Forkhead box M1 mediates metabolic reprogramming in human colorectal cancer cells.

Metabolic reprogramming is recognized as a hallmark of cancer, enabling cancer cells to acquire essential biomolecules for cell growth, often characterized by upregulated glycolysis and/or fatty acid synthesis-related genes. The transcription factor forkhead box M1 (FOXM1) has been implicated in various cancers, contributing significantly to their development, including colorectal cancer (CRC), a major global health concern. Despite FOXM1's established role in cancer, its specific involvement in the Warburg effect and fatty acid biosynthesis in CRC remains unclear. We analyzed The Cancer Genome Atlas (TCGA) Colonic Adenocarcinoma and Rectal Adenocarcinoma (COADREAD) datasets to to derive the correlation of the expression levels between FOXM1 and multiple genes and the survival prognosis based on FOXM1 expression. Using two human CRC cell lines, HT29 and HCT116, we conducted RNAi or plasmid transfection procedures, followed by a series of assays, including RNA extraction, quantitative real-time polymerase chain reaction, Western blot analysis, cell metabolic assays, and immunofluorescence analysis. Higher expression levels of FOXM1 correlated with a poorer survival prognosis, and the expression of FOXM1 was positively correlated with glycolysis-related genes SLC2A1 and LDHA, de novo lipogenesis-related genes ACACA and FASN, and MYC. FOXM1 appeared to modulate AKT/mTOR signaling, the expression of c-Myc, proteins related to glycolysis and fatty acid biosynthesis, as well as extracellular acidification rate in HT29 and HCT116 cells. In summary, FOXM1 plays a regulatory role in glycolysis, fatty acid biosynthesis, and cellular energy consumption, thereby influencing CRC cell growth and patient prognosis.

Targeting CK1δ and CK1ε as a new therapeutic approach for clear cell renal cell carcinoma.

INTRODUCTION: Kidney cancer ranks as the ninth most common cancer in men and the fourteenth in women globally, with renal cell carcinoma (RCC) being the most prevalent type. Despite advances in therapeutic strategies targeting angiogenesis and immune checkpoints, the absence of reliable markers for patient selection and limited duration of disease control underline the need for innovative approaches. CK1δ and CK1ε are highly conserved serine/threonine kinases involved in cell cycle regulation, apoptosis, and circadian rhythm. While CK1δ dysregulation is reportedly associated with breast and bladder cancer progression, their role in RCC remains elusive. This study aims to investigate the feasibility of CK1δ/ε as new therapeutic targets for RCC patients. METHODS: The relationship between CK1δ/ε and RCC progression was evaluated by the analysis of microarray dataset and TCGA database. The anticancer activity of CK1δ/ε inhibitor was examined by MTT/SRB assay , and apoptotic cell death was analyzed by flow cytometry and western blotting. RESULTS: Our data demonstrate that the gene expression of CSNK1D and CSNK1E is significantly higher in clear cell RCC (ccRCC) tissues compared to normal kidney samples, which is correlated with lower survival rates in ccRCC patients. SR3029, a selective inhibitor targeting CK1δ/ε, significantly suppresses the viability and proliferation of ccRCC cell lines regardless of the status of VHL deficiency. Importantly, the inhibitor promotes the population of subG1 cells and induces apoptosis, and ectopically expression of CK1δ partially rescued SR3029-induced apoptosis in ccRCC cells. CONCLUSION: These findings underscore the crucial role of CK1δ and CK1ε in ccRCC progression, suggesting CK1δ/ε inhibitors as new therapeutic options for ccRCC patients.

Dynamic assemblies of parvalbumin interneurons in brain oscillations.

Brain oscillations are crucial for perception, memory, and behavior. Parvalbumin-expressing (PV) interneurons are critical for these oscillations, but their population dynamics remain unclear. Using voltage imaging, we simultaneously recorded membrane potentials in up to 26 PV interneurons in vivo during hippocampal ripple oscillations in mice. We found that PV cells generate ripple-frequency rhythms by forming highly dynamic cell assemblies. These assemblies exhibit rapid and significant changes from cycle to cycle, varying greatly in both size and membership. Importantly, this variability is not just random spiking failures of individual neurons. Rather, the activities of other PV cells contain significant information about whether a PV cell spikes or not in a given cycle. This coordination persists without network oscillations, and it exists in subthreshold potentials even when the cells are not spiking. Dynamic assemblies of interneurons may provide a new mechanism to modulate postsynaptic dynamics and impact cognitive functions flexibly and rapidly.

Do low skeletal muscle bulk and disturbed body fat mass impact tumor recurrence in stage I/II HCC undergoing surgery? An observational cohort study.

INTRODUCTION: The influence of deranged body composition on stage I/II HCC after surgery remains undetermined. The current study aimed to investigate the impact of low skeletal muscle bulk and disturbed body fat mass on the recurrence outcome of stage I/II HCC patients undergoing liver resection. The associated metabolomic alterations were also assessed. METHODS: From 2012 to 2021, stage I and II HCC patients who underwent liver resection at our institute were retrospectively reviewed. Their preoperative body composition including skeletal muscle mass and body fat volume was measured by computed tomography (CT). The recurrence outcome was recorded and analyzed. The preoperative serum was collected and subjected to metabolomic analysis. RESULTS: A total of 450 stage I and II HCC patients were included in the current study. Among them, 76% were male and around 60% had HBV infection. After stratified by normal cutoff values obtained from a healthy cohort, 6.4% of stage I/II HCC patients were found to have a low psoas muscle index (PMI), 17.8% a high subcutaneous adipose tissue (SAT) index, and 27.8% a high visceral adipose tissue (VAT) index. Cox regression multivariate analysis further demonstrated that low PMI and high SAT index were independent prognostic factors for time-to-recurrence (TTR) after surgery. Metabolomic analysis discovered that free fatty acid ß-oxidation was enhanced in with low PMI or high SAT index. CONCLUSION: The current study demonstrated that reduced psoas muscle mass may impair while elevated SAT may prolong the TTR of stage I/II HCC patients undergoing liver resections. VAT, on the other hand, was not associated with recurrence outcome after surgery. Further studies are warranted to validate our findings.

Emergency room visits (ERVs) among occupational groups associated with ambient conditions in Taiwan.

OBJECTIVE: This population-based study explored emergency room visits (ERVs) from all-causes, circulatory and respiratory diseases among different occupational groups in Taiwan associated with ambient average temperature. METHOD: Daily area-age-sex specific ERVs records were obtained from the Taiwan's Ministry of Health and Welfare from 2009 to 2018. Distributed lag-nonlinear model (DLNM) was used to estimate the exposure-response relationships between daily average temperature and ERVs for all-causes, circulatory and respiratory diseases by occupational groups. Random-effects meta-analysis was used to pool the overall cumulative relative risk (RR) and 95% confidence interval (CI). RESULTS: The exposure-response curves showed ERVs of all-cause and respiratory diseases increased with rising temperature across all occupational groups. These effects were consistently stronger among younger (20-64 years old) and outdoor workers. In contrast, ERVs risk from circulatory diseases increased significantly during cold snaps, with a substantially higher risk for female workers. Interestingly, female workers, regardless of indoor or outdoor work, consistently showed a higher risk of respiratory ERVs during hot weather compared to males. Younger workers (20-64 years old) exhibited a higher risk of ERVs, likely due to job profiles with greater exposure to extreme temperatures. Notably, the highest risk of all-causes ERVs was observed in outdoor male laborers (union members), followed by farmers and private employees, with the lowest risk among indoor workers. Conversely, female indoor workers and female farmers faced the highest risk of respiratory ERVs. Again, female farmers with consistent outdoor exposure had the highest risk of circulatory ERVs during cold conditions. CONCLUSION: Our findings highlighted the complexity of temperature-related health risks associated with different occupational contexts. The population-level insights into vulnerable occupational groups could provide valuable comprehension for policymakers and healthcare practitioners.

Oriented Antibody Coupling to an Antifouling Polymer Using Glycan Remodeling for Biosensing by Particle Motion.

Biosensors based on immobilized antibodies require molecular strategies that (i) couple the antibodies in a stable fashion while maintaining the conformation and functionality, (ii) give outward orientation of the paratope regions of the antibodies for good accessibility to analyte molecules in the biofluid, and (iii) surround the antibodies by antibiofouling molecules. Here, we demonstrate a method to achieve oriented coupling of antibodies to an antifouling poly(l-lysine)-grafted-poly(ethylene glycol) (PLL-g-PEG) substrate, using glycan remodeling to create antibody-DNA conjugates. The coupling, orientation, and functionality of the antibodies were studied using two analysis methods with single-molecule resolution, namely single-molecule localization microscopy and continuous biosensing by particle motion. The biosensing functionality of the glycan-remodeled antibodies was demonstrated in a sandwich immunosensor for procalcitonin. The results show that glycan-remodeled antibodies enable oriented immobilization and biosensing functionality with low nonspecific binding on antifouling polymer substrates.

Maryland's Global Budget Revenue Payment Model and Shifts in the Surgical Site of Care Among Medicare Beneficiaries.

OBJECTIVE: To assess the association between the Global Budget Revenue (GBR) payment model and shifts to the outpatient setting for surgical procedures among Medicare fee-for-service beneficiaries in Maryland versus control states. SUMMARY BACKGROUND DATA: The GBR model provides fixed global payments to hospitals to reduce spending growth and incentivize hospitals to reduce the costs of care while improving care quality. Since surgical care is a major contributor to hospital spending, the GBR model might accelerate the ongoing shift from the inpatient to the outpatient setting to generate additional savings. METHODS: A difference-in-differences (DiD) design was used to compare changes in surgical care settings over time from pre-GBR (2011-2013) to post-GBR (2014-2018) for Maryland versus control states for common surgeries that could be performed in the outpatient setting. A cross-sectional approach was used to compare the difference in care settings in 2018 for total knee arthroplasty which was on Medicare's Inpatient-Only List before then. RESULTS: We studied 47,542 surgical procedures from 44,410 beneficiaries in Maryland and control states. GBR's 2014 implementation was associated with an acceleration in the shift from inpatient to outpatient settings for surgical procedures in Maryland (DiD: 3.9 percentage points, 95% CI: 2.3, 5.4). Among patients undergoing total knee arthroplasty in 2018, the proportion of outpatient surgeries in Maryland was substantially higher than that in control states (difference: 27.6 percentage points, 95% CI: 25.6, 29.6). CONCLUSIONS: Implementing Maryland's GBR payment model was associated with an acceleration in the shift from inpatient to outpatient hospital settings for surgical procedures.

A new tau dephosphorylation-targeting chimera for the treatment of tauopathies.

Abnormal accumulation of hyperphosphorylated tau protein plays a pivotal role in a collection of neurodegenerative diseases named tauopathies, including Alzheimer's disease (AD). We have recently conceptualized the design of hetero-bifunctional chimeras for selectively promoting the proximity between tau and phosphatase, thus specifically facilitating tau dephosphorylation and removal. Here, we sought to optimize the construction of tau dephosphorylating-targeting chimera (DEPTAC) and obtained a new chimera D14, which had high efficiency in reducing tau phosphorylation both in cell and tauopathy mouse models, while showing limited cytotoxicity. Moreover, D14 ameliorated neurodegeneration in primary cultured hippocampal neurons treated with toxic tau-K18 fragments, and improved cognitive functions of tauopathy mice. These results suggested D14 as a cost-effective drug candidate for the treatment of tauopathies.

Rest-Activity Rhythm Differences in Acute Rehabilitation Between Poststroke Patients and Non-Brain Disease Controls: Comparative Study.

BACKGROUND: Circadian rhythm disruptions are a common concern for poststroke patients undergoing rehabilitation and might negatively impact their functional outcomes. OBJECTIVE: Our research aimed to uncover unique patterns and disruptions specific to poststroke rehabilitation patients and identify potential differences in specific rest-activity rhythm indicators when compared to inpatient controls with non-brain-related lesions, such as patients with spinal cord injuries. METHODS: We obtained a 7-day recording with a wearable actigraphy device from 25 poststroke patients (n=9, 36% women; median age 56, IQR 46-71) and 25 age- and gender-matched inpatient control participants (n=15, 60% women; median age 57, IQR 46.5-68.5). To assess circadian rhythm, we used a nonparametric method to calculate key rest-activity rhythm indicators-relative amplitude, interdaily stability, and intradaily variability. Relative amplitude, quantifying rest-activity rhythm amplitude while considering daily variations and unbalanced amplitudes, was calculated as the ratio of the difference between the most active 10 continuous hours and the least active 5 continuous hours to the sum of these 10 and 5 continuous hours. We also examined the clinical correlations between rest-activity rhythm indicators and delirium screening tools, such as the 4 A's Test and the Barthel Index, which assess delirium and activities of daily living. RESULTS: Patients who had a stroke had higher least active 5-hour values compared to the control group (median 4.29, IQR 2.88-6.49 vs median 1.84, IQR 0.67-4.34; P=.008). The most active 10-hour values showed no significant differences between the groups (stroke group: median 38.92, IQR 14.60-40.87; control group: median 31.18, IQR 18.02-46.84; P=.93). The stroke group presented a lower relative amplitude compared to the control group (median 0.74, IQR 0.57-0.85 vs median 0.88, IQR 0.71-0.96; P=.009). Further analysis revealed no significant differences in other rest-activity rhythm metrics between the two groups. Among the patients who had a stroke, a negative correlation was observed between the 4 A's Test scores and relative amplitude (ρ=-0.41; P=.045). Across all participants, positive correlations emerged between the Barthel Index scores and both interdaily stability (ρ=0.34; P=.02) and the most active 10-hour value (ρ=0.42; P=.002). CONCLUSIONS: This study highlights the relevance of circadian rhythm disruptions in poststroke rehabilitation and provides insights into potential diagnostic and prognostic implications for rest-activity rhythm indicators as digital biomarkers.

Genetic Risk Loci and Familial Associations in Migraine: A Genome-Wide Association Study in the Han Chinese Population of Taiwan.

BACKGROUND AND PURPOSE: Migraine is a condition that is often observed to run in families, but its complex genetic background remains unclear. This study aimed to identify the genetic factors influencing migraines and their potential association with the family medical history. METHODS: We performed a comprehensive genome-wide association study of a cohort of 1,561 outpatients with migraine and 473 individuals without migraine in Taiwan, including Han Chinese individuals with or without a family history of migraine. By analyzing the detailed headache history of the patients and their relatives we aimed to isolate potential genetic markers associated with migraine while considering factors such as sex, episodic vs. chronic migraine, and the presence of aura. RESULTS: We revealed novel genetic risk loci, including rs2287637 in DEAD-Box helicase 1 and long intergenic non-protein coding RNA 1804 and rs12055943 in engulfment and cell motility 1, that were correlated with the family history of migraine. We also found a genetic location downstream of mesoderm posterior BHLH transcription factor 2 associated with episodic migraine, whereas loci within the ubiquitin-specific peptidase 26 exonic region, dual specificity phosphatase 9 and pregnancy-upregulated non-ubiquitous CaM kinase intergenic regions, and poly (ADP-ribose) polymerase 1 and STUM were linked to chronic migraine. We additionally identified genetic regionsassociated with the presence or absence of aura. A locus between LINC02561 and urocortin 3 was predominantly observed in female patients. Moreover, three different single-nucleotide polymorphisms were associated with the family history of migraine in the control group. CONCLUSIONS: This study has identified new genetic locations associated with migraine and its family history in a Han Chinese population, reinforcing the genetic background of migraine. The findings point to potential candidate genes that should be investigated further.

Optimizing immunofluorescence with high-dynamic-range imaging to enhance PD-L1 expression evaluation for 3D pathology assessment from NSCLC tumor tissue.

Assessing programmed death ligand 1 (PD-L1) expression through immunohistochemistry (IHC) is the golden standard in predicting immunotherapy response of non-small cell lung cancer (NSCLC). However, observation of heterogeneous PD-L1 distribution in tumor space is a challenge using IHC only. Meanwhile, immunofluorescence (IF) could support both planar and three-dimensional (3D) histological analyses by combining tissue optical clearing with confocal microscopy. We optimized clinical tissue preparation for the IF assay focusing on staining, imaging, and post-processing to achieve quality identical to traditional IHC assay. To overcome limited dynamic range of the fluorescence microscope's detection system, we incorporated a high dynamic range (HDR) algorithm to restore the post imaging IF expression pattern and further 3D IF images. Following HDR processing, a noticeable improvement in the accuracy of diagnosis (85.7%) was achieved using IF images by pathologists. Moreover, 3D IF images revealed a 25% change in tumor proportion score for PD-L1 expression at various depths within tumors. We have established an optimal and reproducible process for PD-L1 IF images in NSCLC, yielding high quality data comparable to traditional IHC assays. The ability to discern accurate spatial PD-L1 distribution through 3D pathology analysis could provide more precise evaluation and prediction for immunotherapy targeting advanced NSCLC.

Exploring keratin composition variability for sustainable thermal insulator design.

In pursuing sustainable thermal insulation solutions, this study explores the integration of human hair and feather keratin with alginate. The aim is to assess its potential in thermal insulation materials, focusing on the resultant composites' thermal and mechanical characteristics. The investigation uncovers that the type and proportion of keratin significantly influence the composites' porosity and thermal conductivity. Specifically, higher feather keratin content is associated with lesser sulfur and reduced crosslinking due to shorter amino acids, leading to increased porosity and pore sizes. This, in turn, results in a decrease in ß-structured hydrogen bond networks, raising non-ordered protein structures and diminishing thermal conductivity from 0.044 W/(m·K) for pure alginate matrices to between 0.033 and 0.038 W/(m·K) for keratin-alginate composites, contingent upon the specific ratio of feather to hair keratin used. Mechanical evaluations further indicate that composites with a higher ratio of hair keratin exhibit an enhanced compressive modulus, ranging from 60 to 77 kPa, demonstrating the potential for tailored mechanical properties to suit various applications. The research underscores the critical role of sulfur content and the crosslinking index within keratin's structures, significantly impacting the thermal and mechanical properties of the matrices. The findings position keratin-based composites as environmentally friendly alternatives to traditional insulation materials.

Key risk factors and adverse outcomes in metachronous vertebral osteomyelitis following periprosthetic joint infection: A 5-year retrospective study.

Purpose: Periprosthetic joint infection (PJI) is a leading cause of joint arthroplasty failure, potentially leading to critical complications like vertebral osteomyelitis (VO). The factors contributing to VO after PJI and the outcomes for these patients are not well understood. Our study aims to (1) identify risk factors for VO following PJI and (2) assess the clinical outcomes in these cases. Methods: We included PJI patients treated surgically at our centre from January 2006 to December 2020, excluding those with simultaneous VO post-PJI. Our focus was on patients with VO occurring after PJI, monitored for at least 5 years. Analysis included patient comorbidities, PJI treatment approaches, pathogen identification and clinical outcomes. Results: Of 1701 PJI cases, 21 (1.23%) developed VO. Key risk factors for VO post-PJI were identified: systemic inflammatory response syndrome, substance misuse, polymicrobial infection and undergoing at least three stages of resection arthroplasty (odds ratios: 1.86, 54.28, 52.33 and 31.88, respectively). Adverse outcomes were noted in VO patients, with recurrent VO in 6/21 and repeated PJIs in 18/21 cases. Conclusions: Patients with PJI, especially those with certain risk factors, have an increased likelihood of developing VO and encountering negative outcomes. The potential role of bacteremia in the development of VO after PJI needs further exploration. Level of Evidence: Level III.

[Diagnostic Value of Ultrasound for Thyroid Nodules With a Spoke-Wheel Blood Flow Pattern].

Objective To explore the diagnostic value of ultrasound for thyroid nodules with a spoke-wheel blood flow pattern.Methods The clinical data of the patients with thyroid nodules presenting a spoke-wheel blood flow pattern examined by ultrasound were collected,and the gray-scale ultrasound features of the nodules were recorded.The diagnostic performance of the Thyroid Imaging Reporting and Data System by American College of Radiology (ACR TI-RADS),Chinese Thyroid Imaging Reporting and Data System (C-TIRADS),and combined specific indicators for the thyroid nodules with a spoke-wheel blood flow pattern was evaluated by comparison with the pathological results,which was regarded as the gold standard.Results A total of 64 patients with thyroid nodules were finally included,including 47 patients with malignant nodules and 17 patients with benign nodules.In addition to the general ultrasound features,central scar mostly appeared in malignant nodules (χ2=5.968,P=0.015),while central coarse calcification was more common in benign nodules (χ2=10.899,P=0.001).After the combination of central scar and central gross calcification,the diagnostic performance of ACR TI-RADS and C-TIRADS was improved (both P<0.001).Conclusions When the thyroid nodule shows a spoke-wheel blood flow pattern,one should be cautious of the possibility of malignancy.Combining central scar and central coarse calcification can improve the accuracy of ultrasonic diagnosis.

Risk factors and crucial prognostic indicators of mortality in liver transplant recipients with bloodstream infections: A comprehensives study of 1049 consecutive liver transplants over an 11-year period.

BACKGROUND: Liver transplantation (LT) is a pivotal treatment for end-stage liver disease. However, bloodstream infections (BSI) in the post-operative period present a significant threat to patient survival. This study aims to identify risk factors for post-LT BSI and crucial prognostic indicators for mortality among affected patients. METHODS: We conducted a retrospective study of adults diagnosed with end-stage liver disease who underwent their initial LT between 2010 and 2021. Those who developed BSI post-LT during the same hospital admission were classified into the BSI group. RESULTS: In this cohort of 1049 patients, 89 (8.4%) developed BSI post-LT, while 960 (91.5%) did not contract any infection. Among the BSI cases, 17 (19.1%) patients died. The average time to BSI onset was 48 days, with 46% occurring within the first month post-LT. Of the 123 isolated microorganisms, 97 (78.8%) were gram-negative bacteria. BSI patients had significantly longer stays in the intensive care unit and hospital compared to non-infected patients. The 90-day and in-hospital mortality rates for recipients with BSI were significantly higher than those without infections. Multivariate analysis indicated heightened BSI risk in patients with blood loss >3000 mL during LT (odds ratio [OR] 2.128), re-operation within 30 days (OR 2.341), post-LT bile leakage (OR 3.536), and graft rejection (OR 2.194). Additionally, chronic kidney disease (OR 6.288), each 1000 mL increase in intraoperative blood loss (OR 1.147) significantly raised mortality risk in BSI patients, whereas each 0.1 mg/dL increase in albumin levels correlated with a lower risk of death from BSI (OR 0.810). CONCLUSIONS: This study underscores the need for careful monitoring and management in the post-LT period, especially for patients at higher risk of BSI. It also suggests that serum albumin levels could serve as a valuable prognostic indicator for outcomes in LT recipients experiencing BSI.

Quantification of Resection Margin following Sublobar Resection in Lung Cancer Patients through Pre- and Post-Operative CT Image Comparison: Utilizing a CT-Based 3D Reconstruction Algorithm.

Sublobar resection has emerged as a standard treatment option for early-stage peripheral non-small cell lung cancer. Achieving an adequate resection margin is crucial to prevent local tumor recurrence. However, gross measurement of the resection margin may lack accuracy due to the elasticity of lung tissue and interobserver variability. Therefore, this study aimed to develop an objective measurement method, the CT-based 3D reconstruction algorithm, to quantify the resection margin following sublobar resection in lung cancer patients through pre- and post-operative CT image comparison. An automated subvascular matching technique was first developed to ensure accuracy and reproducibility in the matching process. Following the extraction of matched feature points, another key technique involves calculating the displacement field within the image. This is particularly important for mapping discontinuous deformation fields around the surgical resection area. A transformation based on thin-plate spline is used for medical image registration. Upon completing the final step of image registration, the distance at the resection margin was measured. After developing the CT-based 3D reconstruction algorithm, we included 12 cases for resection margin distance measurement, comprising 4 right middle lobectomies, 6 segmentectomies, and 2 wedge resections. The outcomes obtained with our method revealed that the target registration error for all cases was less than 2.5 mm. Our method demonstrated the feasibility of measuring the resection margin following sublobar resection in lung cancer patients through pre- and post-operative CT image comparison. Further validation with a multicenter, large cohort, and analysis of clinical outcome correlation is necessary in future studies.

Neuromorphic Computing with Emerging Antiferromagnetic Ordering in Spin-Orbit Torque Devices.

Field-free switching (FFS) and spin-orbit torque (SOT)-based neuromorphic characteristics were realized in a W/Pt/Co/NiO/Pt heterostructure with a perpendicular exchange bias (HEB) for brain-inspired neuromorphic computing (NC). Experimental results using NiO-based SOT devices guided the development of fully spin-based artificial synapses and sigmoidal neurons for implementation in a three-layer artificial neural network. This system achieved impressive accuracies of 91-96% when applied to the Modified National Institute of Standards and Technology (MNIST) image data set and 78.85-81.25% when applied to Fashion MNIST images, due presumably to the emergence of robust NiO antiferromagnetic (AFM) ordering. The emergence of AFM ordering favored the FFS with an enhanced HEB, which suppressed the memristivity and reduced the recognition accuracy. This indicates a trade-off between the requirements for solid-state memory and those required for brain-inspired NC devices. Nonetheless, our findings revealed opportunities by which the two technologies could be aligned via controllable exchange coupling.

Cep57 regulates human centrosomes through multivalent interactions.

Human Cep57 is a coiled-coil scaffold at the pericentriolar matrix (PCM), controlling centriole duplication and centrosome maturation for faithful cell division. Genetic truncation mutations of Cep57 are associated with the mosaic-variegated aneuploidy (MVA) syndrome. During interphase, Cep57 forms a complex with Cep63 and Cep152, serving as regulators for centrosome maturation. However, the molecular interplay of Cep57 with these essential scaffolding proteins remains unclear. Here, we demonstrate that Cep57 undergoes liquid-liquid phase separation (LLPS) driven by three critical domains (NTD, CTD, and polybasic LMN). In vitro Cep57 condensates catalyze microtubule nucleation via the LMN motif-mediated tubulin concentration. In cells, the LMN motif is required for centrosomal microtubule aster formation. Moreover, Cep63 restricts Cep57 assembly, expansion, and microtubule polymerization activity. Overexpression of competitive constructs for multivalent interactions, including an MVA mutation, leads to excessive centrosome duplication. In Cep57-depleted cells, self-assembly mutants failed to rescue centriole disengagement and PCM disorganization. Thus, Cep57's multivalent interactions are pivotal for maintaining the accurate structural and functional integrity of human centrosomes.