Westlake University

Zheng J., Dai G., He B., Mu Z., Meng Z., Zhang T., Zhi W., Fan D.

Guo X., Lu J., Miao L., Shen E.

Aging is a time-dependent process of functional decline influenced by genetic and environmental factors. Age-related mitochondrial changes remain incompletely understood. Here, we found that compared to the wild type, the mitochondria of long-lived daf-2 C. elegans maintain youthful morphology and function. Through quantitative proteomic analysis on isolated mitochondria, we identified 257 differentially expressed candidates. Analysis of these changed mitochondrial proteins reveals a significant upregulation of five key mitochondrial metabolic pathways in daf-2 mutants, including branched-chain amino acids (BCAA), reactive oxygen species (ROS), propionate, β-alanine, and fatty acids (FA), all of which are related to daf-2-mediated longevity. In addition, mitochondrial ribosome protein abundance slightly decreased in daf-2 mutants. A mild reduction in mitochondrial elongation factor G (gfm-1) by RNAi extends the lifespan of wild type while decreasing lipid metabolic process and cytoplasmic fatty acid metabolism, suggesting that proper inhibition of mitochondrial translation activity might be important for lifespan extension. Overall, our findings indicate that mitochondrial metabolic modulation contributes to the longevity of daf-2 mutants and further highlights the crucial role of mitochondria in aging.

Zhu J., Zhang S., Wang Y., Yao J., Hong X., Li H.

Li J., Zhu C., Zheng S., Chen P., Sun Y., Li H., Yang L.

Yang Y., Yang W., Son Y., Liu S.

Shen L., Li B., Gou W., Liang X., Zhong H., Xiao C., Shi R., Miao Z., Yan Y., Fu Y., Chen Y., Zheng J.

ImportanceUnderstanding the interplay between trajectories of sleep duration, sleep onset timing, and glycemic dynamics is crucial for improving preventive strategies against diabetes and related metabolic diseases.ObjectiveTo examine the associations of sleep duration and onset timing trajectories with continuous glucose monitoring (CGM)–derived glycemic metrics in adults.Design, Setting, and ParticipantsThis cohort study analyzed data collected from January 2014 to December 2023 in the Guangzhou Nutrition and Health Study, a prospective cohort in Guangdong province, China, among participants aged 46 to 83. Participants who had repeated sleep assessments at several study visits and were equipped with CGM devices at the last visit were included. Data analyses were conducted between January and June 2024.ExposuresThe trajectories of sleep duration and onset timing were constructed using self-report sleep duration and sleep onset timing, recorded at multiple study visit points.Main Outcomes and MeasuresMeasurements of glycemic variability and glycemic control were collected using a masked CGM device worn by patients for 14 consecutive days. Huber robust regression models were used to assess the associations between sleep trajectories and CGM-derived metrics.ResultsIn this study of 1156 participants (mean [SD] age, 63.0 [5.1] years, 816 [70.6%] women), we identified 4 distinct sleep duration trajectory groups: severe inadequate, moderate inadequate, mild inadequate, and adequate. Severe sleep inadequacy was associated with an increment of glycemic variability indicators: 2.87% (95% CI, 1.23%-4.50%) for coefficient of variation and 0.06 (95% CI, 0.02-0.09) mmol/L for mean of daily differences. We found 2 trajectories of sleep onset timing: persistent early and persistent late groups. Late sleep onset was associated with larger coefficient of variation (β = 1.18%; 95% CI, 0.36%-2.01%) and mean of daily differences (β = 0.02 mmol/L; 95% CI, 0.01-0.04 mmol/L). Inappropriate sleep duration and timing trajectories in combination were associated with greater glycemic variability.Conclusions and RelevanceIn this cohort study of middle-aged and older participants, persistent inadequate sleep duration and late sleep onset, whether alone or in combination, were associated with greater glycemic variability. These findings emphasize the importance of considering both sleep duration and timing for optimizing glycemic control in the general population.

Wang G., Liu X., Yuan X.

Coded aperture compressive temporal imaging (CACTI) enables the capture of complex dynamic scenes in a single exposure. In this Letter, we introduce a dual-optical-path (DoP) system with conjugate masks employing a single digital micromirror device (DMD) to simultaneously capture the original and complementary measurements to enhance the reconstruction quality. Our findings demonstrate that combining these measurements improves spatial resolution, while their differential values provide temporal information and cancel out noise. Based on this, we build a Noise-Robust Network with Spatial and Temporal Information Enhancement (NRST) as the reconstruction algorithm, which increases accuracy and robustness against noise. Both experimental and simulation results verify the proposed DoP-CACTI system’s significant noise robustness and spatiotemporal enhancement properties.

Cai C., Lee H., Shi W., Liu Y., Zhang B., Sun L., Wang T.

Shi X., Shen C., Liu C., Zhang L., Du Y., Zhang H., Liu H., Wang J., Chen C., Wu Y., Zhang C., Li Z., Tang H., Yin M., Mao X., et. al.

Background: Medullary thyroid cancer (MTC) is a rare thyroid malignancy, with 70% to 80% of cases being sporadic (sMTC). Current guidelines recommend total thyroidectomy (TT) for all preoperatively suspicious sMTC, though there has been increasing support for reducing the surgical extent in recent years. However, relevant data are limited. This study aimed to comprehensively evaluate the safety of hemithyroidectomy (HT) in sMTC. Patients and Methods: This study included 797 patients with MTC who received curative-intent initial surgery at 19 participating referral centers. Genetic testing was performed to identify disease heredity. We evaluated the safety of HT in sMTC across 5 aspects: (1) prevalence of occult bilateral foci, (2) prevalence of contralateral lobe recurrence, (3) biochemical response, (4) structural recurrence-free survival (SRFS), and (5) overall survival (OS). Results: Of the 797 patients, 648 were genetically confirmed as having sMTC. HT and TT were performed as the index surgery in 232 (35.8%) and 416 (64.2%) patients, respectively. In the TT group, bilateral foci were found in 34 (8.2%) patients, of whom only 10 (2.4%) had sonographically occult foci, and of these, only 3 (0.72%) had a maximal tumor size ≤2 cm. In the HT group, only 1.7% (4/232) had recurrence in the preserved lobe, with only 1 (0.43%) having a maximal tumor size ≤2 cm. After propensity score matching, 230 pairs of patients were included in further analysis. No significant differences were found in OS (log-rank: P=.484; Cox regression: P=.380), SRFS (log-rank: P=.914; Cox regression: P=.309), or biochemical response (chi-square: P=.744; logistic regression: P=.818) between the 2 groups. Subgroup analyses showed that HT conferred comparable structural and biochemical outcomes with TT in small (≤2 cm) sMTCs, even for patients with high-risk factors such as high preoperative calcitonin, multifocal disease, lymph node metastases, RETM918T mutation, and desmoplasia. Conclusions: For small unilateral sMTCs, HT may be considered an alternative treatment that does not compromise prognosis while avoiding additional complications associated with TT.

Hayati H., Aarani S.G., Karimi M., Eskandari R., Sawan M., Gagnon-Turcotte G., Gosselin B.

Lyu S., Lang X., Wang D.

Fang C., Shen Z., Wang Z., Wang C., Zhao S., Tian F., Yang J., Sawan M.

Tian F., Chen J., Zheng J., Wu H., He J., Wang X., Fang C., Yao Y., Yang J., Sawan M., Tsui C., Cheng K.(.

Zhou Y., Lin H., Xie L., Huang Y., Wu L., Li S.Z., Chen W.

The study of protein-protein interactions (PPIs) holds immense significance in understanding various biological activities, as well as in drug discovery and disease diagnosis. Existing deep learning methods for PPI prediction, including graph neural networks (GNNs), have been widely employed as the solutions, while they often experience a decline in performance in the real world. We claim that the topological shortcut is one of the key problems contributing negatively to the performance, according to our analysis. By modeling the PPIs as a graph with protein as nodes and interactions as edge types, the prevailing models tend to learn the pattern of nodes' degrees rather than intrinsic sequence-structure profiles, leading to the problem termed topological shortcut. The huge data growth of PPI leads to intensive computational costs and challenges computing devices, causing infeasibility in practice. To address the discussed problems, we propose a label-aware hierarchical subgraph learning method (laruGL-PPI) that can effectively infer PPIs while being interpretable. Specifically, we introduced edge-based subgraph sampling to effectively alleviate the problems of topological shortcuts and high computing costs. Besides, the inner-outer connections of PPIs are modeled as a hierarchical graph, together with the dependencies between interaction types constructed by a label graph. Extensive experiments conducted across various scales of PPI datasets have conclusively demonstrated that the laruGL-PPI method surpasses the most advanced PPI prediction techniques currently available, particularly in the testing of unseen proteins. Also, our model can recognize crucial sites of proteins, such as surface sites for binding and active sites for catalysis.

Zhang Q., Ren R., Yin L., Sun L.

AbstractAnion exchange membranes (AEMs) based energy conversion and storage devices have attracted attention as an innovative technology due to their advantageous alkaline catalytic kinetics and cost‐effectiveness. AEMs play a crucial role in these devices and have shown significant progress in terms of ionic conductivity, mechanical properties, alkaline stability, and other essential characteristics. Nevertheless, their durability remains a limiting factor preventing the large‐scale deployment of AEMs based devices. The attack of hydroxide ions on the cations is an inherent issue that needs to be addressed to enhance the lifetime of the AEMs. Therefore, the design of more stable cationic groups is essential to maintain the initial properties of AEMs and extend the device lifetime. This concept systematically summarizes the development and stability enhancement strategies of the cationic groups for AEMs in recent years, with particular emphasis on the emerging cyclic cationic groups. Furthermore, the stability differences of cations in small molecules versus AEMs are systematically discussed, as well as prospective research toward stable AEMs.