Targeted plasma proteomic analysis uncovers a high-performance biomarker panel for early diagnosis of gastric cancer.

BACKGROUND: Gastric cancer (GC) is characterized by high morbidity, high mortality and low early diagnosis rate. Early diagnosis plays a crucial role in radically treating GC. The aim of this study was to identify plasma biomarkers for GC and early GC diagnosis. METHODS: We quantified 369 protein levels with plasma samples from discovery cohort (n = 88) and validation cohort (n = 50) via high-throughput proximity extension assay (PEA) utilizing the Olink-Explore-384-Cardiometabolic panel. The multi-protein signatures were derived from LASSO and Ridge regression models. RESULTS: In the discovery cohort, 13 proteins (GDF15, ITIH3, BOC, DPP7, EGFR, AMY2A, CCDC80, CD163, GPNMB, LTBP2, CTSZ, CCL18 and NECTIN2) were identified to distinguish GC (Stage I-IV) and early GC (HGIN-I) groups from control group with AUC of 0.994 and AUC of 0.998, severally. The validation cohort yielded AUC of 0.930 and AUC of 0.818 for GC and early GC, respectively. CONCLUSIONS: This study identified a multi-protein signature with the potential to benefit clinical GC diagnosis, especially for Asian and early GC patients, which may contribute to the development of a less-invasive, convenient, and efficient early screening tool, promoting early diagnosis and treatment of GC and ultimately improving patient survival.

DNA-based molecular classifiers for the profiling of gene expression signatures.

Although gene expression signatures offer tremendous potential in diseases diagnostic and prognostic, but massive gene expression signatures caused challenges for experimental detection and computational analysis in clinical setting. Here, we introduce a universal DNA-based molecular classifier for profiling gene expression signatures and generating immediate diagnostic outcomes. The molecular classifier begins with feature transformation, a modular and programmable strategy was used to capture relative relationships of low-concentration RNAs and convert them to general coding inputs. Then, competitive inhibition of the DNA catalytic reaction enables strict weight assignment for different inputs according to their importance, followed by summation, annihilation and reporting to accurately implement the mathematical model of the classifier. We validated the entire workflow by utilizing miRNA expression levels for the diagnosis of hepatocellular carcinoma (HCC) in clinical samples with an accuracy 85.7%. The results demonstrate the molecular classifier provides a universal solution to explore the correlation between gene expression patterns and disease diagnostics, monitoring, and prognosis, and supports personalized healthcare in primary care.

Synthesis of tunable thickness-to-diameter ratio microcapsules via a diffusion-controlled process for temperature-responsive release.

Designing microcapsules with a complicated functionalized shell to respond to an external stimulus has attracted much attention for triggered release; however, simplifying the synthesis process remains a significant challenge. Herein, we initially propose a novel, simple synthesis strategy that utilizes a mixed solvent as the organic phase to control the diffusion of common monomers during interfacial polymerization, resulting in the successful preparation of microcapsules with tunable thickness-to-diameter ratios (T/D). The morphology of microcapsules is confirmed by scanning electron microscopy. We also observe that the T/D of the designed microcapsules progressively increases as the diffusion of monomers occurs, and the glass transition temperature of microcapsules is controlled. Furthermore, microcapsule-based crosslinking agents are applied to investigate the crosslinking reaction of poly(vinyl chloride). Rotational rheometer results indicate that the microcapsules exhibit an excellent external stimulus response, precisely triggering release at the predetermined temperature. This simple approach for the preparation of microcapsules with tunable physical properties has great potential for triggered release in diverse applications.

A compendium of ruminant gastrointestinal phage genomes revealed a higher proportion of lytic phages than in any other environments.

BACKGROUND: Ruminants are important livestock animals that have a unique digestive system comprising multiple stomach compartments. Despite significant progress in the study of microbiome in the gastrointestinal tract (GIT) sites of ruminants, we still lack an understanding of the viral community of ruminants. Here, we surveyed its viral ecology using 2333 samples from 10 sites along the GIT of 8 ruminant species. RESULTS: We present the Unified Ruminant Phage Catalogue (URPC), a comprehensive survey of phages in the GITs of ruminants including 64,922 non-redundant phage genomes. We characterized the distributions of the phage genomes in different ruminants and GIT sites and found that most phages were organism-specific. We revealed that ~ 60% of the ruminant phages were lytic, which was the highest as compared with those in all other environments and certainly will facilitate their applications in microbial interventions. To further facilitate the future applications of the phages, we also constructed a comprehensive virus-bacteria/archaea interaction network and identified dozens of phages that may have lytic effects on methanogenic archaea. CONCLUSIONS: The URPC dataset represents a useful resource for future microbial interventions to improve ruminant production and ecological environmental qualities. Phages have great potential for controlling pathogenic bacterial/archaeal species and reducing methane emissions. Our findings provide insights into the virome ecology research of the ruminant GIT and offer a starting point for future research on phage therapy in ruminants. Video Abstract.

Investigation on Combustion Characteristics and Molecular Structures of Heiyanquan Mining Area, Xinjiang, China.

In order to comprehend the molecular composition of coal and better understand the process of coal combustion, this study involved the development of a molecular structure model for Heiyanquan coal in Xinjiang, as well as the optimization and annealing dynamics simulation of the model. Thermogravimetric analysis (TG), Fourier transform infrared spectroscopy (FTIR), and high-resolution transmission electron microscopy (HRTEM) were utilized to investigate the spontaneous combustion characteristics of coal at different temperatures (room temperature, 50-500 °C with 50 °C interval). The findings revealed that the coal primarily consists of aromatic carbon, with the aromatic structure mainly comprising naphthalene, anthracene, and phenanthrene, and the aliphatic carbon mainly consisting of CH2 and CH, along with a small quantity of minerals. The empirical molecular formula of Heiyanquan coal was determined to be C175H125O21N3. After the optimization, the total energy of the model was significantly reduced, and the aromatic layers tended to align in a regular parallel manner, with van der Waals energy playing a crucial role in maintaining structural stability. As the temperature increased, the activation energy of the three stages also increased, with the combustion stage exhibiting the highest activation energy. The presence of hydroxyl groups and oxygen-containing functional groups was found to mainly participate in the reaction, while the content of aromatic hydrocarbons remained relatively stable, C=C exhibited a decreasing trend, and C-O displayed an increasing trend. Moreover, it was observed that 1 × 1 and 2 × 2 were the predominant aromatic stripes in the coal samples, accounting for more than 90% of the total stripes.

Development of the Static and Dynamic Gene Expression Regulation Toolkit in Pseudomonas chlororaphis.

The advancement of metabolic engineering and synthetic biology has promoted in-depth research on the nonmodel microbial metabolism, and the potential of nonmodel organisms in industrial biotechnology is becoming increasingly evident. The nonmodel organism Pseudomonas chlororaphis is a safe plant growth promoting bacterium for the production of phenazine compounds; however, its application is seriously hindered due to the lack of an effective gene expression precise regulation toolkit. In this study, we constructed a library of 108 promoter-5'-UTR (PUTR) and characterized them through fluorescent protein detection. Then, 6 PUTRs with stable low, intermediate, and high intensities were further characterized by report genes lacZ encoding ß-galactosidase from Escherichia coli K12 and phzO encoding PCA monooxygenase from P. chlororaphis GP72 and thus developed as a static gene expression regulation system. Furthermore, the stable and high-intensity expressed PMOK_RS0128085UTR was fused with the LacO operator to construct an IPTG-induced plasmid, and a self-induced plasmid was constructed employing the high-intensity PMOK_RS0116635UTR regulated by cell density, resulting in a dynamic gene expression regulation system. In summary, this study established two sets of static and dynamic regulatory systems for P. chlororaphis, providing an effective toolkit for fine-tuning gene expression and reprograming the metabolism flux.

Rapamycin inhibits B16 melanoma cell viability invitro and invivo by inducing autophagy and inhibiting the mTOR/p70­S6k pathway.

Rapamycin is an immunosuppressant that has been shown to prevent tumor growth following organ transplantation. However, its exact mode of antitumor action remains unknown. The present study used the B16-F10 (B16) murine melanoma model to explore the antitumor mechanism of rapamycin, and it was revealed that rapamycin reduced B16 cell viability in vitro and in vivo. In addition, in vitro and in vivo, the results of western blotting showed that rapamycin reduced Bcl2 expression, and enhanced the protein expression levels of cleaved caspase 3 and Bax, indicating that it can induce the apoptosis of B16 melanoma cells. Furthermore, the results of cell cycle analysis and western blotting showed that rapamycin induced B16 cell cycle arrest in the G1 phase, based on the reduction in the protein expression levels of CDK1, cyclin D1 and CDK4, as well as the increase in the percentage of cells in G1 phase. Rapamycin also significantly increased the number of autophagosomes in B16 melanoma cells, as determined by transmission electron microscopy. Furthermore, the results of RT-qPCR and western blotting showed that rapamycin upregulated the protein expression levels of microtubule-associated protein light chain 3 (LC3) and Beclin-1, while downregulating the expression of p62 in vitro and in vivo, thus indicating that rapamycin could trigger cellular autophagy. The present study revealed that rapamycin in combination with chloroquine (CQ) further increased LC3 expression compared with that in the CQ group, suggesting that rapamycin induced an increase in autophagy in B16 cells. Furthermore, the results of western blotting showed that rapamycin blocked the phosphorylation of p70 ribosomal S6 kinase (p70-S6k) and mammalian target of rapamycin (mTOR) proteins in vitro and in vivo, thus suggesting that rapamycin may exert its antitumor effect by inhibiting the phosphorylation of the mTOR/p70-S6k pathway. In conclusion, rapamycin may inhibit tumor growth by inducing cellular G1 phase arrest and apoptosis. In addition, rapamycin may exert its antitumor effects by inducing the autophagy of B16 melanoma cells in vitro and in vivo, and the mTOR/p70-S6k signaling pathway may be involved in this process.

Endomorphin-2 analogs with C-terminal esterification display potent antinociceptive effects in the formalin pain test in mice.

Previously, we have investigated three C-terminal esterified endomorphin-2 (EM-2) analogs EM-2-Me, EM-2-Et and EM-2-Bu with methyl, ethyl and tert-butyl ester modifications, respectively. These analogs produced significant antinociception in acute pain at the spinal and supraspinal levels, with reduced tolerance and gastrointestinal side effects. The present study was undertaken to determine the analgesic effects and opioid mechanisms of these three analogs in the formalin pain test. Our results demonstrated that intracerebroventricular (i.c.v.) administration of 0.67-20 nmol EM-2 analogs EM-2-Me, EM-2-Et and EM-2-Bu produced dose-dependent antinociceptive effects in both phase Ⅰ and phase Ⅱ of formalin pain. EM-2-Me and EM-2-Bu displayed more potent antinociception than morphine. Especially, EM-2-Bu exhibited the highest antinociception in phase Ⅱ of formalin pain, with the ED50 value being 2.1 nmol. Naloxone (80 nmol, i.c.v.) completely antagonized the antinociceptive effects of EM-2-Me, EM-2-Et and EM-2-Bu (20 nmol, i.c.v.) in both phase I and phase Ⅱ of formalin pain, suggesting a central opioid mechanism. Nevertheless, the antinociception induced by EM-2-Me might be involved in the release of dynorphin A, which subsequently acted on κ- opioid receptor. EM-2-Bu produced the antinociception probably by the direct activation of both µ- and δ-opioid receptors. EM-2-Me, EM-2-Et and EM-2-Bu also produced significant analgesic effects after peripheral administration, and the central opioid receptors were involved. Furthermore, EM-2-Bu had no influence on the locomotor activity after i.c.v. injection. The present investigation demonstrated that C-terminal esterified modifications of EM-2 will be beneficial for developing novel therapeutics in formalin pain.

A Circular RNA Generated from Nebulin (NEB) Gene Splicing Promotes Skeletal Muscle Myogenesis in Cattle as Detected by a Multi-Omics Approach.

Cattle and the draught force provided by its skeletal muscle have been integral to agro-ecosystems of agricultural civilization for millennia. However, relatively little is known about the cattle muscle functional genomics (including protein coding genes, non-coding RNA, etc.). Circular RNAs (circRNAs), as a new class of non-coding RNAs, can be effectively translated into detectable peptides, which enlightened us on the importance of circRNAs in cattle muscle physiology function. Here, RNA-seq, Ribosome profiling (Ribo-seq), and peptidome data are integrated from cattle skeletal muscle, and detected five encoded peptides from circRNAs. It is further identified and functionally characterize a 907-amino acids muscle-specific peptide that is named circNEB-peptide because derived by the splicing of Nebulin (NEB) gene. This peptide localizes to the nucleus and cytoplasm and directly interacts with SKP1 and TPM1, key factors regulating physiological activities of myoblasts, via ubiquitination and myoblast fusion, respectively. The circNEB-peptide is found to promote myoblasts proliferation and differentiation in vitro, and induce muscle regeneration in vivo. These findings suggest circNEB-peptide is an important regulator of skeletal muscle regeneration and underscore the possibility that more encoding polypeptides derived by RNAs currently annotated as non-coding exist.

A Spatially Controlled Proximity Split Tweezer Switch for Enhanced DNA Circuit Construction and Multifunctional Transduction.

DNA strand displacement reactions are vital for constructing intricate nucleic acid circuits, owing to their programmability and predictability. However, the scarcity of effective methods for eliminating circuit leakages has hampered the construction of circuits with increased complexity. Herein, a versatile strategy is developed that relies on a spatially controlled proximity split tweezer (PST) switch to transduce the biomolecular signals into the independent oligonucleotides. Leveraging the double-stranded rigidity of the tweezer works synergistically with the hindering effect of the hairpin lock, effectively minimizing circuit leakage compared with sequence-level methods. In addition, the freely designed output strand is independent of the target binding sequence, allowing the PST switch conformation to be modulated by nucleic acids, small molecules, and proteins, exhibiting remarkable adaptability to a wide range of targets. Using this platform, established logical operations between different types of targets for multifunctional transduction are successfully established. Most importantly, the platform can be directly coupled with DNA catalytic circuits to further enhance transduction performance. The uniqueness of this platform lies in its design straightforwardness, flexibility, scalable intricacy, and system compatibility. These attributes pave a broad path toward nucleic acid-based development of sophisticated transduction networks, making them widely applied in basic science research and biomedical applications.

PVGAN: A Pathological Voice Generation Model Incorporating a Progressive Nesting Strategy.

The voice generation task is to solve the problem of limited samples in the voice dataset using computer technology. By increasing the number of samples, the accuracy of voice disorder diagnosis can be improved, which has a wide range of application value in medical diagnosis and other fields. At present, there are insufficient models for detailed features such as pitch, timbre, and different frequency components in pathological voice data. Therefore, this paper proposes a PVGAN network for learning different frequency information of audio to generate pathological voice data. The proposed network captures the multi-scale features and different periodic patterns of audio signals by designing multiscale perceptual residual blocks and periodic discriminators. At the same time, a progressive nesting strategy was proposed to combine the generator and the discriminator to improve the learning ability of different resolution information. In addition, a latent mapping network is designed to fuse the latent vector with the condition information to generate sound features related to specific diseases or pathological states. The loss function is optimized to further improve the model performance. On the Saarbruecken Voice Database(SVD), the average values of each index of the data generated after training with different pathological types as conditional information are similar to the original data. Finally, the generated data were used to expand the SVD dataset, and the accuracy of the two classification experiments was improved to a certain extent.

Novel endomorphin analogues CEMR-1 and CEMR-2 produce potent and long-lasting antinociception with a favourable side effect profile at the spinal level.

BACKGROUND AND PURPOSE: Endomorphins have shown great promise as pharmaceutics for the treatment of pain. We have previously confirmed that novel endomorphin analogues CEMR-1 and CEMR-2 behaved as potent µ agonists and displayed potent antinociceptive activities at the supraspinal and peripheral levels. The present study was undertaken to evaluate the antinociceptive properties of CEMR-1 and CEMR-2 following intrathecal (i.t.) administration. Furthermore, their antinociceptive tolerance and opioid-like side effects were also determined. EXPERIMENTAL APPROACH: The spinal antinociceptive effects of CEMR-1 and CEMR-2 were determined in a series of pain models, including acute radiant heat paw withdrawal test, spared nerve injury-induced neuropathic pain, complete Freund's adjuvant-induced inflammatory pain, visceral pain and formalin pain. Antinociceptive tolerance was evaluated in radiant heat paw withdrawal test. KEY RESULTS: Spinal administration of CEMR-1 and CEMR-2 produced potent and prolonged antinociceptive effects in acute pain. CEMR-1 and CEMR-2 may produce their antinociception through distinct µ receptor subtypes. These two analogues also exhibited significant analgesic activities in neuropathic, inflammatory, visceral and formalin pain at the spinal level. It is noteworthy that CEMR-1 showed non-tolerance-forming analgesic properties, while CEMR-2 exhibited substantially reduced antinociceptive tolerance. Furthermore, both analogues displayed no or reduced side effects on conditioned place preference response, physical dependence, locomotor activity and gastrointestinal transit. CONCLUSIONS AND IMPLICATIONS: The present investigation demonstrated that CEMR-1 and CEMR-2 displayed potent and long-lasting antinociception with a favourable side effect profile at the spinal level. Therefore, CEMR-1 and CEMR-2 might serve as promising analgesic compounds with minimal opioid-like side effects.

Phase separation of BuGZ regulates gut regeneration and aging through interaction with m6A regulators.

Exploring the role of phase separation in intracellular compartment formation is an active area of research. However, the associations of phase separation with intestinal stem cell (ISC)-dependent regeneration and aging remain unclear. Here, we demonstrate that BuGZ, a coacervating mitotic effector, shows age- and injury-associated condensation in Drosophila ISC nuclei during interphase. BuGZ condensation promotes ISC proliferation, affecting Drosophila gut repair and longevity. Moreover, m6A reader YT521-B acts as the transcriptional and functional downstream of BuGZ. The binding of YT521-B promotor or m6A writer Ime4/ Mettl14 to BuGZ controls its coacervation, indicating that the promotor may accelerate the phase transition of its binding transcription factor. Hence, we propose that phase separation and m6A regulators may be critical for ameliorating ISC-dependent gut regeneration and aging and requires further study.

The multi-kingdom microbiome of the goat gastrointestinal tract.

BACKGROUND: Goat is an important livestock worldwide, which plays an indispensable role in human life by providing meat, milk, fiber, and pelts. Despite recent significant advances in microbiome studies, a comprehensive survey on the goat microbiomes covering gastrointestinal tract (GIT) sites, developmental stages, feeding styles, and geographical factors is still unavailable. Here, we surveyed its multi-kingdom microbial communities using 497 samples from ten sites along the goat GIT. RESULTS: We reconstructed a goat multi-kingdom microbiome catalog (GMMC) including 4004 bacterial, 71 archaeal, and 7204 viral genomes and annotated over 4,817,256 non-redundant protein-coding genes. We revealed patterns of feeding-driven microbial community dynamics along the goat GIT sites which were likely associated with gastrointestinal food digestion and absorption capabilities and disease risks, and identified an abundance of large intestine-enriched genera involved in plant fiber digestion. We quantified the effects of various factors affecting the distribution and abundance of methane-producing microbes including the GIT site, age, feeding style, and geography, and identified 68 virulent viruses targeting the methane producers via a comprehensive virus-bacterium/archaea interaction network. CONCLUSIONS: Together, our GMMC catalog provides functional insights of the goat GIT microbiota through microbiome-host interactions and paves the way to microbial interventions for better goat and eco-environmental qualities. Video Abstract.

Global scientific trends update on macrophage polarization in rheumatoid arthritis: A bibliometric and visualized analysis from 2000 to 2022.

The goal of this work was to use bibliometric analysis to help guide future research on macrophage polarization in RA. We looked for studies on macrophage polarization in RA published between January 1, 2000, and December 31, 2022, in the WoSCC database. Research trends and hotspots were shown and assessed using VOSviewer and CiteSpace. A total of 181 articles were gathered. Belgium was among the early adopters of the field. Chinese institutes have produced the most research. Researchers such as Angel Luis Corb, Amaya Puig-Kröger, and Lizbeth Estrada-Capetillo have made major contributions to the field. Frontiers in Immunology has published the most study findings. According to VOSviewer, the most investigated immune cells, biomarkers, and signaling pathways in the previous three years have been "T cells", "gm-csf", and "nf-κb" in that order. We discovered that the most often used terms in the previous three years were "pathway", "oxidative stress", "extracellular capsule" and "nlrp3 inflammasome" using Citespace. We emphasize these concepts in our findings, presenting the exact mechanisms of pathophysiology related to macrophage polarization in RA, as well as current breakthroughs in therapy strategies.

The association of nocturnal hypoxemia with dyslipidemia in sleep-disordered breathing population of Chinese community: a cross-sectional study.

BACKGROUND: Currently, there is limited and controversial clinical research on the correlation between sleep-disordered breathing (SDB) and dyslipidemia. This discrepancy in findings may be because studies that primarily focused on hospital-based populations may not be applicable to community-based populations. Therefore, the primary objective of this research endeavor is to scrutinize the correlation between nocturnal hypoxemia and blood lipid concentrations among adult individuals residing in the community who exhibit symptoms of SDB. Additionally, this study aimed to identify the nocturnal hypoxia parameters having the strongest correlation with this relationship. METHODS: This cross-sectional study collected data from The Guangdong Sleep Health Study, which included 3829 participants. Type IV sleep monitoring was employed to measure hypoxemia parameters, and lipoproteins were evaluated using fasting blood samples. To understand the association between dyslipidemia and hypoxemia parameters, a multivariable logistic regression model was used. Subgroup analyses were conducted to stratify data according to age, sex, waist circumference, and chronic diseases. RESULTS: The age of the individuals involved in the study spanned from 20 to 90 years. The average age of the participants was 56.15 ± 13.11 years. Of the total sample size, 55.7% were male. In the fully adjusted model, the meanSpO2 was negatively associated with hyperlipidemia (0.9303 [95% confidence interval 0.8719, 0.9925]). Upon conducting a nonlinearity test, the relationship between the meanSpO2 and hyperlipidemia was nonlinear. The inflection points were determined to be 95. When meanSpO2 ≥ 95%, a difference of 1 in the meanSpO2 corresponded to a 0.07 difference in the risk of hyperlipidemia. CONCLUSIONS: This study revealed that higher meanSpO2 is significantly and negatively associated with hyperlipidemia in adult community residents with SDB, particularly when the meanSpO2 exceeds 95. This finding emphasizes the importance of close monitoring for dyslipidemia, which is considered an early indicator of atherosclerosis in patients with SDB who experience nocturnal hypoxia.

The saturation effect of 25(OH)D level on sleep duration for older people:The NHANES 2011-2018.

This study aimed to investigate the potential relationship between vitamin D and sleep duration in older adults. The study utilized multivariate linear regression models to estimate the associations between serum 25(OH)D and sleep duration. In addition, a smooth curve fitting approach was used to identify any non-linear trends between the two variables. The study included 15,749 participants over the age of 60. The results showed a positive correlation between serum 25(OH)D levels and sleep duration in the fully-adjusted model. This correlation was observed in both males and females, as well as in non-Hispanic White and non-Hispanic Black participants. No significant interactions were found between serum 25(OH)D levels and the stratifying variables. The curve fitting analysis revealed a non-linear relationship between 25(OH)D and sleep duration, with a saturation point observed at a serum 25(OH)D level of 40.6 ng/mL. In conclusion, the findings suggest that there is a positive correlation between serum 25(OH)D levels and sleep duration, with a saturation effect observed. A positive correlation is evident when serum 25(OH)D falls below 40.6 ng/mL.

CUL4B enhances the malignant phenotype of esophageal squamous cell carcinoma by suppressing TGFBR3 expression.

Cullin 4B (CUL4B), which acts as a scaffold protein in CUL4B-RING ubiquitin ligase complexes (CRL4B), is frequently overexpressed in cancer and represses tumor suppressors through epigenetic mechanisms. However, the expression and function of CUL4B in esophageal squamous cell carcinoma (ESCC) have not been well illustrated. In this study, we show that upregulation of CUL4B in ESCC cells enhances proliferation, invasion and cisplatin (CDDP)-resistance, while knockdown of CUL4B significantly represses the malignant activities. Mechanistically, we demonstrate that CUL4B promotes proliferation and migration of ESCC cells through inhibiting expression of transforming growth factor beta receptor III (TGFBR3). CRL4B complex binds to the promoter of TGFBR3, and represses its transcription by catalyzing monoubiquitination at H2AK119 and coordinating with PRC2 and HDAC complexes. Taken together, our findings establish a critical role for the CUL4B/TGFBR3 axis in the regulation of ESCC malignancy.

Bub1 and Bub3 regulate metabolic adaptation via macrolipophagy in Drosophila.

Lipophagy, the process of selective catabolism of lipid droplets (LDs) by autophagy, maintains lipid homeostasis and provides cellular energy under metabolic adaptation, yet its underlying mechanism remains largely ambiguous. Here, we show that the Bub1-Bub3 complex, the crucial regulator involved in the whole process of chromosome alignment and separation during mitosis, controls the fasting-induced lipid catabolism in the fat body (FB) of Drosophila. Bidirectional deviations of the Bub1 or Bub3 level affect the consumption of triacylglycerol (TAG) of fat bodies and the survival rate of adult flies under starving. Moreover, Bub1 and Bub3 work together to attenuate lipid degradation via macrolipophagy upon fasting. Thus, we uncover physiological roles of the Bub1-Bub3 complex on metabolic adaptation and lipid metabolism beyond their canonical mitotic functions, providing insights into the in vivo functions and molecular mechanisms of macrolipophagy during nutrient deprivation.