Assembly-mediated activation of the SIR2-HerA supramolecular complex for anti-phage defense.

SIR2-HerA, a bacterial two-protein anti-phage defense system, induces bacterial death by depleting NAD+ upon phage infection. Biochemical reconstitution of SIR2, HerA, and the SIR2-HerA complex reveals a dynamic assembly process. Unlike other ATPases, HerA can form various oligomers, ranging from dimers to nonamers. When assembled with SIR2, HerA forms a hexamer and converts SIR2 from a nuclease to an NAD+ hydrolase, representing an unexpected regulatory mechanism mediated by protein assembly. Furthermore, high concentrations of ATP can inhibit NAD+ hydrolysis by the SIR2-HerA complex. Cryo-EM structures of the SIR2-HerA complex reveal a giant supramolecular assembly up to 1 MDa, with SIR2 as a dodecamer and HerA as a hexamer, crucial for anti-phage defense. Unexpectedly, the HerA hexamer resembles a spiral staircase and exhibits helicase activities toward dual-forked DNA. Together, we reveal the supramolecular assembly of SIR2-HerA as a unique mechanism for switching enzymatic activities and bolstering anti-phage defense strategies.

Oligomerization-mediated activation of a short prokaryotic Argonaute.

Although eukaryotic and long prokaryotic Argonaute proteins (pAgos) cleave nucleic acids, some short pAgos lack nuclease activity and hydrolyse NAD(P)+ to induce bacterial cell death1. Here we present a hierarchical activation pathway for SPARTA, a short pAgo consisting of an Argonaute (Ago) protein and TIR-APAZ, an associated protein2. SPARTA progresses through distinct oligomeric forms, including a monomeric apo state, a monomeric RNA-DNA-bound state, two dimeric RNA-DNA-bound states and a tetrameric RNA-DNA-bound active state. These snapshots together identify oligomerization as a mechanistic principle of SPARTA activation. The RNA-DNA-binding channel of apo inactive SPARTA is occupied by an auto-inhibitory motif in TIR-APAZ. After the binding of RNA-DNA, SPARTA transitions from a monomer to a symmetric dimer and then an asymmetric dimer, in which two TIR domains interact through charge and shape complementarity. Next, two dimers assemble into a tetramer with a central TIR cluster responsible for hydrolysing NAD(P)+. In addition, we observe unique features of interactions between SPARTA and RNA-DNA, including competition between the DNA 3' end and the auto-inhibitory motif, interactions between the RNA G2 nucleotide and Ago, and splaying of the RNA-DNA duplex by two loops exclusive to short pAgos. Together, our findings provide a mechanistic basis for the activation of short pAgos, a large section of the Ago superfamily.

HSP90ß prevents aging-related cataract formation through regulation of the charged multivesicular body protein (CHMP4B) and p53.

Cataract is a leading ocular disease causing global blindness. The mechanism of cataractogenesis has not been well defined. Here, we demonstrate that the heat shock protein 90ß (HSP90ß) plays a fundamental role in suppressing cataractogenesis. HSP90ß is the most dominant HSP in normal lens, and its constitutive high level of expression is largely derived from regulation by Sp1 family transcription factors. More importantly, HSP90ß is significantly down-regulated in human cataract patients and in aging mouse lenses, whereas HSP90ß silencing in zebrafish causes cataractogenesis, which can only be rescued by itself but not other HSP90 genes. Mechanistically, HSP90ß can directly interact with CHMP4B, a newly-found client protein involved in control of cytokinesis. HSP90ß silencing causes upregulation of CHMP4B and another client protein, the tumor suppressor p53. CHMP4B upregulation or overexpression induces excessive division of lens epithelial cells without proper differentiation. As a result, these cells were triggered to undergo apoptosis due to activation of the p53/Bak-Bim pathway, leading to cataractogenesis and microphthalmia. Silence of both HSP90ß and CHMP4B restored normal phenotype of zebrafish eye. Together, our results reveal that HSP90ß is a critical inhibitor of cataractogenesis through negative regulation of CHMP4B and the p53-Bak/Bim pathway.

Inhibition of PLK4 remodels histone methylation and activates the immune response via the cGAS-STING pathway in TP53-mutated AML.

Acute myeloid leukemia (AML) with TP53 mutation is one of the most lethal cancers and portends an extremely poor prognosis. Based on in silico analyses of druggable genes and differential gene expression in TP53-mutated AML, we identified pololike kinase 4 (PLK4) as a novel therapeutic target and examined its expression, regulation, pathogenetic mechanisms, and therapeutic potential in TP53-mutated AML. PLK4 expression was suppressed by activated p53 signaling in TP53 wild-type AML and was increased in TP53-mutated AML cell lines and primary samples. Short-term PLK4 inhibition induced DNA damage and apoptosis in TP53 wild-type AML. Prolonged PLK4 inhibition suppressed the growth of TP53-mutated AML and was associated with DNA damage, apoptosis, senescence, polyploidy, and defective cytokinesis. A hitherto undescribed PLK4/PRMT5/EZH2/H3K27me3 axis was demonstrated in both TP53 wild-type and mutated AML, resulting in histone modification through PLK4-induced PRMT5 phosphorylation. In TP53-mutated AML, combined effects of histone modification and polyploidy activated the cGAS-STING pathway, leading to secretion of cytokines and chemokines and activation of macrophages and T cells upon coculture with AML cells. In vivo, PLK4 inhibition also induced cytokine and chemokine expression in mouse recipients, and its combination with anti-CD47 antibody, which inhibited the "don't-eat-me" signal in macrophages, synergistically reduced leukemic burden and prolonged animal survival. The study shed important light on the pathogenetic role of PLK4 and might lead to novel therapeutic strategies in TP53-mutated AML.

Asymmetrical cortical surface area decrease in epilepsy patients with postictal generalized electroencephalography suppression.

Postictal generalized electroencephalographic suppression is a possible electroencephalographic marker for sudden unexpected death in epilepsy. We aimed to investigate the cortical surface area abnormalities in epilepsy patients with postictal generalized electroencephalographic suppression. We retrospectively included 30 epilepsy patients with postictal generalized electroencephalographic suppression (PGES+), 21 epilepsy patients without postictal generalized electroencephalographic suppression (PGES-), and 30 healthy controls. Surface-based analysis on high-resolution T1-weighted images was conducted and cortical surface areas were compared among the three groups, alongside correlation analyses with seizure-related clinical variables. Compared with PGES- group, we identified reduced surface area in the bilateral insula with more extensive distribution in the right hemisphere in PGES+ group. The reduced right insular surface area was associated with younger seizure-onset age. When compared with healthy controls, PGES- group presented reduced surface area in the left caudal middle frontal gyrus; PGES+ group presented more widespread surface area reductions in the right posterior cingulate gyrus, left postcentral gyrus, middle frontal gyrus, and middle temporal gyrus. Our results suggested cortical microstructural impairment in patients with postictal generalized electroencephalographic suppression. The significant surface area reductions in the insular cortex supported the autonomic network involvement in the pathology of postictal generalized electroencephalographic suppression, and its right-sided predominance suggested the potential shared abnormal brain network for postictal generalized electroencephalographic suppression and sudden unexpected death in epilepsy.

Holistic Prediction of AuNP Aggregation in Diverse Aqueous Suspensions Based on Machine Vision and Dark-Field Scattering Imaging.

The localized surface-plasmon resonance of the AuNP in aqueous media is extremely sensitive to environmental changes. By measuring the signal of plasmon scattering light, the dark-field microscopic (DFM) imaging technique has been used to monitor the aggregation of AuNPs, which has attracted great attention because of its simplicity, low cost, high sensitivity, and universal applicability. However, it is still challenging to interpret DFM images of AuNP aggregation due to the heterogeneous characteristics of the isolated and discontinuous color distribution. Herein, we introduce machine vision algorithms for the training of DFM images of AuNPs in different saline aqueous media. A visual deep learning framework based on AlexNet is constructed for studying the aggregation patterns of AuNPs in aqueous suspensions, which allows for rapid and accurate identification of the aggregation extent of AuNPs, with a prediction accuracy higher than 0.96. With the aid of machine learning analysis, we further demonstrate the prediction ability of various aggregation phenomena induced by both cation species and the concentration of the external saline solution. Our results suggest the great potential of machine vision frameworks in the accurate recognition of subtle pattern changes in DFM images, which can help researchers build predictive analytics based on DFM imaging data.

Is postmastectomy radiotherapy necessary for breast cancer patients with clinically node-positive downstaging to ypN0 after neoadjuvant chemotherapy?

PURPOSE: The significance of postmastectomy radiotherapy (PMRT) in breast cancer patients who initially have clinically node-positive (cN +) status but achieve downstaging to ypN0 following neoadjuvant chemotherapy (NAC) remains uncertain. This study aims to assess the impact of PMRT in this patient subset. METHODS: Patients were enrolled from West China Hospital, Sichuan University from 2008 to 2019. Overall survival (OS), Locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and breast cancer-specific survival (BCSS) were estimated using the Kaplan-Meier method and assessed with the log-rank test. The impact of PMRT was further analyzed by the Cox proportional hazards model. Propensity score matching (PSM) was performed to reduce the selection bias. RESULTS: Of the 333 eligible patients, 189 (56.8%) received PMRT, and 144 (43.2%) did not. At a median follow-up period of 71 months, the five-year LRFS, DMFS, BCSS, and OS rates were 99.1%, 93.4%, 96.4%, and 94.3% for the entire cohort, respectively. Additionally, the 5-year LRFS, DMFS, BCSS, and OS rates were 98.9%, 93.8%, 96.7%, and 94.5% with PMRT and 99.2%, 91.3%, 94.9%, and 92.0% without PMRT, respectively (all p-values not statistically significant). After multivariate analysis, PMRT was not a significant risk factor for any of the endpoints. When further stratified by stage, PMRT did not show any survival benefit for patients with stage II-III diseases. CONCLUSION: In the context of comprehensive treatments, PMRT might be exempted in ypN0 breast cancer patients. Further large-scale, randomized controlled studies are required to investigate the significance of PMRT in this patient subset.

Nanoghosts: Harnessing Mesenchymal Stem Cell Membrane for Construction of Drug Delivery Platforms Via Optimized Biomimetics.

Mesenchymal stem cells (MSCs) are becoming hotspots for application in disease therapies recently, combining with biomaterials and drug delivery system. A major advantage of MSCs applied in drug delivery system is that these cells enable specific targeting and releasing of cargos to the disease sites. However, the potential tumor tropic effects of MSCs raised concerns on biosafety. To solve this problem, there are emerging methods of isolating cell membranes and developing nanoformulations to perform drug delivery, which avoids concerns on biosafety without disturbing the membrane functions of specific polarizing and locating. These cargoes are so called "nanoghosts." This review article summarizes the current applications of nanoghosts, the promising potential of MSCs to be applied in membrane isolation and nanoghost construction, and possible approaches to develop better drug delivery system harnessing from MSC ghost cell membranes.

Reticular Chemistry Directed "One-Pot" Strategy to in situ Construct Organic Linkers and Zirconium-Organic Frameworks.

Zirconium-based metal-organic frameworks (Zr-MOFs) have emerged as one of the most studied MOFs due to the unlimited numbers of organic linkers and the varying Zr-oxo clusters. However, the synthesis of carboxylic acids, especially multitopic carboxylic acids, is always a great challenge for the discovery of new Zr-MOFs. As an alternative approach, the in situ "one-pot" strategy can address this limitation, where the generation of organic linkers from the corresponding precursors and the sequential construction of MOFs are integrated into one solvothermal condition. Herein, inspired by benzimidazole-contained compounds synthesized via reaction of aldehyde and o-phenylenediamine, tri-, tetra-, penta- and hexa-topic carboxylic acids and a series of corresponding Zr-MOFs can be prepared via the in situ "one-pot" method under the same solvothermal conditions. This strategy can be utilized not only to prepare reported Zr-MOFs constructed using benzimidazole-contained linkers, but also to rationally design, construct and realize functionalities of zirconium-pentacarboxylate frameworks guided by reticular chemistry. More importantly, in situ "one-pot" method can facilitate the discovery of new Zr-MOFs, such as zirconium-hexacarboxylate frameworks. The present study demonstrates the promising potential of benzimidazole-inspired in situ "one-pot" approach in the crystal engineering of structure- and property-specific Zr-MOFs, especially with the guidance of reticular chemistry.

ScRNA-seq reveals dark- and light-induced differentially expressed gene atlases of seedling leaves in Arachis hypogaea L.

Although the regulatory mechanisms of dark and light-induced plant morphogenesis have been broadly investigated, the biological process in peanuts has not been systematically explored on single-cell resolution. Herein, 10 cell clusters were characterized using scRNA-seq-identified marker genes, based on 13 409 and 11 296 single cells from 1-week-old peanut seedling leaves grown under dark and light conditions. 6104 genes and 50 transcription factors (TFs) displayed significant expression patterns in distinct cell clusters, which provided gene resources for profiling dark/light-induced candidate genes. Further pseudo-time trajectory and cell cycle evidence supported that dark repressed the cell division and perturbed normal cell cycle, especially the PORA abundances correlated with 11 TFs highly enriched in mesophyll to restrict the chlorophyllide synthesis. Additionally, light repressed the epidermis cell developmental trajectory extending by inhibiting the growth hormone pathway, and 21 TFs probably contributed to the different genes transcriptional dynamic. Eventually, peanut AHL17 was identified from the profile of differentially expressed TFs, which encoded protein located in the nucleus promoted leaf epidermal cell enlargement when ectopically overexpressed in Arabidopsis through the regulatory phytohormone pathway. Overall, our study presents the different gene atlases in peanut etiolated and green seedlings, providing novel biological insights to elucidate light-induced leaf cell development at the single-cell level.

Brachytherapy in craniopharyngiomas: a systematic review and meta-analysis of long-term follow-up.

OBJECTIVE: Brachytherapy has been indicated as an alternative option for treating cystic craniopharyngiomas (CPs). The potential benefits of brachytherapy for CPs have not yet been clarified. The purpose of this work was to conduct a meta-analysis to analyze the long-term efficacy and adverse reactions profile of brachytherapy for CPs. MATERIALS AND METHODS: The relevant databases were searched to collect the clinical trials on brachytherapy in patients with CPs. Included studies were limited to publications in full manuscript form with at least 5-year median follow-up, and adequate reporting of treatment outcomes and adverse reactions data. Stata 12.0 was used for data analysis. RESULTS: According to the inclusion and exclusion criteria, a total of 6 clinical trials involving 266 patients with CPs were included in this meta-analysis. The minimum average follow-up was 5 years. The results of the meta-analysis showed that 1-year, 2-3 years and 5 years progression free survival rates (PFS) are 75% (95%CI: 66-84%), 62% (95%CI: 52-72%) and 57% (95%CI: 22-92%), respectively. At the last follow-up, less than 16% of patients with visual outcomes worser than baseline in all included studies. While, for endocrine outcomes, less than 32% of patients worser than baseline level. CONCLUSION: In general, based on the above results, brachytherapy should be considered as a good choice for the treatment of CP.

A subtype of schizophrenia patients with altered methylation level of genes related to immune cell activity.

BACKGROUND: Epigenetic changes are plausible molecular sources of clinical heterogeneity in schizophrenia. A subgroup of schizophrenia patients with elevated inflammatory or immune-dysregulation has been reported by previous studies. However, little is known about epigenetic changes in genes related to immune activation in never-treated first-episode patients with schizophrenia (FES) and its consistency with that in treated long-term ill (LTS) patients. METHODS: In this study, epigenome-wide profiling with a DNA methylation array was applied using blood samples of both FES and LTS patients, as well as their corresponding healthy controls. Non-negative matrix factorization (NMF) and k -means clustering were performed to parse heterogeneity of schizophrenia, and the consistency of subtyping results from two cohorts. was tested. RESULTS: This study identified a subtype of patients in FES participants (47.5%) that exhibited widespread methylation level alterations of genes enriched in immune cell activity and a significantly higher proportion of neutrophils. This clustering of FES patients was validated in LTS patients, with high correspondence in epigenetic and clinical features across two cohorts. CONCLUSIONS: In summary, this study demonstrated a subtype of schizophrenia patients across both FES and LTS cohorts, defined by widespread alterations in methylation profile of genes related to immune function and distinguishing clinical features. This finding illustrates the promise of novel treatment strategies targeting immune dysregulation for a subpopulation of schizophrenia patients.

Adsorption Structures, Vibrational Raman Spectra and Chemical Binding Properties of Thioglycolic Acid on Cu(111) Surfaces: A DFT Study.

Copper is widely used in everyday life and industrial production because of its good electrical and thermal conductivity. To overcome copper oxidation and maintain its good physical properties, small organic molecules adsorbed on the surface of copper make a passivated layer to further avoid copper corrosion. In this work, we have investigated thioglycolic acid (TGA, another name is mercaptoacetic acid) adsorbed on copper surfaces by using density functional theory (DFT) calculations and a periodical slab model. We first get five stable adsorption structures, and the binding interaction between TGA and Cu(111) surfaces by using density of states (DOS), indicating that the most stable configuration adopts a triple-end binding model. Then, we analyze the vibrational Raman spectra of TGA adsorbed on the Cu(111) surface and make vibrational assignments according to the vibrational vectors. Finally, we explore the temperature effect of the thermodynamically Gibbs free energy of TGA on the Cu(111) surface and the antioxidant ability of the small organic molecular layer of copper oxidation on the copper surface. Our calculated results further provide evidences to interpret the stability of adsorption structures and antioxidant properties of copper.

Differential expression and co-localization of transcriptional factors during callus transition to differentiation for shoot organogenesis in the water fern Ceratopteris richardii.

BACKGROUND AND AIMS: In flowering plants, regeneration can be achieved by a variety of approaches, and different sets of transcriptional factors are involved in these processes. However, regeneration in taxa other than flowering plants remains a mystery. Ceratopteris richardii is a representative fern capable of both direct and indirect organogenesis, and we aimed to investigate the genetics underlying the transition from callus proliferation to differentiation. METHODS: Morphological and histological analyses were used to determine the type of regeneration involved. RNA sequencing and differential gene expression were used to investigate how the callus switches from proliferation to differentiation. Phylogenetic analysis and RNA in situ hybridization were used to understand whether transcriptional factors are involved in this transition. KEY RESULTS: The callus formed on nascent leaves and subsequently developed the shoot pro-meristem and shoot meristem, thus completing indirect de novo shoot organogenesis in C. richardii. Genes were differentially expressed during the callus transition from proliferation to differentiation, indicating a role for photosynthesis, stimulus response and transmembrane signalling in this transition and the involvement of almost all cell layers that make up the callus. Transcriptional factors were either downregulated or upregulated, which were generally in many-to-many orthology with genes known to be involved in callus development in flowering plants, suggesting that the genetics of fern callus development are both conserved and divergent. Among them, an STM-like, a PLT-like and an ethylene- and salt-inducible ERF gene3-like gene were expressed simultaneously in the vasculature but not in the other parts of the callus, indicating that the vasculature played a role in the callus transition from proliferation to differentiation. CONCLUSIONS: Indirect de novo shoot organogenesis could occur in ferns, and the callus transition from proliferation to differentiation required physiological changes, differential expression of transcriptional factors and involvement of the vasculature.

Interaction between baseline BMI and baseline disease severity predicts greater improvement in negative symptoms in first-episode schizophrenia.

Several studies have reported that baseline symptom severity in patients with schizophrenia (SCZ) is associated with the efficacy of antipsychotic medication. Overweight/obesity is common in SCZ and has also been reported to be correlated with therapeutic response to antipsychotics. This study aimed to evaluate whether baseline body mass index (BMI) and disease severity were associated with improvements in negative symptoms in patients with first-episode and medication-naïve (FEMN) SCZ. A total of 241 FEMN patients were recruited in this study and treated with oral risperidone over 3 months. Clinical symptoms were measured by the Positive and Negative Syndrome Scale (PANSS) and BMI was assessed at baseline and 3-month follow-up. We found that baseline BMI was correlated with the baseline severity of symptoms. Baseline BMI or baseline disease severity was associated with improvement in negative symptoms after 3 months of treatment. Linear regression analysis indicated that the interaction of BMI and disease severity at baseline was associated with improvement in negative symptoms in the early stage of SCZ after controlling for sex, age, and dose of risperidone. Our study suggests that the interaction of baseline BMI and disease severity may play a role in predicting negative symptom improvement after 3 months of risperidone treatment.

Inflammation-related molecular signatures involved in the anticancer activities of brigatinib as well as the prognosis of EML4-ALK lung adenocarcinoma patient.

Although ALK tyrosine kinase inhibitors (ALK-TKIs) have shown remarkable benefits in EML4-ALK positive NSCLC patients compared to conventional chemotherapy, the optimal sequence of ALK-TKIs treatment remains unclear due to the emergence of primary and acquired resistance and the lack of potential prognostic biomarkers. In this study, we systematically explored the validity of sequential ALK inhibitors (alectinib, lorlatinib, crizotinib, ceritinib and brigatinib) for a heavy-treated patient with EML4-ALK fusion via developing an in vitro and in vivo drug testing system based on patient-derived models. Based on the patient-derived models and clinical responses of the patient, we found that crizotinib might inhibit proliferation of EML4-ALK positive tumors resistant to alectinib and lorlatinib. In addition, NSCLC patients harboring the G1269A mutation, which was identified in alectinib, lorlatinib and crizotinib-resistant NSCLC, showed responsiveness to brigatinib and ceritinib. Transcriptomic analysis revealed that brigatinib suppressed the activation of multiple inflammatory signaling pathways, potentially contributing to its anti-tumor activity. Moreover, we constructed a prognostic model based on the expression of IL6, CXCL1, and CXCL5, providing novel perspectives for predicting prognosis in EML4-ALK positive NSCLC patients. In summary, our results delineate clinical responses of sequential ALK-TKIs treatments and provide insights into the mechanisms underlying the superior effects of brigatinib in patients harboring ALKG1269A mutation and resistant towards alectinib, lorlatinib and crizotinib. The molecular signatures model based on the combination of IL6, CXCL1 and CXCL5 has the potential to predict prognosis of EML4-ALK positive NSCLC patients.

Radiomic features of gray matter in never-treated first-episode schizophrenia.

Alterations of radiomic features (RFs) in gray matter are observed in schizophrenia, of which the results may be limited by small study samples and confounding effects of drug therapies. We tested for RFs alterations of gray matter in never-treated first-episode schizophrenia (NT-FES) patients and examined their associations with known gene expression profiles. RFs were examined in the first sample with 197 NT-FES and 178 healthy controls (HCs) and validated in the second independent sample (90 NT-FES and 74 HCs). One-year follow-up data were available from 87 patients to determine whether RFs were associated with treatment outcomes. Associations between identified RFs in NT-FES and gene expression profiles were evaluated. NT-FES exhibited alterations of 30 RFs, with the greatest involvement of microstructural heterogeneity followed by measures of brain region shape. The identified RFs were mainly located in the central executive network, frontal-temporal network, and limbic system. Two baseline RFs with the involvement of microstructural heterogeneity predicted treatment response with moderate accuracy (78% for the first sample, 70% for the second sample). Exploratory analyses indicated that RF alterations were spatially related to the expression of schizophrenia risk genes. In summary, the present findings link brain abnormalities in schizophrenia with molecular features and treatment response.

Synovial osteoclastogenesis mediated by chondrocyte-secreted TNFα promotes TMJ condylar resorption.

BACKGROUND: Insufficient occlusal support (IOS) frequently causes subchondral bone absorption in temporomandibular joint osteoarthritis, and the underlying mechanism requires further investigation. METHODS: An IOS model was established by abrading rat molars. Micro-computed tomography was used to evaluate subchondral bone changes. Osteoclastogenesis of synovium-derived macrophages (SDMs) was confirmed by TRAP staining. Cartilage-specific TNFα depletion was achieved by intra-articular injection of adeno-associated virus carrying shRNA against murine TNFα under control of collagen type II. In vitro, chondrocytes were mechanically compressed and conditioned medium (CM) was collected to detect its ability to induce osteoclastogenesis of SDMs. RESULTS: Synovial osteoclastogenesis and condyle resorption were observed following IOS. TNFα level was elevated in hypertrophic chondrocytes after IOS. Synovial Wnt5a level increased, but Wnt3a level decreased after IOS. Depletion of TNFα in chondrocytes alleviated the synovial osteoclastogenesis and condyle bone resorption. In vitro compression of chondrocytes potentiated TNFα expression and secretion. The CM promoted osteoclastogenesis of SDMs, which were partially prohibited by TNFα neutralizing antibody. Furthermore, inhibition of Wnt3a facilitated osteoclastogenesis, whereas inhibition of Wnt5a partially suppressed osteoclastogenesis, of SDMs cultured in CM. CONCLUSION: Chondrocyte-secreted TNFα induced by IOS is a critical regulator of synovial osteoclastogenesis and subsequent condylar resorption, partially through non-canonical Wnt5a pathway.

Surface modification prepared porous copper oxide/(Cu-S)n metal-organic framework/reduced graphene oxide hierarchical structure for highly selective electrochemical quercetin detection.

Electrochemical alkalization of (Cu-S)n metal-organic framework (MOF) and graphene oxide ((Cu-S)n MOF/GO) composite yields a new CuO/(Cu-S)n MOF/RGO (reduced GO) composite with porous morphology on screen printed carbon electrode (SPCE) which facilitated the electron transfer properties in electrochemical quercetin (QUE) detection. A selective QUE detection ability has been demonstrated by the constructed electrochemical sensor (CuO/(Cu-S)n MOF/RGO/SPCE), which also has a broad dynamic range of 0.5 to 115 µM in pH 3 by differential pulse voltammetry. The detection limit is 0.083 µM (S/N = 3). In this study, it was  observed that the real samples contained 0.34 mg mL-1 and 27.7 µg g-1 QUE in wine and onion, respectively.

Gas Turbine Anomaly Detection under Time-Varying Operation Conditions Based on Spectra Alignment and Self-Adaptive Normalization.

Gas turbine vibration data may exhibit considerable differences under time-varying conditions, which poses challenges for neural network anomaly detection. We first propose a framework for a gas turbine vibration frequency spectra process under time-varying operation conditions, assisting neural networks' ability to capture weak information. The framework involves scaling spectra for aligning all frequency components related to rotational speed and normalizing frequency amplitude in a self-adaptive way. Degressive beta variational autoencoder is employed for learning spectra characteristics and anomaly detection, while a multi-category anomaly index is proposed to accommodate various operating conditions. Finally, a dataset of blade Foreign Object Damage (FOD) fault occurring under time-varying operating conditions was used to validate the framework and anomaly detection. The results demonstrate that the proposed method can effectively reduce the spectra differences under time-varying conditions, and also detect FOD fault during operation, which are challenging to identify using conventional methods.