Constructing ordered and tunable extrinsic porosity in covalent organic frameworks via water-mediated soft-template strategy.

As one of the most attractive methods for the synthesis of ordered hierarchically porous crystalline materials, the soft-template method has not appeared in covalent organic frameworks (COFs) due to the incompatibility of surfactant self-assembly and guided crystallization process of COF precursors in the organic phase. Herein, we connect the soft templates to the COF backbone through ionic bonds, avoiding their crystallization incompatibilities, thus introducing an additional ordered arrangement of soft templates into the anionic microporous COFs. The ion exchange method is used to remove the templates while maintaining the high crystallinity of COFs, resulting in the construction of COFs with ordered hierarchically micropores/mesopores, herein named OHMMCOFs (OHMMCOF-1 and OHMMCOF-2). OHMMCOFs exhibit significantly enhanced functional group accessibility and faster mass transfer rate. The extrinsic porosity can be adjusted by changing the template length, concentration, and ratio. Cationic guanidine-based COFs (OHMMCOF-3) are also constructed using the same method, which verifies the scalability of the soft-template strategy. This work provides a path for constructing ordered and tunable extrinsic porosity in COFs with greatly improved mass transfer efficiency and functional group accessibility.

Enhancement of ZT in Bi0.5Sb1.5Te3 Thin Film through Lattice Orientation Management.

Thermoelectric power can convert heat and electricity directly and reversibly. Low-dimensional thermoelectric materials, particularly thin films, have been considered a breakthrough for separating electronic and thermal transport relationships. In this study, a series of Bi0.5Sb1.5Te3 thin films with thicknesses of 0.125, 0.25, 0.5, and 1 µm have been fabricated by RF sputtering for the study of thickness effects on thermoelectric properties. We demonstrated that microstructure (texture) changes highly correlate with the growth thickness in the films, and equilibrium annealing significantly improves the thermoelectric performance, resulting in a remarkable enhancement in the thermoelectric performance. Consequently, the 0.5 µm thin films achieve an exceptional power factor of 18.1 µWcm-1K-2 at 400 K. Furthermore, we utilize a novel method that involves exfoliating a nanosized film and cutting with a focused ion beam, enabling precise in-plane thermal conductivity measurements through the 3ω method. We obtain the in-plane thermal conductivity as low as 0.3 Wm-1K-1, leading to a maximum ZT of 1.86, nearing room temperature. Our results provide significant insights into advanced thin-film thermoelectric design and fabrication, boosting high-performance systems.

Recent Advancement in Emerging MXene-Based Photocatalytic Membrane for Revolutionizing Wastewater Treatment.

MXene-based photocatalytic membranes provide significant benefits for wastewater treatment by effectively combining membrane separation and photocatalytic degradation processes. MXene represents a pioneering 2D photocatalyst with a variable elemental composition, substantial surface area, abundant surface terminations, and exceptional photoelectric performance, offering significant advantages in producing high-performance photocatalytic membranes. In this review, an in-depth overview of the latest scientific progress in MXene-based photocatalytic membranes is provided. Initially, a brief introduction to the structure and photocatalytic capabilities of MXene is provided, highlighting their pivotal role in promoting the photocatalytic process. Subsequently, in pursuit of the optimal MXene-based photocatalytic membrane, critical factors such as the morphology, hydrophilicity, and stability of MXenes are meticulously taken into account. Various preparation strategies for MXene-based photocatalytic membranes, including blending, vacuum filtration, and dip coating, are also discussed. Furthermore, the application and mechanism of MXene-based photocatalytic membranes in micropollutant removal, oil-water separation, and antibacterial are examined. Lastly, the challenges in the development and practical application of MXene-based photocatalytic membranes, as well as their future research direction are delineated.

Novel pyxinol amide derivatives bearing an aliphatic heterocycle as P-glycoprotein modulators for overcoming multidrug resistance.

P-glycoprotein (Pgp) modulators are promising agents for overcoming multidrug resistance (MDR) in cancer chemotherapy. In this study, via structural optimization of our lead compound S54 (nonsubstrate allosteric inhibitor of Pgp), 29 novel pyxinol amide derivatives bearing an aliphatic heterocycle were designed, synthesized, and screened for MDR reversal activity in KBV cells. Unlike S54, these active derivatives were shown to transport substrates of Pgp. The most potent derivative 4c exhibited promising MDR reversal activity (IC50 of paclitaxel = 8.80 ± 0.56 nM, reversal fold = 211.8), which was slightly better than that of third-generation Pgp modulator tariquidar (IC50 of paclitaxel = 9.02 ± 0.35 nM, reversal fold = 206.6). Moreover, the cytotoxicity of this derivative was 8-fold lower than that of tariquidar in human normal HK-2 cells. Furthermore, 4c blocked the efflux function of Pgp and displayed high selectivity for Pgp but had no effect on its expression and distribution. Molecular docking revealed that 4c bound preferentially to the drug-binding domain of Pgp. Overall, 4c is a promising lead compound for developing Pgp modulators.

Inflammation in alcohol-associated hepatitis: pathogenesis and therapeutic targets.

Alcohol-associated hepatitis (AH) is an acute-on-chronic liver injury that occurs in patients with chronic alcohol-associated liver disease (ALD). Patients with severe AH have high short-term mortality and lack effective pharmacological therapies. Inflammation is believed to be one of the key factors promoting AH progression and has been actively investigated as therapeutic targets over the last several decades, but no effective inflammatory targets have been identified so far. In this review, we discuss how inflammatory cells and the inflammatory mediators produced by these cells contribute to the development and progression of AH with focus on neutrophils and macrophages. The crosstalk between inflammatory cells and liver nonparenchymal cells in the pathogenesis of AH is elaborated. We also deliberate the application of recent cutting-edge technologies in characterizing liver inflammation in AH. Finally, the potential therapeutic targets of inflammatory mediators for AH are briefly summarized.

Abietane Diterpenoids from the Bark of Cryptomeria japonica and Their Antifungal Activities against Wood Decay Fungi.

Phytochemical investigation of the bark of Cryptomeria japonica led to the isolation of five new abietane diterpenoids, 5-epi-12-hydroxy-6-nor-5,6-secoabieta-8,11,13-trien-7,5-olide (1), 12-hydroxy-6ß-methoxy-6,7-secoabieta-8,11,13-trien-7,6-olide (2), 6ß,12-dihydroxy-7,8-secoabieta-8,11,13-trien-7,8-olide (4), 5,12-dihydroxy-7,8-secoabieta-8,11,13-trien-7,8-olide (5), and 5α,8-epoxy-12-hydroxy-7,8-secoabieta-8,11,13-trien-7-al (6), together with one known abietane diterpenoid, obtuanhydride (3). Their structures were elucidated by analysis of spectroscopic data and comparison with the spectral data of known analogs. At the concentration of 100 µg/mL, compounds 4, 5, and 6 inhibited antifungal activities against wood decay fungi activity by 18.7, 37.2, and 46.7%, respectively.

AIGO-DTI: Predicting Drug-Target Interactions Based on Improved Drug Properties Combined with Adaptive Iterative Algorithms.

Artificial intelligence-based methods for predicting drug-target interactions (DTIs) aim to explore reliable drug candidate targets rapidly and cost-effectively to accelerate the drug development process. However, current methods are often limited by the topological regularities of drug molecules, making them difficult to generalize to a broader chemical space. Additionally, the use of similarity to measure DTI network links often introduces noise, leading to false DTI relationships and affecting the prediction accuracy. To address these issues, this study proposes an Adaptive Iterative Graph Optimization (AIGO)-DTI prediction framework. This framework integrates atomic cluster information and enhances molecular features through the design of functional group prompts and graph encoders, optimizing the construction of DTI association networks. Furthermore, the optimization of graph structure is transformed into a node similarity learning problem, utilizing multihead similarity metric functions to iteratively update the network structure to improve the quality of DTI information. Experimental results demonstrate the outstanding performance of AIGO-DTI on multiple public data sets and label reversal data sets. Case studies, molecular docking, and existing research validate its effectiveness and reliability. Overall, the method proposed in this study can construct comprehensive and reliable DTI association network information, providing new graphing and optimization strategies for DTI prediction, which contribute to efficient drug development and reduce target discovery costs.

Encapsulation of antioxidants with colloidal lipid particles for enhancing the photooxidation stability of phytosterol in Pickering emulsions.

In order to prevent the photooxidation of phytosterols, a new type of Pickering emulsion was developed by regulating the oriented distribution of antioxidants in colloidal lipid particles (CLPs) at the oil-water interface. High-melting-point and low-melting-point lipids were tested to modulate their protective effect against phytosterols photooxidation. Results showed that CLPs could stabilize Pickering emulsion and encapsulate antioxidants, providing a dual functional delivery system for phytosterols protection. The Pickering emulsion formed had a particle size of around 350-820 nm, and the crystallization and melting temperatures of tripalmitin particles were approximately 32 °C and 63.8 °C, respectively. The addition of tributyrin or tricaprylin reduced the crystallization and melting temperatures of Pal CLPs and improved the photooxidation emulsion stability. The prepared Pickering emulsion remained stable for a maximum of 12 days under accelerated light-induced oxidation. Among all formulations, the emulsion primarily composed of tripalmitin CLPs, with added tributyrin and resveratrol, exhibited the highest photooxidation stability.

Estimating the volume of penumbra in rodents using DTI and stack-based ensemble machine learning framework.

BACKGROUND: This study investigates the potential of diffusion tensor imaging (DTI) in identifying penumbral volume (PV) compared to the standard gadolinium-required perfusion-diffusion mismatch (PDM), utilizing a stack-based ensemble machine learning (ML) approach with enhanced explainability. METHODS: Sixteen male rats were subjected to middle cerebral artery occlusion. The penumbra was identified using PDM at 30 and 90 min after occlusion. We used 11 DTI-derived metrics and 14 distance-based features to train five voxel-wise ML models. The model predictions were integrated using stack-based ensemble techniques. ML-estimated and PDM-defined PVs were compared to evaluate model performance through volume similarity assessment, the Pearson correlation analysis, and Bland-Altman analysis. Feature importance was determined for explainability. RESULTS: In the test rats, the ML-estimated median PV was 106.4 mL (interquartile range 44.6-157.3 mL), whereas the PDM-defined median PV was 102.0 mL (52.1-144.9 mL). These PVs had a volume similarity of 0.88 (0.79-0.96), a Pearson correlation coefficient of 0.93 (p < 0.001), and a Bland-Altman bias of 2.5 mL (2.4% of the mean PDM-defined PV), with 95% limits of agreement ranging from -44.9 to 49.9 mL. Among the features used for PV prediction, the mean diffusivity was the most important feature. CONCLUSIONS: Our study confirmed that PV can be estimated using DTI metrics with a stack-based ensemble ML approach, yielding results comparable to the volume defined by the standard PDM. The model explainability enhanced its clinical relevance. Human studies are warranted to validate our findings. RELEVANCE STATEMENT: The proposed DTI-based ML model can estimate PV without the need for contrast agent administration, offering a valuable option for patients with kidney dysfunction. It also can serve as an alternative if perfusion map interpretation fails in the clinical setting. KEY POINTS: • Penumbral volume can be estimated by DTI combined with stack-based ensemble ML. • Mean diffusivity was the most important feature used for predicting penumbral volume. • The proposed approach can be beneficial for patients with kidney dysfunction.

Study on plasma metabolomics profiling of depression in Chinese community-dwelling older adults based on untargeted LC/GC‒MS.

Depression is a serious psychiatric illness that causes great inconvenience to the lives of elderly individuals. However, the diagnosis of depression is somewhat subjective. Nontargeted gas chromatography (GC)/liquid chromatography (LC)-mass spectrometry (MS) was used to study the plasma metabolic profile and identify objective markers for depression and metabolic pathway variation. We recruited 379 Chinese community-dwelling individuals aged ≥ 65. Plasma samples were collected and detected by GC/LC‒MS. Orthogonal partial least squares discriminant analysis and a heatmap were utilized to distinguish the metabolites. Receiver operating characteristic curves were constructed to evaluate the diagnostic value of these differential metabolites. Additionally, metabolic pathway enrichment was performed to reveal metabolic pathway variation. According to our standard, 49 people were included in the depression cohort (DC), and 49 people age- and sex-matched individuals were included in the non-depression cohort (NDC). 64 metabolites identified via GC‒MS and 73 metabolites identified via LC‒MS had significant contributions to the differentiation between the DC and NDC, with VIP values > 1 and p values < 0.05. Three substances were detected by both methods: hypoxanthine, phytosphingosine, and xanthine. Furthermore, 1-(sn-glycero-3-phospho)-1D-myo-inositol had the largest area under the curve (AUC) value (AUC = 0.842). The purine metabolic pathway is the most important change in metabolic pathways. These findings show that there were differences in plasma metabolites between the depression cohort and the non-depression cohort. These identified differential metabolites may be markers of depression and can be used to study the changes in depression metabolic pathways.

D3S-001, a KRAS G12C inhibitor with rapid target engagement kinetics, overcomes nucleotide cycling and demonstrates robust preclinical and clinical activities.

First-generation KRAS G12C inhibitors, such as sotorasib and adagrasib, are limited by the depth and duration of clinical responses. One potential explanation for their modest clinical activity is the dynamic "cycling" of KRAS between its GDP- and GTP-bound states, raising controversy about whether targeting the GDP-bound form can fully block this oncogenic driver. We herein report D3S-001, a next generation GDP-bound G12C inhibitor with faster target engagement (TE) kinetics, depletes cellular active KRAS G12C at nanomolar concentrations. In the presence of growth factors, such as EGF and HGF, the ability of sotorasib and adagrasib to inhibit KRAS was compromised whereas the TE kinetics of D3S-001 was nearly unaffected, a unique feature differentiating D3S-001 from other GDP-bound G12C inhibitors. Furthermore, the high covalent potency and cellular TE efficiency of D3S-001 contributed to robust anti-tumor activity preclinically and translated into promising clinical activity in an ongoing phase 1 trial (NCT05410145).

How does crosstalk influence the jitter of a clock signal?

The stability and accuracy of the clock signal are crucial for the proper operation of various electronic devices and systems, as they directly impact system performance. In high-speed electronic systems, the clock signal is susceptible to interference by crosstalk. Therefore, evaluating the performance of the clock signal under crosstalk disturbance is important. Jitter, commonly used as an indicator to assess the degree of this interference, plays a significant role in this evaluation. In this paper, a method is proposed for assessing crosstalk-induced jitter (CIJ) based on scattering parameters. To verify the effectiveness of the method, CIJ was measured for clock signals with frequencies of 25, 100, and 156.25 MHz. In addition, the experimental results are well in agreement with the theoretical model. Thus, the potential application of this method is to assess the performance of circuits or electronic systems.

Small-molecule Molephantin induces apoptosis and mitophagy flux blockage through ROS production in glioblastoma.

Glioblastoma (GBM), one of the most malignant brain tumors in the world, has limited treatment options and a dismal survival rate. Effective and safe disease-modifying drugs for glioblastoma are urgently needed. Here, we identified a small molecule, Molephantin (EM-5), effectively penetrated the blood-brain barrier (BBB) and demonstrated notable antitumor effects against GBM with good safety profiles both in vitro and in vivo. Mechanistically, EM-5 not only inhibits the proliferation and invasion of GBM cells but also induces cell apoptosis through the reactive oxygen species (ROS)-mediated PI3K/Akt/mTOR pathway. Furthermore, EM-5 causes mitochondrial dysfunction and blocks mitophagy flux by impeding the fusion of mitophagosomes with lysosomes. It is noteworthy that EM-5 does not interfere with the initiation of autophagosome formation or lysosomal function. Additionally, the mitophagy flux blockage caused by EM-5 was driven by the accumulation of intracellular ROS. In vivo, EM-5 exhibited significant efficacy in suppressing tumor growth in a xenograft model. Collectively, our findings not only identified EM-5 as a promising, effective, and safe lead compound for treating GBM but also uncovered its underlying mechanisms from the perspective of apoptosis and mitophagy.

Environmental DNA-based biodiversity profiling along the Houdong River in north-eastern Taiwan.

Background: This paper describes two datasets: species occurrences, which were determined by environmental DNA (eDNA) metabarcoding and their associated DNA sequences, originating from a research project which was carried out along the Houdong River (), Jiaoxi Township, Yilan, Taiwan. The Houdong River begins at an elevation of 860 m and flows for approximately 9 km before it empties into the Pacific Ocean. Meandering through mountains, hills, plains and alluvial valleys, this short river system is representative of the fluvial systems in Taiwan. The primary objective of this study was to determine eukaryotic species occurrences in the riverine ecosystem through the use of the eDNA analysis. The second goal was, based on the current dataset, to establish a metabarcoding eDNA data template that will be useful and replicable for all users, particularly the Taiwan community. The species occurrence data are accessible at the Global Biodiversity Information Facility (GBIF) portal and its associated DNA sequences have been deposited in the European Nucleotide Archive (ENA) at EMBL-EBI, respectively. A total of 12 water samples from the study yielded an average of 1.5 million reads. The subsequent species identification from the collected samples resulted in the classification of 432 Operational Taxonomic Units (OTUs) out of a total of 2,734. Furthermore, a total of 1,356 occurrences with taxon matches in GBIF were documented (excluding 4,941 incertae sedis, accessed 05-12-2023). These data will be of substantial importance for future species and habitat monitoring within the short river, such as assessment of biodiversity patterns across different elevations, zonations and time periods and its correlation to water quality, land uses and anthropogenic activities. Further, these datasets will be of importance for regional ecological studies, in particular the freshwater ecosystem and its status in the current global change scenarios. New information: The datasets are the first species diversity description of the Houdong River system using either eDNA or traditional monitoring processes.

Carbon Corrosion Induced by Surface Defects Accelerates Degradation of Platinum/Graphene Catalysts in Oxygen Reduction Reaction.

Graphene supported electrocatalysts have demonstrated remarkable catalytic performance for oxygen reduction reaction (ORR). However, their durability and cycling performance are greatly limited by Oswald ripening of platinum (Pt) and graphene support corrosion. Moreover, comprehensive studies on the mechanisms of catalysts degradation under 0.6-1.6 V versus RHE (Reversible Hydrogen Electrode) is still lacking. Herein, degradation mechanisms triggered by different defects on graphene supports are investigated by two cycling protocols. In the start-up/shutdown cycling (1.0-1.6 V vs. RHE), carbon oxidation reaction (COR) leads to shedding or swarm-like aggregation of Pt nanoparticles (NPs). Theoretical simulation results show that the expansion of vacancy defects promotes reaction kinetics of the decisive step in COR, reducing its reaction overpotential. While under the load cycling (0.6-1.0 V vs. RHE), oxygen containing defects lead to an elevated content of Pt in its oxidation state which intensifies Oswald ripening of Pt. The presence of vacancy defects can enhance the transfer of electrons from graphene to the Pt surface, reducing the d-band center of Pt and making it more difficult for the oxidation state of platinum to form in the cycling. This work will provide comprehensive understanding on Pt/Graphene catalysts degradation mechanisms.

Research on disease diagnosis based on teacher-student network and Raman spectroscopy.

Diabetic nephropathy is a serious complication of diabetes, and primary Sjögren's syndrome is a disease that poses a major threat to women's health. Therefore, studying these two diseases is of practical significance. In the field of spectral analysis, although common Raman spectral feature selection models can effectively extract features, they have the problem of changing the characteristics of the original data. The teacher-student network combined with Raman spectroscopy can perform feature selection while retaining the original features, and transfer the performance of the complex deep neural network structure to another lightweight network structure model. This study selects five flow learning models as the teacher network, builds a neural network as the student network, uses multi-layer perceptron for classification, and selects the optimal features based on the evaluation indicators accuracy, precision, recall, and F1-score. After five-fold cross-validation, the research results show that in the diagnosis of diabetic nephropathy, the optimal accuracy rate can reach 98.3%, which is 14.02% higher than the existing research; in the diagnosis of primary Sjögren's syndrome, the optimal accuracy rate can be reached 100%, which is 10.48% higher than the existing research. This study proved the feasibility of Raman spectroscopy combined with teacher-student network in the field of disease diagnosis by producing good experimental results in the diagnosis of diabetic nephropathy and primary Sjögren's syndrome.

The cementless taper wedge vs. fit-and-fill stem in primary total hip arthroplasty: risk of stem-related complication differs across Dorr types.

INTRODUCTION: The choice between a cementless taper wedge stem and a fit-and-fill stem in total Hip arthroplasty (THA) for various proximal femoral morphological types has not been thoroughly evaluated. This study aimed to compare the risk of stem-related complications between these two stem types in Dorr type A, B, and C femurs. MATERIALS AND METHODS: From January 2015 through April 2021, we retrospectively reviewed 1995 cementless THA procedures. We stratified all procedures into three groups: Dorr type A (N = 360, 18.0%), B (N = 1489, 74.7%) and C (N = 146, 7.3%). The primary outcome domain was stem-related complications, including stem subsidence ≥ 3 mm, intraoperative fracture, periprosthetic fracture and aseptic stem loosening. We performed multivariate regression analysis to compare the risk of stem-related complication between the two stem types. Other factors included age, sex, body mass index, diagnosis, age-adjusted Charlson comorbidity index, stem alignment and canal fill ratio. RESULTS: The incidence of stem-related complications in the taper wedge and fit-and-fill stem groups was 4.4% (N = 15) and 6.5% (N = 107), respectively. Fit-and-fill stems showed an increased risk of stem-related complications (aOR: 9.903, 95% CI: 1.567-62.597) only in Dorr type C femurs. No significant difference in risk was observed in Dorr type A and B femurs. Furthermore, the canal fill ratio at the lesser trochanter, 2 cm and 7 cm below the lesser trochanter, did not exhibit an association with stem-related complications in any Dorr type. CONCLUSIONS: Concerning the risk of stem-related complications, the taper wedge stem was a better choice in Dorr type C femurs. However, there was no difference in risk between the taper wedge stem and fit-and-fill stem in Dorr type A and B femurs.

Mycobacterium tuberculosis Infection in School Contacts of Tuberculosis Cases: A Systematic Review and Meta-Analysis.

Substantial tuberculosis transmission occurs outside of households, and tuberculosis surveillance in schools has recently been proposed. However, the yield of tuberculosis outcomes from school contacts is not well characterized. We assessed the prevalence of Mycobacterium tuberculosis infection among close school contacts by performing a systematic review. We searched PubMed, Elsevier, China National Knowledge Infrastructure, and Wanfang databases. Studies reporting the number of children who were tested overall and who tested positive were included. Subgroup analyses were performed by study location, index case bacteriological status, type of school, and other relevant factors. In total, 28 studies including 54,707 school contacts screened for M. tuberculosis infection were eligible and included in the analysis. Overall, the prevalence of M. tuberculosis infection determined by the QuantiFERON Gold in-tube test was 33.2% (95% CI, 0.0-73.0%). The prevalences of M. tuberculosis infection based on the tuberculin skin test (TST) using 5 mm, 10 mm, and 15 mm as cutoffs were 27.2% (95% CI, 15.1-39.3%), 24.3% (95% CI, 15.3-33.4%), and 12.7% (95% CI, 6.3-19.0%), respectively. The pooled prevalence of M. tuberculosis infection (using a TST ≥5-mm cutoff) was lower in studies from China (22.8%; 95% CI, 16.8-28.8%) than other regions (36.7%; 95% CI, 18.1-55.2%). The pooled prevalence of M. tuberculosis infection was higher when the index was bacteriologically positive (43.6% [95% CI, 16.5-70.8%] versus 23.8% [95% CI, 16.2-31.4%]). These results suggest that contact investigation and general surveillance in schools from high-burden settings merit consideration as means to improve early case detection in children.

Trends in exposure to drugs and prohibited substances among sports: A nationwide analysis of 2008-2022 inquiry records.

To prevent athletes from unintentional doping, the anti-doping authorities in Taiwan have launched several sports-prohibited substances inquiry services since 2008. This study aimed to enhance the prevention of sports-prohibited substance misuse by analyzing data collected from major nationwide service systems, enabling the identification of trends in athletes' exposure to drugs and prohibited substances. The study collected over 30,000 data points from three major national anti-doping inquiry systems, spanning from 2008 to 2022. The information of the users consulted products, prohibited substances, and sports disciplines in the data were calculated and categorized. The usage of inquiry systems has shown an increasing trend from 2008 to 2022. Athletes comprised the majority of users (> 40%), significantly outnumbering other user groups (all below 20%). Among the inquiries, Western medicine accounted for the highest percentage (up to 79.6%), and it also contained the majority of the prohibited substances. Interestingly, traditional Chinese medicines had a higher chance (35.9%) of containing prohibited substances, as indicated by the mobile application. The prohibited substances mainly belonged to class S6 stimulants and S9 glucocorticoids. Among the daily medicinal products and nutritional supplements encountered by sports personnel, approximately 30% of them were found to contain prohibited substances. Future educational efforts should focus on raising awareness about traditional Chinese medicines and drugs for the common cold, ADHD, and pain relief, as well as their regulation, to prevent the misuse of prohibited substances.

Endogenous mutant Huntingtin alters the corticogenesis via lowering Golgi recruiting ARF1 in cortical organoid.

Pathogenic mutant huntingtin (mHTT) infiltrates the adult Huntington's disease (HD) brain and impairs fetal corticogenesis. However, most HD animal models rarely recapitulate neuroanatomical alterations in adult HD and developing brains. Thus, the human cortical organoid (hCO) is an alternative approach to decode mHTT pathogenesis precisely during human corticogenesis. Here, we replicated the altered corticogenesis in the HD fetal brain using HD patient-derived hCOs. Our HD-hCOs had pathological phenotypes, including deficient junctional complexes in the neural tubes, delayed postmitotic neuronal maturation, dysregulated fate specification of cortical neuron subtypes, and abnormalities in early HD subcortical projections during corticogenesis, revealing a causal link between impaired progenitor cells and chaotic cortical neuronal layering in the HD brain. We identified novel long, oriented, and enriched polyQ assemblies of HTTs that hold large flat Golgi stacks and scaffold clathrin+ vesicles in the neural tubes of hCOs. Flat Golgi stacks conjugated polyQ assemblies by ADP-ribosylation factor 1 (ARF1). Inhibiting ARF1 activation with Brefeldin A (BFA) disassociated polyQ assemblies from Golgi. PolyQ assembles with mHTT scaffolded fewer ARF1 and formed shorter polyQ assembles with fewer and shorter Golgi and clathrin vesicles in neural tubes of HD-hCOs compared with those in hCOs. Inhibiting the activation of ARF1 by BFA in healthy hCOs replicated impaired junctional complexes in the neural tubes. Together, endogenous polyQ assemblies with mHTT reduced the Golgi recruiting ARF1 in the neuroepithelium, impaired the Golgi structure and activities, and altered the corticogenesis in HD-hCO.