4, H3-K27, and H4-K20) trimethylation", "histone H4 acetylation", "kinesin complex", and "ATPase activity", and KEGG pathway functions, such as "DNA replication", "Apoptosis", and "MAPK signaling pathways". Metabolome analysis identified 68 significantly different metabolites from all identified metabolites, and associated with 25 metabolic pathways between the control and hypoxia groups. These pathways included aminoacyl-tRNA biosynthesis, arginine and proline metabolism, and phenylalanine metabolism. Our integrated analysis suggested that pearl oysters were subject to oxidative stress, apoptosis, immune inhibition, and neuronal excitability reduction under long-term hypoxic conditions. We also found a remarkable depression in a variety of biological functions under long-term hypoxia, including metabolic rates, biomineralization activities, and the repression of reorganization of the cytoskeleton and cell metabolism. These findings provide a basis for elucidating the mechanisms used by marine bivalves to cope with long-term hypoxic stress.

Transcriptomic Analysis of Takifugu obscurus Gills under Acute Hypoxic Stress.

Takifugu obscurus has relatively small gills and gill pores, leading to a relatively low respiratory capacity and increased vulnerability to low dissolved oxygen (DO) levels compared to other fish. To investigate the responses of T. obscurus to acute hypoxic stress, high-throughput-sequencing-based transcriptomic analyses were conducted here to assess the responses of T. obscurus gills to acute hypoxic stress. Three environmental conditions were compared including normoxia (DO: 7.0 ± 0.2 mg/L), hypoxic stress (DO: 0.9 ± 0.2 mg/L), and reoxygenation (4, 8, 12, and 24 h after return to normoxia) conditions to identify differentially expressed genes (DEGs) responsive to hypoxia. A total of 992, 877, 1561, 1412, and 679 DEGs were identified in the normoxia and reoxygenation for 4, 8, 12, and 24 h groups in comparison to the hypoxia groups, respectively. The DEGs were primarily associated with oxidative stress, growth and development, and immune responses. Further functional annotation enrichment analysis of the DEGs revealed that they were primarily related to cytokine-cytokine interactions, transforming growth factor ß receptor (TGF-ß), cell adhesion molecules (CAMs), the vascular endothelial growth factor (VEGF) signaling pathway, and the mitogen-activated protein kinase (MAPK) signaling pathway. These results provide new insights into the physiological and biochemical mechanisms of T. obscurus adaptations to hypoxic stress. Furthermore, these results provide a framework for future studies into the molecular mechanisms of hypoxia tolerance and the healthy culture of T. obscurus and other fish.

Adaptation to hypoxic stress involves amino acid metabolism: A case in sea cucumber.

Low dissolved oxygen (LO) in seawater negatively affects aquatic animals and has received considerable attention. However, there is still much to learn about how echinoderms, which are keystone species in benthic ecosystems, respond to hypoxic stress. Here, we detected differentially expressed metabolites (DEMs) in sea cucumber (Apositchopus japonicus) between normoxic conditions (NC group) and hypoxic conditions (2 mg L-1) for 3 and 7 days (i.e., LO3 and LO7 groups). A total of 243, 298, and 178 DEMs were found in the NC versus LO3, NC vs. LO7, and LO3 vs. LO7 comparisons, respectively. Amino acids were the most abundant class of DEMs, and "biosynthesis of amino acids" was an enriched pathway in all three comparisons. Most of the enriched metabolite sets under hypoxic stress were related to metabolism. As the duration of the hypoxia treatment extended, the metabolism-related process maintained an upward trend, and signaling pathways maintained a downward trend. Thus, metabolism-related processes are affected in hypoxia-stressed sea cucumber, and amino acid metabolism is the most important process for adaption to hypoxic conditions, potentially function in osmotic regulation and energy regulation. Our results shed light on the adaptative strategies of sea cucumber to challenging environmental conditions.

Alteration of antioxidant status, glucose metabolism, and hypoxia signal pathway in Eirocheir sinensis after acute hypoxic stress and reoxygenation.

Dissolved oxygen (DO) is crucial for the survival of Chinese mitten crab (Eirocheir sinensis); low DO levels adversely affect the health of these crabs. In this study, we evaluated the underlying response mechanism of E. sinensis to acute hypoxic stress by analyzing antioxidant parameters, glycolytic indicators, and hypoxia signaling factors. The crabs were exposed to hypoxia for 0, 3, 6, 12, and 24 h and reoxygenated for 1, 3, 6, 12, and 24 h. The hepatopancreas, muscle, gill, and hemolymph were sampled at different exposure times to detect the biochemical parameters and gene expression. The results showed that the activity of catalase, antioxidants, and malondialdehyde in tissues significantly increased under acute hypoxia and gradually decreased during the reoxygenation phase. Under acute hypoxic stress, glycolysis indices, including hexokinase (HK), phosphofructokinase, pyruvate kinase (PK), pyruvic acid (PA), lactate dehydrogenase (LDH), lactic acid (LA), succinate dehydrogenase (SDH), glucose, and glycogen in the hepatopancreas, hemolymph, and gills increased to varying degrees but recovered to the control levels after reoxygenation. Gene expression data showed that hypoxia signaling pathway-related genes, including hypoxia-inducible factor-1α/ß (HIF1α/ß), prolyl hydroxylase (PHD), factor inhibiting hypoxia-inducible factor (FIH), and glycolysis-related factors (HK and PK) were upregulated, showing that the HIF signaling pathway was activated under hypoxic conditions. In conclusion, acute hypoxic exposure activated the antioxidant defense system, glycolysis, and HIF pathway to respond to adverse conditions. These data contribute to elucidating the defense and adaptive mechanisms of crustaceans to acute hypoxic stress and reoxygenation.

Molecular Aspects of Hypoxic Stress Effects in Chronic Ethanol Exposure of Neuronal Cells.

Experimental models of a clinical, pathophysiological context are used to understand molecular mechanisms and develop novel therapies. Previous studies revealed better outcomes for spinal cord injury chronic ethanol-consuming patients. This study evaluated cellular and molecular changes in a model mimicking spinal cord injury (hypoxic stress induced by treatment with deferoxamine or cobalt chloride) in chronic ethanol-consuming patients (ethanol-exposed neural cultures (SK-N-SH)) in order to explain the clinical paradigm of better outcomes for spinal cord injury chronic ethanol-consuming patients. The results show that long-term ethanol exposure has a cytotoxic effect, inducing apoptosis. At 24 h after the induction of hypoxic stress (by deferoxamine or cobalt chloride treatments), reduced ROS in long-term ethanol-exposed SK-N-SH cells was observed, which might be due to an adaptation to stressful conditions. In addition, the HIF-1α protein level was increased after hypoxic treatment of long-term ethanol-exposed cells, inducing fluctuations in its target metabolic enzymes proportionally with treatment intensity. The wound healing assay demonstrated that the cells recovered after stress conditions, showing that the ethanol-exposed cells that passed the acute step had the same proliferation profile as the cells unexposed to ethanol. Deferoxamine-treated cells displayed higher proliferative activity than the control cells in the proliferation-migration assay, emphasizing the neuroprotective effect. Cells have overcome the critical point of the alcohol-induced traumatic impact and adapted to ethanol (a chronic phenomenon), sustaining the regeneration process. However, further experiments are needed to ensure recovery efficiency is more effective in chronic ethanol exposure.

Selenium nanoparticles coated with polysaccharide-protein complexes from abalone viscera improve growth and enhance resistance to diseases and hypoxic stress in juvenile Nile tilapia (Oreochromis niloticus).

The use of selenium nanoparticles (SeNPs) in aquaculture has been increasing gradually over the past few years. SeNPs enhance immunity, are highly effective against pathogens, and have low toxicity. In this study, SeNPs were prepared using polysaccharide-protein complexes (PSP) from abalone viscera. The acute toxicity of PSP-SeNPs to juvenile Nile tilapia and their effect on growth performance, intestinal tissue structure, antioxidation capacity, hypoxic stress, and Streptococcus agalactiae infection were investigated. The results showed that the spherical PSP-SeNPs were stable and safe, with an LC50 of 13.645 mg/L against tilapia, which was about 13-fold higher than that of sodium selenite (Na2SeO3). A basal diet supplemented with 0.1-1.5 mg/kg PSP-SeNPs improved the growth performance of tilapia juveniles to a certain extent, increased the intestinal villus length, and significantly enhanced the activities of liver antioxidant enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and catalase (CAT). PSP-SeNPs also enhanced the resistance of tilapia to hypoxic stress and Streptococcus agalactiae infection, with supplementation at 0.1-0.3 mg/kg exerting more obvious effects than 1.5 mg/kg. However, PSP-SeNPs at a concentration of 4.5 mg/kg and Na2SeO3 at 0.3 mg/kg negatively affected the growth, gut health, and the activity of the antioxidant enzymes of tilapia. Quadric polynomial regression analysis revealed that 0.1-1.2 mg/kg was the optimal PSP-SeNP supplementation concentration for tilapia feeds. The findings of this study lay a foundation for the application of PSP-SeNPs in aquaculture.

Integrated transcriptomic and metabolomic analysis sheds new light on adaptation of Pinctada fucata martensii to short-term hypoxic stress.

Analyses of the transcriptome and metabolome were conducted to clarify alterations of key genes and metabolites in pearl oysters following exposure to short-term hypoxic treatment. We totally detected 209 DEGs between the control and hypoxia groups. Enrichment analysis indicated the enrichment of GO terms including "oxidation-reduction process", "ECM organization", "chaperone cofactor-dependent protein refolding", and "ECM-receptor interaction" KEGG pathway by the DEGs. In addition, between the two groups, a total of 28 SDMs were identified, which were implicated in 13 metabolic pathways, such as "phenylalanine metabolism", "D-amino acid metabolism", and "aminoacyl-tRNA biosynthesis". Results suggest that pearl oysters are exposed to oxidative stress and apoptosis under short-term hypoxia. Also, pearl oysters might adapt to short-term hypoxic treatment by increasing antioxidant activity, modulating immune and biomineralization activities, maintaining protein homeostasis, and reorganizing the cytoskeleton. The results of our study help unveil the mechanisms by which pearl oysters respond adaptively to short-term hypoxia.

Postnatal Exposure to Brief Hypoxia Alters Brain VEGF Expression and Capillary Density in Adult Mice.

Perinatal hypoxia leads to changes in cerebral angiogenesis and persistent structural and functional changes in the adult brain. It may also result in greater vulnerability to subsequent challenges. We investigated the effect of postnatal day 2 (P2) hypoxic preconditioning on adult brain capillary density and brain vascular endothelial growth factor (VEGF) expression in mice. P2 mice were exposed to hypoxia (5% O2) in a normobaric chamber for 2 h then returned to normoxia while their littermates remained in normoxia (P2 control). After 2-6 months, they were euthanised and their brains were removed for capillary density determination. Another set of animals (P2 hypoxic mice and P2 controls) were euthanised at 2, 10, 23, and 60 days after birth and brain VEGF expression was assessed by western blot. Adult brain capillary density was significantly increased in the P2 hypoxic mice when compared to the P2 control mice. Additionally, VEGF expression appeared to be elevated in the P2-hypoxia mice when compared to the P2-control mice at all time points, and VEGF levels in P2-hypoxia mice declined with age similarly to P2-control mice. These data demonstrate that transient early-postnatal hypoxic stress leads to an increase in capillary density that persists in the adult, possibly due to increased VEGF expression. These results might be explained by epigenetic factors in the VEGF gene.