Comparative Analysis of Human-Chimpanzee Divergence in Brain Connectivity and its Genetic Correlates.

Chimpanzees (Pan troglodytes) are humans' closest living relatives, making them the most directly relevant comparison point for understanding human brain evolution. Zeroing in on the differences in brain connectivity between humans and chimpanzees can provide key insights into the specific evolutionary changes that might have occured along the human lineage. However, conducting comparisons of brain connectivity between humans and chimpanzees remains challenging, as cross-species brain atlases established within the same framework are currently lacking. Without the availability of cross-species brain atlases, the region-wise connectivity patterns between humans and chimpanzees cannot be directly compared. To address this gap, we built the first Chimpanzee Brainnetome Atlas (ChimpBNA) by following a well-established connectivity-based parcellation framework. Leveraging this new resource, we found substantial divergence in connectivity patterns across most association cortices, notably in the lateral temporal and dorsolateral prefrontal cortex between the two species. Intriguingly, these patterns significantly deviate from the patterns of cortical expansion observed in humans compared to chimpanzees. Additionally, we identified regions displaying connectional asymmetries that differed between species, likely resulting from evolutionary divergence. Genes associated with these divergent connectivities were found to be enriched in cell types crucial for cortical projection circuits and synapse formation. These genes exhibited more pronounced differences in expression patterns in regions with higher connectivity divergence, suggesting a potential foundation for brain connectivity evolution. Therefore, our study not only provides a fine-scale brain atlas of chimpanzees but also highlights the connectivity divergence between humans and chimpanzees in a more rigorous and comparative manner and suggests potential genetic correlates for the observed divergence in brain connectivity patterns between the two species. This can help us better understand the origins and development of uniquely human cognitive capabilities.

Prior-guided individualized thalamic parcellation based on local diffusion characteristics.

Comprising numerous subnuclei, the thalamus intricately interconnects the cortex and subcortex, orchestrating various facets of brain functions. Extracting personalized parcellation patterns for these subnuclei is crucial, as different thalamic nuclei play varying roles in cognition and serve as therapeutic targets for neuromodulation. However, accurately delineating the thalamic nuclei boundary at the individual level is challenging due to intersubject variability. In this study, we proposed a prior-guided parcellation (PG-par) method to achieve robust individualized thalamic parcellation based on a central-boundary prior. We first constructed probabilistic atlas of thalamic nuclei using high-quality diffusion MRI datasets based on the local diffusion characteristics. Subsequently, high-probability voxels in the probabilistic atlas were utilized as prior guidance to train unique multiple classification models for each subject based on a multilayer perceptron. Finally, we employed the trained model to predict the parcellation labels for thalamic voxels and construct individualized thalamic parcellation. Through a test-retest assessment, the proposed prior-guided individualized thalamic parcellation exhibited excellent reproducibility and the capacity to detect individual variability. Compared with group atlas registration and individual clustering parcellation, the proposed PG-par demonstrated superior parcellation performance under different scanning protocols and clinic settings. Furthermore, the prior-guided individualized parcellation exhibited better correspondence with the histological staining atlas. The proposed prior-guided individualized thalamic parcellation method contributes to the personalized modeling of brain parcellation.

Individualized brain mapping for navigated neuromodulation.

ABSTRACT: The brain is a complex organ that requires precise mapping to understand its structure and function. Brain atlases provide a powerful tool for studying brain circuits, discovering biological markers for early diagnosis, and developing personalized treatments for neuropsychiatric disorders. Neuromodulation techniques, such as transcranial magnetic stimulation and deep brain stimulation, have revolutionized clinical therapies for neuropsychiatric disorders. However, the lack of fine-scale brain atlases limits the precision and effectiveness of these techniques. Advances in neuroimaging and machine learning techniques have led to the emergence of stereotactic-assisted neurosurgery and navigation systems. Still, the individual variability among patients and the diversity of brain diseases make it necessary to develop personalized solutions. The article provides an overview of recent advances in individualized brain mapping and navigated neuromodulation and discusses the methodological profiles, advantages, disadvantages, and future trends of these techniques. The article concludes by posing open questions about the future development of individualized brain mapping and navigated neuromodulation.

Titania Nanosheet as a Matrix for Surface-Assisted Laser Desorption/Ionization Mass Spectrometry Analysis and Imaging.

Surface-assisted laser desorption/ionization (SALDI) acts as a soft desorption/ionization technique, which has been widely recognized in small-molecule analysis owing to eliminating the requirement of the organic matrix. Herein, titania nanosheets (TiO2 NSs) were applied as novel substrates for simultaneous analysis and imaging of low-mass molecules and lipid species. A wide variety of representative analytes containing amino acids, bases, drugs, peptides, endogenous small molecules, and saccharide-spiked urine were examined by the TiO2 NS-assisted LDI mass spectrometry (MS). Compared with conventional organic matrices and substrates [Ag nanoparticles (NPs), Au NPs, carbon nanotubes, carbon NPs, CeO2 microparticles, and P25 TiO2], the TiO2 NS-assisted LDI MS method shows higher sensitivity and less spectral interference. Repeatability was evaluated with batch-to-batch relative standard deviations for 5-hydroxytryptophan, glucose-spiked urine, and glucose with addition of internal standard, which were 17.4, 14.9, and 2.8%, respectively. The TiO2 NS-assisted LDI MS method also allows the determination of blood glucose levels in mouse serum with a linear range of 0.5-10 mM. Owing to the nanoscale size and uniform deposition of the TiO2 NS matrix, spatial distributions of 16 endogenous small molecules and 16 lipid species from the horizontal section of the mouse brain tissue can be visualized at a 50 µm spatial resolution. These successful applications confirm that the TiO2-assisted LDI MS method has promising prospects in the field of life science.

Uncovering the genetic profiles underlying the intrinsic organization of the human cerebellum.

The functional diversity of the human cerebellum is largely believed to be derived more from its extensive connections rather than being limited to its mostly invariant architecture. However, whether and how the determination of cerebellar connections in its intrinsic organization interact with microscale gene expression is still unknown. Here we decode the genetic profiles of the cerebellar functional organization by investigating the genetic substrates simultaneously linking cerebellar functional heterogeneity and its drivers, i.e., the connections. We not only identified 443 network-specific genes but also discovered that their co-expression pattern correlated strongly with intra-cerebellar functional connectivity (FC). Ninety of these genes were also linked to the FC of cortico-cerebellar cognitive-limbic networks. To further discover the biological functions of these genes, we performed a "virtual gene knock-out" by observing the change in the coupling between gene co-expression and FC and divided the genes into two subsets, i.e., a positive gene contribution indicator (GCI+) involved in cerebellar neurodevelopment and a negative gene set (GCI-) related to neurotransmission. A more interesting finding is that GCI- is significantly linked with the cerebellar connectivity-behavior association and many recognized brain diseases that are closely linked with the cerebellar functional abnormalities. Our results could collectively help to rethink the genetic substrates underlying the cerebellar functional organization and offer possible micro-macro interacted mechanistic interpretations of the cerebellum-involved high order functions and dysfunctions in neuropsychiatric disorders.

Single-Cell Mass Spectrometry Imaging of Multiple Drugs and Nanomaterials at Organelle Level.

Mass spectrometry imaging (MSI) techniques make possible the spatial chemical identification of analytes, especially for biological samples. As a universal energy source, laser is one of the most commonly used sampling methods in MSI techniques. However, due to the limitation of laser spot size, subcellular spatial resolution imaging, which is significant for life science researches, always remains a challenge for laser-based MSI. In this research, we designed a laser ablation (LA) system with a microlensed fiber and a "three-way" structure ablation chamber, and achieved nanoscale inductively coupled plasma (ICP) MSI with an adjustable spatial resolution down to 400 nm, which surpasses most existing technologies. With this device, the distribution of various photodynamic therapy drugs in the intestine of mouse can be clearly observed. The comparison imaging results showed that the drug distribution in tissue slice could be identified at the subcellular level with the high-resolution mode. More valuably, gold nanorods (GNRs) and carboplatin in a single cell are able to be visualized at organelle level due to the nanoscale resolution, which is able to reveal the mechanism of cell apoptosis. This reliable and economical MSI technique is expected to be used in understanding the precise chemical composition and transportation in small tissues, microorganisms, and single cells.

High-throughput screening of bisphenols using magnetic covalent organic frameworks as a SELDI-TOF-MS probe.

Core-shell structured magnetic covalent organic framework (Fe3O4@COF) nanospheres were rapidly synthesized at room temperature using the monodisperse Fe3O4 nanoparticles (NPs) as magnetic core and benzene-1,3,5-tricarbaldehyde (BTA) and 3,3'-dihydroxybenzidine (DHBD) as two building blocks (denoted as Fe3O4@BTA-DHBD), respectively. They can serve as a mass spectrometry probe for rapid and high-throughput screening of bisphenols (BPs) from pharmaceuticals and personal care products (PPCPs) by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). The Fe3O4@BTA-DHBD nanospheres showed some superior features involving average pore size distribution (2.82 nm), high magnetization values (42.5 emu g-1), high specific surface area (82.96 m2 g-1), and good chemical/thermal stability. It was used as both ideal adsorbent for enrichment of BPs and new substrate to assist ionization in SELDI-TOF-MS. The method exhibited good linearity in the range 0.05-4000 ng mL-1 with correlation coefficients (r) higher than 0.9920. Low limits of detection (LODs) (500 pg mL-1 for bisphenol A (BPA), 2 pg mL-1 for bisphenol B (BPB), 28 pg mL-1 for bisphenol C (BPC), 60 pg mL-1 for bisphenol F (BPF), 33 pg mL-1 for bisphenol AF (BPAF), 200 pg mL-1 for bisphenol BP (BPBP), 10 pg mL-1 for bisphenol S (BPS), 90 pg mL-1 for tetrabromobisphenol A (BPA(Br)4), and 380 pg mL-1 for tetrabromobisphenol S (BPS(Br)4)) and good recoveries (80.6-115%) of BPs in PPCPs were achieved. The relative standard deviations (RSDs) of spot-to-spot (n = 10) and sample-to-sample (n = 5) were in the ranges 5-11% and 5-12%, respectively. The dual-function platform was successfully applied to the quantitative determination of BPs in PPCPs. It not only expanded the scope of the application of COFs but also provided an alternative strategy for the determination of hazardous compounds in PPCPs. Graphical abstract Schematic representation of the synthesis of core-shell structured magnetic covalent organic framework nanospheres (Fe3O4@COFs) and its application in the analysis of bisphenols by using Fe3O4@BTA-DHBD nanospheres as a MS probe based on surface-enhanced laser desorption/ionization time-of-flight mass spectrometry.

Nanoscale laser-induced breakdown spectroscopy imaging reveals chemical distribution with subcellular resolution.

Understanding chemical compositions is one of the most important parts in exploring the microscopic world. As a simple method for elemental detection, laser-induced breakdown spectroscopy (LIBS) is widely used in materials, geological and life science fields. However, due to the long-existing limitation in spatial resolution, it is difficult for LIBS to play an analytical role in the field of micro-world. Herein, we first report a reliable nanoscale resolution LIBS imaging technique by introducing a sampling laser with a micro-lensed fiber. Through the emission enhancement using the double-pulse laser, we obtained the spectral signal from a sampling crater of less than 500 nanometers in diameter, and visualized the chemical distribution of the self-made grid sample, SIM chip and nano-particles in single cells. The relative limits of detection (RLODs) of In and absolute limits of detection (ALODs) of Al can reach 0.6% and 18.3 fg, respectively.

Postsynthetic Functionalization of Zr4+-Immobilized Core-Shell Structured Magnetic Covalent Organic Frameworks for Selective Enrichment of Phosphopeptides.

Chemical modification of covalent organic frameworks (COFs) is indispensable for integrating functionalities of greater complexity and accessing advanced COF materials suitable for more potential applications. Reported here is a novel strategy for fabricating controllable core-shell structured Zr4+-immobilized magnetic COFs (MCNC@COF@Zr4+) composed of a high-magnetic-response magnetic colloid nanocrystal cluster (MCNC) core, Zr4+ ion-functionalized two-dimensional COFs as the shell by sequential postsynthetic functionalization and, for the first time, the application of the MCNC@COF@Zr4+ composites for efficient and selective enrichment of phosphopeptides. The as-prepared MCNC@COF@Zr4+ composites possess regular porosity with large surface areas, high Zr4+ loading amount, strong magnetic responsiveness, and good thermal/chemical stability, which can serve as an ideal adsorbent for selective enrichment of phosphopeptides and simultaneous size exclusion of biomacromolecules, such as proteins. The high detection sensitivity (10 fmol) together with the excellent recovery of phosphopeptides is also obtained. These outstanding features suggest that the MCNC@COF@Zr4+ composites are of great benefit for pretreatment prior to mass spectrometry analysis of phosphopeptides. In addition, the performance of the developed approach in selective enrichment of phosphopeptides from the tryptic digests of defatted milk and directly specific capture of endogenous phosphopeptides from human serum gives powerful proof for its high selectivity and effectiveness in identifying the low-abundance phosphopeptides from complicated biological samples. This study not only provides a strategy for versatile functionalization of magnetic COFs but also opens a new avenue in their use in phosphoproteome analysis.

Room-temperature synthesis of core-shell structured magnetic covalent organic frameworks for efficient enrichment of peptides and simultaneous exclusion of proteins.

Core-shell structured magnetic covalent organic frameworks (Fe3O4@COFs) were synthesized via a facile approach at room temperature. Combining the advantages of high porosity, magnetic responsiveness, chemical stability and selectivity, Fe3O4@COFs can serve as an ideal absorbent for the highly efficient enrichment of peptides and the simultaneous exclusion of proteins from complex biological samples.

Facile synthesis of core-shell structured magnetic covalent organic framework composite nanospheres for selective enrichment of peptides with simultaneous exclusion of proteins.

Selective enrichment of peptides from complex biosamples is essential for mass spectrometry-based proteomics but still remains a challenge. In this work, a facile approach was developed for rapid room-temperature synthesis of core-shell structured magnetic covalent organic framework composite nanospheres (denoted as Fe3O4@TbBd) by using monodisperse Fe3O4 nanoparticles as the magnetic core and 1,3,5-triformylbenzene (Tb) and benzidine (Bd) as two building blocks in the presence of dimethyl sulfoxide (DMSO). The resultant core-shell structured Fe3O4@TbBd nanospheres exhibited high adsorption capacity (28.5 mg g-1), fast adsorption kinetics (<5 min) and excellent reusability (more than 30 times) for peptides, owing to their specific properties of high surface area (196.21 m2 g-1), large pore volume (0.63 cm3 g-1), narrow pore size distribution (∼2.8 nm), strong magnetic response (41.5 emu g-1), as well as good thermal and chemical stability. Moreover, the Fe3O4@TbBd nanospheres also showed good selectivity towards hydrophobic peptides and a size-exclusion effect against proteins due to the inherent π-π stacking interaction and interconnected mesoporous channels of covalent organic framework (COF) shells. Taking advantage of these composite nanospheres, selective extraction and efficient enrichment of low abundance hydrophobic peptides from human serum in the presence of high abundance proteins were achieved. Based on the HPLC-Q-TOF/MS results, 29 hydrophobic peptides assigned to 12 proteins were clearly identified in 5 ng µL-1 human serum digestion upon treatment with Fe3O4@TbBd nanospheres, much better than those obtained without treatment, confirming the outstanding performance of the Fe3O4@TbBd nanospheres in proteome analysis.