Strand displacement-triggered FRET nanoprobe tracking TK1 mRNA in living cells for ratiometric fluorimetry of nucleic acid biomarker.

A precisely designed dual-color biosensor has realized a visual assessment of thymidine kinase 1 (TK1) mRNA in both living cells and cell lysates. The oligonucleotide probe is constructed by hybridizing the antisense strand of the target and two recognition sequences, in which FAM serves as the donor and TAMRA as the acceptor. Once interacting with the target, two recognition strands are replaced, and then the antisense complementary sequence forms a more stable double-stranded structure. Due to the increasing spatial distance between two dyes, the FRET is attenuated, leading to a rapid recovery of FAM fluorescence and a reduction of TAMRA fluorescence. A discernible color response from orange to green could be observed by the naked eye, with a limit of detection (LOD) of 0.38 nM and 5.22 nM for spectrometer- and smartphone-based assays, respectively. The proposed ratiometric method transcends previous reports in its capacities in visualizing TK1 expression toward reliable nucleic acid biomarker analysis, which might establish a general strategy for ratiometric biosensing via strand displacement.

Learnable sparse dictionary compressed sensing for channeled spectropolarimeter.

Channeled spectropolarimetry enables real-time measurement of the polarimetric spectral information of the target. A crucial aspect of this technology is the accurate reconstruction of Stokes parameters spectra from the modulated spectra obtained through snapshot measurements. In this paper, a learnable sparse dictionary compressed sensing method is proposed for channeled spectropolarimeter (CSP) spectral reconstruction. Grounded in the compressive sensing framework, this method defines a variable sparse dictionary. It can learn prior knowledge from the measured modulated spectra, continuously optimizing its own structure and parameters iteratively by removing redundant basis functions and refining the matched basis functions. The learned sparse dictionary, post-training, can provide a more accurate sparse representation of the Stokes parameters spectra, enabling the proposed method to achieve more precise reconstruction results. To assess the efficacy of the proposed method, simulations and experiments were conducted, both of which consistently demonstrated the superior performance of the proposed approach. The suggested method is well-positioned to enhance the efficiency and accuracy of polarimetric spectral information retrieval in CSP applications.

Programmable, High-resolution Printing of Spatially Graded Perovskites for Multispectral Photodetectors.

Micro/nanostructured perovskites with spatially graded compositions and bandgaps are promising in filter-free, chip-level multispectral, and hyperspectral detection. However, achieving high-resolution patterning of perovskites with controlled graded compositions is challenging. Here, a programmable mixed electrohydrodynamic printing (M-ePrinting) technique is presented to realize the one-step direct-printing of arbitrary spatially graded perovskite micro/nanopatterns for the first time. M-ePrinting enables in situ mixing and ejection of solutions with controlled composition/bandgap by programmatically varying driving voltage applied to a multichannel nozzle. Composition can be graded over a single dot, line or complex pattern, and the printed feature size is down to 1 µm, which is the highest printing resolution of graded patterns to the knowledge. Photodetectors based on micro/nanostructured perovskites with halide ions gradually varying from Br to I are constructed, which successfully achieve multispectral detection and full-color imaging, with a high detectivity and responsivity of 3.27 × 1015 Jones and 69.88 A W-1, respectively. The presented method provides a versatile and competitive approach for such miniaturized bandgap-tunable perovskite spectrometer platforms and artificial vision systems, and also opens new avenues for the digital fabrication of composition-programmable structures.

Leveraging a Phage-Encoded Noncanonical Amino Acid: A Novel Pathway to Potent and Selective Epigenetic Reader Protein Inhibitors.

Epigenetic reader proteins interpret histone epigenetic marks to regulate gene expression. Given their vital roles and the link between their dysfunction and various diseases, these proteins present compelling targets for therapeutic interventions. Nevertheless, designing selective inhibitors for these proteins poses significant challenges, primarily due to their unique properties such as shallow binding sites and similarities with homologous proteins. To overcome these challenges, we propose an innovative strategy that uses phage display with a genetically encoded noncanonical amino acid (ncAA) containing an epigenetic mark. This ncAA guides binding to the reader protein's active site, allowing the identification of peptide inhibitors with enhanced affinity and selectivity. In this study, we demonstrate this novel approach's effectiveness by identifying potent inhibitors for the ENL YEATS domain that plays a critical role in leukemogenesis. Our strategy involved genetically incorporating Nε-butyryl-l-lysine (BuK), known for its binding to ENL YEATS, into a phage display library for enriching the pool of potent inhibitors. One resultant hit was further optimized by substituting BuK with other pharmacophores to exploit a unique π-π-π stacking interaction with ENL YEATS. This led to the creation of selective ENL YEATS inhibitors with a KD value of 2.0 nM and a selectivity 28 times higher for ENL YEATS than its close homologue AF9 YEATS. One such inhibitor, tENL-S1f, demonstrated robust cellular target engagement and on-target effects to inhibit leukemia cell growth and suppress the expression of ENL target genes. As a pioneering study, this work opens up extensive avenues for the development of potent and selective peptidyl inhibitors for a broad spectrum of epigenetic reader proteins.

Optimal conditions for adenoviral transduction of immature dendritic cells without affecting the tolerogenic activity of DC-based immunotherapy.

Dendritic cells (DCs) play a pivotal role in maintaining immune tolerance. Using recombinant adenovirus (rAd) to deliver vectors to immature dendritic cells (imDCs) is an important method for studying the tolerogenic function of DCs. We found that using RPMI medium and a higher MOI during transduction increased the expression of CD80, CD86, and MHC-II on the surface of imDCs. Our data reveal a significant increase in the secretion of the pro-inflammatory cytokine IL-6 in the group showing the most pronounced phenotypic changes. In the mouse heart transplant model, imDCs with unstable phenotype and function due to adenoviral transduction resulted in an increased proportion of Th1 and Th17 cells in recipients. However, these effects can be managed, and our proposed optimized transduction strategy significantly minimizes these adverse effects. Our study holds significant implications for the development and optimization of immunotherapy utilizing tolerogenic dendritic cells.

BRD4354 Is a Potent Covalent Inhibitor against the SARS-CoV-2 Main Protease.

Numerous organic molecules are known to inhibit the main protease (MPro) of SARS-CoV-2, the pathogen of Coronavirus Disease 2019 (COVID-19). Guided by previous research on zinc-ligand inhibitors of MPro and zinc-dependent histone deacetylases (HDACs), we identified BRD4354 as a potent inhibitor of MPro. The in vitro protease activity assays show that BRD4354 displays time-dependent inhibition against MPro with an IC50 (concentration that inhibits activity by 50%) of 0.72 ± 0.04 µM after 60 min of incubation. Inactivation follows a two-step process with an initial rapid binding step with a KI of 1.9 ± 0.5 µM followed by a second slow inactivation step, kinact,max of 0.040 ± 0.002 min-1. Native mass spectrometry studies indicate that a covalent intermediate is formed where the ortho-quinone methide fragment of BRD4354 forms a covalent bond with the catalytic cysteine C145 of MPro. Based on these data, a Michael-addition reaction mechanism between MPro C145 and BRD4354 was proposed. These results suggest that both preclinical testing of BRD4354 and structure-activity relationship studies based on BRD4354 are warranted to develop more effective anti-COVID therapeutics.

Contribution of elovl5a to Docosahexaenoic Acid (DHA) Synthesis at the Transcriptional Regulation Level in Common Carp, Cyprinus carpio.

Docosahexaenoic acid (DHA) is an essential nutrient for humans and plays a critical role in human development and health. Freshwater fish, such as the common carp (Cyprinus carpio), have a certain degree of DHA biosynthesis ability and could be a supplemental source of human DHA needs. The elongase of very-long-chain fatty acid 5 (Elovl5) is an important enzyme affecting polyunsaturated fatty acid (PUFA) biosynthesis. However, the function and regulatory mechanism of the elovl5 gene related to DHA synthesis in freshwater fish is not clear yet. Previous studies have found that there are two copies of the elovl5 gene, elovl5a and elovl5b, which have different functions. Our research group found significant DHA content differences among individuals in Yellow River carp (Cyprinus carpio var.), and four candidate genes were found to be related to DHA synthesis through screening. In this study, the expression level of elovl5a is decreased in the high-DHA group compared to the low-DHA group, which indicated the down-regulation of elovl5a in the DHA synthesis pathways of Yellow River carp. In addition, using a dual-luciferase reporter gene assay, we found that by targeting the 3'UTR region of elovl5a, miR-26a-5p could regulate DHA synthesis in common carp. After CRISPR/Cas9 disruption of elovl5a, the DHA content in the disrupted group was significantly higher than in the wildtype group; meanwhile, the expression level of elovl5a in the disrupted group was significantly reduced compared with the wildtype group. These results suggest that elovl5a may be down-regulating DHA synthesis in Yellow River carp. This study could provide useful information for future research on the genes and pathways that affect DHA synthesis.

Necklace-like Te-Au reticula platform with three dimensional hotspots Surface-Enhanced Raman Scattering (SERS) sensor for food hazards analysis.

In this work, we combined three-dimensional (3D) necklace-like Te-Au reticula as novel surface-enhanced Raman scattering (SERS) active substrates with oxidation-reduction displacement reactions to construct a molecular machine for SERS detection. The structurally tunable 3D necklace-like spatial structures generated more active 'hot spots' and thus enhanced the sensitivity of SERS signals. Besides, layers of ultrathin nanowires showed high sequence dependence that ensure the repeatability and abundant hotspots at interparticle gaps and guarantee the high SERS performance of the substrate. A better-localized surface plasmon resonance (LSPR) effect of the sensor was verified by finite-difference time-domain (FDTD) analysis in both Raman intensities and electromagnetic field distributions compared to the citrate-stabilized AuNPs and CTAB-protected AuNRs. The proposed strategy can also serve as a universally amplified and sensitive detection platform for monitoring different molecules, thus achieving an amplification detection of 3,3'-diethylthiatricarbocyanine iodide (DTTCI) are 1 nM and R6G with a low limit of detection of 1 pM. Especially, the intensity of the main vibration of R6G from 30 spots of SERS data with excellent reproducibility (relative standard deviation of 6.25 %). High selectivity and accuracy of the SERS sensor were proved by practical analysis melamine (MM) in milk with a linear calibration curve (R2 = 0.9962) and a limit of detection of 0.75 mg/kg. Our research provides a new perspective to construct 3D SERS sensor from integrated structural design.

Immune-like sandwich multiple hotspots SERS biosensor for ultrasensitive detection of NDKA biomarker in serum.

Developing the rapid, specific, and sensitive tumor marker NDKA biosensor has become an urgent need in the field of early diagnosis of colorectal cancer (CRC). Surface-enhanced Raman spectroscopy (SERS) with the advantages of high sensitivity, high resolution as well as providing sample fingerprint, enables rapid and sensitive detection of tumor markers. However, many SERS biosensors rely on boosting the quantity of Raman reporter molecules on individual nanoparticle surfaces, which can result in nanoparticle agglomeration, diminishing the stability and sensitivity of NDKA detection. Here, we proposed an immune-like sandwich multiple hotspots SERS biosensor for highly sensitive and stable analysis of NDKA in serum based on molecularly imprinted polymers and NDKA antibody. The SERS biosensor employs an array of gold nanoparticles, which are coated with a biocompatible polydopamine molecularly imprinted polymer as a substrate to specifically capture NDKA. Then the biosensor detects NDKA through Raman signals as a result of the specific binding of NDKA to the SERS nanotag affixed to the capture substrate along with the formation of multiple hotspots. This SERS biosensor not only avoids the aggregation of nanoparticles but also presents a solution to the obstacles encountered in immune strategies for certain proteins lacking multiple antibody or aptamer binding sites. Furthermore, the practical application of the SERS biosensor is validated by the detection of NDKA in serum with the lower limit of detection (LOD) of 0.25 pg/mL, meanwhile can detect NDKA of 10 ng/mL in mixed proteins solution, illustrating high sensitivity and specificity. This immune-like sandwich multiple hotspots biosensor makes it quite useful for the early detection of CRC and also provides new ideas for cancer biomarker sensing strategy in the future.

Synthesis of Fe3O4core/MIL-100(Fe) shell nanocomposites for tumor chemo-ferroptosis combination therapy and MR imaging.

The application of both chemotherapy and ferrotherapy together has shown great potential in increasing the effectiveness of cancer treatment. To achieve such a combination, we herein have synthesized Fe3O4core/MIL-100(Fe) shell nanocomposites (FM) that can be used for tumor chemo-ferroptosis combination therapy. In these nanocomposites, the anticancer drug 10-hydroxycamptothecin (HCPT) and iron ions could be co-delivered into tumors. On one hand, the released HCPT molecules can enter the cell nucleus and bind with DNA, resulting in induction of tumor cell apoptosis. On the other hand, the iron ions could react with H2O2leading to the production of ROS through the Fenton reaction, thereby triggering tumor cell ferroptosis. Consequently, a superior antitumor effect was achieved through the combination of the apoptosis and ferroptosis. Additionally, the Fe3O4core endowed FM with high performance for magnetic resonance imaging, which further provided novel avenues for imaging guidance therapy. Therefore, we anticipate that application of these nanocomposites could have great potential in the field of tumor therapy.

Short-term exposure to gaseous pollutants is neglected factors for knee osteoarthritis: evidence from a humid subtropical region of China.

Few studies were performed on the impact of exposure to gaseous pollutants on the risk of knee osteoarthritis (KOA). We conducted this study to analyze the association between short-term exposure to gaseous pollutants and the risk of hospitalizations for KOA. A total of 2952 KOA hospitalizations derived from two hospitals in Hefei, and the relationship between gaseous pollutants and KOA hospitalizations was analyzed by a distributed lag non-linear model combined with a generalized linear model. We found that the decreased risk of hospitalizations for KOA were both related to exposure to NO2 (RR = 0.993, lag19 day) and O3 (RR = 0.984, lag0 day), while exposure to CO could increase the risk of hospitalizations for KOA (RR = 1.076, lag2 day). Stratified analyses suggested that the KOA patients < 65 years were more susceptible to O3 exposure, and the female, male, patients ≥ 65 years, and patients < 65 years were both more sensitive to CO exposure. Our findings demonstrated that exposure to NO2, O3 resulted in a decreased risk for KOA hospitalizations, and CO exposure might increase the risk of KOA hospitalizations.

Aperture division multispectral camera for the Earth's reflected solar radiation observation based on the Lagrange L1 point of the Earth-Moon system.

We propose an aperture division multispectral camera for Earth observation (EAMC) based on the Lagrange L1 point of the Earth-Moon system to measure the Earth's reflected solar radiation (RSR), quantify the effective radiative forcing (ERF) and establish the pixel-scale multispectral angular distribution model (ADM) of the Earth's radiance. The EAMC adopts the snapshot technique to provide multispectral images in the 360-920 nm wavelength, employing nine subsystems sharing a primary system. The camera can capture the entire Earth's two-dimensional morphology and spectral fingerprints at a 10 km spatial resolution, with all spectral images acquired concurrently on a single detector. The camera's optical system is designed and simulated, and the stray light is analyzed and suppressed. Simulation and analysis results show that the camera can obtain high-quality images of the Earth's disk with a 2.5° field of view (FOV). The stray light is suppressed to less than 0.05% of the observed multispectral Earth radiation. The novel EAMC provides a new way to generate climate-relevant knowledge from the perspective of global Earth observation and has great potential for other applications in space-based remote sensing spectral imaging.

Extraction of polysaccharides from Maca enhances the treatment effect of 5-FU by regulating CD4+T cells.

In our previous studies, we used a graded alcohol precipitation method to extract four maca polysaccharide components (MCP1, MCP2, MCP3, and MCP4) from maca with various molecular weights. Compared to other three components, MCP2 had stronger immunoregulatory abilities on CD4+T cells. To avoid the immunosuppressive effect of 5-fluorouracil (5-FU), maca polysaccharides in combination with 5-FU treatment were investigated in this study. The results show that 500 mg/kg and 1000 mg/kg MCP2 could significantly delay the growth of tumor and enhance the anti-tumor effect of 5-FU in vivo. Furthermore, MCP2 can partly recover the proliferation of CD4+T cells after being suppressed by 5-FU in vitro. Additionally, in order to explore the mechanism in which MCP2 acts on CD4+T cells, the MCP2 is marked with FITC fluorescence and synthesis MCP2-Tyr-FITC for the first time. Confocal microscope results show that MCP2-Tyr-FITC can directly bind to the surface of CD4+T cells. Together, our work demonstrates that maca polysaccharides could enhance the anti-tumor effect when combined with 5-FU by regulating CD4+T cells, suggesting a novel potential immunomodulator in tumor therapy.

Automatic detection of indoor occupancy based on improved YOLOv5 model.

Indoor occupancy detection is essential for energy efficiency control and Coronavirus Disease 2019 traceability. The number and location of people can be accurately identified and determined through classroom surveillance video analysis. This information is used to manage environmental equipment such as HVAC and lighting systems to reduce energy use. However, the mainstream one-stage YOLO algorithm still uses an anchor-based mechanism and couples detection heads to predict. This results in slow model convergence and poor detection performance for densely occluded targets. Therefore, this paper proposed a novel decoupled anchor-free VariFocal loss convolutional network algorithm DFV-YOLOv5 for occupancy detection to tackle these problems. The proposed method uses the YOLOv5 algorithm as a baseline. It uses the anchor-free mechanism to reduce the number of design parameters needing heuristic tuning. Afterwards, to reduce the coupling of the model, speed up the model's convergence ability, and improve the model detection performance, the detection head is decoupled based on the YOLOv5 model. It can resolve the conflict between classification and regression tasks. In addition, we use the VariFocal loss to assign more weights to difficult data points to optimize the class imbalance problem and use the training target q to measure positive samples, treating positive and negative samples asymmetrically. The total loss function is redesigned, the L 1 loss is increased, and the ablation experiment verifies the effect of the improved loss. By applying a hybrid activation function of the sigmoid linear unit and rectified linear unit, we improved the model's nonlinear representation and reduced the model's inference time. Finally, a classroom dataset was constructed to validate the occupancy detection performance of the model. The proposed model was compared with mainstream target detection models regarding average mean precision, memory allocation, execution time, and the number of parameters on the VOC2012, CrowdHuman and self-built datasets. The experimental results show that the method significantly improves the detection accuracy and robustness, shortens the inference time, and proves the practicality of the algorithm in occupancy detection compared with the mainstream target detection model and related variants of the model.

Controllable synthesis of variable-sized magnetic nanocrystals self-assembled into porous nanostructures for enhanced cancer chemo-ferroptosis therapy and MR imaging.

Magnetic-based nanomaterials are promising for cancer diagnosis and treatment. Herein, we develop a self-assembled approach for the preparation of a porous magnetic nanosystem, DOX/Mn(0.25)-Fe3O4-III NPs, which can simultaneously achieve chemotherapy, ferroptosis therapy and MRI to improve the therapeutic efficacy. By tuning its porous structures, whole particle sizes and compositions, this nanosystem possesses both a high drug loading capacity and excellent Fenton reaction activity. Owing to the synergetic catalysis effect of iron and manganese ions, the Fenton catalytic activity of Mn(0.25)-Fe3O4-III NPs (K cat = 1.2209 × 10-2 min-1) was six times higher than that of pure porous Fe3O4 NPs (K cat = 1.9476 × 10-3 min-1), making them greatly advantageous in ferroptosis-inducing cancer therapy. Moreover, we found out that these Mn(0.25)-Fe3O4-III NPs show a pH-dependent Fenton reaction activity. At acidic tumorous pH, this nanosystem could catalyze H2O2 to produce the cytotoxic ˙OH to kill cancer cells, while in neutral physiological conditions it decomposed H2O2 into biosafe species (H2O and O2). In vivo studies demonstrated that DOX/Mn(0.25)-Fe3O4-III NPs exhibited a significant synergistic anticancer effect of combining chemotherapy and ferroptosis therapy and effective T2-weighted MRI with minimal side effects. Therefore, this porous magnetic nanoplatform has a great potential for combined diagnosis and therapy in future clinical applications.

Real-Time MRI Monitoring of GelMA-Based Hydrogel-Loaded Kartogenin for In Situ Cartilage Regeneration.

The cartilage has poor ability to mount a sufficient healing response. Herein, kartogenin (KGN), an emerging stable non-protein compound with the ability to recruit bone marrow mesenchyme stem cells (BMSCs) to promote chondrogenic differentiation, was grafted onto dopamine-Fe(III) chelating nanoparticles, followed by involving a gelatin- and dextran-based injectable hydrogel to mimic the extracellular matrix to promote cartilage repair. The in vitro results demonstrated that KGN underwent long-term sustained release behavior and availably promoted the deep migration of BMSC cells in yielding hydrogels. Furthermore, in vivo New Zealand white rabbits' cartilage defect model repairing results showed that cartilage defect obtained significant regeneration post operation in the 12th week, and the defect edge almost disappeared compared to adjacent normal cartilage tissue. Meanwhile, the T2-weighted magnetic resonance imaging (MRI) property resulting from dissociative Fe (III) can significantly monitor the degradation degree of the implanted hydrogels in the defect site. This integrated diagnosis and treatment system gives insight into cartilage regeneration.

Design and evaluation of an exergame system to assist knee disorders patients' rehabilitation based on gesture interaction.

We designed a knee rehabilitation exercise game (Exergame) for home-based rehabilitation of patients with knee disorders. The system includes three functional components: knee exercise plan formulation, exergame, and exercise feedback. The 3D Human Pose Estimation based on images is used as the gesture interaction to capture the patient's primary joint motion data. We recruited 20 knee osteoarthritis (KOA) to evaluate the system's feasibility and user experience. The physician's group formulated the patient's exercise plans. The average accuracy of motion recognition is 95.2%, indicating that the system can effectively guide rehabilitation training for KOA patients. The results of the UEQ-S questionnaire, namely the practical quality value (1.63 ± 0.85), hedonic quality value (1.75 ± 0.86), and the total value (1.69 ± 0.86) of 20 patients, indicate that the system provides an excellent user experience, which improves the willingness and compliance of the patients for the active exercise. The above evidence confirms that the proposed approach is suitable for Knee disorders rehabilitation exercise and has promising application prospects. Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-022-00189-5.

One-Pot Synthesis of Ag/Quaternary Ammonium Salt Co-Decorated Mesoporous Silica Nanoparticles for Synergistic Treatment of Cancer and Bacterial Infections.

Developing drug delivery nanosystems with both anticancer and antibacterial effects is of great clinical value. Herein, we report a facile approach to synthesize Ag and quaternary ammonium salt (QAS) co-decorated mesoporous silica nanoparticles (MSNs), namely, Ag/QAS-MSNs, for synergistic treatment of cancer and bacterial infections. In vitro studies demonstrated that Ag/QAS-MSNs not only had a strong antibacterial activity against the bacterial pathogens but also could efficiently induce cancer cell death through an apoptotic pathway. Moreover, in vivo combination therapy with Ag and QAS in Ag/QAS-MSNs was also tested in a nude mouse tumor model, and a significant synergistic anticancer effect, which is superior to that obtained by therapy with Ag-MSNs or QAS-MSNs alone, was achieved. Such excellent anticancer and antibacterial activity of Ag/QAS-MSNs could be attributed to the synergistic effect of Ag ions and QAS. Thus, Ag/QAS-MSNs have a promising future as potent anticancer agents with high antibacterial performance.

Synthesis and Biological Evaluation of Steviol Derivatives with Improved Cytotoxic Activity and Selectivity.

Steviol is an ent-kaurene diterpenoid with interesting pharmacological activity. Several steviol derivatives with an exo-methylene cyclopentanone unit were discovered as potent antitumor agents. However, their poor selectivity for tumor cells relative to normal cells reduces their prospects as potential anticancer drugs. In this study, based on previous work, 32 steviol derivatives, including 28 new analogues, were synthesized. Their cytotoxicity against tumor cells and normal cells was evaluated. Several new derivatives, such as 7a, 7h, and 8f, with improved cytotoxic selectivity and antiproliferative activity were obtained, and the structure-activity relationship correlations were investigated. The new compound 8f displayed potent antiproliferative activity against Huh7 cells (IC50 = 2.6 µM) and very weak cytotoxicity against the corresponding normal cells HHL5 (IC50 = 97.0 µM). Further investigation showed that 8f arrested the cell cycle at the G0/G1 phase and caused reactive oxygen species overproduction, decreased mitochondrial membrane potential, and induced apoptosis of Huh7 cells through inhibition of the PI3K/Akt/mTOR and NF-κB pathway as well as upregulation of Bax/Bcl-2 ratio. The present study suggested that 8f is a promising lead compound for new cancer therapies, and the results presented herein may encourage the further modification of steviol for additional derivatives with enhanced efficacy and selectivity.

Transcriptome Analysis Reveals Molecular Underpinnings of Common Carp (Cyprinus carpio) Under Hypoxia Stress.

As an essential environmental factor that affects the economic benefits of aquaculture, hypoxia is one of the urgent problems to be solved in the aquaculture fish breeding industry. Common carp (Cyprinus carpio) is a critical economic fish in China, and at present, there are many breeding strains of common carp with different character advantages in China, including Hebao red carp (C. carpio var wuyuanesis) and Songpu mirror carp (C. carpio var specularis). Even if the environmental adaptation of common carp is generally strong, the genetic background of hypoxia tolerance in different strains of common carp is unclear yet. This study tested the hypoxia tolerance of Songpu minor carp, Hebao red carp, and their hybrid F1 population by an acute hypoxia treatment. Muscle and liver tissues were used for transcriptome sequencing analysis to identify the key factors for hypoxia tolerance and explore the potential genetic mechanism for breeding high hypoxia tolerance in common carp. The comparative transcriptomic analysis revealed abundant hypoxia response-related genes and their differential regulation mechanism in these two tissues of different common carp strains under acute hypoxia, including immune response, cellular stress response, HIFs (hypoxia-inducible factors), MAP kinase, iron ion binding, and heme binding. Our findings will facilitate future investigation on the hypoxia response mechanism and provide a solid theoretical basis for breeding projects in common carp.