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1.
Heliyon ; 10(11): e31918, 2024 Jun 15.
Article En | MEDLINE | ID: mdl-38841500

Purpose: Primary medical workers constitute a high-risk group for mental health problems, and psychological resilience might protect them from the negative psychological impacts of their work. Therefore, this study aimed to investigate the current situation of psychological resilience among primary care workers in Wuhan, China, as well as related factors. Methods: In this cross-sectional study, a total of 417 primary care workers (30.0 % men; 38.5 ± 8.5 years old) were randomly selected to complete a questionnaire. The brief version of the National Mental Health Literacy Questionnaire and the Psychological Resilience Scale were used to assess participants' mental health literacy and psychological resilience, respectively. Multiple linear regression was performed to identify factors associated with the psychological resilience of primary care workers. Results: More than four-fifths of the primary care workers included in this study exhibited appropriate levels of mental health knowledge. In terms of mental health skills, participants' attainment rates, ranging from high to low, were 60.9 % for distracting attention, 45.3 % for interpersonal support and 43.9 % for cognitive reappraisal. The average psychological resilience score obtained by primary care workers was 27.81 ± 5.71, and the factors associated with increased psychological resilience included being male, being older, and possessing higher mental health skills, including skills pertaining to interpersonal support and distracting attention. Conclusion: The psychological resilience of primary care workers in Wuhan is at a moderate level and thus requires further improvement. Although these medical staff exhibit appropriate levels of mental health knowledge, their mental health skills are relatively poor, despite the fact that interpersonal support and distracting attention are significantly associated with psychological resilience. Hence, interventions targeting mental health skills are recommended to promote psychological resilience among primary care workers.

2.
Biol Psychiatry Glob Open Sci ; 4(3): 100309, 2024 May.
Article En | MEDLINE | ID: mdl-38690260

Background: Fear overgeneralization is a promising pathogenic mechanism of clinical anxiety. A dominant model posits that hippocampal pattern separation failures drive overgeneralization. Hippocampal network-targeted transcranial magnetic stimulation (HNT-TMS) has been shown to strengthen hippocampal-dependent learning/memory processes. However, no study has examined whether HNT-TMS can alter fear learning/memory. Methods: Continuous theta burst stimulation was delivered to individualized left posterior parietal stimulation sites derived via seed-based connectivity, precision functional mapping, and electric field modeling methods. A vertex control site was also stimulated in a within-participant, randomized controlled design. Continuous theta burst stimulation was delivered prior to 2 visual discrimination tasks (1 fear based, 1 neutral). Multilevel models were used to model and test data. Participants were undergraduates with posttraumatic stress symptoms (final n = 25). Results: Main analyses did not indicate that HNT-TMS strengthened discrimination. However, multilevel interaction analyses revealed that HNT-TMS strengthened fear discrimination in participants with lower fear sensitization (indexed by responses to a control stimulus with no similarity to the conditioned fear cue) across multiple indices (anxiety ratings: ß = 0.10, 95% CI, 0.04 to 0.17, p = .001; risk ratings: ß = 0.07, 95% CI, 0.00 to 0.13, p = .037). Conclusions: Overgeneralization is an associative process that reflects deficient discrimination of the fear cue from similar cues. In contrast, sensitization reflects nonassociative responding unrelated to fear cue similarity. Our results suggest that HNT-TMS may selectively sharpen fear discrimination when associative response patterns, which putatively implicate the hippocampus, are more strongly engaged.


Fear overgeneralization is a promising pathogenic mechanism of clinical anxiety that is thought to be driven by deficient hippocampal discrimination. Using hippocampal network­targeted transcranial magnetic stimulation (HNT-TMS) in healthy participants with symptoms of posttraumatic stress, Webler et al. report that HNT-TMS did not strengthen discrimination overall, but it did strengthen fear discrimination in participants with lower fear sensitization. Sensitization reflects nonassociative fear responding unrelated to fear cue similarity and therefore is not expected to engage the hippocampal discrimination function. These results suggest that HNT-TMS may selectively sharpen fear discrimination when the hippocampal discrimination function is more strongly engaged.

3.
Heliyon ; 10(10): e31258, 2024 May 30.
Article En | MEDLINE | ID: mdl-38803932

It is a well-known fact that political education plays a pivotal role in shaping informed, engaged, and responsible citizens in a country. The empirical literature lacks the exploration of the impact of political education on political participation in addition to political efficacy and social media usage. This study investigates the interconnected relationship between political education, social media usage, political efficacy, and political participation in China. Drawing upon a sample of 843 participants across various regions, this research explores the extent to which these factors influence political participation within the Chinese context by applying the structural equation modelling for empirical results and establishing a positive association between political education and political participation. Furthermore, the mediating role of social media and political efficacy is uncovered in relationship of political education and political participation in China. It is suggested to emphasize and invest in comprehensive political education programs through colleges, universities and social media that promote critical thinking, information literacy, and political responsibility for the well-being of the Chinese society.

4.
Molecules ; 29(9)2024 Apr 30.
Article En | MEDLINE | ID: mdl-38731556

Red rice, a variety of pigmented grain, serves dual purposes as both a food and medicinal resource. In recent years, we have witnessed an increasing interest in the dermatological benefits of fermented rice extracts, particularly their whitening and hydrating effects. However, data on the skincare advantages derived from fermenting red rice with Aspergillus oryzae remain sparse. This study utilized red rice as a substrate for fermentation by Aspergillus oryzae, producing a substance known as red rice Aspergillus oryzae fermentation (RRFA). We conducted a preliminary analysis of RRFA's composition followed by an evaluation of its skincare potential through various in vitro tests. Our objective was to develop a safe and highly effective skincare component for potential cosmetic applications. RRFA's constituents were assessed using high-performance liquid chromatography (HPLC), Kjeldahl nitrogen determination, the phenol-sulfuric acid method, and enzyme-linked immunosorbent assay (ELISA). We employed human dermal fibroblasts (FB) to assess RRFA's anti-aging and antioxidative properties, immortalized keratinocytes (HaCaT cells) and 3D epidermal models to examine its moisturizing and reparative capabilities, and human primary melanocytes (MCs) to study its effects on skin lightening. Our findings revealed that RRFA encompasses several bioactive compounds beneficial for skin health. RRFA can significantly promote the proliferation of FB cells. And it markedly enhances the mRNA expression of ECM-related anti-aging genes and reduces reactive oxygen species production. Furthermore, RRFA significantly boosts the expression of Aquaporin 3 (AQP3), Filaggrin (FLG), and Hyaluronan Synthase 1 (HAS1) mRNA, alongside elevating moisture levels in a 3D epidermal model. Increases were also observed in the mRNA expression of Claudin 1 (CLDN1), Involucrin (IVL), and Zonula Occludens-1 (ZO-1) in keratinocytes. Additionally, RRFA demonstrated an inhibitory effect on melanin synthesis. Collectively, RRFA contains diverse ingredients which are beneficial for skin health and showcases multifaceted skincare effects in terms of anti-aging, antioxidant, moisturizing, repairing, and whitening capabilities in vitro, highlighting its potential for future cosmetic applications.


Aspergillus oryzae , Fermentation , Filaggrin Proteins , Oryza , Aspergillus oryzae/metabolism , Oryza/chemistry , Oryza/metabolism , Humans , Antioxidants/pharmacology , Antioxidants/metabolism , Keratinocytes/metabolism , Keratinocytes/drug effects , HaCaT Cells , Fibroblasts/metabolism , Fibroblasts/drug effects , Melanocytes/metabolism , Melanocytes/drug effects , Skin Care/methods , Skin/metabolism
5.
BMJ Open ; 14(5): e075417, 2024 May 17.
Article En | MEDLINE | ID: mdl-38760054

PURPOSE: The Bone And MicroBiOme Onset (BAMBOO) study is an ongoing prospective observational cohort study conducted in Tianjin, China, aiming to determine age-appropriate trajectories for microbiome maturation and bone development and to identify the influence of dietary factors in the process. PARTICIPANTS: The recruitment started in September 2021 and was completed in February 2023. A total of 1380 subjects were recruited, 690 at birth (group 1) and 690 at 6 months of age (group 2). Groups 1 and 2 will be followed up for 12 months and 36 months, respectively. FINDINGS TO DATE: The age of the mothers was 31.1±3.7 (mean±SD), and the birth weight of infants was 3.3±0.5 kg with an incidence of caesarean section 50.4%. Food diary information of the first 100 subjects showed that 64 food items were introduced by 6 months. A pilot microbiome analysis revealed that at the species level, bacterial communities were composed of mostly Bacteroides dorei, Bacteroides vulgatus and Escherichia coli, which were consistent with that of previous reports. Feasibility assessments of breast milk vitamin D and human milk oligosaccharides were validated through certified reference measurements. The early data assessment showed a high reliability of the data generated from this study. FUTURE PLANS: Data collection will be completed in August 2025. Four stage-statistical analyses will be performed as the cohort reaches certain age thresholds before the final report. Analysis of BAMBOO data will be used to develop age-appropriate trajectories for microbiome maturation and bone development for children aged 0-3 years and investigate the contribution of dietary factors in the process. TRIAL REGISTRATION NUMBER: ChiCTR2100049972.


Bone Development , Humans , China , Infant , Female , Prospective Studies , Infant, Newborn , Male , Bone Development/physiology , Milk, Human/microbiology , Gastrointestinal Microbiome/physiology , Adult , Child, Preschool , Vitamin D , Diet , Cohort Studies
6.
Sci Total Environ ; 931: 173024, 2024 Jun 25.
Article En | MEDLINE | ID: mdl-38719048

Among the problems caused by water eutrophication, the issue of odor compounds has attracted notable attention. ß-Cyclocitral, a widely distributed and versatile odor compound, is commonly derived from both algae and aquatic plants. Planting aquatic plants is a common method of water purification. However, there is limited study on their impact on ß-cyclocitral levels in water. Here, we conducted a study on the ß-cyclocitral levels in water and the submerged plant leaves under three nutrient levels and six plant density treatments. Our findings revealed the following: (1) Chlorophyll-a (Chla), ß-cyclocitral in the water (Wcyc), ß-cyclocitral in Potamogeton lucens leaves (Pcyc) and the biomass of the submerged plants increase with rising nutrient concentration, which increased about 83 %, 95 %, 450 %, 320 % from eutrophic treatment to oligotrophic treatment, respectively. (2) In water, ß-cyclocitral is influenced not only by algae but also by submerged plants, with primary influencing factors varying across different nutrient levels and plant densities. The main source of ß-cyclocitral in water becomes from plants to algae as the water eutrophication and plant density decrease. (3) As submerged plants have the capability to emit ß-cyclocitral, the release of ß-cyclocitral increases with the density of submerged plants. Hence, when considering planting submerged plants for water purification purposes, it is crucial to carefully manage submerged plant density to mitigate the risk of odor pollution emanating from aquatic plants. This study offers fresh insights into selecting optimal water density for submerged plants and their role in mitigating the release of ß-cyclocitral.


Eutrophication , Odorants , Water Pollutants, Chemical , Odorants/analysis , Water Pollutants, Chemical/analysis , Aldehydes/analysis , Plants , Nutrients/analysis , Environmental Monitoring , Diterpenes
7.
Cell Commun Signal ; 22(1): 292, 2024 May 27.
Article En | MEDLINE | ID: mdl-38802843

BACKGROUND: Hematopoietic stem cell (HSC) regeneration underlies hematopoietic recovery from myelosuppression, which is a life-threatening side effect of cytotoxicity. HSC niche is profoundly disrupted after myelosuppressive injury, while if and how the niche is reshaped and regulates HSC regeneration are poorly understood. METHODS: A mouse model of radiation injury-induced myelosuppression was built by exposing mice to a sublethal dose of ionizing radiation. The dynamic changes in the number, distribution and functionality of HSCs and megakaryocytes were determined by flow cytometry, immunofluorescence, colony assay and bone marrow transplantation, in combination with transcriptomic analysis. The communication between HSCs and megakaryocytes was determined using a coculture system and adoptive transfer. The signaling mechanism was investigated both in vivo and in vitro, and was consolidated using megakaryocyte-specific knockout mice and transgenic mice. RESULTS: Megakaryocytes become a predominant component of HSC niche and localize closer to HSCs after radiation injury. Meanwhile, transient insulin-like growth factor 1 (IGF1) hypersecretion is predominantly provoked in megakaryocytes after radiation injury, whereas HSCs regenerate paralleling megakaryocytic IGF1 hypersecretion. Mechanistically, HSCs are particularly susceptible to megakaryocytic IGF1 hypersecretion, and mTOR downstream of IGF1 signaling not only promotes activation including proliferation and mitochondrial oxidative metabolism of HSCs, but also inhibits ferritinophagy to restrict HSC ferroptosis. Consequently, the delicate coordination between proliferation, mitochondrial oxidative metabolism and ferroptosis ensures functional HSC expansion after radiation injury. Importantly, punctual IGF1 administration simultaneously promotes HSC regeneration and hematopoietic recovery after radiation injury, representing a superior therapeutic approach for myelosuppression. CONCLUSIONS: Our study identifies megakaryocytes as a last line of defense against myelosuppressive injury and megakaryocytic IGF1 as a novel niche signal safeguarding HSC regeneration.


Ferroptosis , Hematopoietic Stem Cells , Insulin-Like Growth Factor I , Megakaryocytes , Regeneration , Animals , Hematopoietic Stem Cells/metabolism , Megakaryocytes/metabolism , Megakaryocytes/radiation effects , Insulin-Like Growth Factor I/metabolism , Insulin-Like Growth Factor I/genetics , Ferroptosis/genetics , Mice , Mice, Inbred C57BL , Radiation Injuries/metabolism , Radiation Injuries/pathology , Radiation Injuries/genetics , Signal Transduction/radiation effects
8.
Cogn Neurodyn ; 18(2): 645-657, 2024 Apr.
Article En | MEDLINE | ID: mdl-38699611

Electromagnetic induction plays a crucial impact on the firing activity of biological neurons, since it exists along with the mutual effect between membrane potential and ions transport. Flux-controlled memristor is an available candidate in characterizing the electromagnetic induction effect. Different from the previously reported literature, a non-ideal flux-controlled memristor with cosine mem-conductance function is employed to determine the periodic magnetization and leakage flux processes in neurons. Thereafter, a three-dimensional (3D) memristive Wilson (m-Wilson) neuron model is constructed under the consideration of this kind of electromagnetic induction. Numerical simulations are performed by multiple numerical tools, which demonstrate that the 3D m-Wilson neuron model can generate abundant firing activities. Interestingly, coexisting firing activities, antimonotonicity, and firing frequency regulation are discovered under special parameter settings. Furthermore, a PCB-based analog circuit is designed and hardware measurements are executed to verify the numerical simulations. These explorations in numerical and hardware surveys might provide insights to regulate the firing activities by appropriate electromagnetic induction.

9.
Cogn Neurodyn ; 18(2): 539-555, 2024 Apr.
Article En | MEDLINE | ID: mdl-38699613

Synaptic plasticity makes memristors particularly suitable for simulating the connection synapses between neurons that describe magnetic induction coupling. By applying a memristor to the synaptic coupling between two map-based neuron models, a memristor-coupled dual-neuron mapping (MCDN) model is proposed in this article. The MCDN model has a line fixed point set associated with the memristor initial state, which is always unstable for the model parameters and memristor initial state of interest. Complex spiking/bursting firing patterns and their transitions are disclosed using some dynamical analysis means. The numerical results show that these spiking/bursting firings are significantly relied on the memristor initial state, demonstrating the coexistence of firing patterns. Moreover, the initial effects of complete synchronization are explored for the homogeneous MCDN model, and it is clarified that in addition to being related to the coupling strength, the synchronization activities are extremely dependent on the initial states of the memristor and neurons. Finally, these numerical results are confirmed by the FPGA-based hardware experiments.

10.
Biosens Bioelectron ; 258: 116326, 2024 Aug 15.
Article En | MEDLINE | ID: mdl-38696965

In conventional clinical disease diagnosis and screening based on biomarker detection, most analysis samples are collected from serum, blood. However, these invasive collection methods require specific instruments, professionals, and may lead to infection risks. Additionally, the diagnosis process suffers from untimely results. The identification of skin-related biomarkers plays an unprecedented role in early disease diagnosis. More importantly, these skin-mediated approaches for collecting biomarker-containing biofluid samples are noninvasive or minimally invasive, which is more preferable for point-of-care testing (POCT). Therefore, skin-based biomarker detection patches have been promoted, owing to their unique advantages, such as simple fabrication, desirable transdermal properties and no requirements for professional medical staff. Currently, the skin biomarkers extracted from sweat, interstitial fluid (ISF) and wound exudate, are achieved with wearable sweat patches, transdermal MN patches, and wound patches, respectively. In this review, we detail these three types of skin patches in biofluids collection and diseases-related biomarkers identification. Patch classification and the corresponding manufacturing as well as detection strategies are also summarized. The remaining challenges in clinical applications and current issues in accurate detection are discussed for further advancement of this technology (Scheme 1).


Biomarkers , Biosensing Techniques , Skin , Sweat , Wearable Electronic Devices , Humans , Biomarkers/blood , Biomarkers/analysis , Biosensing Techniques/methods , Biosensing Techniques/instrumentation , Sweat/chemistry , Skin/chemistry , Skin/pathology , Extracellular Fluid/chemistry , Equipment Design , Point-of-Care Testing , Body Fluids/chemistry
11.
Sci Rep ; 14(1): 11350, 2024 05 18.
Article En | MEDLINE | ID: mdl-38762628

A new 3D metal-organic frameworks [Cd6(L)4(bipy)3(H2O)2·H2O] (1) was gained by employing Cd(II) and organic ligand [H3L = 4,4',4''-(benzene-1,3,5-triyltris(oxy))tribenzoic acid)benzene acid; bipy = 4,4'-bipyridine] in the solvothermal condition, which has been fully examined via single-X ray diffraction, FTIR and elemental analysis and so on. Using natural polysaccharides hyaluronic acid (HA) and carboxymethyl chitosan (CMCS) as raw materials, we successfully prepared HA/CMCS hydrogels and observed their internal micromorphology by scanning electron microscopy. Using doxorubicin (Dox) as a drug model, we synthesized a novel metal gel particle loaded with doxorubicin, and their encapsulation and release effects were studied using fluorescence spectroscopy, followed by further investigation of their components through thermogravimetric analysis. Based on this, the therapeutic effect on leukemia was evaluated. Finally, an enhanced learning method for automatically designing new ligand structures from host ligands was proposed. Through generative modeling and molecular docking simulations, the biological behavior of the host and predicted cadmium complexes was extensively studied.


Chitosan , Doxorubicin , Hydrogels , Leukemia , Doxorubicin/chemistry , Doxorubicin/pharmacology , Hydrogels/chemistry , Chitosan/chemistry , Chitosan/analogs & derivatives , Humans , Leukemia/drug therapy , Molecular Docking Simulation , Cadmium/chemistry , Hyaluronic Acid/chemistry , Metal-Organic Frameworks/chemistry , Drug Carriers/chemistry , Cell Line, Tumor , Animals , Antibiotics, Antineoplastic/chemistry , Antibiotics, Antineoplastic/pharmacology
12.
Transl Lung Cancer Res ; 13(3): 526-539, 2024 Mar 29.
Article En | MEDLINE | ID: mdl-38601454

Background: The prognosis of small cell lung cancer (SCLC) patients is poor, and the standard first-line treatment for limited-stage small cell lung cancer (LS-SCLC) is still chemotherapy and thoracic radiotherapy. The primary objectives of our study were to confirm the superior efficacy of first-line immune checkpoint inhibitors (ICIs) plus etoposide and platinum (EP) for LS-SCLC and find crucial biomarkers. Methods: We analyzed LS-SCLC patients from three medical centers, employing propensity score matching for group comparability. Survival outcomes were estimated by Kaplan-Meier and Cox regression analyses. Additionally, we conducted univariate and multivariate analyses to investigate potential predictive factors. Results: Among 150 patients in our study, we successfully matched 41 pairs. The median overall survival (OS) was 29.5 months in the EP + ICIs group and 20.0 months in the EP group {hazard ratio (HR) =0.64 [95% confidence interval (CI): 0.41-1.02], P=0.059}. The median progression-free survival (PFS) was significantly extended in the EP + ICIs group (14.6 months), compared to the EP group (8.6 months) [HR =0.42 (95% CI: 0.28-0.63), P<0.001]. After matching, patients receiving chemo-immunotherapy had a median OS of 36.1 months, significantly surpassing those receiving chemotherapy alone (19.0 months) [HR =0.51 (95% CI: 0.28-0.93), P=0.02]. And the patients in the EP + ICIs group also had longer PFS after matching [HR =0.42 (95% CI: 0.25-0.71), P=0.001]. No significant difference in the objective response rate (ORR) and treatment-related adverse events (trAEs) between the two groups was found (ORR: EP: 81.0%, EP + ICIs: 90.0%, P=0.14; trAEs: EP: grade 1-2, 49.3%; grade 3-4, 42.5%; EP + ICIs: grade 1-2, 40.0%; grade 3-4, 49.1%, P=0.62). The multivariate analysis presented that the history of immunotherapy [EP + PD-1 inhibitors: HR =0.33 (95% CI: 0.17-0.62), P=0.001; EP + PD-L1 inhibitors: HR =0.18 (95% CI: 0.06-0.60), P=0.005] and baseline lung immune prognostic index (LIPI) [intermediate: HR =2.22 (95% CI: 1.20-4.13), P=0.01; poor: HR =2.03 (95% CI: 0.71-5.77), P=0.18] were independent prognostic factors for PFS among all LS-SCLC cases. However, no independent prognostic factor was identified for OS. Conclusions: Our real-world data showed promising clinical efficacy and tolerable safety of first-line programmed cell death protein 1 (PD-1) inhibitors or programmed cell death ligand 1 (PD-L1) inhibitors in cases with LS-SCLC. Additionally, LIPI may serve as a valuable prognostic factor.

13.
Cell Rep ; 43(5): 114119, 2024 May 28.
Article En | MEDLINE | ID: mdl-38630589

Phosphatidylinositol 3-kinase α (PI3Kα) is a heterodimer of p110α catalytic and p85 adaptor subunits that is activated by agonist-stimulated receptor tyrosine kinases. Although p85α recruits p110α to activated receptors on membranes, p85α loss, which occurs commonly in cancer, paradoxically promotes agonist-stimulated PI3K/Akt signaling. p110α localizes to microtubules via microtubule-associated protein 4 (MAP4), facilitating its interaction with activated receptor kinases on endosomes to initiate PI3K/Akt signaling. Here, we demonstrate that in response to agonist stimulation and p85α knockdown, the residual p110α, coupled predominantly to p85ß, exhibits enhanced recruitment with receptor tyrosine kinases to endosomes. Moreover, the p110α C2 domain binds PI3-phosphate, and this interaction is also required to recruit p110α to endosomes and for PI3K/Akt signaling. Stable knockdown of p85α, which mimics the reduced p85α levels observed in cancer, enhances cell growth and tumorsphere formation, and these effects are abrogated by MAP4 or p85ß knockdown, underscoring their role in the tumor-promoting activity of p85α loss.


Class Ia Phosphatidylinositol 3-Kinase , Endosomes , Microtubule-Associated Proteins , Phosphatidylinositol Phosphates , Signal Transduction , Endosomes/metabolism , Humans , Phosphatidylinositol Phosphates/metabolism , Class Ia Phosphatidylinositol 3-Kinase/metabolism , Class Ia Phosphatidylinositol 3-Kinase/genetics , Microtubule-Associated Proteins/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Animals , Enzyme Activation , Phosphatidylinositol 3-Kinases/metabolism , Cell Proliferation , Protein Binding
14.
Biomaterials ; 309: 122582, 2024 Sep.
Article En | MEDLINE | ID: mdl-38678699

Cold atmospheric plasma (CAP) is a unique form of physical plasma that has shown great potential for cancer therapy. CAP uses ionized gas to induce lethal oxidative stress on cancer cells; however, the efficacy of CAP therapy continues to be improved. Here, we report an injectable hydrogel-mediated approach to enhance the anti-tumor efficacy of CAP by regulating the phosphorylation of eIF2α. We discovered that reactive oxygen and nitrogen species (ROS/RNS), two main anti-tumor components in CAP, can lead to lethal oxidative stress on tumor cells. Elevated oxidative stress subsequently induces eIF2α phosphorylation, a pathognomonic marker of immunogenic cell death (ICD). Trehalose, a natural disaccharide sugar, can further enhance CAP-induced ICD by elevating the phosphorylation of eIF2α. Moreover, injectable hydrogel-mediated delivery of CAP/trehalose treatment promoted dendritic cell (DC) maturation, initiating tumor-specific T-cell mediated anti-tumor immune responses. The combination therapy also supported the polarization of tumor-associated macrophages to an M1-like phenotype, reversing the immunosuppressive tumor microenvironment and promoting tumor antigen presentation to T cells. In combination with immune checkpoint inhibitors (i.e., anti-programmed cell death protein 1 antibody, aPD1), CAP/trehalose therapy further inhibited tumor growth. Importantly, our findings also indicated that this hydrogel-mediated local combination therapy engaged the host systemic innate and adaptive immune systems to impair the growth of distant tumors.


Plasma Gases , Trehalose , Trehalose/chemistry , Trehalose/pharmacology , Animals , Mice , Cell Line, Tumor , Humans , Dendritic Cells/drug effects , Mice, Inbred C57BL , Neoplasms/therapy , Neoplasms/drug therapy , Reactive Oxygen Species/metabolism , Oxidative Stress/drug effects , Hydrogels/chemistry , Tumor Microenvironment/drug effects , Female , Immunogenic Cell Death/drug effects , Phosphorylation/drug effects
15.
Toxicon ; 241: 107675, 2024 Apr.
Article En | MEDLINE | ID: mdl-38432611

Gastric cancer (GC) is a common, life-threatening malignancy that contributes to the global burden of cancer-related mortality, as conventional therapeutic modalities show limited effects on GC. Hence, it is critical to develop novel agents for GC therapy. Morusin, a typical prenylated flavonoid, possesses antitumor effects against various cancers. The present study aimed to demonstrate the inhibitory effect and mechanism of morusin on the stemness characteristics of human GC in vitro under hypoxia and to explore the potential molecular mechanisms. The effects of morusin on cell proliferation and cancer stem cell-like properties of the human GC cell lines SNU-1 and AGS were assessed by MTT assay, colony formation test, qRT-PCR, flow cytometry analysis, and sphere formation test under hypoxia or normoxia condition through in vitro assays. The potential molecular mechanisms underlying the effects of morusin on the stem-cell-like properties of human GC cells in vitro were investigated by qRT-PCR, western blotting assay, and immunofluorescence assay by evaluating the nuclear translocation and expression level of hypoxia-inducible factor-1α (HIF-1α). The results showed that morusin exerted growth inhibitory effects on SNU-1 and AGS cells under hypoxia in vitro. Moreover, the proportions of CD44+/CD24- cells and the sphere formation ability of SNU-1 and AGS reduced in a dose-dependent manner following morusin treatment. The expression levels of stem cell-related genes, namely Nanog, OCT4, SOX2, and HIF-1α, gradually decreased, and the nuclear translocation of the HIF-1α protein was apparently attenuated. HIF-1α overexpression partially reversed the abovementioned effects of morusin. Taken together, morusin could restrain stemness characteristics of GC cells by inhibiting HIF-1α accumulation and nuclear translocation and could serve as a promising compound for GC treatment.


Flavonoids , Stomach Neoplasms , Humans , Cell Line, Tumor , Cell Proliferation , Flavonoids/pharmacology , Hypoxia/metabolism , Hypoxia/pathology , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Tumor Microenvironment/drug effects , Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & inhibitors , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
16.
J Colloid Interface Sci ; 663: 775-786, 2024 Jun.
Article En | MEDLINE | ID: mdl-38442519

Photocatalytic aerobic oxidation is a promising sustainable strategy for the selective organic synthesis of industrially valuable chemicals. However, the poor charge separation and insufficient molecular activation restrict the overall photocatalytic efficiency. To address these issues, we have developed a novel approach involving molecular dipole modulation and polar molecular self-assembly to modulate the built-in electric field (BEF) in perylene diimide (PDI) supramolecular polarization photocatalysts by adjusting the electronegativity of terminal substituents. The optimized methylphosphate-substituted PDI (P-PDIP) supramolecular system features the strongest BEF induced by its large molecular dipole, with an intensity 3.89 times higher than that observed in methylcarboxy-substituted PDI (P-PDIC) and 5.64 times higher than that observed in P-PDI. This significant enhancement in BEF generates a powerful driving force within P-PDIP, facilitating directional charge separation toward active sites. Additionally, the incorporation of methylphosphate groups improves the activation efficiency of O2 and thioether molecules, resulting in a remarkable photocatalytic performance for selective aerobic oxidation of sulfides into sulfoxide (up to 99.9% conversion and 99.8% selectivity). This study highlights that enhancing BEF through manipulating molecular dipoles can significantly improve photocatalytic activity, offering great potential for constructing efficient organic polarization photocatalysts in green chemistry and sustainable production.

17.
J Ovarian Res ; 17(1): 61, 2024 Mar 14.
Article En | MEDLINE | ID: mdl-38486335

BACKGROUND: Lymph node metastasis (LNM) is a major factor contributing to the high mortality rate of ovarian cancer, making the treatment of this disease challenging. However, the molecular mechanism underlying LNM in ovarian cancer is still not well understood, posing a significant obstacle to overcome. RESULTS: Through data mining from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we have identified MEOX1 as a specific gene associated with LNM in ovarian cancer. The expression of MEOX1 was found to be relatively high in serous ovarian adenocarcinoma, and its higher expression were associated with increased tumor grade and poorer clinical prognosis for ovarian cancer patients. Bioinformatics analysis revealed that MEOX1 exhibited the highest mRNA levels among all cancer types in ovarian cancer tissues and cell lines. Furthermore, gene set enrichment analysis (GSEA) and pathway analysis demonstrated that MEOX1 was involved in various LNM-related biological activities, such as lymphangiogenesis, lymphatic vessel formation during metastasis, epithelial-mesenchymal transition (EMT), G2/M checkpoint, degradation of extracellular matrix, and collagen formation. Additionally, the expression of MEOX1 was positively correlated with the expression of numerous prolymphangiogenic factors in ovarian cancer. To validate our findings, we conducted experiments using clinical tissue specimens and cell lines, which confirmed that MEOX1 was highly expressed in high-grade serous ovarian cancer (HGSOC) tissues and various ovarian cancer cell lines (A2780, SKOV3, HO8910, and OVCAR5) compared to normal ovarian tissues and normal ovarian epithelial cell line IOSE-80, respectively. Notably, we observed a higher protein level of MEOX1 in tumor tissues of LNM-positive HGSOC compared to LNM-negative HGSOC. Moreover, our fundamental experiments demonstrated that suppression of MEOX1 led to inhibitory effects on ovarian cancer cell proliferation and EMT, while overexpression of MEOX1 enhanced the proliferation and EMT capacities of ovarian cancer cells. CONCLUSIONS: The results of our study indicate that MEOX1 plays a role in the lymph node metastasis of ovarian cancer by regulating multiple biological activities, including the proliferation and EMT of ovarian cancer, lymphangiogenesis, and ECM remodeling. Our findings suggest that MEOX1 could serve as a potential biomarker for the diagnosis and treatment of ovarian cancer with LNM.


Ovarian Neoplasms , Humans , Female , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Cell Line, Tumor , Lymphatic Metastasis , Carcinoma, Ovarian Epithelial , Cell Proliferation , Transcription Factors/genetics , Homeodomain Proteins
18.
Materials (Basel) ; 17(6)2024 Mar 20.
Article En | MEDLINE | ID: mdl-38541582

In this research, the adsorption performance of individual atoms on the surface of monolayer graphene surface was systematically investigated using machine learning methods to accelerate density functional theory. The adsorption behaviors of over thirty different atoms on the graphene surface were computationally analyzed. The adsorption energy and distance were extracted as the research targets, and the basic information of atoms (such as atomic radius, ionic radius, etc.) were used as the feature values to establish the dataset. Through feature engineering selection, the corresponding input feature values for the input-output relationship were determined. By comparing different models on the dataset using five-fold cross-validation, the mathematical model that best fits the dataset was identified. The optimal model was further fine-tuned by adjusting of the best mathematical ML model. Subsequently, we verified the accuracy of the established machine learning model. Finally, the precision of the machine learning model forecasts was verified by the method of comparing and contrasting machine learning results with density functional theory. The results suggest that elements such as Zr, Ti, Sc, and Si possess some potential in controlling the interfacial reaction of graphene/aluminum composites. By using machine learning to accelerate first-principles calculations, we have further expanded our choice of research methods and accelerated the pace of studying element-graphene interactions.

19.
World J Gastroenterol ; 30(2): 184-195, 2024 Jan 14.
Article En | MEDLINE | ID: mdl-38312120

BACKGROUND: Resistance to clarithromycin (CLA) and levofloxacin (LFX) of Helicobacter pylori (H. pylori) is increasing in severity, and successful eradication is essential. Presently, the eradication success rate has greatly declined, leaving a large number of patients with previous treatment histories. AIM: To investigate secondary resistance rates, explore risk factors for antibiotic resistance, and assess the efficacy of susceptibility-guided therapy. METHODS: We recruited 154 subjects positive for Urea Breath Test who attended The First Affiliated Hospital of China Medical University between July 2022 and April 2023. Participants underwent a string test after an overnight fast. The gastric juice was obtained and transferred to vials containing storage solution. Subsequently, DNA extraction and the specific DNA amplification were performed using quantitative polymerase chain reaction (qPCR). Demographic information was also analyzed as part of the study. Based on these results, the participants were administered susceptibility-guided treatment. Efficacy was compared with that of the empiric treatment group. RESULTS: A total of 132 individuals tested positive for the H. pylori ureA gene by qPCR technique. CLA resistance rate reached a high level of 82.6% (n = 109), LFX resistance rate was 69.7% (n = 92) and dual resistance was 62.1% (n = 82). Gastric symptoms [odds ratio (OR) = 2.782; 95% confidence interval (95%CI): 1.076-7.194; P = 0.035] and rural residence (OR = 5.152; 95%CI: 1.407-18.861; P = 0.013) were independent risk factors for secondary resistance to CLA and LFX, respectively. A total of 102 and 100 individuals received susceptibility-guided therapies and empiric treatment, respectively. The antibiotic susceptibility-guided treatment and empiric treatment groups achieved successful eradication rates of 75.5% (77/102) and 59.0% (59/411) by the intention-to-treat (ITT) analysis and 90.6% (77/85) and 70.2% (59/84) by the per-protocol (PP) analysis, respectively. The eradication rates of these two treatment strategies were significantly different in both ITT (P = 0.001) and PP (P = 0.012) analyses. CONCLUSION: H. pylori presented high secondary resistance rates to CLA and LFX. For patients with previous treatment failures, treatments should be guided by antibiotic susceptibility tests or regional antibiotic resistance profile.


Helicobacter Infections , Helicobacter pylori , Humans , Clarithromycin/pharmacology , Clarithromycin/therapeutic use , Levofloxacin/therapeutic use , Helicobacter pylori/genetics , Helicobacter Infections/diagnosis , Helicobacter Infections/drug therapy , Drug Therapy, Combination , Anti-Bacterial Agents/therapeutic use , Urea , DNA , Treatment Outcome , Amoxicillin/therapeutic use , Drug Resistance, Bacterial
20.
Ther Adv Med Oncol ; 16: 17588359231225036, 2024.
Article En | MEDLINE | ID: mdl-38420602

Background: Immunotherapy is an emerging antitumor therapy that can improve the survival of patients with advanced non-small-cell lung cancer (NSCLC). However, only about 20% of NSCLC patients can benefit from this treatment. At present, whether patients with driving gene-positive NSCLC can benefit from immunotherapy is one of the hot issues. Therefore, we conducted a meta-analysis to evaluate the efficacy of immunotherapy in patients with oncogene-driven NSCLC and concluded the efficacy of altered subtypes. Methods: A literature search was performed using PubMed, Web of Science, and Cochrane databases. The primary endpoints included the objective response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) in patients with oncogene-driven NSCLC. Results: In all, 86 studies involving 4524 patients with oncogene-driven NSCLC were included in this meta-analysis. The pooled ORRs in clinical trials treated with monoimmunotherapy of EGFR, ALK, and KRAS alteration were 6%, 0%, and 23%, respectively. In retrospective studies, the pooled ORRs of EGFR, ALK, KRAS, BRAF, MET, HER2, RET, and ROS1 alteration were 8%, 3%, 28%, 24%, 23%, 14%, 7%, and 8%, respectively. Among them, the pooled ORRs of KRAS non-G12C mutation, KRAS G12C mutation, BRAF V600E mutation, BRAF non-V600E mutation, MET-exon 14 skipping, and MET-amplification were 33% 40%, 20%, 34%, 17%, and 60%, respectively. In addition, the pooled mPFS rates of EGFR, KRAS, MET, HER2, and RET alteration were 2.77, 3.24, 2.48, 2.31, and 2.68 months, while the pooled mOS rates of EGFR and KRAS alteration were 9.98 and 12.29 months, respectively. In prospective data concerning EGFR mutation, the pooled ORR and mPFS treated with chemo-immunotherapy (IC) reached 38% and 6.20 months, while 58% and 8.48 months with chemo-immunotherapy plus anti-angiogenesis therapy (ICA). Moreover, the pooled mPFS and mOS of monoimmunotherapy was 2.33 months and 12.43 months. Conclusions: EGFR-, ALK-, HER2-, RET-, and ROS1-altered NSCLC patients have poor reactivity to monoimmunotherapy but the efficacy of immune-based combined therapy is significantly improved. KRAS G12C mutation, BRAF non-V600E mutation, and MET amplification have better responses to immunotherapy, and more prospective studies are needed for further research.


Efficacy of immunotherapy in patients with oncogene-driven non-small cell lung cancer: a systematic review and meta analysis Immunotherapy is an emerging antitumor therapy that can improve the survival of patients with advanced NSCLC. However, only about 20% of NSCLC patients can benefit from this treatment. At present, whether patients with driving gene positive NSCLC can benefit from immunotherapy is one of the hot issues. Therefore, we conducted a meta-analysis to evaluate the efficacy of immunotherapy in patients with oncogene-driven NSCLC, and concluded the efficacy of altered subtypes. 86 studies involving 4524 patients with oncogene-driven NSCLC were included in this meta-analysis. The pooled ORR in clinical trials treated with monoimmunotherapy was of EGFR, ALK and KRAS alteration was 6%, 0%, and 23%, respectively. While in retrospective studies, the pooled ORR of EGFR, ALK, KRAS, BRAF, MET, HER2, RET and ROS1 alteration was 8%, 3%, 28%, 24%, 23%, 14%, 7% and 8%, respectively. Among them, the pooled ORR of KRAS non-G12C mutation, KRAS G12C mutation, BRAF V600E mutation, BRAF non-V600E mutation, MET-exon 14 skipping and MET-amplification was 33% 40%, 20%, 34%, 17% and 60%, respectively. Additionally, the pooled mPFS of EGFR, KRAS, MET, HER2 and RET alteration was 2.77, 3.24, 2.48, 2.31 and 2.68 months, while the pooled mOS of EGFR and KRAS alteration was 9.98 and 12.29 months. In prospective data concerning EGFR mutation, the pooled ORR and mPFS treated with chemo-immunotherapy (IC) was reached 38% and 6.20 months, while 58% and 8.48 months with chemo-immunotherapy plus anti-angiogenesis therapy (ICA). Moreover, the pooled mPFS and mOS of monoimmunotherapy was 2.33 months and 12.43 months. EGFR, ALK, HER2, RET and ROS1-altered NSCLC patients have poor reactivity to monoimmunotherapy, but the efficacy of immune-based combined therapy is significantly improved. KRAS G12C mutation, BRAF non-V600E mutation and MET amplification have better response to immunotherapy, and more prospective studies are needed for further research.

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