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"Li, Hongyu"
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Existence of Nontrivial Solutions for Boundary Value Problems of Fourth-Order Differential Equations
This article investigates the solvability problem of fourth-order differential equations with two-point boundary conditions; specifically, conclusions regarding sign-changing solutions are obtained. The methods used in this article are fixed-point theorems on lattices. Firstly, under some sublinear conditions, the existence of three nontrivial solutions is demonstrated, including a sign-changing solution, a negative solution and a positive solution. Secondly, under some unilaterally asymptotically linear and superlinear conditions, the existence of at least one sign-changing solution is proved. Finally, this article provides several specific examples to illustrate the obtained conclusions.
Journal Article
Reactive oxygen species-responsive and Raman-traceable hydrogel combining photodynamic and immune therapy for postsurgical cancer treatment
Combining immune checkpoint blockade (ICB) therapy with photodynamic therapy (PDT) holds great potential in treating immunologically “cold” tumors, but photo-generated reactive oxygen species (ROS) can inevitably damage co-administered ICB antibodies, hence hampering the therapeutic outcome. Here we create a ROS-responsive hydrogel to realize the sustained co-delivery of photosensitizers and ICB antibodies. During PDT, the hydrogel skeleton poly(deca-4,6-diynedioic acid) (PDDA) protects ICB antibodies by scavenging the harmful ROS, and at the same time, triggers the gradual degradation of the hydrogel to release the drugs in a controlled manner. More interestingly, we can visualize the ROS-responsive hydrogel degradation by Raman imaging, given the ultrastrong and degradation-correlative Raman signal of PDDA in the cellular silent window. A single administration of the hydrogel not only completely inhibits the long-term postoperative recurrence and metastasis of 4T1-tumor-bearing mice, but also effectively restrains the growth of re-challenged tumors. The PDDA-based ROS-responsive hydrogel herein paves a promising way for the durable synergy of PDT and ICB therapy.
Combined immune checkpoint blockade (ICB) and photodynamic therapies have huge potential but suffer from possible damage of the antibodies. Here, the authors create a ROS-responsive hydrogel that protects the ICB antibodies and allows for sustained co-delivery and demonstrate restrained regrowth of tumours in vivo.
Journal Article
New insight into neurological degeneration: Inflammatory cytokines and blood–brain barrier
Neurological degeneration after neuroinflammation, such as that resulting from Alzheimer’s disease (AD), stroke, multiple sclerosis (MS), and post-traumatic brain injury (TBI), is typically associated with high mortality and morbidity and with permanent cognitive dysfunction, which places a heavy economic burden on families and society. Diagnosing and curing these diseases in their early stages remains a challenge for clinical investigation and treatment. Recent insight into the onset and progression of these diseases highlights the permeability of the blood–brain barrier (BBB). The primary factor that influences BBB structure and function is inflammation, especially the main cytokines including IL-1β, TNFα, and IL-6, the mechanism on the disruption of which are critical component of the aforementioned diseases. Surprisingly, the main cytokines from systematic inflammation can also induce as much worse as from neurological diseases or injuries do. In this review, we will therefore discuss the physiological structure of BBB, the main cytokines including IL-1β, TNFα, IL-6, and their mechanism on the disruption of BBB and recent research about the main cytokines from systematic inflammation inducing the disruption of BBB and cognitive impairment, and we will eventually discuss the need to prevent the disruption of BBB.
Journal Article
PERADIGM: Phenotype embedding similarity-based rare disease gene mapping
Identifying genes associated with rare diseases remains challenging due to the scarcity of patients and the limited statistical power of traditional association methods. Here, we introduce PERADIGM ( P henotype E mbedding similarity-based RA re DI sease G ene M apping), a novel framework that leverages natural language processing techniques to integrate comprehensive phenotype information from electronic health records for rare disease gene discovery. PERADIGM employs an embedding model to capture relationships between ICD-10 codes, providing a nuanced representation of individual phenotypes. By utilizing patient similarity scores, it enhances the identification of candidate genes associated with disease-specific phenotypes, surpassing conventional methods that rely on binary disease status. We applied PERADIGM to the UK Biobank dataset for three rare diseases: autosomal dominant polycystic kidney disease (ADPKD), Marfan syndrome, and neurofibromatosis type 1 (NF1). PERADIGM identified additional candidate genes associated with ADPKD-related and Marfan syndrome-related phenotypes, some of which are supported by existing literature, and demonstrated enhanced signal detection for NF1-specific phenotypes beyond traditional methods. Our findings demonstrate the potential of PERADIGM to identify genes associated with rare diseases and related phenotypes by incorporating phenotype embeddings and patient similarity, providing a powerful tool for precision medicine and a deeper understanding of rare disease genetics and clinical manifestations.
Journal Article
Can China’s Regional Industrial Chain Innovation and Reform Policy Make the Impossible Triangle of Energy Attainable? A Causal Inference Study on the Effect of Improving Industrial Chain Resilience
This study used a double machine learning model (based on the random forest algorithm) and spatial Durbin DIDs model to conduct quasi-natural experiments. The results are as follows: (1) innovation and reform policy regarding regional industrial chains as well as their resilience can significantly and positively address the development of China’s impossible triangle coupling of energy; (2) implementing the innovation and reform policy for regional industrial chains in other regions can have a significant positive spatial transmission effect on the impossible triangle coupling coordinated development of energy in the region; (3) regional industrial chain resilience can produce a significant positive mediating effect between the innovation and reform policy of regional industrial chains and the safety, reliability, and economic feasibility of green and clean energy systems; (4) under the counterfactual framework, the mechanism path “innovation and reform policy of the regional industry chain→regional industry chain resilience→coordination degree of impossible triangle coupling of energy” has significantly positive direct and indirect effects in both the treatment group and the control group. However, “innovation and reform policy of the regional industrial chain→regional industrial chain resilience→the energy sector’s impossible triangle coupling coordination degree” and “innovation and reform policy of the regional industrial chain→leading power of the regional industrial chain→the energy sector’s impossible triangle coupling coordination degree” have significantly positive direct and indirect effects in the treatment group, but only the direct effect is significant in the control group.
Journal Article
Psychobiotic Lactobacillus plantarum JYLP-326 relieves anxiety, depression, and insomnia symptoms in test anxious college via modulating the gut microbiota and its metabolism
Test anxiety is a common issue among college students, which can affect their physical and psychological health. However, effective interventions or therapeutic strategies are still lacking. This study aims to evaluate the potential effects of
JYLP-326 on test anxious college students.
Sixty anxious students were enrolled and randomly allocated to the placebo group and the probiotic group. Both groups were instructed to take placebo and JYLP-326 products twice per day for three weeks, respectively. Thirty unanxious students with no treatments were assigned to a regular control group. The anxiety, depression, and insomnia questionnaires were used to measure students' mental states at the baseline and the end of this study. 16S rRNA sequencing and untargeted metabolomics were performed to analyze the changes in the gut microbiota and fecal metabolism.
The questionnaire results suggested that JYLP-326 administration could relieve the symptoms of anxiety, depression, and insomnia in test anxious students. The gut microbiomes of the placebo group showed a significantly greater diversity index than the control group (p < 0.05). An increased abundance of
and
at the genus level was observed in the placebo group, and the relative abundance of
and
decreased. Whereas, JYLP-326 administration could partly restore the disturbed gut microbiota. Additionally, test anxiety was correlated with disordered fecal metabolomics such as a higher Ethyl sulfate and a lower Cyclohexylamine, which could be reversed after taking JYLP-326. Furthermore, the changed microbiota and fecal metabolites were significantly associated with anxiety-related symptoms.
The results indicate that the intervention of
JYLP-326 could be an effective strategy to alleviate anxiety, depression, and insomnia in test anxious college students. The potential mechanism underlying this effect could be related to the regulation of gut microbiota and fecal metabolites.
Journal Article
Blockchain-Based Data Preservation System for Medical Data
Medical care has become an indispensable part of people’s lives, with a dramatic increase in the volume of medical data (e.g., diagnosis certificates and medical records). Medical data, however, is easily stolen, tampered with, or even completely deleted. If the above occurs, medical data cannot be recorded or retrieved in a reliable manner, resulting in delay treatment progress, even endanger the patient’s life. In this paper, we propose a novel blockchain-based data preservation system (DPS) for medical data. To provide a reliable storage solution to ensure the primitiveness and verifiability of stored data while preserving privacy for users, we leverage the blockchain framework. With the proposed DPS, users can preserve important data in perpetuity, and the originality of the data can be verified if tampering is suspected. In addition, we use prudent data storage strategies and a variety of cryptographic algorithms to guarantee user privacy; e.g., an adversary is unable to read the plain text even if the data are stolen. We implement a prototype of the DPS based on the real world blockchain-based platform Ethereum. Performance evaluation results demonstrate the effectiveness and efficiency of the proposed system.
Journal Article
Development and psychometric evaluation of the needs assessment questionnaire for family caregivers of end-of-life older adults in home hospice care
As care moves from disease-centered to family-centered, meeting the needs of caregivers becomes more and more important. The study was to develop and validate a family caregiver needs assessment questionnaire for home hospice care of the end-of-life older adult in Mainland China. Based on the guidance of Harmony Nursing Theory, 48 initial questionnaire items were initially drafted through literature review, interviews with 12 family caregivers of the end-of-life older adult, and group discussions among research team members. Two rounds of expert review and small sample testing resulted in a 36-item prediction questionnaire. From October to December 2023, 223 family caregivers of the end-of-life older adult in Jinzhou City, Liaoning Province were selected to verify the questionnaire. The final questionnaire included 34 items. With a cumulative variance contribution rate of 71.281%, the exploratory factor analysis identified six common factors. The questionnaire’s total Cronbach coefficient was 0.910, and the retest reliability was 0.868. Its content validity index was 0.982, and the items’ content validity index ranged from 0.83 to 1.00. The questionnaire items compilation and screening methods are scientifically reliable. In the future, healthcare can utilize the questionnaire to fully assess the needs of family caregivers of older adult patients end-of-life at home.
Journal Article
The mechanism of low blue light-induced leaf senescence mediated by GmCRY1s in soybean
Leaf senescence is a crucial trait that has a significant impact on crop quality and yield. Previous studies have demonstrated that light is a key factor in modulating the senescence process. However, the precise mechanism by which plants sense light and control senescence remains largely unknown, particularly in crop species. In this study, we reveal that the reduction in blue light under shading conditions can efficiently induce leaf senescence in soybean. The blue light receptors GmCRY1s rather than GmCRY2s, primarily regulate leaf senescence in response to blue light signals. Our results show that GmCRY1s interact with DELLA proteins under light-activated conditions, stabilizing them and consequently suppressing the transcription of
GmWRKY100
to delay senescence. Conversely, LBL reduces the interaction between GmCRY1s and the DELLA proteins, leading to their degradation and premature senescence of leaves. Our findings suggest a GmCRY1s-GmDELLAs-GmWRKY100 regulatory cascade that is involved in mediating LBL-induced leaf senescence in soybean, providing insight into the mechanism of how light signals regulate leaf senescence. Additionally, we generate
GmWRKY100
knockout soybeans that show delayed leaf senescence and improved yield under natural field conditions, indicating potential applications in enhancing soybean production by manipulating the leaf senescence trait.
This study provides insights into how shade induces leaf senescence in soybean. The reduction of blue light intensity deactivates GmCRY1s, leading to the degradation of GmRGAs and the upregulation of
WRKY100
, ultimately promoting leaf senescence.
Journal Article