Advances in Resistance Welding of Fiber-Reinforced Thermoplastics.

Fiber-reinforced thermoplastics (FRTPs) have become a new generation of lightweight materials due to their superior mechanical properties, good weldability and environmental resistance, potential for recycling, etc. The market for FRTPs is expected to grow at a compound annual growth rate (CAGR) of 7.8% from 2022 to 2030. Many researchers have been trying to solve the problems in their processing and joining process, and gradually expand their application. Resistance welding is one of the most suitable techniques to join FRTPs. This paper summarizes the research progress of FRTP resistance welding in terms of the basic process of FRTP resistance welding, factors affecting joint performance, joint failure behavior, numerical simulation, weld quality control, and resistance welding of thermoplastic/thermoset composites. The objective of this paper is to provide a deeper insight into the knowledge of FRTP resistance welding and provide reference for the further development and application of FRTP resistance welding.

E-cigarette use and associated factors among adults aged 18-44 years in China: Findings from an online survey.

INTRODUCTION: There needs to be more up-to-date evidence on the prevalence of e-cigarette use among Chinese adults. This study aims to investigate the prevalence and associated factors of e-cigarette use among adults aged 18-44 years in China. METHODS: Cross-sectional design and convenience sampling were used. The data for this study were obtained from an online survey conducted in mainland China from April to May 2023. The target population was adults aged 18-44 years. Descriptive analysis was employed to report the prevalence of e-cigarette use, while adjusted multivariable logistic regression was performed to examine the association between e-cigarette use and related factors. RESULTS: A total of 4256 participants were included in this study; 12.9% were current e-cigarette users, 5.9% were frequent users, and 7.0% were occasional users. The descriptive analysis results indicated that males and cigarette users had a higher prevalence of e-cigarette use. Multivariable analysis showed that e-cigarette use was significantly associated with female gender (AOR=0.76, 95% CI: 0.60-0.96), those aged 25-34 years with monthly income 6000-8999 CNY (AOR=2.01; 95% CI: 1.18-3.41), those aged 25-34 years with monthly income ≥9000 CNY (AOR=2.20; 95% CI: 1.26-3.82), college or undergraduate degree (AOR=1.91; 95% CI: 1.22-3.00), urban residence (AOR=1.72; 95% CI: 1.34-2.20), being a current smoker (AOR=3.32; 95% CI: 2.64-4.16), perception of harm (AOR=0.66; 95% CI: 0.60-0.73), and perception of benefit (AOR=2.31; 95% CI: 2.04-2.61). CONCLUSIONS: The prevalence of current e-cigarette use among adults in China was 12.9% within our sample. In addition to sociodemographic factors, individuals with a higher perception of the harm associated with e-cigarettes were less likely to engage in e-cigarette consumption. Conversely, individuals who perceive the 'benefits' of e-cigarettes more favorably use them. Targeted interventions, such as health education, are recommended to help adults develop a correct understanding of e-cigarettes and lower the prevalence of e-cigarette use.

Dissection of triple-negative breast cancer microenvironment and identification of potential therapeutic drugs using single-cell RNA sequencing analysis.

Breast cancer remains a leading cause of mortality in women worldwide. Triple-negative breast cancer (TNBC) is a particularly aggressive subtype characterized by rapid progression, poor prognosis, and lack of clear therapeutic targets. In the clinic, delineation of tumor heterogeneity and development of effective drugs continue to pose considerable challenges. Within the scope of our study, high heterogeneity inherent to breast cancer was uncovered based on the landscape constructed from both tumor and healthy breast tissue samples. Notably, TNBC exhibited significant specificity regarding cell proliferation, differentiation, and disease progression. Significant associations between tumor grade, prognosis, and TNBC oncogenes were established via pseudotime trajectory analysis. Consequently, we further performed comprehensive characterization of the TNBC microenvironment. A crucial epithelial subcluster, E8, was identified as highly malignant and strongly associated with tumor cell proliferation in TNBC. Additionally, epithelial-mesenchymal transition (EMT)-associated fibroblast and M2 macrophage subclusters exerted an influence on E8 through cellular interactions, contributing to tumor growth. Characteristic genes in these three cluster cells could therefore serve as potential therapeutic targets for TNBC. The collective findings provided valuable insights that assisted in the screening of a series of therapeutic drugs, such as pelitinib. We further confirmed the anti-cancer effect of pelitinib in an orthotopic 4T1 tumor-bearing mouse model. Overall, our study sheds light on the unique characteristics of TNBC at single-cell resolution and the crucial cell types associated with tumor cell proliferation that may serve as potent tools in the development of effective anti-cancer drugs.

Irisin Ameliorates Muscle Atrophy by Inhibiting the Upregulation of the Ubiquitin‒Proteasome System in Chronic Kidney Disease.

Muscle atrophy is a common complication of chronic kidney disease (CKD). Irisin, a novel muscle cytokine, protects against muscle atrophy, but its specific role in CKD-associated muscle atrophy requires further elucidation. Because the ubiquitin-proteasome system (UPS) plays an important role in CKD muscle atrophy, our study will explore whether irisin affects UPS and alleviate CKD-associated muscle atrophy. In this study, an adenine-fed mouse model of CKD and urotension II (UII)-induced C2C12 myotubes were used as in vivo and in vitro models of muscle atrophy. The results showed that renal function, mouse weight, and the cross-sectional area (CSA) of skeletal muscles were significantly improved in CKD mice treated with irisin. Moreover, irisin effectively mitigated the decreases in phosphorylated Forkhead box O 3a (p-FOXO3A) levels and increases in the levels of E3 ubiquitin ligases, such as muscle RING finger 1 (MuRF1) and muscle atrophy F-box (MAFbx/atrogin1), in both the muscles of CKD mice and UII-induced C2C12 myotubes. In addition, irisin significantly increased the expression levels of myogenic differentiation factor D (MyoD) in the muscles of CKD mice. Our study is the first to demonstrate that irisin ameliorates skeletal muscle atrophy by inhibiting UPS upregulation and improving satellite cell differentiation in CKD.

MFS Transporter as the Molecular Switch Unlocking the Production of Cage-Like Acresorbicillinol C.

Sorbicillinoids are a class of fungal polyketides with diverse structures and distinguished bioactivities. Although remarkable progress has been achieved in their chemistry and biosynthesis, the efflux of sorbicillinoids is poorly understood. Here, we found MFS transporter AcsorT was responsible for the biosynthesis of sorbicillinoids in Acremonium chrysogenum. Combinatorial knockout and subcellular location demonstrated that the plasma membrane-associated AcsorT was responsible for the transportation of sorbicillinol and subsequent formation of oxosorbicillinol and acresorbicillinol C via the berberine bridge enzyme-like oxidase AcsorD in the periplasm. Homology modeling and site-directed mutation revealed that Tyr303 and Arg436 were the key residues of AcsorT, which was further explained by molecular dynamics simulation. Based on our study, it was suggested that AcsorT modulates sorbicillinoid production by coordinating its biosynthesis and export, and a transport model of sorbicillinoids was proposed in A. chrysogenum.

Dual roles of the MPK3 and MPK6 mitogen-activated protein kinases in regulating Arabidopsis stomatal development.

An Arabidopsis (Arabidopsis thaliana) mitogen-activated protein kinase (MAPK) cascade composed of YODA (YDA)-MKK4/MKK5-MPK3/MPK6 plays an essential role downstream of the ERECTA (ER)/ER-LIKE (ERL) receptor complex in regulating stomatal development in the leaf epidermis. STOMAGEN (STO), a peptide ligand produced in mesophyll cells, competes with EPIDERMAL PATTERNING FACTOR2 (EPF2) for binding ER/ERL receptors to promote stomatal formation. In this study, we found that activation of MPK3/MPK6 suppresses STO expression. Using MUTE and STO promoters that confer epidermis- and mesophyll-specific expression, respectively, we generated lines with cell-specific activation and suppression of MPK3/MPK6. The activation or suppression of MPK3/MPK6 in either epidermis or mesophyll cells is sufficient to alter stomatal differentiation. Epistatic analyses demonstrated that STO overexpression can rescue the suppression of stomatal formation conferred by the mesophyll-specific expression of the constitutively active MKK4DD or MKK5DD, but not by the epidermis-specific expression of these constitutively active MKKs. These data suggest that STO is downstream of MPK3/MPK6 in mesophyll cells, but upstream of MPK3/MPK6 in epidermal cells in stomatal development signaling. This function of the MPK3/MPK6 cascade allows it to coordinate plant epidermis development based on its activity in mesophyll cells during leaf development.

Recurrent Cerebral Venous Sinus Thrombosis Occurred in an Acute Lymphoblastic Leukemia Child with Mutated Lipoprotein Lipase Gene during Asparaginase Therapy.

Cerebral venous sinus thrombosis (CVST) and hyperlipidemia are severe complications of L-Asparaginase (L-Asp) during the treatment of B-cell acute lymphoblastic leukemia (B-ALL). Herein, we reported a 9-year-old B-ALL boy who underwent abnormal hypertriglyceridemia and CVST presenting as seizures and disturbance of consciousness twice during the induction therapy. Fortunately, he survived treatment with anticoagulant and lipid-lowering therapy. No thrombophilia-related gene mutation was detected, but a heterozygous mutation in lipoprotein lipase (LPL) gene was identified. His neurological symptoms were managed with short-term anticoagulant therapy and long-term lipid-lowering therapy. This case illustrated the manifestation and potential pathogenesis of CVST and highlighted the essentiality of screening baseline lipid profile and dyslipidemia- and thrombophilia-related gene mutation.

Automated segmentation of brain metastases with deep learning: a multi-center, randomized crossover, multi-reader evaluation study.

BACKGROUND: Artificial intelligence has been proposed for brain metastasis (BM) segmentation but it has not been fully clinically validated. The aim of this study was to develop and evaluate a system for BM segmentation. METHODS: A deep-learning-based BM segmentation system (BMSS) was developed using contrast-enhanced MR images from 488 patients with 10,338 brain metastases. A randomized crossover, multi-reader study was then conducted to evaluate the performance of the BMSS for BM segmentation using data prospectively collected from 50 patients with 203 metastases at five centers. Five radiology residents and five attending radiologists were randomly assigned to contour the same prospective set in assisted and unassisted modes. Aided and unaided Dice similarity coefficients (DSCs) and contouring times per lesion were compared. RESULTS: The BMSS alone yielded a median DSC of 0.91 (95% confidence interval, 0.90-0.92) in the multi-center set and showed comparable performance between the internal and external sets (p = 0.67). With BMSS assistance, the readers increased the median DSC from 0.87 (0.87-0.88) to 0.92 (0.92-0.92) (p < 0.001) with a median time saving of 42% (40-45%) per lesion. Resident readers showed a greater improvement than attending readers in contouring accuracy (improved median DSC, 0.05 [0.05-0.05] vs. 0.03 [0.03-0.03]; p < 0.001), but a similar time reduction (reduced median time, 44% [40-47%] vs. 40% [37-44%]; p = 0.92) with BMSS assistance. CONCLUSIONS: The BMSS can be optimally applied to improve the efficiency of brain metastasis delineation in clinical practice.

Multi-omic characterization of allele-specific regulatory variation in hybrid pigs.

Hybrid mapping is a powerful approach to efficiently identify and characterize genes regulated through mechanisms in cis. In this study, using reciprocal crosses of the phenotypically divergent Duroc and Lulai pig breeds, we perform a comprehensive multi-omic characterization of regulatory variation across the brain, liver, muscle, and placenta through four developmental stages. We produce one of the largest multi-omic datasets in pigs to date, including 16 whole genome sequenced individuals, as well as 48 whole genome bisulfite sequencing, 168 ATAC-Seq and 168 RNA-Seq samples. We develop a read count-based method to reliably assess allele-specific methylation, chromatin accessibility, and RNA expression. We show that tissue specificity was much stronger than developmental stage specificity in all of DNA methylation, chromatin accessibility, and gene expression. We identify 573 genes showing allele specific expression, including those influenced by parent-of-origin as well as allele genotype effects. We integrate methylation, chromatin accessibility, and gene expression data to show that allele specific expression can be explained in great part by allele specific methylation and/or chromatin accessibility. This study provides a comprehensive characterization of regulatory variation across multiple tissues and developmental stages in pigs.

Mixed T-domain and TF-domain Magnitude and Phase representations for GAN-based speech enhancement.

Deep learning has made significant advancements in speech enhancement, which plays a crucial role in improving the quality of speech signals in noisy conditions. In this paper, we propose a new approach called M-DGAN, which introduces a time (T)-domain encoder-decoder structure with rich channel representations into the time-frequency (TF)-domain generator framework, resulting in a new generator structure with mixed magnitude and phase representations in the T and TF-domains. The proposed mixed T-domain and TF-domain generator, incorporating the cascaded reworked conformer (CRC) structure, exhibits improved modeling capability and adaptability. Test results on the Voice Bank + DEMAND public dataset show that our method achieves the highest score with P S E Q = 3.52 and performs well on all the remaining metrics when compared to the current state-of-the-art methods. In addition, tests on the NISQA_TEST_LIVETALK real dataset of the NISQA Corpus show the breadth and robustness of our model on speech enhancement tasks.

Integrated analysis of patients with bladder cancer from prospective transcription factor activity: Implications for personalized treatment approaches.

Transcription factors are a specialized group of proteins that play important roles in regulating gene expression in human. These proteins control the transcription and translation of genes by binding to specific sites on DNA, thereby regulating key biological processes such as cell differentiation, proliferation, immune response, and neural development. Moreover, transcription factors are also involved in apoptosis and the pathogenesis of various diseases. By investigating transcription factors, researchers can uncover the mechanisms of gene regulation in organisms and develop more effective methods for preventing and treating human diseases. In the present study, the Virtual Inference of Protein-activity by Enriched Regulon algorithm was utilized to calculate the protein activity of transcription factors, and the metabolic-related protein activity were used for classifying bladder cancer patients into different subtype. To identify chemotherapy drugs with clinical benefits, the differences in prognosis and drug sensitivity between two distinct subtypes of bladder cancer patients were investigated. Simultaneously, the master regulators that display varying levels of transcription factor activity between two different bladder cancer subtypes were explored. Additionally, the potential transcriptional regulatory mechanisms and targets of these factors were investigated, thereby generating novel insights into bladder cancer research at the transcriptional regulation level.

STAT transcription factor is indispensable for oogenesis in silkworm.

Signal Transducer and Activator of Transcription (STAT) proteins represent a critical transcription factor family with multifaceted roles in diverse fundamental eukaryotic processes. In Drosophila, STAT exerts a pivotal regulatory influence on oogenesis, governing the early differentiation of follicular cells and ensuring proper encapsulation of germ-line cells. However, the role of STAT in egg development in silkworms remains unknown. In the present study, using CRISPR/Cas9 technology, we successfully generated a strain of silkworms with targeted deletion of the STAT-L gene, which resulted in significant reproductive abnormalities observed in female moths, including shortened fallopian tubes and reduced egg production. The ovaries dissected from STAT-L knockout silkworms during the pupal stage of silkworm exhibited varying degrees of fusion among egg chambers. Additionally, paraffin sections of prepupal ovaries also revealed evidence of egg chambers fusion. To elucidate the molecular mechanism underlying the role of the STAT-L gene regulation on egg development in silkworm, we performed ovarian transcriptomic analysis following STAT-L knockout. Our findings indicated that STAT-L gene can modulate Notch signaling pathway by down-regulating APH-1 gene expression. These results suggest that STAT-L gene plays a crucial role in normal egg chamber formation in silkworms, potentially through its influence on Notch signaling pathway expression.

Prevalence of kidney disease in patients with different types of cancer or hematological malignancies: a cross-sectional study.

PURPOSE: This study investigated the prevalence and risk factors of acute kidney injury (AKI) and chronic kidney disease (CKD) in cancer patients with the aim of providing guidance for clinical treatment of cancer patients. METHODS: A retrospective study was conducted on all cancer and hematological malignancy patients admitted to Xuanwu Hospital, Capital Medical University, from January 2018 to July 2023. The study population included patients aged 18-80 years with a confirmed cancer or malignancy diagnosis. Chi-square tests, Spearman's correlation, and logistic regression were used to evaluate the relationships between demographic factors, comorbidities, cancer types, antitumor drugs and the prevalence of AKI/CKD. RESULTS: Among the 2438 participants, the prevalence rates of AKI and CKD were 3.69% and 7.88%, respectively. Patients with diabetes had higher prevalence of AKI/CKD than those without diabetes (OR = 1.66, 95% CI 1.01-2.68, p = 0.040; OR = 1.60, 95% CI 1.10-2.31, p = 0.012, respectively). In addition, a higher prevalence of CKD was observed in patients with hypertension (OR = 3.49, 95% CI 2.43-5.06, p < 0.001). Underweight patients were more likely to develop AKI (OR = 2.66, 95% CI 1.03-6.08, p = 0.029). Anthracyclines may contribute to a higher risk of AKI, and antimetabolites and immunomodulators may be associated with the development of CKD. Overall, patients with hematological malignancies had significantly higher rates of AKI/CKD than those with solid tumors. Among solid tumor patients, the prevalence of AKI/CKD was low in patients with lung and breast cancer. CONCLUSIONS: AKI and CKD prevalence varies across cancer types, influenced by factors, such as diabetes, hypertension, body weight, and antitumor drugs. Tailored treatment plans are essential for improving cancer patient outcomes.

Cerebrospinal fluid α-synuclein adds the risk of cognitive decline and is associated with tau pathology among non-demented older adults.

BACKGROUND: The role of α-synuclein in dementia has been recognized, yet its exact influence on cognitive decline in non-demented older adults is still not fully understood. METHODS: A total of 331 non-demented individuals were included in the study from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Participants were divided into two distinct groups based on their α-synuclein levels: one with lower levels (α-synuclein-L) and another with higher levels (α-synuclein-H). Measurements included neuropsychiatric scales, cerebrospinal fluid (CSF) biomarkers, and blood transcriptomics. The linear mixed-effects model investigated the longitudinal changes in cognition. Kaplan-Meier survival analysis and the Cox proportional hazards model were utilized to evaluate the effects of different levels of α-synuclein on dementia. Gene set enrichment analysis (GSEA) was utilized to investigate the biological pathways related to cognitive impairment. Pearson correlation, multiple linear regression models, and mediation analysis were employed to investigate the relationship between α-synuclein and neurodegenerative biomarkers, and their potential mechanisms affecting cognition. RESULTS: Higher CSF α-synuclein levels were associated with increased risk of cognitive decline and progression to dementia. Enrichment analysis highlighted the activation of tau-associated and immune response pathways in the α-synuclein-H group. Further correlation and regression analysis indicated that the CSF α-synuclein levels were positively correlated with CSF total tau (t-tau), phosphorylated tau (p-tau) 181, tumor necrosis factor receptor 1 (TNFR1) and intercellular cell adhesion molecule-1 (ICAM-1). Mediation analysis further elucidated that the detrimental effects of CSF α-synuclein on cognition were primarily mediated through CSF t-tau and p-tau. Additionally, it was observed that CSF α-synuclein influenced CSF t-tau and p-tau181 levels via inflammatory pathways involving CSF TNFR1 and ICAM-1. CONCLUSIONS: These findings elucidate a significant connection between elevated levels of CSF α-synuclein and the progression of cognitive decline, highlighting the critical roles of activated inflammatory pathways and tau pathology in this association. They underscore the importance of monitoring CSF α-synuclein levels as a promising biomarker for identifying individuals at increased risk of cognitive deterioration and developing dementia.

Handgrip strength is associated with cognitive function in older patients with stage 3-5 chronic kidney disease: results from the NHANES.

In this study, we aimed to investigate the association between handgrip strength (HGS) and cognitive performance in stage 3-5 chronic kidney disease (CKD) patients aged ≥ 60 years. This cross-sectional study analyzed data from National Health and Nutrition Examination Survey (NHANES) database 2011-2014. Three tests were used to assess the cognitive performance, including consortium to establish a registry for Alzheimer's disease (CERAD), animal fluency test (AFT), and digit symbol substitution test (DSST). The multivariate linear regression analyses adjusting for confounding factors were utilized to evaluate the association of HGS with cognitive performance. A total of 678 older stage 3-5 CKD patients were included in this study. After adjusting for multiple factors, a higher HGS was positively associated with a higher CERAD-delayed recall and DSST score. In addition, our analysis indicated that HGS probably correlated with better performance of immediate learning ability in male, while working memory, sustained attention, and processing speed in female. HGS may be an important indicator for cognitive deficits in stage 3-5 CKD patients, especially for learning ability and executive function. Further research to explore the sex-specific and domain-specific and possible mechanisms are required.

Comparative evaluation of soundscapes in human activities spatial contexts of pedestrian spaces adjacent to arterial roads.

Pedestrian spaces adjacent to arterial roads are characterized by the dominance of traffic noise alongside various human activities. Research on the impact of traffic noise on the soundscape evaluation of pedestrian spaces has not considered human activities spatial contexts. To address this research gap, the present study constructed auditory environments for pedestrian spaces in the contexts of commuting, residential, and commercial activities. A total of seven auditory environments were subjected to laboratory auditory evaluations, including perceived dominance of sound source, acoustic comfort, and perceived affective quality of the soundscape. The results indicated that in pedestrian spaces with constant traffic noise, the presence of significant human activity sounds led to a decreased perceived dominance of traffic noise and an increased acoustic comfort, despite the higher acoustic energy. Thus, pedestrian spaces with a variety of human activity received better soundscape evaluations. The elements that reflected the human activities spatial contexts, including the types and intensity of human activities, played a crucial role in soundscape evaluations. Better acoustic comfort was reported in pedestrian spaces characterized by low-intensity residential activities and high-intensity commercial activities. Additionally, pedestrian spaces with more intense activities offered an actively engaging soundscape. The findings can provide reference for a more accurate evaluation of the soundscape in pedestrian spaces and guide the soundscape design of pedestrian environments.

Oscillating paramagnetic Meissner effect and Berezinskii-Kosterlitz-Thouless transition in underdoped Bi2Sr2CaCu2O8+δ.

Superconducting phase transitions in two dimensions lie beyond the description of the Ginzburg-Landau symmetry-breaking paradigm for three-dimensional superconductors. They are Berezinskii-Kosterlitz-Thouless (BKT) transitions of paired-electron condensate driven by the unbinding of topological excitations, i.e. vortices. The recently discovered monolayers of layered high-transition-temperature ([Formula: see text]) cuprate superconductor Bi2Sr2CaCu2O8+δ (Bi2212) meant that this 2D superconductor promised to be ideal for the study of unconventional superconductivity. But inhomogeneity posed challenges for distinguishing BKT physics from charge correlations in this material. Here, we utilize the phase sensitivity of scanning superconducting quantum interference device microscopy susceptometry to image the local magnetic response of underdoped Bi2212 from the monolayer to the bulk throughout its phase transition. The monolayer segregates into domains with independent phases at elevated temperatures below [Formula: see text]. Within a single domain, we find that the susceptibility oscillates with flux between diamagnetism and paramagnetism in a Fraunhofer-like pattern up to [Formula: see text]. The finite modulation period, as well as the broadening of the peaks when approaching [Formula: see text] from below, suggests well-defined vortices that are increasingly screened by the dissociation of vortex-antivortex plasma through a BKT transition. In the multilayers, the susceptibility oscillation differs in a small temperature regime below [Formula: see text], consistent with a dimensional crossover led by interlayer coupling. Serving as strong evidence for BKT transition in the bulk, we observe a sharp jump in phase stiffness and paramagnetism at small fields just below [Formula: see text]. These results unify the superconducting phase transitions from the monolayer to the bulk underdoped Bi2212, and can be collectively referred to as the BKT transition with interlayer coupling.

Identification of Novel FZD4 Mutations in Familial Exudative Vitreoretinopathy and Investigating the Pathogenic Mechanisms of FZD4 Mutations.

Purpose: The purpose of this study is to report five novel FZD4 mutations identified in familial exudative vitreoretinopathy (FEVR) and to analyze and summarize the pathogenic mechanisms of 34 of 96 reported missense mutations in FZD4. Methods: Five probands diagnosed with FEVR and their family members were enrolled in the study. Ocular examinations and targeted gene panel sequencing were conducted on all participants. Plasmids, each carrying 29 previously reported FZD4 missense mutations and five novel mutations, were constructed based on the selection of mutations from each domain of FZD4. These plasmids were used to investigate the effects of mutations on protein expression levels, Norrin/ß-catenin activation capacity, membrane localization, norrin binding ability, and DVL2 recruitment ability in HEK293T, HEK293STF, and HeLa cells. Results: All five novel mutations (S91F, V103E, C145S, E160K, C377F) responsible for FEVR were found to compromise Norrin/ß-catenin activation of FZD4 protein. After reviewing a total of 34 reported missense mutations, we categorized all mutations based on their functional changes: signal peptide mutations, cysteine mutations affecting disulfide bonds, extracellular domain mutations influencing norrin binding, transmembrane domain (TM) 1 and TM7 mutations impacting membrane localization, and intracellular domain mutations affecting DVL2 recruitment. Conclusions: We expanded the spectrum of FZD4 mutations relevant to FEVR and experimentally demonstrated that missense mutations in FZD4 can be classified into five categories based on different functional changes.

Pulsed Laser Manufactured Heteroatom Doped Carbon Dots via Heterocyclic Aromatic Hydrocarbons for Improved Tribology Performance.

Traditional laser-assisted method (top-down synthesis strategy) is applied in the preparation of carbon dots (CDs) by cutting larger carbon materials, which requires harsh conditions, and the size distribution of the CDs is seldom monodisperse. In this work, heteroatom-doped CDs, represented by N,S co-doped CDs (N,S-CDs), can be prepared successfully by pulsed laser irradiation of heterocyclic aromatic hydrocarbons-based small molecule compound solution. The friction coefficient (COF) of base oil PAO decreases from 0.650 to 0.093, and the wear volume reduces by 92.0% accompanied by 1 wt.% N,S-CDs addition, while the load-bearing capacity is improved from 100 to 950 N. The excellent lubrication performance is mainly attributed to the formation of a robust tribofilm via a tribochemical reaction between N,S-CDs and friction pairs, and the N,S-CDs can play a mending effect and polishing effect for worn surfaces. Furthermore, the lubricant containing heteroatom doped CDs are capable of being prepared in situ via pulsed laser irradiation of heterocyclic aromatic hydrocarbons in base oil, which can avoid the redispersed problem of nano-additive in base oil to maintain long-term dispersion, with COF of 0.103 and low wear volume ≈1.99 × 105 µm3 (76.9% reduction) even after standing for 9 months.

Comprehensive Parameter Space Mapping of Cell Cycle Dynamics under Network Perturbations.

Studies of quantitative systems and synthetic biology have extensively utilized models to interpret data, make predictions, and guide experimental designs. However, models often simplify complex biological systems and lack experimentally validated parameters, making their reliability in perturbed systems unclear. Here, we developed a droplet-based synthetic cell system to continuously tune parameters at the single-cell level in multiple dimensions with full dynamic ranges, providing an experimental framework for global parameter space scans. We systematically perturbed a cell-cycle oscillator centered on cyclin-dependent kinase (Cdk1), enabling comprehensive mapping of period landscapes in response to network perturbations. The data allowed us to challenge existing models and refine a new model that matches the observed response. Our analysis demonstrated that Cdk1 positive feedback inhibition restricts the cell cycle frequency range, confirming model predictions; furthermore, it revealed new cellular responses to the inhibition of the Cdk1-counteracting phosphatase PP2A: monomodal or bimodal distributions across varying inhibition levels, underscoring the complex nature of cell cycle regulation that can be explained by our model. This comprehensive perturbation platform may be generalizable to exploring other complex dynamic systems.