Oxidative stress promotes oral carcinogenesis via Thbs1-mediated M1-like tumor-associated macrophages polarization.

Although oxidative stress is closely associated with tumor invasion and metastasis, its' exact role and mechanism in the initial stage of oral cancer remain ambiguous. Glutamine uptake mediated by alanine-serine-cysteine transporter 2 (ASCT2) participates in glutathione synthesis to resolve oxidative stress. Currently, we firstly found that ASCT2 deletion caused oxidative stress in oral mucosa and promoted oral carcinogenesis induced by 4-Nitroquinoline-1-oxide (4-NQO) using transgenic mice of ASCT2 knockout in oral epithelium. Subsequently, we identified an upregulated gene Thbs1 linked to macrophage infiltration by mRNA sequencing and immunohistochemistry. Importantly, multiplex immunohistochemistry showed M1-like tumor-associated macrophages (TAMs) were enriched in cancerous area. Mechanically, targeted ASCT2 effectively curbed glutamine uptake and caused intracellular reactive oxygen species (ROS) accumulation, which upregulated Thbs1 in oral keratinocytes and then activated p38, Akt and SAPK/JNK signaling to polarize M1-like TAMs via exosome-transferred pathway. Moreover, we demonstrated M1-like TAMs promoted malignant progression of oral squamous cell carcinoma (OSCC) both in vitro and in vivo by a DOK transformed cell line induced by 4-NQO. All these results establish that oxidative stress triggered by ASCT2 deletion promotes oral carcinogenesis through Thbs1-mediated M1 polarization, and indicate that restore redox homeostasis is a new approach to prevent malignant progression of oral potentially malignant disorders.

Efficient expression and purification of rat CRP in Pichia pastoris.

C-reactive protein (CRP) plays a crucial role in the diagnosis and monitoring of the non-specific acute phase response in humans. In contrast, rat CRP (rCRP) is an atypical acute-phase protein that possesses unique features, such as a possible incapacity to trigger the complement system and markedly elevated baseline plasma concentrations. To facilitate in vitro studies on these unique characteristics, obtaining high-quality pure rCRP is essential. Here we explored various strategies for rCRP purification, including direct isolation from rat plasma and recombinant expression in both prokaryotic and eukaryotic systems. Our study optimized the recombinant expression system to enhance the secretion and purification efficiency of rCRP. Compared to traditional purification methods, we present a streamlined and effective approach for the expression and purification of rCRP in the Pichia pastoris system. This refined methodology offers significant improvements in the efficiency and effectiveness of rCRP purification, thereby facilitating further structural and functional studies on rCRP.

Loss of OsMATE6 Function Enhances Drought Resistance Without Yield Penalty by Regulating Stomatal Closure in Rice.

Drought is one of the most severe environmental factors limiting plant growth and crop yield, necessitating the identification of genes that enhance drought resistance for crop improvement. Through screening an ethyl methyl sulfonate-mutagenized rice mutant library, we isolated the PEG tolerance mutant 97-1 (ptm97-1), which displays enhanced resistance to osmotic and drought stress, and increased yield under drought conditions. A point mutation in OsMATE6 was identified as being associated with the drought-resistant phenotype of ptm97-1. The role of OsMATE6 in conferring drought resistance was confirmed by additional OsMATE6 knockout mutants. OsMATE6 is expressed in guard cells, shoots and roots and the OsMATE6-GFP fusion protein predominantly localizes to the plasma membrane. Our ABA efflux assays suggest that OsMATE6 functions as an ABA efflux transporter; mutant protoplasts exhibited a slower ABA release rate compared to the wild type. We hypothesize that OsMATE6 regulates ABA levels in guard cells, influencing stomatal closure and enhancing drought resistance. Notably, OsMATE6 knockout mutants demonstrated greater yields under field drought conditions compared to wild-type plants, highlighting OsMATE6 as a promising candidate for improving crop drought resistance.

Flexible Temperature Sensor with High Reproducibility and Wireless Closed-Loop System for Decoupled Multimodal Health Monitoring and Personalized Thermoregulation.

Temperature and pulse waves are two fundamental indicators of body health. Specifically, thermoresistive flexible temperature sensors are one of the most applied sensors. However, they suffer from poor reproducibility of resistivity; and decoupling temperature from pressure/strain is still challenging. Besides, autonomous thermoregulation by wearable sensory systems is in high demand, but conventional commercial apparatuses are cumbersome and not suitable for long-term portable use. Here, a material-design strategy is developed to overcome the problem of poor reproducibility of resistivity by tuning the thermal expansion coefficient to nearly zero, precluding the detriment caused by shape expansion/shrinkage with temperature variation and achieving high reproducibility. The strategy also obtains more reliable sensitivity and higher stability, and the designed thermoresistive fiber has strain-insensitive sensing performance and fast response/recovery time. A smart textile woven by the thermoresistive fiber can decouple temperature and pulse without crosstalk; and a flexible wireless closed-loop system comprising the smart textile, a heating textile, a flexible diminutive control patch, and a smartphone is designed and constructed to monitor health status in real-time and autonomously regulate body temperature. This work offers a new route to circumvent temperature-sensitive effects for flexible sensors and new insights for personalized thermoregulation.

A graph-learning based model for automatic diagnosis of Sjögren's syndrome on digital pathological images: a multicentre cohort study.

BACKGROUND: Sjögren's Syndrome (SS) is a rare chronic autoimmune disorder primarily affecting adult females, characterized by chronic inflammation and salivary and lacrimal gland dysfunction. It is often associated with systemic lupus erythematosus, rheumatoid arthritis and kidney disease, which can lead to increased mortality. Early diagnosis is critical, but traditional methods for diagnosing SS, mainly through histopathological evaluation of salivary gland tissue, have limitations. METHODS: The study used 100 labial gland biopsy, creating whole-slide images (WSIs) for analysis. The proposed model, named Cell-tissue-graph-based pathological image analysis model (CTG-PAM) and based on graph theory, characterizes single-cell feature, cell-cell feature, and cell-tissue feature. Building upon these features, CTG-PAM achieves cellular-level classification, enabling lymphocyte recognition. Furthermore, it leverages connected component analysis techniques in the cell graph structure to perform SS diagnosis based on lymphocyte counts. FINDINGS: CTG-PAM outperforms traditional deep learning methods in diagnosing SS. Its area under the receiver operating characteristic curve (AUC) is 1.0 for the internal validation dataset and 0.8035 for the external test dataset. This indicates high accuracy. The sensitivity of CTG-PAM for the external dataset is 98.21%, while the accuracy is 93.75%. In comparison, the sensitivity and accuracy for traditional deep learning methods (ResNet-50) are lower. The study also shows that CTG-PAM's diagnostic accuracy is closer to skilled pathologists compared to beginners. INTERPRETATION: Our findings indicate that CTG-PAM is a reliable method for diagnosing SS. Additionally, CTG-PAM shows promise in enhancing the prognosis of SS patients and holds significant potential for the differential diagnosis of both non-neoplastic and neoplastic diseases. The AI model potentially extends its application to diagnosing immune cells in tumor microenvironments.

Quantum computational finance for martingale asset pricing in incomplete markets.

A derivative is a financial asset whose future payoff is a function of underlying assets. Pricing a financial derivative involves setting up a market model, finding a martingale ("fair game") probability measure for the model from the existing asset prices, and using that probability measure to price the derivative. When the number of underlying assets and/or the number of market outcomes in the model is large, pricing can be computationally demanding. In this work, we first formulate the pricing problem in a linear algebra setting, including the realistic setting of incomplete markets where derivatives do not have a unique price. We show that the problem can be solved with a variety of quantum techniques such as quantum linear programming and the quantum linear systems algorithm. While in previous works the martingale measure is assumed to be given, here it is extracted from market variables akin to bootstrapping, a common practice among financial institutions. We discuss the quantum zero-sum game algorithm and the quantum simplex algorithm as viable subroutines. For quantum linear systems solvers, we formalize a new market assumption milder than market completeness, which allows the potential for large speedups. Towards prototype use cases, we conduct numerical experiments motivated by the Black-Scholes-Merton model.

Improved Measurement of the Differential Polarizability Using Co-Trapped Ions.

We present a novel approach for measuring the differential static scalar polarizability of a target ion utilizing a "polarizability scale" scheme with a reference ion co-trapped in a linear Paul trap. The differential static scalar polarizability of the target ion can be precisely extracted by measuring the ratio of the ac Stark shifts induced by an add-on infrared laser shed on both ions. This method circumvents the need for the calibration of the intensity of the add-on laser, which is usually the bottleneck for measurements of the polarizability of trapped ions. As a demonstration, ^{27}Al^{+} (the target ion) and ^{40}Ca^{+} (the reference ion) are used in this work, with an add-on laser at 1068 nm injected into the ion trap along the trap axis. The differential static scalar polarizability of ^{27}Al^{+} is extracted to be 0.416(14) a.u. by measuring the ratio of the ac Stark shifts of both ions. Compared to the most recent result [Phys. Rev. Lett. 123, 033201 (2019)PRLTAO0031-900710.1103/PhysRevLett.123.033201], the relative uncertainty of the differential static scalar polarizability of ^{27}Al^{+} is reduced by approximately a factor of 4, to 3.4%. This improvement is expected to be further enhanced by using an add-on laser with a longer wavelength.

Expression and prognostic analysis of PFKFB4 in oral squamous cell carcinoma.

Fructose-6-phosphate 2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) is a crucial enzyme in the glycolysis pathway, possessing both kinase and phosphatase capabilities. Although it has emerged as an important oncogene in various cancer types, its function in oral squamous cell carcinoma (OSCC) is still not well understood. In our research, PFKFB4 expression was assessed via immunohistochemical (IHC) staining of tissue microarrays and OSCC patient specimens. The transcriptional expression of PFKFB4 in OSCC was analyzed by utilizing The Cancer Genome Atlas (TCGA) dataset. Correlation between PFKFB4 expression and clinicopathological features was examined using the χ2 test. Prognostic investigation of PFKFB4 was conducted via Kaplan-Meier and Cox analyses. PFKFB4 levels were notably elevated in OSCC samples in comparison to adjacent normal tissues (P < 0.001). Elevated PFKFB4 expression was associated with higher histologic grade (P = 0.0438), higher T stage (P = 0.031), and more advanced clinical stage (P = 0.0063). The ROC curve demonstrated the diagnostic potential of PFKFB4 (AUC = 0.827). Increased levels of PFKFB4 were linked to decreased overall survival (OS) (P = 0.04), poorer disease-specific survival (DSS) (P = 0.04), and shorter progression-free interval (PFI) (P < 0.001). PFKFB4 expression was identified as an independent risk factor for OS based on Cox regression analysis [hazard ratio (HR) = 1.517, P = 0.044)]. An OS nomogram was constructed with a concordance index of 0.690. Our findings reveal that upregulated PFKFB4 expression in OSCC tissues could serve as a potential prognostic biomarker.

Mechanochemically Reprogrammed Tantalum Interfaces Enhance Osseointegration Via Immunomodulation.

Bone and tooth defects can considerably affect the quality of life and health of patients, and orthopedic implants remain the primary method of addressing such defects. However, implant materials cannot coordinate with the immune microenvironment because of their biological inertness, which may lead to implant loosening or failure. Motivated by the microstructure of nacre, we engineered a biomimetic micro/nanoscale topography on a tantalum surface using a straightforward method. This comprised an organized array of tantalum nanotubes arranged in a brick wall structure, with epigallocatechin gallate acting as "mortar." The coating improved the corrosion resistance, biocompatibility, and antioxidant properties. In vitro and in vivo evaluations further confirmed that coatings can create a favorable bone immune microenvironment through the synergistic effects of mechanochemistry and enhance bone integration. This research offers a new viewpoint on the creation of sophisticated functional implants, possessing vast potential for use in the regeneration and repair of bone tissue.

[Lycium barbarum miR2911-loaded exosomes promote spermatogenic function recovery in rats with non-obstructive azoospermia by regulating Wnt/ß-catenin signaling pathways].

OBJECTIVE: To investigate the effect of exosomes loaded with Lycium barbarum miRNA (Lb-miR2911) on spermatogenic function recovery in non-obstructive azoospermia (NOA) rats through cross-regulation of the Wnt/ß-catenin signaling pathways. METHODS: We established an NOA model in 30 four-week-old male SD rats by intraperitoneal injection of busulfan. At 5 weeks after modeling, we equally randomized the rats into a model control group (MC，untreated), an Lb-miR2911EXO group (Lb-miR2911EXO ，treated by intratesticular injection of Lb-miR2911-loaded exosomes), and a sham group (Shame，treated by intratesticular injection of exosomes-empty drug), with another 10 male SD rats taken as normal controls（NC）. We observed the uptake and metabolic changes of Lb-miR2911 in the testis tissue of the rats by RNA FISH at 2 and 6 weeks after treatment, detected cell proliferation, spermatogenesis and gene expressions of the Wnt/ß-catenin signaling pathways in the testis tissue by Transcriptome sequencing analysis combined with Western blot and RT-PCR at 12 weeks, evaluated the recovery of the spermatogenic function based on the testis tissue morphology and sperm quality, and assessed the organ toxicity of Lb-miR2911 in the tissue and organs of the rats based on histomorphological analysis and the levels of serum TNF-α, IL-1ß, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and other relevant indicators. RESULTS: After 12 weeks of treatment, histomorphological analysis showed regular arrangement of spermatogenic cells at all levels in the testis tissue, with a large number of mature sperm in the tubular lumen, and with significantly higher Johnsen scores, testis weight, testicular index, sperm concentration and sperm motility in the Lb-miR2911EXO than in the sham group (all P< 0.05). Compared with the model controls, the Lb-miR2911EXO group exhibited remarkably down-regulated gene expression of DACT3 (P< 0.05), up-regulated expressions of DVL2 and ß-catenin (P< 0.05), elevated levels of p-DVL2 and ß-catenin (nucleus) proteins (P< 0.05), increased expressions of cell proliferation-related genes CCND1, CCNE1 and CCNE2 (P< 0.05) and spermatogenesis-related genes DMC1, CCR6, JAM2 and KLC3 (P< 0.05). No pathological changes were observed in the lung, liver and kidney tissues of the rats, or in the levels of serum TNF-α, IL-1ß, AST, ALT, creatinine and urea nitrogen in the rats treated with Lb-miR2911EXO compared with the normal controls (P > 0.05). CONCLUSION: Lb-miR2911-loaded exosomes promote spermatogenic function recovery in NOA rats through cross-regulation of the DACT3, Wnt and ß-catenin signaling pathways.

The influence of task-irrelevant color perception on flanker task performance: Insights from behavioral and ERP data.

Perception of color as a task-relevant stimulus can affect cognition and behavior in the flanker task; however, it remains unclear whether it has the same impact when it is a task-irrelevant stimulus dimension. To this end, we applied four-letter flanker tasks with or without colored (red/blue) to 23 healthy young adults, while recording the event-related potentials (ERPs) and behavioral performance. The flanker task included four kinds of color types: non-color letter (NC), all color letter (AC), flanker color letter (FC), and target color letter (TC), each flanker task included congruent and incongruent conditions. The behavioral data demonstrated the classic conflict effect across all color types of flanker tasks in both reaction times (RTs) and accuracy, the significant interaction and main effect of color type factors were only observed in accuracy. The ERP results showed significant interaction between conflict factor (congruent, incongruent) and color type (NC, AC, FC, and TC), and the color type factor enhanced the fronto-central P2 (180-200 ms), descended the fronto-centro-parietal N2b (260-320 ms), and increased the fronto-central P3b (360-520 ms). The fronto-central P2 and the fronto-central P3b were larger for TC than NC, AC, and FC in the congruent condition, while the fronto-central P3b was smaller for NC than AC, FC, and TC in the incongruent condition. Furthermore, the fronto-centro-parietal N2b was decreased successively in NC, AC, FC, and TC in both congruent and incongruent conditions. Overall, our findings suggested that the task-irrelevant stimuli dimension of color can capture some attentional resources and is affected by the location of color (target/flanker) and the type of task trial (congruent/incongruent) in the flanker task.

Maternal prenatal immune activation associated with brain tissue microstructure and metabolite concentrations in newborn infants.

Few human studies have assessed the association of prenatal maternal immune activation (MIA) with measures of brain development and psychiatric risk in newborn offspring. Our goal was to identify the effects of MIA during the 2nd and 3rd trimesters of pregnancy on newborn measures of brain metabolite concentrations, tissue microstructure, and motor development. This was a prospective longitudinal cohort study conducted with nulliparous pregnant women who were aged 14 to 19 years and recruited in their 2nd trimester, as well as their children who were followed through 14 months of age. MIA was indexed by maternal interleukin-6 (IL-6) and C-reactive protein (CRP) in both trimesters of pregnancy. Primary outcomes included: (1) newborn brain metabolite concentrations as ratios to creatine (N-acetylaspartate (NAA)/creatine (Cr) and choline (Cho)/Cr) measured using Magnetic Resonance Spectroscopy; (2) newborn fractional anisotropy and mean diffusivity, measured using Diffusion Tensor Imaging; and (3) indices of motor development, assessed prenatally and postnatally at ages 4- and 14-months. Maternal IL-6 and CRP levels associated significantly with both metabolites in the putamen, thalamus, insula, and the internal capsule. Maternal IL-6 associated significantly with fractional anisotropy in the putamen, caudate, thalamus, insula, and precuneus, and with mean diffusivity in the inferior parietal and middle temporal gyrus. CRP associated significantly with fractional anisotropy in the thalamus, insula, and putamen. Significant associations were found in common regions across imaging modalities, though the direction of associations differed by immune marker. In addition, both maternal IL-6 and CRP (in both trimesters) prenatally associated significantly with offspring motor development at 4- and 14-months of age. The left thalamus mediated effects of IL-6 on postnatal motor development. These findings demonstrate that levels of MIA in mid- to late pregnancy in a generally healthy sample associate with tissue characteristics in newborn brain regions that primarily support motor integration and coordination, as well as behavioral regulation. Those brain effects may contribute to differences in motor development.

Alterations in the gut microbiome after transjugular intrahepatic portosystemic shunt in patients with hepatitis B virus-related portal hypertension.

BACKGROUND: Gut microbiota (GM) affects the progression and response to treatment in liver diseases. The GM composition is diverse and associated with different etiologies of liver diseases. Notably, alterations in GM alterations are observed in patients with portal hypertension (PH) secondary to cirrhosis, with hepatitis B virus (HBV) infection being a major cause of cirrhosis in China. Thus, understanding the role of GM alterations in patients with HBV infection-related PH is essential. AIM: To evaluate GM alterations in patients with HBV-related PH after transjugular intrahepatic portosystemic shunt (TIPS) placement. METHODS: This was a prospective, observational clinical study. There were 30 patients (with a 100% technical success rate) recruited in the present study. Patients with esophagogastric variceal bleeding due to HBV infection-associated PH who underwent TIPS were enrolled. Stool samples were obtained before and one month after TIPS treatment, and GM was analyzed using 16S ribosomal RNA amplicon sequencing. RESULTS: One month after TIPS placement, 8 patients developed hepatic encephalopathy (HE) and were assigned to the HE group; the other 22 patients were assigned to the non-HE group. There was no substantial disparity in the abundance of GM at the phylum level between the two groups, regardless of TIPS treatment (all, P > 0.05). However, following TIPS placement, the following results were observed: (1) The abundance of Haemophilus and Eggerthella increased, whereas that of Anaerostipes, Dialister, Butyricicoccus, and Oscillospira declined in the HE group; (2) The richness of Eggerthella, Streptococcus, and Bilophila increased, whereas that of Roseburia and Ruminococcus decreased in the non-HE group; and (3) Members from the pathogenic genus Morganella appeared in the HE group but not in the non-HE group. CONCLUSION: Intestinal microbiota-related synergism may predict the risk of HE following TIPS placement in patients with HBV-related PH. Prophylactic microbiome therapies may be useful for preventing and treating HE after TIPS placement.

First-principles modeling of H2CO3 molecular adsorption on CaSiO3(001) surface for application in the sequestration and utilization of CO2.

This work employed density functional theory (DFT) to further study the adsorption of H2CO3, HCO3-, and CO32- on the CaSiO3(001) surface, which could provide additional insights into the mechanism of carbonation on the CaSiO3 surface. It was concluded that the carbonation of CO2 promoted carbon sequestration, whereby the aqueous carbonation route increased the reaction rate substantially compared to direct gas-solid carbonation. H2CO3 is more conducive to CO2 sequestration, which can be attributed to the interaction of H atoms with the surface. Further, H2CO3 can be converted into HCO3- or CO32- on the CaO-terminated (001) surface, whereas only HCO3- was formed on the SiO-terminated (001) surface. All the adsorption energies of H2CO3 were negative, suggesting that H2CO3 adsorption was energetically stable and spontaneous. The most likely adsorption model of HCO3-, having negative adsorption energy, was the one adsorbed on the SiO-terminated (001) surface, in which HCO3- is transformed into CO32-. The other adsorption models of HCO3- and all the adsorption models of CO32- have positive adsorption energies. Considering the adsorption process of H2CO3, HCO3- and CO32- adsorption reactions may occur successively to some extent depending on the environment.

Extracellular vesicles meet mitochondria: Potential roles in regenerative medicine.

Extracellular vesicles (EVs), secreted by most cells, act as natural cell-derived carriers for delivering proteins, nucleic acids, and organelles between cells. Mitochondria are highly dynamic organelles responsible for energy production and cellular physiological processes. Recent evidence has highlighted the pivotal role of EVs in intercellular mitochondrial content transfer, including mitochondrial DNA (mtDNA), proteins, and intact mitochondria. Intriguingly, mitochondria are crucial mediators of EVs release, suggesting an interplay between EVs and mitochondria and their potential implications in physiology and pathology. However, in this expanding field, much remains unknown regarding the function and mechanism of crosstalk between EVs and mitochondria and the transport of mitochondrial EVs. Herein, we shed light on the physiological and pathological functions of EVs and mitochondria, potential mechanisms underlying their interactions, delivery of mitochondria-rich EVs, and their clinical applications in regenerative medicine.

Diagnosing Solid Lesions in the Pancreas With Multimodal Artificial Intelligence: A Randomized Crossover Trial.

Importance: Diagnosing solid lesions in the pancreas via endoscopic ultrasonographic (EUS) images is challenging. Artificial intelligence (AI) has the potential to help with such diagnosis, but existing AI models focus solely on a single modality. Objective: To advance the clinical diagnosis of solid lesions in the pancreas through developing a multimodal AI model integrating both clinical information and EUS images. Design, Setting, and Participants: In this randomized crossover trial conducted from January 1 to June 30, 2023, from 4 centers across China, 12 endoscopists of varying levels of expertise were randomly assigned to diagnose solid lesions in the pancreas with or without AI assistance. Endoscopic ultrasonographic images and clinical information of 439 patients from 1 institution who had solid lesions in the pancreas between January 1, 2014, and December 31, 2022, were collected to train and validate the joint-AI model, while 189 patients from 3 external institutions were used to evaluate the robustness and generalizability of the model. Intervention: Conventional or AI-assisted diagnosis of solid lesions in the pancreas. Main Outcomes and Measures: In the retrospective dataset, the performance of the joint-AI model was evaluated internally and externally. In the prospective dataset, diagnostic performance of the endoscopists with or without the AI assistance was compared. Results: The retrospective dataset included 628 patients (400 men [63.7%]; mean [SD] age, 57.7 [27.4] years) who underwent EUS procedures. A total of 130 patients (81 men [62.3%]; mean [SD] age, 58.4 [11.7] years) were prospectively recruited for the crossover trial. The area under the curve of the joint-AI model ranged from 0.996 (95% CI, 0.993-0.998) in the internal test dataset to 0.955 (95% CI, 0.940-0.968), 0.924 (95% CI, 0.888-0.955), and 0.976 (95% CI, 0.942-0.995) in the 3 external test datasets, respectively. The diagnostic accuracy of novice endoscopists was significantly enhanced with AI assistance (0.69 [95% CI, 0.61-0.76] vs 0.90 [95% CI, 0.83-0.94]; P < .001), and the supplementary interpretability information alleviated the skepticism of the experienced endoscopists. Conclusions and Relevance: In this randomized crossover trial of diagnosing solid lesions in the pancreas with or without AI assistance, the joint-AI model demonstrated positive human-AI interaction, which suggested its potential to facilitate a clinical diagnosis. Nevertheless, future randomized clinical trials are warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT05476978.

Selective and quasi-continuous switching of ferroelectric Chern insulator devices for neuromorphic computing.

Quantum materials exhibit dissipationless topological edge state transport with quantized Hall conductance, offering notable potential for fault-tolerant computing technologies. However, the development of topological edge state-based computing devices remains a challenge. Here we report the selective and quasi-continuous ferroelectric switching of topological Chern insulator devices, showcasing a proof-of-concept demonstration in noise-immune neuromorphic computing. We fabricate this ferroelectric Chern insulator device by encapsulating magic-angle twisted bilayer graphene with doubly aligned h-BN layers and observe the coexistence of the interfacial ferroelectricity and the topological Chern insulating states. The observed ferroelectricity exhibits an anisotropic dependence on the in-plane magnetic field. By tuning the amplitude of the gate voltage pulses, we achieve ferroelectric switching between any pair of Chern insulating states in the presence of a finite magnetic field, resulting in 1,280 ferroelectric states with distinguishable Hall resistance levels on a single device. Furthermore, we demonstrate deterministic switching between two arbitrary levels among the record-high number of ferroelectric states. This unique switching capability enables the implementation of a convolutional neural network resistant to external noise, utilizing the quantized Hall conductance levels of the Chern insulator device as weights. Our study provides a promising avenue towards the development of topological quantum neuromorphic computing, where functionality and performance can be drastically enhanced by topological quantum materials.

Poly(p-coumaric acid) nanoparticles alleviate temporomandibular joint osteoarthritis by inhibiting chondrocyte ferroptosis.

Oxidative stress and inflammation are key drivers of osteoarthritis (OA) pathogenesis and disease progression. Herein we report the synthesis of poly(p-coumaric) nanoparticles (PCA NPs) from p-courmaic acid (p-CA), a naturally occurring phytophenolic acid, to be a multifunctional and drug-free therapeutic for temporomandibular joint osteoarthritis (TMJOA). Compared to hyaluronic acid (HA) that is clinically given as viscosupplementation, PCA NPs exhibited long-term efficacy, superior anti-oxidant and anti-inflammatory properties in alleviating TMJOA and repairing the TMJ cartilage and subchondral bone in a rat model of TMJOA. Notably, TMJ repair mediated by PCA NPs could be attributed to their anti-oxidant and anti-inflammatory properties in enhancing cell proliferation and matrix synthesis, while reducing inflammation, oxidative stress, matrix degradation, and chondrocyte ferroptosis. Overall, our study demonstrates a multifunctional nanoparticle, synthesized from natural p-coumaric acid, that is stable and possess potent antioxidant, anti-inflammatory properties and ferroptosis inhibition, beneficial for treatment of TMJOA.

C-reactive protein: structure, function, regulation, and role in clinical diseases.

C-reactive protein (CRP) is a plasma protein that is evolutionarily conserved, found in both vertebrates and many invertebrates. It is a member of the pentraxin superfamily, characterized by its pentameric structure and calcium-dependent binding to ligands like phosphocholine (PC). In humans and various other species, the plasma concentration of this protein is markedly elevated during inflammatory conditions, establishing it as a prototypical acute phase protein that plays a role in innate immune responses. This feature can also be used clinically to evaluate the severity of inflammation in the organism. Human CRP (huCRP) can exhibit contrasting biological functions due to conformational transitions, while CRP in various species retains conserved protective functions in vivo. The focus of this review will be on the structural traits of CRP, the regulation of its expression, activate complement, and its function in related diseases in vivo.