PRMT5-mediated homologous recombination repair is essential to maintain genomic integrity of neural progenitor cells.

Maintaining genomic stability is a prerequisite for proliferating NPCs to ensure genetic fidelity. Though histone arginine methylation has been shown to play important roles in safeguarding genomic stability, the underlying mechanism during brain development is not fully understood. Protein arginine N-methyltransferase 5 (PRMT5) is a type II protein arginine methyltransferase that plays a role in transcriptional regulation. Here, we identify PRMT5 as a key regulator of DNA repair in response to double-strand breaks (DSBs) during NPC proliferation. Prmt5F/F; Emx1-Cre (cKO-Emx1) mice show a distinctive microcephaly phenotype, with partial loss of the dorsal medial cerebral cortex and complete loss of the corpus callosum and hippocampus. This phenotype is resulted from DSBs accumulation in the medial dorsal cortex followed by cell apoptosis. Both RNA sequencing and in vitro DNA repair analyses reveal that PRMT5 is required for DNA homologous recombination (HR) repair. PRMT5 specifically catalyzes H3R2me2s in proliferating NPCs in the developing mouse brain to enhance HR-related gene expression during DNA repair. Finally, overexpression of BRCA1 significantly rescues DSBs accumulation and cell apoptosis in PRMT5-deficient NSCs. Taken together, our results show that PRMT5 maintains genomic stability by regulating histone arginine methylation in proliferating NPCs.

Dysregulation of AMPK-mTOR signaling leads to comorbid anxiety in Dip2a KO mice.

Autism is often comorbid with other psychiatric disorders. We have previously shown that Dip2a knockout (KO) induces autism-like behaviors in mice. However, the role of Dip2a in other psychiatric disorders remains unclear. In this paper, we revealed that Dip2a KO mice had comorbid anxiety. Dip2a KO led to a reduction in the dendritic length of cortical and hippocampal excitatory neurons. Molecular mechanism studies suggested that AMPK was overactivated and suppressed the mTOR cascade, contributing to defects in dendritic morphology. Deletion of Dip2a in adult-born hippocampal neurons (Dip2a conditional knockout (cKO)) increased susceptibility to anxiety upon acute stress exposure. Application of (2R,6R)-hydroxynorketamine (HNK), an inhibitor of mTOR, rescued anxiety-like behaviors in Dip2a KO and Dip2a cKO mice. In addition, 6 weeks of high-fat diet intake alleviated AMPK-mTOR signaling and attenuated the severity of anxiety in both Dip2a KO mice and Dip2a cKO mice. Taken together, these results reveal an unrecognized function of DIP2A in anxiety pathophysiology via regulation of AMPK-mTOR signaling.

The regulatory role of autophagy between TAMs and tumor cells.

Cancer has become a global public health problem and its harmful effects have received widespread attention. Conventional treatments such as surgical resection, radiotherapy and other techniques are applicable to clinical practice, but new drugs are constantly being developed and other therapeutic approaches, such as immunotherapy are being applied. In addition to studying the effects on individual tumor cells, it is important to explore the role of tumor microenvironment on tumor cell development since tumor cells do not exist alone but in the tumor microenvironment. In the tumor microenvironment, tumor cells are interconnected with other stromal cells and influence each other, among which tumor-associated macrophages (TAMs) are the most numerous immune cells. At the same time, it was found that cancer cells have different levels of autophagy from normal cells. In cancer therapy, the occurrence of autophagy plays an important role in promoting tumor cell death or inhibiting tumor cell death, and is closely related to the environment. Therefore, elucidating the regulatory role of autophagy between TAMs and tumor cells may be an important breakthrough, providing new perspectives for further research on antitumor immune mechanisms and improving the efficacy of cancer immunotherapy.

A Genotype-Phenotype Model for Predicting Resistance Training Effects on Leg Press Performance.

This study develops a comprehensive genotype-phenotype model for predicting the effects of resistance training on leg press performance. A cohort of physically inactive adults (N=193) underwent 12 weeks of resistance training, and measurements of maximum isokinetic leg press peak force, muscle mass, and thickness were taken before and after the intervention. Whole-genome genotyping was performed, and genome-wide association analysis identified 85 novel SNPs significantly associated with changes in leg press strength after training. A prediction model was constructed using stepwise linear regression, incorporating seven lead SNPs that explained 40.4% of the training effect variance. The polygenic score showed a significant positive correlation with changes in leg press strength. By integrating genomic markers and phenotypic indicators, the comprehensive prediction model explained 75.4% of the variance in the training effect. Additionally, five SNPs were found to potentially impact muscle contraction, metabolism, growth, and development through their association with REACTOME pathways. Individual responses to resistance training varied, with changes in leg press strength ranging from -55.83% to 151.20%. The study highlights the importance of genetic factors in predicting training outcomes and provides insights into the potential biological functions underlying resistance training effects. The comprehensive model offers valuable guidance for personalized fitness programs based on individual genetic profiles and phenotypic characteristics.

Netrin-1 Is an Important Mediator in Microglia Migration.

Microglia migrate to the cerebral cortex during early embryonic stages. However, the precise mechanisms underlying microglia migration remain incompletely understood. As an extracellular matrix protein, Netrin-1 is involved in modulating the motility of diverse cells. In this paper, we found that Netrin-1 promoted microglial BV2 cell migration in vitro. Mechanism studies indicated that the activation of GSK3ß activity contributed to Netrin-1-mediated microglia migration. Furthermore, Integrin α6/ß1 might be the relevant receptor. Single-cell data analysis revealed the higher expression of Integrin α6 subunit and ß1 subunit in microglia in comparison with classical receptors, including Dcc, Neo1, Unc5a, Unc5b, Unc5c, Unc5d, and Dscam. Microscale thermophoresis (MST) measurement confirmed the high binding affinity between Integrin α6/ß1 and Netrin-1. Importantly, activation of Integrin α6/ß1 with IKVAV peptides mirrored the microglia migration and GSK3 activation induced by Netrin-1. Finally, conditional knockout (CKO) of Netrin-1 in radial glial cells and their progeny led to a reduction in microglia population in the cerebral cortex at early developmental stages. Together, our findings highlight the role of Netrin-1 in microglia migration and underscore its therapeutic potential in microglia-related brain diseases.

Phosphonium Iodide Featuring Blue Thermally Activated Delayed Fluorescence for Highly Efficient X-ray Scintillator.

Organic scintillators are praised for their abundant element reserves, facile preparation procedures, and rich structures. Herein, a new family of highly efficient organic phosphonium halide salts with thermally activated delayed fluorescence (TADF) are designed by innovatively adopting quaternary phosphonium as the electron acceptor, while dimethylamine group and halide anions (I-) serve as the electron donor. The prepared butyl(2-[2-(dimethylamino)phenyl]phenyl)diphenylphosphonium iodide (C4-I) exhibits bright blue emission and an ultra-high photoluminescence quantum yield (PLQY) of 100%. Efficient charge transfer is realized through the unique n-π and anion-π stacking in solid-state C4-I. Photophysical studies of C4-I suggest that the incorporation of I accounts for high intersystem crossing rate (kISC) and reverse intersystem crossing rate (kRISC), suppressing the intrinsic prompt fluorescence and enabling near-pure TADF emission at room temperature. Benefitting from the large Stokes shift, high PLQY, efficient exciton utilization, and remarkable X-ray attenuation ability endowed by I, C4-I delivers an outstanding light yield of 80721 photons/MeV and a low limit of detection (LoD) of 22.79 nGy·s-1. This work would provide a rational design concept and open up an appealing road for developing efficient organic scintillators with tunable emission, strong X-ray attenuation ability, and excellent scintillator performance.

Human antigen R-regulated mRNA metabolism promotes the cell motility of migrating mouse neurons.

Neocortex development during embryonic stages requires the precise control of mRNA metabolism. Human antigen R (HuR) is a well-studied mRNA-binding protein that regulates mRNA metabolism, and it is highly expressed in the neocortex during developmental stages. Deletion of HuR does not impair neural progenitor cell proliferation or differentiation, but it disturbs the laminar structure of the neocortex. We report that HuR is expressed in postmitotic projection neurons during mouse brain development. Specifically, depletion of HuR in these neurons led to a mislocalization of CDP+ neurons in deeper layers of the cortex. Time-lapse microscopy showed that HuR was required for the promotion of cell motility in migrating neurons. PCR array identified profilin 1 (Pfn1) mRNA as a major binding partner of HuR in neurons. HuR positively mediated the stability of Pfn1 mRNA and influenced actin polymerization. Overexpression of Pfn1 successfully rescued the migration defects of HuR-deleted neurons. Our data reveal a post-transcriptional mechanism that maintains actin dynamics during neuronal migration.

Combined metabolome and transcriptome analysis reveals a critical role of lignin biosynthesis and lignification in stem-like pneumatophore development of the mangrove Avicennia marina.

MAIN CONCLUSION: Transcriptional and metabolic regulation of lignin biosynthesis and lignification plays crucial roles in Avicennia marina pneumatophore development, facilitating its adaptation to coastal habitats. Avicennia marina is a pioneer mangrove species in coastal wetland. To cope with the periodic intertidal flooding and hypoxia environment, this species has developed a complex and extensive root system, with its most unique feature being a pneumatophore with a distinct above- and below-ground morphology and vascular structure. However, the characteristics of pneumatophore lignification remain unknown. Studies comparing the anatomy among above-ground pneumatophore, below-ground pneumatophore, and feeding root have suggested that vascular structure development in the pneumatophore is more like the development of a stem than of a root. Metabolome and transcriptome analysis illustrated that the accumulation of syringyl (S) and guaiacyl (G) units in the pneumatophore plays a critical role in lignification of the stem-like structure. Fourteen differentially accumulated metabolites (DAMs) and 10 differentially expressed genes involved in the lignin biosynthesis pathway were targeted. To identify genes significantly associated with lignification, we analyzed the correlation between 14 genes and 8 metabolites and further built a co-expression network between 10 transcription factors (TFs), including 5 for each of MYB and NAC, and 23 enzyme-coding genes involved in lignin biosynthesis. 4-Coumarate-CoA ligase, shikimate/quinate hydroxycinnamoyl transferase, cinnamyl alcohol dehydrogenase, caffeic acid 3-O-methyltransferase, phenylalanine ammonia-lyase, and peroxidase were identified to be strongly correlated with these TFs. Finally, we examined 9 key candidate genes through quantitative real-time PCR to validate the reliability of transcriptome data. Together, our metabolome and transcriptome findings reveal that lignin biosynthesis and lignification regulate pneumatophore development in the mangrove species A. marina and facilitate its adaptation to coastal habitats.

Community assembly of comammox Nitrospira in coastal wetlands across southeastern China.

Complete ammonia oxidizers (comammox Nitrospira) are ubiquitous in coastal wetland sediments and play an important role in nitrification. Our study examined the impact of habitat modifications on comammox Nitrospira communities in coastal wetland sediments across tropical and subtropical regions of southeastern China. Samples were collected from 21 coastal wetlands in five provinces where native mudflats were invaded by Spartina alterniflora and subsequently converted to aquaculture ponds. The results showed that comammox Nitrospira abundances were mainly influenced by sediment grain size rather than by habitat modifications. Compared to S. alterniflora marshes and native mudflats, aquaculture pond sediments had lower comammox Nitrospira diversity, lower clade A.1 abundance, and higher clade A.2 abundance. Sulfate concentration was the most important factor controlling the diversity of comammox Nitrospira. The response of comammox Nitrospira community to habitat change varied significantly by location, and environmental variables accounted for only 11.2% of the variations in community structure across all sites. In all three habitat types, dispersal limitation largely controlled the comammox Nitrospira community assembly process, indicating the stochastic nature of these sediment communities in coastal wetlands. IMPORTANCE Comammox Nitrospira have recently gained attention for their potential role in nitrification and nitrous oxide (N2O) emissions in soil and sediment. However, their distribution and assembly in impacted coastal wetland are poorly understood, particularly on a large spatial scale. Our study provides novel evidence that the effects of habitat modification on comammox Nitrospira communities are dependent on the location of the wetland. We also found that the assembly of comammox Nitrospira communities in coastal wetlands was mainly governed by stochastic processes. Nevertheless, sediment grain size and sulfate concentration were identified as key variables affecting comammox Nitrospira abundance and diversity in coastal sediments. These findings are significant as they advance our understanding of the environmental adaptation of comammox Nitrospira and how future landscape modifications may impact their abundance and diversity in coastal wetlands.

Plant Species-Driven Distribution of Individual Clades of Comammox Nitrospira in a Subtropical Estuarine Wetland.

Plant species play a crucial role in mediating the activity and community structure of soil microbiomes through differential inputs of litter and rhizosphere exudates, but we have a poor understanding of how plant species influence comammox Nitrospira, a newly discovered ammonia oxidizer with pivotal functionality. Here, we investigate the abundance, diversity, and community structure of comammox Nitrospira underneath five plant species and a bare tidal flat at three soil depths in a subtropical estuarine wetland. Plant species played a critical role in driving the distribution of individual clades of comammox Nitrospira, explaining 59.3% of the variation of community structure. Clade A.1 was widely detected in all samples, while clades A.2.1, A.2.2, A.3 and B showed plant species-dependent distribution patterns. Compared with the native species Cyperus malaccensis, the invasion of Spartina alterniflora increased the network complexity and changed the community structure of comammox Nitrospira, while the invasive effects from Kandelia obovata and Phragmites australis were relatively weak. Soil depths significantly influenced the community structure of comammox Nitrospira, but the effect was much weaker than that from plant species. Altogether, our results highlight the previously unrecognized critical role of plant species in driving the distribution of comammox Nitrospira in a subtropical estuarine wetland.

Non-native Plant Species Invasion Increases the Importance of Deterministic Processes in Fungal Community Assembly in a Coastal Wetland.

Fungal communities are essential to the maintenance of soil multifunctionality. Plant invasion represents a growing challenge for the conservation of soil biodiversity across the globe, but the impact of non-native species invasion on fungal diversity, community structure, and assembly processes remains largely unknown. Here, we examined the diversity, community composition, functional guilds, and assembly process of fungi at three soil depths underneath a native species, three non-native species, and a bare tidal flat from a coastal wetland. Plant species was more important than soil depth in regulating the diversity, community structure, and functional groups of fungi. Non-native species, especially Spartina alterniflora, increased fungal diversity, altered fungal community structure, and increased the relative abundance of saprotrophic and pathogenic fungi in coastal wetland soils. Stochastic processes played a predominant role in driving fungal community assembly, explaining more than 70% of the relative contributions. However, compared to a native species, non-native species, especially S. alterniflora, reduced the relative influence of stochastic processes in fungal community assembly. Collectively, our results provide novel evidence that non-native species can increase fungal diversity, the relative abundance of saprotrophic and pathogenic fungi, and deterministic processes in the assembly of fungi in coastal wetlands, which can expand our knowledge of the dynamics of fungal communities in subtropical coastal wetlands.

One-Pot Synthesis of Robust Fluorescent Nanocomposite Gel via Frontal Polymerization.

Fluorescent nanocomposite gels have attracted increasing attention due to their excellent optical properties, as well as enhanced mechanical strength originating from the nanoparticles. At present, two-step methods are usually employed, where fluorescent nanoparticles are firstly prepared, followed by mixing with gel precursor to achieve the final products after gelation, which suffer from the disadvantages of a tedious and time-consuming process. Thus, the development of a facile strategy is highly desirable, which still remains an obstacle. Herein, a new one-pot synthesis method towards robust fluorescent nanocomposite gels via frontal polymerization (FP) is proposed, where small molecular precursors (citric acid (CA) and urea, or L-cysteine) and gel precursor (vinyl monomers) are mixed together as co-reactants. During the FP process, a lot of heat release gives rise to the generation of carbonized polymer dots (CPDs). Thus, companying with the propagating of the polymerization, the production of fluorescent CPDs/gel composite is completed. In addition, as a nanofiller, CPDs dramatically enhance the mechanical property of the CPDs/gel composite. This work proposes a new fast and efficient one-pot strategy for the production of CPDs/gel composite, which will guide the development of high-performance polymer nanocomposites through an in situ synchronous reaction fashion.

Flavonoids dimers from the fruits of Psoralea corylifolia and their cytotoxicity against MCF-7 cells.

Nine new flavonoids dimers, psocorylins R-Z (1-9), were isolated from the fruits of Psoralea corylifolia L. (Psoraleae Fructus), a traditional Chinese medicine. The structures of these compounds were elucidated via multiple spectroscopic techniques and X-ray diffraction. Psocorylins R (1) and S (2) were rare cyclobutane-containing chalcone dimers, and psocorylins T-Z (3-9) were established by CC or COC bond of two flavonoid monomers. The structural-types, flavonoids dimers, were isolated from the plant for the first time, enriching the chemical diversity. The cytotoxicity assay suggested that compounds 1, 2, 4, 5, 6 and 8 exhibited cytotoxic activities against MCF-7 cells. Furthermore, compounds 1 and 8 significantly increased intracellular ROS levels, decreased MMP and induced apoptosis of MCF-7 cells. They markedly upregulated the expression of Bax and cleaved caspase-3, and suppressed Bcl-2 and caspase-3 levels, indicating their mechanism of Bcl-2/Bax/Cleaved caspase-3 pathway. Hence, our findings not only promoted the chemical investigation of Psoraleae Fructus, but also provided potential bioactive natural products for anti-cancer.

Various detailed characteristics of a new enhanced neurotrophic factor secreting rat derived bone marrow mesenchymal stem cells and its preliminary application in rat models of ischemic stroke.

Because MSC-NTF has a higher ability to secrete neurotrophic factors, it may have a greater potential than ordinary MSC in clinical applications. At present, research on MSC-NTF mainly focuses on clinical aspects, but its basic research is relatively few. In particular, the research on the comprehensive and detailed characteristics of MSC-NTF is missing. And its in vivo research in animals is also rare. Since the transplantation of human-derived MSC-NTF into rats is cross-species, its survival in the rat and the therapeutic effect may be seriously affected due to severe immune rejection. This will inevitably affect the research on the basic characteristics and the therapeutic mechanisms of MSC-NTF in vivo. Therefore, we chose the rat-derived MSCs to be induced as the MSC-NTF which had a stronger neurotrophic factor secretion function. This will also be helpful to perform the research of the basic therapeutic mechanisms of MSC-NTF in vivo. In addition, we have established some important characteristics that can be used to distinguish between MSC-NTF and MSCs: different multi-factor secretion ability and secretion characteristics, immunogenicity, three-line differentiation ability, stemness, etc. In addition to paying attention to their safety differences, this study also explored the differences in their in vivo survivability. Finally, we applied this newly induced rat-derived MSC-NTF in a rat model of ischemic stroke, and obtained beneficial therapeutic effects.

m6A-related lncRNA-based immune infiltration characteristic analysis and prognostic model for colonic adenocarcinoma.

BACKGROUND: Colonic adenocarcinoma (COAD) is a common gastrointestinal tract tumor, and its occurrence and progression are typically associated with genomic instability, tumor-suppressor gene and oncogene mutations, and tumor mutational load. N6-methyladenosine (m6A) modification of RNAs and long non-coding RNA (lncRNA) expression are important in tumorigenesis and progression. However, the regulatory roles of m6A-associated lncRNAs in the tumor microenvironment, stratification of prognosis, and immunotherapy are unclear. METHODS: We screened 43 prognostic lncRNAs linked to m6A and performed consistent molecular typing of COAD using consensus clustering. The single-sample Gene Set Enrichment Analysis and ESTIMATE algorithms were used to assess the immune characteristics of different subgroups. Covariation between methylation-related prognostic lncRNAs was eliminated by least absolute shrinkage and selection operator Cox regression. A nomogram was created and evaluated by combining the methylation-related prognostic lncRNA model with other clinical factors. The relationship between the prognostic model grouping and microsatellite instability, immunophenotype score, and tumor mutation burden was validated using R scripts. Finally, we used a linkage map to filter sensitive medicines to suppress the expression of high-risk genes. Three m6A-associated lncRNA modes were identified in 446 COAD specimens with different clinical endpoints and biological statuses. Risk scores were constructed based on the m6A-associated lncRNA signature genes. Patients with lower risk scores showed superior immunotherapy responses and clinical benefits compared to those with higher risk scores. Lower risk scores were also correlated with higher immunophenotype scores, tumor mutation burden, and mutation rates in significantly mutated genes (e.g., FAT4 and MUC16). Piperidolate, quinostatin, and mecamylamin were screened for their abilities to suppress the expression of high-risk genes in the model. CONCLUSIONS: Quantitative assessment of m6A-associated lncRNAs in single tumors can enhance the understanding of tumor microenvironment profiles. The prognostic model constructed using m6A-associated lncRNAs may facilitate prognosis and immunotherapy stratification of patients with COAD; finally, three drugs with potential therapeutic value were screened based on the model.

Pial arteriovenous fistula resembling the vein of Galen aneurysmal malformation, treated with staged endovascular embolization: a case report.

A 41-month-old boy was presented to our hospital because of an intracranial mass suspected of cerebrovascular malformation. He was admitted and received cerebral angiography. The angiography result confirmed the intracranial mass was the dilated vein of Galen resulting from a pial arteriovenous fistula, which quite resembling the vein of Galen aneurysmal malformation. Considering one-time embolization of the fistula may greatly change the distribution of intracranial blood flow, we decided to perform staged embolization. In the first stage, we partially embolized the fistula, resulting in a sharp decrease in blood flow to the lesion. The second intervention was performed one month later, and completely embolized the fistula. The boy recoverd well and returned to normal childhood without any neurological deficits. Follow-up MR images obtained at 10 months after the last procedure showing total obliteration of the pAVF, gradually shrinking of the varix, and remodeling of the vein of Galen.

A Nucleus Accumbens Tac1 Neural Circuit Regulates Avoidance Responses to Aversive Stimuli.

Neural circuits that control aversion are essential for motivational regulation and survival in animals. The nucleus accumbens (NAc) plays an important role in predicting aversive events and translating motivations into actions. However, the NAc circuits that mediate aversive behaviors remain elusive. Here, we report that tachykinin precursor 1 (Tac1) neurons in the NAc medial shell regulate avoidance responses to aversive stimuli. We show that NAcTac1 neurons project to the lateral hypothalamic area (LH) and that the NAcTac1→LH pathway contributes to avoidance responses. Moreover, the medial prefrontal cortex (mPFC) sends excitatory inputs to the NAc, and this circuit is involved in the regulation of avoidance responses to aversive stimuli. Overall, our study reveals a discrete NAc Tac1 circuit that senses aversive stimuli and drives avoidance behaviors.

A Melt-Quenched Luminescent Glass of an Organic-Inorganic Manganese Halide as a Large-Area Scintillator for Radiation Detection.

Glass is a group of materials with appealing qualities, including simplicity in fabrication, durability, and high transparency, and they play a crucial role in the optics field. In this paper, a new organic-inorganic metal halide luminescent glass exhibiting >78 % transmittance at 506-800 nm range together with a high photoluminescence quantum yield (PLQY) of 28.5 % is reported through a low-temperature melt-quenching approach of pre-synthesized (HTPP)2 MnBr4 (HTPP=hexyltriphenylphosphonium) single crystal. Temperature-dependent X-ray diffraction, polarizing microscopy, and molecular dynamics simulations were combined to investigate the glass-crystal interconversion process, revealing the disordered nature of the glassy state. Benefiting from the transparent nature, (HTPP)2 MnBr4 glass yields an outstanding spatial resolution of 10 lp mm-1 for X-ray imaging. The superb optical properties and facility of large-scale fabrication distinguish the organic-inorganic metal halide glass as a highly promising class of materials for optical devices.

Photoinduced Five-Component Radical Relay Aminocarbonylation of Alkenes.

Radical single carbonylation reactions with CO constitute a direct and robust strategy toward various carbonyl compounds from readily available chemicals, and have been extensively studied over the past decades. However, realizing highly selective catalytic systems for controlled radical double carbonylation reactions has remained a substantial challenge, particularly for the more advanced multicomponent variants, despite their great potential value. Herein, we report a visible-light-driven radical relay five-component radical double aminocarbonylation reaction of unactivated alkenes using CO under metal-free conditions. This protocol provides direct access to valuable γ-trifluoromethyl α-ketoamides with good yields and high chemoselectivity. Crucial was the identification of distinct dual roles of amine coupling partners, sequentially acting as electron donors for the formation of photoactive electron donor-acceptor (EDA) complexes with radical precursors and then as a CO acceptor via nitrogen radical cations to form carbamoyl radicals. Cross-coupling of carbamoyl radicals with the acyl radicals that are formed in an alkene-based relay process affords double aminocarbonylation products.

Catalytic Asymmetric Construction of Axially and Centrally Chiral Heterobiaryls by Minisci Reaction.

Axially chiral biaryls and heterobiaryls constitute the most represented subclass of atropisomers with prevalence in natural products, bioactive compounds, privileged chiral ligand/catalysts, and optically pure materials. Despite many ionic protocols for their construction, radical-based variants represent another highly desirable and intriguing strategy but are far less developed. Moreover, efficient synthesis of axially chiral heterobiaryl molecules, especially ones having multiple heteroatoms and other types of chiral elements, through radical routes remains extremely limited. We herein disclose the first catalytic asymmetric, metal-free construction of axially and centrally chiral heterobiaryls by Minisci reaction of 5-arylpyrimidines and α-amino acid-derived redox-active esters. This is enabled by the use of 4CzIPN as an organic photoredox catalyst in conjunction with a chiral phosphoric acid catalyst. The reaction achieved a variety of interesting 5-arylpyrimidines featuring the union of an axially chiral heterobiaryl and a centrally chiral α-branched amine with generally excellent regio-, diastereo-, and enantioselectivity (up to 82% yield; >19:1 dr; >99% ee). This finding also builds up a new platform for the development of desymmetrization methods via radical-involved atroposelective functionalization at heteroarene of prochiral heterobiaryls.