Modulating macrophage phenotype for accelerated wound healing with chlorogenic acid-loaded nanocomposite hydrogel.

Wound healing involves distinct phases, including hemostasis, inflammation, proliferation, and remodeling, which is a complex and dynamic process. Conventional preparations often fail to meet multiple demands and provide prompt information about wound status. Here, a pH/ROS dual-responsive hydrogel (OHA-PP@Z-CA@EGF) was constructed based on oxidized hyaluronic acid (OHA), phenylboronic acid-grafted ε-polylysine (PP), chlorogenic acid (CA)-loaded ZIF-8 (Z-CA), and epidermal growth factor (EGF), which possesses intrinsic antibacterial, antioxidant, and angiogenic capacities. Due to the Schiff base and Phenylboronate ester bonds, the hydrogel exhibited excellent mechanical properties, strong adhesion, good biodegradability, high biocompatibility, stable rheological properties, and self-healing ability. Moreover, introducing Z-CA as an initiator and nanofiller led to the additional cross-linking of hydrogel through coordination bonds, which further improved the mechanical properties and antioxidant capabilities. Bleeding models of liver and tail amputations demonstrated rapid hemostatic properties of the hydrogel. Besides, the hydrogel regulated macrophage phenotypes via the NF-κB/JAK-STAT pathways, relieved oxidative stress, promoted cell migration and angiogenesis, and accelerated diabetic wound healing. The hydrogel also enabled real-time monitoring of the wound healing stages by colorimetric detection. This multifunctional hydrogel opens new avenues for the treatment and management of full-thickness diabetic wounds.

Aged polystyrene microplastics exacerbate alopecia associated with tight junction injuries and apoptosis via oxidative stress pathway in skin.

Microplastics (MPs) are pervasive pollutants in the natural environment and contribute to increased levels of illness in both animals and humans. However, thespecific impacts of MPs on skin damage and alopeciaare not yet well understood. In this study, we have examined the effects of two types of polystyrene MPs (pristine and aged) on skin and hair follicle damage in mice. UV irradiation changed the chemical and physical properties of the aged MPs, including functional groups, surface roughness, and contact angles. In both in vivo and in vitro experiments, skin and cell injuries related to oxidative stress, apoptosis, tight junctions (TJs), alopecia, mitochondrial dysfunction, and other damages were observed. Mechanistically, MPs and aged MPs can induce TJs damage via the oxidative stress pathway and inhibition of antioxidant-related proteins, and this can lead to alopecia. The regulation of cell apoptosis was also observed, and this is involved in the ROS-mediated mitochondrial signaling pathway. Importantly, aged MPs showed exacerbated toxicity, which may be due to their elevated surface irregularities and altered chemical compositions. Collectively, this study suggests a potential therapeutic approach for alopecia and hair follicle damage caused by MPs pollution.

Single-cell transcriptome profiling reveals cell type-specific variation and development in HLA expression of human skin.

Skin, the largest organ of body, is a highly immunogenic tissue with a diverse collection of immune cells. Highly polymorphic human leukocyte antigen (HLA) molecules have a central role in coordinating immune responses as recognition molecules. Nevertheless, HLA gene expression patterns among diverse cell types within a specific organ, like the skin, have yet to be thoroughly investigated, with stromal cells attracting much less attention than immune cells. To illustrate HLA expression profiles across different cell types in the skin, we performed single-cell RNA sequencing (scRNA-seq) analyses on skin datasets, covering adult and fetal skin, and hair follicles as the skin appendages. We revealed the variation in HLA expression between different skin populations by examining normal adult skin datasets. Moreover, we evaluated the potential immunogenicity of multiple skin populations based on the expression of classical HLA class I genes, which were well represented in all cell types. Furthermore, we generated scRNA-seq data of developing skin from fetuses of 15 post conception weeks (PCW), 17 PCW, and 22 PCW, delineating the dynamic expression of HLA genes with cell type-dependent variation among various cell types during development. Notably, the pseudotime trajectory analysis unraveled the significant variance in HLA genes during the evolution of vascular endothelial cells. Moreover, we uncovered the immune-privileged properties of hair follicles at single-cell resolution. Our study presents a comprehensive single-cell transcriptomic landscape of HLA genes in the skin, which provides new insights into variation in HLA molecules and offers a clue for allogeneic skin transplantation.

Multimodal joint deconvolution and integrative signature selection in proteomics.

Deconvolution is an efficient approach for detecting cell-type-specific (cs) transcriptomic signals without cellular segmentation. However, this type of methods may require a reference profile from the same molecular source and tissue type. Here, we present a method to dissect bulk proteome by leveraging tissue-matched transcriptome and proteome without using a proteomics reference panel. Our method also selects the proteins contributing to the cellular heterogeneity shared between bulk transcriptome and proteome. The deconvoluted result enables downstream analyses such as cs-protein Quantitative Trait Loci (cspQTL) mapping. We benchmarked the performance of this multimodal deconvolution approach through CITE-seq pseudo bulk data, a simulation study, and the bulk multi-omics data from human brain normal tissues and breast cancer tumors, individually, showing robust and accurate cell abundance quantification across different datasets. This algorithm is implemented in a tool MICSQTL that also provides cspQTL and multi-omics integrative visualization, available at https://bioconductor.org/packages/MICSQTL .

Precision and Accuracy of Single-Cell/Nuclei RNA Sequencing Data.

Single-cell/nuclei RNA sequencing (sc/snRNA-Seq) is widely used for profiling cell-type gene expressions in biomedical research. An important but underappreciated issue is the quality of sc/snRNA-Seq data that would impact the reliability of downstream analyses. Here we evaluated the precision and accuracy in 18 sc/snRNA-Seq datasets. The precision was assessed on data from human brain studies with a total of 3,483,905 cells from 297 individuals, by utilizing technical replicates. The accuracy was evaluated with sample-matched scRNA-Seq and pooled-cell RNA-Seq data of cultured mononuclear phagocytes from four species. The results revealed low precision and accuracy at the single-cell level across all evaluated data. Cell number and RNA quality were highlighted as two key factors determining the expression precision, accuracy, and reproducibility of differential expression analysis in sc/snRNA-Seq. This study underscores the necessity of sequencing enough high-quality cells per cell type per individual, preferably in the hundreds, to mitigate noise in expression quantification.

Tetraspanin CD82 Correlates with and May Regulate S100A7 Expression in Oral Cancer.

Many metastatic cancers with poor prognoses correlate to downregulated CD82, but exceptions exist. Understanding the context of this correlation is essential to CD82 as a prognostic biomarker and therapeutic target. Oral squamous cell carcinoma (OSCC) constitutes over 90% of oral cancer. We aimed to uncover the function and mechanism of CD82 in OSCC. We investigated CD82 in human OSCC cell lines, tissues, and healthy controls using the CRISPR-Cas9 gene knockout, transcriptomics, proteomics, etc. CD82 expression is elevated in CAL 27 cells. Knockout CD82 altered over 300 genes and proteins and inhibited cell migration. Furthermore, CD82 expression correlates with S100 proteins in CAL 27, CD82KO, SCC-25, and S-G cells and some OSCC tissues. The 37-50 kDa CD82 protein in CAL 27 cells is upregulated, glycosylated, and truncated. CD82 correlates with S100 proteins and may regulate their expression and cell migration. The truncated CD82 explains the invasive metastasis and poor outcome of the CAL 27 donor. OSCC with upregulated truncated CD82 and S100A7 may represent a distinct subtype with a poor prognosis. Differing alternatives from wild-type CD82 may elucidate the contradictory functions and pave the way for CD82 as a prognostic biomarker and therapeutic target.

Research on aquatic microcosm: Bibliometric analysis, toxicity comparison and model prediction.

Recently, aquatic microcosms have attracted considerable attention because they can be used to simulate natural aquatic ecosystems. First, to evaluate the development of trends, hotspots, and national cooperation networks in the field, bibliometric analysis was performed based on 1841 articles on aquatic microcosm (1962-2022). The results of the bibliometric analysis can be categorized as follows: (1) Aquatic microcosm research can be summarized in two sections, with the first part focusing on the ecological processes and services of aquatic ecosystems, and the second focusing on the toxicity and degradation of pollutants. (2) The United States (number of publications: 541, proportion: 29.5%) and China (248, 13.5%) are the two most active countries. Second, to determine whether there is a difference between single-species and microcosm tests, that is, to perform different-tier assessments, the recommended aquatic safety thresholds in risk assessment [i.e., the community-level no effect concentration (NOECcommunity), hazardous concentrations for 5% of species (HC5) and predicted no effect concentration (PNEC)] were compared based on these tests. There was a significant difference between the NOECcommunity and HC5 (P < 0.05). Moreover, regression models predicting microcosm toxicity values were constructed to provide a reference for ecological systemic risk assessments based on aquatic microcosms.

Cycloplatinated (II) Complex Based on Isoquinoline Alkaloid Elicits Ferritinophagy-Dependent Ferroptosis in Triple-Negative Breast Cancer Cells.

The development and optimization of metal-based anticancer drugs with novel cytotoxic mechanisms have emerged as key strategies to overcome chemotherapeutic resistance and side effects. Agents that simultaneously induce ferroptosis and autophagic death have received extensive attention as potential modalities for cancer therapy. However, only a limited set of drugs or treatment modalities can synergistically induce ferroptosis and autophagic tumor cell death. In this work, we designed and synthesized four new cycloplatinated (II) complexes harboring an isoquinoline alkaloid C∧N ligand. On screening the in vitro activity of these agents, we found that Pt-3 exhibited greater selectivity of cytotoxicity, decreased resistance factors, and improved anticancer activity compared to cisplatin. Furthermore, Pt-3, which we demonstrate can initiate potent ferritinophagy-dependent ferroptosis, exhibits less toxic and better therapeutic activity than cisplatin in vivo. Our results identify Pt-3 as a promising candidate or paradigm for further drug development in cancer treatment.

A revamped rat reference genome improves the discovery of genetic diversity in laboratory rats.

The seventh iteration of the reference genome assembly for Rattus norvegicus-mRatBN7.2-corrects numerous misplaced segments and reduces base-level errors by approximately 9-fold and increases contiguity by 290-fold compared with its predecessor. Gene annotations are now more complete, improving the mapping precision of genomic, transcriptomic, and proteomics datasets. We jointly analyzed 163 short-read whole-genome sequencing datasets representing 120 laboratory rat strains and substrains using mRatBN7.2. We defined ∼20.0 million sequence variations, of which 18,700 are predicted to potentially impact the function of 6,677 genes. We also generated a new rat genetic map from 1,893 heterogeneous stock rats and annotated transcription start sites and alternative polyadenylation sites. The mRatBN7.2 assembly, along with the extensive analysis of genomic variations among rat strains, enhances our understanding of the rat genome, providing researchers with an expanded resource for studies involving rats.

Profiling Protein-Protein Interactions in the Human Brain by Refined Cofractionation Mass Spectrometry.

Proteins usually execute their biological functions through interactions with other proteins and by forming macromolecular complexes, but global profiling of protein complexes directly from human tissue samples has been limited. In this study, we utilized cofractionation mass spectrometry (CF-MS) to map protein complexes within the postmortem human brain with experimental replicates. First, we used concatenated anion and cation Ion Exchange Chromatography (IEX) to separate native protein complexes in 192 fractions and then proceeded with Data-Independent Acquisition (DIA) mass spectrometry to analyze the proteins in each fraction, quantifying a total of 4,804 proteins with 3,260 overlapping in both replicates. We improved the DIA's quantitative accuracy by implementing a constant amount of bovine serum albumin (BSA) in each fraction as an internal standard. Next, advanced computational pipelines, which integrate both a database-based complex analysis and an unbiased protein-protein interaction (PPI) search, were applied to identify protein complexes and construct protein-protein interaction networks in the human brain. Our study led to the identification of 486 protein complexes and 10054 binary protein-protein interactions, which represents the first global profiling of human brain PPIs using CF-MS. Overall, this study offers a resource and tool for a wide range of human brain research, including the identification of disease-specific protein complexes in the future.

Precisely Controlled Polymerization of Two-Dimensional Conducting Polymers in Quasi-Liquid Layer Enables Ultrahigh Sensing Performance.

Gas sensors based on conducting polymers offer great potential for high-performance room temperature applications due to their cost-effectiveness, high-sensitivity, and operational advantage. However, their current performance is limited by the deficiency of control in conventional polymerization methods, leading to poor crystallinity and inconsistent material properties. Here, the quasi-liquid layer (QLL) on the ice surface acts as a self-regulating nano-reactor for precise control of thermodynamics and kinetics in the polymerization, resulting in a 7.62 nm thick two-dimensional (2D) polyaniline (PANI) film matching the QLL thickness. The ultra-thin film optimizes the exposure of active sites, enhancing the detection of analyte gases at low concentrations. It is validated by fabricating a chemiresistive gas sensor with the 2D PANI film, demonstrating stable room-temperature detection of ammonia down to 10 ppt in ambient air with an impressive 10% response. This achievement represents the highest sensitivity among sensors of this kind while maintaining excellent selectivity and repeatability. Moreover, the QLL-controlled polymerization strategy offers an alternative route for precise control of the polymerization process for conducting polymers, enabling the creation of advanced materials with enhanced properties.

Photothermal Conversion of the Oleophilic PVDF/Ti3 C2 Tx Porous Foam Enables Non-Aqueous Liquid System Applicable Actuator.

Various physical and chemical reaction processes occur in non-aqueous liquid systems, particularly in oil phase systems. Therefore, achieving efficient, accurate, controllable, and cost-effective movement and transfer of substances in the oil phase is crucial. Liquid-phase photothermal actuators (LPAs) are commonly used for material transport in liquid-phase systems due to their remote operability and precise control. However, existing LPAs typically rely on materials like hydrogels and flexible polymers, commonly unsuitable for non-aqueous liquids. Herein, a 3D porous poly(vinylidene fluoride) (PVDF)/Ti3 C2 Tx actuator is developed using a solvent displacement method. It demonstrates directional movement and controlled material transport in non-aqueous liquid systems. When subject to infrared light irradiation (2.0 W cm-2 ), the actuator achieves motion velocities of 7.3 and 6 mm s-1 vertically and horizontally, respectively. The actuator's controllable motion capability is primarily attributed to the foam's oil-wettable properties, 3D porous oil transport network, and the excellent photothermal conversion performance of Ti3 C2 Tx , facilitating thermal diffusion and the Marangoni effect. Apart from multidimensional directions, the actuator enables material delivery and obstacle avoidance by transporting and releasing target objects to a predetermined position. Hence, the developed controllable actuator offers a viable solution for effective motion control and material handling in non-aqueous liquid environments.

High-sensitivity hybrid MoSe2/AgInGaS quantum dot heterojunction photodetector.

Zero-dimensional (0D)-two-dimensional (2D) hybrid photodetectors have received widespread attention due to their outstanding photoelectric performances. However, these devices with high performances mainly employ quantum dots that contain toxic elements as sensitizing layers, which restricts their practical applications. In this work, we used eco-friendly AgInGaS quantum dots (AIGS-QDs) as a highly light-absorbing layer and molybdenum diselenide (MoSe2) as a charge transfer layer to construct a 0D-2D hybrid photodetector. Notably, we observed that MoSe2 strongly quenches the photoluminescence (PL) of AIGS-QDs and decreases the decay time of PL in the MoSe2/AIGS-QDs heterojunction. The MoSe2/AIGS-QDs hybrid photodetector demonstrates a responsivity of 14.3 A W-1 and a high detectivity of 6.4 × 1011 Jones. Moreover, the detectivity of the hybrid phototransistor is significantly enhanced by more than three times compared with that of the MoSe2 photodetector. Our work suggests that 0D-2D hybrid photodetectors with multiplex I-III-VI QDs provide promising potential for future high-sensitivity photodetectors.

Selective CK1α degraders exert antiproliferative activity against a broad range of human cancer cell lines.

Molecular-glue degraders are small molecules that induce a specific interaction between an E3 ligase and a target protein, resulting in the target proteolysis. The discovery of molecular glue degraders currently relies mostly on screening approaches. Here, we describe screening of a library of cereblon (CRBN) ligands against a panel of patient-derived cancer cell lines, leading to the discovery of SJ7095, a potent degrader of CK1α, IKZF1 and IKZF3 proteins. Through a structure-informed exploration of structure activity relationship (SAR) around this small molecule we develop SJ3149, a selective and potent degrader of CK1α protein in vitro and in vivo. The structure of SJ3149 co-crystalized in complex with CK1α + CRBN + DDB1 provides a rationale for the improved degradation properties of this compound. In a panel of 115 cancer cell lines SJ3149 displays a broad antiproliferative activity profile, which shows statistically significant correlation with MDM2 inhibitor Nutlin-3a. These findings suggest potential utility of selective CK1α degraders for treatment of hematological cancers and solid tumors.

Bioavailability (BA)-based risk assessment of soil heavy metals in provinces of China through the predictive BA-models.

The real biological effect is not generated by the total content of heavy metals (HMs), but rather by bioavailable content. A new bioavailability-based ecological risk assessment (BA-based ERA) framework was developed for deriving bioavailability-based soil quality criteria (BA-based SQC) and accurately assessing the ecological risk of soil HMs at a multi-regional scale in this study. Through the random forest (RF) models and BA-based ERA framework, the 217 BA-based SQC for HMs in 31 Chinese provinces were derived and the BA-based ERA was comprehensively assessed. This study found that bioavailable HMs extraction methods (BHEMs) and total HMs content play the predominant role in affecting HMs (As, Cd, Cr, Cu, Ni, Pb, and Zn) bioavailability by explaining 27.55-56.11% and 9.20-62.09% of the variation, respectively. The RF model had accurate and stable prediction ability for the bioavailability of soil HMs with the mean R2 and RMSE of 0.83 and 0.43 for the test set, respectively. The results of BA-based ERA showed that bioavailability could avoid the overestimation of ecological risks to some extent after reducing the uncertainty of soil differences. This study confirmed the feasibility of using bioavailability for ERA and will utilised to revise the soil environmental standards based on bioavailability for HMs.

Identifying Sex-Specific Serum Patterns of Alzheimer's Mice through Deep TMT Profiling and a Concentration-Dependent Concatenation Strategy.

Alzheimer's disease (AD) is the most prevalent form of dementia, disproportionately affecting women in disease prevalence and progression. Comprehensive analysis of the serum proteome in a common AD mouse model offers potential in identifying possible AD pathology- and gender-associated biomarkers. Here, we introduce a multiplexed, nondepleted mouse serum proteome profiling via tandem mass-tag (TMTpro) labeling. The labeled sample was separated into 475 fractions using basic reversed-phase liquid chromatography (RPLC), which were categorized into low-, medium-, and high-concentration fractions for concatenation. This concentration-dependent concatenation strategy resulted in 128 fractions for acidic RPLC-tandem mass spectrometry (MS/MS) analysis, collecting ∼5 million MS/MS scans and identifying 3972 unique proteins (3413 genes) that cover a dynamic range spanning at least 6 orders of magnitude. The differential expression analysis between wild type and the commonly used AD model (5xFAD) mice exhibited minimal significant protein alterations. However, we detected 60 statistically significant (FDR < 0.05), sex-specific proteins, including complement components, serpins, carboxylesterases, major urinary proteins, cysteine-rich secretory protein 1, pregnancy-associated murine protein 1, prolactin, amyloid P component, epidermal growth factor receptor, fibrinogen-like protein 1, and hepcidin. The results suggest that our platform possesses the sensitivity and reproducibility required to detect sex-specific differentially expressed proteins in mouse serum samples.

An adaptive stress response that confers cellular resilience to decreased ubiquitination.

Ubiquitination is a post-translational modification initiated by the E1 enzyme UBA1, which transfers ubiquitin to ~35 E2 ubiquitin-conjugating enzymes. While UBA1 loss is cell lethal, it remains unknown how partial reduction in UBA1 activity is endured. Here, we utilize deep-coverage mass spectrometry to define the E1-E2 interactome and to determine the proteins that are modulated by knockdown of UBA1 and of each E2 in human cells. These analyses define the UBA1/E2-sensitive proteome and the E2 specificity in protein modulation. Interestingly, profound adaptations in peroxisomes and other organelles are triggered by decreased ubiquitination. While the cargo receptor PEX5 depends on its mono-ubiquitination for binding to peroxisomal proteins and importing them into peroxisomes, we find that UBA1/E2 knockdown induces the compensatory upregulation of other PEX proteins necessary for PEX5 docking to the peroxisomal membrane. Altogether, this study defines a homeostatic mechanism that sustains peroxisomal protein import in cells with decreased ubiquitination capacity.

Natural product rhynchophylline prevents stress-induced hair graying by preserving melanocyte stem cells via the ß2 adrenergic pathway suppression.

Norepinephrine (NA), a stress hormone, can accelerate hair graying by binding to ß2 adrenergic receptors (ß2AR) on melanocyte stem cells (McSCs). From this, NA-ß2AR axis could be a potential target for preventing the stress effect. However, identifying selective blockers for ß2AR has been a key challenge. Therefore, in this study, advanced computer-aided drug design (CADD) techniques were harnessed to screen natural molecules, leading to the discovery of rhynchophylline as a promising compound. Rhynchophylline exhibited strong and stable binding within the active site of ß2AR, as verified by molecular docking and dynamic simulation assays. When administered to cells, rhynchophylline effectively inhibited NA-ß2AR signaling. This intervention resulted in a significant reduction of hair graying in a stress-induced mouse model, from 28.5% to 8.2%. To gain a deeper understanding of the underlying mechanisms, transcriptome sequencing was employed, which revealed that NA might disrupt melanogenesis by affecting intracellular calcium balance and promoting cell apoptosis. Importantly, rhynchophylline acted as a potent inhibitor of these downstream pathways. In conclusion, the study demonstrated that rhynchophylline has the potential to mitigate the negative impact of NA on melanogenesis by targeting ß2AR, thus offering a promising solution for preventing stress-induced hair graying.

Signaling pathways in hair aging.

Hair follicle (HF) homeostasis is regulated by various signaling pathways. Disruption of such homeostasis leads to HF disorders, such as alopecia, pigment loss, and hair aging, which is causing severe health problems and aesthetic concerns. Among these disorders, hair aging is characterized by hair graying, hair loss, hair follicle miniaturization (HFM), and structural changes to the hair shaft. Hair aging occurs under physiological conditions, while premature hair aging is often associated with certain pathological conditions. Numerous investigations have been made to determine the mechanisms and explore treatments to prevent hair aging. The most well-known hypotheses about hair aging include oxidative stress, hormonal disorders, inflammation, as well as DNA damage and repair defects. Ultimately, these factors pose threats to HF cells, especially stem cells such as hair follicle stem cells, melanocyte stem cells, and mesenchymal stem cells, which hamper hair regeneration and pigmentation. Here, we summarize previous studies investigating the above mechanisms and the existing therapeutic methods for hair aging. We also provide insights into hair aging research and discuss the limitations and outlook.

The impact of common variants on gene expression in the human brain: from RNA to protein to schizophrenia risk.

Background: The impact of genetic variants on gene expression has been intensely studied at the transcription level, yielding in valuable insights into the association between genes and the risk of complex disorders, such as schizophrenia (SCZ). However, the downstream impact of these variants and the molecular mechanisms connecting transcription variation to disease risk are not well understood. Results: We quantitated ribosome occupancy in prefrontal cortex samples of the BrainGVEX cohort. Together with transcriptomics and proteomics data from the same cohort, we performed cis-Quantitative Trait Locus (QTL) mapping and identified 3,253 expression QTLs (eQTLs), 1,344 ribosome occupancy QTLs (rQTLs), and 657 protein QTLs (pQTLs) out of 7,458 genes quantitated in all three omics types from 185 samples. Of the eQTLs identified, only 34% have their effects propagated to the protein level. Further analysis on the effect size of prefrontal cortex eQTLs identified from an independent dataset showed clear post-transcriptional attenuation of eQTL effects. To investigate the biological relevance of the attenuated eQTLs, we identified 70 expression-specific QTLs (esQTLs), 51 ribosome-occupancy-specific QTLs (rsQTLs), and 107 protein-specific QTLs (psQTLs). Five of these omics-specific QTLs showed strong colocalization with SCZ GWAS signals, three of them are esQTLs. The limited number of GWAS colocalization discoveries from omics-specific QTLs and the apparent prevalence of eQTL attenuation prompted us to take a complementary approach to investigate the functional relevance of attenuated eQTLs. Using S-PrediXcan we identified 74 SCZ risk genes, 34% of which were novel, and 67% of these risk genes were replicated in a MR-Egger test. Notably, 52 out of 74 risk genes were identified using eQTL data and 70% of these SCZ-risk-gene-driving eQTLs show little to no evidence of driving corresponding variations at the protein level. Conclusion: The effect of eQTLs on gene expression in the prefrontal cortex is commonly attenuated post-transcriptionally. Many of the attenuated eQTLs still correlate with SCZ GWAS signal. Further investigation is needed to elucidate a mechanistic link between attenuated eQTLs and SCZ disease risk.