Transport and spatio-temporal conversion of sugar facilitate the formation of spatial gradients of starch in wheat caryopses.

Wheat grain starch content displays large variations within different pearling fractions, which affecting the processing quality of corresponding flour, while the underlying mechanism on starch gradient formation is unclear. Here, we show that wheat caryopses acquire sugar through the transfer of cells (TCs), inner endosperm (IE), outer endosperm (OE), and finally aleurone (AL) via micro positron emission tomography-computed tomography (PET-CT). To obtain integrated information on spatial transcript distributions, developing caryopses are laser microdissected into AL, OE, IE, and TC. Most genes encoding carbohydrate transporters are upregulated or specifically expressed, and sugar metabolites are more highly enriched in the TC group than in the AL group, in line with the PET-CT results. Genes encoding enzymes in sucrose metabolism, such as sucrose synthase, beta-fructofuranosidase, glucose-1-phosphate adenylyltransferase show significantly lower expression in AL than in OE and IE, indicating that substrate supply is crucial for the formation of starch gradients. Furthermore, the low expressions of gene encoding starch synthase contribute to low starch content in AL. Our results imply that transcriptional regulation represents an important means of impacting starch distribution in wheat grains and suggests breeding targets for enhancing specially pearled wheat with higher quality.

Associations of serum arginine acid with sarcopenia in Chinese eldely women.

BACKGROUND: The prevalence of sarcopenia is increasing in worldwide with accelerated aging process. The high dietary protein intakes are associated with improved muscle mass and strength especially in Asian countries. However, there are few researches on amino acid levels or mechanism exploration. We conducted a case-control study to explore the amino acid metabolic characteristics and potential mechanism of elderly women with sarcopenia using targeted amino acid metabolomics approach combined with an analysis of dietary intake. METHODS: For our case-control study, we recruited women (65-75 y) from a Shanghai community with 50 patients with sarcopenia and 50 healthy controls. The consensus updated by the Asian Working Group on Sarcopenia in 2019 was used to screening for sarcopenia and control groups. We collected fasting blood samples and evaluated dietary intake. We used the amino acid-targeted metabolomics by ultra performance liquid chromatography tandem mass spectrometry to identify metabolic differentials between the case and control groups and significantly enriched metabolic pathways. RESULTS: The case (sarcopenia) group had a lower intake of energy, protein, and high-quality protein (P < 0.05) compared to the control (healthy) group. We identified four differential amino acids: arginine (P < 0.001) and cystine (P = 0.003) were lower, and taurine (P = 0.001) were higher in the case group. CONCLUSION: Low levels of arginine in elderly women are associated with a higher risk of sarcopenia.

miR-223-5p serves as a diagnostic biomarker for acute coronary syndrome and its predictive value for the clinical outcome after PCI.

BACKGROUND: Acute coronary syndrome (ACS) is a serious cardiovascular disease that severely affects the quality of life and longevity of patients. MicroRNAs (miRNAs) play a key role in the progression of ACS with significant clinical value. The aim of this study was to examine the clinical value of miR-223-5p in ACS and on the occurrence of major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI). METHODS: The plasma expression of miR-223-5p was detected by RT-qPCR. The correlation of miR-223-5p and cTnI or Gensini score was shown by the Pearson method. Risk factors for the development of ACS were analyzed by multivariate logistic regression. The efficacy of miR-223-5p in identifying patients with ACS was shown by ROC curve. The predictive value of miR-223-5p for MACE development in ACS patients within 6 months after PCI was assessed by Kaplan-Meier curve and multivariate Cox regression. RESULTS: miR-223-5p levels were markedly elevated in ACS patients. miR-223-5p was found to be positively related to cTnI or Gensini score. miR-223-5p was a risk factor for ACS and significantly identified patients with ACS. MACE was more likely to occur after PCI in patients with high miR-223-5p levels, and miR-223-5p was an independent prognostic indicator of MACE. CONCLUSIONS: miR-223-5p had diagnostic value for ACS and predicted MACE after PCI.

Chiral absorption enhancement via critically coupled resonances in atomically thin photonic crystal exciton-polaritons.

Atomically thin transition metal dichalcogenides (TMDS) offer a promising route to the scaling down of optoelectronic devices to the ultimate thickness limit. But the weak light-matter interaction caused by their atomically thin nature makes them inevitably rely on external photonic structures to enhance optical absorption. Here, we report chiral absorption enhancement in atomically thin tungsten diselenide (WSe2) using chiral resonances in photonic crystal (PhC) nanostructures patterned directly in WSe2 itself. We show that the quality factors (Q factors) of the resonances grow exponentially as the PhC thickness approaches atomic limit. As such, the strong interaction of high Q factor photonic resonance with the coexisting exciton resonance in WSe2 results into self-coupled exciton-polaritons. By balancing the light coupling and absorption rates, the incident light can critically couple to chiral resonances in WSe2 PhC exciton-polaritons, leading to the theoretically limited 50% optical absorptance with over 84% circular dichroism (CD).

Causal relationship between immune cell phenotypes and risk of biliary tract cancer: evidence from Mendelian randomization analysis.

Background: Biliary tract cancer stands as a prevalent illness, posing significant risks to human health, where immune cells are pivotal in both its development and recovery processes. Due to the diverse functionalities exhibited by different immune cell phenotypes within the organism, and the relatively limited research on their relationship with biliary tract cancer, this study employed Mendelian randomization (MR) to explore their potential association, thereby aiding in a better understanding of the causal link between immune cell phenotypes and biliary tract cancer. Methods: In this study, the causative association of 731 immunophenotype with biliary tract cancer was established using publicly accessible genome-wide association study (GWAS) genetic data through two-sample MR analysis. Sensitivity analyses assess horizontal pleiotropy and heterogeneity of the study findings. Results: Among the 731 immunophenotypes examined, a total of 26 immune cell phenotypes were found to exhibit positive results, indicating a significant association with the risk of biliary tract cancer. We confirmed that among these 26 types of immune cells, there are primarily 13 types of B cells; three types of classical dendritic cells (CDCs), including CD80 on myeloid DC, HLA DR on myeloid DC, and Myeloid DC %DC; one type of mature stage T cell,CD4RA on TD CD4+; six types of regulatory T cells; and three types of myeloid cells.

Spin-Locked WS2 Vortex Emission via Photonic Crystal Bound States in the Continuum.

Owing to their strong exciton effects and valley polarization properties, monolayer transition-metal dichalcogenides (1L TMDs) have unfolded the prospects of spin-polarized light-emitting devices. However, the wavefront control of exciton emission, which is critical to generate structured optical fields, remains elusive. In this work, the experimental demonstration of spin-locked vortex emission from monolayer Tungsten Disulfide (1L WS2) integrated with Silicon Nitride (SiNx) PhC slabs is presented. The symmetry-protected bound states in the continuum (BIC) in the SiNx PhC slabs engender azimuthal polarization field distribution in the momentum space with a topological singularity in the center of the Brillouin zone, which imposes the resonantly enhanced WS2 exciton emission with a spin-correlated spiral phase front by taking advantage of the winding topologies of resonances with the assistance of geometric phase scheme. As a result, exciton emission from 1L WS2 exhibits helical wavefront and doughnut-shaped intensity beam profile in the momentum space with topological charges locked to the spins of light. This strategy on spin-dependent excitonic vortex emission may offer the unparalleled capability of valley-polarized structured light generation for 1L TMDs.

Excitonic van der Waals Metasurfaces for Resonant Wavefront Shaping at Deep Subwavelength Thickness Scale.

Dielectric phase gradient metasurfaces have emerged as promising candidates to shrink bulky optical elements to subwavelength thickness scale based on dielectric meta-atoms. These meta-atoms strongly interact with light, thus offering excellent phase manipulation of incident light. However, to fulfill 2π phase control using meta-atoms, the metasurface thickness, to date, is limited to the order of 102 nm. Here, we present the thickness scaling down of phase gradient metasurfaces to <λ/20 by using excitonic van der Waals metasurfaces. High-refractive-index enabled by exciton resonances and symmetry-breaking nanostructures in the patterned layered tungsten disulfide (WS2) corporately enable quasibound states in the continuum in WS2 metasurfaces, which consequently yield complete phase regulation of 2π with the thickness down to 35 nm. To illustrate the concept, we have experimentally demonstrated beam steering, focusing, and holographic display using WS2 metasurfaces. We envision our results unveiling new venues for ultimate thin phase gradient metasurfaces.

A wearable non-enzymatic sensor for continuous monitoring of glucose in human sweat.

To enhance personalized diabetes management, there is a critical need for non-invasive wearable electrochemical sensors made from flexible materials to enable continuous monitoring of sweat glucose levels. The main challenge lies in developing glucose sensors with superior electrochemical characteristics and high adaptability. Herein, we present a wearable sensor for non-enzymatic electrochemical glucose analysis. The sensor was synthesized using hydrothermal and one-pot preparation methods, incorporating gold nanoparticles (AuNPs) functionalized onto aminated multi-walled carbon nanotubes (AMWCNTs) as an efficient catalyst, and crosslinked with carboxylated styrene butadiene rubber (XSBR) and PEDOT:PSS. The sensors were then integrated onto screen-printed electrodes (SPEs) to create flexible glucose sensors (XSBR-PEDOT:PSS-AMWCNTs/AuNPs/SPE). Operating under neutral conditions, the sensor exhibits a linear range of 50 µmol/L to 600 µmol/L, with a limit of detection limit of 3.2 µmol/L (S/N = 3), enabling the detection of minute glucose concentrations. The flexible glucose sensor maintains functionality after 500 repetitions of bending at a 180° angle, without significant degradation in performance. Furthermore, the sensor exhibits exceptional stability, repeatability, and resistance to interference. Importantly, we successfully monitored changes in sweat glucose levels by applying screen-printed electrodes to human skin, with results consistent with normal physiological blood glucose fluctuations. This study details the fabrication of a wearable sensor characterized by ease of manufacture, remarkable flexibility, high sensitivity, and adaptability for non-invasive blood glucose monitoring through non-enzymatic electrochemical analysis. Thus, this streamlined fabrication process presents a novel approach for non-invasive, real-time blood glucose level monitoring.

Theoretical Study of Dissolved Gas Molecules in Transformer Oil Adsorbed on Intrinsic and TM (Ta, V)-Doped MoTe2 Monolayer.

In this paper, CH4, C2H2, H2, and CO adsorbed on intrinsic MoTe2 monolayer and transition metal atom (Ta, V)-doped MoTe2 monolayer have been investigated with density functional theory based on first-principles study. The adsorption energy, geometries, band structures, and density of states of four gases (CH4, C2H2, H2, and CO) adsorbed on the MoTe2 and doped MoTe2 surfaces were analyzed. The results shown that the gas adsorption performance of transition metal atom (Ta, V)-doped MoTe2 monolayers is more superior than that of intrinsic MoTe2, and the adsorption energy and charge transfer of the adsorbed gases on the TM-MoTe2 monolayer are significantly increased in comparison with both sides. Among them, Ta-MoTe2 has the largest Eads value in the adsorbed CO system with a very small adsorption distance, as well as a more suitable recovery time of CO at room temperature, so Ta-MoTe2 can be a candidate material for CO detection. New atoms were introduced during the doping process, which increased the carrier density and carrier mobility of the material, thus improving the charge transfer at the surface of the material. which provides a direction for the gas-sensitive properties of metal Ta-modified MoTe2 materials.

Dihydroartemisinin Modulates Enteric Glial Cell Heterogeneity to Alleviate Colitis.

The precise mechanism underlying the therapeutic effects of dihydroartemisinin (DHA) in alleviating colitis remains incompletely understood. A strong correlation existed between the elevation of glial fibrillary acidic protein (GFAP)+/S100 calcium binding protein B (S100ß)+ enteric glial cells (EGCs) in inflamed colonic tissues and the disruption of the intestinal epithelial barrier (IEB) and gut vascular barrier (GVB) observed in chronic colitis. DHA demonstrated efficacy in restoring the functionality of the dual gut barrier while concurrently attenuating intestinal inflammation. Mechanistically, DHA inhibited the transformation of GFAP+ EGCs into GFAP+/S100ß+ EGCs while promoting the differentiation of GFAP+/S100ß+ EGCs back into GFAP+ EGCs. Furthermore, DHA induced apoptosis in GFAP+/S100ß+ EGCs by inducing cell cycle arrest at the G0/G1 phase. The initial mechanism is further validated that DHA regulates EGC heterogeneity by improving dysbiosis in colitis. These findings underscore the multifaceted therapeutic potential of DHA in ameliorating colitis by improving dysbiosis, modulating EGC heterogeneity, and preserving gut barrier integrity, thus offering promising avenues for novel therapeutic strategies for inflammatory bowel diseases.

Analysis of optical properties and response mechanism of H2S fluorescent probe based on rhodamine derivatives.

H2S plays a crucial role in numerous physiological and pathological processes. In this project, a new fluorescent probe, SG-H2S, for the detection of H2S, was developed by introducing the recognition group 2,4-dinitrophenyl ether. The combination of rhodamine derivatives can produce both colorimetric reactions and fluorescence reactions. Compared with the current H2S probes, the main advantages of SG-H2S are its wide pH range (5-9), fast response (30 min), and high selectivity in competitive species (including biological mercaptan). The probe SG-H2S has low cytotoxicity and has been successfully applied to imaging in MCF-7 cells, HeLa cells, and BALB/c nude mice. We hope that SG-H2S will provide a vital method for the field of biology.

Revitalizing gut barrier integrity: role of miR-192-5p in enhancing autophagy via Rictor in enteritis.

Intestinal inflammation and compromised barrier function are critical factors in the pathogenesis of gastrointestinal disorders. This study aimed to investigate the role of miR-192-5p in modulating intestinal epithelial barrier (IEB) integrity and its association with autophagy. A DSS-induced colitis model was used to assess the effects of miR-192-5p on intestinal inflammation. In vitro experiments involved cell culture and transient transfection techniques. Various assays, including dual-luciferase reporter gene assays, quantitative real-time PCR, Western blotting, and measurements of transepithelial electrical resistance, were performed to evaluate changes in miR-192-5p expression, Rictor levels, and autophagy flux. Immunofluorescence staining, H&E staining, TEER measurements, and FITC-dextran analysis were also used. Our findings revealed a reduced expression of miR-192-5p in inflamed intestinal tissues, correlating with impaired IEB function. Overexpression of miR-192-5p alleviated TNF-induced IEB dysfunction by targeting Rictor, resulting in enhanced autophagy flux in enterocytes (ECs). Moreover, the therapeutic potential of miR-192-5p was substantiated in colitis mice, wherein increased miR-192-5p expression ameliorated intestinal inflammatory injury by enhancing autophagy flux in ECs through the modulation of Rictor. Our study highlights the therapeutic potential of miR-192-5p in enteritis by demonstrating its role in regulating autophagy and preserving IEB function. Targeting the miR-192-5p/Rictor axis is a promising approach for mitigating gut inflammatory injury and improving barrier integrity in patients with enteritis.NEW & NOTEWORTHY We uncover the pivotal role of miR-192-5p in fortifying intestinal barriers amidst inflammation. Reduced miR-192-5p levels correlated with compromised gut integrity during inflammation. Notably, boosting miR-192-5p reversed gut damage by enhancing autophagy via suppressing Rictor, offering a potential therapeutic strategy for fortifying the intestinal barrier and alleviating inflammation in patients with enteritis.

Investigation of the impact of planar microelectrodes on macrophage-mediated mesenchymal stem cell osteogenesis.

Osseointegration commences with foreign body inflammation upon implant placement, where macrophages play a crucial role in the immune response. Subsequently, during the intermediate and late stages of osseointegration, mesenchymal stem cells (MSCs) migrate and initiate their osteogenic functions, while macrophages support MSCs in osteogenesis. The utilization of ferroelectric P(VDF-TrFE) covered ITO planar microelectrodes facilitated the simulation of various surface charge to investigate their effects on MSCs' osteogenic differentiation and macrophage polarization and the results indicated a parabolic increase in the promotional effect of both with the rise in piezoelectric coefficient. Furthermore, the surface charge with a piezoelectric coefficient of -18 exhibited the strongest influence on the promotion of M1 polarization of macrophages and the promotion of MSCs' osteogenic differentiation. The impact of macrophage polarization and MSC osteogenesis following the interaction of macrophages affected by surface charge and MSC was ultimately investigated. It was observed that macrophages affected by the surface charge of -18 piezoelectric coefficient still exerted the most profound induced osteogenic effect, validating the essential role of M1-type macrophages in the osteogenic differentiation of MSCs.

WTAP participates in neuronal damage by protein translation of NLRP3 in an m6A-YTHDF1-dependent manner after traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a common complication of acute and severe neurosurgery. Remodeling of N6-methyladenosine (m6A) stabilization may be an attractive treatment option for neurological dysfunction after TBI. In the present study, we explored the epigenetic methylation of RNA-mediated NLRP3 inflammasome activation after TBI. METHODS: Neurological dysfunction, histopathology, and associated molecules were examined in conditional knockout (CKO) WTAP[flox/flox, Camk2a-cre], WTAPflox/flox, and pAAV-U6-shRNA-YTHDF1-transfected mice. Primary neurons were used in vitro to further explore the molecular mechanisms of action of WTAP/YTHDF1 following neural damage. RESULTS: We found that WTAP and m6A levels were upregulated at an early stage after TBI, and conditional deletion of WTAP in neurons did not affect neurological function but promoted functional recovery after TBI. Conditional deletion of WTAP in neurons suppressed neuroinflammation at the TBI early phase: WTAP could directly act on NLRP3 mRNA, regulate NLRP3 mRNA m6A level, and promote NLRP3 expression after neuronal injury. Further investigation found that YTH domain of YTHDF1 could directly bind to NLRP3 mRNA and regulate NLRP3 protein expression. YTHDF1 mutation or silencing improved neuronal injury, inhibited Caspase-1 activation, and decreased IL-1ß levels. This effect was mediated via suppression of NLRP3 protein translation, which also reversed the stimulative effect of WTAP overexpression on NLRP3 expression and inflammation. CONCLUSION: Our results indicate that WTAP participates in neuronal damage by protein translation of NLRP3 in an m6A-YTHDF1-dependent manner after TBI and that WTAP/m6A/YTHDF1 downregulation therapeutics is a viable and promising approach for preserving neuronal function after TBI, which can provide support for targeted drug development.

Artemisinin and its derivatives modulate glucose homeostasis and gut microbiota remodeling in a nutritional context.

Glucose metabolic disorders, prevalent in numerous metabolic diseases, have become a pressing global public health concern. Artemisinin (ART) and its derivatives, including artesunate (ARTs) and artemether (ARTe), have shown potential as metabolic regulators. However, the specific effects of ART and its derivatives on glucose metabolism under varying nutritional conditions and the associated molecular mechanisms remain largely unexplored. In this study, we examined the impact of ART, ARTs, and ARTe on glucose homeostasis using a mouse model subjected to different dietary regimens. Our findings revealed that ART, ARTs, and ARTe increased blood glucose levels in mice on a normal-chow diet (ND) while mitigating glucose imbalances in high-fat diet (HFD) mice. Notably, treatment with ART, ARTs, and ARTe had contrasting effects on in vivo insulin signaling, impairing it in ND mice and enhancing it in HFD mice. Moreover, the composition of gut microbiota underwent significant alterations following administration of ART and its derivatives. In ND mice, these treatments reduced the populations of bacteria beneficial for improving glucose homeostasis, including Parasutterella, Alloprevotella, Bifidobacterium, Ileibacterium, and Alistipes. In HFD mice, there was an increase in the abundance of beneficial bacteria (Alistipes, Akkermanisia) and a decrease in bacteria known to negatively impact glucose metabolism (Coprobacillus, Helicobacter, Mucispirillum, Enterorhabdus). Altogether, ART, ARTs, and ARTe exhibited distinct effects on the regulation of glucose metabolism, depending on the nutritional context, and these effects were closely associated with modifications in gut microbiota composition.

High fidelity detection of miRNAs from complex physiological samples through electrochemical nanosensors empowered by proximity catalysis and magnetic separation.

Electrochemical detection of miRNA biomarkers in complex physiological samples holds great promise for accurate evaluation of tumor burden in the perioperative period, yet limited by reproducibility and bias issues. Here, nanosensors installed with hybrid probes that responsively release catalytic DNAzymes (G-quadruplexes/hemin) were developed to solve the fidelity challenge in an immobilization-free detection. miRNA targets triggered toehold-mediated strand displacement reactions on the sensor surface and resulted in amplified shedding of DNAzymes. Subsequently, the interference background was removed by Fe3O4 core-facilitated magnetic separation. Binding aptamers of the electrochemical reporter (dopamine) were tethered closely to the catalytic units for boosting H2O2-mediated oxidation through proximity catalysis. The one-to-many conversion by dual amplification from biological-chemical catalysis facilitated sufficient homogeneous sensing signals on electrodes. Thereby, the nanosensor exhibited a low detection limit (2.08 fM), and high reproducibility (relative standard deviation of 1.99%). Most importantly, smaller variations (RSD of 0.51-1.04%) of quantified miRNAs were observed for detection from cell lysates, multiplexed detection from unprocessed serum, and successful discrimination of small upregulations in lysates of tumor tissue samples. The nanosensor showed superior diagnostic performance with an area under curve (AUC) of 0.97 and 94% accuracy in classifying breast cancer patients and healthy donors. These findings demonstrated the synergy of signal amplification and interference removal in achieving high-fidelity miRNA detection for practical clinical applications.

Correction: Halogen-bonded charge-transfer co-crystal scintillators for high-resolution X-ray imaging.

[This corrects the article DOI: 10.1039/D4SC00735B.].

Halogen-bonded charge-transfer co-crystal scintillators for high-resolution X-ray imaging.

The development of high-quality organic scintillators encounters challenges primarily associated with the weak X-ray absorption ability resulting from the presence of low atomic number elements. An effective strategy involves the incorporation of halogen-containing molecules into the system through co-crystal engineering. Herein, we synthesized a highly fluorescent dye, 2,5-di(4-pyridyl)thiazolo[5,4-d]thiazole (Py2TTz), with a fluorescence quantum yield of 12.09%. Subsequently, Py2TTz was co-crystallized with 1,4-diiodotetrafluorobenzene (I2F4B) and 1,3,5-trifluoro-2,4,6-triiodobenzene (I3F3B) obtaining Py2TTz-I2F4 and Py2TTz-I3F3. Among them, Py2TTz-I2F4 exhibited exceptional scintillation properties, including an ultrafast decay time (1.426 ns), a significant radiation luminescence intensity (146% higher than Bi3Ge4O12), and a low detection limit (70.49 nGy s-1), equivalent to 1/78th of the detection limit for medical applications (5.5 µGy s-1). This outstanding scintillation performance can be attributed to the formation of halogen-bonding between I2F4B and Py2TTz. Theoretical calculations and single-crystal structures demonstrate the formation of halogen-bond-induced rather than π-π-induced charge-transfer cocrystals, which not only enhances the X-ray absorption ability and material conductivity under X-ray exposure, but also constrains molecular vibration and rotation, and thereby reducing non-radiative transition rate and sharply increasing its fluorescence quantum yields. Based on this, the flexible X-ray film prepared based on Py2TTz-I2F4 achieved an ultrahigh spatial resolution of 26.8 lp per mm, underscoring the superiority of this strategy in developing high-performance organic scintillators.

Monocytes release cystatin F dimer to associate with Aß and aggravate amyloid pathology and cognitive deficits in Alzheimer's disease.

BACKGROUND: Understanding the molecular mechanisms of Alzheimer's disease (AD) has important clinical implications for guiding therapy. Impaired amyloid beta (Aß) clearance is critical in the pathogenesis of sporadic AD, and blood monocytes play an important role in Aß clearance in the periphery. However, the mechanism underlying the defective phagocytosis of Aß by monocytes in AD remains unclear. METHODS: Initially, we collected whole blood samples from sporadic AD patients and isolated the monocytes for RNA sequencing analysis. By establishing APP/PS1 transgenic model mice with monocyte-specific cystatin F overexpression, we assessed the influence of monocyte-derived cystatin F on AD development. We further used a nondenaturing gel to identify the structure of the secreted cystatin F in plasma. Flow cytometry, enzyme-linked immunosorbent assays and laser scanning confocal microscopy were used to analyse the internalization of Aß by monocytes. Pull down assays, bimolecular fluorescence complementation assays and total internal reflection fluorescence microscopy were used to determine the interactions and potential interactional amino acids between the cystatin F protein and Aß. Finally, the cystatin F protein was purified and injected via the tail vein into 5XFAD mice to assess AD pathology. RESULTS: Our results demonstrated that the expression of the cystatin F protein was specifically increased in the monocytes of AD patients. Monocyte-derived cystatin F increased Aß deposition and exacerbated cognitive deficits in APP/PS1 mice. Furthermore, secreted cystatin F in the plasma of AD patients has a dimeric structure that is closely related to clinical signs of AD. Moreover, we noted that the cystatin F dimer blocks the phagocytosis of Aß by monocytes. Mechanistically, the cystatin F dimer physically interacts with Aß to inhibit its recognition and internalization by monocytes through certain amino acid interactions between the cystatin F dimer and Aß. We found that high levels of the cystatin F dimer protein in blood contributed to amyloid pathology and cognitive deficits as a risk factor in 5XFAD mice. CONCLUSIONS: Our findings highlight that the cystatin F dimer plays a crucial role in regulating Aß metabolism via its peripheral clearance pathway, providing us with a potential biomarker for diagnosis and potential target for therapeutic intervention.

Evolution and Antigenic Differentiation of Avian Influenza A(H7N9) Virus, China.

We characterized the evolution and molecular characteristics of avian influenza A(H7N9) viruses isolated in China during 2021-2023. We systematically analyzed the 10-year evolution of the hemagglutinin gene to determine the evolutionary branch. Our results showed recent antigenic drift, providing crucial clues for updating the H7N9 vaccine and disease prevention and control.