Superior Hole Injection Material PEGDT/TPF/PVDF with p-Doping Capability for Highly Efficient Solution-Processed Organic Light-Emitting Diode.

The ability to charge injection is a key factor in determining the performance of the organic light-emitting diode (OLED) devices. Improving the work function of the anode surface via interface modification, thus lowering the hole injection barrier, stands as a crucial strategy for enhancing the performance of the OLED device. Herein, we propose an innovative p-doping hole injection material, namely, PEGDT/TPF/PVDF that exhibits excellent performance in OLED devices with the value of maximum current efficiency at 56.4 Cd A-1, maximum luminescence at 25,564 Cd m-2, and a high EQE of 19.8%. The results for PEGDT/TPF/PVDF showed good conductivity, excellent film-forming property, and high transmittance over 98% in the spectrum range of 500-700 nm. Changes in the hole-injection energy barriers observed from the surface of the anode suggest a modified anode with PEGDT/TPF/PVDF deepened the work function at a value of 0.2 eV, which dramatically improves the hole-injection properties. This work not only provides novel structural materials with exceptional hole-injection properties but also proposes a promising alternative to PEDOT/PSS.

The primary systemic vasculitis associated optic neuritis: a retrospective analysis in a single center over 10 years.

OBJECTIVES: To investigate the clinical and image characteristics of primary systemic vasculitis-associated optic neuritis patients. METHODS: This is a retrospective study. The patients clinically diagnosed with primary system vasculitis-induced optic neuritis were recruited from March 2013 to December 2023. All cases received orbital magnetic resonance imaging scans were analyzed. The ocular findings, systemic manifestations, laboratory data and prognosis were reviewed retrospectively. In addition, the related literature was reviewed. RESULTS: Fourteen patients (21 eyes), including 10 men and 4 women, were enrolled in this study. The ages ranged from 30 to 86 years in this cohort. Orbits MRI detects the enlargement and/or enhancement of the optic nerve. Cases 1-5 reported a confirmed diagnosis of Takayasu's arteritis, and cases 6-8 had giant cell arteritis. Cases 9-13 were antineutrophil cytoplasmic antibody-associated vasculitis. Case 14 was Cogan's syndrome. Mult organs and tissues, such as the kidneys, heart, paranasal sinuses, meninges, and respiratory system, were involved. In all of the 14 involved patients, the disease onset was either during the fall or winter season. There were no or only slight improvements in visual activity after conventional therapies. CONCLUSIONS: The autoantibodies' attack on the optic nerve, ischemic damage, or destruction of the blood-brain barrier may be the potential pathogenesis of vasculitis-associated optic neuritis. Even with prompt and aggressive clinical interventions, the prognosis remains unsatisfactory.

Enhancing Fire Safety and Softness: Efficacy of Ethanolamine Polyphosphate as a Fire Retardant for Textiles.

The rising awareness of fire safety among consumers has driven the demand for fire retardants (FRs) that are both cost-effective and efficient across various industries, particularly in textiles. Traditional FRs often compromise fabric softness, resulting in undesirable tactile texture and stiffness changes. While the external addition of softeners can mitigate the stiffness, it may introduce issues such as a greasy texture and increased flammability. This study introduces ethanolamine polyphosphate (EAPP), an innovative organic polyphosphate, as an effective fire retardant that preserves the softness of textiles. Comprehensive evaluations are conducted on EAPP-treated textiles, revealing significant improvements in fire retardancy without compromising fabric quality. EAPP treatment (15 wt.% aqueous solutions) increases the limiting oxygen index (LOI) of pure cotton textiles from 17% to 36% and significantly reduces the peak heat release rate (pHRR) and total smoke rate (TSR) as measured by cone calorimetry. Unlike conventional FR products that form FR-salt crystal particles on the fabric surface after drying, EAPP forms a smooth FR protective layer on the fabric, enhancing mechanical fastness and maintaining tactile qualities. These findings highlight EAPP's potential as a non-washing durable, spray-on fire retardant solution for textiles, combining safety with user comfort.

Insights into the mechanism of Danggui Liuhuang Tang in treating night sweats: A network pharmacology and molecular docking approach.

BACKGROUND: Night sweats can occur independently or in association with a number of medical conditions and can significantly disrupt daily life. This study focuses on the treatment of primary night sweats. Despite the considerable interest in Danggui Liuhuang Tang (DGLHT), an effective traditional Chinese medicine formula, its mechanism of action remains unknown. There is also no existing literature on the subject. METHODS: Network pharmacology and molecular docking techniques. RESULTS: Network pharmacology techniques were employed to identify 109 active ingredients and 808 potential targets of DGLHT, as well as 2385 targets associated with night sweating diseases. The screening process yielded 375 common targets shared between DGLHT and night sweating. These included the active ingredients baicalein, quercetin, huarangiin, and tetrahydroafrican antipyrine, and the core targets interleukin 6, serine/threonine protein kinase 1, tumor necrosis factor, GAPDH enzyme, and Src protein kinase were identified. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that DGLHT exerts its therapeutic effects primarily by modulating the PI3K-Akt signaling pathway, neuroactive ligand-receptor interactions, lipid metabolism, and atherosclerosis pathways. Molecular docking revealed strong binding activity between the main active ingredients and their potential targets. CONCLUSION: The research identifies promising active ingredients and targets related to the effectiveness of DGLHT in controlling night sweats, thus contributing to the further exploration of potential therapeutics for this condition. In addition, the results of this experiment provide a basis for future research into night sweats.

Beneficial Effects of Ginger Extract on Eye Fatigue and Shoulder Stiffness: A Randomized, Double-Blind, and Placebo-Controlled Parallel Study.

This study aimed to assess ginger extract's impact on ocular and peripheral blood flow and its potential to alleviate eye fatigue and shoulder stiffness. This study included 100 healthy individuals aged 20-73 years with eye fatigue and shoulder stiffness. Participants were randomly assigned to receive either placebo capsules or ginger extract capsules daily for eight weeks. Ocular blood flow, peripheral blood flow, eye fatigue (visual analog scale [VAS]), shoulder stiffness (VAS), body warmth (VAS), and shoulder muscle stiffness were assessed at weeks 0, 4, and 8, respectively. No improvement in ocular blood flow was observed under the study conditions. Conversely, peripheral blood flow in deep areas was enhanced in females (p = 0.033). Subgroup analysis by age (≥51 or <51 years) revealed that ginger's effect on enhancing peripheral blood flow in deep vessels was restricted in females under 51 (p = 0.017). Similarly, subjective complaints of eye fatigue and shoulder stiffness were improved by ginger consumption in females under 51. Body warmth was favorably changed significantly in males ≥51 years due to ginger consumption. The muscle stiffness showed no statistically significant changes. In conclusion, ginger consumption reduces eye fatigue and shoulder stiffness by enhancing peripheral blood flow in relatively young females.

The Research on the Effect of Nutritional Stage-based Care Intervention in Elderly Patients with Severe Pneumonia.

Objective: To evaluate the efficacy of a nutritional stage-based care intervention in improving outcomes for elderly patients with severe pneumonia. Methods: A retrospective analysis of clinical data was conducted on 203 elderly patients with severe pneumonia admitted to our hospital from January 2022 to January 2023. All patients met the inclusion and exclusion criteria. Upon admission, all patients received relevant symptomatic treatment and basic care. Based on the nutritional care intervention received by the patients, they were divided into a control group (n=101) and an observation group (n=102). The control group received routine nutritional care intervention, while the observation group received nutritional stage-based care intervention. The study compared the levels of organ recovery indicators (mechanical ventilation time, ICU hospitalization time), nutritional status indicators [serum albumin (Alb), prealbumin (PAB), hemoglobin (Hb)], immune function indicators [immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM)], blood gas status indicators [arterial oxygen pressure (PaO2), arterial carbon dioxide pressure (PaCO2)], and the occurrence of complications between the two groups. Results: Organ Recovery Indicators: The observation group showed significantly lower mechanical ventilation time and ICU hospitalization time compared to the control group (P < .05). Nutritional Status Indicators: Before the intervention, there was no significant difference in albumin (Alb), prealbumin (PAB), and hemoglobin (Hb) levels between the two groups (P > .05). After the intervention, the Alb, PAB, and Hb levels in the observation group were significantly higher than the control group (P < .05). Immune Function Indicators: Before intervention, there was no significant difference in IgA, IgG, and IgM levels between the two groups (P > .05). After intervention, the levels of IgA, IgG, and IgM in the observation group were significantly higher than the control group (P < .05). Blood Gas Status Indicators: Before intervention, there was no significant difference in PaO2 and PaCO2 levels between the two groups (P > .05). After intervention, the PaO2 level in the observation group was significantly higher, while the PaCO2 level was significantly lower compared to the control group (P < .05). Complication Incidence: The complication incidence in the control group was 25.74%, while in the observation group it was 9.80%, which was significantly lower (P < .05). Conclusion: The application of nutritional stage-based care intervention in the management of elderly patients with severe pneumonia is shown to be highly beneficial. Compared to routine nutritional care, the nutritional stage-based approach significantly improved patients' nutritional status, immune function, blood gas conditions, and accelerated their organ recovery. Importantly, this intervention also led to a markedly lower incidence of complications. These findings suggest that incorporating nutritional stage-based care into standard treatment protocols for elderly patients with severe pneumonia may significantly enhance recovery rates and long-term health outcomes for this vulnerable patient population. Given the positive impact demonstrated in this study, the nutritional stage-based care intervention is worthy of broader clinical adoption and promotion.

Platelet indices and inflammatory bowel disease: a Mendelian randomization study.

Background: Platelets play a significant role in the innate and adaptive processes of immunity and inflammation. Inflammatory bowel disease (IBD) is an autoimmune disease that is widely understood to be caused by a combination of genetic predisposition, aberrant immune responses, etc. Methods: To examine the relationships between genetically determined platelet indices and IBD, we conducted a Mendelian randomization (MR) study. Data associated with platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT) were used from the UK Biobank. The outcome data, including IBD, Crohn's disease (CD), ulcerative colitis (UC), were from the FinnGen database. The inverse variance-weighted (IVW), MR-Egger, weighted median methods were used for MR analyses. Results: The MR estimations from the IVW approach show a significant connection between PLT and IBD. Similarly, PCT and IBD have a relationship following the IVW and MR-Egger approaches. While PLT and PCT have strong relationships with CD, according to the findings of all three approaches respectively. Nevertheless, PDW was the only relevant indicator of UC. The only significant result was IVW's. Conclusion: Our findings suggest that the fluctuation of platelet indicators is of great significance in the development of IBD. PLT and PCT have a close association with IBD and CD, respectively; PDW only has a connection with UC. Platelets play an important role in the progression of IBD (UC, CD).

End-to-end Autonomous Driving: Challenges and Frontiers.

The autonomous driving community has witnessed a rapid growth in approaches that embrace an end-to-end algorithm framework, utilizing raw sensor input to generate vehicle motion plans, instead of concentrating on individual tasks such as detection and motion prediction. End-to-end systems, in comparison to modular pipelines, benefit from joint feature optimization for perception and planning. This field has flourished due to the availability of large-scale datasets, closed-loop evaluation, and the increasing need for autonomous driving algorithms to perform effectively in challenging scenarios. In this survey, we provide a comprehensive analysis of more than 270 papers, covering the motivation, roadmap, methodology, challenges, and future trends in end-to-end autonomous driving. We delve into several critical challenges, including multi-modality, interpretability, causal confusion, robustness, and world models, amongst others. Additionally, we discuss current advancements in foundation models and visual pre-training, as well as how to incorporate these techniques within the end-to-end driving framework.We maintain an active repository that contains up-to-date literature and open-source projects at https://github.com/OpenDriveLab/End-to-end-Autonomous-Driving.

Self-powered triboelectric-responsive microneedles with controllable release of optogenetically engineered extracellular vesicles for intervertebral disc degeneration repair.

Excessive exercise is an etiological factor of intervertebral disc degeneration (IVDD). Engineered extracellular vesicles (EVs) exhibit excellent therapeutic potential for disease-modifying treatments. Herein, we fabricate an exercise self-powered triboelectric-responsive microneedle (MN) assay with the sustainable release of optogenetically engineered EVs for IVDD repair. Mechanically, exercise promotes cytosolic DNA sensing-mediated inflammatory activation in senescent nucleus pulposus (NP) cells (the master cell population for IVD homeostasis maintenance), which accelerates IVDD. TREX1 serves as a crucial nuclease, and disassembly of TRAM1-TREX1 complex disrupts the subcellular localization of TREX1, triggering TREX1-dependent genomic DNA damage during NP cell senescence. Optogenetically engineered EVs deliver TRAM1 protein into senescent NP cells, which effectively reconstructs the elimination function of TREX1. Triboelectric nanogenerator (TENG) harvests mechanical energy and triggers the controllable release of engineered EVs. Notably, an optogenetically engineered EV-based targeting treatment strategy is used for the treatment of IVDD, showing promising clinical potential for the treatment of degeneration-associated disorders.

Sappanone A ameliorated imiquimod-induced psoriasis-like dermatitis in BALB/c mice via suppressing Mmp8 expression and IL-17 signaling pathway.

Psoriasis is a prevalent immune-mediated inflammatory skin disease characterized by excessive abnormal proliferation of keratinocytes and infiltration of immune cells, which have significant impact on the life quality of individuals. Although biological agents and small molecule targeted drugs have brought significant clinical benefits to psoriasis patients, adverse reactions and high prices remains key issues in clinical medication of psoriasis, while natural product monomers possess high efficiency, low toxicity, anti-inflammatory and immunomodulatory properties, and bring new hope for the clinical treatment of psoriasis. Sappanone A (SA), a small molecule compound isolated from Caesalpinia sappan L, exhibits significant anti-inflammatory properties in various models, such as kidney inflammation and LPS-induced mice inflammation. Among these effects, the anti-inflammatory property of SA has received significant attention. In our study, we found that SA exhibited anti-proliferation and anti-inflammatory effects in HaCaT cells, and significantly alleviated imiquimod-induced psoriasis-like skin lesions via the inhibition of the excessive proliferation of keratinocytes and the infiltration of lymphocytes. Furthermore, the combinational analysis of network pharmacology and transcriptome sequencing revealed that SA exerted anti-psoriasis effects by inhibiting the matrix metalloproteinase 8 (Mmp8) expression and IL-17 pathway activation. In summary, we have first demonstrated that SA can be used as a novel anti-psoriasis drug, which may provide a novel strategy for the clinical treatment of psoriasis.

Circ_0000758 Facilitates Bladder Cancer Cell Growth, Migration and Angiogenesis Via Severing as miR-1236-3p Sponge.

Circular RNA (circRNA) has been reported to regulate the development of bladder cancer (BCa). However, the role of circ_0000758 in BCa progression is unknown. Circ_0000758 and miR-1236-3p expression, as well as ZEB2 mRNA expression were determined by qRT-PCR. BCa cell biological functions were determined by MTT assay, EdU assay, flow cytometry, wound healing assay and tube formation assay. Protein expression was detected by western blot analysis. RNA pull-down assay and dual-luciferase reporter assay were used to confirm RNA interaction. Xenograft mice models were constructed to assess the effect of circ_0000758 on BCa tumor growth. Circ_0000758 had increased expression in BCa tissues and cells. Circ_0000758 silencing could inhibit BCa cell growth, migration, angiogenesis in vitro, and tumor growth in vivo. Circ_0000758 served as a molecular sponge for miR-1236-3p, and miR-1236-3p inhibitor reversed circ_0000758 knockdown-mediated the inhibition effect on BCa cell progression. ZEB2 was targeted by miR-1236-3p, and its overexpression also revoked the suppressive effect of miR-1236-3p on BCa cell growth, migration, and angiogenesis. Besides, circ_0000758 knockdown also restrained BCa tumor growth. Circ_0000758 might promote BCa cell growth, migration, and angiogenesis by regulating the miR-1236-3p/ZEB2 axis.

Exerkine FNDC5/irisin-enriched exosomes promote proliferation and inhibit ferroptosis of osteoblasts through interaction with Caveolin-1.

Postmenopausal osteoporosis is a prevalent metabolic bone disorder characterized by a decrease in bone mineral density and deterioration of bone microstructure. Despite the high prevalence of this disease, no effective treatment for osteoporosis has been developed. Exercise has long been considered a potent anabolic factor that promotes bone mass via upregulation of myokines secreted by skeletal muscle, exerting long-term osteoprotective effects and few side effects. Irisin was recently identified as a novel myokine that is significantly upregulated by exercise and could increase bone mass. However, the mechanisms underlying exercise-induced muscle-bone crosstalk remain unclear. Here, we identified that polyunsaturated fatty acids (arachidonic acid and docosahexaenoic acid) are increased in skeletal muscles following a 10-week treadmill exercise programme, which then promotes the expression and release of FNDC5/irisin. In osteoblasts, irisin binds directly to Cav1, which recruits and interacts with AMP-activated protein kinase α (AMPKα) to activate the AMPK pathway. Nrf2 is the downstream target of the AMPK pathway and increases the transcription of HMOX1 and Fpn. HMOX1 is involved in regulating the cell cycle and promotes the proliferation of osteoblasts. Moreover, upregulation of Fpn in osteoblasts enhanced iron removal, thereby suppressing ferroptosis in osteoblasts. Additionally, we confirmed that myotube-derived exosomes are involved in the transportation of irisin and enter osteoblasts through caveolae-mediated endocytosis. In conclusion, our findings highlight the crucial role of irisin, present in myotube-derived exosomes, as a crucial regulator of exercise-induced protective effects on bone, which provides novel insights into the mechanisms underlying exercise-dependent treatment of osteoporosis.

Fusion of biomedical imaging studies for increased sample size and diversity: a case study of brain MRI.

Data collection, curation, and cleaning constitute a crucial phase in Machine Learning (ML) projects. In biomedical ML, it is often desirable to leverage multiple datasets to increase sample size and diversity, but this poses unique challenges, which arise from heterogeneity in study design, data descriptors, file system organization, and metadata. In this study, we present an approach to the integration of multiple brain MRI datasets with a focus on homogenization of their organization and preprocessing for ML. We use our own fusion example (approximately 84,000 images from 54,000 subjects, 12 studies, and 88 individual scanners) to illustrate and discuss the issues faced by study fusion efforts, and we examine key decisions necessary during dataset homogenization, presenting in detail a database structure flexible enough to accommodate multiple observational MRI datasets. We believe our approach can provide a basis for future similarly-minded biomedical ML projects.

Temperature Self-Compensating Intelligent Wireless Measuring Contact Lens for Quantitative Intraocular Pressure Monitoring.

Flexible bioelectronic devices that can perform real-time and accurate intraocular pressure (IOP) monitoring in both clinical and home settings hold significant implications for the diagnosis and treatment of glaucoma, yet they face challenges due to the open physiological environment of the ocular. Herein, we develop an intelligent wireless measuring contact lens (WMCL) incorporating a dual inductor-capacitor-resistor (LCR) resonant system to achieve temperature self-compensation for quantitative IOP monitoring in different application environments. The WMCL utilizes a compact circuitry design, which enables the integration of low-frequency and high-frequency resonators within a single layer of a sensing circuit without causing visual impairment. Mechanically guided microscale 3D encapsulation strategy combined with flexible circuit printing techniques achieves the surface-adaptive fabrication of the WMCL. The specific design of frequency separation imparts distinct temperature response characteristics to the dual resonators, and the linear combination of the dual resonators can eliminate the impact of temperature variations on measurement accuracy. The WMCL demonstrates outstanding sensitivity and linearity in monitoring the IOP of porcine eyes in vitro while maintaining satisfactory measurement accuracy even with internal temperature variations exceeding 10 °C. Overcoming the impact of temperature variations on IOP monitoring from the system level, the WMCL showcases immense potential as the next generation of all-weather IOP monitoring devices.

Isoperimetric Constraint Inference for Discrete-Time Nonlinear Systems Based on Inverse Optimal Control.

In this article, the problem of inferring unknown isoperimetric constraints is considered given optimal state and control trajectories that solve the optimal control problem with isoperimetric constraints. By exploiting Pontryagin's principle, the recovery equations for unknown isoperimetric constraints are established. Under verifiable dimensionality condition and matrix rank condition, the proposed method is guaranteed to infer the unknown isoperimetric constraints exactly. Furthermore, the proposed method is extended to multiple trajectory setting. Finally, the effectiveness of the proposed method is illustrated by two simulation examples with various settings.

Research on the relationship between CEO career variety, digital knowledge base extension, and digital transformation in the context of digital merger and acquisition: The case of China's new generation of information technology firms.

This study examines the relationship between CEO career variety, digital knowledge base extension, and digital transformation in a digital M&A context. An empirical test was conducted using regression analysis with the digital M&A events of the new generation of information technology firms in China as the research sample. The results reveal that CEO career variety has a positive effect on digital transformation in the digital M&A context and that digital knowledge-base extension plays a mediating role. Moreover, the heterogeneity impact analysis indicated that the moderating effects of geographical distance, knowledge disparity, and cultural difference between target and acquirer firms on the above relationships vary greatly: geographical distance has a negative moderating effect, cultural difference has a positive moderating effect, and the moderating effects of both geographical distance and cultural difference are realized through mediating effects, but none of the moderating effects of knowledge disparity are significant.

HPCDNet: Hybrid position coding and dual-frquency domain transform network for low-light image enhancement.

Low-light image enhancement (LLIE) improves lighting to obtain natural normal-light images from images captured under poor illumination. However, existing LLIE methods do not effectively utilize positional and frequency domain image information. To address this limitation, we proposed an end-to-end low-light image enhancement network called HPCDNet. HPCDNet uniquely integrates a hybrid positional coding technique into the self-attention mechanism by appending hybrid positional codes to the query and key, which better retains spatial positional information in the image. The hybrid positional coding can adaptively emphasize important local structures to improve modeling of spatial dependencies within low-light images. Meanwhile, frequency domain image information lost under low-light is recovered via discrete wavelet and cosine transforms. The resulting two frequency domain feature types are weighted and merged using a dual-attention module. More effective use of frequency domain information enhances the network's ability to recreate details, improving visual quality of enhanced low-light images. Experiments demonstrated that our approach can heighten visibility, contrast and color properties of low-light images while better preserving details and textures than previous techniques.

Triboelectric-Responsive Drug Delivery Hydrogel for Accelerating Infected Wound Healing.

Electrotherapy is of great interest in the field of tissue repair as an effective, well-tolerated, and noninvasive treatment. Triboelectric nanogenerator (TENG) has shown advantages in promoting wound healing due to its peak output characteristic and low Joule heating effect. However, it is limited in infected wound healing due to poor antimicrobial capacity. Here, a wearable triboelectric stimulator (WTS) is developed that consists of a flexible TENG (F-TENG) and a triboelectric-responsive drug delivery hydrogel (TR-DDH) for healing of bacterium-infected wounds. F-TENG can generate pulsed current to wounds by converting mechanical energy from body movements. Polypyrrole is prone to reduction and volume contraction under electrical stimulation, resulting in desorption of curcumin nanoparticles (CUR NPs) from the polypyrrole in TR-DDH. Therefore, the highly efficient and controllable release of CUR NPs can be achieved by triboelectric stimulation. According to the in vitro and in vivo experiments, WTS has the greatest antimicrobial effect and the fastest promotion of infected wound healing compared to treatment with electrical stimulation or curcumin. Finally, the safety assessment demonstrates that the WTS has excellent tissue safety for chronic wound healing. Synergistic therapy with WTS provides an efficient strategy for chronic wound healing and smart-responsive drug delivery systems.

Identification of structural origins of complex charge heterogeneity in therapeutic ACE2Fc fusion protein facilitated by free-flow isoelectric focusing.

Fc Fusion protein represents a versatile molecular platform with considerable potential as protein therapeutics of which the charge heterogeneity should be well characterized according to regulatory guidelines. Angiotensin-converting enzyme 2 Fc fusion protein (ACE2Fc) has been investigated as a potential neutralizing agent to various coronaviruses, including the lingering SARS-CoV-2, as this coronavirus must bind to ACE2 to allow for its entry into host cells. ACE2Fc, an investigational new drug developed by Henlius (Shanghai China), has passed the Phase I clinical trial, but its huge amount of charge isoforms and complicated charge heterogeneity posed a challenge to charge variant investigation in pharmaceutical development. We employed offline free-flow isoelectric focusing (FF-IEF) fractionation, followed by detailed characterization of enriched ACE2Fc fractions, to unveil the structural origins of charge heterogeneity in ACE2Fc expressed by recombinant CHO cells. We adopted a well-tuned 3-component separation medium for ACE2Fc fractionation, the highest allowable voltage to maximize the FF-IEF separation window and a mild Protein A elution method for preservation of protein structural integrity. Through peptide mapping and other characterizations, we revealed that the intricate profiles of ACE2Fc charge heterogeneity are mainly caused by highly sialylated multi-antenna N-glycosylation. In addition, based on fraction characterization and in silico glycoprotein model analysis, we discovered that the large acidic glycans at N36, N73, and N305 of ACE2Fc were able to decrease the binding activity towards Spike (S) protein of SARS-CoV-2. Our study exemplifies the value of FF-IEF in highly complex fusion protein characterization and revealed a quantitative sialylation-activity relationship in ACE2Fc.

Multidomain interventions based on a life-course model to prevent dementia in at-risk Chinese older adults: A randomized controlled trial.

BACKGROUND: Due to the time-dependent effect of specific risk factors for dementia, multidomain interventions based on a life-course model might achieve optimal preventive effects against dementia. OBJECTIVE: The purpose of this study was to investigate the effectiveness of multidomain interventions based on a life-course model of modifiable risk factors for dementia in at-risk Chinese older adults. DESIGN: This was a two-arm, proof-of-concept, randomized controlled trial. SETTING AND PARTICIPANTS: We randomly assigned 96 community-dwelling at-risk adults aged 60 years or older in a 1:1 ratio to either the 6-month multidomain intervention group (dementia literacy, physical activity, cognitive training, social activity and optional modules) or the control group (health education). METHODS: The primary outcomes were the dementia risk score and cognitive composite Z score. The secondary outcomes included the individual components of the dementia risk score (protective and risk factors) and cognitive composite Z score (global cognition, memory, executive function and language), social isolation (loneliness, social contact, and social participation), dementia literacy and prevention belief. Linear mixed models with maximum likelihood estimation were used to calculate the outcomes between the groups over time. RESULTS: The primary analyses showed that the dementia risk score was significantly lower (p < 0.001) and that the cognitive composite Z score was significantly higher (p = 0.013) in the multidomain intervention group than in the control group. Baseline characteristics did not modify the effects of the multidomain interventions (p value for interaction > 0.05). For secondary outcomes, statistically significant group × time interactions were observed for the protective (p = 0.001) and risk factors (p = 0.049), as well as in executive function (p = 0.020), loneliness (p = 0.029), dementia literacy (p < 0.001) and prevention belief (p < 0.001). CONCLUSIONS: Multidomain interventions based on a life-course model are feasible and have the potential to reduce dementia risk and improve cognitive function in at-risk Chinese older adults. REGISTRATION: The trial was registered at the Chinese Clinical Trials Registry (ChiCTR2100053417).