HGT is widespread in insects and contributes to male courtship in lepidopterans.

Horizontal gene transfer (HGT) is an important evolutionary force shaping prokaryotic and eukaryotic genomes. HGT-acquired genes have been sporadically reported in insects, a lineage containing >50% of animals. We systematically examined HGT in 218 high-quality genomes of diverse insects and found that they acquired 1,410 genes exhibiting diverse functions, including many not previously reported, via 741 distinct transfers from non-metazoan donors. Lepidopterans had the highest average number of HGT-acquired genes. HGT-acquired genes containing introns exhibited substantially higher expression levels than genes lacking introns, suggesting that intron gains were likely involved in HGT adaptation. Lastly, we used the CRISPR-Cas9 system to edit the prevalent unreported gene LOC105383139, which was transferred into the last common ancestor of moths and butterflies. In diamondback moths, males lacking LOC105383139 courted females significantly less. We conclude that HGT has been a major contributor to insect adaptation.

Population dynamics of head-direction neurons during drift and reorientation.

The head direction (HD) system functions as the brain's internal compass1,2, classically formalized as a one-dimensional ring attractor network3,4. In contrast to a globally consistent magnetic compass, the HD system does not have a universal reference frame. Instead, it anchors to local cues, maintaining a stable offset when cues rotate5-8 and drifting in the absence of referents5,8-10. However, questions about the mechanisms that underlie anchoring and drift remain unresolved and are best addressed at the population level. For example, the extent to which the one-dimensional description of population activity holds under conditions of reorientation and drift is unclear. Here we performed population recordings of thalamic HD cells using calcium imaging during controlled rotations of a visual landmark. Across experiments, population activity varied along a second dimension, which we refer to as network gain, especially under circumstances of cue conflict and ambiguity. Activity along this dimension predicted realignment and drift dynamics, including the speed of network realignment. In the dark, network gain maintained a 'memory trace' of the previously displayed landmark. Further experiments demonstrated that the HD network returned to its baseline orientation after brief, but not longer, exposures to a rotated cue. This experience dependence suggests that memory of previous associations between HD neurons and allocentric cues is maintained and influences the internal HD representation. Building on these results, we show that continuous rotation of a visual landmark induced rotation of the HD representation that persisted in darkness, demonstrating experience-dependent recalibration of the HD system. Finally, we propose a computational model to formalize how the neural compass flexibly adapts to changing environmental cues to maintain a reliable representation of HD. These results challenge classical one-dimensional interpretations of the HD system and provide insights into the interactions between this system and the cues to which it anchors.

Neural tuning and representational geometry.

A central goal of neuroscience is to understand the representations formed by brain activity patterns and their connection to behaviour. The classic approach is to investigate how individual neurons encode stimuli and how their tuning determines the fidelity of the neural representation. Tuning analyses often use the Fisher information to characterize the sensitivity of neural responses to small changes of the stimulus. In recent decades, measurements of large populations of neurons have motivated a complementary approach, which focuses on the information available to linear decoders. The decodable information is captured by the geometry of the representational patterns in the multivariate response space. Here we review neural tuning and representational geometry with the goal of clarifying the relationship between them. The tuning induces the geometry, but different sets of tuned neurons can induce the same geometry. The geometry determines the Fisher information, the mutual information and the behavioural performance of an ideal observer in a range of psychophysical tasks. We argue that future studies can benefit from considering both tuning and geometry to understand neural codes and reveal the connections between stimuli, brain activity and behaviour.

The influence of the number of tree searches on maximum likelihood inference in phylogenomics.

Maximum likelihood (ML) phylogenetic inference is widely used in phylogenomics. As heuristic searches most likely find suboptimal trees, it is recommended to conduct multiple (e.g., ten) tree searches in phylogenetic analyses. However, beyond its positive role, how and to what extent multiple tree searches aid ML phylogenetic inference remains poorly explored. Here, we found that a random starting tree was not as effective as the BioNJ and parsimony starting trees in inferring ML gene tree and that RAxML-NG and PhyML were less sensitive to different starting trees than IQ-TREE. We then examined the effect of the number of tree searches on ML tree inference with IQ-TREE and RAxML-NG, by running 100 tree searches on 19,414 gene alignments from 15 animal, plant, and fungal phylogenomic datasets. We found that the number of tree searches substantially impacted the recovery of the best-of-100 ML gene tree topology among 100 searches for a given ML program. In addition, all of the concatenation-based trees were topologically identical if the number of tree searches was ≥ 10. Quartet-based ASTRAL trees inferred from 1 to 80 tree searches differed topologically from those inferred from 100 tree searches for 6 /15 phylogenomic datasets. Lastly, our simulations showed that gene alignments with lower difficulty scores had a higher chance of finding the best-of-100 gene tree topology and were more likely to yield the correct trees.

Emergent neural dynamics and geometry for generalization in a transitive inference task.

Relational cognition-the ability to infer relationships that generalize to novel combinations of objects-is fundamental to human and animal intelligence. Despite this importance, it remains unclear how relational cognition is implemented in the brain due in part to a lack of hypotheses and predictions at the levels of collective neural activity and behavior. Here we discovered, analyzed, and experimentally tested neural networks (NNs) that perform transitive inference (TI), a classic relational task (if A > B and B > C, then A > C). We found NNs that (i) generalized perfectly, despite lacking overt transitive structure prior to training, (ii) generalized when the task required working memory (WM), a capacity thought to be essential to inference in the brain, (iii) emergently expressed behaviors long observed in living subjects, in addition to a novel order-dependent behavior, and (iv) expressed different task solutions yielding alternative behavioral and neural predictions. Further, in a large-scale experiment, we found that human subjects performing WM-based TI showed behavior inconsistent with a class of NNs that characteristically expressed an intuitive task solution. These findings provide neural insights into a classical relational ability, with wider implications for how the brain realizes relational cognition.

Effects of individual metabolic brain network changes co-affected by T2DM and aging on the probabilities of T2DM: protective and risk factors.

Neuroimaging markers for risk and protective factors related to type 2 diabetes mellitus are critical for clinical prevention and intervention. In this work, the individual metabolic brain networks were constructed with Jensen-Shannon divergence for 4 groups (elderly type 2 diabetes mellitus and healthy controls, and middle-aged type 2 diabetes mellitus and healthy controls). Regional network properties were used to identify hub regions. Rich-club, feeder, and local connections were subsequently obtained, intergroup differences in connections and correlations between them and age (or fasting plasma glucose) were analyzed. Multinomial logistic regression was performed to explore effects of network changes on the probability of type 2 diabetes mellitus. The elderly had increased rich-club and feeder connections, and decreased local connection than the middle-aged among type 2 diabetes mellitus; type 2 diabetes mellitus had decreased rich-club and feeder connections than healthy controls. Protective factors including glucose metabolism in triangle part of inferior frontal gyrus, metabolic connectivity between triangle of the inferior frontal gyrus and anterior cingulate cortex, degree centrality of putamen, and risk factors including metabolic connectivities between triangle of the inferior frontal gyrus and Heschl's gyri were identified for the probability of type 2 diabetes mellitus. Metabolic interactions among critical brain regions increased in type 2 diabetes mellitus with aging. Individual metabolic network changes co-affected by type 2 diabetes mellitus and aging were identified as protective and risk factors for the likelihood of type 2 diabetes mellitus, providing guiding evidence for clinical interventions.

White matter fiber integrity and structural brain network topology: implications for balance function in postischemic stroke patients.

Previous studies have suggested that ischemic stroke can result in white matter fiber injury and modifications in the structural brain network. However, the relationship with balance function scores remains insufficiently explored. Therefore, this study aims to explore the alterations in the microstructural properties of brain white matter and the topological characteristics of the structural brain network in postischemic stroke patients and their potential correlations with balance function. We enrolled 21 postischemic stroke patients and 21 age, sex, and education-matched healthy controls (HC). All participants underwent balance function assessment and brain diffusion tensor imaging. Tract-based spatial statistics (TBSS) were used to compare the fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity of white matter fibers between the two groups. The white matter structural brain network was constructed based on the automated anatomical labeling atlas, and we conducted a graph theory-based analysis of its topological properties, including global network properties and local node properties. Additionally, the correlation between the significant structural differences and balance function score was analyzed. The TBSS results showed that in comparison to the HC, postischemic stroke patients exhibited extensive damage to their whole-brain white matter fiber tracts (P < 0.05). Graph theory analysis showed that in comparison to the HC, postischemic stroke patients exhibited statistically significant reductions in the values of global efficiency, local efficiency, and clustering coefficient, as well as an increase in characteristic path length (P < 0.05). In addition, the degree centrality and nodal efficiency of some nodes in postischemic stroke patients were significantly reduced (P < 0.05). The white matter fibers of the entire brain in postischemic stroke patients are extensively damaged, and the topological properties of the structural brain network are altered, which are closely related to balance function. This study is helpful in further understanding the neural mechanism of balance function after ischemic stroke from the white matter fiber and structural brain network topological properties.

Self-Powered and Broadband Photodetectors Based on High-performance Mixed Dimensional Sb2O3/PdTe2/Si Heterojunction for Multiplex Environmental Monitoring.

Solar-blind ultraviolet (SBUV) to near-infrared (NIR) broadband photodetectors (BB-PD) have important applications in environmental monitoring and other applications. However, it is challenging to prepare SBUV-IR photosensitive materials via simple steps and to construct SBUV-IR broadband devices for multiplex detection with high sensitivity at different wavelengths. Here, self-powered and broadband photodetectors using a high-performance mixed dimensional Sb2O3 nanorod 1-dimension (1D)/monodisperse microdiamond-like PdTe2 3-dimension (3D)/Si (3D) heterojunction for multiplex detection of environmental pollutants with high sensitivity at broadband wavelength are developed. The 1D/3D mixed dimensional Sb2O3/PdTe2/Si structure combines the advantages of strong light absorption, high carrier transport efficiency of 1D Sb2O3 nanorods, and expansion of interface barrier caused by 3D microdiamond-like PdTe2 interlayer to improve the photocurrent density and self-powered ability. The efficient photogenerated charge separation enables anon/off ratio of more than 5 × 106. The device exhibits excellent photoelectric properties from 255 to 980 nm with the responsivity from 4.56 × 10-2 to 6.55 × 10-1 AW-1, the detectivity from 2.36 × 1012 to 3.39 × 1013 Jones, and the sensitivity from 3.90 × 107 to 1.10 × 1010 cm2 W-1 without external bias. Finally, the proposed device is applied for the multiplex monitoring of environmental pollution gases NO2 with the detection limit of 200 ppb and PM2.5 particles at mild pollution at broadband wavelength. The proposed BB-PD has great potential for multiplex detection of environmental pollutants and other analytes at broadband wavelength.

CProMG: controllable protein-oriented molecule generation with desired binding affinity and drug-like properties.

MOTIVATION: Deep learning-based molecule generation becomes a new paradigm of de novo molecule design since it enables fast and directional exploration in the vast chemical space. However, it is still an open issue to generate molecules, which bind to specific proteins with high-binding affinities while owning desired drug-like physicochemical properties. RESULTS: To address these issues, we elaborate a novel framework for controllable protein-oriented molecule generation, named CProMG, which contains a 3D protein embedding module, a dual-view protein encoder, a molecule embedding module, and a novel drug-like molecule decoder. Based on fusing the hierarchical views of proteins, it enhances the representation of protein binding pockets significantly by associating amino acid residues with their comprising atoms. Through jointly embedding molecule sequences, their drug-like properties, and binding affinities w.r.t. proteins, it autoregressively generates novel molecules having specific properties in a controllable manner by measuring the proximity of molecule tokens to protein residues and atoms. The comparison with state-of-the-art deep generative methods demonstrates the superiority of our CProMG. Furthermore, the progressive control of properties demonstrates the effectiveness of CProMG when controlling binding affinity and drug-like properties. After that, the ablation studies reveal how its crucial components contribute to the model respectively, including hierarchical protein views, Laplacian position encoding as well as property control. Last, a case study w.r.t. protein illustrates the novelty of CProMG and the ability to capture crucial interactions between protein pockets and molecules. It's anticipated that this work can boost de novo molecule design. AVAILABILITY AND IMPLEMENTATION: The code and data underlying this article are freely available at https://github.com/lijianing0902/CProMG.

Circuit-based neuromodulation enhances delayed recall in amnestic mild cognitive impairment.

BACKGROUND: This study aimed to investigate the efficacy of circuits-based paired associative stimulation (PAS) in adults with amnestic mild cognitive impairment (aMCI). METHODS: We conducted a parallel-group, randomised, controlled clinical trial. Initially, a cohort of healthy subjects was recruited to establish the cortical-hippocampal circuits by tracking white matter fibre connections using diffusion tensor imaging. Subsequently, patients diagnosed with aMCI, matched for age and education, were randomly allocated in a 1:1 ratio to undergo a 2-week intervention, either circuit-based PAS or sham PAS. Additionally, we explored the relationship between changes in cognitive performance and the functional connectivity (FC) of cortical-hippocampal circuits. RESULTS: FCs between hippocampus and precuneus and between hippocampus and superior frontal gyrus (orbital part) were most closely associated with the Auditory Verbal Learning Test (AVLT)_N5 score in 42 aMCI patients, thus designated as target circuits. The AVLT_N5 score improved from 2.43 (1.43) to 5.29 (1.98) in the circuit-based PAS group, compared with 2.52 (1.44) to 3.86 (2.39) in the sham PAS group (p=0.003; Cohen's d=0.97). A significant decrease was noted in FC between the left hippocampus and left precuneus in the circuit-based PAS group from baseline to postintervention (p=0.013). Using a generalised linear model, significant group×FC interaction effects for the improvements in AVLT_N5 scores were found within the circuit-based PAS group (B=3.4, p=0.017). CONCLUSIONS: Circuit-based PAS effectively enhances long-term delayed recall in adults diagnosed with aMCI, which includes individuals aged 50-80 years. This enhancement is potentially linked to the decreased functional connectivity between the left hippocampus and left precuneus. TRIAL REGISTRATION NUMBER: ChiCTR2100053315; Chinese Clinical Trial Registry.

Design and synthesis 1H-Pyrrolo[2,3-b]pyridine derivatives as FLT3 inhibitors for the treatment of Acute myeloid Leukemia.

Acute myeloid leukemia (AML) is the most common type of blood cancer and has been strongly correlated with the overexpression of Fms-like tyrosine kinase 3 (FLT3), a member of the class III receptor tyrosine kinase family. With the emergence of FLT3 internal tandem duplication alteration (ITD) and tyrosine kinase domain (TKD) mutations, the development of FLT3 small molecule inhibitors has become an effective medicinal chemistry strategy for AML. Herein, we have designed and synthesized two series of 1H-pyrrolo[2,3-b]pyridine derivatives CM1-CM24, as FLT3 inhibitors based on F14, which we previously reported, that can target the hydrophobic FLT3 back pocket. Among these derivates, CM5 showed significant inhibition of FLT3 and FLT3-ITD, with inhibitory percentages of 57.72 % and 53.77 % respectively at the concentration of 1 µΜ. Furthermore, CM5 demonstrated potent inhibition against FLT3-dependent human AML cell lines MOLM-13 and MV4-11 (both harboring FLT3-ITD mutant), with IC50 values of 0.75 µM and 0.64 µM respectively. In our cellular mechanistic studies, CM5 also effectively induces apoptosis by arresting cell cycle progression in the G0/G1 phase. In addition, the amide and urea linker function were discussed in detail based on computational simulations studies. CM5 will serve as a novel lead compound for further structural modification and development of FLT3 inhibitors specifically targeting AML with FLT3-ITD mutations.

GL-V9 ameliorates liver fibrosis by inhibiting TGF-ß/smad pathway.

Liver fibrosis is a wound-healing response that arises from various aetiologies. Flavonoid compounds have been proved of their anti-liver fibrosis effects. This study aimed to elucidate the protective effect and mechanism of flavonoid compound GL-V9 on CCl4-induced and DDC-induced liver fibrosis. Treatment with GL-V9 alleviated hepatic injury and exhibited a dramatic protection effect of liver fibrosis. Further experiments found that GL-V9 treatment inhibited extracellular matrix (ECM) expression. Activation of hepatic stellate cells (HSCs) is a central driver of fibrosis. GL-V9 could inhibit the activation of HSCs through directly binding to TGFßRI, subsequently inhibit TGF-ß/Smad pathway. In conclusion, this study proved that GL-V9 executed a protective effect on liver fibrosis by inhibiting TGF-ß/Smad pathway.

Research Progress of Small Plant Peptides on the Regulation of Plant Growth, Development, and Abiotic Stress.

Small peptides in plants are typically characterized as being shorter than 120 amino acids, with their biologically active variants comprising fewer than 20 amino acids. These peptides are instrumental in regulating plant growth, development, and physiological processes, even at minimal concentrations. They play a critical role in long-distance signal transduction within plants and act as primary responders to a range of stress conditions, including salinity, alkalinity, drought, high temperatures, and cold. This review highlights the crucial roles of various small peptides in plant growth and development, plant resistance to abiotic stress, and their involvement in long-distance transport. Furthermore, it elaborates their roles in the regulation of plant hormone biosynthesis. Special emphasis is given to the functions and mechanisms of small peptides in plants responding to abiotic stress conditions, aiming to provide valuable insights for researchers working on the comprehensive study and practical application of small peptides.

Halotolerant Bacillus sp. strain RA coordinates myo-inositol metabolism to confer salt tolerance to tomato.

Soil salinity is a worldwide problem threatening crop yields. Some plant growth-promoting rhizobacteria (PGPR) could survive in high salt environment and assist plant adaptation to stress. Nevertheless, the genomic and metabolic features, as well as the regulatory mechanisms promoting salt tolerance in plants by these bacteria remain largely unknown. In the current work, a novel halotolerant PGPR strain, namely, Bacillus sp. strain RA can enhance tomato tolerance to salt stress. Comparative genomic analysis of strain RA with its closely related species indicated a high level of evolutionary plasticity exhibited by strain-specific genes and evolutionary constraints driven by purifying selection, which facilitated its genomic adaptation to salt-affected soils. The transcriptome further showed that strain RA could tolerate salt stress by balancing energy metabolism via the reprogramming of biosynthetic pathways. Plants exude a plethora of metabolites that can strongly influence plant fitness. The accumulation of myo-inositol in leaves under salt stress was observed, leading to the promotion of plant growth triggered by Bacillus sp. strain RA. Importantly, myo-inositol serves as a selective force in the assembly of the phyllosphere microbiome and the recruitment of plant-beneficial species. It promotes destabilizing properties in phyllosphere bacterial co-occurrence networks, but not in fungal networks. Furthermore, interdomain interactions between bacteria and fungi were strengthened by myo-inositol in response to salt stress. This work highlights the genetic adaptation of RA to salt-affected soils and its ability to impact phyllosphere microorganisms through the adjustment of myo-inositol metabolites, thereby imparting enduring resistance against salt stress in tomato.

A Variable Clock Underlies Internally Generated Hippocampal Sequences.

Humans have the ability to store and retrieve memories with various degrees of specificity, and recent advances in reinforcement learning have identified benefits to learning when past experience is represented at different levels of temporal abstraction. How this flexibility might be implemented in the brain remains unclear. We analyzed the temporal organization of male rat hippocampal population spiking to identify potential substrates for temporally flexible representations. We examined activity both during locomotion and during memory-associated population events known as sharp-wave ripples (SWRs). We found that spiking during SWRs is rhythmically organized with higher event-to-event variability than spiking during locomotion-associated population events. Decoding analyses using clusterless methods further indicate that a similar spatial experience can be replayed in multiple SWRs, each time with a different rhythmic structure whose periodicity is sampled from a log-normal distribution. This variability increases with experience despite the decline in SWR rates that occurs as environments become more familiar. We hypothesize that the variability in temporal organization of hippocampal spiking provides a mechanism for storing experiences with various degrees of specificity.SIGNIFICANCE STATEMENT One of the most remarkable properties of memory is its flexibility: the brain can retrieve stored representations at varying levels of detail where, for example, we can begin with a memory of an entire extended event and then zoom in on a particular episode. The neural mechanisms that support this flexibility are not understood. Here we show that hippocampal sharp-wave ripples, which mark the times of memory replay and are important for memory storage, have a highly variable temporal structure that is well suited to support the storage of memories at different levels of detail.

How has horizontal gene transfer shaped the evolution of insect genomes?

As the most diverse group of animals on Earth, insects are key organisms in ecosystems. Horizontal gene transfer (HGT) refers to the transfer of genetic material between species by non-reproductive means. HGT is a major evolutionary force in prokaryotic genome evolution, but its importance in different eukaryotic groups, such as insects, has only recently begun to be understood. Genomic data from hundreds of insect species have enabled the detection of large numbers of HGT events and the elucidation of the functions of some of these foreign genes. Although quantification of the extent of HGT in insects broadens our understanding of its role in insect evolution, the scope of its influence and underlying mechanism(s) of its occurrence remain open questions for the field.

Multi-omics analysis of fecal microbiota transplantation's impact on functional constipation and comorbid depression and anxiety.

BACKGROUND: Depression and anxiety are common comorbid diseases of constipation. Fecal microbiota transplantation (FMT) significantly relieves gastrointestinal-related symptoms, but its impact on psychiatric symptoms remains uncharted. METHODS: We collected fecal and serum samples before and after FMT from 4 functional constipation patients with psychiatric symptoms and corresponding donor stool samples. We categorized the samples into two groups: before FMT (Fb) and after FMT (Fa). Parameters associated with constipation, depression, and anxiety symptoms were evaluated. Metagenomics and targeted neurotransmitter metabolomics were performed to investigate the gut microbiota and metabolites. 5-hydroxytryptamine (5-HT) biosynthesis was detected in patients' fecal supernatants exposed to the QGP-1 cell model in vitro. RESULTS: Our study demonstrated that patient's constipation, depression, and anxiety were improved after FMT intervention. At the genus level, relative abundance of g_Bacteroides and g_Klebsiella decreased in the Fa group, while g_Lactobacillus, and g_Selenomonas content increased in the same group. These observations suggest a potential involvement of these genera in the pathogenesis of constipation with psychiatric symptoms. Metabolomics analysis showed that FMT intervention decreased serum 5-HT levels. Additionally, we found that species, including s_Klebsiella sp. 1_1_55, s_Odoribacter splanchnicus, and s_Ruminococcus gnavus CAG:126, were positively correlated with 5-HT levels. In contrast, s_Acetobacterium bakii, s_Enterococcus hermanniensis, s_Prevotella falsenii, s_Propionispira arboris, s_Schwartzia succinivorans, s_Selenomonas artemidis, and s_Selenomonas sp. FC4001 were negatively correlated with 5-HT levels. Furthermore, we observed that patients' fecal supernatants increased 5-HT biosynthesis in QGP-1 cells. CONCLUSION: FMT can relieve patients' constipation, depression, and anxiety symptoms by reshaping gut microbiota. The 5-HT level was associated with an altered abundance of specific bacteria or metabolites. This study provides specific evidence for FMT intervention in constipation patients with psychiatric symptoms.

Association between the triglyceride-glucose index and left ventricular global longitudinal strain in patients with coronary heart disease in Jilin Province, China: a cross-sectional study.

BACKGROUND: This study aimed to investigate the association between the triglyceride-glucose (TyG) index and left ventricular global longitudinal strain (GLS) in patients with coronary heart disease and to examine the role of left ventricular GLS in detecting early changes in cardiac function in patients with coronary heart disease in the subclinical stage. METHODS: A cross-sectional study involving 178 participants with symptomatic coronary artery disease excluding myocardial infarction or left ventricular dysfunction was conducted in Jilin Province, China. Basic clinical, biochemical, and echocardiographic data were obtained from all participants. Myocardial strain parameters were compared between patients with higher TyG index and those with lower TyG index, and the association between the gradually elevated TyG index and on subclinical cardiac function in patients with coronary heart disease was evaluated. RESULTS: The GLS of left ventricle was lower in the higher TyG index group than in the lower TyG index group. As the TyG index increases, the GLS progressively decreases. The results remained stable after adjusting for confounding factors. CONCLUSIONS: A higher TyG index maybe independently associated with subclinical left ventricular dysfunction in patients with coronary heart disease.

PET/NIR Fluorescence Bimodal Imaging for Targeted Tumor Detection.

Cancer is one of the greatest threats to human health due to late diagnosis and incomplete resection. The bimodal probe combines positron emission tomography (PET) imaging for noninvasive whole-body scanning with intraoperative near-infrared fluorescence (NIRF) surgical guidance for preoperative tumor detection, tumor resection during surgery, and postoperative monitoring. We developed a new PET/NIRF bimodal imaging agent, [68Ga]Ga-DOTA-NPC, covalently coupled to DCDSTCY and DOTA via ethylenediamine and radiolabeled with gallium-68, and investigated it in vitro and in vivo. The probe was found to be preferential for colon cancer cells due to the organic anion-transporting polypeptide1B3 (OATP1B3). PET/NIRF imaging allowed us to confirm [68Ga]Ga-DOTA-NPC as a promising probe for tumor detection, as it provides good biosafety and high-contrast tumor accumulation. Orthotopic and subcutaneous colon tumors were successfully resected under real-time NIRF guidance. [68Ga]Ga-DOTA-NPC provides highly sensitive and unlimited tissue-penetrating PET/NIRF imaging, helping to visualize and differentiate tumors from adjacent tissue.