Single-cell spatial transcriptome reveals cell-type organization in the macaque cortex.

Elucidating the cellular organization of the cerebral cortex is critical for understanding brain structure and function. Using large-scale single-nucleus RNA sequencing and spatial transcriptomic analysis of 143 macaque cortical regions, we obtained a comprehensive atlas of 264 transcriptome-defined cortical cell types and mapped their spatial distribution across the entire cortex. We characterized the cortical layer and region preferences of glutamatergic, GABAergic, and non-neuronal cell types, as well as regional differences in cell-type composition and neighborhood complexity. Notably, we discovered a relationship between the regional distribution of various cell types and the region's hierarchical level in the visual and somatosensory systems. Cross-species comparison of transcriptomic data from human, macaque, and mouse cortices further revealed primate-specific cell types that are enriched in layer 4, with their marker genes expressed in a region-dependent manner. Our data provide a cellular and molecular basis for understanding the evolution, development, aging, and pathogenesis of the primate brain.

Multi-omics blood atlas reveals unique features of immune and platelet responses to SARS-CoV-2 Omicron breakthrough infection.

Although host responses to the ancestral SARS-CoV-2 strain are well described, those to the new Omicron variants are less resolved. We profiled the clinical phenomes, transcriptomes, proteomes, metabolomes, and immune repertoires of >1,000 blood cell or plasma specimens from SARS-CoV-2 Omicron patients. Using in-depth integrated multi-omics, we dissected the host response dynamics during multiple disease phases to reveal the molecular and cellular landscapes in the blood. Specifically, we detected enhanced interferon-mediated antiviral signatures of platelets in Omicron-infected patients, and platelets preferentially formed widespread aggregates with leukocytes to modulate immune cell functions. In addition, patients who were re-tested positive for viral RNA showed marked reductions in B cell receptor clones, antibody generation, and neutralizing capacity against Omicron. Finally, we developed a machine learning model that accurately predicted the probability of re-positivity in Omicron patients. Our study may inspire a paradigm shift in studying systemic diseases and emerging public health concerns.

Rice false smut virulence protein subverts host chitin perception and signaling at lemma and palea for floral infection.

The flower-infecting fungus Ustilaginoidea virens causes rice false smut, which is a severe emerging disease threatening rice (Oryza sativa) production worldwide. False smut not only reduces yield, but more importantly produces toxins on grains, posing a great threat to food safety. U. virens invades spikelets via the gap between the 2 bracts (lemma and palea) enclosing the floret and specifically infects the stamen and pistil. Molecular mechanisms for the U. virens-rice interaction are largely unknown. Here, we demonstrate that rice flowers predominantly employ chitin-triggered immunity against U. virens in the lemma and palea, rather than in the stamen and pistil. We identify a crucial U. virens virulence factor, named UvGH18.1, which carries glycoside hydrolase activity. Mechanistically, UvGH18.1 functions by binding to and hydrolyzing immune elicitor chitin and interacting with the chitin receptor CHITIN ELICITOR BINDING PROTEIN (OsCEBiP) and co-receptor CHITIN ELICITOR RECEPTOR KINASE1 (OsCERK1) to impair their chitin-induced dimerization, suppressing host immunity exerted at the lemma and palea for gaining access to the stamen and pistil. Conversely, pretreatment on spikelets with chitin induces a defense response in the lemma and palea, promoting resistance against U. virens. Collectively, our data uncover a mechanism for a U. virens virulence factor and the critical location of the host-pathogen interaction in flowers and provide a potential strategy to control rice false smut disease.

Double-helical assembly of heterodimeric nanoclusters into supercrystals.

DNA has long been used as a template for the construction of helical assemblies of inorganic nanoparticles1-5. For example, gold nanoparticles decorated with DNA (or with peptides) can create helical assemblies6-9. But without such biological ligands, helices are difficult to achieve and their mechanism of formation is challenging to understand10,11. Atomically precise nanoclusters that are protected by ligands such as thiolate12,13 have demonstrated hierarchical structural complexity in their assembly at the interparticle and intraparticle levels, similar to biomolecules and their assemblies14. Furthermore, carrier dynamics can be controlled by engineering the structure of the nanoclusters15. But these nanoclusters usually have isotropic structures16,17 and often assemble into commonly found supercrystals18. Here we report the synthesis of homodimeric and heterodimeric gold nanoclusters and their self-assembly into superstructures. While the homodimeric nanoclusters form layer-by-layer superstructures, the heterodimeric nanoclusters self-assemble into double- and quadruple-helical superstructures. These complex arrangements are the result of two different motif pairs, one pair per monomer, where each motif bonds with its paired motif on a neighbouring heterodimer. This motif pairing is reminiscent of the paired interactions of nucleobases in DNA helices. Meanwhile, the surrounding ligands on the clusters show doubly or triply paired steric interactions. The helical assembly is driven by van der Waals interactions through particle rotation and conformational matching. Furthermore, the heterodimeric clusters have a carrier lifetime that is roughly 65 times longer than that of the homodimeric clusters. Our findings suggest new approaches for increasing complexity in the structural design and engineering of precision in supercrystals.

Barley yellow dwarf virus-GAV 17K protein disrupts thiamine biosynthesis to facilitate viral infection in plants.

Thiamine functions as a crucial activator modulating plant health and broad-spectrum stress tolerances. However, the role of thiamine in regulating plant virus infection is largely unknown. Here, we report that the multifunctional 17K protein encoded by barley yellow dwarf virus-GAV (BYDV-GAV) interacted with barley pyrimidine synthase (HvTHIC), a key enzyme in thiamine biosynthesis. HvTHIC was found to be localized in chloroplast via an N-terminal 74-amino acid domain. However, the 17K-HvTHIC interaction restricted HvTHIC targeting to chloroplasts and triggered autophagy-mediated HvTHIC degradation. Upon BYDV-GAV infection, the expression of the HvTHIC gene was significantly induced, and this was accompanied by accumulation of thiamine and salicylic acid. Silencing of HvTHIC expression promoted BYDV-GAV accumulation. Transcriptomic analysis of HvTHIC silenced and non-silenced barley plants showed that the differentially expressed genes were mainly involved in plant-pathogen interaction, plant hormone signal induction, phenylpropanoid biosynthesis, starch and sucrose metabolism, photosynthesis-antenna protein, and MAPK signaling pathway. Thiamine treatment enhanced barley resistance to BYDV-GAV. Taken together, our findings reveal a molecular mechanism underlying how BYDV impedes thiamine biosynthesis to uphold viral infection in plants.

ETLD: an encoder-transformation layer-decoder architecture for protein contact and mutation effects prediction.

The latent features extracted from the multiple sequence alignments (MSAs) of homologous protein families are useful for identifying residue-residue contacts, predicting mutation effects, shaping protein evolution, etc. Over the past three decades, a growing body of supervised and unsupervised machine learning methods have been applied to this field, yielding fruitful results. Here, we propose a novel self-supervised model, called encoder-transformation layer-decoder (ETLD) architecture, capable of capturing protein sequence latent features directly from MSAs. Compared to the typical autoencoder model, ETLD introduces a transformation layer with the ability to learn inter-site couplings, which can be used to parse out the two-dimensional residue-residue contacts map after a simple mathematical derivation or an additional supervised neural network. ETLD retains the process of encoding and decoding sequences, and the predicted probabilities of amino acids at each site can be further used to construct the mutation landscapes for mutation effects prediction, outperforming advanced models such as GEMME, DeepSequence and EVmutation in general. Overall, ETLD is a highly interpretable unsupervised model with great potential for improvement and can be further combined with supervised methods for more extensive and accurate predictions.

Romantic relationships attenuated competition between lovers: evidence from brain synchronization.

Competition is an essential component of social interaction and is influenced by interpersonal relationships. This study is based on social exchange theory and explores the relationship between brain synchronization and competition in the binary system of romantic relationships through electroencephalogram hyperscanning technology. The results found that females had a greater win rate in the romantic and friend groups. During the early stage (0-200 ms), when the competitive target appeared, the stranger group exhibited greater interbrain synchronicity in the Alpha frequency band. However, during the later stage (600-800 ms), the romantic group showed higher Alpha band interbrain synchrony when the competitive target appeared. Significant interbrain synchronizations were observed in the Theta frequency band of the stranger and friend groups at 400-600 ms and 800-1000 ms. Moreover, these interbrain synchronizations were significantly positively correlated with the winning rates of females in the competition. These findings suggest a close relationship between interpersonal coordination and interbrain synchronization. Furthermore, romantic relationships reduce participants' willingness to compete, affecting their attention regulation, emotional processing, and goal orientation, thus influencing competition. This study investigated the impact of romantic relationships on competition, providing a theoretical foundation for promoting the positive and healthy development of romantic relationships.

The shorter a man is, the more he defends fairness: relative height disadvantage promoting third-party punishment-evidence from inter-brain synchronization.

Third-party punishment occurs in interpersonal interactions to sustain social norms, and is strongly influenced by the characteristics of the interacting individuals. During social interactions, height is the striking physical appearance features first observed, height disadvantage may critically influence men's behavior and mental health. Herein, we explored the influence of height disadvantage on third-party punishment through time-frequency analysis and electroencephalography hyperscanning. Two participants were randomly designated as the recipient and third party after height comparison and instructed to complete third-party punishment task. Compared with when the third party's height is higher than the recipient's height, when the third party's height is lower, the punishment rate and transfer amount were significantly higher. Only for highly unfair offers, the theta power was significantly greater when the third party's height was lower. The inter-brain synchronization between the recipient and the third party was significantly stronger when the third party's height was lower. Compared with the fair and medium unfair offers, the inter-brain synchronization was strongest for highly unfair offers. Our findings indicate that the height disadvantage-induced anger and reputation concern promote third-party punishment and inter-brain synchronization. This study enriches research perspective and expands the application of the theory of Napoleon complex.

Intimate relationships regulate female brain activity in a competitive context: evidence from EEG and functional connectivity analysis.

Competition is common in life, and intimate relationships are essential. Understanding how intimate relationships impact an individual's competitive process is crucial. This study explored the impact of competitor gender on female competition using electroencephalography analysis. The results revealed that females exhibited a smaller median of the absolute value of reaction time difference (DRT) between their partners and their competitors when their partners were absent compared to when their partners were present. Additionally, females showed greater average amplitudes of N2 posterior contralateral component (N2pc) and Late Positive Potential (LPP), increased activation of the alpha frequency band, and enhanced theta frequency band functional connectivity between the central parietal lobe and occipital lobe. Furthermore, when competing with individuals of the same gender as opposed to individuals of the opposite gender, females exhibited greater average amplitudes of percentage of wins and N2pc. A significant negative correlation was noted between the DRT and the average wave amplitudes of N2pc and LPP. These findings suggest that females are more engaged in competitive tasks when partners are not present and have improved decision-making when competing with same-gender individuals. This study provides evidence for the influence of lovers on female competition, helping females adapt to social competition and promoting healthy relationships.

Who takes the lead in consumer choices within romantic relationships: the evidence from electroencephalography hyperscanning and granger causality analysis.

In real-life scenarios, joint consumption is common, particularly influenced by social relationships such as romantic ones. However, how romantic relationships affect consumption decisions and determine dominance remains unclear. This study employs electroencephalography hyperscanning to examine the neural dynamics of couples during joint-consumption decisions. Results show that couples, compared to friends and strangers, prefer healthier foods, while friends have significantly faster reaction times when selecting food. Time-frequency analysis indicates that couples exhibit significantly higher theta power, reflecting deeper emotional and cognitive involvement. Strangers show greater beta1 power, indicating increased cognitive effort and alertness due to unfamiliarity. Friends demonstrate higher alpha2 power when choosing unhealthy foods, suggesting increased cognitive inhibition. Inter-brain phase synchrony analysis reveals that couples display significantly higher inter-brain phase synchrony in the beta1 and theta bands across the frontal-central, parietal, and occipital regions, indicating more coordinated cognitive processing and stronger emotional bonds. Females in couples may be more influenced by emotions during consumption decisions, with detailed sensory information processing, while males exhibit higher cognitive control and spatial integration. Granger-causality analysis shows a pattern of male dominance and female dependence in joint consumption within romantic relationships. This study highlights gender-related neural synchronous patterns during joint consumption among couples, providing insights for further research in consumer decision-making.

Favoritism or bias? Cooperation and competition under different intergroup relationships: evidence from EEG hyperscanning.

Cooperation and competition are the most common forms of social interaction in various social relationships. Intergroup relationships have been posited to influence individuals' interpersonal interactions significantly. Using electroencephalography hyperscanning, this study aimed to establish whether intergroup relationships influence interpersonal cooperation and competition and the underlying neural mechanisms. According to the results, the in-group Coop-index is better than the out-group, whereas the out-group Comp-index is stronger than the in-group. The in-group functional connectivity between the frontal-central region and the right temporoparietal junction in the ß band was stronger in competition than cooperation. The out-group functional connectivity between the frontal-central region and the left temporoparietal junction in the α band was stronger in cooperation than competition. In both cooperation and competition, the in-group exhibited higher interbrain synchronization between the prefrontal cortex and parietal region in the θ band, as well as between the frontal-central region and frontal-central region in the α band, compared to the out-group. The intrabrain phase-locking value in both the α and ß bands can effectively predict performance in competition tasks. Interbrain phase-locking value in both the α and θ bands can be effectively predicted in a performance cooperation task. This study offers neuroscientific evidence for in-group favoritism and out-group bias at an interpersonal level.

Identifying Patients With Rapid Progression From Hormone-Sensitive to Castration-Resistant Prostate Cancer: A Retrospective Study.

Prostate cancer (PCa) is the second most prevalent malignancy and the fifth cause of cancer-related deaths in men. A crucial challenge is identifying the population at risk of rapid progression from hormone-sensitive prostate cancer (HSPC) to lethal castration-resistant prostate cancer (CRPC). We collected 78 HSPC biopsies and measured their proteomes using pressure cycling technology and a pulsed data-independent acquisition pipeline. We quantified 7355 proteins using these HSPC biopsies. A total of 251 proteins showed differential expression between patients with a long- or short-term progression to CRPC. Using a random forest model, we identified seven proteins that significantly discriminated long- from short-term progression patients, which were used to classify PCa patients with an area under the curve of 0.873. Next, one clinical feature (Gleason sum) and two proteins (BGN and MAPK11) were found to be significantly associated with rapid disease progression. A nomogram model using these three features was generated for stratifying patients into groups with significant progression differences (p-value = 1.3×10-4). To conclude, we identified proteins associated with a fast progression to CRPC and an unfavorable prognosis. Based on these proteins, our machine learning and nomogram models stratified HSPC into high- and low-risk groups and predicted their prognoses. These models may aid clinicians in predicting the progression of patients, guiding individualized clinical management and decisions.

High Spatial Resolution 2D Imaging of Current Density and Pressure for Graphene Devices under High Pressure Using Nitrogen-Vacancy Centers in Diamond.

Current density imaging is helpful for discovering interesting electronic phenomena and understanding carrier dynamics, and by combining pressure distributions, several pressure-induced novel physics may be comprehended. In this work, noninvasive, high-resolution two-dimensional images of the current density and pressure gradient for graphene ribbon and hBN-graphene-hBN devices are explored using nitrogen-vacancy (NV) centers in diamond under high pressure. The two-dimensional vector current density is reconstructed by the vector magnetic field mapped by the near-surface NV center layer in the diamond. The current density images accurately and clearly reproduce the complicated structure and current flow of graphene under high pressure. Additionally, the spatial distribution of the pressure is simultaneously mapped, rationalizing the nonuniformity of the current density under high pressure. The current method opens a significant new avenue to investigate electronic transport and conductance variations in two-dimensional materials and electrical devices under high pressure as well as for nondestructive evaluation of semiconductor circuits.

Proteomic profiling of ovarian clear cell carcinomas identifies prognostic biomarkers for chemotherapy.

Clear cell ovarian carcinoma (CCOC) is a relatively rare subtype of ovarian cancer (OC) with high degree of resistance to standard chemotherapy. Little is known about the underlying molecular mechanisms, and it remains a challenge to predict its prognosis after chemotherapy. Here, we first analyzed the proteome of 35 formalin-fixed paraffin-embedded (FFPE) CCOC tissue specimens from a cohort of 32 patients with CCOC (H1 cohort) and characterized 8697 proteins using data-independent acquisition mass spectrometry (DIA-MS). We then performed proteomic analysis of 28 fresh frozen (FF) CCOC tissue specimens from an independent cohort of 24 patients with CCOC (H2 cohort), leading to the identification of 9409 proteins with DIA-MS. After bioinformatics analysis, we narrowed our focus to 15 proteins significantly correlated with the recurrence free survival (RFS) in both cohorts. These proteins are mainly involved in DNA damage response, extracellular matrix (ECM), and mitochondrial metabolism. Parallel reaction monitoring (PRM)-MS was adopted to validate the prognostic potential of the 15 proteins in the H1 cohort and an independent confirmation cohort (H3 cohort). Interferon-inducible transmembrane protein 1 (IFITM1) was observed as a robust prognostic marker for CCOC in both PRM data and immunohistochemistry (IHC) data. Taken together, this study presents a CCOC proteomic data resource and a single promising protein, IFITM1, which could potentially predict the recurrence and survival of CCOC.

Homotopic functional connectivity disruptions in schizophrenia and their associated gene expression.

It has been revealed that abnormal voxel-mirrored homotopic connectivity (VMHC) is present in patients with schizophrenia, yet there are inconsistencies in the relevant findings. Moreover, little is known about their association with brain gene expression profiles. In this study, transcription-neuroimaging association analyses using gene expression data from Allen Human Brain Atlas and case-control VMHC differences from both the discovery (meta-analysis, including 9 studies with a total of 386 patients and 357 controls) and replication (separate group-level comparisons within two datasets, including a total of 258 patients and 287 controls) phases were performed to identify genes associated with VMHC alterations. Enrichment analyses were conducted to characterize the biological functions and specific expression of identified genes, and Neurosynth decoding analysis was performed to examine the correlation between cognitive-related processes and VMHC alterations in schizophrenia. In the discovery and replication phases, patients with schizophrenia exhibited consistent VMHC changes compared to controls, which were correlated with a series of cognitive-related processes; meta-regression analysis revealed that illness duration was negatively correlated with VMHC abnormalities in the cerebellum and postcentral/precentral gyrus. The abnormal VMHC patterns were stably correlated with 1287 genes enriched for fundamental biological processes like regulation of cell communication, nervous system development, and cell communication. In addition, these genes were overexpressed in astrocytes and immune cells, enriched in extensive cortical regions and wide developmental time windows. The present findings may contribute to a more comprehensive understanding of the molecular mechanisms underlying VMHC alterations in patients with schizophrenia.

Happy people are always similar: The evidence from brain morphological and functional inter-subject correlations.

A fundamental question in the study of happiness is whether there is neural evidence to support a well-known hypothesis that happy people are always similar while unfortunate people have their own misfortunes. To investigate this, we employed several happiness-related questionnaires to identify potential components of happiness, and further investigated and confirmed their associations with personality, mood, aggressive behaviors, and amygdala reactivity to fearful faces within a substantial sample size of college students (n = 570). Additionally, we examined the functional and morphological similarities and differences among happy individuals using the inter-subject representational similarity analysis (IS-RSA). IS-RSA emphasizes the geometric properties in a high-dimensional space constructed by brain or behavioral patterns and focuses on individual subjects. Our behavioral findings unveiled two factors of happiness: individual and social, both of which mediated the effect of personality traits on individual aggression. Subsequently, mood mediated the impact of happiness on aggressive behaviors across two subgroup splits. Functional imaging data revealed that individuals with higher levels of happiness exhibited reduced amygdala reactivity to fearful faces, as evidenced by a conventional face-matching task (n = 104). Moreover, IS-RSA demonstrated that these participants manifested similar neural activation patterns when processing fearful faces within the visual pathway, but not within the emotional network (e.g., amygdala). Morphological observations (n = 425) indicated that individuals with similar high happiness levels exhibited comparable gray matter volume patterns within several networks, including the default mode network, fronto-parietal network, visual network, and attention network. Collectively, these findings offer early neural evidence supporting the proposition that happy individuals may share common neural characteristics.

Bottom-Up Construction of Metal-Organic Framework Loricae on Metal Nanoclusters with Consecutive Single Nonmetal Atom Tuning for Tailored Catalysis.

The introduction of single or multiple heterometal atoms into metal nanoparticles is a well-known strategy for altering their structures (compositions) and properties. However, surface single nonmetal atom doping is challenging and rarely reported. For the first time, we have developed synthetic methods, realizing "surgery"-like, successive surface single nonmetal atom doping, replacement, and addition for ultrasmall metal nanoparticles (metal nanoclusters, NCs), and successfully synthesized and characterized three novel bcc metal NCs Au38I(S-Adm)19, Au38S(S-Adm)20, and Au38IS(S-Adm)19 (S-Adm: 1-adamantanethiolate). The influences of single nonmetal atom replacement and addition on the NC structure and optical properties (including absorption and photoluminescence) were carefully investigated, providing insights into the structure (composition)-property correlation. Furthermore, a bottom-up method was employed to construct a metal-organic framework (MOF) on the NC surface, which did not essentially alter the metal NC structure but led to the partial release of surface ligands and stimulated metal NC activity for catalyzing p-nitrophenol reduction. Furthermore, surface MOF construction enhanced NC stability and water solubility, providing another dimension for tunning NC catalytic activity by modifying MOF functional groups.

Introducing Hydrogen-Bonding Microenvironment in Close Proximity to Single-Atom Sites for Boosting Photocatalytic Hydrogen Production.

Inspired by enzymatic catalysis, it is crucial to construct hydrogen-bonding-rich microenvironment around catalytic sites; unfortunately, its precise construction and understanding how the distance between such microenvironment and catalytic sites affects the catalysis remain significantly challenging. In this work, a series of metal-organic framework (MOF)-based single-atom Ru1 catalysts, namely, Ru1/UiO-67-X (X = -H, -m-(NH2)2, -o-(NH2)2), have been synthesized, where the distance between the hydrogen-bonding microenvironment and Ru1 sites is modulated by altering the location of amino groups. The -NH2 group can form hydrogen bonds with H2O, constituting a unique microenvironment that causes an increased water concentration around the Ru1 sites. Remarkably, Ru1/UiO-67-o-(NH2)2 displays a superior photocatalytic hydrogen production rate, ∼4.6 and ∼146.6 times of Ru1/UiO-67-m-(NH2)2 and Ru1/UiO-67, respectively. Both experimental and computational results suggest that the close proximity of amino groups to the Ru1 sites in Ru1/UiO-67-o-(NH2)2 improves charge transfer and H2O dissociation, accounting for the promoted photocatalytic hydrogen production.

Clemastine-induced enhancement of hippocampal myelination alleviates memory impairment in mice with chronic pain.

Patients with chronic pain often experience memory impairment, but the underlying mechanisms remain elusive. The myelin sheath is crucial for rapid and accurate action potential conduction, playing a pivotal role in the development of cognitive abilities in the central nervous system. The study reveals that myelin degradation occurs in the hippocampus of chronic constriction injury (CCI) mice, which display both chronic pain and memory impairment. Using fiber photometry, we observed diminished task-related neuronal activity in the hippocampus of CCI mice. Interestingly, the repeated administration with clemastine, which promotes myelination, counteracts the CCI-induced myelin loss and reduced neuronal activity. Notably, clemastine specifically ameliorates the impaired memory without affecting chronic pain in CCI mice. Overall, our findings highlight the significant role of myelin abnormalities in CCI-induced memory impairment, suggesting a potential therapeutic approach for treating memory impairments associated with neuropathic pain.

The effects of P2 segment of posterior cerebral artery to thalamus blood supply pattern on gait in cerebral small vessel disease: A 7 T MRI based study.

Gait disturbance is a manifestation of cerebral small vessel disease (CSVD). The posterolateral thalamus (PL), whose blood is mainly supplied by the P2 segment of posterior cerebral artery (P2-PCA), plays pivotal roles in gait regulation. We investigated the influence of the distance between P2-PCA and PL on gait with varying CSVD burden. 71 participants were divided into low and high CSVD burden groups. The distance from P2-PCA to PL was measured using 7 T TOF-MRA and categorized into an immediate or distant PCA-to-thalamus pattern. Functional connectivity (FC) and voxel-based morphometry were assessed to evaluate functional and structural alterations. In the low CSVD burden group, immediate PCA-to-thalamus supply strongly correlates with longer step length and higher wave phase time percent, and exhibited enhanced FCs in left supplementary motor area, right precentral cortex (PreCG.R). While in the high CSVD burden group, no association between PCA-to-thalamus pattern and gait was found, and we observed reduced FC in PreCG.R with immediate PCA-to-thalamus pattern. Higher CSVD burden was associated with decreased gray matter density in bilateral thalamus. However, no significant structural thalamic change was observed between the two types of PCA-to-thalamus patterns in all patients. Our study demonstrated patients with immediate PCA-to-thalamus supply exhibited better gait performance in low CSVD burden populations, which also correlated with enhanced FCs in motor-related cortex, indicating the beneficial effects of the immediate PCA-to-thalamus supply pattern. In the higher burden CSVD populations, the effects of PCA-to-thalamus pattern on gait are void, attributable to the CSVD-related thalamic destruction and impairment of thalamus-related FC.