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1.
Pain Res Manag ; 2024: 7347876, 2024.
Article En | MEDLINE | ID: mdl-38872993

Objectives: Opioid nonadherence represents a significant barrier to cancer pain treatment efficacy. However, there is currently no effective prediction method for opioid adherence in patients with cancer pain. We aimed to develop and validate a machine learning (ML) model and evaluate its feasibility to predict opioid nonadherence in patients with cancer pain. Methods: This was a secondary analysis from a cross-sectional study that included 1195 patients from March 1, 2018, to October 31, 2019. Five ML algorithms, such as logistic regression (LR), random forest, eXtreme Gradient Boosting, multilayer perceptron, and support vector machine, were used to predict opioid nonadherence in patients with cancer pain using 43 demographic and clinical factors as predictors. The predictive effects of the models were compared by the area under the receiver operating characteristic curve (AUC_ROC), accuracy, precision, sensitivity, specificity, and F1 scores. The value of the best model for clinical application was assessed using decision curve analysis (DCA). Results: The best model obtained in this study, the LR model, had an AUC_ROC of 0.82, accuracy of 0.82, and specificity of 0.71. The DCA showed that clinical interventions for patients at high risk of opioid nonadherence based on the LR model can benefit patients. The strongest predictors for adherence were, in order of importance, beliefs about medicines questionnaire (BMQ)-harm, time since the start of opioid, and BMQ-necessity. Discussion. ML algorithms can be used as an effective means of predicting adherence to opioids in patients with cancer pain, which allows for proactive clinical intervention to optimize cancer pain management. This trial is registered with ChiCTR2000033576.


Analgesics, Opioid , Cancer Pain , Machine Learning , Medication Adherence , Humans , Female , Male , Cancer Pain/drug therapy , Middle Aged , Analgesics, Opioid/therapeutic use , Cross-Sectional Studies , Medication Adherence/statistics & numerical data , Aged , Adult , Algorithms
2.
Anal Chem ; 96(24): 9961-9968, 2024 Jun 18.
Article En | MEDLINE | ID: mdl-38838250

In this study, a novel europium dual-ligand metal-organic gel (Eu-D-MOGs) with high-efficient anodic annihilation electrochemiluminescence (ECL) was synthesized as an ECL emitter to construct a biosensor for ultrasensitive detection of microRNA-221 (miR-221). Impressively, compared to the ECL signal of europium single-ligand metal-organic gels (Eu-S-MOGs), the ECL signal of Eu-D-MOGs was significantly improved since the two organic ligands could jointly replace the H2O and coordinate with Eu3+, which could remarkably reduce the nonradiative vibrational energy transfer caused by the coordination between H2O and Eu3+ with a high coordination demand. In addition, Eu-D-MOGs could be electrochemically oxidized to Eu-D-MOGs•+ at 1.45 V and reduced to Eu-D-MOGs•- at 0.65 V to achieve effective annihilation of ECL, which overcame the side reaction brought by the remaining emitters at negative potential. This benefited from the annihilation ECL performance of the central ion Eu3+ caused by its redox in the electrochemical process. Furthermore, the annihilation ECL signal of Eu3+ could be improved by sensitizing Eu3+ via the antenna effect. In addition, combined with the improved rolling circle amplification-assisted strand displacement amplification strategy (RCA-SDA), a sensitive biosensor was constructed for the sensitive detection of miR-221 with a low detection limit of 5.12 aM and could be successfully applied for the detection of miR-221 in the lysate of cancer cells. This strategy offered a unique approach to synthesizing metal-organic gels as ECL emitters without a coreactant for the construction of ECL biosensing platforms in biomarker detection and disease diagnosis.


Electrochemical Techniques , Electrodes , Europium , Gels , Luminescent Measurements , MicroRNAs , Europium/chemistry , MicroRNAs/analysis , Electrochemical Techniques/methods , Ligands , Gels/chemistry , Biosensing Techniques/methods , Limit of Detection , Humans
3.
Eur J Pharmacol ; 977: 176708, 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38843945

Excessive transforming growth factor ß1 (TGF-ß1) secreted by activated hepatic stellate cells (aHSCs) aggravates liver fibrosis via over-activation of TGF-ß1-mediated signaling pathways in a TGF-ß type I receptor (TßRI) dependent manner. TßRI with the C-terminal valine truncated (RIPΔ), as a novel TßRI-mimicking peptide, is an appealing anti-fibrotic candidate by competitive binding of TGF-ß1 to block TGF-ß1 signal transduction. Platelet-derived growth factor receptor ß (PDGFßR) is highly expressed on the surface of aHSCs in liver fibrosis. Herein, we designed a novel RIPΔ variant Z-RIPΔ (PDGFßR-specific affibody ZPDGFßR fused to the N-terminus of RIPΔ) for liver fibrosis therapy, and expect to improve the anti-liver fibrosis efficacy by specifically inhibiting the TGF-ß1 activity in aHSCs. Target peptide Z-RIPΔ was prepared in Escherichia coli by SUMO fusion system. Moreover, Z-RIPΔ specifically bound to TGF-ß1-activated aHSCs, inhibited cell proliferation and migration, and reduced the expression of fibrosis markers (α-SMA and FN) and TGF-ß1 pathway-related effectors (p-Smad2/3 and p-p38) in vitro. Furthermore, Z-RIPΔ specifically targeted the fibrotic liver, alleviated the liver histopathology, mitigated the fibrosis responses, and blocked TGF-ß1-mediated Smad and p38 MAPK cascades. More importantly, Z-RIPΔ exhibited a higher fibrotic liver-targeting capacity and stronger anti-fibrotic effects than its parent RIPΔ. Besides, Z-RIPΔ showed no obvious toxicity effects in treating both an in vitro cell model and an in vivo mouse model of liver fibrosis. In conclusion, Z-RIPΔ represents a promising targeted candidate for liver fibrosis therapy.

4.
Arch Gerontol Geriatr ; 125: 105500, 2024 May 27.
Article En | MEDLINE | ID: mdl-38851092

Total saponins from Panax japonicus (TSPJ) have many beneficial physiological activities, particularly in alleviating the damages of aging and abnormal lipid metabolism. This work used mice models to investigate if TSPJ reduced obesity and regulated metabolic functions via the intestinal microbiota, the disturbance of which has been shown to cause aging-related diseases. The results showed that TSPJ significantly reduced the weight and blood lipid level of aging mice. Further analyses showed that TSPJ significantly inhibited adipogenesis, changed the composition of the intestinal flora, and protected the integrity of the intestinal barrier. It was inferred from the accumulated experimental data that TSPJ helped to combat obesity in aging mice by regulating the intestinal microbiota and promoting microbial metabolism.

5.
PLoS One ; 19(6): e0305729, 2024.
Article En | MEDLINE | ID: mdl-38913625

BACKGROUND: Informal caregivers of persons with dementia (PWD) often suffer adverse impacts on their mental health and require interventions for effective support. As they are often occupied with providing care, web-based interventions could be more convenient and efficient for them. However, there is currently a dearth of evidence-based mobile interventions to enhance the mental well-being of dementia caregivers locally, especially ones that are user-centered and culturally relevant. Hence, having designed an app based on feedback from local dementia caregivers, this study will evaluate the effectiveness of this mobile app in promoting the mental health of informal caregivers of PWD in Singapore. METHODS: A pilot two-armed randomised controlled trial will be conducted on 60 informal caregivers of PWD recruited via convenience and snowball sampling. Thirty participants will be assigned to the intervention group, while another 30 will be in a waiting-list control group. Questionnaires will be administered at baseline and one month after, with the primary outcome being the difference in the change of depressive symptoms among the two groups. STATISTICAL ANALYSIS: Primary analyses will follow the intention-to-treat principle and compare changes from baseline to the one-month follow-up time point relative to the control group. A repeated measures ANOVA will be conducted to examine differences between the groups over time. SIGNIFICANCE: To our knowledge, this is the first study in Singapore that seeks to promote the mental health of informal dementia caregivers through a mobile-based intervention. The findings can inform the development and evaluation of future evidence-based digital interventions for local informal caregivers of PWD to address the gap in availability of such resources for them. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05551533). Registration date: September 22, 2022.


Caregivers , Dementia , Mental Health , Mobile Applications , Humans , Caregivers/psychology , Dementia/therapy , Dementia/nursing , Singapore , Pilot Projects , Female , Male , Surveys and Questionnaires , Middle Aged
6.
Mini Rev Med Chem ; 2024 Apr 22.
Article En | MEDLINE | ID: mdl-38716553

The intensification of the aging population is often accompanied by an increase in agerelated diseases, which impair the quality of life of the elderly. The characteristic feature of aging is progressive physiological decline, which is the largest cause of human pathology and death worldwide. However, natural aging interacts in exceptionally complex ways within and between organs, but its underlying mechanisms are still poorly understood. Long non-coding RNA (lncRNA) is a type of noncoding RNA that exceeds 200 nucleotides in length and does not possess protein-coding ability. It plays a crucial role in the occurrence and development of diseases. ANRIL, also known as CDKN2B-AS1, is an antisense ncRNA located at the INK4 site. It can play a crucial role in agerelated disease progression by regulating single nucleotide polymorphism, histone modifications, or post-transcriptional modifications (such as RNA stability and microRNA), such as cardiovascular disease, diabetes, tumor, arthritis, and osteoporosis. Therefore, a deeper understanding of the molecular mechanisms of lncRNA ANRIL in age-related diseases will help provide new diagnostic and therapeutic targets for clinical practice.

7.
Rev Sci Instrum ; 95(5)2024 May 01.
Article En | MEDLINE | ID: mdl-38727574

A pulsed power supply with a short rise time and high repetition frequency is favorable to driving diffusive plasma for strongly oxidizing radical (O3, OH) generation and increasing the system's energy efficiency. In this paper, a 10-stage solid-state linear transformer driver (LTD) with a nanosecond rise time is developed to drive plasma for wastewater treatment. To decrease the rise time, a control system with low jitter is developed to improve the synchronization of pulses using an optocoupler isolation chip. A 10-stage LTD with a rise time of 6.2 ns is realized in the case that the rise time of the single-stage LTD is 5.4 ns. The results show that the LTD can generate pulses on a 300 Ω resistive load with a repetition frequency of 10 kHz, an amplitude of 8.80 kV, an overshoot less than 3.97%, and a reverse overshoot less than 4.82%. The rise time (6.2-33.0 ns), the pulse width (35.9-200.0 ns), and the fall time (10.5-27.6 ns) can be adjusted flexibly and independently by controlling the drive signals of metal oxide semiconductor field effect transistors. The pulsed generator is utilized to drive plasma in the needle-water electrode system. The preliminary experimental results show that the plasma includes abundant oxygen atoms and hydroxyl radicals with high activity, and it is suitable for wastewater treatment.

8.
Front Immunol ; 15: 1371584, 2024.
Article En | MEDLINE | ID: mdl-38694509

Backgrounds: Extracellular matrix (ECM) is an important component of tumor microenvironment, and its abnormal expression promotes tumor formation, progression and metastasis. Methods: Weighted gene co-expression network analysis (WGCNA) was used to identify ECM-related hub genes based on The Cancer Genome Atlas (TCGA) colon adenocarcinoma (COAD) data. COAD clinical samples were used to verify the expression of potential biomarkers in tumor tissues, and siRNA was used to explore the role of potential biomarkers in cell proliferation and epithelial-mesenchymal transition (EMT). Results: Three potential biomarkers (LEP, NGF and PCOLCE2) related to prognosis of COAD patients were identified and used to construct ERGPI. Immunohistochemical analysis of clinical samples showed that the three potential biomarkers were highly expressed in tumor tissues of COAD patients. Knockdown of LEP, NGF or PCOLCE2 inhibited COAD cell proliferation and EMT. Dictamnine inhibited tumor cell growth by binding to these three potential biomarkers based on molecular docking and transplanted tumor model. Conclusion: The three biomarkers can provide new ideas for the diagnosis and targeted therapy of COAD patients.


Adenocarcinoma , Biomarkers, Tumor , Colonic Neoplasms , Computational Biology , Epithelial-Mesenchymal Transition , Extracellular Matrix , Humans , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , Colonic Neoplasms/diagnosis , Colonic Neoplasms/metabolism , Adenocarcinoma/genetics , Adenocarcinoma/diagnosis , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Computational Biology/methods , Extracellular Matrix/metabolism , Animals , Epithelial-Mesenchymal Transition/genetics , Mice , Cell Proliferation/genetics , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Prognosis , Tumor Microenvironment , Molecular Docking Simulation , Gene Expression Profiling , Male , Gene Regulatory Networks
9.
Redox Rep ; 29(1): 2354625, 2024 Dec.
Article En | MEDLINE | ID: mdl-38794801

Deficiency of TOM5, a mitochondrial protein, causes organizing pneumonia (OP) in mice. The clinical significance and mechanisms of TOM5 in the pathogenesis of OP remain elusive. We demonstrated that TOM5 was significantly increased in the lung tissues of OP patients, which was positively correlated with the collagen deposition. In a bleomycin-induced murine model of chronic OP, increased TOM5 was in line with lung fibrosis. In vitro, TOM5 regulated the mitochondrial membrane potential in alveolar epithelial cells. TOM5 reduced the proportion of early apoptotic cells and promoted cell proliferation. Our study shed light on the roles of TOM5 in OP.


Alveolar Epithelial Cells , Membrane Potential, Mitochondrial , Animals , Alveolar Epithelial Cells/metabolism , Alveolar Epithelial Cells/pathology , Mice , Humans , Membrane Potential, Mitochondrial/physiology , Mitochondrial Precursor Protein Import Complex Proteins , Male , Apoptosis , Female , Cell Proliferation , Mice, Inbred C57BL , Disease Models, Animal , Cryptogenic Organizing Pneumonia/pathology , Cryptogenic Organizing Pneumonia/metabolism , Organizing Pneumonia
10.
ACS Appl Mater Interfaces ; 16(22): 29141-29152, 2024 Jun 05.
Article En | MEDLINE | ID: mdl-38773701

Poor interfacial quality and low refractive index contrast (Δn) are critical challenges for the development of high-performance one-dimensional photonic crystals (1DPhCs) via solution methods that impede their optical efficiency. Herein, we introduce an innovative approach by hybridizing hollow SiO2 with poly(vinyl alcohol), referred to as PHS, followed by alternate assembly with TiO2 via spin-coating, achieving a 1DPhC with Δn = 0.76 at the wavelength of 550 nm. This method circumvents the need for high-temperature treatment and complex curing conditions, resulting in a 1DPhC with superior interfacial and optical characteristics. By adjusting the thickness of the PHS layers, we can finely tune the reflectance spectrum, attaining over 99% reflectance at the photonic band gap. Furthermore, 1DPhC demonstrates excellent adhesion to polycarbonate substrates and retains its optimal optical performance even after rigorous environmental testing, including hygrothermal cycles, exposure to hot water, friction, and solvent sonication. This research paves the way for the facile fabrication of high-performance 1DPhCs under mild conditions, offering new perspectives for photonic material processing.

11.
Cell Signal ; 120: 111232, 2024 Aug.
Article En | MEDLINE | ID: mdl-38763183

Aging affects lipid metabolism and can cause obesity as it is closely related to the disorder of many lipogenic regulatory factors. LncRNAs have been recognized as pivotal regulators across diverse biological processes, but their effects on lipogenesis in aging remain to be further studied. In this work, using RNA sequencing (RNA-Seq), we found that the expression of lncRNA AI504432 was significantly upregulated in the eWAT (epididymal white adipose tissue) of aging mice, and the knockdown of AI504432 notably reduced the expression of several adipogenic genes (e.g., Cebp/α, Srebp-1c, Fasn, Acaca, and Scd1) in senescent adipocytes. The bioinformatics investigation revealed that AI504432 possessed a binding site for miR-1a-3p, and the discovery was verified by the luciferase reporter assay. The expression of Fasn was increased upon the inhibition of miR-1a-3p but restored upon the simultaneous silencing of AI504432. Taken together, our results suggested that AI504432 controlled lipogenesis through the miR-1a-3p/Fasn signaling pathway. The findings may inspire new therapeutic approaches to target imbalanced lipid homeostasis due to aging.


Adipocytes , Cellular Senescence , Fatty Acid Synthase, Type I , Lipogenesis , MicroRNAs , RNA, Long Noncoding , Up-Regulation , Animals , MicroRNAs/metabolism , MicroRNAs/genetics , Lipogenesis/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Mice , Adipocytes/metabolism , Fatty Acid Synthase, Type I/metabolism , Fatty Acid Synthase, Type I/genetics , Up-Regulation/drug effects , Male , Mice, Inbred C57BL , Aging/metabolism , Aging/genetics
12.
J Pharm Biomed Anal ; 246: 116252, 2024 Aug 15.
Article En | MEDLINE | ID: mdl-38788622

Balanophora harlandii Hook (B. harlandii), a folk medicine, has been traditionally employed to treat traumatic bleeding, gastroenteritis, icteric hepatitis, hemorrhoids, and other conditions. In this work, polysaccharides with anti-inflammatory effects were extracted from B. harlandii and purified. The extraction conditions were optimized, and the properties of one purified neutral fraction, denoted as BHPs-W-S3, were analyzed. BHPs-W-S3 has a molecular weight of 14.1 kDa, and its three main monosaccharides are glucose, galactose, and xylose, with a molar ratio of 6.4:1.7:1.1. Its main chain consists of →6)-α-D-Glcp-(1→, →4,6)-α-D-Glcp-(1→, →6)-ß-D-Galp-(1→, →3,6)-ß-D-Galp-(1→, and it has branch chains at the O-4 and/or O-3 positions. In addition, in vitro experiments showed that the polysaccharides from B. harlandi can decrease the phosphorylation level of p65 and IκBα in LPS-induced RAW264.7 cells to reduce the expression of the pro-inflammatory genes such as TNF-α, IL-6, and IL-1ß.


Anti-Inflammatory Agents , Polysaccharides , Mice , Animals , Polysaccharides/pharmacology , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , RAW 264.7 Cells , Molecular Weight , Balanophoraceae/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Macrophages/drug effects , Macrophages/metabolism , Lipopolysaccharides/pharmacology , NF-kappa B/metabolism , Tumor Necrosis Factor-alpha/metabolism , Inflammation/drug therapy
13.
Biomed Pharmacother ; 175: 116737, 2024 Jun.
Article En | MEDLINE | ID: mdl-38749176

Antisense oligonucleotide (ASO) has emerged as a promising therapeutic approach for treating central nervous system (CNS) disorders by modulating gene expression with high selectivity and specificity. However, the poor permeability of ASO across the blood-brain barrier (BBB) diminishes its therapeutic success. Here, we designed and synthesized a series of BBB-penetrating peptides (BPP) derived from either the receptor-binding domain of apolipoprotein E (ApoE) or a transferrin receptor-binding peptide (THR). The BPPs were conjugated to phosphorodiamidate morpholino oligomers (PMO) that are chemically analogous to the 2'-O-(2-methoxyethyl) (MOE)-modified ASO approved by the FDA for treating spinal muscular atrophy (SMA). The BPP-PMO conjugates significantly increased the level of full-length SMN2 in the patient-derived SMA fibroblasts in a concentration-dependent manner with minimal to no toxicity. Furthermore, the systemic administration of the most potent BPP-PMO conjugates significantly increased the expression of full-length SMN2 in the brain and spinal cord of SMN2 transgenic adult mice. Notably, BPP8-PMO conjugate showed a 1.25-fold increase in the expression of full-length functional SMN2 in the brain. Fluorescence imaging studies confirmed that 78% of the fluorescently (Cy7)-labelled BPP8-PMO reached brain parenchyma, with 11% uptake in neuronal cells. Additionally, the BPP-PMO conjugates containing retro-inverso (RI) D-BPPs were found to possess extended half-lives compared to their L-counterparts, indicating increased stability against protease degradation while preserving the bioactivity. This delivery platform based on BPP enhances the CNS bioavailability of PMO targeting the SMN2 gene, paving the way for the development of systemically administered neurotherapeutics for CNS disorders.


Apolipoproteins E , Blood-Brain Barrier , Mice, Transgenic , Oligonucleotides, Antisense , Animals , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/drug effects , Oligonucleotides, Antisense/administration & dosage , Oligonucleotides, Antisense/pharmacology , Oligonucleotides, Antisense/pharmacokinetics , Humans , Apolipoproteins E/metabolism , Mice , Morpholinos/administration & dosage , Morpholinos/pharmacokinetics , Morpholinos/pharmacology , Survival of Motor Neuron 2 Protein/genetics , Survival of Motor Neuron 2 Protein/metabolism , Muscular Atrophy, Spinal/drug therapy , Drug Delivery Systems/methods , Fibroblasts/metabolism , Fibroblasts/drug effects , Brain/metabolism , Brain/drug effects , Peptides/administration & dosage , Peptides/pharmacology , Peptides/chemistry , Peptides/pharmacokinetics , Cell-Penetrating Peptides/chemistry
14.
Per Med ; 2024 Apr 29.
Article En | MEDLINE | ID: mdl-38682747

Background: This study investigated the influence of ADRB1 gene rs1801253 polymorphism on the treatment response of ticagrelor and aspirin in patients with acute coronary syndrome (ACS). Methods: Genetic typing was detected by Sanger sequencing. Platelet inhibition was assessed using thromboelastography. Kaplan-Meier and Cox regression were applied for prognosis analysis. Results: Out of 200 participants, 94 cases with rs1801253-CC genotype and 106 cases with CG+GG genotype were found. There was no significant difference between the rs1801253-CC and CG+GG groups in the number of ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction and unstable angina patients. There was no statistical difference in the basic data of patients in the two groups in terms of age, sex, medical history and medicine use in the dominant model. The rs1801253-CC genotype was a risk prognostic factor for ACS patients based on the Cox regression analysis results. Conclusion: Detecting ADRB1 polymorphism is crucial for ACS patients undergoing treatment with ticagrelor and aspirin.

15.
Brain Commun ; 6(2): fcae096, 2024.
Article En | MEDLINE | ID: mdl-38562310

Aging and Alzheimer's disease are associated with chronic elevations in neuronal calcium influx via L-type calcium channels. The hippocampus, a primary memory encoding structure in the brain, is more vulnerable to calcium dysregulation in Alzheimer's disease. Recent research has suggested a link between L-type calcium channels and tau hyperphosphorylation. However, the precise mechanism of L-type calcium channel-mediated tau toxicity is not understood. In this study, we seeded a human tau pseudophosphorylated at 14 amino acid sites in rat hippocampal cornu ammonis 1 region to mimic soluble pretangle tau. Impaired spatial learning was observed in human tau pseudophosphorylated at 14 amino acid sites-infused rats as early as 1-3 months and worsened at 9-10 months post-infusion. Rats infused with wild-type human tau exhibited milder behavioural deficiency only at 9-10 months post-infusion. No tangles or plaques were observed in all time points examined in both human tau pseudophosphorylated at 14 amino acid sites and human tau-infused brains. However, human tau pseudophosphorylated at 14 amino acid sites-infused hippocampus exhibited a higher amount of tau phosphorylation at S262 and S356 than the human tau-infused rats at 3 months post-infusion, paralleling the behavioural deficiency observed in human tau pseudophosphorylated at 14 amino acid sites-infused rats. Neuroinflammation indexed by increased Iba1 in the cornu ammonis 1 was observed in human tau pseudophosphorylated at 14 amino acid sites-infused rats at 1-3 but not 9 months post-infusion. Spatial learning deficiency in human tau pseudophosphorylated at 14 amino acid sites-infused rats at 1-3 months post-infusion was paralleled by decreased neuronal excitability, impaired NMDA receptor-dependent long-term potentiation and augmented L-type calcium channel-dependent long-term potentiation at the cornu ammonis 1 synapses. L-type calcium channel expression was elevated in the soma of the cornu ammonis 1 neurons in human tau pseudophosphorylated at 14 amino acid sites-infused rats. Chronic L-type calcium channel blockade with nimodipine injections for 6 weeks normalized neuronal excitability and synaptic plasticity and rescued spatial learning deficiency in human tau pseudophosphorylated at 14 amino acid sites-infused rats. The early onset of L-type calcium channel-mediated pretangle tau pathology and rectification by nimodipine in our model have significant implications for preclinical Alzheimer's disease prevention and intervention.

16.
Front Physiol ; 15: 1386413, 2024.
Article En | MEDLINE | ID: mdl-38645688

Lysosomes-associated membrane proteins (LAMPs), a family of glycosylated proteins and major constituents of the lysosomal membranes, play a dominant role in various cellular processes, including phagocytosis, autophagy and immunity in mammals. However, their roles in aquatic species remain poorly known. In the present study, three lamp genes were cloned and characterized from Micropterus salmoides. Subsequently, their transcriptional levels in response to different nutritional status were investigated. The full-length coding sequences of lamp1, lamp2 and lamp3 were 1251bp, 1224bp and 771bp, encoding 416, 407 and 256 amino acids, respectively. Multiple sequence alignment showed that LAMP1-3 were highly conserved among the different fish species, respectively. 3-D structure prediction, genomic survey, and phylogenetic analysis were further confirmed that these genes are widely existed in vertebrates. The mRNA expression of the three genes was ubiquitously expressed in all selected tissues, including liver, brain, gill, heart, muscle, spleen, kidney, stomach, adipose and intestine, lamp1 shows highly transcript levels in brain and muscle, lamp2 displays highly expression level in heart, muscle and spleen, but lamp3 shows highly transcript level in spleen, liver and kidney. To analyze the function of the three genes under starvation stress in largemouth bass, three experimental treatment groups (fasted group and refeeding group, control group) were established in the current study. The results indicated that the expression of lamp1 was significant induced after starvation, and then returned to normal levels after refeeding in the liver. The expression of lamp2 and lamp3 exhibited the same trend in the liver. In addition, in the spleen and the kidney, the transcript level of lamp1 and lamp2 was remarkably increased in the fasted treatment group and slightly decreased in the refed treatment group, respectively. Collectively, our findings suggest that three lamp genes may have differential function in the immune and energetic organism in largemouth bass, which is helpful in understanding roles of lamps in aquatic species.

17.
Technol Cancer Res Treat ; 23: 15330338241246651, 2024.
Article En | MEDLINE | ID: mdl-38613344

OBJECTIVE: To investigate the predictive value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for the efficacy and prognosis of programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors in driver-gene-negative advanced non-small-cell lung cancer (NSCLC). METHODS: A retrospective analysis of 107 advanced NSCLC patients without gene mutations who received PD-1/PD-L1 inhibitors in our hospital from January 2020 to June 2022 was performed. NLR and PLR were collected before PD-1/PD-L1 inhibitors, the optimal cut-off values of NLR and PLR were determined according to the receiver operating characteristic (ROC) curve, and the effects of NLR and PLR on the efficacy of PD-1/PD-L1 inhibitors in advanced NSCLC patients were analyzed. RESULTS: A total of 107 patients were included in this study. Receiver operating characteristic analysis showed that the optimal cut-off values of NLR and PLR were 3.825, 179, respectively. Kaplan-Meier curve showed that low baseline levels NLR and PLR were associated with an improvement in both progression-free survival (PFS) (P < .001, < .001, respectively) and overall survival (OS) (P = .009, .006, respectively). In first-line treatment and non-first-line treatment, low baseline levels NLR and PLR were associated with an improvement in PFS. In multivariate analysis, low baseline NLR and PLR showed a strong association with both better PFS (P = .011, .027, respectively) and longer OS (P = .042, .039, respectively). CONCLUSION: Low baseline NLR and PLR levels are significantly associated with better response in advanced NSCLC patients treated with PD-1/PD-L1 inhibitors, which may be indicators to predict the efficacy of immunotherapy in advanced NSCLC with driver-gene-negative.


Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Cohort Studies , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Programmed Cell Death 1 Receptor , Retrospective Studies , Neutrophils , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lymphocytes
18.
Sensors (Basel) ; 24(5)2024 Mar 06.
Article En | MEDLINE | ID: mdl-38475244

Roads are the fundamental elements of transportation, connecting cities and rural areas, as well as people's lives and work. They play a significant role in various areas such as map updates, economic development, tourism, and disaster management. The automatic extraction of road features from high-resolution remote sensing images has always been a hot and challenging topic in the field of remote sensing, and deep learning network models are widely used to extract roads from remote sensing images in recent years. In light of this, this paper systematically reviews and summarizes the deep-learning-based techniques for automatic road extraction from high-resolution remote sensing images. It reviews the application of deep learning network models in road extraction tasks and classifies these models into fully supervised learning, semi-supervised learning, and weakly supervised learning based on their use of labels. Finally, a summary and outlook of the current development of deep learning techniques in road extraction are provided.

19.
Front Mol Neurosci ; 17: 1355140, 2024.
Article En | MEDLINE | ID: mdl-38550251

Introduction: Cumulative evidence suggests that sensory cortices interact with the basolateral amygdala (BLA) defense circuitry to mediate threat conditioning, memory retrieval, and extinction learning. The olfactory piriform cortex (PC) has been posited as a critical site for olfactory associative memory. Recently, we have shown that N-methyl-D-aspartate receptor (NMDAR)-dependent plasticity in the PC critically underpins olfactory threat extinction. Aging-associated impairment of olfactory threat extinction is related to the hypofunction of NMDARs in the PC. Methods: In this study, we investigated activation of neuronal cFos and epigenetic marks in the BLA and PC using immunohistochemistry, following olfactory threat conditioning and extinction learning in rats. Results: We found highly correlated cFos activation between the posterior PC (pPC) and BLA. cFos was correlated with the degree of behavioral freezing in the pPC in both adult and aged rats, and in the BLA only in adult rats. Markers of DNA methylation 5 mC and histone acetylation H3K9/K14ac, H3K27ac, and H4ac exhibited distinct training-, region-, and age-dependent patterns of activation. Strong correlations of epigenetic marks between the BLA and pPC in adult rats were found to be a general feature. Conversely, aged rats only exhibited correlations of H3 acetylations between the two structures. Histone acetylation varied as a function of aging, revealed by a reduction of H3K9/K14ac and an increase of H4ac in aged brains at basal condition and following threat conditioning. Discussion: These findings underscore the coordinated role of PC and BLA in olfactory associative memory storage and extinction, with implications for understanding aging related cognitive decline.

20.
Article En | MEDLINE | ID: mdl-38502619

Photorealistic stylization of 3D scenes aims to generate photorealistic images from arbitrary novel views according to a given style image, while ensuring consistency when rendering video from different viewpoints. Some existing stylization methods using neural radiance fields can effectively predict stylized scenes by combining the features of the style image with multi-view images to train 3D scenes. However, these methods generate novel view images that contain undesirable artifacts. In addition, they cannot achieve universal photorealistic stylization for a 3D scene. Therefore, a stylization image needs to retrain a 3D scene representation network based on a neural radiation field. We propose a novel photorealistic 3D scene stylization transfer framework to address these issues. It can realize photorealistic 3D scene style transfer with a 2D style image for novel view video rendering. We first pre-trained a 2D photorealistic style transfer network, which can satisfy the photorealistic style transfer between any content image and style image. Then, we use voxel features to optimize a 3D scene and obtain the geometric representation of the scene. Finally, we jointly optimize a hypernetwork to realize the photorealistic style transfer of arbitrary style images. In the transfer stage, we use a pre-trained 2D photorealistic network to constrain the photorealistic style of different views and different style images in the 3D scene. The experimental results show that our method not only realizes the 3D photorealistic style transfer of arbitrary style images, but also outperforms the existing methods in terms of visual quality and consistency. Project page:https://semchan.github.io/UPST_NeRF/.

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