Effects of isoprene on the ozonolysis of Δ3-carene and ß-caryophyllene: Mechanisms of secondary organic aerosol formation and cross-dimerization.

Elucidating the mutual effects between the different volatile organic compounds (VOCs) is crucial for comprehending the formation mechanism of atmospheric secondary organic aerosols (SOA). Here, the mixed VOCs experiments of isoprene and Δ3-carene/ß-caryophyllene were carried out in the presence of O3 using an indoor smog chamber. The suppression effect of isoprene was recognized by the scanning mobility particle sizer spectrometer, online vacuum ultraviolet free electron laser (VUV-FEL) photoionization aerosol mass spectrometry, and quantum chemical calculations. The results indicate that the suppression effect of isoprene on the ozonolysis of Δ3-carene and ß-caryophyllene shows fluctuating and monotonous trends, respectively. The carbon content of the precursor could be the main factor for regulating the strength of the suppression effect. Plausible structures and formation mechanisms of several new products generated from the single VOC precursor and VOC-cross-reaction are proposed, which enrich the category of VOC oxidation products. Meanwhile, a new dimerization mechanism of the RO2 + R'O2 reaction is suggested, which offers an intriguing perspective on the gas phase formation process of particle phase accretion products. The present findings provide valuable insights into clarifying the pivotal roles played by isoprene in the interplay between different VOCs and understanding of SOA formation mechanisms of VOC mixtures, especially nearby the emission origins.

Uncovering neural substrates across Alzheimer's disease stages using contrastive variational autoencoder.

Alzheimer's disease is the most common major neurocognitive disorder. Although currently, no cure exists, understanding the neurobiological substrate underlying Alzheimer's disease progression will facilitate early diagnosis and treatment, slow disease progression, and improve prognosis. In this study, we aimed to understand the morphological changes underlying Alzheimer's disease progression using structural magnetic resonance imaging data from cognitively normal individuals, individuals with mild cognitive impairment, and Alzheimer's disease via a contrastive variational autoencoder model. We used contrastive variational autoencoder to generate synthetic data to boost the downstream classification performance. Due to the ability to parse out the nonclinical factors such as age and gender, contrastive variational autoencoder facilitated a purer comparison between different Alzheimer's disease stages to identify the pathological changes specific to Alzheimer's disease progression. We showed that brain morphological changes across Alzheimer's disease stages were significantly associated with individuals' neurofilament light chain concentration, a potential biomarker for Alzheimer's disease, highlighting the biological plausibility of our results.

Left inferior phrenic arterial malformation mimicking gastric varices: A case report and review of literature.

BACKGROUND: Gastric submucosal arterial dilation resulting from splenic artery occlusion represents an exceedingly rare etiology of acute upper gastrointestinal bleeding (UGIB). Although endoscopy is a widely utilized diagnostic and therapeutic modality for gastrointestinal bleeding, it has limitations in detecting arterial abnormalities. CASE SUMMARY: This report presents a rare case of massive UGIB in a 57-year-old male with a tortuous left inferior phrenic artery accompanied by splenic artery occlusion. "Gastric varices" was identified during the patient's endoscopy one year before hemorrhage. Despite initial hemostasis by endoscopic clipping, the patient experienced massive rebleeding after one month, requiring intervention with transcatheter arterial embolization (TAE) to achieve hemostasis. CONCLUSION: This is the first case to report UGIB due to a tortuous left inferior phrenic artery. This case highlights the limitations of endoscopy in identifying arterial abnormalities and emphasizes the potential of TAE as a viable alternative for the management of arterial bleeding in the gastrointestinal tract.

Application of preoperative MRI lesion identification algorithm in pediatric and young adult focal cortical dysplasia-related epilepsy.

OBJECTIVE: The purpose of this study was to evaluate the performance and generalizability of an automated, interpretable surface-based MRI classifier for the detection of focal cortical dysplasia. METHODS: This was a retrospective cohort incorporating MRIs from the epilepsy surgery (FCD and MRI-negative) and neuroimaging (healthy controls) databases at Children's National Hospital (CNH), and a publicly-available FCD Type II dataset from Bonn, Germany. Clinical characteristics and outcomes were abstracted from patient records and/or existing databases. Subjects were included if they had 3T epilepsy-protocol MRI. Manually-segmented FCD masks were compared to the automated masks generated by the Multi-centre Epilepsy Lesion Detection (MELD) FCD detection algorithm. Sensitivity/specificity were calculated. RESULTS: From CNH, 39 FCD pharmacoresistant epilepsy (PRE) patients, 19 healthy controls, and 19 MRI-negative patients were included. From Bonn, 85 FCD Type II were included, of which 68 passed preprocessing. MELD had varying performance (sensitivity) in these datasets: CNH FCD-PRE (54 %); Bonn (68 %); MRI-negative (44 %). In multivariate regression, FCD Type IIB pathology predicted higher chance of MELD automated lesion detection. All four patients who underwent resection/ablation of MELD-identified clusters achieved Engel I outcome. SIGNIFICANCE: We validate the performance of MELD automated, interpretable FCD classifier in a diverse pediatric cohort with FCD-PRE. We also demonstrate the classifier has relatively good performance in an independent FCD Type II cohort with pediatric-onset epilepsy, as well as simulated real-world value in a pediatric population with MRI-negative PRE.

Serum albumin level is associated with mortality and hospital stays: a real-world data analysis.

BACKGROUND & AIMS: The value of serum albumin might be underestimated, especially in cancer patients. We thus aimed to evaluate the association between serum albumin level at hospital admission and clinical outcomes in hospitalized patients with cancer. METHODS: This is a retrospective, cross-sectional, and real-world data analysis. Hospitalized adult patients with malignant cancer were recruited from two tertiary hospitals. Serum level of albumin, which was measured within 24 hours after hospital admission, was the exposure. Length of hospital stays (LOS) was the primary and all-cause in-hospital mortality was the secondary outcomes. Other information, including age, sex, types of cancer, history of hypertension and diabetes, surgery, blood routine test, liver and renal function, and dietary intake, were also abstracted from medical records. RESULTS: A total number of 5,187 adult patients with cancer (2,949 were men and 2,238 women; average age 61.6±12.4 years and average albumin 40.3±5.2 g/L) were included. The prevalence of hypoalbuminemia was 12.2% (634/5,187). Older patients, patients with liver injury, anemia, and with high level of WBC were positively, while those with overweight and high level of total triglycerides, were negatively associated with hypoalbuminemia. After adjustment of covariates, hypoalbuminemia was significantly associated with longer LOS in the current study. The increase of 5 g/L in serum level of albumin could result in 1.09 days (95%CI: -1.38, -0.80 days) shorter in LOS. The increase of 5 g/L in serum level of albumin was also associated with 45% lower in risk of mortality (OR=0.55; 95% CI: 0.43, 0.7) after fully adjustment. CONCLUSIONS: Serum albumin level at admission was associated with both LOS and mortality in patients with malignant cancer.

Corrigendum: Effectiveness, safety, and treatment pattern of sodium zirconium cyclosilicate in Chinese patients with hyperkalemia: interim analysis from a multicenter, prospective, real-world study (Actualize Study).

[This corrects the article DOI: 10.3389/fphar.2024.1398953.].

H3PO4-Impregnated Covalent Organic Framework Membrane on Separators to Prevent Lithium Metal Anode Dendrite Growth.

Inhibiting the growth of lithium dendrites is crucial for battery safety. For separators, their favorable electrolyte wettability, uniform current density, and high ionic conductivity are beneficial for avoiding Li dendrite growth. In this work, we propose a separator (PA@COF/PP) by modifying a polypropylene separator with H3PO4-functionalized covalent organic frameworks. The uniform channels of the covalent organic frameworks and H3PO4 can homogenize the current and act as ionic conductors for efficient Li+ migration. The synthesized separator effectively suppresses the growth of lithium dendrites and improves the stability of the batteries. A symmetric cell with the PA@COF/PP separator exhibits a stable life span over 4000 hours at a high current density of 5 mA cm-2, compared to the commercial PP separator, which lasts only 159 hours. This work provides an efficient method and novel inspiration for the construction of dendrite-free lithium metal batteries.

A few-shot learning framework for the diagnosis of osteopenia and osteoporosis using knee X-ray images.

OBJECTIVE: We developed a few-shot learning (FSL) framework for the diagnosis of osteopenia and osteoporosis in knee X-ray images. METHODS: Computer vision models containing deep convolutional neural networks were fine-tuned to enable generalization from natural images (ImageNet) to chest X-ray images (normal vs. pneumonia, base images). Then, a series of automated machine learning classifiers based on the Euclidean distances of base images were developed to make predictions for novel images (normal vs. osteopenia vs. osteoporosis). The performance of the FSL framework was compared with that of junior and senior radiologists. In addition, the gradient-weighted class activation mapping algorithm was used for visual interpretation. RESULTS: In Cohort #1, the mean accuracy (0.728) and sensitivity (0.774) of the FSL models were higher than those of the radiologists (0.512 and 0.448). A diagnostic pipeline of FSL model (first)-radiologists (second) achieved better performance (0.653 accuracy, 0.582 sensitivity, and 0.816 specificity) than radiologists alone. In Cohort #2, the diagnostic pipeline also showed improved performance. CONCLUSIONS: The FSL framework yielded practical performance with respect to the diagnosis of osteopenia and osteoporosis in comparison with radiologists. This retrospective study supports the use of promising FSL methods in computer-aided diagnosis tasks involving limited samples.

Symptom dimensions of resting-state electroencephalographic functional connectivity in autism.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by social and communication deficits (SCDs), restricted and repetitive behaviors (RRBs) and fixated interests. Despite its prevalence, development of effective therapy for ASD is hindered by its symptomatic and neurophysiological heterogeneities. To comprehensively explore these heterogeneities, we developed a new analytical framework combining contrastive learning and sparse canonical correlation analysis that identifies symptom-linked resting-state electroencephalographic connectivity dimensions within 392 ASD samples. We present two dimensions with multivariate connectivity basis exhibiting significant correlations with SCD and RRB, confirm their robustness through cross-validation and demonstrate their conceptual generalizability using an independent dataset (n = 222). Specifically, the right inferior parietal lobe is the core region for RRB, while connectivity between the left angular gyrus and the right middle temporal gyrus show key contribution to SCD. These findings provide a promising avenue to parse ASD heterogeneity with high clinical translatability, paving the way for ASD treatment development and precision medicine.

Male breast cancer metastasising to the liver: A case report.

Breast cancer (BC) remains one of the most common malignant diseases affecting female patients, and it can metastasize to nearly every part of the body. BC is rare in men, and therefore men rarely develop BC liver metastases (BCLMs). However, the present study reports a 55-year-old male patient who underwent surgery 5 years ago for BC. After treatment, the patient was actively followed up regularly. Recently, the patient was examined for chest tightness, and liver space-occupying lesions were found. The upper abdominal enhanced computed tomography images of the patient showed that the liver density was not uniform and that the liver had a mass. A crude needle biopsy was used to examine the liver tumour under the guidance of ultrasound. The pathology revealed that the patient was positive for E-cadherin, oestrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, GATA binding protein 3 and CK7. The patient was subsequently diagnosed with BCLM. The patient was treated with doxorubicin hydrochloride, cyclophosphamide, Docetaxel and followed up regularly. The present case report emphasizes that BC is found not only in women but also in an increasing number of men, and that liver metastasis can occur in males with BC. BCLM is a complex process, and therefore it is hoped this case report will improve the understanding of male BCLM and the mechanism of this disease.

Discriminative functional connectivity signature of cocaine use disorder links to rTMS treatment response.

Cocaine use disorder (CUD) is prevalent, and repetitive transcranial magnetic stimulation (rTMS) shows promise in reducing cravings. However, the association between a consistent CUD-specific functional connectivity signature and treatment response remains unclear. Here we identify a validated functional connectivity signature from functional magnetic resonance imaging to discriminate CUD, with successful independent replication. We found increased connectivity within the visual and dorsal attention networks and between the frontoparietal control and ventral attention networks, alongside reduced connectivity between the default mode and limbic networks in patients with CUD. These connections were associated with drug use history and cognitive impairments. Using data from a randomized clinical trial, we also established the prognostic value of these functional connectivities for rTMS treatment outcomes in CUD, especially involving the frontoparietal control and default mode networks. Our findings reveal insights into the neurobiological mechanisms of CUD and link functional connectivity biomarkers with rTMS treatment response, offering potential targets for future therapeutic development.

Novel evidence of CNV deletion in KCTD13 related to the severity of isolated hypospadias in Chinese population.

Background: CNV in KCTD13 has been identified to influence androgen receptor function via its changes in gene dosage, which might contribute to hypospadias. However, there is lack of population-level evidence to assess the contribution of KCTD13 CNV to hypospadias. Methods: 349 isolated hypospadias patients were recruited and their genotyping was performed using real-time qPCR. We use Database of Genomic Variants (DGV) and CNV calls from SNP-array intensity data in 1,008 Chinese healthy men as reference. Results: 11.17% of patients were identified to have KCTD13 CNV deletion, significantly higher than 0.05% in DGV (P < 0.001), but no cases found to have CNV duplication. Meanwhile, no CNV calls encompassing KCTD13 region were detected in Chinese healthy men. Incidence of KCTD13 CNV deletion was significantly increased with the severity of hypospadias, P _trend = 9.00 × 10-6. Compared to distal hypospadias, ORs for the proximal and midshaft were 10.07 (2.91-34.84) and 6.08 (1.69-21.84) respectively. In addition, the association between genital characteristics (stretched penile length and glans width) and KCTD13 CNV showed no significance in hypospadias children (P > 0.05). Conclusions: We demonstrate KCTD13 CNV deletion is strongly associated with hypospadias and its severity, but duplication is not, characterizing KCTD13 genetic variation in more detail than previously described.

Effectiveness, safety, and treatment pattern of sodium zirconium cyclosilicate in Chinese patients with hyperkalemia: interim analysis from a multicenter, prospective, real-world study (Actualize Study).

Introduction: Sodium zirconium cyclosilicate (SZC) is a nonabsorbed cation-exchanger approved in China for the treatment of hyperkalemia [HK; serum potassium (sK+) levels >5.0 mmol/L]. This is the first real-world study aimed to assess the effectiveness, safety, and treatment patterns of SZC in Chinese patients with HK. Here we present the results of the first interim analysis. Methods: This multicenter, prospective, cohort study included patients aged ≥18 years with documented HK within 1-year before study enrollment day. These patients were followed up for 6 months from the enrollment day after initiating SZC treatment. The treatment was categorized into correction phase (FAS-P1) and maintenance phase (FAS-P2 new and ongoing users). Subgroup analysis was performed in patients on hemodialysis (FAS-H). The primary objective was evaluation of safety profile of SZC; secondary objectives included assessment of treatment patterns of SZC and its effectiveness. Results: Of 421 screened patients, 193, 354, and 162 patients were enrolled in the FAS-P1, FAS-P2, and FAS-H groups, respectively. sK+ levels were reduced significantly from 5.9 mmol/L to 5.0 mmol/L after the correction phase. For the maintenance phase, the mean sK+ levels were maintained at 5.2 mmol/L and 5.0 mmol/L in the FAS-P2 new and ongoing user, respectively, and 5.3 mmol/L in the FAS-H subgroup. A considerable proportion of patients showed normokalemia after 48 h of SZC treatment (FAS-P1:51.3%) which was maintained up to 6 months in the maintenance phase (FAS-P2:44%). SZC was well-tolerated. Conclusion: SZC was effective and safe for the treatment of HK in real-world clinical practice in China.

Mapping Functional Connectivity Signatures of Pharmacoresistant Focal Cortical Dysplasia-Related Epilepsy.

OBJECTIVE: To determine common network alterations in focal cortical dysplasia pharmacoresistant epilepsy (FCD-PRE) using functional connectivity analysis of resting-state functional magnetic resonance imaging (rsfMRI). METHODS: This is a retrospective imaging cohort from Children's National Hospital (Washington, DC, USA) from January, 2011 to January, 2022. Patients with 3-T MRI-confirmed FCD-PRE underwent rsfMRI as part of routine clinical care. Patients were included if they were age 5-22 years at the time of the scan, and had a minimum of 18 months of follow-up. Healthy, typically-developing controls were included from Children's National Hospital (n = 16) and matched from Human Connectome Project-Development public dataset (n = 100). RESULTS: A total of 42 FCD-PRE patients (20 M:22 F, aged 14.2 ± 4.1 years) and 116 healthy controls (56 M:60 F, aged 13.7 ± 3.3 years) with rsfMRI were included. Seed-based functional connectivity maps were generated for each FCD, and each seed was used to generate a patient-specific z-scored connectivity map on 116 controls. FCD-PRE patients had mutual altered connectivity in regions of dorsal attention, default mode, and control networks. Functional connectivity was diminished within the FCD dominant functional network, as well as in homotopic regions. Cluster specific connectivity patterns varied by pathological subtype. Higher FCD connectivity to the limbic network was associated with increased odds of Engel I outcome. INTERPRETATION: This study demonstrates diminished functional connectivity patterns in FCD-PRE, which may represent a neuromarker for the disease, independent of FCD location, involving the dorsal attention, default mode, and control functional networks. Higher connectivity to the limbic network is associated with a seizure-free outcome. Future multicenter, prospective studies are needed to allow for much earlier detection of signatures of treatment-resistant epilepsy. ANN NEUROL 2024.

Structure-Based Drug Design of 2-Amino-[1,1'-biphenyl]-3-carboxamide Derivatives as Selective PKMYT1 Inhibitors for the Treatment of CCNE1-Amplified Breast Cancer.

CCNE1 amplification occurs in breast cancer and currently lacks effective therapies. PKMYT1 as a synthetic lethal target for CCNE1 amplification holds promise for the treatment of CCNE1-amplified breast cancer. Herein, we discover a series of 2-amino-[1,1'-biphenyl]-3-carboxamide derivatives as potent and selective PKMYT1 inhibitors using structure-based drug design. The representative compound 8ma exhibited excellent potency against PKMYT1, while sparing WEE1. It also suppressed proliferation of the CCNE1-amplified HCC1569 breast cancer cell line and showed synergistic cytotoxicity in combination with gemcitabine. PKMYT1 X-ray cocrystallography confirmed that introduction of key binding interactions between the inhibitors and residues Asp251 and Tyr121 of PKMYT1 greatly enhanced the potency and selectivity of the compounds.

A dual-functional NIR fluorescence probe for detecting hypochlorous acid and bisulfite in biosystem.

BACKGROUND: Bisulfite (HSO3-) serves as a bleaching agent, antioxidant, antimicrobial, and regulator of enzymatic reactions in biosystem. However, abnormal levels of bisulfite can be detrimental to health. Hypochlorous acid (HOCl), which acts as bioactive small molecules, is crucial for maintaining normal biological functions in living organisms. Disruption of its equilibrium can lead to oxidative stress and various diseases. Therefore, it's essential to monitor the fluctuations of HOCl and HSO3- at cellular and in vivo levels to study their physiological and pathological functions. RESULTS: This study constructed a novel NIR bifunctional colorimetric fluorescent probe using thienocoumarin-indanedione structures to identify hypochlorite (ClO-) and bisulfite (HSO3-). By using CSO-IO to recognize HSO3- and HOCl, two distinct products were generated, displaying green and blue fluorescence, respectively. This property effectively allows for the simultaneous dual-functional detection of HSO3- (LOD: 113 nM) and HOCl (LOD: 43 nM). SIGNIFICANCE: In this work, the biocompatible molecule CSO-IO has been effectively designed to detect HOCl/HSO3- in living cells and zebrafish. As a result, the dual-functional fluorescent probe has the potential to be utilized as a molecular tool to detect HSO3- derived compounds and HOCl simultaneously within the complex biological system.

Branched-chain amino acid transaminase 1 confers EGFR-TKI resistance through epigenetic glycolytic activation.

Third-generation EGFR tyrosine kinase inhibitors (TKIs), exemplified by osimertinib, have demonstrated promising clinical efficacy in the treatment of non-small cell lung cancer (NSCLC). Our previous work has identified ASK120067 as a novel third-generation EGFR TKI with remarkable antitumor effects that has undergone New Drug Application (NDA) submission in China. Despite substantial progress, acquired resistance to EGFR-TKIs remains a significant challenge, impeding the long-term effectiveness of therapeutic approaches. In this study, we conducted a comprehensive investigation utilizing high-throughput proteomics analysis on established TKI-resistant tumor models, and found a notable upregulation of branched-chain amino acid transaminase 1 (BCAT1) expression in both osimertinib- and ASK120067-resistant tumors compared with the parental TKI-sensitive NSCLC tumors. Genetic depletion or pharmacological inhibition of BCAT1 impaired the growth of resistant cells and partially re-sensitized tumor cells to EGFR TKIs. Mechanistically, upregulated BCAT1 in resistant cells reprogrammed branched-chain amino acid (BCAA) metabolism and promoted alpha ketoglutarate (α-KG)-dependent demethylation of lysine 27 on histone H3 (H3K27) and subsequent transcriptional derepression of glycolysis-related genes, thereby enhancing glycolysis and promoting tumor progression. Moreover, we identified WQQ-345 as a novel BCAT1 inhibitor exhibiting antitumor activity both in vitro and in vivo against TKI-resistant lung cancer with high BCAT1 expression. In summary, our study highlighted the crucial role of BCAT1 in mediating resistance to third-generation EGFR-TKIs through epigenetic activation of glycolysis in NSCLC, thereby supporting BCAT1 as a promising therapeutic target for the treatment of TKI-resistant NSCLC.

Probing the toxic hypochlorous acid in natural waters and biosystem by a coumarin-based fluorescence probe.

Since the onset of the SARS-CoV-2 pandemic in early 2020, there has been a notable rise in sodium hypochlorite disinfectants. Sodium hypochlorite undergoes hydrolysis to generate hypochlorous acid for virus eradication. This chlorine-based disinfectant is widely utilized for public disinfection due to its effectiveness. Although sodium hypochlorite disinfection is convenient, its excessive and indiscriminate use can harm the water environment and pose a risk to human health. Hypochlorous acid, a reactive oxygen species, plays a crucial role in the troposphere, stratospheric chemistry, and oxidizing capacity. Additionally, hypochlorous acid is vital as a reactive oxygen species in biological systems, and its irregular metabolism and level is associated with several illnesses. Thus, it is crucial to identify hypochlorous acid to comprehend its environmental and biological functions precisely. Here, we constructed a new fluorescent probe, utilizing the twisted intramolecular charge transfer mechanism to quickly and accurately detect hypochlorous acid in environmental water and biosystems. The probe showed a notable increase in fluorescence when exposed to hypochlorous acid, demonstrating its excellent selectivity, fast response time (less than 10 seconds), a large Stokes shift (∼ 102 nm), and a low detection limit of 15.5 nM.

Fabrication of Flame-Retardant Ammonium Polyphosphate Modified Phytic Acid-Based Rigid Polyurethane Foam with Enhanced Mechanical Properties.

Ammonium polyphosphate (APP) and self-made nickel phytate (PANi) were used as modified materials to prepare green biomass rigid polyurethane foam (RPUF). The flame retardancy, thermal stability, smoke toxicity and mechanical properties of the modified RPUF were investigated by limiting oxygen index (LOI), a cone calorimetry (CONE) test, thermogravimetric analysis and a compression test. The results showed that the RPUF with 10 wt% APP (PANi/APP10) had the highest LOI of 26.5%. Its peak heat release rate (PHRR) and total heat release (THR) were reduced by 29.64% and 24.05% compared with PANi/APP0 without APP. And its smoke production rate (SPR) and total smoke release (TSR) decreased by 33.14% and 19.88%, respectively. Compared with pure RPUF, the compressive strength of PANi/APP10 was increased by 50%, mainly because APP itself was an ultra-fine powder, which was better compatible with the matrix and improved the hardness of the material. The results showed that the synergistic effect of the gas phase and the condensed phase mechanism could effectively improve the flame-retardant effect. The current research results provided a new strategy for the preparation of green and low-toxicity RPUF.

Confirming the enzymatic activity and neurodevelopmental trajectory of PYCR1 mutation in one child with autosomal-recessive cutis laxa type 2.

Autosomal-recessive cutis laxa type 2 (ARCL2) is a rare genetic disorder caused by pyrroline-5-carboxylate reductase 1 (PYCR1) mutations and characterized by loose and sagging skin, typical facial features, intrauterine growth retardation, and developmental delay. To study the effect of PYCR1 mutations on protein function and clinical features, we identified a homozygous missense mutation c.559G > A (p.Ala187Thr) in PYCR1 in a Chinese child with typical clinical features, especially severe developmental delays. The three-dimensional (3D) model showed the modification of the hydrogen bonds produce a misfolding in the mutant PYCR1 protein. Mutagenesis and enzyme assay study revealed decreased activity of the mutant protein in vitro, indicating that this mutation impairs PYCR1 function. Our findings confirmed abnormal enzymatic activity and neurodevelopmental trajectory of this PYCR1 mutation.