GTPBP8 modulates mitochondrial fission through a Drp1-dependent process.

Mitochondrial fission is a tightly regulated process involving multiple proteins and cell signaling. Despite extensive studies on mitochondrial fission factors, our understanding of the regulatory mechanisms remains limited. This study shows the critical role of a mitochondrial GTPase, GTPBP8, in orchestrating mitochondrial fission in mammalian cells. Depletion of GTPBP8 resulted in drastic elongation and interconnectedness of mitochondria. Conversely, overexpression of GTPBP8 shifted mitochondrial morphology from tubular to fragmented. Notably, the induced mitochondrial fragmentation from GTPBP8 overexpression was inhibited in cells either depleted of the mitochondrial fission protein Drp1 (also known as DNM1L) or carrying mutated forms of Drp1. Importantly, downregulation of GTPBP8 caused an increase in oxidative stress, modulating cell signaling involved in the increased phosphorylation of Drp1 at Ser637. This phosphorylation hindered the recruitment of Drp1 to mitochondria, leading to mitochondrial fission defects. By contrast, GTPBP8 overexpression triggered enhanced recruitment and assembly of Drp1 at mitochondria. In summary, our study illuminates the cellular function of GTPBP8 as a pivotal modulator of the mitochondrial division apparatus, inherently reliant on its influence on Drp1.

LUZP1 regulates the maturation of contractile actomyosin bundles.

Contractile actomyosin bundles play crucial roles in various physiological processes, including cell migration, morphogenesis, and muscle contraction. The intricate assembly of actomyosin bundles involves the precise alignment and fusion of myosin II filaments, yet the underlying mechanisms and factors involved in these processes remain elusive. Our study reveals that LUZP1 plays a central role in orchestrating the maturation of thick actomyosin bundles. Loss of LUZP1 caused abnormal cell morphogenesis, migration, and the ability to exert forces on the environment. Importantly, knockout of LUZP1 results in significant defects in the concatenation and persistent association of myosin II filaments, severely impairing the assembly of myosin II stacks. The disruption of these processes in LUZP1 knockout cells provides mechanistic insights into the defective assembly of thick ventral stress fibers and the associated cellular contractility abnormalities. Overall, these results significantly contribute to our understanding of the molecular mechanism involved in actomyosin bundle formation and highlight the essential role of LUZP1 in this process.

Histone H2A phosphorylation recruits topoisomerase IIα to centromeres to safeguard genomic stability.

Chromosome segregation in mitosis requires the removal of catenation between sister chromatids. Timely decatenation of sister DNAs at mitotic centromeres by topoisomerase IIα (TOP2A) is crucial to maintain genomic stability. The chromatin factors that recruit TOP2A to centromeres during mitosis remain unknown. Here, we show that histone H2A Thr-120 phosphorylation (H2ApT120), a modification generated by the mitotic kinase Bub1, is necessary and sufficient for the centromeric localization of TOP2A. Phosphorylation at residue-120 enhances histone H2A binding to TOP2A in vitro. The C-gate and the extreme C-terminal region are important for H2ApT120-dependent localization of TOP2A at centromeres. Preventing H2ApT120-mediated accumulation of TOP2A at mitotic centromeres interferes with sister chromatid disjunction, as evidenced by increased frequency of anaphase ultra-fine bridges (UFBs) that contain catenated DNA. Tethering TOP2A to centromeres bypasses the requirement for H2ApT120 in suppressing anaphase UFBs. These results demonstrate that H2ApT120 acts as a landmark that recruits TOP2A to mitotic centromeres to decatenate sister DNAs. Our study reveals a fundamental role for histone phosphorylation in resolving centromere DNA entanglements and safeguarding genomic stability during mitosis.

Vaginal microbial profile of cervical cancer patients receiving chemoradiotherapy: the potential involvement of Lactobacillus iners in recurrence.

The vaginal microbiome is an immune defense against reproductive diseases and can serve as an important biomarker for cervical cancer. However, the intrinsic relationship between the recurrence and the vaginal microbiome in patients with cervical cancer before and after concurrent chemoradiotherapy is poorly understood. Here, we analyzed 125 vaginal microbial profiles from a patient cohort of stage IB-IVB cervical cancer using 16S metagenomic sequencing and deciphered the microbial composition and functional characteristics of the recurrent and non-recurrent both before and after chemoradiotherapy. We demonstrated that the abundance of beneficial bacteria and stability of the microbial community in the vagina decreased in the recurrence group, implying the unique characteristics of the vaginal microbiome for recurrent cervical cancer. Moreover, using machine learning, we identified Lactobacillus iners as the most important biomarker, combined with age and other biomarkers (such as Ndongobacter massiliensis, Corynebacterium pyruviciproducens ATCC BAA-1742, and Prevotella buccalis), and could predict cancer recurrence phenotype before chemoradiotherapy. This study prospectively employed rigorous bioinformatics analysis and highlights the critical role of vaginal microbiota in post-treatment cervical cancer recurrence, identifying promising biomarkers with prognostic significance in the context of concurrent chemoradiotherapy for cervical cancer. The role of L. iners in determining chemoradiation resistance in cervical cancer warrants further detailed investigation. Our results expand our understanding of cervical cancer recurrence and help develop better strategies for prognosis prediction and personalized therapy.

New Strategies for Probing the Biological Functions of Protein Post-translational Modifications in Mammalian Cells with Genetic Code Expansion.

Protein post-translational modification (PTM) is a major mechanism for functional diversification of the human genome and plays a crucial role in almost every aspect of cellular processes, and the dysregulation of the protein PTM network has been associated with a variety of human diseases. Using high-resolution mass spectrometry, protein PTMs can be efficiently discovered and profiled under various biological and physiological conditions. However, it is often challenging to address the biological function of PTMs with biochemical and mutagenesis-based approaches. Specifically, this field lacks methods that allow gain-of-function studies of protein PTMs to understand their functional consequences in living cells. In this context, the genetic code expansion (GCE) strategy has made tremendous progress in the direct installation of PTMs and their analogs in the form of noncanonical amino acids (ncAAs) for gain-of-function investigations.In addition to studying the biological functions of known protein PTMs, the discovery of new protein PTMs is even more challenging due to the lack of chemical information for designing specific enrichment methods. Genetically encoded ncAAs in the proteome can be used as specific baits to enrich and subsequently identify new PTMs by mass spectrometry.In this Account, we discuss recent developments in the investigation of the biological functions of protein PTMs and the discovery of protein PTMs using new GCE strategies. First, we leveraged a chimeric design to construct several broadly orthogonal translation systems (OTSs). These broad OTSs can be engineered to efficiently incorporate different ncAAs in both E. coli and mammalian cells. With these broad OTSs, we accomplish the following: (1) We develop a computer-aided strategy for the design and genetic incorporation of length-tunable lipidation mimics. These lipidation mimics can fully recapitulate the biochemical properties of natural lipidation in membrane association for probing its biological functions on signaling proteins and in albumin binding for designing long-acting protein drugs. (2) We demonstrate that the binding affinity between histone methylations and their corresponding readers can be substantially increased with genetically encoded electron-rich Trp derivatives. These engineered affinity-enhanced readers can be applied to enrich, image, and profile the interactome of chromatin methylations. (3) We report the identification and verification of a novel type of protein PTM, aminoacylated lysine ubiquitination, using genetically encoded PTM ncAAs as chemical probes. This approach provides a general strategy for the identification of unknown PTMs by increasing the abundance of PTM bait probes.

Computational Simulations of Adsorption Behavior of Anionic Surfactants at the Portlandite-Water Interface under Sulfate and Calcium Ions.

The adsorption behaviors of two kinds of anionic surfactants (called HSO4 and HPO4, respectively) with different negatively charged hydrophilic head groups (sulfate and phosphate groups) under different concentrations of sulfate and calcium ions at the portlandite-water interface are investigated by molecular dynamics simulations. Although the adsorption strength of HPO4 is much greater than that of HSO4, the desorption energy of HSO4 is slightly greater at an early stage of desorption due to a more perpendicular orientation and denser packing of hydrophobic tail chains. After adding ions, the sulfate ion has a significant weakening effect due to competitive adsorption, and the negative influence of the calcium ion is weaker, and it even slightly promotes the adsorption at low concentration. Due to the stronger electrostatic interaction of phosphate head groups with the portlandite surface, adsorption strength and adsorption stability for HPO4 are always greater than that of HSO4 under the interference of sulfate ions. The competitive adsorption of the sulfate ion significantly weakens the interaction of hydrophilic head groups with portlandite and the dense packing of two surfactants. The calcium ion with low concentration approaches the portlandite surface and acts as an ion bridge to slightly enhance the adsorption of the surfactant. The ion bridging effect is stronger in the HPO4 system than in the HSO4 system.

Highly selective Cu2+ detection with a naphthalimide-functionalised pillar[5]arene fluorescent chemosensor.

Ligand 1, a rim-differentiated pillar[5]arene macrocycle modified with five naphthalimide groups through click chemistry, serves as an effective ratiometric fluorescent chemosensor for Cu2+. In contrast to the monomeric naphthalimide control compound 2, which shows only monomer emission, ligand 1 demonstrates dual emission characteristics encompassing both the monomer and excimer of the naphthalimide moieties. The binding properties of ligand 1 toward 15 different metal ions were systematically investigated in CH2Cl2/CH3CN (v/v, 1 : 1) by UV-vis and fluorescence spectroscopy. Remarkably, ligand 1 exhibits exceptional selectivity for Cu2+ ions. Upon complexation with Cu2+, the excimer emission of ligand 1 diminishes, concomitant with an enhancement of its monomer emission. The binding ratio for 1·Cu2+ was determined to be 1 : 1, with an association constant of (3.39 ± 0.40) × 105 M-1 calculated using a nonlinear least-squares curve-fitting method. Furthermore, the limit of detection (LOD) was found to be 185 ± 7 nM. Our results from 1H NMR titration, high-resolution mass spectrometry analysis and density functional theory calculations of 1·Cu2+ suggest synergistic coordination between Cu2+ and the triazole groups on ligand 1.

Advances in the variations and biomedical applications of stimuli-responsive nanodrug delivery systems.

Chemotherapy is an important cancer treatment modality, but the clinical utility of chemotherapeutics is limited by their toxic side effects, inadequate distribution and insufficient intracellular concentrations. Nanodrug delivery systems (NDDSs) have shown significant advantages in cancer diagnosis and treatment. Variable NDDSs that respond to endogenous and exogenous triggers have attracted much research interest. Here, we summarized nanomaterials commonly used for tumor therapy, such as peptides, liposomes, and carbon nanotubes, as well as the responses of NDDSs to pH, enzymes, magnetic fields, light, and multiple stimuli. Specifically, well-designed NDDSs can change in size or morphology or rupture when induced by one or more stimuli. The varying responses of NDDSs to stimulation contribute to the molecular design and development of novel NDDSs, providing new ideas for improving drug penetration and accumulation, inhibiting tumor resistance and metastasis, and enhancing immunotherapy.

GTPBP8 is required for mitoribosomal biogenesis and mitochondrial translation.

Mitochondrial translation occurs on the mitochondrial ribosome, also known as the mitoribosome. The assembly of mitoribosomes is a highly coordinated process. During mitoribosome biogenesis, various assembly factors transiently associate with the nascent ribosome, facilitating the accurate and efficient construction of the mitoribosome. However, the specific factors involved in the assembly process, the precise mechanisms, and the cellular compartments involved in this vital process are not yet fully understood. In this study, we discovered a crucial role for GTP-binding protein 8 (GTPBP8) in the assembly of the mitoribosomal large subunit (mt-LSU) and mitochondrial translation. GTPBP8 is identified as a novel GTPase located in the matrix and peripherally bound to the inner mitochondrial membrane. Importantly, GTPBP8 is specifically associated with the mt-LSU during its assembly. Depletion of GTPBP8 leads to an abnormal accumulation of mt-LSU, indicating that GTPBP8 is critical for proper mt-LSU assembly. Furthermore, the absence of GTPBP8 results in reduced levels of fully assembled 55S monosomes. This impaired assembly leads to compromised mitochondrial translation and, consequently, impaired mitochondrial function. The identification of GTPBP8 as an important player in these processes provides new insights into the molecular mechanisms underlying mitochondrial protein synthesis and its regulation.

Genome-wide association studies for the number of piglets born alive and dead in Dongliao black pigs.

Litter size (total number born) trait has a great impact on the economic success of pork production. The total number born consists of the number of piglets born alive and dead. To clarify the genetic background of litter size, genome-wide association studies were undertaken in the present study. Samples of DNA were collected and genotyped using the Porcine 50K BeadChip from 723 Dongliao Black sows. Using three different models (BLINK, FarmCPU, and MLM), a total of 155 significant SNPs were discovered, six of which had been reported in previous pig reproduction association studies. We suggest that rs81318434, located in the GLI3 gene, might be the promising candidate affecting litter size trait. Our findings may provide insights for uncovering the genetic mechanisms for the litter size of pigs.

Olanzapine-induced weight gain and lipid dysfunction in mice between different gender.

As one of the most common antipsychotics, olanzapine may cause metabolic-related adverse effects, but it is still unknown how olanzapine alters lipid metabolism. In this study, we found that olanzapine-treated mice showed varying degrees of dyslipidemia, which was particularly pronounced in female mice. Based on ultra-performance liquid chromatography-quadrupole time-of-flight-MS (UPLC-Q-TOF-MS) technology and lipid metabolomics, we mapped the changes in lipid metabolism in olanzapine-treated mice and then compared the changes in lipid metabolism between male and female mice. There were 98 metabolic differentiators between the olanzapine-treated and control groups in females and 79 in males. These metabolites were glycerolipids, glycerophospholipids, fatty amides, and sphingolipids, which are involved in glycerolipid metabolism, glycerophospholipid metabolism, and fatty acid metabolism. These results suggest that olanzapine-induced changes in the levels of lipid metabolites are closely associated with disturbances in lipid metabolic pathways, which may underlie lipemia. This lipidome profiling study not only visualizes changes in lipid metabolism in liver tissue but also provides a foundation for understanding the regulatory pathways and mechanisms involved in olanzapine-induced lipid metabolism disorders. Furthermore, this study demonstrates differences in lipid metabolism between males and females, providing a reference for clinical treatment regimen selection.

Prevalence and molecular characterization of multi-resistant Escherichia coli isolates from clinical bovine mastitis in China.

Different antibiotics are used to treat mastitis in dairy cows that is caused by Escherichia coli (E. coli). Antimicrobial resistance in food-producing animals in China has been monitored since 2000. Surveillance data have shown that the prevalence of multiresistant E. coli in animals has increased significantly. This study aimed to investigate the occurrence and molecular characteristics of resistance determinants in E. coli strains (n = 105) obtained from lactating cows with clinical bovine mastitis (CBM) in China. A total of 220 cows with clinical mastitis, which has swollen mammary udder with reduced and red or gangrenous milk, were selected from 5000 cows. The results showed 94.3% of the isolates were recognized as multidrug resistant. The isolates (30.5%) were positive for the class I integrase gene along with seven gene cassettes that were accountable for resistance to trimethoprim resistance (dfrA17, dfr2d and dfrA1), aminoglycosides resistance (aadA1 and aadA5) and chloramphenicol resistance (catB3 and catB2), respectively. The blaTEM gene was present in all the isolates, and these carried the blaCTX gene. A double mutation in gyrA (i.e., Ser83Leu and Asp87Asn) was observed in all fluoroquinolone-resistant isolates. In total, nine fluoroquinolone-resistant E. coli isolates were identified with five different types of mutations in parC. In four (44.4%) isolates, Ser458Ala was present in parE, and in all nine (9/9) fluoroquinolone-resistant isolates, Pro385Ala was present in gyrB. Meanwhile, fluoroquinolone was observed as highly resistant, especially in isolates with gyrA and parC mutations. In summary, the findings of this research recognize the fluoroquinolone resistance mechanism and disclose integron prevalence and ESBLs in E. coli isolates from lactating cattle with CBM.

Manipulating Cation-π Interactions of Reader Proteins in Living Cells with Genetic Code Expansion.

Despite tremendous success in understanding the chemical nature and the importance of cation-π interactions in a range of biological processes, particularly in epigenetic regulation, the design and synthesis of stronger cation-π interactions in living cells remain largely elusive. Here, we design several electron-rich Trp derivatives and incorporate them into histone methylation reader domains to enhance the affinity of the reader domains for histone methylation marks via cation-π interactions in living cells. We show that this site-specific Trp replacement strategy is generally applicable for the engineering of high-affinity reader domains for the major histone H3 trimethylation marks, such as H3K4me3, H3K9me3, H3K27me3, and H3K36me3, with high specificity. Furthermore, we demonstrate that engineered reader domains can serve as powerful tools for the enrichment and imaging of histone methylation, as well as for capturing the protein interactome at chromatin marks in living cells. Therefore, our study paves the way for the design of enhanced cation-π interactions in reader proteins in living cells for various biological applications.

Lake Sinai virus is a diverse, globally distributed but not emerging multi-strain honeybee virus.

Domesticated honeybees and wild bees are some of the most important beneficial insects for human and environmental health, but infectious diseases pose a serious risk to these pollinators, particularly following the emergence of the ectoparasitic mite Varroa destructor as a viral vector. The acquisition of this novel viral vector from the Asian honeybee Apis ceranae has fundamentally changed viral epidemiology in its new host, the western honeybee A. mellifera. While the recently discovered Lake Sinai Viruses (LSV) have been associated with weak honeybee colonies, they have not been associated with vector-borne transmission. By combining a large-scale multi-year survey of LSV in Chinese A. mellifera and A. cerana honeybee colonies with globally available LSV-sequence data, we investigate the global epidemiology of this virus. We find that globally distributed LSV is a highly diverse multi-strain virus, which is predominantly associated with the western honeybee A. mellifera. In contrast to the vector-borne deformed wing virus, LSV is not an emerging disease. Instead, demographic reconstruction and strong global and local population structure indicates that it is a highly variable multi-strain virus in a stable association with its main host, the western honeybee. Prevalence patterns in China suggest a potential role for migratory beekeeping in the spread of this pathogen, demonstrating the potential for disease transmission with the man-made transport of beneficial insects.

MicroRNA ame-let-7 targets Amdop2 to increase sucrose sensitivity in honey bees (Apis mellifera).

BACKGROUND: As an important catecholamine neurotransmitter in invertebrates and vertebrates, dopamine plays multiple roles in the life of the honey bee. Dopamine receptors (DA), which specifically bind to dopamine to activate downstream cascades, have been reported to be involved in honey bee reproduction, division of labour, as well as learning and motor behaviour. However, how dopamine receptors regulate honey bee behavior remains uninvestigated. RESULTS: The expression level of Amdop2 in the brain increased with the age of worker bees, which was just the opposite trend of ame-let-7. Inhibition of ame-let-7 through feeding an inhibitor upregulated Amdop2 expression; conversely, overexpression of ame-let-7 through a mimic downregulated Amdop2. Moreover, knockdown of Amdop2 in forager brain led to significantly higher sucrose responsiveness, which is similar to the phenotype of overexpression of ame-let-7. Finally, we confirmed that ame-let-7 directly targets Amdop2 in vitro by a luciferase reporter assay. CONCLUSIONS: ame-let-7 is involved in the dopamine receptor signaling pathway to modulate the sucrose sensitivity in honey bees. Specifically, it down-regulates Amdop2, which then induces higher responses to sucrose. These results further unraveled the diverse mechanisms of the dopamine pathway in the regulation of insect behavior.

Label-Free Chemiresistive Sensors Based on Self-Assembled Ti3C2Tx MXene Films for Monitoring of Microcystin-LR in Water Samples.

Herein, we propose a label-free chemiresistive sensor for the highly sensitive and selective detection of microcystin (MC)-LR in water samples. The sensor uses a layer-by-layer (LBL) assembled conductive film consisting of Ti3C2Tx nanosheets as the sensing channel. It is further modified by using an aptamer for the specific recognition of MC-LR. The response signal is based on the change in resistance of the conductive channel upon binding of MC-LR with the aptamer. Our novel strategy is the first concept proposed for immobilizing the aptamer containing -SH on the channel surface through a Ti-S bond under weakly alkaline condition. The resulting sensor is highly sensitive and stable for the detection of MC-LR, with a detection limit of 0.18 ng L-1 and a wide linear range from 1 to 104 ng L-1. We used the sensor to continuously monitor MC-LR released by cultivated Microcystis aeruginosa, showing a strong relationship between MC-LR and cell density. Furthermore, the sensor was successfully used to measure MC-LR in freshwater lakes with moderate algal blooms, and the results agreed well with those obtained by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The present study provides a reliable method for highly sensitive and selective detection of MC-LR in environmental waters.

Influences of protein-corona on stability and aggregation kinetics of Ti3C2Tx nanosheets in aquatic environment.

Proteins existed in aquatic environments strongly influence the transport, fate of nanomaterials due to the formation of protein-corona surrounding nanomaterials. To date, how do proteins affect the aggregation behaviors of MXene, a new family of two-dimensional materials, in aquatic environment remains unknown. Here the aggregation kinetics of MXene Ti3C2Tx nanosheets in various electrolytes (NaCl, CaCl2 and Na2SO4) was investigated by time-resolved dynamic light scattering in absence or presence of bovine serum albumin (BSA). Results showed that BSA affected the aggregation of Ti3C2Tx in a concentration-dependent manner. Addition of 3 mg/L BSA decreased the critical coagulation concentrations (CCCs) of Ti3C2Tx about 1.6-2.1 times, showing obvious destabilization effect; while BSA greater than 30 mg/L created a high-protein environment covering Ti3C2Tx, producing high spatial repulsion and enhancing the dispersibility of Ti3C2Tx. Ca2+ ions have greater effect on the aggregation of Ti3C2Tx due to the larger surface charge and bridging effect. The interaction between Ti3C2Tx and BSA followed Derjaguin-Landau-Verwey-Overbeek (DLVO) theory, and mainly attributed to hydrogen bonding and van der Waals forces, while positively charged lysine and arginine in BSA might attract onto Ti3C2Tx through electrostatic attraction. The interaction decreased the content of α-helix structure in BSA from 74.7% to 53.1%. Ti3C2Tx easily suffered from aggregation and their long-distance transport seemed impossible in synthetic or natural waters. The present findings provided new insights for understanding the transfer and fate of this nanomaterial in aquatic environments.

Research Advances on Fiber-Optic SPR Sensors with Temperature Self-Compensation.

The fiber-optic surface plasmon resonance sensor has very promising applications in environmental monitoring, biochemical sensing, and medical diagnosis, due to the superiority of high sensitivity and novel label-free microstructure. However, the influence of ambient temperature is inevitable in practical sensing applications, and even the higher the sensitivity, the greater the influence. Therefore, how to eliminate temperature interference in the sensing process has become one of the hot issues of this research field in recent years, and some accomplishments have been achieved. This paper mainly reviews the research results on temperature self-compensating fiber-optic surface plasmon sensors. Firstly, it introduces the mechanism of a temperature self-compensating fiber-optic surface plasmon resonance sensor. Then, the latest development of temperature self-compensated sensor is reviewed from the perspective of various fiber-optic sensing structures. Finally, this paper discusses the most recent applications and development prospects of temperature self-compensated fiber-optic surface plasmon resonance sensors.

Integrating Untargeted and Targeted Metabolomics Coupled with Pathway Analysis Reveals Muscle Disorder in Osteoporosis on Orchiectomized Mice.

Most osteoporosis (OP) fracture accidents in men are due not only to a low BMD but also because of unhealthy muscle support. However, there has been a limited number of reports about how muscle metabolism is disturbed by OP in males. In this work, a pathway analysis based on metabolomic research was carried out to fill this gap. A classical orchiectomy procedure was adapted to create an OP animal model. A micro-CT and pathological section were applied for a bone and muscle phenotype assessment and a pathology analysis. UPLC-Q-TOF/MS and UPLC-QQQ-MS/MS were applied to measure metabolites in skeletal muscle samples among groups. In total, 31 significantly differential metabolites were detected by comparing healthy models and OP animals, and 7 representative metabolites among the 31 significantly differential metabolites were identified and validated experimentally by UPLC-QQQ-MS/MS (xanthine, L-phenylalanine, choline, hypoxanthine, L-tryptophan, succinic acid, and L-tyrosine). An ingenuity pathway analysis (IPA) analysis revealed significantly enriched pathways involved in inflammation, oxidative stress, and necrosis. To our best knowledge, this is the first study to investigate early muscle disorder processes in Cases of OP at a metabolic level, facilitating early intervention and protection from OP fractures for aged men.

NIR-II Light Powered Asymmetric Hydrogel Nanomotors for Enhanced Immunochemotherapy.

Nanomotors are appealing drug carriers, and the strength of the propelling force is important for their motion capability. Though high motion efficiency has been achieved with 808 nm light driven Janus-structured noble metal nanomotors, the NIR-I light penetration depth and material biocompatibility limit their broad application. Herein, we develop a 1064 nm NIR-II light driven asymmetric hydrogel nanomotor (AHNM) with high motion capability and load it with doxorubicin for enhanced immunochemotherapy. Magnetic field assisted photopolymerization generates an asymmetric distribution of Fe3 O4 @Cu9 S8 nanoparticles in the AHNM, producing self-thermophoresis as driving force under NIR-II irradiation. The AHNM is also functionalized with dopamine for the capture and retention of tumor-associated antigens to boost immune activation. The as-obtained NIR-II light driven AHNM has a high tumor tissue penetration capability and enhances immunochemotherapy, providing a promising strategy for cancer therapy.