Prognostic Value of a Combined Nomogram Model Integrating 3-Dimensional Deep Learning and Radiomics for Head and Neck Cancer.

OBJECTIVE: The preoperative prediction of the overall survival (OS) status of patients with head and neck cancer (HNC) is significant value for their individualized treatment and prognosis. This study aims to evaluate the impact of adding 3D deep learning features to radiomics models for predicting 5-year OS status. METHODS: Two hundred twenty cases from The Cancer Imaging Archive public dataset were included in this study; 2212 radiomics features and 304 deep features were extracted from each case. The features were selected by univariate analysis and the least absolute shrinkage and selection operator, and then grouped into a radiomics model containing Positron Emission Tomography /Computed Tomography (PET/CT) radiomics features score, a deep model containing deep features score, and a combined model containing PET/CT radiomics features score +3D deep features score. TumorStage model was also constructed using initial patient tumor node metastasis stage to compare the performance of the combined model. A nomogram was constructed to analyze the influence of deep features on the performance of the model. The 10-fold cross-validation of the average area under the receiver operating characteristic curve and calibration curve were used to evaluate performance, and Shapley Additive exPlanations (SHAP) was developed for interpretation. RESULTS: The TumorStage model, radiomics model, deep model, and the combined model achieved areas under the receiver operating characteristic curve of 0.604, 0.851, 0.840, and 0.895 on the train set and 0.571, 0.849, 0.832, and 0.900 on the test set. The combined model showed better performance of predicting the 5-year OS status of HNC patients than the radiomics model and deep model. The combined model was shown to provide a favorable fit in calibration curves and be clinically useful in decision curve analysis. SHAP summary plot and SHAP The SHAP summary plot and SHAP force plot visually interpreted the influence of deep features and radiomics features on the model results. CONCLUSIONS: In predicting 5-year OS status in patients with HNC, 3D deep features could provide richer features for combined model, which showed outperformance compared with the radiomics model and deep model.

Deep learning PET/CT-based radiomics integrates clinical data: A feasibility study to distinguish between tuberculosis nodules and lung cancer.

BACKGROUND: Radiomic diagnosis models generally consider only a single dimension of information, leading to limitations in their diagnostic accuracy and reliability. The integration of multiple dimensions of information into the deep learning model have the potential to improve its diagnostic capabilities. The purpose of study was to evaluate the performance of deep learning model in distinguishing tuberculosis (TB) nodules and lung cancer (LC) based on deep learning features, radiomic features, and clinical information. METHODS: Positron emission tomography (PET) and computed tomography (CT) image data from 97 patients with LC and 77 patients with TB nodules were collected. One hundred radiomic features were extracted from both PET and CT imaging using the pyradiomics platform, and 2048 deep learning features were obtained through a residual neural network approach. Four models included traditional machine learning model with radiomic features as input (traditional radiomics), a deep learning model with separate input of image features (deep convolutional neural networks [DCNN]), a deep learning model with two inputs of radiomic features and deep learning features (radiomics-DCNN) and a deep learning model with inputs of radiomic features and deep learning features and clinical information (integrated model). The models were evaluated using area under the curve (AUC), sensitivity, accuracy, specificity, and F1-score metrics. RESULTS: The results of the classification of TB nodules and LC showed that the integrated model achieved an AUC of 0.84 (0.82-0.88), sensitivity of 0.85 (0.80-0.88), and specificity of 0.84 (0.83-0.87), performing better than the other models. CONCLUSION: The integrated model was found to be the best classification model in the diagnosis of TB nodules and solid LC.

DLBCL-associated NOTCH2 mutations escape ubiquitin-dependent degradation and promote chemoresistance.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Up to 40% of patients with DLBCL display refractory disease or relapse after standard chemotherapy treatment (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP]), leading to significant morbidity and mortality. The molecular mechanisms of chemoresistance in DLBCL remain incompletely understood. Using a cullin-really interesting new gene (RING) ligase-based CRISPR-Cas9 library, we identify that inactivation of the E3 ubiquitin ligase KLHL6 promotes DLBCL chemoresistance. Furthermore, proteomic approaches helped identify KLHL6 as a novel master regulator of plasma membrane-associated NOTCH2 via proteasome-dependent degradation. In CHOP-resistant DLBCL tumors, mutations of NOTCH2 result in a protein that escapes the mechanism of ubiquitin-dependent proteolysis, leading to protein stabilization and activation of the oncogenic RAS signaling pathway. Targeting CHOP-resistant DLBCL tumors with the phase 3 clinical trial molecules nirogacestat, a selective γ-secretase inhibitor, and ipatasertib, a pan-AKT inhibitor, synergistically promotes DLBCL destruction. These findings establish the rationale for therapeutic strategies aimed at targeting the oncogenic pathway activated in KLHL6- or NOTCH2-mutated DLBCL.

Data of MSCs combined with LITUS treatment to improve cognitive impairment in a moderate traumatic brain injury model in rats.

Here, we treated moderately traumatic brain injury (TBI) rats with different modalities, including transplantation with mesenchymal stem cells (MSCs), treatment with low-intensity transcranial ultrasound stimulation (LITUS), and a combination of the two. After the TBI rat model was established, MSCs (in situ injection within 24 h after injury), LITUS (continuous uninterrupted treatment for 28 days) or combined MSCs + LITUS were administered, and mNSS score, performance of behavior and multiple protein levels were compared between groups by behavioral observation, neurological function assessment and pathological analysis. Nestin, neuron-specific enolase (NSE), growth-associated protein 43 (GAP-43) and postsynaptic density protein (PSD-95) were significantly increased and glial fibrillary acidic protein (GFAP) was significantly decreased in the hippocampus of rats in the combination treatment group; brain-derived neurotrophic factor (BDNF), tumor necrosis factor-α (TNF-α) and aquaporin-4 (AQP-4) were significantly decreased in the injured peripheral cortex. The result of mNSS scores was: TBI group > LITUS group > MSCs group > MSCs+LITUS group > sham group. The alternate correct rate of Y-maze was: sham group > MSCs+LITUS group > MSCs group > LITUS group > TBI group. This data compares the efficacy of MSCs, LITUS, and combination therapy on the level expression of stem cell differentiation related proteins, synaptic plasticity-related proteins, neurotrophic factors, inflammatory factors, and edema-related proteins after TBI by quantitative pathological examination. For a complete description, interpretation, and discussion of the data refer to the article in press [1].

Prognostic value of 18F-FDG PET/CT-based radiomics combining dosiomics and dose volume histogram for head and neck cancer.

OBJECTIVES: By comparing the prognostic performance of 18F-FDG PET/CT-based radiomics combining dose features [Includes Dosiomics feature and the dose volume histogram (DVH) features] with that of conventional radiomics in head and neck cancer (HNC), multidimensional prognostic models were constructed to investigate the overall survival (OS) in HNC. MATERIALS AND METHODS: A total of 220 cases from four centres based on the Cancer Imaging Archive public dataset were used in this study, 2260 radiomics features and 1116 dosiomics features and 8 DVH features were extracted for each case, and classified into seven different models of PET, CT, Dose, PET+CT, PET+Dose, CT+Dose and PET+CT+Dose. Features were selected by univariate Cox and Spearman correlation coefficients, and the selected features were brought into the least absolute shrinkage and selection operator (LASSO)-Cox model. A nomogram was constructed to visually analyse the prognostic impact of the incorporated dose features. C-index and Kaplan-Meier curves (log-rank analysis) were used to evaluate and compare these models. RESULTS: The cases from the four centres were divided into three different training and validation sets according to the hospitals. The PET+CT+Dose model had C-indexes of 0.873 (95% CI 0.812-0.934), 0.759 (95% CI 0.663-0.855) and 0.835 (95% CI 0.745-0.925) in the validation set respectively, outperforming the rest models overall. The PET+CT+Dose model did well in classifying patients into high- and low-risk groups under all three different sets of experiments (p < 0.05). CONCLUSION: Multidimensional model of radiomics features combining dosiomics features and DVH features showed high prognostic performance for predicting OS in patients with HNC.

Dissection of the MEF2D-IRF8 transcriptional circuit dependency in acute myeloid leukemia.

Transcriptional dysregulation is a prominent feature in leukemia. Here, we systematically surveyed transcription factor (TF) vulnerabilities in leukemia and uncovered TF clusters that exhibit context-specific vulnerabilities within and between different subtypes of leukemia. Among these TF clusters, we demonstrated that acute myeloid leukemia (AML) with high IRF8 expression was addicted to MEF2D. MEF2D and IRF8 form an autoregulatory loop via direct binding to mutual enhancer elements. One important function of this circuit in AML is to sustain PU.1/MEIS1 co-regulated transcriptional outputs via stabilizing PU.1's chromatin occupancy. We illustrated that AML could acquire dependency on this circuit through various oncogenic mechanisms that results in the activation of their enhancers. In addition to forming a circuit, MEF2D and IRF8 can also separately regulate gene expression, and dual perturbation of these two TFs leads to a more robust inhibition of AML proliferation. Collectively, our results revealed a TF circuit essential for AML survival.

Study of the mechanism by which MSCs combined with LITUS treatment improve cognitive dysfunction caused by traumatic brain injury.

Traumatic brain injury (TBI) substantially affects the quality of life of patients, and an effective therapy is unavailable. Previous studies have shown that mesenchymal stem cells (MSCs) and low-intensity transcranial ultrasound (LITUS) are effective treatments for neurological damage, inflammation, edema and cognitive impairment caused by TBI. However, it is unclear whether the combination of the two treatments exerts an additive effect. In this study, a rat TBI model was established using the controlled cortical impact (CCI) method. Neurological function was assessed by determining the rat modified neurological score (mNSS), and cognitive function was assessed using the Y-maze. Pathological changes in the injured tissue were observed using hematoxylin-eosin (HE) staining and immunohistochemistry (IHC), and western blot was performed to detect the expression levels of Nestin, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), growth-associated protein-43 (GAP-43), postsynaptic density protein (PSD-95), brain-derived neurotrophic factor (BDNF), tumor necrosis factor-α (TNF-α), and aquaporin-4 (AQP-4). Real-time fluorescence quantitative polymerase chain reaction (RT-PCR) was performed to detect the expression levels of GAP-43, PSD-95, BDNF, TNF-α, and AQP-4 mRNA to investigate whether MSCs combined with LITUS exert an additive therapeutic effect of alleviating the cognitive dysfunction caused by TBI and the possible mechanisms involved. Rats exhibited cognitive dysfunction 28 days after TBI, and MSCs combined with LITUS treatment ameliorated the cognitive deficits caused by TBI via increasing Nestin, NSE, GAP-43, PSD-95, and BDNF expression and attenuating the inflammatory response and edema caused by TBI via reducing TNF-α and AQP-4 expression. According to these results, MSCs combined with LITUS is more effective than MSCs alone for the treatment of TBI, and the mechanism may be the promotion of neuronal proliferation and differentiation, and the attenuation of the inflammatory response and edema, which ameliorates the spatial learning memory impairment caused by TBI. MSCs combined with LITUS treatment represents a new approach for the clinical treatment of patients with TBI.

A new species of beaded lacewings (Neuroptera, Berothidae) from mid-Cretaceous Myanmar amber.

A new species of Berothidae, Jersiberothamusivum sp. nov., is described and illustrated from mid-Cretaceous (lowest Cenomanian) Myanmar amber. It is easily distinguished from other species of Berothidae by the configuration of the wing venation including: forewing with distinct areas of infuscation surrounding cross-veins and vein forks, all cross-veins simple prior to ScP-RA fusion, presence of two cross-veins ra-rp; absence of inner or outer graduate series of cross-veins; RP with three branches; and absence of ma-mp cross-veins and cua-cup cross-veins; while hind wing has cross-vein 1r-m absent. The previous diagnoses of Iceloberotha Grimaldi, 2000 and Jersiberotha Grimaldi, 2000 are quite unclear because some characters occur mosaically in both genera. In order to solve this problem and distinguish J.musivum from other species in the family, a new key to species of Berothidae from Myanmar amber has been provided and the diagnoses of Iceloberotha and Jersiberotha have been revised.

ZMYND8-regulated IRF8 transcription axis is an acute myeloid leukemia dependency.

The transformed state in acute leukemia requires gene regulatory programs involving transcription factors and chromatin modulators. Here, we uncover an IRF8-MEF2D transcriptional circuit as an acute myeloid leukemia (AML)-biased dependency. We discover and characterize the mechanism by which the chromatin "reader" ZMYND8 directly activates IRF8 in parallel with the MYC proto-oncogene through their lineage-specific enhancers. ZMYND8 is essential for AML proliferation in vitro and in vivo and associates with MYC and IRF8 enhancer elements that we define in cell lines and in patient samples. ZMYND8 occupancy at IRF8 and MYC enhancers requires BRD4, a transcription coactivator also necessary for AML proliferation. We show that ZMYND8 binds to the ET domain of BRD4 via its chromatin reader cassette, which in turn is required for proper chromatin occupancy and maintenance of leukemic growth in vivo. Our results rationalize ZMYND8 as a potential therapeutic target for modulating essential transcriptional programs in AML.

In vivo CD8+ T cell CRISPR screening reveals control by Fli1 in infection and cancer.

Improving effector activity of antigen-specific T cells is a major goal in cancer immunotherapy. Despite the identification of several effector T cell (TEFF)-driving transcription factors (TFs), the transcriptional coordination of TEFF biology remains poorly understood. We developed an in vivo T cell CRISPR screening platform and identified a key mechanism restraining TEFF biology through the ETS family TF, Fli1. Genetic deletion of Fli1 enhanced TEFF responses without compromising memory or exhaustion precursors. Fli1 restrained TEFF lineage differentiation by binding to cis-regulatory elements of effector-associated genes. Loss of Fli1 increased chromatin accessibility at ETS:RUNX motifs, allowing more efficient Runx3-driven TEFF biology. CD8+ T cells lacking Fli1 provided substantially better protection against multiple infections and tumors. These data indicate that Fli1 safeguards the developing CD8+ T cell transcriptional landscape from excessive ETS:RUNX-driven TEFF cell differentiation. Moreover, genetic deletion of Fli1 improves TEFF differentiation and protective immunity in infections and cancer.

H3K27me3-rich genomic regions can function as silencers to repress gene expression via chromatin interactions.

The mechanisms underlying gene repression and silencers are poorly understood. Here we investigate the hypothesis that H3K27me3-rich regions of the genome, defined from clusters of H3K27me3 peaks, may be used to identify silencers that can regulate gene expression via proximity or looping. We find that H3K27me3-rich regions are associated with chromatin interactions and interact preferentially with each other. H3K27me3-rich regions component removal at interaction anchors by CRISPR leads to upregulation of interacting target genes, altered H3K27me3 and H3K27ac levels at interacting regions, and altered chromatin interactions. Chromatin interactions did not change at regions with high H3K27me3, but regions with low H3K27me3 and high H3K27ac levels showed changes in chromatin interactions. Cells with H3K27me3-rich regions knockout also show changes in phenotype associated with cell identity, and altered xenograft tumor growth. Finally, we observe that H3K27me3-rich regions-associated genes and long-range chromatin interactions are susceptible to H3K27me3 depletion. Our results characterize H3K27me3-rich regions and their mechanisms of functioning via looping.

ALC1 links chromatin accessibility to PARP inhibitor response in homologous recombination-deficient cells.

The response to poly(ADP-ribose) polymerase inhibitors (PARPi) is dictated by homologous recombination (HR) DNA repair and the abundance of lesions that trap PARP enzymes. It remains unclear, however, if the established role of PARP in promoting chromatin accessibility impacts viability in these settings. Using a CRISPR-based screen, we identified the PAR-binding chromatin remodeller ALC1/CHD1L as a key determinant of PARPi toxicity in HR-deficient cells. ALC1 loss reduced viability of breast cancer gene (BRCA)-mutant cells and enhanced sensitivity to PARPi by up to 250-fold, while overcoming several resistance mechanisms. ALC1 deficiency reduced chromatin accessibility concomitant with a decrease in the association of base damage repair factors. This resulted in an accumulation of replication-associated DNA damage, increased PARP trapping and a reliance on HR. These findings establish PAR-dependent chromatin remodelling as a mechanistically distinct aspect of PARPi responses and therapeutic target in HR-deficient cancers.

High-performance CRISPR-Cas12a genome editing for combinatorial genetic screening.

CRISPR-based genetic screening has revolutionized cancer drug target discovery, yet reliable, multiplex gene editing to reveal synergies between gene targets remains a major challenge. Here, we present a simple and robust CRISPR-Cas12a-based approach for combinatorial genetic screening in cancer cells. By engineering the CRISPR-AsCas12a system with key modifications to the Cas protein and its CRISPR RNA (crRNA), we can achieve high efficiency combinatorial genetic screening. We demonstrate the performance of our optimized AsCas12a (opAsCas12a) through double knockout screening against epigenetic regulators. This screen reveals synthetic sick interactions between Brd9&Jmjd6, Kat6a&Jmjd6, and Brpf1&Jmjd6 in leukemia cells.

Deciphering the biodegradation of petroleum hydrocarbons using FTIR spectroscopy: application to a contaminated site.

The chemical composition of groundwater in a petroleum-contaminated site is determined by the present functional groups and these play a vital role in a feasibility remediation technique. Based on the in situ investigation of a contaminated shallow groundwater in an oilfield, Fourier transform infrared (FTIR) spectroscopy associated with chemometric treatments, principal component analysis (PCA), and simple-to-use interactive self-modeling mixture analysis (SIMPLISMA), were used to decipher the biodegradation process by analyzing the conversion of functional groups. Environmental factors that can influence microbial metabolism were also evaluated for a comprehensive explanation. FTIR spectroscopy and PCA results showed that the contamination in the study area can be divided into three parts based on FTIR spectra: (1) regular contamination plume distribution and biodegradation level to fresh oil, (2) moderate biodegradation area, and (3) intensive biodegradation area. FTIR spectra further revealed the present functional groups as aliphatic, aromatic, and polar family compounds. SIMPLISMA was used to discuss the degree of biodegradation along the flow path quantitatively and qualitatively and elucidated that the aliphatic and aromatic compounds were mainly metabolized into polar compounds with nitrogen, sulfur, and oxygen via microbes. During metabolism, microbial indices, such as the Shannon-Weaver, Simpson, and Pielou indices, indicated that microbial diversity did not greatly change; hence, hydrocarbons were constantly consumed to feed dominant microbes. Dissolved oxygen concentrations decreased from 4.58 ± 0.31 mg/L (in monitoring well Z1) to 3.21 ± 0.26 mg/L (in monitoring well Z16) and then became constant in the down-gradient area, demonstrating that aerobic biodegradation was the dominant process at the up-gradient plume. Results were in accordance with the oxidation index, which continuously increased from 0.028 ± 0.013 (in monitoring well Z1) to 0.669 ± 0.047 (in monitoring well Z10), showing that oxygen was consumed along the flow path. Similarly, concentration changes in Fe2+, Mn2+, and SO4 2- proved that the down-gradient area was in reduction condition.

Predation experience underlies the relationship between locomotion capability and survival.

The positive relationship between locomotion performance and survival under predation has long been suggested yet seldom demonstrated with direct evidence. We investigate the effects of predator exposure on locomotion capacity (both fast-start escape and critical swimming performance), survival under predation and the relationships between these factors in juvenile Chinese bream (Parabramis pekinensis). This study aims to test whether there is a positive relationship between the above factors and whether such relationships are context dependent (i.e., with or without 20 d of predator exposure). We found that predator-exposed Chinese bream showed higher rates of survival under predation and improved fast-start swimming performance compared with individuals not exposed to predation. At individual level, no relationship was found between survival and any locomotion performance component in the no-predator group, but mean fast-start swimming speed, maneuverability and responsiveness were all positively related to survival in the predator group after 20 d of exposure. This finding indicates that the recognition of and vigilance for predators achieved through predation experience can be crucial preconditions for prey to employ the fast-start escape response, especially to escape ambush predators. Furthermore, a tradeoff was observed between the critical and fast-start swimming performances in the predator group, but not in the no-predator group, which may have been due to the intensified competition throughout the entire locomotion-support system (e.g., energy, proportions of slow- and fast-twitch muscle fibers) between critical and fast-start swimming because the increased demand for fast-start escape capacity constrains (or compromises) critical swimming performance under the threat of predation.

A Transcription Factor Addiction in Leukemia Imposed by the MLL Promoter Sequence.

The Mixed Lineage Leukemia gene (MLL) is altered in leukemia by chromosomal translocations to produce oncoproteins composed of the MLL N-terminus fused to the C-terminus of a partner protein. Here, we used domain-focused CRISPR screening to identify ZFP64 as an essential transcription factor in MLL-rearranged leukemia. We show that the critical function of ZFP64 in leukemia is to maintain MLL expression via binding to the MLL promoter, which is the most enriched location of ZFP64 occupancy in the human genome. The specificity of ZFP64 for MLL is accounted for by an exceptional density of ZFP64 motifs embedded within the MLL promoter. These findings demonstrate how a sequence anomaly of an oncogene promoter can impose a transcriptional addiction in cancer.

5C-ID: Increased resolution Chromosome-Conformation-Capture-Carbon-Copy with in situ 3C and double alternating primer design.

Mammalian genomes are folded in a hierarchy of compartments, topologically associating domains (TADs), subTADs, and looping interactions. Currently, there is a great need to evaluate the link between chromatin topology and genome function across many biological conditions and genetic perturbations. Hi-C can generate genome-wide maps of looping interactions but is intractable for high-throughput comparison of loops across multiple conditions due to the enormous number of reads (>6 Billion) required per library. Here, we describe 5C-ID, a new version of Chromosome-Conformation-Capture-Carbon-Copy (5C) with restriction digest and ligation performed in the nucleus (in situ Chromosome-Conformation-Capture (3C)) and ligation-mediated amplification performed with a double alternating primer design. We demonstrate that 5C-ID produces higher-resolution 3D genome folding maps with reduced spatial noise using markedly lower cell numbers than canonical 5C. 5C-ID enables the creation of high-resolution, high-coverage maps of chromatin loops in up to a 30 Megabase subset of the genome at a fraction of the cost of Hi-C.

Efficacy of a Chinese Herbal Medicine Compound Zhangpi Ointment against Hydroxyurea-Induced Leg Ulcers: A Prospective, Randomized, Open-Label, Controlled Clinical Trial.

Objective. The randomized controlled trial was to evaluate the efficacy of topical Chinese herbal Zhangpi Ointment for hydroxyurea-induced leg ulcers in patients with myeloproliferative neoplasms. Patients and Methods. This single-center, prospective, randomized, open-label, controlled clinical trial conducted at Shanghai Ninth People's Hospital enrolled 54 patients with hydroxyurea-induced leg ulcers. Patients were randomly assigned to the control group (n = 27) treated with chlorhexidine dressing or the intervention group (n = 27) treated with the Zhangpi Ointment. Finally, 26 patients in the control group and 23 patients in the intervention group completed 8 weeks of observation. Results. The rate of complete healing was 100% for the intervention group, which was significantly higher than that of the control group (96.15%) (P<0.05). Furthermore, the intervention group achieved a significantly higher rate of wound healing (95.56%) than the control group (69.02%) at week 4 (P<0.01). The intervention group took 34 ± 5 days to achieve complete healing while the control group took 41 ± 7 days (P < 0.01). Moreover, grade 3/4 side effects were observed in neither group. Conclusion. The Zhangpi Ointment is effective in promoting the healing of hydroxyurea-induced leg ulcers in patients with myeloproliferative neoplasms, providing a therapeutic option for a condition that is recalcitrant to conventional therapy.

Ethanol metabolism varies with hypoxia tolerance in ten cyprinid species.

During periods of severe hypoxia or anoxia, Carassius spp. are known for their ability to produce ethanol as their anaerobic end product, which diffuses into the environment thereby reducing the osmotic and acidotic load associated with "anaerobic" glycolysis. However, the relationship between alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) activities, key ethanol metabolizing enzymes, and hypoxia tolerance among Carassius spp. and their closely related non-ethanol-producing cyprinids remains unclear. To address this, we quantified the activity levels of key anaerobic enzymes in liver and muscle in species of cyprinids over 48 h of severe hypoxia exposure (0.7 kPa). As predicted, muscle ADH activity was highest in the two most hypoxia-tolerant species (Carassius spp.), with very low levels present in the other species examined. However, liver ADH activities showed an inverse relationship with hypoxia tolerance, with the most hypoxia-tolerant fish having the lowest ADH activity. There was no correlation between hypoxia tolerance and ALDH and LDH activities in muscle or liver. All species produced lactate, reaching their highest levels after 8 h, but returning to near-baseline levels by 48 h of sustained exposure to hypoxia, suggesting lactate oxidation or depressed ATP demand. Liver glycogen content was not affected by 48 h hypoxia exposure in the most hypoxia-tolerant species, whereas the least tolerant species consumed the majority of the liver glycogen stores, which is probably due to the greater relative hypoxia exposure experienced by these species. Our findings that liver ADH activities were inversely related to hypoxia tolerance suggests that in all but Carassius spp., the ethanol metabolizing pathways in cyprinids is largely similar to that observed in other vertebrates and plays a role in the detoxification of ethanol. Furthermore, conservation of glycogen stores may be the result of metabolic-depressing pathways in the more tolerant species, regardless of the ability to produce ethanol, or adaptations that improve oxygen uptake to reduce metabolic demands due to hypoxia.

Standard metabolic rate predicts growth trajectory of juvenile Chinese crucian carp (Carassius auratus) under changing food availability.

Phenotypic traits vary greatly within populations and can have a significant influence on aspects of performance. The present study aimed to investigate the effects of individual variation in standard metabolic rate (SMR) on growth rate and tolerance to food deprivation in juvenile Chinese crucian carp (Carassius auratus) under varying levels of food availability. To address this issue, 19 high and 16 low SMR individuals were randomly assigned to a satiation diet for 3 weeks, whereas another 20 high and 16 low SMR individuals were assigned to a restricted diet (approximately 50% of satiation) for the same period. Then, all fish were completely food-deprived for another 3 weeks. High SMR individuals showed a higher growth rate when fed to satiation, but this advantage of SMR did not exist in food-restricted fish. This result was related to improved feeding efficiency with decreased food intake in low SMR individuals, due to their low food processing capacity and maintenance costs. High SMR individuals experienced more mass loss during food deprivation as compared to low SMR individuals. Our results here illustrate context-dependent costs and benefits of intraspecific variation in SMR whereby high SMR individuals show increased growth performance under high food availability but had a cost under stressful environments (i.e. food shortage).