Utilizing the oxygen-atom trapping effect of Co3O4 with oxygen vacancies to promote chlorite activation for water decontamination.

Heterogeneous high-valent cobalt-oxo [≡Co(IV)=O] is a widely focused reactive species in oxidant activation; however, the relationship between the catalyst interfacial defects and ≡Co(IV)=O formation remains poorly understood. Herein, photoexcited oxygen vacancies (OVs) were introduced into Co3O4 (OV-Co3O4) by a UV-induced modification method to facilitate chlorite (ClO2-) activation. Density functional theory calculations indicate that OVs result in low-coordinated Co atom, which can directionally anchor chlorite under the oxygen-atom trapping effect. Chlorite first undergoes homolytic O-Cl cleavage and transfers the dissociated O atom to the low-coordinated Co atom to form reactive ≡Co(IV)=O with a higher spin state. The reactive ≡Co(IV)=O rapidly extracts one electron from ClO2- to form chlorine dioxide (ClO2), accompanied by the Co atom returning a lower spin state. As a result of the oxygen-atom trapping effect, the OV-Co3O4/chlorite system achieved a 3.5 times higher efficiency of sulfamethoxazole degradation (~0.1331 min-1) than the pristine Co3O4/chlorite system. Besides, the refiled OVs can be easily restored by re-exposure to UV light, indicating the sustainability of the oxygen atom trap. The OV-Co3O4 was further fabricated on a polyacrylonitrile membrane for back-end water purification, achieving continuous flow degradation of pollutants with low cobalt leakage. This work presents an enhancement strategy for constructing OV as an oxygen-atom trapping site in heterogeneous advanced oxidation processes and provides insight into modulating the formation of ≡Co(IV)=O via defect engineering.

Bioinspired iontronic synapse fibers for ultralow-power multiplexing neuromorphic sensorimotor textiles.

Artificial neuromorphic devices can emulate dendric integration, axonal parallel transmission, along with superior energy efficiency in facilitating efficient information processing, offering enormous potential for wearable electronics. However, integrating such circuits into textiles to achieve biomimetic information perception, processing, and control motion feedback remains a formidable challenge. Here, we engineer a quasi-solid-state iontronic synapse fiber (ISF) comprising photoresponsive TiO2, ion storage Co-MoS2, and an ion transport layer. The resulting ISF achieves inherent short-term synaptic plasticity, femtojoule-range energy consumption, and the ability to transduce chemical/optical signals. Multiple ISFs are interwoven into a synthetic neural fabric, allowing the simultaneous propagation of distinct optical signals for transmitting parallel information. Importantly, IFSs with multiple input electrodes exhibit spatiotemporal information integration. As a proof of concept, a textile-based multiplexing neuromorphic sensorimotor system is constructed to connect synaptic fibers with artificial fiber muscles, enabling preneuronal sensing information integration, parallel transmission, and postneuronal information output to control the coordinated motor of fiber muscles. The proposed fiber system holds enormous promise in wearable electronics, soft robotics, and biomedical engineering.

AptaDB: a comprehensive database integrating aptamer-target interactions.

Aptamers have emerged as research hotspots of the next generation due to excellent performance benefits and application potentials in pharmacology, medicine, and analytical chemistry. Despite the numerous aptamer investigations, the lack of comprehensive data integration has hindered the development of computational methods for aptamers and the reuse of aptamers. A public access database named AptaDB, derived from experimentally validated data manually collected from the literature, was hence developed, integrating comprehensive aptamer-related data, which include six key components: (i) experimentally validated aptamer-target interaction information, (ii) aptamer property information, (iii) structure information of aptamer, (iv) target information, (v) experimental activity information, and (vi) algorithmically calculated similar aptamers. AptaDB currently contains 1350 experimentally validated aptamer-target interactions, 1230 binding affinity constants, 1293 aptamer sequences, and more. Compared to other aptamer databases, it contains twice the number of entries found in available databases. The collection and integration of the above information categories is unique among available aptamer databases and provides a user-friendly interface. AptaDB will also be continuously updated as aptamer research evolves. We expect that AptaDB will become a powerful source for aptamer rational design and a valuable tool for aptamer screening in the future. For access to AptaDB, please visit http://lmmd.ecust.edu.cn/aptadb/.

admetSAR3.0: a comprehensive platform for exploration, prediction and optimization of chemical ADMET properties.

Absorption, distribution, metabolism, excretion and toxicity (ADMET) properties play a crucial role in drug discovery and chemical safety assessment. Built on the achievements of admetSAR and its successor, admetSAR2.0, this paper introduced the new version of the series, admetSAR3.0, as a comprehensive platform for chemical ADMET assessment, including search, prediction and optimization modules. In the search module, admetSAR3.0 hosted over 370 000 high-quality experimental ADMET data for 104 652 unique compounds, and supplemented chemical structure similarity search function to facilitate read-across. In the prediction module, we introduced comprehensive ADMET endpoints and two new sections for environmental and cosmetic risk assessments, empowering admetSAR3.0 to provide prediction for 119 endpoints, more than double numbers compared to the previous version. Furthermore, the advanced multi-task graph neural network framework offered robust and reliable support for ADMET prediction. In particular, a module named ADMETopt was added to automatically optimize the ADMET properties of query molecules through transformation rules or scaffold hopping. Finally, admetSAR3.0 provides user-friendly interfaces for multiple types of input data, such as SMILES string, chemical structure and batch molecule file, and supports various output types, including digital, chart displays and file downloads. In summary, admetSAR3.0 is anticipated to be a valuable and powerful tool in drug discovery and chemical safety assessment at http://lmmd.ecust.edu.cn/admetsar3/.

The disordered protein SERF promotes α-Synuclein aggregation through liquid-liquid phase separation.

The aggregation of α-Synuclein (α-Syn) into amyloid fibrils is the hallmark of Parkinson's disease. Under stress or other pathological conditions, the accumulation of α-Syn oligomers is the main contributor to the cytotoxicity. A potential approach for treating Parkinson's disease involves preventing the accumulation of these α-Syn oligomers. In this study, we present a novel mechanism involving a conserved group of disorderly proteins known as small EDRK-rich factor (SERF), which promotes the aggregation of α-Syn through a cophase separation process. Using diverse methods like confocal microscopy, fluorescence recovery after photobleaching assays, solution-state NMR spectroscopy, and Western blot, we determined that the N-terminal domain of SERF1a plays a role in the interactions that occur during cophase separation. Within these droplets, α-Syn undergoes a gradual transformation from solid condensates to amyloid fibrils, while SERF1a is excluded from the condensates and dissolves into the solution. Notably, in vivo experiments show that SERF1a cophase separation with α-Syn significantly reduces the deposition of α-Syn oligomers and decreases its cellular toxicity under stress. These findings suggest that SERF1a accelerates the conversion of α-Syn from highly toxic oligomers to less toxic fibrils through cophase separation, thereby mitigating the biological damage of α-Syn aggregation.

2D Conjugated Metal-Organic Frameworks: Defined Synthesis and Tailor-Made Functions.

Conspectus2D conjugated metal-organic frameworks (2D -MOFs) have emerged as a class of graphene-like materials with fully π-conjugated aromatic structures. Their unique structural characteristics provide abundant physiochemical features, including regular nanochannels, high electrical conductivity, and customizable band gaps. Recent intensive research has significantly advanced this field, yet the exploration of 2D c-MOFs with enhanced features is limited by the availability of organic linkages and topologies. Designing novel ligands is essential for the construction of new 2D c-MOFs with high crystallinity, excellent conductivity, and tailor-made functions.In this Account, we summarize our recent contributions in fine-tuning the topology of 2D c-MOFs through precise ligand design, thereby giving them fantastic structures and tailor-made functions. First, we propose the concept of replacing planar ligands by nonplanar ligands on conductive MOF skeletons. The incorporation of nonplanar ligands improves the solubility of large π-conjugated organic molecules without interfering with the interlayer π-stacking. Our investigation discovered that conjugate polycyclic aromatics-based ligands can be synthesized through in situ Scholl reactions by means of oxidative cyclodehydrogenation of a nonplanar precursor ligand during the solvothermal synthesis process. Hence, fully conjugated 2D c-MOFs can be directly synthesized from nonplanar organic ligands, simplifying and diversifying the preparation of 2D c-MOFs. Accordingly, the design flexibility of the ligands expands the topological structures and pore types. By controlling the synthesis conditions, we can successfully induce either a rhombus or a kagome topology from a nonplanar D2 symmetric ligand. Moreover, by employing a ligand engineering strategy, we incrementally increase the number of coordination functional groups on a twisted hexabenzocoronene core, resulting in the formation of three distinct symmetric hydroxyl ligands. These ligands elicit diverse target topologies and pore sizes, resulting in variances in the coordination node density on the skeletons. This, in turn, leads to differences in electron transfer abilities, ultimately causing variations in the electrical conductivity and mobility. In addition, we employ a straightforward coupling method to incorporate redox components, such as salphen and pyrazine, into nonplanar ligands, facilitating the synthesis of 2D c-MOFs with highly active centers. This strategy confers upon the resulting frameworks substantial capacity for catalysis and energy storage, offering a good platform for elucidating the structure-property relationships at the molecular level. Moreover, the well-defined synthesis of 2D c-MOFs imparts them with specific properties, particularly in the fields of electrical, electrochemical, and spintronic applications. At the end, the primary challenges facing 2D c-MOFs in achieving tailor functions and their practical applications are proposed. This account is expected to evoke new inspirations and innovative research in the field of 2D c-MOFs, especially in emerging interdisciplinary research areas.

Tuning Topology Phases by Controlling Effective Screening and Depolarization in Oxide Superlattices.

Polar topological phases in oxide superlattices attracted significant attention due to their unique properties. Previous work revealed that a polar vortex and polar skyrmions exist in (PTO)/(STO) superlattices under different elastic constraints, i.e., on different substrates. Here, our phase-field simulation demonstrates that manipulating the PTO and STO layers' thickness can control the effective screening provided by STO and the depolarization degree in PTO, thus switching the system among the polar skyrmions, vortex labyrinth, or paraelectric phase without changing elastic constraints. Additionally, reducing the STO thickness creates interlayer coupling among PTO layers, generating the long-range order of topological phases within superlattices. Furthermore, we construct a PTO-STO thickness topological phase diagram. These findings offer insights into the polar topological phases' formation in oxide superlattices, elucidating the roles of ferroelectric and paraelectric layers in their formation.

Self-Adhesive, Stretchable, and Thermosensitive Iontronic Hydrogels for Highly Sensitive Neuromorphic Sensing-Synaptic Systems.

Artificial sensory afferent nerves that emulate receptor nanochannel perception and synaptic ionic information processing in chemical environments are highly desirable for bioelectronics. However, challenges persist in achieving life-like nanoscale conformal contact, agile multimodal sensing response, and synaptic feedback with ions. Here, a precisely tuned phase transition poly(N-isopropylacrylamide) (PNIPAM) hydrogel is introduced through the water molecule reservoir strategy. The resulting hydrogel with strongly cross-linked networks exhibits excellent mechanical performance (∼2000% elongation) and robust adhesive strength. Importantly, the hydrogel's enhanced ionic conductance and heterogeneous structure of the temperature-sensitive component enable highly sensitive strain information perception (GFmax = 7.94, response time ∼ 87 ms), temperature information perception (TCRmax = -1.974%/°C, response time ∼ 270 ms), and low energy consumption synaptic plasticity (42.2 fJ/spike). As a demonstration, a neuromorphic sensing-synaptic system is constructed integrating iontronic strain/temperature sensors with fiber synapses for real-time information sensing, discrimination, and feedback. This work holds enormous potential in bioinspired robotics and bioelectronics.

Interlayer Coupling Controlled Ordering and Phases in Polar Vortex Superlattices.

The recent discovery of polar topological structures has opened the door for exciting physics and emergent properties. There is, however, little methodology to engineer stability and ordering in these systems, properties of interest for engineering emergent functionalities. Notably, when the surface area is extended to arbitrary thicknesses, the topological polar texture becomes unstable. Here we show that this instability of the phase is due to electrical coupling between successive layers. We demonstrate that this electrical coupling is indicative of an effective screening length in the dielectric, similar to the conductor-ferroelectric interface. Controlling the electrostatics of the superlattice interfaces, the system can be tuned between a pure topological vortex state and a mixed classical-topological phase. This coupling also enables engineering coherency among the vortices, not only tuning the bulk phase diagram but also enabling the emergence of a 3D lattice of polar textures.

A potassium-chloride co-transporter with altered genome architecture functions as a suppressor in glioma.

Gliomas, the most lethal tumours in brain, have a poor prognosis despite accepting standard treatment. Limited benefits from current therapies can be attributed to genetic, epigenetic and microenvironmental cues that affect cell programming and drive tumour heterogeneity. Through the analysis of Hi-C data, we identified a potassium-chloride co-transporter SLC12A5 associated with disrupted topologically associating domain which was downregulated in tumour tissues. Multiple independent glioma cohorts were included to analyse the characterization of SLC12A5 and found it was significantly associated with pathological features, prognostic value, genomic alterations, transcriptional landscape and drug response. We constructed two SLC12A5 overexpression cell lines to verify the function of SLC12A5 that suppressed tumour cell proliferation and migration in vitro. In addition, SLC12A5 was also positively associated with GABAA receptor activity and negatively associated with pro-tumour immune signatures and immunotherapy response. Collectively, our study provides a comprehensive characterization of SLC12A5 in glioma and supports SLC12A5 as a potential suppressor of disease progression.

De Novo Design and Facile Synthesis of Highly Crystalline 2D Conductive Metal-Organic Frameworks: A "Rotor-Stator" Strategy.

Two-dimensional conductive metal-organic frameworks (2D c-MOFs), which feature high electrical conductivity and large charge carrier mobility, hold great promise in electronics and optoelectronics. Nevertheless, the limited solubility of commonly used planar ligands inevitably brings challenges in synthesis and purification and causes laborious coordination conditions for screening. Moreover, most reported 2D c-MOFs are polycrystalline powders with relatively low crystallinity and irregular morphology, hindering the unveiling of the detailed structure-function relationship. Herein, we developed a "rotor-stator" molecular design strategy to construct 2D c-MOFs using a delicately designed nonplanar biscarbazole ligand (8OH-DCB). Benefiting from the special "rotor-stator" structure of the ligand, crystals of Cu-DCB-MOF were successfully prepared, allowing for the precise determination of their crystal structure. Interestingly, the crystals of Cu-DCB-MOF can be obtained in various organic solvents, indicating excellent solvent compatibility. The versatility of the "rotor-stator" molecular design strategy was further demonstrated by another two new ligands with a "rotor-stator" structure, and afford corresponding 2D c-MOF crystals (Cu-DCBT-MOF and Cu-DCBBT-MOF). The current work presents a facile approach toward the rational design and direct construction of highly crystalline 2D c-MOFs using nonplanar ligands.

Graphdiyne Enabled Nitrogen Vacancy Formation in Copper Nitride for Efficient Ammonia Synthesis.

The electrocatalytic reduction of nitrate is promising for sustainable ammonia synthesis but suffers from slow reduction kinetics and multiple competing reactions. Here, we report a catalyst featuring copper nitride (Cu3N) anchored on a novel graphdiyne support (termed Cu3N/GDY), which is used for electrocatalytic reduction of nitrate to produce ammonia. The GDY absorbed hydrogen and enabled nitrogen (N) vacancy formation in Cu3N for the fast nitrate reduction reaction (NO3RR). Further, the distinct absorption sites formed by GDY and N vacancy enabled the excellent selectivity and stability of NO3RR. Notably, the Cu3N/GDY catalyst achieved a high ammonia yield (YNH3) up to 35280 µg h-1 mgcat.-1 and a high Faradaic efficiency (FE) of 98.1% using 0.1 M NO3- at -0.9 V versus a reversible hydrogen electrode (RHE). Using electron paramagnetic resonance (EPR) technology and in situ X-ray absorption fine structure (XAFS) spectroscopy measurement, we visualized the N vacancy formation in Cu3N and electrocatalytic NO3RR enabled by GDY. These findings show the promise of GDY in sustainable ammonia synthesis and highlight the efficacy of Cu3N/GDY as a catalyst.

Designing Advanced Electrolytes for High-Safety and Long-Lifetime Sodium-Ion Batteries via Anion-Cation Interaction Modulation.

Safety hazards caused by flammable electrolytes have been major obstacles to the practical application of sodium-ion batteries (SIBs). The adoption of nonflammable all-phosphate electrolytes can effectively improve the safety of SIBs; however, traditional low-concentration phosphate electrolytes are not compatible with carbon-based anodes. Herein, we report an anion-cation interaction modulation strategy to design low-concentration phosphate electrolytes with superior physicochemical properties. Tris(2,2,2-trifluoroethyl) phosphate (TFEP) is introduced as a cosolvent to regulate the ion-solvent-coordinated (ISC) structure through enhancing the anion-cation interactions, forming the stable anion-induced ISC (AI-ISC) structure, even at a low salt concentration (1.22 M). Through spectroscopy analyses and theoretical calculations, we reveal the underlying mechanism responsible for the stabilization of these electrolytes. Impressively, both the hard carbon (HC) anode and Na4Fe2.91(PO4)2(P2O7) (NFPP) cathode work well with the developed electrolytes. The designed phosphate electrolyte enables Ah-level HC//NFPP pouch cells with an average Coulombic efficiency (CE) of over 99.9% and a capacity retention of 84.5% after 2000 cycles. In addition, the pouch cells can operate in a wide temperature range (-20 to 60 °C) and successfully pass rigorous safety testing. This work provides new insight into the design of the electrochemically compatibility electrolyte for high-safety and long-lifetime SIBs.

Ultrahigh-Efficiency Superior Energy Storage in Lead-Free Films with a Simple Composition.

Dielectric capacitors are highly desired in modern electronic devices and power systems to store and recycle electric energy. However, achieving simultaneous high energy density and efficiency remains a challenge. Here, guided by theoretical and phase-field simulations, we are able to achieve a superior comprehensive property of ultrahigh efficiency of 90-94% and high energy density of 85-90 J cm-3 remarkably in strontium titanate (SrTiO3), a linear dielectric of a simple chemical composition, by manipulating local symmetry breaking through introducing Ti/O defects. Atomic-scale characterizations confirm that these Ti/O defects lead to local symmetry breaking and local lattice strains, thus leading to the formation of the isolated ultrafine polar nanoclusters with varying sizes from 2 to 8 nm. These nanoclusters account for both considerable dielectric polarization and negligible polarization hysteresis. The present study opens a new realm of designing high-performance dielectric capacitors utilizing a large family of readily available linear dielectrics with very simple chemistry.

Isotope Effect-Enabled Crystal Enlargement in Metal-Organic Frameworks.

Synthesizing large metal-organic framework (MOF) single crystals has garnered significant research interest, although it is hindered by the fast nucleation kinetics that gives rise to numerous small nuclei. Given the different chemical origins inherent in various types of MOFs, the development of a general approach to enhancing their crystal sizes presents a formidable challenge. Here, we propose a simple isotopic substitution strategy to promote size growth in MOFs by inhibiting nucleation, resulting in a substantial increase in the crystal volume ranging from 1.7- to 165-fold. Impressively, the crystals prepared under optimized conditions by normal approaches can be further enlarged by the isotope effect, yielding the largest MOF single crystal (2.9 cm × 0.48 cm × 0.23 cm) among the one-pot synthesis method. Detailed in situ characterizations reveal that the isotope effect can retard crystallization kinetics, establish a higher nucleation energy barrier, and consequently generate fewer nuclei that eventually grow larger. Compared with the smaller crystals, the isotope effect-enlarged crystal shows 33% improvement in the X-ray dose rate detection limit. This work enriches the understanding of the isotope effect on regulating the crystallization process and provides inspiration for exploring potential applications of large MOF single crystals.

Constructing Ultra-Strong SERS Tags in the Cellular Raman-Silent Region by Orthogonal Array Testing Strategy.

Surface-enhanced Raman spectroscopy (SERS) tags have the advantages of unique fingerprint vibration spectrum, ultranarrow spectral line widths, and weak photobleaching effect, showing great potential for bioimaging. However, SERS imaging is still hindered for further application due to its weak spontaneous Raman scattering, biomolecular signal interference, and long acquisition times. Here, we develop a novel SERS tag of the core (Au)-shell (N-doped graphene) structure (Au@NGs) with ultrastrong and stable Raman signal (2180 cm-1) in the cellular Raman-silent region (1800-2800 cm-1) through base-promoted oxidative decarboxylation of amino acids. Exploring the factors (metal salts, amino acids, catalysts, temperature, etc.) to obtain Au@NGs with the strongest Raman signal commonly requires more than 100,000 separate experiments, while that using an orthogonal array testing strategy is reduced to 56. The existence of deep charge transfer between the Au surface and C≡N-graphene is proved by theoretical calculations, which means the ultrastrong signal of Au@NGs is the joint effect of electromagnetic and chemical enhancement. The Au@NGs have a detection sensitivity down to a single-nanoparticle level, and high-speed and high-resolution cellular imaging (4453 pixels) is obtained within 10 s by global Raman imaging. The combination of Au@NGs-based tags with ultrastrong intrinsic Raman imaging capability and global imaging technology holds great promise for high-speed Raman imaging.

A dynamic regulatory switch for phase separation of FUS protein: Zinc ions and zinc finger domain.

Zinc is an important trace element in the human body, and its homeostasis is closely related to amyotrophic lateral sclerosis (ALS). Cytoplasmic FUS proteins from patients with ALS aggregate their important pathologic markers. Liquid-liquid phase separation (LLPS) of FUS can lead to its aggregation. However, whether and how zinc homeostasis affects the aggregation of disease-associated FUS proteins in the cytoplasm remains unclear. Here, we found that zinc ion enhances LLPS and promotes the aggregation in the cytoplasm for FUS protein. In the FUS, the cysteine of the zinc finger (ZnF), recognizes and binds to zinc ions, reducing droplet mobility and enhancing protein aggregation in the cytoplasm. The mutation of FUS cysteine disrupts the dynamic regulatory switch of zinc ions and ZnF, resulting in insensitivity to zinc ions. These results suggest that the dynamic regulation of LLPS by binding with zinc ions may be a widespread mechanism and provide a new understanding of neurological diseases such as ALS and other ZnF protein-related diseases.

Comparative transcriptome revealed the molecular responses of Aconitum carmichaelii Debx. to downy mildew at different stages of disease development.

BACKGROUND: Aconitum carmichaelii Debx. has been widely used as a traditional medicinal herb for a long history in China. It is highly susceptible to various dangerous diseases during the cultivation process. Downy mildew is the most serious leaf disease of A. carmichaelii, affecting plant growth and ultimately leading to a reduction in yield. To better understand the response mechanism of A. carmichaelii leaves subjected to downy mildew, the contents of endogenous plant hormones as well as transcriptome sequencing were analyzed at five different infected stages. RESULTS: The content of 3-indoleacetic acid, abscisic acid, salicylic acid and jasmonic acid has changed significantly in A. carmichaelii leaves with the development of downy mildew, and related synthetic genes such as 9-cis-epoxycarotenoid dioxygenase and phenylalanine ammonia lyase were also significant for disease responses. The transcriptomic data indicated that the differentially expressed genes were primarily associated with plant hormone signal transduction, plant-pathogen interaction, the mitogen-activated protein kinase signaling pathway in plants, and phenylpropanoid biosynthesis. Many of these genes also showed potential functions for resisting downy mildew. Through weighted gene co-expression network analysis, the hub genes and genes that have high connectivity to them were identified, which could participate in plant immune responses. CONCLUSIONS: In this study, we elucidated the response and potential genes of A. carmichaelii to downy mildew, and observed the changes of endogenous hormones content at different infection stages, so as to contribute to the further screening and identification of genes involved in the defense of downy mildew.

Identification and experimental validation of KMO as a critical immune-associated mitochondrial gene in unstable atherosclerotic plaque.

BACKGROUND: The heightened risk of cardiovascular and cerebrovascular events is associated with the increased instability of atherosclerotic plaques. However, the lack of effective diagnostic biomarkers has impeded the assessment of plaque instability currently. This study was aimed to investigate and identify hub genes associated with unstable plaques through the integration of various bioinformatics tools, providing novel insights into the detection and treatment of this condition. METHODS: Weighted Gene Co-expression Network Analysis (WGCNA) combined with two machine learning methods were used to identify hub genes strongly associated with plaque instability. The cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) method was utilized to assess immune cell infiltration patterns in atherosclerosis patients. Additionally, Gene Set Variation Analysis (GSVA) was conducted to investigate the potential biological functions, pathways, and mechanisms of hub genes associated with unstable plaques. To further validate the diagnostic efficiency and expression of the hub genes, immunohistochemistry (IHC), quantitative real-time polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA) were performed on collected human carotid plaque and blood samples. Immunofluorescence co-staining was also utilized to confirm the association between hub genes and immune cells, as well as their colocalization with mitochondria. RESULTS: The CIBERSORT analysis demonstrated a significant decrease in the infiltration of CD8 T cells and an obvious increase in the infiltration of M0 macrophages in patients with atherosclerosis. Subsequently, two highly relevant modules (blue and green) strongly associated with atherosclerotic plaque instability were identified. Through intersection with mitochondria-related genes, 50 crucial genes were identified. Further analysis employing least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine recursive feature elimination (SVM-RFE) algorithms revealed six hub genes significantly associated with plaque instability. Among them, NT5DC3, ACADL, SLC25A4, ALDH1B1, and MAOB exhibited positive correlations with CD8 T cells and negative correlations with M0 macrophages, while kynurenine 3-monooxygenas (KMO) demonstrated a positive correlation with M0 macrophages and a negative correlation with CD8 T cells. IHC and RT-qPCR analyses of human carotid plaque samples, as well as ELISA analyses of blood samples, revealed significant upregulation of KMO and MAOB expression, along with decreased ALDH1B1 expression, in both stable and unstable samples compared to the control samples. However, among the three key genes mentioned above, only KMO showed a significant increase in expression in unstable plaque samples compared to stable plaque samples. Furthermore, the expression patterns of KMO in human carotid unstable plaque tissues and cultured mouse macrophage cell lines were assessed using immunofluorescence co-staining techniques. Finally, lentivirus-mediated KMO silencing was successfully transduced into the aortas of high-fat-fed ApoE-/- mice, with results indicating that KMO silencing attenuated plaque formation and promoted plaque stability in ApoE-/- mice. CONCLUSIONS: The results suggest that KMO, a mitochondria-targeted gene associated with macrophage cells, holds promise as a valuable diagnostic biomarker for assessing the instability of atherosclerotic plaques.

Epidemiological characteristics and antibody kinetics of elderly population with booster vaccination following both Omicron BA.5 and XBB waves in China.

After the termination of zero-COVID-19 policy, the populace in China has experienced both Omicron BA.5 and XBB waves. Considering the poor antibody responses and severe outcomes observed among the elderly following infection, we conducted a longitudinal investigation to examine the epidemiological characteristics and antibody kinetics among 107 boosted elderly participants following the Omicron BA.5 and XBB waves. We observed that 96 participants (89.7%) were infected with Omicron BA.5, while 59 (55.1%) participants were infected with Omicron XBB. Notably, 52 participants (48.6%) experienced dual infections of both Omicron BA.5 and XBB. The proportion of symptomatic cases appeared to decrease following the XBB wave (18.6%) compared to that after the BA.5 wave (59.3%). Omicron BA.5 breakthrough infection induced lower neutralizing antibody titers against XBB.1.5, BA.2.86, and JN.1, while reinfection with Omicron XBB broadened the antibody responses against all measured Omicron subvariants and may alleviate the wild type-vaccination induced immune imprinting. Boosted vaccination type and comorbidities were the significant factors associated with antibody responses. Updated vaccines based on emerging severe acute respiratory syndrome coronavirus 2 variants are needed to control the Coronavirus Disease 2019 pandemic in the elderly.