Exercise-induced α-ketoglutaric acid stimulates muscle hypertrophy and fat loss through OXGR1-dependent adrenal activation.

Beneficial effects of resistance exercise on metabolic health and particularly muscle hypertrophy and fat loss are well established, but the underlying chemical and physiological mechanisms are not fully understood. Here, we identified a myometabolite-mediated metabolic pathway that is essential for the beneficial metabolic effects of resistance exercise in mice. We showed that substantial accumulation of the tricarboxylic acid cycle intermediate α-ketoglutaric acid (AKG) is a metabolic signature of resistance exercise performance. Interestingly, human plasma AKG level is also negatively correlated with BMI. Pharmacological elevation of circulating AKG induces muscle hypertrophy, brown adipose tissue (BAT) thermogenesis, and white adipose tissue (WAT) lipolysis in vivo. We further found that AKG stimulates the adrenal release of adrenaline through 2-oxoglutarate receptor 1 (OXGR1) expressed in adrenal glands. Finally, by using both loss-of-function and gain-of-function mouse models, we showed that OXGR1 is essential for AKG-mediated exercise-induced beneficial metabolic effects. These findings reveal an unappreciated mechanism for the salutary effects of resistance exercise, using AKG as a systemically derived molecule for adrenal stimulation of muscle hypertrophy and fat loss.

Strong Quantum Computational Advantage Using a Superconducting Quantum Processor.

Scaling up to a large number of qubits with high-precision control is essential in the demonstrations of quantum computational advantage to exponentially outpace the classical hardware and algorithmic improvements. Here, we develop a two-dimensional programmable superconducting quantum processor, Zuchongzhi, which is composed of 66 functional qubits in a tunable coupling architecture. To characterize the performance of the whole system, we perform random quantum circuits sampling for benchmarking, up to a system size of 56 qubits and 20 cycles. The computational cost of the classical simulation of this task is estimated to be 2-3 orders of magnitude higher than the previous work on 53-qubit Sycamore processor [Nature 574, 505 (2019)NATUAS0028-083610.1038/s41586-019-1666-5. We estimate that the sampling task finished by Zuchongzhi in about 1.2 h will take the most powerful supercomputer at least 8 yr. Our work establishes an unambiguous quantum computational advantage that is infeasible for classical computation in a reasonable amount of time. The high-precision and programmable quantum computing platform opens a new door to explore novel many-body phenomena and implement complex quantum algorithms.

Succinate induces skeletal muscle fiber remodeling via SUNCR1 signaling.

The conversion of skeletal muscle fiber from fast twitch to slow-twitch is important for sustained and tonic contractile events, maintenance of energy homeostasis, and the alleviation of fatigue. Skeletal muscle remodeling is effectively induced by endurance or aerobic exercise, which also generates several tricarboxylic acid (TCA) cycle intermediates, including succinate. However, whether succinate regulates muscle fiber-type transitions remains unclear. Here, we found that dietary succinate supplementation increased endurance exercise ability, myosin heavy chain I expression, aerobic enzyme activity, oxygen consumption, and mitochondrial biogenesis in mouse skeletal muscle. By contrast, succinate decreased lactate dehydrogenase activity, lactate production, and myosin heavy chain IIb expression. Further, by using pharmacological or genetic loss-of-function models generated by phospholipase Cß antagonists, SUNCR1 global knockout, or SUNCR1 gastrocnemius-specific knockdown, we found that the effects of succinate on skeletal muscle fiber-type remodeling are mediated by SUNCR1 and its downstream calcium/NFAT signaling pathway. In summary, our results demonstrate succinate induces transition of skeletal muscle fiber via SUNCR1 signaling pathway. These findings suggest the potential beneficial use of succinate-based compounds in both athletic and sedentary populations.

POLR1D promotes colorectal cancer progression and predicts poor prognosis of patients.

RNA polymerase I subunit D (POLR1D), which is involved in synthesis of ribosomal RNA precursors and small RNAs, has been shown to be overexpressed in several human cancer types. Nevertheless, the role of POLR1D in the progression of colorectal cancer (CRC) remains unknown. The following study aimed to investigate the role and underlying mechanism of POLR1D in CRC progression. In this report, we found that POLR1D was significantly up-regulated in CRC through data mining of oncomine database. Furthermore, the immunohistochemistry (IHC) staining of a tissue microarray (TMA) of 75 human CRC patients showed that the expression level of POLR1D was positively correlated to tumor size and poor survival of CRC patients. Aberrant expression of POLR1D significantly promoted cell proliferation and migration in vitro, as well as tumor growth in vivo. Conversely, POLR1D knockdown displayed the opposite effects. The flow Cytometry assays showed that POLR1D fostered cell cycle progression at G1-S transition and inhibited cell apoptosis. Finally, at the molecular level, we demonstrated that POLR1D-induced the promotion of G1-S cell cycle transition was mediated by activation of wnt-ß-catenin signaling and inactivation of p53 signaling. Our results suggested that POLR1D may function as a risk factor for predicting the outcome of CRC patients, as well as a potential therapeutic target for CRC.

Quantum computational advantage via 60-qubit 24-cycle random circuit sampling.

To ensure a long-term quantum computational advantage, the quantum hardware should be upgraded to withstand the competition of continuously improved classical algorithms and hardwares. Here, we demonstrate a superconducting quantum computing systems Zuchongzhi 2.1, which has 66 qubits in a two-dimensional array in a tunable coupler architecture. The readout fidelity of Zuchongzhi 2.1 is considerably improved to an average of 97.74%. The more powerful quantum processor enables us to achieve larger-scale random quantum circuit sampling, with a system scale of up to 60 qubits and 24 cycles, and fidelity of FXEB=(3.66±0.345)×10-4. The achieved sampling task is about 6 orders of magnitude more difficult than that of Sycamore [Nature 574, 505 (2019)] in the classic simulation, and 3 orders of magnitude more difficult than the sampling task on Zuchongzhi 2.0 [arXiv:2106.14734 (2021)]. The time consumption of classically simulating random circuit sampling experiment using state-of-the-art classical algorithm and supercomputer is extended to tens of thousands of years (about 4.8×104 years), while Zuchongzhi 2.1 only takes about 4.2 h, thereby significantly enhancing the quantum computational advantage.

[Screening active ingredients of Shenkangwan that regulate endothelial-mesenchymal transition of endothelial cells in vitro].

OBJECTIVE: To screen the effective components of Shenkangwan that regulate endothelial-mesenchymal transition in endothelial cells for optimizing prescription of Shenkangwan. METHODS: ALK5 was identified as one of the target receptors that regulate endothelial-mesenchymal transition of endothelial cells using molecular docking technique. Nine molecules were screened as the candidate effective components in Shenkangwan, among which calycosin, ononin and stigmasterol were selected for testing. Glomerular epithelial cells were exposed to high glucose and treated with calycosin, ononin, or stigmasterol, and the cellular expressions of α-smooth muscle actin (α-SMA) and vimentin mRNA were detected with real-time fluorescence quantitative PCR. The phosphorylation of SMAD2/3 in the cells was detected using Western blotting. RESULTS: Calycosin, ononin and stigmasterol did not produce significant cytotoxicity in glomerular epithelial cells (P>0.05). The cells exposed to high glucose and calycosin treatment showed significantly decreased mRNA levels of α-SMA and vimentin (P<0.05) and inhibited phosphorylation of SMAD2/3. Ononin and stigmasterol did not produce such effects in the cells. CONCLUSION: In endothelial cells with high glucose-induced injury, calycosin can inhibit the up-regulation of α-SMA and vimentin and inhibit phosphorylation of SMAD2/3 to regulate endothelial-mesenchymal transition and improve diabetic nephropathy.

Rate-constrained 3D surface estimation from noise-corrupted multiview depth videos.

Transmitting compactly represented geometry of a dynamic 3D scene from a sender can enable a multitude of imaging functionalities at a receiver, such as synthesis of virtual images at freely chosen viewpoints via depth-image-based rendering. While depth maps­projections of 3D geometry onto 2D image planes at chosen camera viewpoints-can nowadays be readily captured by inexpensive depth sensors, they are often corrupted by non-negligible acquisition noise. Given depth maps need to be denoised and compressed at the encoder for efficient network transmission to the decoder, in this paper, we consider the denoising and compression problems jointly, arguing that doing so will result in a better overall performance than the alternative of solving the two problems separately in two stages. Specifically, we formulate a rate-constrained estimation problem, where given a set of observed noise-corrupted depth maps, the most probable (maximum a posteriori (MAP)) 3D surface is sought within a search space of surfaces with representation size no larger than a prespecified rate constraint. Our rate-constrained MAP solution reduces to the conventional unconstrained MAP 3D surface reconstruction solution if the rate constraint is loose. To solve our posed rate-constrained estimation problem, we propose an iterative algorithm, where in each iteration the structure (object boundaries) and the texture (surfaces within the object boundaries) of the depth maps are optimized alternately. Using the MVC codec for compression of multiview depth video and MPEG free viewpoint video sequences as input, experimental results show that rate-constrained estimated 3D surfaces computed by our algorithm can reduce coding rate of depth maps by up to 32% compared with unconstrained estimated surfaces for the same quality of synthesized virtual views at the decoder.