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1.
Planta ; 260(1): 21, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38847829

ABSTRACT

MAIN CONCLUSION: Petal developmental characteristics in Fumarioideae were similar at early stages, and the specialized nectar holder/pollen container formed by the outer/inner petals. The micro-morphology of these two structures, however, shows diversity in seven species. Elaborate petals have been modified to form different types, including petal lobes, ridges, protuberances, and spurs, each with specialized functions. Nectar holder and pollen container presumably have a function in plant-pollinator interactions. In Fumarioideae, four elaborate petals of the disymmetric/zygomorphic flower present architecture forming the "nectar holder" and "pollen container" structure at the bottom and top separately. In the present study, the petals of seven species in Fumarioideae were investigated by scanning electron microscopy, light microscope, and transmission electron microscopes. The results show that petal development could divided into six stages: initiation, enlargement, adaxial/abaxial differentiation, elaborate specializations (sacs, spurs, and lobes formed), extension, and maturation, while the specialized "nectar holder" and "pollen container" structures mainly formed in stage 4. "Nectar holder" is developed from the shallow sac/spur differentiated at the base of the outer petal, eventually forming a multi-organized complex structure, together with staminal nectaries (1-2) with individual sizes. A semi-closed ellipsoidal "pollen container" is developed from the apical part of the 3-lobed inner petals fused by middle lobes and attain different sizes. The adaxial epidermis cells are specialized, with more distinct punctate/dense columnar protrusions or wavy cuticles presented on obviously thickening cell walls. In addition, a large and well-developed cavity appears between the inner and outer epidermis of the petals. As an exception, Hypecoum erectum middle lobes present stamen mimicry. Elaborate petal structure is crucial for comprehending the petal diversity in Fumarioideae and provides more evidence for further exploration of the reproductive study in Papaveraceae.


Subject(s)
Flowers , Microscopy, Electron, Scanning , Plant Nectar , Pollen , Flowers/anatomy & histology , Flowers/ultrastructure , Flowers/growth & development , Pollen/ultrastructure , Microscopy, Electron, Transmission , Pollination
2.
BMC Cancer ; 24(1): 684, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38840087

ABSTRACT

BACKGROUND: Many randomized controlled trials (RCTs) and network meta-analyses have demonstrated that the progression-free survival (PFS) and overall survival (OS) of advanced non-small cell lung cancer (NSCLC) patients can be improved through combination immunotherapy or monotherapies. However, time-dependent analysis of the treatment effect is currently lacking. Thus, we aimed to evaluate the efficacy of first-line immunotherapy, and establish a hazard ratio function to reflect the time-varying progression or mortality risk of patients with NSCLC. METHODS: Seventeen clinical trials were selected based on search strategy. Baseline characteristics, including the age, sex, smoking status, geographical region, and Eastern Cooperative Oncology Group (ECOG) performance status of patients, were balanced, resulting in ten immunotherapies from nine appropriate clinical trials to conduct treatment effect comparison. RESULTS: We found that nivolumab plus ipilimumab (nivo + ipi) improved the PFS and OS over time. The hazard ratio of nivo + ipi, relative to that of pembrolizumab, decreased from 1.11 to 0.36 for PFS, and from 0.93 to 0.49 for OS over a 10-year period. In terms of the response to immunotherapy in patients with different PD-L1 expression levels, patients with PD-L1 > = 50% experienced lower rates of progression and a reduced mortality risk over time. The hazard ratio of patients with PD-L1 > = 50% relative to all of the patients decreased from 0.73 to 0.69 for PFS, and from 0.78 to 0.67 for OS. CONCLUSIONS: Based on the fact that time-dependent progression and mortality risk existed during the treatment duration, physicians should select a suitable treatment regimen for patients based on the hazard ratio.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Immunotherapy , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/therapy , Lung Neoplasms/mortality , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Immunotherapy/methods , Time Factors , Progression-Free Survival , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Male , Nivolumab/therapeutic use , Ipilimumab/therapeutic use , Ipilimumab/administration & dosage , Antibodies, Monoclonal, Humanized/therapeutic use , Treatment Outcome , Randomized Controlled Trials as Topic
3.
PLoS One ; 19(6): e0303170, 2024.
Article in English | MEDLINE | ID: mdl-38857222

ABSTRACT

OBJECTIVE: The aim of this study is to investigate the potential causal relationship between autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and Type 1 diabetes, and age-related macular degeneration (AMD). By utilizing the two-sample Mendelian Randomization (MR) approach, we endeavor to address this complex medical issue. METHODS: Genome-wide association study (GWAS) data for autoimmune diseases and AMD were obtained from the IEU Open GWAS database and the FinnGen consortium. A series of stringent SNP filtering steps was applied to ensure the reliability of the genetic instruments. MR analyses were conducted using the TwoSampleMR and MR-PRESSO packages in R. The inverse-variance weighted (IVW) method served as the primary analysis, complemented by multiple supplementary analyses and sensitivity tests. RESULTS: Within the discovery sample, only a statistically significant inverse causal relationship between multiple sclerosis (MS) and AMD was observed (OR = 0.92, 95% CI: 0.88-0.97, P = 0.003). This finding was confirmed in the replication sample (OR = 0.85, 95% CI: 0.80-0.89, P = 3.32×10-12). No statistically significant associations were detected between systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, and Type 1 diabetes and AMD. CONCLUSION: Strong evidence is provided by this study to support the existence of an inverse causal relationship between multiple sclerosis and age-related macular degeneration. However, no causal evidence was found linking other autoimmune diseases with AMD. These findings not only offer novel insights into the potential etiological mechanisms underlying AMD but also suggest possible directions for future clinical interventions.


Subject(s)
Autoimmune Diseases , Genome-Wide Association Study , Macular Degeneration , Mendelian Randomization Analysis , Polymorphism, Single Nucleotide , Humans , Macular Degeneration/genetics , Autoimmune Diseases/genetics , Autoimmune Diseases/epidemiology , Multiple Sclerosis/genetics , Arthritis, Rheumatoid/genetics , Male , Diabetes Mellitus, Type 1/genetics , Inflammatory Bowel Diseases/genetics , Female
4.
Chem Biodivers ; : e202400568, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38771291

ABSTRACT

 Four new monoterpene rhamnosides, graphiumisides A-D (1-4), along with four known steroid compounds (5-8) were isolated from the fermentation extract of animal-derived endophytic fungus, Graphium sp. GD-11. The chemical structures of all compounds were elucidated using 1D and 2D NMR, HRESIMS spectroscopic analyses, and other spectroscopic methods. Compounds 1-4 exhibit a distinctive structure connected by one p-menthane type monoterpene and one L-rhamnose. This is the first report of monoterpene glycosides from Graphium sp. All compounds (1-8) were tested for cytotoxic activities against four cancer cell lines (HepG2, SMMC7721, SW480, and A549), and only compound 1 showed weak anti-tumor activity against SMMC7721 cells.

5.
Eur J Pediatr ; 2024 May 29.
Article in English | MEDLINE | ID: mdl-38809454

ABSTRACT

The objective of this study was to assess the quality and consistency of recommendations in clinical practice guidelines (CPGs) and expert consensus on paediatric cow's milk protein allergy (CMPA) to serve as a foundation for future revisions and enhancements of clinical guidelines and consensus documents. We conducted a comprehensive literature search across several databases, including the Chinese Biomedical Literature Database (CBM), PubMed, Embase, Web of Science, UpToDate, ClinicalKey, DynaMed Plus and BMJ Best Practice. We spanned the search period from the inception of each database through October 1, 2023. We integrated subject headings (MeSH/Emtree) and keywords into the search strategy, used the search methodologies of existing literature and developed it in collaboration with a librarian. Two trained researchers independently conducted the literature screening and data extraction. We evaluated methodological quality and recommendations by using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) and AGREE-Recommendations for Excellence (AGREE-REX) tools. Moreover, we compared and summarized key recommendations from high-quality CPGs. Our study included 27 CPGs and expert consensus documents on CMPA. Only four CPGs (14.8%) achieved a high-quality AGREE II rating. The four high-quality CPGs consistently provided recommendations for CMPA. The highest scoring domains for AGREE II were 'scope and purpose' (77 ± 12%) and 'clarity of presentation' (75 ± 22%). The lowest scoring domains were 'stakeholder involvement' (49 ± 21%), 'rigor of development' (34 ± 20%) and 'applicability' (12 ± 20%). Evaluation with AGREE-REX generally demonstrated low scores across its domains.   Conclusion: Recommendations within high-quality CPGs for the paediatric CMPA showed fundamental consistency. Nevertheless, the methodology and recommendation content of CPGs and the expert consensus exhibited low quality, thus indicating a substantial scope for enhancement. Guideline developers should rigorously follow the AGREE II and AGREE-REX standards in creating CPGs or expert consensuses to guarantee their clinical efficacy in managing paediatric CMPA. What is Known: • The quality of clinical practice guidelines and expert consensus on paediatric cow's milk protein allergy (CMPA) remains uncertain. • There is a lack of clarity regarding the consistency of crucial recommendations for CMPA management. What is New: • Improving the methodological quality of guidelines and consensus on CMPA requires greater emphasis on stakeholder engagement, rigorous development processes, and practical applicability. • The recommendations from four high-quality guidelines align. However, addressing clinical applicability, integrating values and preferences, and ensuring actionable implementation are critical to improving the quality of all guidelines.

6.
Med Sci Monit ; 30: e944022, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38768093

ABSTRACT

BACKGROUND The concept of driving pressure (ΔP) has been established to optimize mechanical ventilation-induced lung injury. However, little is known about the specific effects of setting individualized positive end-expiratory pressure (PEEP) with driving pressure guidance on patient diaphragm function. MATERIAL AND METHODS Ninety patients were randomized into 3 groups, with PEEP set to 0 in group C; 5 cmH2O in group F; and individualized PEEP in group I, based on esophageal manometry. Diaphragm ultrasound was performed in the supine position at 6 consecutive time points from T0-T5: diaphragm excursion, end-expiratory diaphragm thickness (Tdi-ee), and diaphragm thickening fraction (DTF) were measured. Primary indicators included diaphragm excursion, Tdi-ee, and DTF at T0-T5, and the correlation between postoperative DTF and ΔP. Secondary indicators included respiratory mechanics, hemodynamic changes at intraoperative d0-d4 time points, and postoperative clinical pulmonary infection scores. RESULTS (1) Diaphragm function parameters reached the lowest point at T1 in all groups (P<0.001). (2) Compared with group C, diaphragm excursion decreased, Tdi-ee increased, and DTF was lower in groups I and F at T1-T5, with significant differences (P<0.05), but the differences between groups I and F were not significant (P>0.05). (3) DTF was significantly and positively correlated with mean intraoperative ΔP in each group at T3, and the correlation was stronger at higher levels of ΔP. CONCLUSIONS Individualized PEEP, achieved by esophageal manometry, minimizes diaphragmatic injury caused by mechanical ventilation based on lung protection, but its protection of the diaphragm during laparoscopic surgery is not superior to that of conventional ventilation strategies.


Subject(s)
Colorectal Neoplasms , Diaphragm , Laparoscopy , Positive-Pressure Respiration , Humans , Positive-Pressure Respiration/methods , Diaphragm/physiopathology , Male , Female , Middle Aged , Laparoscopy/methods , Aged , Colorectal Neoplasms/surgery , Respiratory Mechanics/physiology , Adult , Pressure , Ultrasonography/methods
8.
Int J Biol Macromol ; 271(Pt 2): 132663, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38797291

ABSTRACT

This study investigated the release of aromatic compounds with distinct functional groups within bilayer microcapsules. Bilayer microcapsules of four distinctive core materials (benzyl alcohol, eugenol, cinnamaldehyde, and benzoic acid) were synthesized via freeze-drying. Chitosan (CS) and sodium alginate (ALG) were used as wall materials. CS concentration, using orthogonal experiments with the loading ratio as a metric. Under optimal conditions, three other types of microcapsules (cinnamic aldehyde, benzoic acid, and benzyl alcohol) were obtained. The four types of microcapsules were characterized using Fourier-transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), transmission electron microscope (TEM), and thermogravimetric analysis (TGA), and their sustained release characteristics were evaluated. The optimal conditions were: CS dosage, 1.2 %; CS-to-eugenol mass ratio, 1:2; and CS-to-ALG mass ratio, 1:1. By comparing the IR spectra of the four types of microcapsules, wall material, and core material, the core materials were revealed to be encapsulated within the wall material. SEM results revealed that the granular protuberances on the surface of the microcapsules were closely aligned and persistent when magnified 2000×. The TEM results indicated that all four microcapsules had a spherical and bilayer structure. The thermal stability and sustained release results showed that the four microcapsules were more resilient and less volatile than the four core materials. The release conformed to first-order kinetics, and the release ratios of the four microcapsules were as follows: benzyl alcohol microcapsules Ëƒ eugenol microcapsules Ëƒ cinnamaldehyde microcapsules Ëƒ benzoic acid microcapsules. The prepared bilayer microcapsules encapsulated four different core materials with good sustained release properties.

9.
Chem Soc Rev ; 53(10): 4877-4925, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38595056

ABSTRACT

Batteries play a pivotal role in various electrochemical energy storage systems, functioning as essential components to enhance energy utilization efficiency and expedite the realization of energy and environmental sustainability. Zn-based batteries have attracted increasing attention as a promising alternative to lithium-ion batteries owing to their cost effectiveness, enhanced intrinsic safety, and favorable electrochemical performance. In this context, substantial endeavors have been dedicated to crafting and advancing high-performance Zn-based batteries. However, some challenges, including limited discharging capacity, low operating voltage, low energy density, short cycle life, and complicated energy storage mechanism, need to be addressed in order to render large-scale practical applications. In this review, we comprehensively present recent advances in designing high-performance Zn-based batteries and in elucidating energy storage mechanisms. First, various redox mechanisms in Zn-based batteries are systematically summarized, including insertion-type, conversion-type, coordination-type, and catalysis-type mechanisms. Subsequently, the design strategies aiming at enhancing the electrochemical performance of Zn-based batteries are underscored, focusing on several aspects, including output voltage, capacity, energy density, and cycle life. Finally, challenges and future prospects of Zn-based batteries are discussed.

10.
Biomed Pharmacother ; 174: 116558, 2024 May.
Article in English | MEDLINE | ID: mdl-38603887

ABSTRACT

Human adenovirus (HAdV) infection is a major cause of respiratory disease, yet no antiviral drugs have been approved for its treatment. Herein, we evaluated the antiviral and anti-inflammatory effects of cyclin-dependent protein kinase (CDK) inhibitor indirubin-3'-monoxime (IM) against HAdV infection in cells and a transgenic mouse model. After evaluating its cytotoxicity, cytopathic effect reduction, antiviral replication kinetics, and viral yield reduction assays were performed to assess the anti-HAdV activity of IM. Quantitative real-time polymerase chain reaction (qPCR), quantitative reverse transcription PCR (qRT-PCR), and western blotting were used to assess the effects of IM on HAdV DNA replication, transcription, and protein expression, respectively. IM significantly inhibited HAdV DNA replication as well as E1A and Hexon transcription, in addition to significantly suppressing the phosphorylation of the RNA polymerase II C-terminal domain (CTD). IM mitigated body weight loss, reduced viral burden, and lung injury, decreasing cytokine and chemokine secretion to a greater extent than cidofovir. Altogether, IM inhibits HAdV replication by downregulating CTD phosphorylation to suppress viral infection and corresponding innate immune reactions as a promising therapeutic agent.


Subject(s)
Adenoviruses, Human , Anti-Inflammatory Agents , Antiviral Agents , Indoles , Oximes , Virus Replication , Indoles/pharmacology , Animals , Oximes/pharmacology , Humans , Antiviral Agents/pharmacology , Adenoviruses, Human/drug effects , Virus Replication/drug effects , Anti-Inflammatory Agents/pharmacology , Mice , Mice, Transgenic , Adenovirus Infections, Human/drug therapy , Adenovirus Infections, Human/virology , A549 Cells , Cytokines/metabolism , Phosphorylation/drug effects
11.
Angew Chem Int Ed Engl ; 63(24): e202318035, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38586975

ABSTRACT

Environmentally friendly crosslinked polymer networks feature degradable covalent or non-covalent bonds, with many of them manifesting dynamic characteristics. These attributes enable convenient degradation, facile reprocessibility, and self-healing capabilities. However, the inherent instability of these crosslinking bonds often compromises the mechanical properties of polymer networks, limiting their practical applications. In this context, environmentally friendly dual-crosslinking polymer networks (denoted EF-DCPNs) have emerged as promising alternatives to address this challenge. These materials effectively balance the need for high mechanical properties with the ability to degrade, recycle, and/or self-heal. Despite their promising potential, investigations into EF-DCPNs remain in their nascent stages, and several gaps and limitations persist. This Review provides a comprehensive overview of the synthesis, properties, and applications of recent progress in EF-DCPNs. Firstly, synthetic routes to a rich variety of EF-DCPNs possessing two distinct types of dynamic bonds (i.e., imine, disulfide, ester, hydrogen bond, coordination bond, and other bonds) are introduced. Subsequently, complex structure- and dynamic nature-dependent mechanical, thermal, and electrical properties of EF-DCPNs are discussed, followed by their exemplary applications in electronics and biotechnology. Finally, future research directions in this rapidly evolving field are outlined.

12.
Microorganisms ; 12(4)2024 Mar 31.
Article in English | MEDLINE | ID: mdl-38674657

ABSTRACT

Bacteria and phages are two of the most abundant biological entities in the gut microbiome, and diet and host phylogeny are two of the most critical factors influencing the gut microbiome. A stable gut bacterial community plays a pivotal role in the host's physiological development and immune health. A phage is a virus that directly infects bacteria, and phages' close associations and interactions with bacteria are essential for maintaining the stability of the gut bacterial community and the entire microbial ecosystem. Here, we utilized 99 published metagenomic datasets from 38 mammalian species to investigate the relationship (diversity and composition) and potential interactions between gut bacterial and phage communities and the impact of diet and phylogeny on these communities. Our results highlight the co-evolutionary potential of bacterial-phage interactions within the mammalian gut. We observed a higher alpha diversity in gut bacteria than in phages and identified positive correlations between bacterial and phage compositions. Furthermore, our study revealed the significant influence of diet and phylogeny on mammalian gut bacterial and phage communities. We discovered that the impact of dietary factors on these communities was more pronounced than that of phylogenetic factors at the order level. In contrast, phylogenetic characteristics had a more substantial influence at the family level. The similar omnivorous dietary preference and closer phylogenetic relationship (family Ursidae) may contribute to the similarity of gut bacterial and phage communities between captive giant panda populations (GPCD and GPYA) and omnivorous animals (OC; including Sun bear, brown bear, and Asian black bear). This study employed co-occurrence microbial network analysis to reveal the potential interaction patterns between bacteria and phages. Compared to other mammalian groups (carnivores, herbivores, and omnivores), the gut bacterial and phage communities of bamboo-eating species (giant pandas and red pandas) exhibited a higher level of interaction. Additionally, keystone species and modular analysis showed the potential role of phages in driving and maintaining the interaction patterns between bacteria and phages in captive giant pandas. In sum, gaining a comprehensive understanding of the interaction between the gut microbiota and phages in mammals is of great significance, which is of great value in promoting healthy and sustainable mammals and may provide valuable insights into the conservation of wildlife populations, especially endangered animal species.

13.
Adv Sci (Weinh) ; 11(22): e2309538, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38491732

ABSTRACT

Memristors offer a promising solution to address the performance and energy challenges faced by conventional von Neumann computer systems. Yet, stochastic ion migration in conductive filament often leads to an undesired performance tradeoff between memory window, retention, and endurance. Herein, a robust memristor based on oxygen-rich SnO2 nanoflowers switching medium, enabled by seed-mediated wet chemistry, to overcome the ion migration issue for enhanced analog in-memory computing is reported. Notably, the interplay between the oxygen vacancy (Vo) and Ag ions (Ag+) in the Ag/SnO2/p++-Si memristor can efficiently modulate the formation and abruption of conductive filaments, thereby resulting in a high on/off ratio (>106), long memory retention (10-year extrapolation), and low switching variability (SV = 6.85%). Multiple synaptic functions, such as paired-pulse facilitation, long-term potentiation/depression, and spike-time dependent plasticity, are demonstrated. Finally, facilitated by the symmetric analog weight updating and multiple conductance states, a high image recognition accuracy of ≥ 91.39% is achieved, substantiating its feasibility for analog in-memory computing. This study highlights the significance of synergistically modulating conductive filaments in optimizing performance trade-offs, balancing memory window, retention, and endurance, which demonstrates techniques for regulating ion migration, rendering them a promising approach for enabling cutting-edge neuromorphic applications.

14.
Heliyon ; 10(5): e26957, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38449641

ABSTRACT

Narcotic drugs refer to drugs that have anesthetic effects on the central nervous system, and they easily produce physical dependence and mental dependence and can be addictive due to continuous use, abuse or unreasonable use. In this paper, bioinformatics and data analysis and mining techniques were used to analyze the methylation differences in transcriptional and clinical data of narcotic addiction in public databases, to explore the mechanism of narcotic addiction, and to mine some norepinephrine drugs. This study confirmed the possibility of using norepinephrine as an auxiliary drug for drug addiction rehabilitation. In addition, we also conducted a similar analysis on the addiction of three drugs. The results showed that the differences in the body caused by the ingestion of opiates and cocaine were significantly greater than those caused by the ingestion of methamphetamine.

15.
Nat Commun ; 15(1): 2262, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38480732

ABSTRACT

The inter-subspecific indica-japonica hybrid rice confer potential higher yield than the widely used indica-indica intra-subspecific hybrid rice. Nevertheless, the utilization of this strong heterosis is currently hindered by asynchronous diurnal floret opening time (DFOT) of indica and japonica parental lines. Here, we identify OsMYB8 as a key regulator of rice DFOT. OsMYB8 induces the transcription of JA-Ile synthetase OsJAR1, thereby regulating the expression of genes related to cell osmolality and cell wall remodeling in lodicules to promote floret opening. Natural variations of OsMYB8 promoter contribute to its differential expression, thus differential transcription of OsJAR1 and accumulation of JA-Ile in lodicules of indica and japonica subspecies. Furthermore, introgression of the indica haplotype of OsMYB8 into japonica effectively promotes DFOT in japonica. Our findings reveal an OsMYB8-OsJAR1 module that regulates differential DFOT in indica and japonica, and provide a strategy for breeding early DFOT japonica to facilitate breeding of indica-japonica hybrids.


Subject(s)
Genes, Plant , Isoleucine/analogs & derivatives , Oryza , Plant Breeding , Hybrid Vigor , Cyclopentanes/metabolism , Oryza/metabolism
16.
J Affect Disord ; 354: 26-35, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38452938

ABSTRACT

BACKGROUND: The retrieval-extinction paradigm based on memory reconsolidation can prevent fear memory recurrence more effectively than the extinction paradigm. High-intensity fear memories tend to resist reconsolidation. Novelty-retrieval-extinction can promote the reconsolidation of fear memory lacking neuroplasticity in rodents; however, whether it could effectively promote high-intensity fear memory reconsolidation in humans remains unclear. METHODS: Using 120 human participants, we implemented the use of the environment (novel vs. familiar) with the help of virtual reality technology. Novelty environment exploration was combined with retrieval-extinction in fear memory of two intensity levels (normal vs. high) to examine whether novelty facilitates the reconsolidation of high-intensity fear memory and prevents recurrence. Skin conductance responses were used to clarify novelty-retrieval-extinction effects at the behavioral level across three experiments. RESULTS: Retrieval-extinction could prevent the reinstatement of normal-intensity fear memory; however, for high-intensity fear memory, only the novelty-retrieval-extinction could prevent recurrence; we further validated that novelty-retrieval-extinction may be effective only when the environment is novel. LIMITATIONS: Although the high-intensity fear memory is higher than normal-intensity in this study, it may be insufficient relative to fear experienced in real-world contexts or by individuals with mental disorders. CONCLUSIONS: To some extent, these findings indicate that the novelty-retrieval-extinction paradigm could prevent the recurrence of high-intensity fear memory, and we infer that novelty of environment may play an important role in novelty-retrieval-extinction paradigm. The results of this study have positive implications for the existing retrieval extinction paradigm and the clinical treatment of phobia.


Subject(s)
Extinction, Psychological , Phobic Disorders , Humans , Extinction, Psychological/physiology , Fear/physiology
17.
J Leukoc Biol ; 2024 Feb 09.
Article in English | MEDLINE | ID: mdl-38334307

ABSTRACT

Poly (ADP ribose) polymerase family member 11(PARP11) has important immune regulatory functions in viral infection and tumor immune response. Particularly, PARP11 showed protumor activities in multiple preclinical murine models. However, no systematic pan-cancer analysis has been conducted to explore PARP11 function. In this study we used multiple databases to assess PARP11 expression, which associations with clinical outcomes, immune checkpoint factors, prognostic significance, genomic characteristics, and immunological aspects. The analysis revealed varying expression levels of PARP11 across different cancer types and a significant correlation between its expression and immune cell infiltration. Insights from the CellMiner database suggest a strong link between PARP11 expression and sensitivity to anticancer drugs, highlighting its potential as a therapeutic target. Moreover, PARP11 expression correlates with patient survival during anti-PD1 and anti-CTLA4 treatments, suggested that PARP11 would be a predictor of immune checkpoint inhibitor (ICI) treatment. In summary, PARP11 would be a potential immunoregulatory target and a diagnosis and prognosis marker for certain types of cancers. The detailed mechanisms of PARP11 in tumor immune responses need to be further investigated.

18.
Article in English | MEDLINE | ID: mdl-38415456

ABSTRACT

BACKGROUND: Ovarian carcinoma is an aggressive gynecological malignancy. Kirenol, a diterpene compound, has recently gained attention for its potential anticancer properties. However, its exact anti-tumor mechanism remains largely unexplored. OBJECTIVE: In this study, we explored the inhibitory effects of Kirenol on ovarian cancer using network pharmacology and in vitro experiments and elucidated its underlying mechanisms. METHODS: Through the utilization of molecular docking, we established a network of proteinprotein interactions (PPI), which unveiled CDK4 as an essential target. Additionally, gene enrichment and pathway analysis highlighted the significance of the PI3K/AKT pathway. The viability of ovarian cancer cells and normal ovarian epithelial cells was evaluated using CCK8 assays to determine the effect of Kirenol. Following in vitro tests, cell colony formation, wound healing, flow cytometry, and Western blotting were conducted to assess its impact on cell proliferation, metastasis, apoptosis, and the cell cycle. RESULTS: Kirenol significantly reduced the viability of ovarian cancer cells (SKOV3 and A2780) compared to normal ovarian epithelial cells (IOSE-80). Moreover, Kirenol efficiently suppressed the growth and movement, caused a cell cycle halt, and stimulated programmed cell death in SKOV3 and A2780 cells. Through molecular analysis, it was observed that Kirenol increased the expression of Bax while decreasing the expression of MMP2, MMP9, and Bcl-2. It also attenuated the phosphorylation of PI3K, AKT, and RB and downregulated CDK4 and CCND1 expression. Notably, co-treatment with the PI3K pathway inhibitor LY294002 enhanced the inhibitory effect of Kirenol on ovarian cancer cells. CONCLUSION: In summary, the combined results of our network pharmacology analysis and in vitro tests emphasized that Kirenol hinders the growth of ovarian cancer cells, causes cell cycle arrest, enhances apoptosis, and hampers migration, possibly by regulating the PI3K/AKT/CDK4 signaling pathway.

19.
Small ; 20(22): e2308213, 2024 May.
Article in English | MEDLINE | ID: mdl-38183335

ABSTRACT

Single-atom catalysts (SACs) hold immense promise in facilitating the rational use of metal resources and achieving atomic economy due to their exceptional atom-utilization efficiency and distinct characteristics. Despite the growing interest in SACs, only limited reviews have holistically summarized their advancements centering on performance metrics. In this review, first, a thorough overview on the research progress in SACs is presented from a performance perspective and the strategies, advancements, and intriguing approaches employed to enhance the critical attributes in SACs are discussed. Subsequently, a comprehensive summary and critical analysis of the electrochemical applications of SACs are provided, with a particular focus on their efficacy in the oxygen reduction reaction , oxygen evolution reaction, hydrogen evolution reaction , CO2 reduction reaction, and N2 reduction reaction . Finally, the outline future research directions on SACs by concentrating on performance-driven investigation, where potential areas for improvement are identified and promising avenues for further study are highlighted, addressing challenges to unlock the full potential of SACs as high-performance catalysts.

20.
Small ; : e2310915, 2024 Jan 24.
Article in English | MEDLINE | ID: mdl-38267813

ABSTRACT

Lithium dendrites are easily generated for excessively-solved lithium ions (Li+ ) inside the lithium metal batteries, which will lead serious safety issues. In this experiment, carbon spheres (CS) are successfully anchored on TiO2  (CS@TiO2 ) in the hydrothermal polymerization, which is filtrated on the commercial PE separator (CS@TiO2 @PE). The negative charge in CS can suppress random diffusion of anions through electrostatic interactions. Density functional theory (DFT) calculations show that CS contributes to the desolvation of Li+ , thereby increasing the migration rate of Li+ . Furthermore, TiO2  exhibits high affinity to liquid electrolytes and acts as a physical barrier to lithium dendrite formation. CS@TiO2 is a combination of the advantages of CS and TiO2 . As results, the Li+  transference number of the CS@TiO2 @PE separator can be promoted to 0.63. The Li||Li cell with the CS@TiO2 @PE separator exhibits a stable cycle performance for more than 600 h and lower polarization voltage (17 mV) at 1 mA cm-2 . The coulombic efficiency (CE) of the Li||Cu cells employe the CS@TiO2 @PE separator is 81.63% over 130 cycles. The discharge capacity of LiFePO4 ||Li cells based on the CS@TiO2 @PE separator is 1.73 mAh (capacity retention = 91.53% after 260 cycles). Thus, the CS@TiO2 layer inhibits lithium dendrite formation.

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