Integrating massive RNA-seq data to elucidate transcriptome dynamics in Drosophila melanogaster.

The volume of ribonucleic acid (RNA)-seq data has increased exponentially, providing numerous new insights into various biological processes. However, due to significant practical challenges, such as data heterogeneity, it is still difficult to ensure the quality of these data when integrated. Although some quality control methods have been developed, sample consistency is rarely considered and these methods are susceptible to artificial factors. Here, we developed MassiveQC, an unsupervised machine learning-based approach, to automatically download and filter large-scale high-throughput data. In addition to the read quality used in other tools, MassiveQC also uses the alignment and expression quality as model features. Meanwhile, it is user-friendly since the cutoff is generated from self-reporting and is applicable to multimodal data. To explore its value, we applied MassiveQC to Drosophila RNA-seq data and generated a comprehensive transcriptome atlas across 28 tissues from embryogenesis to adulthood. We systematically characterized fly gene expression dynamics and found that genes with high expression dynamics were likely to be evolutionarily young and expressed at late developmental stages, exhibiting high nonsynonymous substitution rates and low phenotypic severity, and they were involved in simple regulatory programs. We also discovered that human and Drosophila had strong positive correlations in gene expression in orthologous organs, revealing the great potential of the Drosophila system for studying human development and disease.

Prediction model of crowd noise in large waiting halls.

Crowd noise is usually the primary noise in large waiting halls, and it is difficult to predict because it is influenced by several factors such as room acoustics and crowd characteristics. This study developed a crowd noise prediction model based on the superposition of direct and reverberant sound energy using the factors of the spatial layout of waiting halls, number and distribution of crowds, behavior ratio (ratio of vocal passengers to the total number of passengers), and average crowd sound power. To verify the model, on-site measurements were conducted in two large waiting halls to obtain the necessary input parameters. The crowd noise levels in one of the waiting halls were obtained from 1-s noise level data after excluding broadcast periods. A method for determining an individual's average sound power based on the model was also presented and found to be approximately 70.6 dB. Finally, the model was verified using measured data, and it showed that the model could accurately predict the average crowd noise level and changing trend of crowd noise in temporal and spatial dimensions with an average R-square of approximately 0.55 and average difference of approximately 1.1 dBA between the predicted and measured results.

Mannose and phosphomannose isomerase regulate energy metabolism under glucose starvation in leukemia.

Diverse metabolic changes are induced by various driver oncogenes during the onset and progression of leukemia. By upregulating glycolysis, cancer cells acquire a proliferative advantage over normal hematopoietic cells; in addition, these changes in energy metabolism contribute to anticancer drug resistance. Because leukemia cells proliferate by consuming glucose as an energy source, an alternative nutrient source is essential when glucose levels in bone marrow are insufficient. We profiled sugar metabolism in leukemia cells and found that mannose is an energy source for glycolysis, the tricarboxylic acid (TCA) cycle, and the pentose phosphate pathway. Leukemia cells express high levels of phosphomannose isomerase (PMI), which mobilizes mannose to glycolysis; consequently, even mannose in the blood can be used as an energy source for glycolysis. Conversely, suppression of PMI expression or a mannose load exceeding the processing capacity of PMI inhibited transcription of genes related to mitochondrial metabolism and the TCA cycle, therefore suppressing the growth of leukemia cells. High PMI expression was also a poor prognostic factor for acute myeloid leukemia. Our findings reveal a new mechanism for glucose starvation resistance in leukemia. Furthermore, the combination of PMI suppression and mannose loading has potential as a novel treatment for driver oncogene-independent leukemia.

Hybrid-type and two-tetrad antiparallel telomere DNA G-quadruplex structures in living human cells.

Although the telomeric sequence has been reported to form various G-quadruplex topologies in vitro and in Xenopus laevis oocytes, in living human cells, the topology of telomeric DNA G-quadruplex remains a challenge. To investigate the human telomeric DNA G-quadruplex in a more realistic human cell environment, in the present study, we demonstrated that the telomeric DNA sequence can form two hybrid-type and two-tetrad antiparallel G-quadruplex structures by in-cell 19F NMR in living human cells (HELA CELLS). This result provides valuable information for understanding the structures of human telomeric DNA in living human cells and for the design of new drugs that target telomeric DNA.

Adherence of Mobile App-Based Surveys and Comparison With Traditional Surveys: eCohort Study.

BACKGROUND: eCohort studies offer an efficient approach for data collection. However, eCohort studies are challenged by volunteer bias and low adherence. We designed an eCohort embedded in the Framingham Heart Study (eFHS) to address these challenges and to compare the digital data to traditional data collection. OBJECTIVE: The aim of this study was to evaluate adherence of the eFHS app-based surveys deployed at baseline (time of enrollment in the eCohort) and every 3 months up to 1 year, and to compare baseline digital surveys with surveys collected at the research center. METHODS: We defined adherence rates as the proportion of participants who completed at least one survey at a given 3-month period and computed adherence rates for each 3-month period. To evaluate agreement, we compared several baseline measures obtained in the eFHS app survey to those obtained at the in-person research center exam using the concordance correlation coefficient (CCC). RESULTS: Among the 1948 eFHS participants (mean age 53, SD 9 years; 57% women), we found high adherence to baseline surveys (89%) and a decrease in adherence over time (58% at 3 months, 52% at 6 months, 41% at 9 months, and 40% at 12 months). eFHS participants who returned surveys were more likely to be women (adjusted odds ratio [aOR] 1.58, 95% CI 1.18-2.11) and less likely to be smokers (aOR 0.53, 95% CI 0.32-0.90). Compared to in-person exam data, we observed moderate agreement for baseline app-based surveys of the Physical Activity Index (mean difference 2.27, CCC=0.56), and high agreement for average drinks per week (mean difference 0.54, CCC=0.82) and depressive symptoms scores (mean difference 0.03, CCC=0.77). CONCLUSIONS: We observed that eFHS participants had a high survey return at baseline and each 3-month survey period over the 12 months of follow up. We observed moderate to high agreement between digital and research center measures for several types of surveys, including physical activity, depressive symptoms, and alcohol use. Thus, this digital data collection mechanism is a promising tool to collect data related to cardiovascular disease and its risk factors.

A Nucleoside Derivative 5-Vinyluridine (VrU) for Imaging RNA in Cells and Animals.

In the present study, we used a nucleoside derivative 5-vinyluridine (VrU) for labeling during cell division and for tumor imaging in living mice. We demonstrated that the functional nucleoside bearing a 5-vinyl group is metabolically incorporated into cellular RNA and can be used to image RNA using a Diels-Alder reaction. The reagent allows for simultaneous and clear imaging of DNA and RNA in mammalian cells at single-cell resolution. We extended this approach to observe DNA and RNA behaviors in several basic stages of cell division. We further demonstrated that the derivative can be used for fluorescence imaging of tumor in live mice.

Species Identification of Oaks (Quercus L., Fagaceae) from Gene to Genome.

Species identification of oaks (Quercus) is always a challenge because many species exhibit variable phenotypes that overlap with other species. Oaks are notorious for interspecific hybridization and introgression, and complex speciation patterns involving incomplete lineage sorting. Therefore, accurately identifying Quercus species barcodes has been unsuccessful. In this study, we used chloroplast genome sequence data to identify molecular markers for oak species identification. Using next generation sequencing methods, we sequenced 14 chloroplast genomes of Quercus species in this study and added 10 additional chloroplast genome sequences from GenBank to develop a DNA barcode for oaks. Chloroplast genome sequence divergence was low. We identified four mutation hotspots as candidate Quercus DNA barcodes; two intergenic regions (matK-trnK-rps16 and trnR-atpA) were located in the large single copy region, and two coding regions (ndhF and ycf1b) were located in the small single copy region. The standard plant DNA barcode (rbcL and matK) had lower variability than that of the newly identified markers. Our data provide complete chloroplast genome sequences that improve the phylogenetic resolution and species level discrimination of Quercus. This study demonstrates that the complete chloroplast genome can substantially increase species discriminatory power and resolve phylogenetic relationships in plants.

Earliella scabrosa-associated postoperative Endophthalmitis after Phacoemulsification with intraocular lens implantation: a case report.

BACKGROUND: Postoperative endophthalmitis after cataract surgery is a severe eye infection that can lead to irreversible blindness in the affected eye. The characteristics, treatment and prognosis of this disease vary because of its association with different pathogens. Here, we report what is possibly the first case of endophthalmitis after cataract surgery to be associated with the rare pathogen Earliella scabrosa. CASE PRESENTATION: A 56-year-old man from Hainan Island (China) with a history of phacoemulsification and type II diabetes mellitus underwent intraocular lens (IOL) implantation. He later presented with progressive endophthalmitis in his right eye. IOL explantation with capsular bag removal and a 23G pars plana vitrectomy combined with a silicone oil tamponade was performed. The infection was cleared without recurrence, and the patient's visual acuity improved from light perception to 20/200 in the right eye. An in vitro culture determined that the causative pathogen was Earliella scabrosa, and this result was confirmed by an internal transcribed spacer (ITS) sequence analysis. CONCLUSION: Earliella scabrosa has never been reported as an infectious agent in human eyes, and its clinical significance remains unknown. Here, we report a rare case of Earliella scabrosa-associated endophthalmitis after cataract surgery. The fungal infection presented as an acute attack and was successfully treated with vitrectomy.

Ecological stoichiometry-based study of the influence of soil saline-alkali stress on nutrient homeostasis in L. chinensis.

Soil salinization is a major cause of land degradation and hinders the effective utilization of agricultural land resources. Leymus chinensis (L. chinensis), as a dominant species with wide ecological amplitude, plays an important role in improving saline-alkali grasslands and indicating the degree of salinization. In this study, a sand culture experiment (nitrogen and phosphorus addition accompanied by saline-alkali stress) was designed to investigate the impact of different saline-alkali environments on the ecological stoichiometric homeostasis of L. chinensis with the aim of elucidating the saline-alkali resistance mechanisms. The results showed that the homeostasis indexes of N, P and N:P in the aboveground part of L. chinensis were generally higher than those in the belowground part under different saline-alkali conditions. Furthermore, the homeostasis index of N (HN) was greater than that of P (HP) in the aboveground part, whereas HN was less than HP in the belowground part. This indicates that the growth aboveground of L. chinensis was mainly dependent on N, whereas the growth belowground was mainly affected by P. The homeostasis index of the aboveground organs was 4.45-12.93 under pH 7-9.8. In contrast, HN and HN:P(+N) in the belowground organs did not conform to a homeostasis model when pH > 9.1. Consequently, when L. chinensis is subjected to high saline-alkali stress, the homeostasis reaction of the roots is more sensitive than that of the aboveground organs.

Loss of MAP3K1 enhances proliferation and apoptosis during retinal development.

Precise coordination of progenitor cell proliferation and differentiation is essential for proper organ morphogenesis and function during mammalian development. The mitogen-activated protein kinase kinase kinase 1 (MAP3K1) has a well-established role in anterior eyelid development, as Map3k1-knockout mice have defective embryonic eyelid closure and an `eye-open at birth' (EOB) phenotype. Here, we show that MAP3K1 is highly expressed in the posterior of the developing eye and is required for retina development. The MAP3K1-deficient mice exhibit increased proliferation and apoptosis, and Müller glial cell overproduction in the developing retinas. Consequently, the retinas of these mice show localized rosette-like arrangements in the outer nuclear layer, and develop abnormal vascularization, broken down retinal pigment epithelium, photoreceptor loss and early onset of retinal degeneration. Although the retinal defect is associated with increased cyclin D1 and CDK4/6 expression, and RB phosphorylation and E2F-target gene upregulation, it is independent of the EOB phenotype and of JNK. The retinal developmental defect still occurs in knockout mice that have undergone tarsorrhaphy, but is absent in compound mutant Map3k1(+/ΔKD)Jnk1(-/-) and Map3k1(+/ΔKD)Jnk(+/-)Jnk2(+/-) mice that have EOB and reduced JNK signaling. Our results unveil a novel role for MAP3K1 in which it crosstalks with the cell cycle regulatory pathways in the prevention of retina malformation and degeneration.

Ocular delivery of pRNA nanoparticles: distribution and clearance after subconjunctival injection.

PURPOSE: RNA nanoparticles derived from the three-way junction (3WJ) of the pRNA of bacteriophage phi29 DNA packaging motor were previously found to be thermodynamically stable. As the nanoparticles could have potential in ocular drug delivery, the objectives in the present study were to investigate the distribution of pRNA nanoparticles after subconjunctival injection and examine the feasibility to deliver the nanoparticles to the cells of cornea and retina. METHODS: Alexa647-labeled pRNA nanoparticles (pRNA-3WJ and pRNA-X) and double-stranded RNA (dsRNA) were administered via subconjunctival injection in mice. Alexa647 dye was a control. Topical administration was performed for comparison. Ocular clearance of pRNA nanoparticles and dsRNA after the injection was assessed using whole-body fluorescence imaging of the eyes. The numbers of cells in the ocular tissues with nanoparticle cell internalization were determined in fluorescence microscopy of dissected eye tissues. RESULTS: After subconjunctival injection, pRNA nanoparticles and dsRNA were observed to distribute into the eyes and cleared through the lymph. pRNA-3WJ, pRNA-X, and dsRNA were found in the cells of the conjunctiva, cornea, and sclera, but only pRNA-X was in the cells of the retina. Topical administration was not effective in delivering the nanoparticles to the eye. CONCLUSIONS: The pRNA nanoparticles were delivered to the cells in the eye via subconjunctival injection, and cell internalization was achieved in the cornea with pRNA-3WJ and pRNA-X and in the retina with pRNA-X. Only the X-shape pRNA-X could enter the retina.

Epitaxial Growth of GaN Films on Chemical-Vapor-Deposited 2D MoS2 Layers by Plasma-Assisted Molecular Beam Epitaxy.

The van der Waals epitaxy of wafer-scale GaN on 2D MoS2 and the integration of GaN/MoS2 heterostructures were investigated in this report. GaN films have been successfully grown on 2D MoS2 layers using three different Ga fluxes via a plasma-assisted molecular beam epitaxy (PA-MBE) system. The substrate for the growth was a few-layer 2D MoS2 deposited on sapphire using chemical vapor deposition (CVD). Three different Ga fluxes were provided by the gallium source of the K-cell at temperatures of 825, 875, and 925 °C, respectively. After the growth, RHEED, HR-XRD, and TEM were conducted to study the crystal structure of GaN films. The surface morphology was obtained using FE-SEM and AFM. Chemical composition was confirmed by XPS and EDS. Raman and PL spectra were carried out to investigate the optical properties of GaN films. According to the characterizations of GaN films, the van der Waals epitaxial growth mechanism of GaN films changed from 3D to 2D with the increase in Ga flux, provided by higher temperatures of the K-cell. GaN films grown at 750 °C for 3 h with a K-cell temperature of 925 °C demonstrated the greatest crystal quality, chemical composition, and optical properties. The heterostructure of 3D GaN on 2D MoS2 was integrated successfully using the low-temperature PA-MBE technique, which could be applied to novel electronics and optoelectronics.

Structurally constrained and pathology-aware convolutional transformer generative adversarial network for virtual histology staining of human coronary optical coherence tomography images.

Significance: There is a significant need for the generation of virtual histological information from coronary optical coherence tomography (OCT) images to better guide the treatment of coronary artery disease (CAD). However, existing methods either require a large pixel-wise paired training dataset or have limited capability to map pathological regions. Aim: The aim of this work is to generate virtual histological information from coronary OCT images, without a pixel-wise paired training dataset while capable of providing pathological patterns. Approach: We design a structurally constrained, pathology-aware, transformer generative adversarial network, namely structurally constrained pathology-aware convolutional transformer generative adversarial network (SCPAT-GAN), to generate virtual stained H&E histology from OCT images. We quantitatively evaluate the quality of virtual stained histology images by measuring the Fréchet inception distance (FID) and perceptual hash value (PHV). Moreover, we invite experienced pathologists to evaluate the virtual stained images. Furthermore, we visually inspect the virtual stained image generated by SCPAT-GAN. Also, we perform an ablation study to validate the design of the proposed SCPAT-GAN. Finally, we demonstrate 3D virtual stained histology images. Results: Compared to previous research, the proposed SCPAT-GAN achieves better FID and PHV scores. The visual inspection suggests that the virtual histology images generated by SCPAT-GAN resemble both normal and pathological features without artifacts. As confirmed by the pathologists, the virtual stained images have good quality compared to real histology images. The ablation study confirms the effectiveness of the combination of proposed pathological awareness and structural constraining modules. Conclusions: The proposed SCPAT-GAN is the first to demonstrate the feasibility of generating both normal and pathological patterns without pixel-wisely supervised training. We expect the SCPAT-GAN to assist in the clinical evaluation of treating the CAD by providing 2D and 3D histopathological visualizations.

Smartphone App Designed to Collect Health Information in Older Adults: Usability Study.

BACKGROUND: Studies evaluating the usability of mobile-phone assessments in older adults are limited. OBJECTIVE: This study aims to identify design-based barriers and facilitators to mobile app survey completion among 2 samples of older adults; those in the Framingham Heart Study and a more diverse sample from a hospital-based setting. METHODS: We used mixed methods to identify challenging and beneficial features of the mobile app in participants from the electronic Framingham Heart Study (n=15; mean age of 72 years; 6/15, 40% women; 15/15, 100% non-Hispanic and White) and among participants recruited from a hospital-based setting (n=15; mean age of 71 years; 7/15, 47% women; 3/15, 20% Hispanic; and 8/15, 53% non-White). A variety of app-based measures with different response formats were tested, including self-reported surveys, pictorial assessments (to indicate body pain sites), and cognitive testing tasks (eg, Trail Making Test and Stroop). Participants completed each measure using a think-aloud protocol, while being audio- and video-recorded with a qualitative interview conducted at the end of the session. Recordings were coded for participant usability errors by 2 pairs of coders. Participants completed the Mobile App Rating Scale to assess the app (response range 1=inadequate to 5=excellent). RESULTS: In electronic Framingham Heart Study participants, the average total Mobile App Rating Scale score was 7.6 (SD 1.1), with no significant differences in the hospital-based sample. In general, participants were pleased with the app and found it easy to use. A large minority had at least 1 navigational issue, most committed only once. Most older adults did not have difficulty completing the self-reported multiple-choice measures unless it included lengthy instructions but participants had usability issues with the Stroop and Trail Making Test. CONCLUSIONS: Our methods and results help guide app development and app-based survey construction for older adults, while also giving consideration to sociodemographic differences.

Collagen V is a dominant regulator of collagen fibrillogenesis: dysfunctional regulation of structure and function in a corneal-stroma-specific Col5a1-null mouse model.

Collagen V is a regulatory fibril-forming collagen that forms heterotypic fibrils with collagen I. Deletion of collagen V in the mouse is associated with a lack of fibril assembly in the embryonic mesenchyme, with a resultant lethal phenotype. The current work elucidates the regulatory roles of collagen V during development and growth of tissues. A conditional mouse model with a mutation in Col5a1 was developed using a Cre-loxP approach. Col5a1 was ablated in Col5a1(flox/flox) mice using a cornea stroma-specific Kera-Cre driver mouse to produce a bitransgenic Col5a1(Δst/Δst) line that is null for collagen V. This permits analyses of the corneal stroma, a widely used model for studies of collagen V. The collagen-V-knockout stroma demonstrated severe dysfunctional regulation of fibrillogenesis. Fibril diameters were significantly increased, with an abnormal, heterogeneous distribution; fibril structure was abnormal, fibril number was decreased and lamellae were disorganized with decreased stroma thickness. The phenotype was more severe in the anterior versus posterior stroma. Opacity was demonstrated throughout the Col5a1(Δst/Δst) stroma, with significantly increased haze intensity compared with control mice. These data indicate central regulatory roles for collagen V in fibril and matrix assembly during tissue development, with dysfunctional regulation resulting in a functional loss of transparency.

Wakayama symposium: challenges of future research in ocular surface cell biology.

During embryonic development, surface ectoderm differentiates to form corneal, conjunctival, and eyelid epidermal epithelia, and glandular epithelium (lacrimal and meibomian glands). Periocular mesenchymal cells of neural crest origin migrate and differentiate, leading to the formation of corneal endothelium and the stromas of the cornea, conjunctiva, eyelids, and trabecular meshwork. The formation of functional ocular surface tissues requires coordinated spatial and temporal expression of transcription factors and signaling molecules of various cytokines and signaling pathways, and the synthesis and remodeling of unique extracellular matrix. Although bidirectional interactions and signaling between mesenchyme and epithelium are considered necessary for embryonic formation of ocular surface tissues and homeostasis in adults, the molecular and cellular mechanisms that regulate such processes remain largely unknown. To investigate possible mechanisms, we have developed mouse models in which the gene functions of ocular surface epithelia and stromas can be altered by Doxycycline induction in spatial and temporal specific manners.

Direct light-up of cAMP derivatives in living cells by click reactions.

8-Azidoadenosine 3',5'-cyclic monophosphate (8-azido cAMP) was directly detected in living cells, by applying Cu-free azide-alkyne cycloaddition to probe cAMP derivatives by fluorescence light-up. Fluorescence emission was generated by two non-fluorescent molecules, 8-azido cAMP as a model target and difluorinated cyclooctyne (DIFO) reagent as a probe. The azide-alkyne cycloaddition reaction between 8-azido cAMP and DIFO induces fluorescence in 8-azido cAMP. The fluorescence emission serves as a way to probe 8-azido cAMP in cells.

Frequency-aware optical coherence tomography image super-resolution via conditional generative adversarial neural network.

Optical coherence tomography (OCT) has stimulated a wide range of medical image-based diagnosis and treatment in fields such as cardiology and ophthalmology. Such applications can be further facilitated by deep learning-based super-resolution technology, which improves the capability of resolving morphological structures. However, existing deep learning-based method only focuses on spatial distribution and disregard frequency fidelity in image reconstruction, leading to a frequency bias. To overcome this limitation, we propose a frequency-aware super-resolution framework that integrates three critical frequency-based modules (i.e., frequency transformation, frequency skip connection, and frequency alignment) and frequency-based loss function into a conditional generative adversarial network (cGAN). We conducted a large-scale quantitative study from an existing coronary OCT dataset to demonstrate the superiority of our proposed framework over existing deep learning frameworks. In addition, we confirmed the generalizability of our framework by applying it to fish corneal images and rat retinal images, demonstrating its capability to super-resolve morphological details in eye imaging.

Frequency-aware optical coherence tomography image super-resolution via conditional generative adversarial neural network.

Optical coherence tomography (OCT) has stimulated a wide range of medical image-based diagnosis and treatment in fields such as cardiology and ophthalmology. Such applications can be further facilitated by deep learning-based super-resolution technology, which improves the capability of resolving morphological structures. However, existing deep learning-based method only focuses on spatial distribution and disregards frequency fidelity in image reconstruction, leading to a frequency bias. To overcome this limitation, we propose a frequency-aware super-resolution framework that integrates three critical frequency-based modules (i.e., frequency transformation, frequency skip connection, and frequency alignment) and frequency-based loss function into a conditional generative adversarial network (cGAN). We conducted a large-scale quantitative study from an existing coronary OCT dataset to demonstrate the superiority of our proposed framework over existing deep learning frameworks. In addition, we confirmed the generalizability of our framework by applying it to fish corneal images and rat retinal images, demonstrating its capability to super-resolve morphological details in eye imaging.

A comparison of average daily gain, apparent digestibilities, energy balance, rumen fermentation parameters, and serum metabolites between yaks (Bos grunniens) and Qaidam cattle (Bos taurus) consuming diets differing in energy level.

Yaks (Bos grunniens), indigenous to the harsh Qinghai-Tibetan Plateau, are well adapted to the severe conditions, and graze natural pasture without supplements all year round. Qaidam cattle (Bos taurus), introduced to the Qinghai-Tibetan Plateau 1,700 years ago, are raised at a lower altitude than yaks, provided with shelter at night and offered supplements in winter. Based on their different backgrounds, we hypothesized that yaks have lower energy requirements for maintenance than cattle. To test this hypothesis, we measured average daily gain (ADG), apparent digestibilities, energy balance, rumen fermentation parameters, and serum metabolites in growing yaks and cattle offered diets differing in metabolizable energy (ME) levels (6.62, 8.02, 9.42 and 10.80 MJ/kg), but with the same crude protein concentration. Six castrated yaks (155 ± 5.8 kg) and 6 castrated Qaidam cattle (154 ± 8.0 kg), all 2.5 years old, were used in 2 concurrent 4 × 4 Latin square designs. Neutral and acid detergent fiber digestibilities were greater (P < 0.05) in yaks than in cattle, and decreased linearly (P < 0.05) with increasing dietary energy level; whereas, digestibilities of dry matter, organic matter, crude protein and ether extract increased (P < 0.05) linearly with increasing energy level. The ADG was greater (P < 0.001) in yaks than in cattle, and increased (P < 0.05) linearly with increasing energy levels. From the regressions of ADG on ME intake, the estimated ME requirement for maintenance was lower (P < 0.05) in yaks than in cattle (0.43 vs. 0.57 MJ/kg BW0.75). The ratios of digestible energy (DE):gross energy and ME:DE were higher (P < 0.05) in yaks than in cattle, and increased (P < 0.05) linearly with increasing dietary energy level. Ruminal pH decreased (P < 0.05), whereas concentrations of total volatile fatty acids (VFAs) and ammonia increased (P < 0.01) with increasing dietary energy level, and all were greater (P < 0.05) in yaks than in cattle. Concentrations of ruminal acetate and iso-VFAs were greater (P < 0.05), whereas propionate was lower (P < 0.05) in yaks than in cattle; acetate decreased (P < 0.001), whereas butyrate and propionate increased (P < 0.001) linearly with increasing dietary energy level. Serum concentrations of ß-hydroxybutyrate were lower (interaction, P < 0.001) in yaks than in cattle fed diets of 9.42 and 10.80 MJ/kg, whereas non-esterified fatty acids were greater (interaction, P < 0.01) in yaks than in cattle fed diets of 6.62 and 8.02 MJ/kg. Concentrations of serum leptin and growth hormone were greater in yaks than in cattle and serum insulin and growth hormone increased (P < 0.01) linearly with increasing dietary energy level. Our hypothesis that yaks have lower energy requirements for maintenance than cattle was supported. This lower requirement confers an advantage to yaks over Qaidam cattle in consuming low energy diets during the long winter on the Qinghai-Tibetan Plateau.