Synthesis and evaluation of 1,2,4-oxadiazole derivatives as potential anti-inflammatory agents by inhibiting NF-κB signaling pathway in LPS-stimulated RAW 264.7 cells.

In this study, a series of compounds with 1,2,4-oxadiazole core was designed and synthesized for the optimization of JC01, an anti-inflammatory hit identified from our in-house compound library using NF-κB pathway luciferase assay and NO production assay. All the synthetic compounds 1-29 have been screened for their anti-inflammatory effects by evaluating their inhibition against LPS-induced NO release, and compound 17 exhibited the highest activity. Western blotting and immunofluorescence analysis revealed that 17 prominently inhibited LPS-induced activation of NF-κB in RAW264.7 cells and blocked the phosphorylation of p65. Consistent with these results, it was found that 17 prevented the nuclear translocation of NF-κB induced by LPS. These data highlighted 17 as a promising anti-inflammatory agent by inhibiting NF-κB activity.

De novo transcriptome sequencing and analysis of male and female swimming crab (Portunus trituberculatus) reproductive systems during mating embrace (stage II).

BACKGROUND: The swimming crab Portunus trituberculatus is one of the most commonly farmed crustaceans in China. As one of the most widely known and high-value edible crabs, it crab supports large crab fishery and aquaculture in China. Only large and sexually mature crabs can provide the greatest economic benefits, suggesting the considerable effect of reproductive system development on fishery. Studies are rarely conducted on the molecular regulatory mechanism underlying the development of the reproductive system during the mating embrace stage in this species. In this study, we used high-throughput sequencing to sequence all transcriptomes of the P. trituberculatus reproductive system. RESULTS: Transcriptome sequencing of the reproductive system produced 81,688,878 raw reads (38,801,152 and 42,887,726 reads from female and male crabs, respectively). Low-quality (quality <20) reads were trimmed and removed, leaving only high-quality reads (37,020,664 and 41,021,030 from female and male crabs, respectively). A total of 126,188 (female) and 164,616 (male) transcripts were then generated by de novo transcriptome assembly using Trinity. Functional annotation of the obtained unigenes revealed that a large number of key genes and some important pathways may participate in cell proliferation and signal transduction. On the basis of our transcriptome analyses and as confirmed by quantitative real-time PCR, a number of genes potentially involved in the regulation of gonadal development and reproduction of P. trituberculatus were identified: ADRA1B, BAP1, ARL3, and TRPA1. CONCLUSION: This study is the first to report on the whole reproductive system transcriptome information in stage II of P. trituberculatus gonadal development and provides rich resources for further studies to elucidate the molecular basis of the development of reproductive systems and reproduction in crabs. The current study can be used to further investigate functional genomics in this species.

Transcriptome analysis and discovery of genes involved in immune pathways from coelomocytes of Onchidium struma after bacterial challenge.

Onchidium struma widely distributes in subtidal and low-tidal zones, which is considered to be an economical species with rich nutrition, a valuable biomonitor for heavy metal pollution and a representative species for evolution from ocean to land. However, there is limited genetic information available for O. struma development. This study compared transcriptomic profiles of coelomocytes from normal and bacteria infected O. struma by Illumina-based paired-end sequencing to explore the molecular immune mechanism of O. struma against bacterial infection. After assembly, a total of 92,450 unigenes with an average length of 1019 bp were obtained. Approximately 34,964 (37.82%) unigenes were annotated in the Nr NCBI database and 40.1% of unigenes were similar with that of Aplysia californica. Among them, 7609 unigenes were classified into three Gene Ontology (GO) categories: biological process (3250 unigenes, 42.7%), cellular component (2,281, 30.0%) and molecular function (2078 unigenes, 27.3%). A total of 22,776 unigenes were aligned to the Clusters of Orthologous Groups (COG) of proteins and classified into 25 functional categories. Following bacterial infection, 10,623 differently expressed unigenes (DEGs) were identified, including 7644 up-regulated and 2979 down-regulated unigenes. Further KEGG analysis annotated 11,681 DEGs to 42 pathways, and 11 pathways were identified to be related with diseases and immune system. To our knowledge, it was first time to analyze transcriptome profiles of O. struma. Results of the present study will provide valuable theoretical resources for future genetic and genomic research on O. struma. The research results will be helpful for improving the efficiency and quality of artificial breeding, establishing genetic linkage map, and enhancing health management for this species.

Cellulose-based biomass composite films for plastic replacement: Synergistic UV shielding, antibacterial and antioxidant properties.

With the gradual increase in environmental awareness and the growing demand for food safety, sustainable and environmentally friendly cellulose-based materials have become a promising alternative to petroleum-based plastics. However, in practice, packaging materials prepared from cellulose-based materials still have some unsatisfactory properties, such as monofunctionality, low transparency, and lack of UV shielding, antibacterial or antioxidant properties. Herein, a novel synthetic strategy is proposed in this paper, specifically, tannic acid (TA), a green natural extract with antibacterial and antioxidant properties, is used as a plasticizer and cross-linker, and oxidized cellulose nanocellulose (TOCN) modified with folic acid (FA) grafting is blended with TA, and cellulose-based biomass thin films with ultraviolet (UV) shielding, antibacterial, and antioxidant properties have been successfully prepared by using a simple vacuum-assisted filtration. The experimental results showed that the films could completely block ultraviolet light at wavelengths of 200-400 nm while providing 81.47 % transparency in the visible spectrum, while the introduction of TA conferred excellent antibacterial and antioxidant capabilities with antioxidant activity of up to 95 %, and also resulted in films with excellent mechanical properties. Therefore, this work provides ideas for the design and manufacture of competitive biomass green packaging materials, laying the foundation for future applications in food packaging.

Preparation of sustainable oxidized nanocellulose films with high UV shielding effect, high transparency and high strength.

UV protection has become crucial as increasing environmental pollution has led to the destruction of the ozone layer, which has a weakened ability to block UV rays. In this paper, we successfully prepared cellulose-based biomass films with high UV shielding effect, high transparency and high tensile strength by graft-modifying oxidized cellulose nanocellulose (TOCN) with folic acid (FA) and borrowing vacuum-assisted filtration. The films had tunable UV shielding properties depending on the amount of FA added. When the FA addition was 20 % (V/V), the film showed 0 % transmittance in the UV region (200-400 nm) and 90.61 % transmittance in the visible region (600 nm), while the tensile strength was up to 150.04 MPa. This study provides a new integrated process for the value-added utilization of nanocellulose and a new route for the production of functional biomass packaging materials. The film is expected to be applied in the field of food packaging with UV shielding.

Hydroxyapatite: An antibiotic recruiting moiety for local treatment and prevention of bone infections.

Treatment of chronic osteomyelitis by radical debridement and filling of the dead space with antibiotic containing calcium sulfate/hydroxyapatite (CaS/HA) bone substitute has shown excellent long-term outcomes. However, in extensive infections, sessile bacteria may remain in bone cells or soft tissues protected by biofilm leading to recurrences. The primary aim of this study was to evaluate if systemically administrated tetracycline (TET) could bind to pre-implanted HA particles and impart an antibacterial effect locally. In vitro studies indicated that the binding of TET to nano- and micro-sized HA particles was rapid and plateaued already at 1 h. Since protein passivation of HA after in-vivo implantation could affect HA-TET interaction, we investigated the effect of serum exposure on HA-TET binding in an antibacterial assay. Although, serum exposure reduced the zone of inhibition (ZOI) of Staphylococcus aureus, a significant ZOI could still be observed after pre-incubation of HA with serum. We could in addition show that zoledronic acid (ZA) competes for the same binding sites as TET and that exposure to high doses of ZA led to reduced TET-HA binding. In an in-vivo setting, we then confirmed that systemically administered TET seeks HA particles that were pre-implanted in muscle and subcutaneous pouches in rats and mice respectively, preventing HA particles from being colonized by S. aureus. Clinical Significance: This study describes a new drug delivery method that could prevent bacterial colonization of a HA biomaterial and reduce recurrences in bone infection.

Structurally Diverse Phenylpropanamides from Cannabis Fructus and Their Potential Neuroprotective Effects.

This study aimed to investigate the chemical components and potential health benefits of the fruits of Cannabis sativa L. Fourteen new phenylpropanamides designated as cannabisin I-XIV (1-14) and 40 known analogs were isolated and characterized via nuclear magnetic resonance spectroscopy, high-resolution electrospray ionization mass spectrometry, and electronic circular dichroism. In vitro bioassay using H2O2-induced PC12 cell damage models demonstrated that hempseeds extract and compounds 1, 3, 15, 26, 30, 36, 41, and 48 exhibited neuroprotective properties. 3,3'-Demethylgrossamide (30) displayed encouraging protection activity, which was further investigated to relieve the oxidative stress and apoptosis of PC12 cells treated with H2O2. The isolation and characterization of these neuroprotective phenylpropanamides from the fruits of C. sativa provide insights into its health-promoting properties as a healthy food and herbal medicine for preventing and treating neurodegenerative diseases, especially Alzheimer's disease.

Systemically administered zoledronic acid activates locally implanted synthetic hydroxyapatite particles enhancing peri-implant bone formation: A regenerative medicine approach to improve fracture fixation.

Fracture fixation in an ageing population is challenging and fixation failure increases mortality and societal costs. We report a novel fracture fixation treatment by applying a hydroxyapatite (HA) based biomaterial at the bone-implant interface and biologically activating the biomaterial by systemic administration of a bisphosphonate (zoledronic acid, ZA). We first used an animal model of implant integration and applied a calcium sulphate (CaS)/HA biomaterial around a metallic screw in the tibia of osteoporotic rats. Using systemic ZA administration at 2-weeks post-surgery, we demonstrated that the implant surrounded by HA particles showed significantly higher peri­implant bone formation compared to the unaugmented implants at 6-weeks. We then evaluated the optimal timing (day 1, 3, 7 and 14) of ZA administration to achieve a robust effect on peri­implant bone formation. Using fluorescent ZA, we demonstrated that the uptake of ZA in the CaS/HA material was the highest at 3- and 7-days post-implantation and the uptake kinetics had a profound effect on the eventual peri­implant bone formation. We furthered our concept in a feasibility study on trochanteric fracture patients randomized to either CaS/HA augmentation or no augmentation followed by systemic ZA treatment. Radiographically, the CaS/HA group showed signs of increased peri­implant bone formation compared with the controls. Finally, apart from HA, we demonstrated that the concept of biologically activating a ceramic material by ZA could also be applied to ß-tricalcium phosphate. This novel approach for fracture treatment that enhances immediate and long-term fracture fixation in osteoporotic bone could potentially reduce reoperations, morbidity and mortality. STATEMENT OF SIGNIFICANCE: • Fracture fixation in an ageing population is challenging. Biomaterial-based augmentation of fracture fixation devices has been attempted but lack of satisfactory biological response limits their widespread use. • We report the biological activation of locally implanted microparticulate hydroxyapatite (HA) particles placed around an implant by systemic administration of the bisphosphonate zoledronic acid (ZA). The biological activation of HA by ZA enhances peri­implant bone formation. •Timing of ZA administration after HA implantation is critical for optimal ZA uptake and consequently determines the extent of peri­implant bone formation. • We translate the developed concept from small animal models of implant integration to a proof-of-concept clinical study on osteoporotic trochanteric fracture patients. • ZA based biological activation can also be applied to other calcium phosphate biomaterials.

Systemic rifampicin shows accretion to locally implanted hydroxyapatite particles in a rat abdominal muscle pouch model.

Introduction: biomaterials combined with antibiotics are routinely used for the management of bone infections. After eluting high concentrations of antibiotics during the first week, sub-inhibitory concentrations of antibiotics may lead to late repopulation of recalcitrant bacteria. Recent studies have shown that systemically given antibiotics like tetracycline and rifampicin (RIF) could seek and bind to locally implanted hydroxyapatite (HA). The aim of this in vivo study was to test if systemically administered rifampicin could replenish HA-based biomaterials with or without prior antibiotic loading to protect the material from late bacterial repopulation. Methods: in vivo accretion of systemically administered RIF to three different types of HA-based materials was tested. In group 1, nano (n)- and micro (m)-sized HA particles were used, while group 2 consisted of a calcium sulfate / hydroxyapatite (CaS / HA) biomaterial without preloaded antibiotics gentamycin (GEN) or vancomycin (VAN), and in group 3, the CaS / HA material contained GEN (CaS / HA + GEN) or VAN (CaS / HA + VAN). The above materials were implanted in an abdominal muscle pouch model in rats, and at 7 d post-surgery, the animals were assigned to a control group (i.e., no systemic antibiotic) and a test group (i.e., animals receiving one single intraperitoneal injection of RIF each day (4 mg per rat) for 3 consecutive days). Twenty-four hours after the third injection, the animals were sacrificed and the implanted pellets were retrieved and tested against Staphylococcus aureus ATCC 25923 in an agar diffusion assay. After overnight incubation, the zone of inhibition (ZOI) around the pellets were measured. Results: in the control group, 2 / 6 CaS / HA + GEN pellets had a ZOI, while all other harvested pellets had no ZOI. No pellets from animals in test group 1 had a ZOI. In test group 2, 10 / 10 CaS / HA pellets showed a ZOI. In test group 3, 5 / 6 CaS / HA + GEN and 4 / 6 CaS / HA + VAN pellets showed a ZOI. Conclusions: in this proof-of-concept study, we have shown that a locally implanted biphasic CaS / HA carrier after 1 week can be loaded by systemic RIF administration and exert an antibacterial effect. Further in vivo infection models are necessary to validate our findings.

T-cell lymphoma in a Himalayan black bear in China.

A 12-y-old Himalayan black bear suddenly developed depression, anorexia, cough, and dyspnea and died at the Ordos Zoo, China. At autopsy, the mesenteric and cranial mediastinal lymph nodes (LNs) were enlarged; the largest cranial mediastinal LN was ~13 cm in diameter. Scattered-to-diffuse, rounded-or-oval, gray, firm 1-6-mm nodules were observed on the surfaces of the spleen, liver, lungs, and small intestine. Histologically, the enlarged cranial mediastinal and mesenteric LNs, spleen, small intestine, lungs, and liver contained dense populations of neoplastic lymphoid cells (NLCs). The NLCs were round-or-oval with small amounts of mildly eosinophilic cytoplasm and round-or-oval hyperchromatic nuclei with indistinct nucleoli; the mitotic count was 55 in 2.37 mm2. Immunohistochemically, cell membranes and the cytoplasm of NLCs were CD3+, CD79a-, CD20-, CD15-, CD30-, and CD45RA-; hence, the NLCs were derived from T lymphocytes. To our knowledge, T-cell lymphoma has not been reported previously in a Himalayan black bear.

Large-Scale Fabrication of Graded Convex Structure for Superhydrophobic Coating Inspired by Nature.

The addition of toxic substances and poor durability severely limit the market applications of superhydrophobic coatings in the oil−water-separation industry, anti-icing, and self-cleaning surfaces. In order to solve the above problems, a stable, strong, fluorine-free superhydrophobic coating was prepared according to natural inspiration. In this study, polydivinylbenzene (PDVB) was produced by the hydrothermal method, and micro-nanoparticle clusters composed of PDVB particles of different sizes were prepared by controlling the ratio of raw materials, which was then attached to the substrate surface by a simple spraying technique. A rough coating with a lotus-leaf-like layered protruding structure was constructed by depositing particle clusters of different sizes. In the end, the prepared coating showed attractive superhydrophobicity, with a maximum contact angle (CA) that reached up to 160°. In addition, the coating had long-lasting superhydrophobic properties in various environments, such as common liquid and acidic and alkaline solutions. Moreover, in the oil−water-separation process, the superhydrophobic filter paper was still able to obtain a separation efficiency of more than 85% after being used 50 times, and it maintained a contact angle of >150°. At the same time, the coating had excellent dye resistance and self-cleaning performance.

Longitudinal in vivo biodistribution of nano and micro sized hydroxyapatite particles implanted in a bone defect.

Hydroxyapatite (HA) has been widely used as a bone substitute and more recently as a carrier for local delivery of bone targeted drugs. Majority of the approved HA based biomaterials and drug carriers comprise of micrometer sized particulate HA (mHA) or granules and can therefore only be used for extracellular drug release. This shortcoming could be overcome with the use of cell penetrating HA nanoparticles (nHA) but a major concern with the clinical use of nHA is the lack of data on its in vivo biodistribution after implantation. In this study, we aimed to study the in vivo biodistribution of locally implanted nHA in a clinically relevant tibial void in rats and compare it with mHA or a combination of mHA and nHA. To enable in vivo tracking, HA particles were first labelled with 14C-zoledronic acid (14C-ZA), known to have a high binding affinity to HA. The labelled particles were then implanted in the animals and the radioactivity in the proximal tibia and vital organs was detected at various time points (Day 1, 7 and 28) post-implantation using scintillation counting. The local distribution of the particles in the bone was studied with micro-CT. We found that majority (>99.9%) of the implanted HA particles, irrespective of the size, stayed locally at the implantation site even after 28 days and the findings were confirmed using micro-CT. Less than 0.1% radioactivity was observed in the kidney and the spleen at later time points of day 7 and 28. No pathological changes in any of the vital organs could be observed histologically. This is the first longitudinal in vivo HA biodistribution study showing that the local implantation of nHA particles in bone is safe and that nHA could potentially be used for localized drug delivery.

Transparent, conductive and superhydrophobic cellulose films for flexible electrode application.

Cellulose has shown encouraging properties in many applications, such as energy storage, optical instrument and catalysis. In particular, cellulose films have shown potential applications in flexible transparent devices and are expected to replace indium-tin oxide (ITO). However, cellulose is highly hydrophilic and electrically insulating, which limits its scope of application. In this study, the conductivity (R s = 40.3 Ω sq-1), transparency (81.4%) and superhydrophobicity (static contact angle = 153.2°, sliding angle = 4.1°) of cellulose film (CTSC-P) are reported. First, before suction filtration to prepare the film, cellulose was oxidized to improve dispersibility and mechanical strength. Then, the obtained film was hydrophobically modified by grafting long-chain silanes on the surface, followed by electrospinning and electroless plating. In general, the design is an ingenious way to manufacture transparent, conductive, and super-hydrophobic films in the future, and is transformed into a flexible electronic technically feasible device.

Apiosporamide, A 4-hydroxy-2-pyridone Alkaloid, Induces Apoptosis Via PI3K/Akt Signaling Pathway In Osteosarcoma Cells.

BACKGROUND: Osteosarcoma (OS) is a common primary malignant bone tumour in children and young adults. Apiosporamide, a 4-hydroxy-2-pyridone alkaloid from a deep-sea-derived fungus, Arthrinium sp. UJNMF0008, showed anti-proliferative effects toward a panel of human cancer cell lines, and the molecular mechanism in MG63 cells was then investigated in the current work. METHODS: Cell viability was determined with MTT method. Cell proliferation was detected using colony-formation assay. Screening electron microscope was used for morphology observation. Cell cycle and apoptosis was analysed via flow cytometry. Real-time PCR was conducted to evaluate the mRNA expression related with cell apoptosis. The expression levels of proteins related to capase-mediated apoptotic pathway and PI3K/Akt signalling pathway were detected by Western blotting. RESULTS: Apiosporamide significantly decreased cell viability in cancer cells, and also exhibited excellent anti-proliferative effect. Apiosporamide caused cell cycle arrests at G0/G1 phase in MG63 cells. Moreover, apiosporamide induced apoptosis, activated caspase-3, caspase-8 and caspase-9, and regulated expression of Bax and Bcl-2 in MG63 cells. In addition, apiosporamide also attenuated PI3K/Akt signaling pathway. CONCLUSION: Apiosporamide effectively suppressed MG63 cells proliferation by inducing apoptosis through PI3K/Akt and caspase-associated apoptotic pathway.

Heavy metal contamination assessment of surface sediments of the Subei Shoal, China: Spatial distribution, source apportionment and ecological risk.

This study investigated heavy metals (Ni, Zn, Cr, Cu, As, Pb, Cd and Hg) concentrations in surface sediment of Subei Shoal, China, to illustrate their spatial distribution characteristics, sources and potential ecological risk of pollution. Contents of total organic carbon (TOC), clay, silt and sand were 1.7 ±â€¯0.8%, 3.3 ±â€¯3.2%, 13.6 ±â€¯14.2% and 83.1 ±â€¯17.4%, respectively. The spatial distribution of TOC, clay and silt were similar; however, distribution of Hg was inverse. Concentrations of Ni, Zn, Cr, Cu, As, Pb, Cd and Hg were 47.88 ±â€¯8.93, 38.18 ±â€¯8.86, 19.22 ±â€¯5.14, 11.32 ±â€¯5.07, 6.97 ±â€¯2.45, 0.13 ±â€¯0.72, 0.56 ±â€¯0.77 and 0.06 ±â€¯0.02 mg kg-1 sediment, respectively. Principal component analysis suggested that Cu, Zn, Cd, Cr and Ni were mainly derived from natural sources, whereas Pb, Cd, As and Hg from industrial and agricultural sources. Results of geo-accumulation index, potential ecological risk index (RI), pollution load index (PLI), toxic risk index (TRI) and contamination severity index (CSI) demonstrated that pollution levels of Cd and Hg were moderate, which should attract more attention as main pollution factors. The pollution was mainly distributed in the central and northern parts, and the southern part had a good ecological environment. Moreover, the contaminated stations accounted respective for 33.4%, 25.9%, 33.3% and 70.4% of RI, PLI, TRI and CSI, of which 70.4% of the contamination severity index stations contained 66.7% of much lower severity stations. These findings could contribute to more effective exploitation of tidal flat resources, and the prevention and treatment of tidal marsh environment.

Multiwall-carbon-nanotube/cellulose composite fibers with enhanced mechanical and electrical properties by cellulose grafting.

Multiwall-carbon-nanotube (MWCNT)-cellulose/cellulose composite fibers with promoted mechanical and electronic activities were synthesized. Remarkably, the dispersion of MWCNTs in the composite fibers was facilitated through cellulose grafting, resulting in the tensile strength of the obtained MWCNT-cellulose/cellulose composite fibers being increased to 304.6 MPa with 10 wt% MWCNTs involved, which was almost 106.8% higher than that of pristine MWCNT/cellulose fibers with the same amount of MWCNTs. In addition, the electrical conductivity of the MWCNT-cellulose/cellulose composite fibers was enhanced to 1.3 × 10-1 S cm-1 with the dispersion of 10 wt% MWCNTs, which was almost 108 times higher than that of pristine MWCNT/cellulose fibers with the same amount of MWCNTs.

The role of aryl hydrocarbon receptor in bone remodeling.

Bone remodeling is a persistent process for maintaining skeletal system homeostasis, and it depends on the dynamic equilibrium between bone-forming osteoblasts and bone-resorbing osteoclasts. Aryl hydrocarbon receptor (Ahr), a ligand-activated transcription factor, plays a pivotal role in regulating skeletal system. In order to better understand the role of Ahr in bone remodeling, we focused on bone remodeling characteristic, and the effects of Ahr on bone formation and differentiation, which suggest that Ahr is a critical control factor in the process of bone remodeling. Moreover, we discussed the impacts of Ahr on several signaling pathways related to bone remodeling, hoping to provide a theoretical basis to improve bone remodeling.

Enhancement of lignocellulose-carbon nanotubes composites by lignocellulose grafting.

Lignocellulose (LNC) multi-walled carbon nanotubes (MWCNTs) composites were synthesized by covalently grafting a natural polymer, lignocellulose, onto MWCNTs in an ionic liquid, 1-allyl-3-methylimidazolium chloride (AmimCl). Furthermore, the grafting of LNC facilitated the dispersion of the MWCNTs in AmimCl and MWCNTs/LNC films. The elongation at break and tensile strength of grafted-MWCNTs/LNC films with 3wt% of MWCNTs content were 12.2% and 106.7MPa respectively, which was almost 93.7% and 10.7% higher than those of the pristine MWCNTs/LNC films. This finding clearly revealed that the mechanical properties of grafted-MWCNTs/LNC films were dramatically superior to those of the MWCNTs/LNC films.

Cloning of hemoglobin-α1 from half-smooth tongue sole (Cynoglossus semilaevis) and its expression under short-term hypoxia.

This study cloned the hemoglobin α1 from the marine teleost, the half-smooth tongue sole (Cynoglossus semilaevis), and then examined its expression under hypoxia exposure. The full-length of CsHb-α1 (594 bp) cDNA contains an open reading frame encoding 144 amino acids. Sequence analysis shows that the predicted CsHb-α1 amino acids shares high identities with that of other species. Real-time PCR showed that CsHb-α1 was highly expressed in the heart, liver, spleen, kidney and blood. Five to 120 min esposure and long-term (36 h) exposure to hypoxia (1.0 mg/L) significantly increased CsHb-α1 mRNA expression in most tissues compared to those fish held in normoxic conditions (dissolved oxygen (DO): 6.2 mg/L). These results suggested that the up-regulation of Hb-α1 is an important component for adaptation of half-smooth tongue sole to short-term hypoxia.