Bicontinuous vitrimer heterogels with wide-span switchable stiffness-gated iontronic coordination.

Currently, it remains challenging to balance intrinsic stiffness with programmability in most vitrimers. Simultaneously, coordinating materials with gel-like iontronic properties for intrinsic ion transmission while maintaining vitrimer programmable features remains underexplored. Here, we introduce a phase-engineering strategy to fabricate bicontinuous vitrimer heterogel (VHG) materials. Such VHGs exhibited high mechanical strength, with an elastic modulus of up to 116 MPa, a high strain performance exceeding 1000%, and a switchable stiffness ratio surpassing 5 × 103. Moreover, highly programmable reprocessing and shape memory morphing were realized owing to the ion liquid-enhanced VHG network reconfiguration. Derived from the ion transmission pathway in the ILgel, which responded to the wide-span switchable mechanics, the VHG iontronics had a unique bidirectional stiffness-gated piezoresistivity, coordinating both positive and negative piezoresistive properties. Our findings indicate that the VHG system can act as a foundational material in various promising applications, including smart sensors, soft machines, and bioelectronics.

Dynamic-Bond-Mediated Chain Reptation Enhances Energy Dissipation of Elastomers.

Vibrations with various frequencies in daily life and industry can cause health hazards and fatigue failure of critical structures, which requires the development of elastomers with high energy dissipation at desired frequencies. Current strategies relying on tuning characteristic relaxation time of polymer chains are mostly qualitative empirical methods, and it is difficult to precisely control damping performances. Here, we report a general strategy for constructing dynamic crosslinked polymer fluid gels that provide controllable ultrahigh energy dissipation. This is realized by dynamic-bond-mediated chain reptation of polymer fluids in a crosslinked network, where the characteristic time of chain reptation is dominated by the presence of well-defined dissociation time of dynamic bonds and almost independent of their molar mass. Using prototypical supramolecular polydimethylsiloxane elastomers, we demonstrate that dynamic crosslinked polymer fluid gels exhibit a controllable ultrahigh damping performance at desired frequencies (10-2~102 Hz), exceeding that of typical state-of-the-art silicone damping materials. Their shock absorption is over 300 % higher than that of commercial silicone rubber under the same impact force.

Research progress on the relationship between epilepsy and circRNA.

OBJECTIVE: This review aims to provide a comprehensive summary of the latest research progress regarding the relationship between epilepsy and circular RNA (circRNA). METHODS: Relevant literature from the PubMed database was meticulously searched and reviewed. The selected articles focused on investigating the association between epilepsy and circRNA, including studies on expression patterns, diagnostic markers, therapeutic targets, and functional mechanisms. RESULTS: Epilepsy, characterized by recurrent seizures, is a neurological disorder. Numerous studies have demonstrated significant alterations in the expression profiles of circRNA in epileptic brain tissues, animal models, and peripheral blood samples. These differential expressions of circRNA are believed to be closely linked with the occurrence and development of epilepsy. Moreover, circRNA has shown promising potential as diagnostic markers for epilepsy, as well as prognostic indicators for predicting disease outcomes. Furthermore, circRNA has emerged as a potential therapeutic target for epilepsy treatment, offering prospects for gene therapy interventions. CONCLUSION: The dysregulation of circRNA expression in epilepsy suggests its potential involvement in the pathogenesis and progression of this disorder. Identifying specific circRNA molecules associated with epilepsy may pave the way for novel diagnostic approaches and therapeutic strategies. However, further investigations are imperative to elucidate the precise functional mechanisms of circRNA in epilepsy and validate its clinical utility.

Tough, Antifreezing, and Piezoelectric Organohydrogel as a Flexible Wearable Sensor for Human-Machine Interaction.

Piezoelectric hydrogel sensors are becoming increasingly popular for wearable sensing applications due to their high sensitivity, self-powered performance, and simple preparation process. However, conventional piezoelectric hydrogels lack antifreezing properties and are thus confronted with the liability of rupture in low temperatures owing to the use of water as the dispersion medium. Herein, a kind of piezoelectric organohydrogel that integrates piezoelectricity, low-temperature tolerance, mechanical robustness, and stable electrical performance is reported by using poly(vinylidene fluoride) (PVDF), acrylonitrile (AN), acrylamide (AAm), p-styrenesulfonate (NaSS), glycerol, and zinc chloride. In detail, the dipolar interaction of the PVDF chain with the PAN chain facilitates the crystal phase transition of PVDF from the α to ß phase, which endows the organohydrogels with a high piezoelectric constant d33 of 35 pC/N. In addition, the organohydrogels are highly ductile and can withstand significant tensile and compressive forces through the synergy of the dipolar interaction and amide hydrogen bonding. Besides, by incorporating glycerol and zinc chloride, the growth of ice crystals is inhibited, allowing the organohydrogels to maintain stable flexibility and sensitivity even at -20 °C. The real-time monitoring of the pulse signal for up to 2 min indicates that the gel sensor has stable sensitivity. It is believed that our organohydrogels will have good prospects in future wearable electronics.

A global comparative field study to evaluate the factor VIII activity of efanesoctocog alfa by one-stage clotting and chromogenic substrate assays at clinical haemostasis laboratories.

INTRODUCTION: Structural and chemical modifications of factor VIII (FVIII) products may influence their behaviour in FVIII activity assays. Hence, it is important to assess the performance of FVIII products in these assays. Efanesoctocog alfa is a new class of FVIII replacement therapy designed to provide both high sustained factor activity levels and prolonged plasma half-life. AIM: Evaluate the accuracy of measuring efanesoctocog alfa FVIII activity in one-stage clotting assays (OSAs) and chromogenic substrate assays (CSAs). METHODS: Human plasma with no detectable FVIII activity was spiked with efanesoctocog alfa or a full-length recombinant FVIII product comparator, octocog alfa, at nominal concentrations of 0.80 IU/mL, 0.20 IU/mL, or 0.05 IU/mL, based on labelled potency. Clinical haemostasis laboratories (N = 35) tested blinded samples using in-house assays. Data from 51 OSAs (14 activated partial thromboplastin time [aPTT] reagents) and 42 CSAs (eight kits) were analyzed. RESULTS: Efanesoctocog alfa activity was reliably (±25% of nominal activity) measured across all concentrations using OSAs with Actin FSL and multiple other aPTT reagents. Under- and overestimation of FVIII activity occurred with some reagents. No specific trend was observed for any class of aPTT activators. A two- to three-fold overestimation was consistently observed using CSAs and the OSA with Actin FS as the aPTT reagent across evaluated concentrations. CONCLUSION: Under- or overestimation occurred with some specific OSAs and most CSAs, which has been previously observed with other modified FVIII replacement products. Efanesoctocog alfa FVIII activity was measured with acceptable accuracy and reliability using several OSA methods and commercial plasma standards.

Treatment of landfill leachate by coagulation: A review.

Landfill leachate is a seriously polluted and hazardous liquid, which contains a high concentration of refractory organics, ammonia nitrogen, heavy metals, inorganic salts, and various suspended solids. The favorable disposal of landfill leachate has always been a hot and challenging issue in wastewater treatment. As one of the best available technologies for landfill leachate disposal, coagulation has been studied extensively. However, there is an absence of a systematic review regarding coagulation in landfill leachate treatment. In this paper, a review focusing on the characteristics, mechanisms, and application of coagulation in landfill leachate treatment was provided. Different coagulants and factors influencing the coagulation effect were synthetically summarized. The performance of coagulation coupled with other processes and their complementary advantages were elucidated. Additionally, the economic analysis conducted in this study suggests the cost-effectiveness of the coagulation process. Based on previous studies, challenges and perspectives met by landfill leachate coagulation treatment were also put forward. Overall, this review will provide a reference for the coagulation treatment of landfill leachate and promote the development of efficient and eco-friendly leachate treatment technology.

Ionic Liquids: An Ideal Solvent for Tuning the UCST Phase Behavior of Polymer Gels.

Liquid-liquid phase separation (LLPS) is a common stimulus-responsive phenomenon widely studied and applied in constructing intelligent systems such as microfluidic valves, smart windows, and biosensors. However, LLPS in an aqueous solution has limited applicability confined to a narrow temperature range within 0-100 °C. In addition, for easy exploitation of thermoresponsive behavior, phase separation must be stable and accurately predictable under varying conditions. This study proposes a gel system exhibiting UCST phase behavior using ionic liquids (ILs) and hydrophilic polymers, whose phase transition temperature can be linearly tuned within a wide range (from subzero to over 100 °C) by varying the mixing ratio of ILs in their blends. Similar to the mixing of ILs with structurally similar cations, mixing ILs containing different anions proved to be an effective ideal random mixing method based on experimental results and molecular dynamics simulations. This mixing mechanism of ILs accounts for the linear regulation of the UCST of the ionogels when the mixing ratio of ILs in their blends varies. Moreover, the unique feature of ILs was further demonstrated using other hydrophilic polymer networks and multiple combinations of ILs, suggesting the generality of this strategy for UCST regulation in the ionogels.

Enhancing the Conductivity of PEDOT:PSS Films by the Confinement of Ice Crystals.

Rapid developments in organic electronics demand highly conductive and freestanding (PEDOT:PSS) films. However, the synthesis of highly conductive PEDOT:PSS films requires toxic reagents, such as high-concentration acids and bases. Herein, an eco-friendly and cost-effective strategy is reported for improving the conductivity of PEDOT:PSS films through the confinement of ice crystals. The crystallization of water swelled by the film facilitated the phase separation of PEDOT and PSS, and the excess PSS in the skin layer is effectively removed. Moreover, under the confinement effect, the carrier mobility of the film is enhanced through the formation of a well-crystallized PEDOT molecular morphology. A detailed elucidation of aggregate structure evolution in PEDOT:PSS films during annealing, solvent post-treatment, and subsequent confined crystallization is presented herein. After multiple water crystallization cycles, the conductivity of the PEDOT:PSS film increased by over 85%, achieving a maximum of 2564 ± 142 S cm-1 . Finally, compared to post-treatment with dimethyl sulfoxide (DMSO), the current strategy can improve the Seebeck coefficient by 5.6% and the power factor by 139%.

Combined transcriptome and proteome analysis reveal the key physiological processes in seed germination stimulated by decreased salinity in the seagrass Zostera marina L.

BACKGROUND: Zostera marina L., or eelgrass, is the most widespread seagrass species throughout the temperate northern hemisphere. Unlike the dry seeds of terrestrial plants, eelgrass seeds must survive in water, and salinity is the key factor influencing eelgrass seed germination. In the present study, transcriptome and proteome analysis were combined to investigate the mechanisms via which eelgrass seed germination was stimulated by low salinity, in addition to the dynamics of key metabolic pathways under germination. RESULTS: According to the results, low salinity stimulated the activation of Ca2+ signaling and phosphatidylinositol signaling, and further initiated various germination-related physiological processes through the MAPK transduction cascade. Starch, lipids, and storage proteins were mobilized actively to provide the energy and material basis for germination; abscisic acid synthesis and signal transduction were inhibited whereas gibberellin synthesis and signal transduction were activated, weakening seed dormancy and preparing for germination; cell wall weakening and remodeling processes were activated to provide protection for cotyledon protrusion; in addition, multiple antioxidant systems were activated to alleviate oxidative stress generated during the germination process; ERF transcription factor has the highest number in both stages suggested an active role in eelgrass seed germination. CONCLUSION: In summary, for the first time, the present study investigated the mechanisms by which eelgrass seed germination was stimulated by low salinity and analyzed the transcriptomic and proteomic features during eelgrass seed germination comprehensively. The results of the present study enhanced our understanding of seagrass seed germination, especially the molecular ecology of seagrass seeds.

Intensify Standardized Anticoagulation for Cancer-associated Pulmonary Embolism: From Single-center Real-world Data.

PURPOSE: Pulmonary embolism (PE) is a significant contributor to mortality in patients with cancer. Although anticoagulation serves as the cornerstone of treatment for cancer-associated PE, it has not been emphasized in real-world settings. The aim of this study was to examine the impact of suboptimal anticoagulant treatment on the prognosis of cancer-associated PE. METHODS: A cohort of 356 individuals newly diagnosed with acute PE were enrolled. The primary outcome of the study was recurrent venous thromboembolism (VTE), and the secondary outcomes were all-cause mortality and major bleeding (consisting of a reduction in the hemoglobin level by at least 20 g/L, transfusion of at least 2 units of blood, or symptomatic bleeding in a critical area or organ or fatal bleeding). FINDINGS: Of the total participants, 156 (43.8%) were diagnosed with cancer. A comparison between the cancer and noncancer groups revealed that patients with cancer were more frequently asymptomatic (41.0% vs 4.5%; P < 0.001), less likely to have right ventricular dysfunction (4.5% vs 14.0%; P = 0.001), received less anticoagulant treatment during hospitalization (85.3% vs 98.5%; P < 0.001), and had a shorter duration of anticoagulation (5.02 [7.40] months vs 14.19 [10.65] months; P < 0.001). In addition, patients with cancer were found to be at a higher risk of recurrent VTE (17.3% vs 4.0%; P < 0.001) and all-cause mortality (23.7% vs 10.5%; P = 0.001). Multiple Cox regression analysis indicated that discontinuation of anticoagulation at 3 months was a significant risk factor for recurrent VTE in the cancer group (HR, 15.815; 95% CI, 3.047-82.079; P = 0.001). IMPLICATIONS: The brief duration of anticoagulation therapy and elevated likelihood of recurrent VTE serve as cautionary indicators for the need to enhance awareness of standardized anticoagulant treatment for cancer-associated PE. The ultimate goal is to enhance patient prognosis and quality of life.

Evolutionary characterization and pathogenicity of Getah virus from pigs in Guangdong Province of China.

Getah virus (GETV) is an emerging zoonotic virus that can infect humans and many mammals through mosquitoes. In this study, a novel pathogenic GETV strain, GDQY2022, was isolated from a pig farm in Guangdong Province, China. Sequence comparisons and phylogenetic analysis showed that GDQY2022 belongs to group III (GIII) and was most closely related to strain HeN202009-2, with 99.78% nucleotide sequence identity. Histopathological examination revealed significant pathological changes, such as widened alveolar septum in the lungs with mild congestion and hemorrhage. Differences in viral load between tissues were assessed by real-time RT-PCR, and significantly higher levels of GETV were found in abdominal lymph nodes and lungs of subclinically and clinically affected pigs (P < 0.01). This study provides valuable data for understanding the risk of GETV infection in the pig industry and a reliable basis for studying the pathogenic mechanisms and diagnostic surveillance of GETV.

Gut Microbiota Metabolites Mediate Bax to Reduce Neuronal Apoptosis via cGAS/STING Axis in Epilepsy.

The beneficial effects of gut flora on reducing nerve cell apoptosis and inflammation and improving epilepsy (EP) symptoms have been reported, but the specific mechanism of action is still unclear. A series of in vitro and in vivo experiments revealed the relationship between gut microbiota metabolites and the cGAS/STING axis and their role in EP. These results suggest that antibiotic-induced dysbiosis of gut microbiota exacerbated epileptic symptoms, probiotic supplements reduced epileptic symptoms in mice. Antibiotics and probiotics altered the diversity and composition of gut microbiota. The changes in gut bacteria composition, such as in the abundance of Firmicutes, Bacteroidetes, Lactobacillus and Ruminococcus, were associated with the production of short-chain fatty acids (SCFA) in the gut. The concentrations of propionate, butyrate and isovalerate were changed after feeding antibiotics and probiotics, and the increase in butyrate levels reduced the expression of cGAS/STING in nerve cell further reduced Bax protein expression. The reduction of Bax protein attenuated the hippocampal neuron cell apoptosis in PTZ-induced EP and EP progression. Our findings provide new insights into the roles and mechanisms of action of the gut microbiota in attenuating EP symptoms and progression.

Genetic Analysis of Orf Virus (ORFV) Strains Isolated from Goats in China: Insights into Epidemiological Characteristics and Evolutionary Patterns.

Contagious ecthyma (CE) is an acute infectious zoonosis caused by orf virus (ORFV) that mainly infects sheep and goats and causes obvious lesions and low market value of livestock, resulting in huge economic losses for farmers. In this study, two strains of ORFV were isolated from Shaanxi Province and Yunnan Province in China, named FX and LX. The two ORFVs were located in the major clades of domestic strains respectively, and exhibited distinct sequence homology. We analyzed the genetic data of core genes (B2L, F1L, VIR, ORF109) and variable genes (GIF, ORF125 and vIL-10) of ORFV to investigate its epidemiological and evolutionary characteristics. The sequences from 2007 to 2018 constituted the majority of the viral population, predominantly concentrated in India and China. Most genes were clustered into SA00-like type and IA82-like type, and the hotspots in East and South Asia were identified in the ORFV transmission trajectories. For these genes, VIR had the highest substitution rate of 4.85 × 10-4, both VIR and vIL-10 suffered the positive selection pressure during ORFV evolution. Many motifs associated with viral survival were distributed among ORFVs. In addition, some possible viral epitopes have been predicted, which still require validation in vivo and in vitro. This work gives more insight into the prevalence and phylogenetic relationships of existing orf viruses and facilitate better vaccine design.

[Meta-analysis of the effect of hollow nail and bone plate on Lisfranc injury].

OBJECTIVE: To compare the clinical efficacy of screw and bone plate internal fixation in the treatment of Lisfranc injury. METHODS: The databases of Wanfang, CNKI, Pubmed, EMBASE, VIP, BIOSIS and other databases were retrieved by computer, and the clinical trial literature from January 1, 2000 to August 1, 2021 was retrieved, the methodological quality of the included studies was strictly evaluated and the data were extracted, and the obtained data were meta-analyzed by Revman 5.4 software. RESULTS: Nine randomized controlled trial literature and 10 retrospective cohort studies were included, of which 416 patients in the experimental group were treated with screw internal fixation, and 435 patients in the control group were treated with bone plate internal fixation. Meta-analysis showed that the surgical time of the bone plate internal fixation group was longer than that of the screw internal fixation group [MD=-14.40, 95%CI(-17.21, -11.60), P<0.000 01], the postoperative X-ray anatomical reduction of the bone plate internal fixation group [MD=0.47, 95%CI(0.25, 0.86), P=0.01], the excellent and good rate of postoperative American orthopedic foot and ankle society(AOFAS) foot function score[MD=0.25, 95%CI(0.15, 0.42), P<0.000 01], postoperative AOFAS foot function score [MD=-5.51, 95%CI(-10.10, -0.92), P=0.02] of the bone plate fixation group was better than those of the screw internal fixation group. Two kinds of operation method had no statistical different for postoperative fracture healing time[MD=1.91, 95%CI(-1.36, 5.18), P=0.25], postoperative visual analgue scale(VAS)[MD=0.38, 95%CI(0.09, 0.86), P=0.11], postoperative complications [MD=1.32, 95%CI(0.73, 2.40), P=0.36], the postoperative infection [MD=0.84, 95%CI(0.48, 1.46), P=0.53], the postoperative fracture internal fixation loosening [MD=1.25, 95% CI(0.61, 2.53), P=0.54], the postoperative incidence of traumatic arthritis [MD=1.80, 95%CI(0.83, 3.91), P=0.14]. CONCLUSION: Bone plate fixation has better short-term and medium-term results and lower reoperation rate in the treatment of Lisfranc injury, so it is recommended to use bone plate fixation in the treatment of Lisfranc injury.

Guanidinium-based covalent organic framework membrane for single-acid recovery.

Acids are extensively used in contemporary industries. However, time-consuming and environmentally unfriendly processes hinder single-acid recovery from wastes containing various ionic species. Although membrane technology can overcome these challenges by efficiently extracting analytes of interest, the associated processes typically exhibit inadequate ion-specific selectivity. In this regard, we rationally designed a membrane with uniform angstrom-sized pore channels and built-in charge-assisted hydrogen bond donors that preferentially conducted HCl while exhibiting negligible conductance for other compounds. The selectivity originates from the size-screening ability of angstrom-sized channels between protons and other hydrated cations. The built-in charge-assisted hydrogen bond donor enables the screening of acids by exerting host-guest interactions to varying extents, thus acting as an anion filter. The resulting membrane exhibited exceptional permeation for protons over other cations and for Cl- over SO42- and HnPO4(3-n)- with selectivities up to 4334 and 183, respectively, demonstrating prospects for HCl extraction from waste streams. These findings will aid in designing advanced multifunctional membranes for sophisticated separation.

A simple, flexible, and high-efficiency western blot analysis for age-related human induced neurons.

High-throughput western blot (WB) analysis can be used to obtain more consistent, comparable, and informative data from precious samples and materials with extremely limited availability, such as various age-related, subtype-specific human induced neurons (hiNs). In this study, p-toluenesulfonic acid (PTSA), an odorless tissue fixative, was used to inactivate horseradish peroxidase (HRP) and develop a high-throughput WB method. PTSA-treated blots demonstrated rapid and efficient HRP inactivation without detectable protein loss or epitope damage. With a brief PTSA treatment (1 min at room temperature [RT]) before every subsequent probing, 10 dopaminergic hiN proteins could be sequentially, sensitively, and specifically detected in the blot. The resulting WB data confirmed the age-associated and neuron-specific features of hiNs and revealed a significant reduction in two Parkinson's disease-associated proteins, UCHL1 and GAP43, in normal aging dopaminergic neurons. Overall, this study developed a unique and high-efficiency WB analysis method for capturing robust and useful data from limited, precious samples.

Blending Aryl Ketone in Covalent Organic Frameworks to Promote Photoinduced Electron Transfer.

Aryl-ketone derivatives have been acknowledged as promising organic photocatalysts for photosynthesis. However, they are limited by their photostability and have been less explored for photoinduced electron transfer (PET) applications. Herein we demonstrate a novel strategy to cover the shortage of aryl-ketone photocatalysts and control the photoreactivity by implanting symmetric aryl ketones into the conjugated covalent organic frameworks (COFs). To prove the concept, three comparative materials with the same topology and varied electronic structures were built, adopting truxenone knot and functionalized terephthalaldehyde linkers. Spectroscopic investigation and excited carrier dynamics analysis disclosed improvements in the photostability and electronic transfer efficiency as well as the structure-performance relationships toward N-aryl tetrahydroisoquinoline oxidation. This system provides a robust rule of thumb for designing new-generation aryl-ketone photocatalysts.

Diagnostic and prognostic performance of plasma neurofilament light chain in multiple system atrophy: a cross-sectional and longitudinal study.

BACKGROUND: The longitudinal dynamics of neurofilament light chain (NfL) in multiple system atrophy (MSA) were incompletely illuminated. This study aimed to explore whether the plasma NfL (pNfL) could serve as a potential biomarker of clinical diagnosis and disease progression for MSA. METHODS: We quantified pNfL concentrations in both a large cross-sectional cohort with 214 MSA individuals, 65 PD individuals, and 211 healthy controls (HC), and a longitudinal cohort of 84 MSA patients. Propensity score matching (PSM) was used to balance the age between the three groups. The pNfL levels between groups were compared using Kruskal-Wallis test. Linear mixed models were performed to explore the disease progression-associated factors in longitudinal MSA cohort. Random forest model as a complement to linear models was employed to quantify the importance of predictors. RESULTS: Before and after matching the age by PSM, the pNfL levels could reliably differentiate MSA from HC and PD groups, but only had mild potential to distinguish PD from HC. By combining linear and nonlinear models, we demonstrated that pNfL levels at baseline, rather than the change rate of pNfL, displayed potential prognostic value for progression of MSA. The combination of baseline pNfL levels and other modifiers, such as subtypes, Hoehn-Yahr stage at baseline, was first shown to improve the diagnosis accuracy. CONCLUSIONS: Our study contributed to a better understanding of longitudinal dynamics of pNfL in MSA, and validated the values of pNfL as a non-invasive sensitive biomarker for the diagnosis and progression. The combination of pNfL and other factors is recommended for better monitoring and prediction of MSA progression.

Organohydrogels with High-Speed Lubrication by Confining Polymer Chain Mobility by an Interpenetrated Heteronetwork.

Hydrogels with pure hydrophilic network have received much attention due to their excellent low frictional behavior. However, the lubrication performance of hydrogels is not satisfied under high-speed condition due to the energy dissipation caused by adsorbed polymer chains as well as the failure of lubricating mechanisms accompanied by the transition of lubrication regime. In this work, interpenetrating double-network organohydrogels were constructed by combining hydrophilic and oleophilic polymer networks to modify the physiochemical properties of surface polymer chains, especially the chain mobility. The oleophilic polymer network spatially restricting the mobility of the swollen hydrophilic network in water, resulted in a low coefficient of friction (ca. 0.01) compared with conventional hydrogels at high speed (0.1 m s-1 ). Meanwhile, the organohydrogels had superior wear resistance, with almost no wear observed on the sliding track after 5 k cycles of rubbing at high speed. The design concept of organohydrogels can be extended to a variety of low-wear, highly-lubricating materials.

CENP-I directly targets centromeric DNA to support CENP-A deposition and centromere maintenance.

The enrichment of histone H3 variant CENP-A is the epigenetic mark of centromere and initiates the assembly of the kinetochore at centromere. The kinetochore is a multi-subunit complex that ensures accurate attachment of microtubule centromere and faithful segregation of sister chromatids during mitosis. As a subunit of kinetochore, CENP-I localization at centromere also depends on CENP-A. However, whether and how CENP-I regulates CENP-A deposition and centromere identity remains unclear. Here, we identified that CENP-I directly interacts with the centromeric DNA and preferentially recognizes AT-rich elements of DNA via a consecutive DNA-binding surface formed by conserved charged residues at the end of N-terminal HEAT repeats. The DNA binding-deficient mutants of CENP-I retained the interaction with CENP-H/K and CENP-M, but significantly diminished the centromeric localization of CENP-I and chromosome alignment in mitosis. Moreover, the DNA binding of CENP-I is required for the centromeric loading of newly synthesized CENP-A. CENP-I stabilizes CENP-A nucleosomes upon binding to nucleosomal DNA instead of histones. These findings unveiled the molecular mechanism of how CENP-I promotes and stabilizes CENP-A deposition and would be insightful for understanding the dynamic interplay of centromere and kinetochore during cell cycle.