Structural Insights into Non-canonical Ubiquitination Catalyzed by SidE.

Ubiquitination constitutes one of the most important signaling mechanisms in eukaryotes. Conventional ubiquitination is catalyzed by the universally conserved E1-E2-E3 three-enzyme cascade in an ATP-dependent manner. The newly identified SidE family effectors of the pathogen Legionella pneumophila ubiquitinate several human proteins by a different mechanism without engaging any of the conventional ubiquitination machinery. We now report the crystal structures of SidE alone and in complex with ubiquitin, NAD, and ADP-ribose, thereby capturing different conformations of SidE before and after ubiquitin and ligand binding. The structures of ubiquitin bound to both mART and PDE domains reveal several unique features of the two reaction steps catalyzed by SidE. Further, the structural and biochemical results demonstrate that SidE family members do not recognize specific structural folds of the substrate proteins. Our studies provide both structural explanations for the functional observations and new insights into the molecular mechanisms of this non-canonical ubiquitination machinery.

Recognition of cyclic dinucleotides and folates by human SLC19A1.

Cyclic dinucleotides (CDNs) are ubiquitous signalling molecules in all domains of life1,2. Mammalian cells produce one CDN, 2'3'-cGAMP, through cyclic GMP-AMP synthase after detecting cytosolic DNA signals3-7. 2'3'-cGAMP, as well as bacterial and synthetic CDN analogues, can act as second messengers to activate stimulator of interferon genes (STING) and elicit broad downstream responses8-21. Extracellular CDNs must traverse the cell membrane to activate STING, a process that is dependent on the solute carrier SLC19A122,23. Moreover, SLC19A1 represents the major transporter for folate nutrients and antifolate therapeutics24,25, thereby placing SLC19A1 as a key factor in multiple physiological and pathological processes. How SLC19A1 recognizes and transports CDNs, folate and antifolate is unclear. Here we report cryo-electron microscopy structures of human SLC19A1 (hSLC19A1) in a substrate-free state and in complexes with multiple CDNs from different sources, a predominant natural folate and a new-generation antifolate drug. The structural and mutagenesis results demonstrate that hSLC19A1 uses unique yet divergent mechanisms to recognize CDN- and folate-type substrates. Two CDN molecules bind within the hSLC19A1 cavity as a compact dual-molecule unit, whereas folate and antifolate bind as a monomer and occupy a distinct pocket of the cavity. Moreover, the structures enable accurate mapping and potential mechanistic interpretation of hSLC19A1 with loss-of-activity and disease-related mutations. Our research provides a framework for understanding the mechanism of SLC19-family transporters and is a foundation for the development of potential therapeutics.

Diverse Mechanisms of CRISPR-Cas9 Inhibition by Type IIC Anti-CRISPR Proteins.

Anti-CRISPR proteins (Acrs) targeting CRISPR-Cas9 systems represent natural "off switches" for Cas9-based applications. Recently, AcrIIC1, AcrIIC2, and AcrIIC3 proteins were found to inhibit Neisseria meningitidis Cas9 (NmeCas9) activity in bacterial and human cells. Here we report biochemical and structural data that suggest molecular mechanisms of AcrIIC2- and AcrIIC3-mediated Cas9 inhibition. AcrIIC2 dimer interacts with the bridge helix of Cas9, interferes with RNA binding, and prevents DNA loading into Cas9. AcrIIC3 blocks the DNA loading step through binding to a non-conserved surface of the HNH domain of Cas9. AcrIIC3 also forms additional interactions with the REC lobe of Cas9 and induces the dimerization of the AcrIIC3-Cas9 complex. While AcrIIC2 targets Cas9 orthologs from different subtypes, albeit with different efficiency, AcrIIC3 specifically inhibits NmeCas9. Structure-guided changes in NmeCas9 orthologs convert them into anti-CRISPR-sensitive proteins. Our studies provide insights into anti-CRISPR-mediated suppression mechanisms and guidelines for designing regulatory tools in Cas9-based applications.

PKM2-TMEM33 axis regulates lipid homeostasis in cancer cells by controlling SCAP stability.

The pyruvate kinase M2 isoform (PKM2) is preferentially expressed in cancer cells to regulate anabolic metabolism. Although PKM2 was recently reported to regulate lipid homeostasis, the molecular mechanism remains unclear. Herein, we discovered an ER transmembrane protein 33 (TMEM33) as a downstream effector of PKM2 that regulates activation of SREBPs and lipid metabolism. Loss of PKM2 leads to up-regulation of TMEM33, which recruits RNF5, an E3 ligase, to promote SREBP-cleavage activating protein (SCAP) degradation. TMEM33 is transcriptionally regulated by nuclear factor erythroid 2-like 1 (NRF1), whose cleavage and activation are controlled by PKM2 levels. Total plasma cholesterol levels are elevated by either treatment with PKM2 tetramer-promoting agent TEPP-46 or by global PKM2 knockout in mice, highlighting the essential function of PKM2 in lipid metabolism. Although depletion of PKM2 decreases cancer cell growth, global PKM2 knockout accelerates allografted tumor growth. Together, our findings reveal the cell-autonomous and systemic effects of PKM2 in lipid homeostasis and carcinogenesis, as well as TMEM33 as a bona fide regulator of lipid metabolism.

Ferroelastically protected reversible orthorhombic to monoclinic-like phase transition in ZrO2 nanocrystals.

Robust ferroelectricity in nanoscale fluorite oxide-based thin films enables promising applications in silicon-compatible non-volatile memories and logic devices. However, the polar orthorhombic (O) phase of fluorite oxides is a metastable phase that is prone to transforming into the ground-state non-polar monoclinic (M) phase, leading to macroscopic ferroelectric degradation. Here we investigate the reversibility of the O-M phase transition in ZrO2 nanocrystals via in situ visualization of the martensitic transformation at the atomic scale. We reveal that the reversible shear deformation pathway from the O phase to the monoclinic-like (M') state, a compressive-strained M phase, is protected by 90° ferroelectric-ferroelastic switching. Nevertheless, as the M' state gradually accumulates localized strain, a critical tensile strain can pin the ferroelastic domain, resulting in an irreversible M'-M strain relaxation and the loss of ferroelectricity. These findings demonstrate the key role of ferroelastic switching in the reversibility of phase transition and also provide a tensile-strain threshold for stabilizing the metastable ferroelectric phase in fluorite oxide thin films.

Sustainable LiCoO2 by collective glide of CoO6 slabs upon charge/discharge.

SignificanceTraditional views indicate that the well-known layered LiCoO2 cathode delivers a typical solid-solution reaction upon delithiation. The problem is that "solid solution" is a vague concept, and the phase transition remains ambiguous. Here, we reveal a mechanism with the collective and quasi-continuous glide of CoO6 slabs in layered LiCoO2 through combining in situ XRD and ex situ STEM characterizations. Such a delithiation mechanism does not involve the nucleation-and-growth-type delithiation process and represents a completely different manner from the conventional two-phase or solid solution-phase transition processes. The lessons provide a different insight into understanding the working mechanism of layered oxide materials.

New Insight into Bulk Structural Degradation of High-Voltage LiCoO2 at 4.55 V.

The aggravated mechanical and structural degradation of layered oxide cathode materials upon high-voltage charging invariably causes fast capacity fading, but the underlying degradation mechanisms remain elusive. Here we report a new type of mechanical degradation through the formation of a kink band in a Mg and Ti co-doped LiCoO2 cathode charged to 4.55 V (vs Li/Li+). The local stress accommodated by the kink band can impede crack propagation, improving the structural integrity in a highly delithiated state. Additionally, machine-learning-aided atomic-resolution imaging reveals that the formation of kink bands is often accompanied by the transformation from the O3 to O1 phase, which is energetically favorable as demonstrated by first-principles calculations. Our results provide new insights into the mechanical degradation mechanism of high-voltage LiCoO2 and the coupling between electrochemically triggered mechanical failures and structural transition, which may provide valuable guidance for enhancing the electrochemical performance of high-voltage layered oxide cathode materials for lithium-ion batteries.

A Fully Elastic Wearable Electrochemical Sweat Detection System of Tree-Bionic Microfluidic Structure for Real-Time Monitoring.

Fresh sweat contains a diverse range of physiological indicators that can effectively reflect changes in the body. However, existing wearable sweat detection systems face challenges in efficiently collecting and detecting fresh sweat in real-time. Additionally, they often lack the necessary deformation capabilities, resulting in discomfort for the wearer. Here, a fully elastic wearable electrochemical sweat detection system is developed that integrates a sweat-collecting microfluidic chip, a multi-parameter electrochemical sensor, a micro-heater, and a sweat detection elastic circuit board system. The unique tree-bionic structure of the microfluidic chip significantly enhances the efficiency of fresh sweat collection and discharge, enabling real-time detection by the electrochemical sensors. The sweat multi-parameter electrochemical sensor offers high-precision and high-sensitivity measurements of sodium ions, potassium ions, lactate, and glucose. The electronic system is built on an elastic circuit board that matches perfectly to wrinkled skin, ensuring improved wearing comfort and enabling multi-channel data sampling, processing, and wireless transmission. This state-of-the-art system represents a significant advancement in the field of elastic wearable sweat detection and holds promising potential for extending its capabilities to the detection of other sweat markers or various wearable applications.

Association Between Substance Abuse and Mental Illness Symptoms Screener (SAMISS) Scores and HIV Care Continuum Outcomes in People Newly Diagnosed with HIV in the US South.

Mental illness (MI) and substance use (SU) are highly prevalent among people with HIV (PWH) and impact care outcomes. The Substance Abuse and Mental Illness Symptoms Screener (SAMISS) is a validated screener for MI and SU, but it is unknown how screening results at entry to care correlate with subsequent HIV outcomes. This is a retrospective chart review of individuals newly diagnosed with HIV between 2016 and 2019 in a Southern US, safety-net clinic. Baseline demographics, HIV risk factors, socioeconomic variables, and SAMISS screening scores were collected. Outcomes included retention in care, achieving virologic suppression (VS), and continuous VS. Data analyses included stepwise Cox and logistic multivariate regression modeling. Among the 544 newly diagnosed PWH, mean age was 35, 76% were male, 46% non-Hispanic Black, 40% Hispanic/other. Overall, 35% screened positive for SU and 41% for MI. A positive SU (odds ratio (OR) 0.66, p = 0.04) or MI (OR 0.65, p = 0.03) SAMISS screening was associated with lower retention in care in univariate analysis, but was not statistically significant after adjusting for other variables. Positive SAMISS screening for SU and MI were both associated with reduced continuous VS in univariate and multivariate analyses (SU: adjusted OR (aOR) 0.67, p = 0.05; MI: aOR 0.66, p = 0.03). SAMISS is a useful tool for prospectively identifying individuals at risk for low retention in care and for not achieving sustained VS. Future interventions guided by SAMISS may improve HIV care continuum outcomes.

Up-regulation of Dsg2 confered stem cells with malignancy through wnt/ß-catenin signaling pathway.

In the previous study, we originally developed cancer stem cells (CSCs) models from mouse induced pluripotent stem cells (miPSCs) by culturing miPSCs in the conditioned medium of cancer cell lines, which mimiced as carcinoma microenvironment. However, the molecular mechanism of conversion in detail remains to be uncovered. Microarray analysis of the CSCs models in this study revealed Dsg2, one of the members of the desmosomal cadherin family, was up-regulated when compared with the original miPSCs. Moreover, the expression of key factors in Wnt/ß-catenin signaling pathway were also found up-regulated in one of the CSCs models, named miPS-LLCcm. An autocrine loop was implied between Dsg2 and Wnt/ß-catenin signaling pathway when miPSCs were treated with Wnt/ß-catenin signaling pathway activators, Wnt3a and CHIR99021, and when the CSCs model were treated with inhibitors, IWR-1 and IWP-2. Furthermore, the ability of proliferation and self-renewal in the CSCs model was markedly decreased in vitro and in vivo when Dsg2 gene was knocked down by shRNA. Our results showed that the Wnt/ß-catenin signaling pathway is activated by the up-regulation of Dsg2 expresssion during the conversion of miPSCs into CSCs implying a potential mechanism of the tranformation of stem cells into malignant phenotype.

Adenovirus-vectored vaccine containing multidimensionally conserved parts of the HIV proteome is immunogenic in rhesus macaques.

An effective vaccine that can protect against HIV infection does not exist. A major reason why a vaccine is not available is the high mutability of the virus, which enables it to evolve mutations that can evade human immune responses. This challenge is exacerbated by the ability of the virus to evolve compensatory mutations that can partially restore the fitness cost of immune-evading mutations. Based on the fitness landscapes of HIV proteins that account for the effects of coupled mutations, we designed a single long peptide immunogen comprising parts of the HIV proteome wherein mutations are likely to be deleterious regardless of the sequence of the rest of the viral protein. This immunogen was then stably expressed in adenovirus vectors that are currently in clinical development. Macaques immunized with these vaccine constructs exhibited T-cell responses that were comparable in magnitude to animals immunized with adenovirus vectors with whole HIV protein inserts. Moreover, the T-cell responses in immunized macaques strongly targeted regions contained in our immunogen. These results suggest that further studies aimed toward using our vaccine construct for HIV prophylaxis and cure are warranted.

Nonspecific immune, histology and accumulation of marine worm, Urechis unicinctus in response to bisphenol A (BPA).

Bisphenol A (BPA) is one of the environmental endocrine disruptors, due to its chemical stability it exists in abundant concentrations in water and soil consequently accumulating in the food chain and causing many endocrine-related health problems. So far, studies on the effects of BPA on marine invertebrates have focused on acute toxicity, endocrine regulation, reproduction, and development. However, fewer studies have been conducted on marine benthos. The current study aimed to detect the accumulation of BPA and its impact on tissue structure, antioxidant capacity, and immune indexes in marine worm, Urechis unicinctus. U. unicinctus, as a common marine benthic animal, were exposed to different concentrations of BPA. Blood cells and intestinal tract were taken for tissue structure inspection, and supernatant of the coelomic fluid was collected for oxidative and antioxidant biomarkers. Results showed that the accumulation of BPA in muscles of U. unicinctus tended to increase with exposure time. BPA induced a rise in H2O2 and MDA content, and altered the activities of CAT, T-SOD, GST, LSZ and ACP, weaken the immune system functions. Moreover, pathological observation showed that BPA caused severe histopathology in the respiratory intestine, stomach, and midgut. These results will be helpful to understand the response mechanism of U. unicinctus under BPA exposure and provide a reference for controlling the aquaculture conditions and marine water quality of U. unicinctus.

Multi-d Electron Synergy in LaNi1-x Cox Ru Intermetallics Boosts Electrocatalytic Hydrogen Evolution.

Despite the fact that d-band center theory links the d electron structure of transition metals to their catalytic activity, it is yet unknown how the synergistic effect of multi-d electrons impacts catalytic performance. Herein, novel LaNi1-x Cox Ru intermetallics containing 5d, 4d, and 3d electrons were prepared. In these compounds, the 5d orbital of La transfers electrons to the 4d orbital of Ru, which provides adsorption sites for H*. The 3d orbitals of Ni and Co interact with the 5d and 4d orbitals to generate an anisotropic electron distribution, which facilitates the adsorption and desorption of OH*. The synergistic effect of multi-d electrons ensures efficient catalytic activity. The optimized LaNi0.5 Co0.5 Ru has an overpotential of 43mV at 10 mA cm-2 for alkaline electrocatalytic hydrogen evolution reaction. Beyond offering a variety of new electrocatalysts, this work reveals the multi-d electron synergy in promoting catalytic reaction.

Diptoindonesin G is a middle domain HSP90 modulator for cancer treatment.

HSP90 inhibitors can target many oncoproteins simultaneously, but none have made it through clinical trials due to dose-limiting toxicity and induction of heat shock response, leading to clinical resistance. We identified diptoindonesin G (dip G) as an HSP90 modulator that can promote degradation of HSP90 clients by binding to the middle domain of HSP90 (Kd = 0.13 ± 0.02 µM) without inducing heat shock response. This is likely because dip G does not interfere with the HSP90-HSF1 interaction like N-terminal inhibitors, maintaining HSF1 in a transcriptionally silent state. We found that binding of dip G to HSP90 promotes degradation of HSP90 client protein estrogen receptor α (ER), a major oncogenic driver protein in most breast cancers. Mutations in the ER ligand-binding domain (LBD) are an established mechanism of endocrine resistance and decrease the binding affinity of mainstay endocrine therapies targeting ER, reducing their ability to promote ER degradation or transcriptionally silence ER. Because dip G binds to HSP90 and does not bind to the LBD of ER, unlike endocrine therapies, it is insensitive to ER LBD mutations that drive endocrine resistance. Additionally, we determined that dip G promoted degradation of WT and mutant ER with similar efficacy, downregulated ER- and mutant ER-regulated gene expression, and inhibited WT and mutant cell proliferation. Our data suggest that dip G is not only a molecular probe to study HSP90 biology and the HSP90 conformation cycle, but also a new therapeutic avenue for various cancers, particularly endocrine-resistant breast cancer harboring ER LBD mutations.

Cu(I)-Catalyzed Chemo- and Enantioselective Desymmetrizing C-O Bond Coupling of Acyl Radicals.

Transition-metal-catalyzed enantioselective functionalization of acyl radicals has so far not been realized, probably due to their relatively high reactivity, which renders the chemo- and stereocontrol challenging. Herein, we describe Cu(I)-catalyzed enantioselective desymmetrizing C-O bond coupling of acyl radicals. This reaction is compatible with (hetero)aryl and alkyl aldehydes and, more importantly, displays a very broad scope of challenging alcohol substrates, such as 2,2-disubstituted 1,3-diols, 2-substituted-2-chloro-1,3-diols, 2-substituted 1,2,3-triols, 2-substituted serinols, and meso primary 1,4-diols, providing enantioenriched esters characterized by challenging acyclic tetrasubstituted carbon stereocenters. Partnered by one- or two-step follow-up transformations, this reaction provides a convenient and practical strategy for the rapid preparation of chiral C3 building blocks from readily available alcohols, particularly the industrially relevant glycerol. Mechanistic studies supported the proposed C-O bond coupling of acyl radicals.

Influenza A Virus Uses PSMA2 for Downregulation of the NRF2-Mediated Oxidative Stress Response.

Influenza A virus (IAV), an obligatory intracellular parasite, uses host cellular molecules to complete its replication cycle and suppress immune responses. Proteasome subunit alpha type 2 (PSMA2) is a cellular protein highly expressed in IAV-infected human lung epithelial A549 cells. PSMA2 is part of the 20S proteasome complex that degrades or recycles defective proteins and involves proteolytic modification of many cellular regulatory proteins. However, the role of PSMA2 in IAV replication is not well understood. In this study, PSMA2 knockdown (KD) in A549 cells caused a significant reduction in extracellular progeny IAV, but intracellular viral protein translation and viral RNA transcription were not affected. This indicates that PSMA2 is a critical host factor for IAV maturation. To better understand the interplay between PSMA2 KD and IAV infection at the proteomic level, we used the SomaScan 1.3K version, which measures 1,307 proteins to analyze alterations induced by these treatments. We found seven cellular signaling pathways, including phospholipase C signaling, Pak signaling, and nuclear factor erythroid 2p45-related factor 2 (NRF2)-mediated oxidative stress response signaling, that were inhibited by IAV infection but significantly activated by PSMA2 KD. Further analysis of NRF2-mediated oxidative stress response signaling indicated IAV inhibits accumulation of reactive oxygen species (ROS), but ROS levels significantly increased during IAV infection in PSMA2 KD cells. However, IAV infection caused significantly higher NFR2 nuclear translocation that was inhibited in PSMA2 KD cells. This indicates that PSMA2 is required for NRF2-mediated ROS neutralization and that IAV uses PSMA2 to escape viral clearance via the NRF2-mediated cellular oxidative response. IMPORTANCE Influenza A virus (IAV) remains one of the most significant infectious agents, responsible for 3 million to 5 million illnesses each year and more than 50 million deaths during the 20th century. The cellular processes that promote and inhibit IAV infection and pathogenesis remain only partially understood. PSMA2 is a critical component of the 20S proteasome and ubiquitin-proteasome system, which is important in the replication of numerous viruses. This study examined host protein responses to IAV infection alone, PSMA2 knockdown alone, and IAV infection in the presence of PSMA2 knockdown and determined that interfering with PSMA2 function affected IAV maturation. These results help us better understand the importance of PSMA2 in IAV replication and may pave the way for designing additional IAV antivirals targeting PSMA2 or the host proteasome for the treatment of seasonal flu.

Plant lipid phosphate phosphatases: current advances and future outlooks.

Lipids are widely distributed in various tissues of an organism, mainly in plant storage organs (e.g., fruits, seeds, etc.). Lipids are vital biological substances that are involved in: signal transduction, membrane biogenesis, energy storage, and the formation of transmembrane fat-soluble substances. Some lipids and related lipid derivatives could be changed in their: content, location, or physiological activity by the external environment, such as biotic or abiotic stresses. Lipid phosphate phosphatases (LPPs) play important roles in regulating intermediary lipid metabolism and cellular signal response. LPPs can dephosphorylate lipid phosphates containing phosphate monolipid bonds such as: phosphatidic acid, lysophosphatidic acid (LPA), and diacylglycerol pyrophosphate, etc. These processes can change the contents of some important lipid signal mediation such as diacylglycerol and LPA, affecting lipid signal transmission. Here, we summarize the research progress of LPPs in plants, emphasizing the structural and biochemical characteristics of LPPs and their role in spatio-temporal regulation. In the future, more in-depth studies are required to boost our understanding of the key role of plant LPPs and lipid metabolism in: signal regulation, stress tolerance pathway, and plant growth and development.

Short solvent model for ion correlations and hydrophobic association.

Coulomb interactions play a major role in determining the thermodynamics, structure, and dynamics of condensed-phase systems, but often present significant challenges. Computer simulations usually use periodic boundary conditions to minimize corrections from finite cell boundaries but the long range of the Coulomb interactions generates significant contributions from distant periodic images of the simulation cell, usually calculated by Ewald sum techniques. This can add significant overhead to computer simulations and hampers the development of intuitive local pictures and simple analytic theory. In this paper, we present a general framework based on local molecular field theory to accurately determine the contributions from long-ranged Coulomb interactions to the potential of mean force between ionic or apolar hydrophobic solutes in dilute aqueous solutions described by standard classical point charge water models. The simplest approximation leads to a short solvent (SS) model, with truncated solvent-solvent and solute-solvent Coulomb interactions and long-ranged but screened Coulomb interactions only between charged solutes. The SS model accurately describes the interplay between strong short-ranged solute core interactions, local hydrogen-bond configurations, and long-ranged dielectric screening of distant charges, competing effects that are difficult to capture in standard implicit solvent models.

YOLO-Weld: A Modified YOLOv5-Based Weld Feature Detection Network for Extreme Weld Noise.

Weld feature point detection is a key technology for welding trajectory planning and tracking. Existing two-stage detection methods and conventional convolutional neural network (CNN)-based approaches encounter performance bottlenecks under extreme welding noise conditions. To better obtain accurate weld feature point locations in high-noise environments, we propose a feature point detection network, YOLO-Weld, based on an improved You Only Look Once version 5 (YOLOv5). By introducing the reparameterized convolutional neural network (RepVGG) module, the network structure is optimized, enhancing detection speed. The utilization of a normalization-based attention module (NAM) in the network enhances the network's perception of feature points. A lightweight decoupled head, RD-Head, is designed to improve classification and regression accuracy. Furthermore, a welding noise generation method is proposed, increasing the model's robustness in extreme noise environments. Finally, the model is tested on a custom dataset of five weld types, demonstrating better performance than two-stage detection methods and conventional CNN approaches. The proposed model can accurately detect feature points in high-noise environments while meeting real-time welding requirements. In terms of the model's performance, the average error of detecting feature points in images is 2.100 pixels, while the average error in the world coordinate system is 0.114 mm, sufficiently meeting the accuracy needs of various practical welding tasks.

Deep Learning-Based Multiclass Brain Tissue Segmentation in Fetal MRIs.

Fetal brain tissue segmentation is essential for quantifying the presence of congenital disorders in the developing fetus. Manual segmentation of fetal brain tissue is cumbersome and time-consuming, so using an automatic segmentation method can greatly simplify the process. In addition, the fetal brain undergoes a variety of changes throughout pregnancy, such as increased brain volume, neuronal migration, and synaptogenesis. In this case, the contrast between tissues, especially between gray matter and white matter, constantly changes throughout pregnancy, increasing the complexity and difficulty of our segmentation. To reduce the burden of manual refinement of segmentation, we proposed a new deep learning-based segmentation method. Our approach utilized a novel attentional structural block, the contextual transformer block (CoT-Block), which was applied in the backbone network model of the encoder-decoder to guide the learning of dynamic attentional matrices and enhance image feature extraction. Additionally, in the last layer of the decoder, we introduced a hybrid dilated convolution module, which can expand the receptive field and retain detailed spatial information, effectively extracting the global contextual information in fetal brain MRI. We quantitatively evaluated our method according to several performance measures: dice, precision, sensitivity, and specificity. In 80 fetal brain MRI scans with gestational ages ranging from 20 to 35 weeks, we obtained an average Dice similarity coefficient (DSC) of 83.79%, an average Volume Similarity (VS) of 84.84%, and an average Hausdorff95 Distance (HD95) of 35.66 mm. We also used several advanced deep learning segmentation models for comparison under equivalent conditions, and the results showed that our method was superior to other methods and exhibited an excellent segmentation performance.