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JOURNAL/nrgr/04.03/01300535-202503000-00027/figure1/v/2024-06-17T092413Z/r/image-tiff Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus, leading to long-term cognitive impairment. However, the mechanism underlying this neurogenesis impairment remains unknown. In this study, we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury. Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development, delayed neuronal maturation, and reduced the complexity of neuronal dendrites and spines. Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval. Moreover, following repetitive traumatic brain injury, neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased, C1q binding protein levels were decreased, and canonical Wnt/ß-catenin signaling was downregulated. An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function. These findings suggest that repetitive traumatic brain injury-induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.
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Air sensitivity remains a substantial barrier to the commercialization of sodium (Na)-layered oxides (NLOs). This problem has puzzled the community for decades because of the complexity of interactions between air components and their impact on both bulk and surfaces of NLOs. We show here that water vapor plays a pivotal role in initiating destructive acid and oxidative degradations of NLOs only when coupled with carbon dioxide or oxygen, respectively. Quantification analysis revealed that reducing the defined cation competition coefficient (η), which integrates the effects of ionic potential and sodium content, and increasing the particle size can enhance the resistance to acid attack, whereas using high-potential redox couples can eliminate oxidative degradation. These findings elucidate the underlying air deterioration mechanisms and rationalize the design of air-stable NLOs.
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BACKGROUND: Drug-coated balloon (DCB) angioplasty and drug-eluting stents (DES) are two widely used treatments for in-stent restenosis (ISR). Focal and non-focal types of ISR affect the clinical outcomes. The present study aims to compare DES reimplantation versus DCB angioplasty in acute coronary syndrome (ACS) patients with focal ISR and non-focal ISR lesions. METHODS: Patients with ISR lesions underwent percutaneous coronary intervention (PCI) were retrospectively evaluated and divided into DES group and DCB group. The primary endpoint was the incidence of target lesion failure (TLF) at 24â¯months follow up. Propensity score matching (PSM) was conducted to balance the baseline characteristics. RESULTS: For focal ISR, TLF was comparable in the DES and DCB groups at 24â¯months of follow-up (Before PSM, hazard ratio [HR]: 0.70; 95% confidence interval [CI]: 0.39-1.27; pâ¯=â¯0.244; After PSM, HR: 0.83; 95% CI: 0.40-1.73; pâ¯=â¯0.625). For non-focal ISR, TLF was significantly decreased in DES compared with DCB group (Before PSM, HR: 0.43; 95% CI: 0.29-0.63; pâ¯<â¯0.001; After PSM, HR: 0.33; 95% CI: 0.19-0.59; pâ¯<â¯0.001), which was mainly attributed to the lower incidence of clinically indicated target lesion revascularization (CD-TLR) (Before PSM, HR: 0.39; 95% CI: 0.26-0.59; pâ¯<â¯0.001; After PSM, HR: 0.28; 95% CI: 0.15-0.54; pâ¯<â¯0.001). CONCLUSIONS: The clinical outcomes for DES and DCB treatment are similar in focal type of ISR lesions. For non-focal ISR, the treatment of DES showed a significant decrease in TLF which was mainly attributed to a lower incidence of CD-TLR.
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Alloy-type materials are attractive for anodes in sodium-ion batteries (SIBs) owing to their high theoretical capacities and overall performance. However, the accumulation of stress/strain during repeated cycling results in electrode pulverization, leading to rapid capacity decay and eventual disintegration, thus hindering their practical applications. Herein, we report a 3D coral-like Sb-Cu alloy nanoarray with gradient distribution of both elements. The array features a Sb-rich bottom and a Cu-rich top with increasing Sb and decreasing Cu concentrations from top to bottom. The former is the active component that provides the high capacity, whereas the latter serves as an inert additive that acts against volume variation. The gradual transition in composition within the electrode introduces a ladder-type volume expansion effect, facilitating a smooth distribution and effective release of stress, thereby ensuring the wanted mechanical stability and structural integrity. The as-developed nanoarray affords a high reversible capacity (460 mAh g-1 at 0.5 C), stable cycling (89% retention over 120 cycles at 1.0 C), and superior rate capability (354 mAh g-1 at 10 C). The concentration dual-gradient strategy paves a new pathway of designing alloy-type materials for SIBs.
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Marine microorganisms are increasingly recognized as primary producers of marine secondary metabolites, drawing growing research interest. Many of these organisms are unculturable, posing challenges for study. Metagenomic techniques enable research on these unculturable microorganisms, identifying various biosynthetic gene clusters (BGCs) related to marine microbial secondary metabolites, thereby unveiling their secrets. This review comprehensively analyses metagenomic methods used in discovering marine microbial secondary metabolites, highlighting tools commonly employed in BGC identification, and discussing the potential and challenges in this field. It emphasizes the key role of metagenomics in unveiling secondary metabolites, particularly in marine sponges and tunicates. The review also explores current limitations in studying these metabolites through metagenomics, noting how long-read sequencing technologies and the evolution of computational biology tools offer more possibilities for BGC discovery. Furthermore, the development of synthetic biology allows experimental validation of computationally identified BGCs, showcasing the vast potential of metagenomics in mining marine microbial secondary metabolites.
Subject(s)
Aquatic Organisms , Metagenomics , Secondary Metabolism , Metagenomics/methods , Secondary Metabolism/genetics , Aquatic Organisms/genetics , Aquatic Organisms/metabolism , Animals , Multigene Family , Porifera/microbiology , Bacteria/genetics , Bacteria/metabolism , Bacteria/classification , Biological Products/metabolism , Computational Biology/methods , Biosynthetic Pathways/genetics , Urochordata/microbiologyABSTRACT
Palladium ion (Pd2+) plays an important role in our daily life, but poses a great threat to the environment and human health. Thus, it is desirable to exploit a rapid and sensitive approach to realize the detection of Pd2+. In this study, a cellulose acetate-based macromolecular fluorescent probe CA-NA-PA was successfully prepared for tracking amounts of Pd2+. CA-NA-PA showed an obvious "on-off" fluorescence response to Pd2+, accompanied by the fluorescence color changed from bright yellow to colorless. CA-NA-PA had some outstanding detection performances such as low detection limit (26 nM), extremely short response time (1 min), good selectivity and anti-interference ability. Based on the advantages of probe mentioned above, CA-NA-PA could realize recognition of Pd2+ concentration in environmental water and soil samples. What's more, the probe CA-NA-PA was applied to image Pd2+ in zebrafish as well as in live onion tissue due to the good biocompatibility and cell membrane permeability of cellulose, suggesting its wide application prospect in biosystems.
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Antiferromagnets have attracted significant attention in the field of magnonics, as promising candidates for ultralow-energy carriers for information transfer for future computing. The role of crystalline orientation distribution on magnon transport has received very little attention. In multiferroics such as BiFeO3 the coupling between antiferromagnetic and polar order imposes yet another boundary condition on spin transport. Thus, understanding the fundamentals of spin transport in such systems requires a single domain, a single crystal. We show that through Lanthanum (La) substitution, a single ferroelectric domain can be engineered with a stable, single-variant spin cycloid, controllable by an electric field. The spin transport in such a single domain displays a strong anisotropy, arising from the underlying spin cycloid lattice. Our work shows a pathway to understanding the fundamental origins of magnon transport in such a single domain multiferroic.
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Immunosuppressive tumor-associated macrophages (TAMs) account for a high proportion of the tumor tissue and significantly impede immunoefficacy. Furthermore, the signal regulatory protein α (SIRPα) expressed in TAMs adversely correlates with macrophage activation and phagocytosis, resulting in immunosurveillance escape. To address these difficulties, a mannose-modified, pH-responsive nanoplatform with resiquimod (R848) and 2', 3'-cyclic GMP-AMP (cGAMP) co-encapsulation (named M-PNP@R@C) is designed to polarize TAMs and lower SIRPα expression. The co-delivery of R848 and cGAMP synergistically facilitates the polarization of TAMs from the anti-inflammatory M2 phenotype into the pro-inflammatory M1 phenotype, thereby enhancing antitumor immunotherapy. Remarkably, activation of the cGAMP-mediated stimulator of interferon genes (STING) in TAMs significantly downregulates the expression of SIRPα, which synergizes with the cluster of differentiation 47 (CD47) antibody for the dual blockade of the CD47-SIRPα axis. Further analysis of single-cell RNA sequencing indicates that STING activation downregulates SIRPα by regulating intracellular fatty acid oxidation metabolism. In vivo studies indicate that M-PNP@R@C significantly inhibits tumor growth with a potent antitumor immune response in melanoma graft tumor models. After synergy with anti-CD47, the double blockade strategies of the SIRPα/CD47 axis result in a notable inhibition of lung metastasis. A prolonged survival rate is observed after combination treatment with CD47 and programmed death ligand-1 antibodies for the triple immune checkpoint blockade. In summary, our study provides original insights into the potential role of the STING pathway in macrophage-based immunotherapy, thus offering a potential combinatorial strategy for cancer therapy.
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BACKGROUND: About 186 million people in the world suffer from infertility, and there is one infertile couple in every 4-6 couples. It is thus essential to find effective psychological treatment. OBJECTIVE: To conduct a systematic review of previous meta-analyses on mindfulness-based therapy outcomes in infertile female patients and a meta-analysis of studies nested within these meta-analyses. METHODS: Randomized controlled trials (RCTS) on the efficacy of mindset-based interventions in infertile female patients were retrieved from PubMed, The Cochrane Library, Embase, Web of Science, CNI, VIP Database, and Wanfang Database until March 1, 2023. Two researchers screened the literature, extracted data according to inclusion and exclusion criteria, and conducted quality control according to Cochrane Handbook 5.1.0. When there was ambiguity, a third party determined it. The meta-analysis was performed using RevMan 5.3 software. RESULT: 14 randomized controlled trials involving 1784 patients were included. Meta-analysis showed that compared with conventional care, mindfulness-based intervention can effectively relieve anxiety in female infertility patients [SMD =-2.25, 95% CI (-2.90, -1.60), P< 0.00001], depression [SMD =-2.25, 95% CI (-2.99, -1.52), P< 0.00001], perceived stress [SMD =-0.99, 95% CI (-1.27, -0.71), P< 0.00001], improved quality of life, physiological function [MD = 14.03, 95% CI (11.98, 16.07), P< 0.00001], Role limitations due to physical problems [MD = 11.30, 95% CI (5.71, 16.90), P< 0.0001], vitality [MD = 11.55, 95% CI (9.46, 13.65), P< 0.00001], mental health [MD = 17.32, 95% CI (15.29, 19.35), P< 0.00001]. CONCLUSION: Existing evidence shows that mindfulness therapy can effectively relieve the anxiety and depression of infertile women, reduce the level of stress, and improve the quality of life and sleep quality. However, due to the limited quantity and quality of the literature, multi-center, large-sample, and high-quality randomized controlled studies should be conducted in the future.
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Chlorinated anthracenes (Cl-Ants), persistent organic pollutants, are widely detected in the environment, posing potential lung toxicity risks due to frequent respiratory exposure. However, direct evidence and a comprehensive understanding of their toxicity mechanisms are lacking. Building on our prior findings of Cl-Ants' immunotoxic risks, this study developed a three-dimensional coculture spheroid model mimicking the lung's immune microenvironment. The objective is to explore the pulmonary immunotoxicity and comprehend its mechanisms, taking into account the heightened immune reactivity and frequent lung exposure of Cl-Ants. The results demonstrated that Cl-Ants exposure led to reduced spheroid size, increased macrophage migration outward, lowered cell viability, elevated 8-OHdG levels, disturbed anti-infection balance, and altered cytokine production. Specifically, the chlorine substituent number correlates with the extent of disruption of spheroid indicators caused by Cl-Ants, with stronger immunotoxic effects observed in dichlorinated Ant compared to those in monochlorinated Ant. Furthermore, we identified critical regulatory genes associated with cell viability (ALDOC and ALDOA), bacterial response (TLR5 and MAP2K6), and GM-CSF production (CEBPB). Overall, this study offers initial in vitro evidence of low-dose Cl-PAHs' pulmonary immunotoxicity, advancing the understanding of Cl-Ants' structure-related toxicity and improving external toxicity assessment methods for environmental pollutants, which holds significance for future monitoring and evaluation.
Subject(s)
Lung , Lung/drug effects , Anthracenes/toxicity , Humans , Coculture Techniques , Cell Survival/drug effectsABSTRACT
Pulmonary delivery of immunostimulatory agents such as poly(I:C) to activate double-stranded RNA sensors MDA5 and RIG-I within lung-resident antigen-presenting cells is a potential strategy to enhance antitumor immunity by promoting type I interferon secretion. Nevertheless, following pulmonary delivery, poly(I:C) suffers from rapid degradation and poor endosomal escape, thus limiting its potency. Inspired by the structure of a virus that utilizes internal viral proteins to tune the loading and cytosolic delivery of viral nucleic acids, we developed a liponanogel (LNG)-based platform to overcome the delivery challenges of poly(I:C). The LNG comprised an anionic polymer hyaluronic acid-based nanogel core coated by a lipid shell, which served as a protective layer to stabilize the nanogel core in the lungs. The nanogel core was protonated within acidic endosomes to enhance the endosomal membrane permeability and cytosolic delivery of poly(I:C). After pulmonary delivery, LNG-poly(I:C) induced 13.7-fold more IFNß than poly(I:C) alone and two-fold more than poly(I:C) loaded in the state-of-art lipid nanoparticles [LNP-poly(I:C)]. Additionally, LNG-poly(I:C) induced more potent CD8+ T-cell immunity and stronger therapeutic effects than LNP-poly(I:C). The combination of LNG-poly(I:C) and PD-L1 targeting led to regression of established lung metastases. Due to the ease of manufacturing and the high biocompatibility of LNG, pulmonary delivery of LNG may be broadly applicable to the treatment of different lung tumors and may spur the development of innovative strategies for cancer immunotherapy. Significance: Pulmonary delivery of poly(I:C) with a virus-inspired inhalable liponanogel strongly activates cytosolic MDA5 and RIG-I and stimulates antitumor immunity, representing a promising strategy for safe and effective treatment of metastatic lung tumors.
Subject(s)
Lung Neoplasms , Poly I-C , Lung Neoplasms/secondary , Lung Neoplasms/immunology , Lung Neoplasms/drug therapy , Animals , Mice , Poly I-C/administration & dosage , Humans , Mice, Inbred C57BL , Nanogels/chemistry , Cell Line, Tumor , Female , Administration, Inhalation , Lipids/chemistry , Lipids/administration & dosageABSTRACT
Reactive oxygen species (ROS) play an important role in regulating the immune system by affecting pathogens, cancer cells, and immune cells. Recent advances in biomaterials have leveraged this mechanism to precisely modulate ROS levels in target tissues for improving the effectiveness of immunotherapies in infectious diseases, cancer, and autoimmune diseases. Moreover, ROS-responsive biomaterials can trigger the release of immunotherapeutics and provide tunable release kinetics, which can further boost their efficacy. This review will discuss the latest biomaterial-based approaches for both precise modulation of ROS levels and using ROS as a stimulus to control the release kinetics of immunotherapeutics. Finally, we will discuss the existing challenges and potential solutions for clinical translation of ROS-modulating and ROS-responsive approaches for immunotherapy, and provide an outlook for future research.
Subject(s)
Immunotherapy , Reactive Oxygen Species , Humans , Reactive Oxygen Species/metabolism , Immunotherapy/methods , Animals , Neoplasms/therapy , Neoplasms/immunology , Neoplasms/metabolism , Biocompatible Materials/chemistryABSTRACT
Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs that have been implicated in mediating granulosa cell (GC) proliferation and apoptosis. CircRAB11A was found to have a significantly higher expression in normal follicles compared to atrophic follicles. In this study, we determined that the knockdown of circRAB11A resulted in the inhibition of proliferation and promotion of apoptosis in GCs of chicken. Moreover, circRAB11A was found to act as a sponge for miR-24-5p, both member RAS oncogene family (RAB11A) and epidermal growth factor receptor (EGFR) were revealed to be targets of miR-24-5p through a dual-luciferase reporter assay. RAB11A or EGFR promoted proliferation and suppressed apoptosis in GCs through the phosphatidylinositol-kinase (PI3K)/AKT or extracellular signal-regulated kinase (ERK)1/2 pathway. These findings suggest that circRAB11A may function as a competing endogenous RNA (ceRNA) by targeting the miR-24-5p/RAB11A and miR-24-5p/EGFR axes and activating the ERK1/2 and PI3K/AKT pathways, offering a potential avenue for exploring the mechanism of follicle development.
Subject(s)
Apoptosis , Cell Proliferation , Chickens , ErbB Receptors , Granulosa Cells , MicroRNAs , RNA, Circular , rab GTP-Binding Proteins , Animals , Granulosa Cells/physiology , Granulosa Cells/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Chickens/genetics , Female , RNA, Circular/genetics , RNA, Circular/metabolism , rab GTP-Binding Proteins/genetics , rab GTP-Binding Proteins/metabolism , ErbB Receptors/metabolism , ErbB Receptors/genetics , Phosphatidylinositol 3-Kinases/metabolism , Phosphatidylinositol 3-Kinases/genetics , Signal Transduction , MAP Kinase Signaling System , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/genetics , Avian Proteins/metabolism , Avian Proteins/geneticsABSTRACT
BACKGROUND: Discrepancies in the utilization of reactive oxygen species (ROS) between cancer cells and their normal counterparts constitute a pivotal juncture for the precise treatment of cancer, delineating a noteworthy trajectory in the field of targeted therapies. This phenomenon is particularly conspicuous in the domain of nano-drug precision treatment. Despite substantial strides in employing nanoparticles to disrupt ROS for cancer therapy, current strategies continue to grapple with challenges pertaining to efficacy and specificity. One of the primary hurdles lies in the elevated levels of intracellular glutathione (GSH). Presently, predominant methods to mitigate intracellular GSH involve inhibiting its synthesis or promoting GSH efflux. However, a conspicuous gap remains in the absence of a strategy capable of directly and efficiently clearing GSH. METHODS: We initially elucidated the chemical mechanism underpinning oridonin, a diminutive pharmacological agent demonstrated to perturb reactive oxygen species, through its covalent interaction with glutathione. Subsequently, we employed the incorporation of maleimide-liposomes, renowned for their capacity to disrupt the ROS delivery system, to ameliorate the drug's water solubility and pharmacokinetics, thereby enhancing its ROS-disruptive efficacy. In a pursuit to further refine the targeting for acute myeloid leukemia (AML), we harnessed the maleic imide and thiol reaction mechanism, facilitating the coupling of Toll-like receptor 2 (TLR2) peptides to the liposomes' surface via maleic imide. This strategic approach offers a novel method for the precise removal of GSH, and its enhancement endeavors are directed towards fortifying the precision and efficacy of the drug's impact on AML targets. RESULTS: We demonstrated that this peptide-liposome-small molecule machinery targets AML and consequently induces cell apoptosis both in vitro and in vivo through three disparate mechanisms: (I) Oridonin, as a Michael acceptor molecule, inhibits GSH function through covalent bonding, triggering an initial imbalance of oxidative stress. (II) Maleimide further induces GSH exhaustion, aggravating redox imbalance as a complementary augment with oridonin. (III) Peptide targets TLR2, enhances the directivity and enrichment of oridonin within AML cells. CONCLUSION: The rationally designed nanocomplex provides a ROS drug enhancement and targeted delivery platform, representing a potential solution by disrupting redox balance for AML therapy.
Subject(s)
Diterpenes, Kaurane , Glutathione , Leukemia, Myeloid, Acute , Liposomes , Reactive Oxygen Species , Diterpenes, Kaurane/chemistry , Diterpenes, Kaurane/pharmacology , Glutathione/metabolism , Glutathione/chemistry , Liposomes/chemistry , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/metabolism , Humans , Reactive Oxygen Species/metabolism , Animals , Mice , Cell Line, Tumor , Toll-Like Receptor 2/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Apoptosis/drug effectsABSTRACT
BACKGROUND: Understanding how medical students respond to financial and non-financial incentives is crucial for recruiting health workers and attracting health talents in medical education. However, both incentives are integrated in working practice, and existing theoretical studies have suggested that various income levels may influence the substitution effect of both incentives, while the empirical evidence is lacking. Furthermore, little attention has been paid to the intrinsic motivation. This study aimed to explore the substitution effect of extrinsic incentives at different income levels, also taking intrinsic altruism into account. METHODS: We used the behavioral data from Zhang et al.'s experiments, which involved discrete choice experiments (DCEs) to assess the job preferences of medical students from six teaching hospitals in Beijing, China. The incentive factors included monthly income, work location, work environment, training and career development opportunities, work load, and professional recognition. Additionally, a lab-like experiment in the medical decision-making context was conducted to quantify altruism based on utility function. Furthermore, we separated the choice sets based on the actual income and distinguished the medical students on altruism. The willingness to pay (WTP) was used to estimate the substitution effect of incentives through conditional logit model. RESULTS: There was a significant substitution effect between non-financial and financial incentives. As income increased, non-financial incentives such as an excellent work environment, and sufficient career development became relatively more important. The impact of the increase in income on the substitution effect was more pronounced among individuals with higher altruism. Concerning the non-financial incentive work environment, in contrast to the growth of 546 CNY (84 USD) observed in the low-altruism group, the high-altruism group experienced a growth of 1040 CNY (160 USD) in the substitution effect. CONCLUSIONS: The increase in the income level exerted an influence on the substitution effect of non-financial incentives and financial incentives, especially in high-altruism medical students. Policymakers should attach importance to a favorable environment and promising career prospects on the basis of ensuring a higher income level. Medical school administrations should focus on promoting altruistic values in medical education, enhancing talent incentives and teaching strategies to encourage medical students to devote themselves to the medical professions.
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Altruism , Career Choice , Income , Motivation , Personnel Selection , Students, Medical , Humans , Students, Medical/psychology , China , Female , Male , Adult , Young Adult , Physicians/psychologyABSTRACT
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a highly toxic persistent organic pollutant (POP) that can induce DNA damage within cells. Although oxidative stress is one of the primary mechanisms causing DNA damage, its role in the process of TCDD-induced DNA damage remains unclear. In this study, the TCDD-induced production of reactive oxygen species (ROS) and the occurrence of DNA damage at the AP site were monitored simultaneously. Further investigation revealed that TCDD impaired the activities of superoxide dismutase (SOD) and catalase (CAT), compromising the cellular antioxidant defense system. Consequently, this led to an increase in the production of O2.- and NO, thus inducing DNA damage at the AP site under oxidative stress. Our findings were further substantiated by the upregulation of key genes in the base excision repair (BER) pathway and the absence of DNA AP site damage after inhibiting O2.- and NO. In addition, transcriptome sequencing revealed that TCDD induces DNA damage by upregulating genes associated with oxidative stress in the mitogen-activated protein kinase (MAPK), cyclic adenosine monophosphate (cAMP), and breast cancer pathways. This study provides important insights into the toxicity mechanisms of TCDD.
Subject(s)
DNA Damage , Oxidative Stress , Polychlorinated Dibenzodioxins , Reactive Oxygen Species , Polychlorinated Dibenzodioxins/toxicity , Oxidative Stress/drug effects , DNA Damage/drug effects , Reactive Oxygen Species/metabolism , Catalase/metabolism , Superoxide Dismutase/metabolism , DNA Repair/drug effects , Humans , Environmental Pollutants/toxicityABSTRACT
Robust ferroelectricity in nanoscale fluorite oxide-based thin films enables promising applications in silicon-compatible non-volatile memories and logic devices. However, the polar orthorhombic (O) phase of fluorite oxides is a metastable phase that is prone to transforming into the ground-state non-polar monoclinic (M) phase, leading to macroscopic ferroelectric degradation. Here we investigate the reversibility of the O-M phase transition in ZrO2 nanocrystals via in situ visualization of the martensitic transformation at the atomic scale. We reveal that the reversible shear deformation pathway from the O phase to the monoclinic-like (M') state, a compressive-strained M phase, is protected by 90° ferroelectric-ferroelastic switching. Nevertheless, as the M' state gradually accumulates localized strain, a critical tensile strain can pin the ferroelastic domain, resulting in an irreversible M'-M strain relaxation and the loss of ferroelectricity. These findings demonstrate the key role of ferroelastic switching in the reversibility of phase transition and also provide a tensile-strain threshold for stabilizing the metastable ferroelectric phase in fluorite oxide thin films.
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OBJECTIVES: This study aimed to assess the level of public trust in general practitioners (GPs) and its association with primary care contract services (PCCS) in China. STUDY DESIGN: Cross-sectional study. METHODS: Between September and December 2021, 4158 residents across eastern, central, and western China completed a structured self-administered questionnaire. Trust was assessed using the Chinese version of Wake Forest Physician Trust Scale. Multivariable linear regression models were established to identify predictors of trust. The effect size of PCCS on trust was estimated by the average treatment effect for the treated (ATT) through propensity score matching. RESULTS: The study participants had a mean Wake Forest Physician Trust Scale score of 36.82 (standard deviation = 5.45). Enrollment with PCCS (ß = 0.14, P < 0.01), Han ethnicity (ß = 0.03, P < 0.05), lower educational attainment (ß = -0.06, P < 0.01), higher individual monthly income (ß = 0.03, P < 0.05), better self-rated health (ß = 0.04, P < 0.05), chronic conditions (ß = 0.07, P < 0.01), and higher familiarity with primary care services (ß = 0.12, P < 0.01) and PCCS (ß = 0.21, P < 0.01) were associated with higher trust in GPs. The ATT of PCCS exceeded 1 (P < 0.05). CONCLUSIONS: PCCS are associated with higher levels of trust in GPs. PCCS may become an effective tool to attract public trust in GPs, although the relationship between the two may be bi-directional.
Subject(s)
General Practitioners , Primary Health Care , Trust , Humans , Cross-Sectional Studies , China , Male , Female , Primary Health Care/statistics & numerical data , Middle Aged , Adult , General Practitioners/psychology , General Practitioners/statistics & numerical data , Surveys and Questionnaires , Physician-Patient Relations , Contract Services , Aged , Young Adult , AdolescentABSTRACT
Cervical medial branch block (CMBB) has been recognized as an effective treatment for cervicogenic pain. Previous studies mostly used ultrasound-guided out-of-plane puncture for CMBB, while this prospective study was designed to investigate the efficacy of ultrasound-guided in-plane puncture, specifically focusing on the new target of CMBB for cervical pain. This study includes two parts: the accuracy study (N = 15, CMBB was completed by ultrasound and confirmed by computed tomography [CT], in which a good distribution percentage of the analgesic solution was observed) and the efficacy study (N = 40, CMBB was completed by ultrasound or CT, while the proportion of pain relief (numerical rating scale) decrease by more than 50% postoperatively was analyzed). The results showed that the good distribution percentage of the analgesic solution was 97.8%. Furthermore, in the early period (30 min and 2 h postoperatively), the proportion of patients with pain relief was lower in the ultrasound group than that in the CT group, especially at 2 h postoperatively (52% vs. 94%). However, at 24 h postoperatively and later, the proportion of patients with pain relief gradually stabilized to about 60%-70%, and lasted for about 2 weeks to 1 month. Therefore, the new target for CMBB, guided by ultrasound in-plane, offers high visibility and accuracy. A single CMBB performed under ultrasound guidance resulted in pain relief comparable to that of a CT-guided procedure (1 day to 1 month postoperatively). This study indicated that CMBB guided by ultrasound in-plane could be regarded as a promising approach for treatment of cervicogenic pain.
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Background: Ionomics is used to study levels of ionome in different states of organisms and their correlations. Bone cancer pain (BCP) severely reduces quality of life of patients or their lifespan. However, the relationship between BCP and ionome remains unclear. Methods: The BCP rat model was constructed through inoculation of Walker 256 cells into the left tibia. Von Frey test, whole-cell patch-clamp recording and inductively coupled plasma mass spectrometry (ICP-MS) technologies were conducted for measuring tactile hypersensitivity, the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) of neurons of spinal slices, and ionome of spinal cord samples, respectively. Principal component analysis (PCA) was used to explore ionomic patterns of the spinal cord. Results: The BCP rat model was successfully constructed through implantation of Walker 256 cells into the left tibia. The frequency and amplitude of mEPSCs of neurons in the spinal cord slices from the BCP model rats were notably greater than those in the sham control. In terms of ionomics, the spinal cord levels of two macroelements (Ca and S), four microelements (Fe, Mn, Li and Sr) and the toxic element Ti in the BCP group of rats were significantly increased by inoculation of Walker 256 cancer cells, compared to the sham control. In addition, the correlation patterns between the elements were greatly changed between the sham control and BCP groups. PCA showed that inoculation of Walker 256 cells into the tibia altered the overall ionomic profiles of the spinal cord. There was a significant separation trend between the two groups. Conclusion: Taken together, inoculation of Walker 256 cells into the left tibia contributes to BCP, which could be closely correlated by some elements. The findings provided novel information on the relationship between the ionome and BCP.