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1.
Bioconjug Chem ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38722674

ABSTRACT

In clinical practice, the treatment of colon cancer is faced with the dilemma of metastasis and recurrence, which is related to immunosuppression and hypoxia. Immune checkpoint blockade (ICB) is a negative regulatory pathway of immunity. Immune checkpoint blockade (ICB) is an important immunotherapy method. However, inadequate immunogenicity reduces the overall response rate of ICB. In this study, a tumor microenvironment-responsive nanomedicine (Cu-FACD@MnO2@FA) was prepared to increase host immune response and increase intracellular oxygen levels. Cu-FACD@MnO2@FA preferentially enriched at the tumor site, combined with the immune checkpoint inhibitor alpha PD-L1, induced sufficient immunogenicity to treat colon cancer. Immunofluorescence detection of tumor cells and tissues showed that the expression of hypoxa-inducing factor 1α was significantly down-regulated after treatment and the expression of immunoactivity-related proteins was significantly changed. In vivo treatment in a bilateral tumor mouse model showed complete ablation of the primary tumor and efficient inhibition of the distal tumor. In this study, for the first time, the oxygenation effects of MnO2-coated Cu-doped carbon dots and chemodynamic therapy and a strategy of combining with immuno-blocking therapy were used for treating colon cancer.

2.
Nat Commun ; 15(1): 3691, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38693179

ABSTRACT

Voltage-gated sodium (NaV) channels mediate a plethora of electrical activities. NaV channels govern cellular excitability in response to depolarizing stimuli. Inactivation is an intrinsic property of NaV channels that regulates cellular excitability by controlling the channel availability. The fast inactivation, mediated by the Ile-Phe-Met (IFM) motif and the N-terminal helix (N-helix), has been well-characterized. However, the molecular mechanism underlying NaV channel slow inactivation remains elusive. Here, we demonstrate that the removal of the N-helix of NaVEh (NaVEhΔN) results in a slow-inactivated channel, and present cryo-EM structure of NaVEhΔN in a potential slow-inactivated state. The structure features a closed activation gate and a dilated selectivity filter (SF), indicating that the upper SF and the inner gate could serve as a gate for slow inactivation. In comparison to the NaVEh structure, NaVEhΔN undergoes marked conformational shifts on the intracellular side. Together, our results provide important mechanistic insights into NaV channel slow inactivation.


Subject(s)
Cryoelectron Microscopy , Ion Channel Gating , Voltage-Gated Sodium Channels , Voltage-Gated Sodium Channels/metabolism , Voltage-Gated Sodium Channels/chemistry , Humans , Animals , HEK293 Cells , Models, Molecular
3.
Front Pharmacol ; 15: 1338471, 2024.
Article in English | MEDLINE | ID: mdl-38698812

ABSTRACT

Objective: The aim of this study is to uncover the traditional Chinese medicine (TCM) treatments for chronic gastritis and their potential targets and pathways involved in the "inflammation-cancer" conversion in four stages. These findings can provide further support for future research into TCM and its active components. Materials and methods: The literature search encompassed PubMed, Web of Science, Google Scholar, CNKI, WanFang, and VIP, employing keywords such as "chronic gastritis", "gastric cancer", "traditional Chinese medicine", "medicinal herb", "Chinese herb", and "natural plant". Results: Herbal remedies may regulate the signaling pathways linked to the advancement of chronic gastritis. Under the multi-target and multi-pathway independent or combined reaction, the inflammatory microenvironment may be enhanced, leading to repair of damaged gastric mucosal cells, buffering the progress of mucosal atrophic degeneration via the decrease of inflammatory factor expression, inhibition of oxidative stress-induced damage, facilitation of microvascular neovascularization in the gastric mucosa and regulation of the processes of gastric mucosal cell differentiation and proliferation. Simultaneously, the decreased expression of inflammatory factors may impact the expression of associated oncogenes and regulate the malignant proliferation of cells, thereby achieving the treatment and prevention objectives of gastric cancer through the reduction of cell metastasis and apoptosis. Conclusion: Chinese medicine formulations and individual drugs can be utilised at various stages of the "inflammation-cancer" progression of chronic gastritis to prevent and treat gastric cancer in a multi-level, multi-targeted, and multi-directional fashion. This can provide guidance for the accurate application of medicines during different stages of "inflammation-cancer" transformation. New insights into the mechanism of inflammation-cancer transformation and the development of novel drugs for chronic gastritis can be gained through an extensive investigation of TCM treatment in this condition.

4.
Heliyon ; 10(10): e30855, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38774327

ABSTRACT

President Xi set a long-term mitigation target of carbon neutrality by 2060 in September 2020 to cut carbon emissions and improve environmental performance. As a result, the current study aims to investigate how green human resource management and green innovation affect environmental performance in pursuit of the ultimate objective of carbon neutrality. Furthermore, the research considers the potential mediating effect of a green competitive advantage to clarify the mechanisms by which GHRM and green innovation impact environmental performance. Data from 278 employees in the manufacturing industry of Heilongjiang Province were collected through a questionnaire, for which we used a quantitative random sampling technique. The study employed the Smart PLS-4 structural equation modeling technique and revealed that all three factors significantly influenced environmental performance: green HRM, innovation, and competitive advantage. Resource-based view (RBV) theory served as the theoretical foundation for the study. The study uniquely contributes to the literature on GHRM, green innovation, competitive advantage, and environmental performance.

5.
J Colloid Interface Sci ; 668: 618-633, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38696990

ABSTRACT

Tumor metastasis and recurrence are closely related to immune escape and hypoxia. Chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT) can induce immunogenic cell death (ICD), and their combination with immune checkpoint agents is a promising therapeutic strategy. Iron based nanomaterials have received more and more attention, but their low Fenton reaction efficiency has hindered their clinical application. In this study, Fe3O4-carbon dots complex (Fe3O4-CDs) was synthesized, which was modified with ferrocenedicarboxylic acid by amide bond, and crosslinked into Fe3O4-CDs@Fc nano complex. The CDs catalyzed the Fenton reaction activity of Fe3O4 by helping to improve the electron transfer efficiency, extended the reaction pH condition to 7.4. The Fe3O4-CDs@Fc exhibit exceptional optical activity, achieving a thermal conversion efficiency of 56.43 % under 808 nm light and a photosensitive single-line state oxygen quantum yield of 33 % under 660 nm light. Fe3O4-CDs@Fc improved intracellular oxygen level and inhibited hypoxia-inducing factor (HIF-1α) by in-situ oxygen production based on Fenton reaction. The multimodal combination of Fe3O4-CDs@Fc (CDT/PDT/PTT) strongly induced immune cell death (ICD). The expression of immune-related protein and HIF-1α was investigated by immunofluorescence method. In vivo, Fe3O4-CDs@Fc combined with immune checkpoint blocker (antibody PD-L1, αPD-L1) effectively ablated primary tumors and inhibited distal tumor growth. Fe3O4-CDs@Fc is a promising immune-antitumor drug.


Subject(s)
Carbon , Oxygen , Quantum Dots , Mice , Animals , Quantum Dots/chemistry , Carbon/chemistry , Humans , Catalysis , Oxygen/chemistry , Immunotherapy , Particle Size , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Photochemotherapy , Mice, Inbred BALB C , Cell Line, Tumor , Iron/chemistry , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/pharmacology , Surface Properties , Cell Survival/drug effects , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor , Female
6.
Mol Carcinog ; 2024 May 23.
Article in English | MEDLINE | ID: mdl-38780182

ABSTRACT

Lactate dehydrogenase A (LDHA) is known to promote the growth and invasion of various types of tumors, affects tumor resistance, and is associated with tumor immune escape. But how LDHA reshapes the tumor microenvironment and promotes the progression of renal cell carcinoma (RCC) remains unclear. In this study, we found that LDHA was highly expressed in clear cell RCC (ccRCC), and this high expression was associated with macrophage infiltration, while macrophages were highly infiltrated in ccRCC, affecting patient prognosis via M2-type polarization. Our in vivo and in vitro experiments demonstrated that LDHA and M2-type macrophages could enhance the proliferation, invasion, and migration abilities of ccRCC cells. Mechanistically, high expression of LDHA in ccRCC cells upregulated the expression of EPHA2 in exosomes derived from renal cancer. Exosomal EPHA2 promoted M2-type polarization of macrophages by promoting activation of the PI3K/AKT/mTOR pathway in macrophages, thereby promoting the progression of ccRCC. All these findings suggest that EPHA2 may prove to be a potential therapeutic target for advanced RCC.

7.
Hum Vaccin Immunother ; 20(1): 2341454, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-38695296

ABSTRACT

Pertussis is a vaccine-preventable infectious disease; however, data on pertussis antibody levels in a nationwide population are still limited in China. We aimed to pool the seropositivity rates of IgG antibodies against pertussis toxin (PT-IgG) across the country. We systematically searched PubMed, Web of Science, Embase, and the China National Knowledge Infrastructure Database for studies published between January 1, 2010, and June 30, 2023. Studies reporting the seroprevalence of PT-IgG among a healthy Chinese population were included. Pooled estimates were obtained using random-effects meta-analyzes. The meta-analysis included 39 studies (47,778 participants) reporting anti-PT IgG seropositivity rates. The pooled rate for all ages was 7.06% (95% CI, 5.50%-9.07%). Subgroup analyzes showed rates ranging from 6.36% to 12.50% across different age groups. This meta-analysis indicated a low anti-PT IgG seropositivity rate in the Chinese population, particularly among school-aged children and young adults. This finding underscores the urgent need to refine immunization strategies.


Subject(s)
Antibodies, Bacterial , Immunoglobulin G , Pertussis Toxin , Whooping Cough , Humans , Seroepidemiologic Studies , Pertussis Toxin/immunology , Immunoglobulin G/blood , Whooping Cough/epidemiology , Whooping Cough/immunology , Whooping Cough/prevention & control , China/epidemiology , Antibodies, Bacterial/blood , Child , Adult , Young Adult , Adolescent , Child, Preschool , Middle Aged , Pertussis Vaccine/immunology , Pertussis Vaccine/administration & dosage , East Asian People
8.
Plant Physiol Biochem ; 212: 108707, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38763002

ABSTRACT

Apple (Malus domestica Borkh.) is a widely cultivated fruit crop worldwide but often suffers from abiotic stresses such as salt and cold. Gibberellic acid (GA) plays a pivotal in controlling plant development, environmental adaptability, and secondary metabolism. The GA2-oxidase (GA2ox) is responsible for the deactivation of bioactive GA. In this study, seventeen GA2-oxidase genes were identified in the apple genome, and these members could be clustered into four clades based on phylogenetic relationships and conserved domain structures. MdGA2ox7 exhibited robust expression across various tissues, responded to cold and salt treatments, and was triggered in apple fruit peels via light-induced anthocyanin accumulation. Subcellular localization prediction and experiments confirmed that MdGA2ox7 was located in the cytoplasm. Overexpression of MdGA2ox7 in Arabidopsis caused a lower level of active GA and led to GA-deficient phenotypes, such as dwarfism and delayed flowering. MdGA2ox7 alleviated cold and salt stress damage in both Arabidopsis and apple in concert with melatonin (MT). Additionally, MdGA2ox7 enhanced anthocyanin biosynthesis in apple calli and activated genes involved in anthocyanin synthesis. These findings provide new insights into the functions of apple GA2ox in regulating development, stress tolerance, and secondary metabolism.

9.
Angew Chem Int Ed Engl ; : e202404019, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38622071

ABSTRACT

Accelerating sulfur conversion catalysis to alleviate the shuttle effect has become a novel paradigm for effective Li-S batteries. Although nitrogen-coordinated metal single-atom (M-N4) catalysts have been investigated, further optimizing its utilization rate and catalytic activities is urgently needed for practical applications. Inspired by the natural alveoli tissue with interconnected structure and well-distributed enzyme catalytic sites on the wall for the simultaneously fast diffusion and in situ catalytic conversion of substrates, here, we proposed the controllable synthesis of bioinspired carbon cathode with interconnected porous structure and asymmetric coordinated V-S1N3 sites for efficient and stable Li-S batteries. The enzyme-mimetic V-S1N3 shows asymmetric electronic distribution and high tunability, therefore enhancing in situ polysulfide conversion activities. Experimental and theoretical results reveal that the high charge asymmetry degree and large atom radius of S in V-S1N3 result in sloping adsorption for polysulfide, thereby exhibiting low thermodynamic energy barriers and long-range stability (0.076 % decay over 600 cycles).

10.
Catheter Cardiovasc Interv ; 103(6): 897-908, 2024 May.
Article in English | MEDLINE | ID: mdl-38654635

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) is a frequent and potentially life-threatening complication after percutaneous coronary intervention (PCI) in patients with ST-segment-elevation myocardial infarction (STEMI). However, the relationship between obesity and the risk of AKI in this specific patient population has not been previously examined. METHODS: We queried the National Inpatient Sample (2016-2019) using ICD-10 codes to obtain a sample of adults with STEMI undergoing PCI. All patients were further subcategorized into obese and nonobese cohorts. The primary outcome was the incidence of AKI. Multivariate regression analysis was performed to assess the impact of obesity on AKI. The consistency of this correlation between subgroups was investigated using subgroup analysis and interaction testing. RESULTS: A total of 62,599 (weighted national estimate of 529,016) patients were identified, of which 9.80% (n = 6137) had AKI. Obesity comprised 19.78% (n = 1214) of the AKI cohort. Obese patients were on average younger, male, white, and had more comorbidities. Additionally, there was a significant positive association between obesity and AKI incidence (adjusted odds ratio [aOR]: 1.24, 95% confidence interval [CI]: 1.15-1.34), which was more pronounced in female patients (aOR: 1.56, 95% CI: 1.33-1.82, p < 0.001, p-interaction = 0.008). The AKI incidence in these patients increased steadily during the 4-year study period, and it was consistently higher in obese patients than in nonobese patients (p-trend < 0.001 for all). CONCLUSIONS: Obesity was independently associated with a greater risk of AKI among adults with STEMI undergoing PCI, particularly in female patients.


Subject(s)
Acute Kidney Injury , Databases, Factual , Obesity , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Percutaneous Coronary Intervention/adverse effects , Female , Male , ST Elevation Myocardial Infarction/therapy , ST Elevation Myocardial Infarction/epidemiology , ST Elevation Myocardial Infarction/complications , Acute Kidney Injury/epidemiology , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , Middle Aged , Risk Factors , Obesity/epidemiology , Obesity/complications , United States/epidemiology , Incidence , Aged , Risk Assessment , Treatment Outcome , Time Factors , Retrospective Studies
11.
Article in English | MEDLINE | ID: mdl-38641484

ABSTRACT

BACKGROUND AND OBJECTIVES: The 1 + X certificate system, introduced in China in 2019, integrates academic credentials with vocational skill certificates to meet the heightened demand for skilled talents in the growing economy. This study aims to innovate and evaluate the vocational pharmaceutical education system under the 1 + X certificate framework, specifically addressing the gap between theoretical education and workplace requirements. MATERIALS AND METHODS: A retrospective observational approach analyzed 490 pharmacy students over two academic years. The 2021 cohort underwent 1 + X integrated education, while the 2020 cohort followed conventional education. We collaborated closely with industry partners to identify and compile typical job competencies, formulating work projects aligned with industry demands. Combining the skill level standards and assessment content of "1+X Pharmaceutical Purchasing and Sales" and "1+X Pharmaceutical Preparation", we revised the course standards, incorporating typical work projects into the 2021 pharmacy professional teaching curriculum. This constituted the fundamental content of the 1 + X education reform. Statistical analysis compared course scores and 1 + X certificate examination performance. RESULTS: The 2021 cohort, under the 1 + X educational model, demonstrated higher average scores in pharmacy courses, with significant improvements in pharmacology (1 + X vs. Traditional education: 58.40 ± 14.20 vs. 53.44 ± 14.67), clinical pharmacotherapy (72.74 ± 10.28 vs. 63.15 ± 11.03), and pharmaceutical distribution and marketing (79.34 ± 10.96 vs. 67.50 ± 15.82). 1 + X certificate pass rates and satisfaction with the model were also higher than the 2020 cohort. CONCLUSION: The 1 + X certificate system is useful for developing talent in Chinese vocational education, effectively integrating assessments with industry standards. Future research should aim at evaluating long-term outcomes and improving quantitative skills assessments for enhanced effectiveness.

12.
ACS Appl Mater Interfaces ; 16(15): 18534-18550, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38574189

ABSTRACT

The metastasis and recurrence of cancer are related to immunosuppression and hypoxia in the tumor microenvironment. Activating immune activity and improving the hypoxic environment face essential challenges. This paper reports on a multifunctional nanomaterial, HSCCMBC, that induces immunogenic cell death through powerful photodynamic therapy/chemodynamic therapy synergistic antitumor effects. The tumor microenvironment changed from the immunosuppressive type to immune type, activated the immune activity of the system, decomposed hydrogen peroxide to generate oxygen based on Fenton-like reaction, and effectively increased the level of intracellular O2 with the assistance of 3-bromopyruvate, a cell respiratory inhibitor. The structure and composition of HSCCMBC were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, infrared spectroscopy, etc. Oxygen probe RDPP was used to investigate the oxygen level inside and outside the cell, and hydroxyl radical probe tetramethylbenzidine was used to investigate the Fenton-like reaction ability. The immunofluorescence method investigated the expression of various immune markers and hypoxia-inducing factors in vitro and in vivo after treatment. In vitro and in vivo experiments indicate that HSCCMBC is an excellent antitumor agent and is expected to be a candidate drug for antitumor immunotherapy.


Subject(s)
Nanoparticles , Neoplasms , Humans , Silicon Dioxide/pharmacology , Copper/chemistry , Carbon/pharmacology , Immunogenic Cell Death , Neoplasms/drug therapy , Oxygen/chemistry , Hypoxia , Cell Line, Tumor , Hydrogen Peroxide/chemistry , Tumor Microenvironment , Nanoparticles/chemistry
13.
Medicine (Baltimore) ; 103(15): e37778, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38608115

ABSTRACT

The impact of pulmonary rehabilitation (PR) on patients with different chronic respiratory diseases (CRDs) during hospitalization has not been thoroughly evaluated before. The objectives of the current research were to assess the effect of comprehensive PR management on inpatients' self-management skills, exercise capacity, nutrition assessment and mental health issues and explore whether impacts of PR vary in different CRDs. This retrospective study analyzed the clinical data from 272 inpatients with CRDs receiving PR management during hospitalization between October 2020 and March 2022 in Beijing Chao-Yang Hospital. Significant improvements were found in the patients' ability of daily living (ADL), dyspnea (assessed by modified medical research council dyspnea scale (MMRC)), handgrip strength, maximal inspiratory and expiratory pressure, anxiety (using the 7-item generalized anxiety disorder scale (GAD-7)) and depression (the 9-item patient health questionnaire score (PHQ-9)). There was no significant change in nutrition assessment pre-post PR management during hospitalization. The subgroup analyses were conducted on hospitalized patients with chronic obstructive pulmonary disease (COPD), bronchiectasis, asthma, interstitial lung diseases (ILDs) and other CRDs (e.g., lung cancer, diaphragm hemiparesis, obesity, etc.). The results showed that ADL, MMRC score, MIP, MEP, PHQ-9 score improved in all subgroups with CRDs. Handgrip strength of left hand was increased in COPD inpatients and anxiety was improved in all subgroups except for ILDs. Comprehensive PR management was necessary and beneficial for patients with different CRDs during hospitalization.


Subject(s)
Pulmonary Disease, Chronic Obstructive , Respiration Disorders , Humans , Hand Strength , Retrospective Studies , Hospitalization , Dyspnea
14.
Microorganisms ; 12(4)2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38674717

ABSTRACT

Chitin, a polymer of ß-1,4-linked N-acetylglucosamine (GlcNAc), can be degraded into valuable oligosaccharides by various chitinases. In this study, the genome of Shewanella khirikhana JW44, displaying remarkable chitinolytic activity, was investigated to understand its chitin-degradation potential. A chitinase gene SkChi65 from this strain was then cloned, expressed, and purified to characterize its enzymatic properties and substrate hydrolysis. Genome analysis showed that, of the 14 genes related to chitin utilization in JW44, six belonged to glycoside hydrolase (GH) families because of their functional domains for chitin binding and catalysis. The recombinant chitinase SkChi65, consisting of 1129 amino acids, was identified as a member of the GH18 family and possessed two chitin-binding domains with a typical motif of [A/N]KWWT[N/S/Q] and one catalytic domain with motifs of DxxDxDxE, SxGG, YxR, and [E/D]xx[V/I]. SkChi65 was heterologously expressed as an active protein of 139.95 kDa best at 37 °C with 1.0 mM isopropyl-ß-d-thiogalactopyranoside induction for 6 h. Purified SkChi65 displayed high stability over the ranges of 30-50 °C and pH 5.5-8.0 with optima at 40 °C and pH 7.0. The kinetic parameters Km, Vmax, and kcat of SkChi65 towards colloidal chitin were 27.2 µM, 299.2 µMs-1, and 10,203 s-1, respectively. In addition to colloidal chitin, SkChi65 showed high activity towards glycol chitosan and crystalline chitin. After analysis by thin-layer chromatography, the main products were N,N'-diacetylchitobiose, and GlcNAc with (GlcNAc)2-6 used as substrates. Collectively, SkChi65 could exhibit both exo- and endochitinase activities towards diverse substrates, and strain JW44 has a high potential for industrial application with an excellent capacity for chitin bioconversion.

15.
Sci Rep ; 14(1): 9464, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38658580

ABSTRACT

Aquifer confinement represents a pivotal property that significantly influences the vulnerability and contamination risk of groundwater resources. Several methods have been proposed for determining aquifer confinement by analyzing the response of well water level to Earth tides and atmospheric tides. In this study, we evaluated the performance of the existing single methods and put forward an optimized comprehensive approach. We compared the determination results of the three single methods with those of a comprehensive method using water-level data from 39 earthquake precursor monitoring wells in North China. The results demonstrate that the comprehensive method effectively determined aquifer confinement, significantly reducing the uncertainty associated with the three single methods. The application of the comprehensive method in North China reveals that aquifer confinement may undergo temporal variations during long-term continuous observation, especially in areas where the confining properties of aquifers may vary due to human activities and earthquakes. In such areas, the comprehensive method facilitates accurate assessment of groundwater vulnerability, as well as the potential dispersion of underground pollutants.

16.
Article in English | MEDLINE | ID: mdl-38558145

ABSTRACT

Previous studies about anhedonia symptoms in bipolar depression (BD) ignored the unique role of gender on brain function. This study aims to explore the regional brain neuroimaging features of BD with anhedonia and the sex differences in these patients. The resting-fMRI by applying fractional amplitude of low-frequency fluctuation (fALFF) method was estimated in 263 patients with BD (174 high anhedonia [HA], 89 low anhedonia [LA]) and 213 healthy controls. The effects of two different factors in patients with BD were analyzed using a 3 (group: HA, LA, HC) × 2 (sex: male, female) ANOVA. The fALFF values were higher in the HA group than in the LA group in the right medial cingulate gyrus and supplementary motor area. For the sex-by-group interaction, the fALFF values of the right hippocampus, left medial occipital gyrus, right insula, and bilateral medial cingulate gyrus were significantly higher in HA males than in LA males but not females. These results suggested that the pattern of high activation could be a marker of anhedonia symptoms in BD males, and the sex differences should be considered in future studies of BD with anhedonia symptoms.

17.
Psychol Med ; : 1-10, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38571298

ABSTRACT

BACKGROUND: Extensive research has explored altered structural and functional networks in major depressive disorder (MDD). However, studies examining the relationships between structure and function yielded heterogeneous and inconclusive results. Recent work has suggested that the structure-function relationship is not uniform throughout the brain but varies across different levels of functional hierarchy. This study aims to investigate changes in structure-function couplings (SFC) and their relevance to antidepressant response in MDD from a functional hierarchical perspective. METHODS: We compared regional SFC between individuals with MDD (n = 258) and healthy controls (HC, n = 99) using resting-state functional magnetic resonance imaging and diffusion tensor imaging. We also compared antidepressant non-responders (n = 55) and responders (n = 68, defined by a reduction in depressive severity of >50%). To evaluate variations in altered and response-associated SFC across the functional hierarchy, we ranked significantly different regions by their principal gradient values and assessed patterns of increase or decrease along the gradient axis. The principal gradient value, calculated from 219 healthy individuals in the Human Connectome Project, represents a region's position along the principal gradient axis. RESULTS: Compared to HC, MDD patients exhibited increased SFC in unimodal regions (lower principal gradient) and decreased SFC in transmodal regions (higher principal gradient) (p < 0.001). Responders primarily had higher SFC in unimodal regions and lower SFC in attentional networks (median principal gradient) (p < 0.001). CONCLUSIONS: Our findings reveal opposing SFC alterations in low-level unimodal and high-level transmodal networks, underscoring spatial variability in MDD pathology. Moreover, hierarchy-specific antidepressant effects provide valuable insights into predicting treatment outcomes.

18.
J Dig Dis ; 25(2): 109-122, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38503514

ABSTRACT

OBJECTIVE: We aimed to explore the geographic differences in psychological symptoms, sleep quality, and quality of life (QoL) among adult patients with inflammatory bowel disease (IBD). METHODS: A unified questionnaire was developed to collect data on psychological status and QoL of IBD patients from 42 hospitals across 22 provinces, municipalities, and autonomous regions in China's mainland from September 2021 to May 2022. RESULTS: A total of 2478 patients with IBD were surveyed. The proportions of patients with anxiety (28.5% vs 23.1%), depression (32.3% vs 27.8%), and poor QoL (44.8% vs 32.2%) were significantly higher in patients from the northern region compared to the southern region (all P < 0.05). In the western region, the proportions of patients with anxiety (31.9% vs 23.0%), depression (37.7% vs 26.7%), sleep disturbances (64.5% vs 58.5%), and poor QoL (44.9% vs 34.8%) were significantly higher than in the eastern and central regions (all P < 0.01). Patients from inland regions had significantly higher rates of anxiety (27.1% vs 23.3%), depression (32.5% vs 26.0%), sleep disturbance (62.0% vs 57.7%), and poor QoL (43.5% vs 29.9%) compared to those from coastal regions (all P < 0.05). In economically underdeveloped areas, the proportions of patients with depression (33.1% vs 28.5%) and poor QoL (52.0% vs 32.4%) were significantly higher than in economically (relatively) developed areas (both P < 0.05). CONCLUSION: There are significant geographic differences in psychological symptoms, sleep quality, and QoL among Chinese patients with IBD, which might provide valuable insights for global IBD research and clinical practice.


Subject(s)
Inflammatory Bowel Diseases , Quality of Life , Adult , Humans , Quality of Life/psychology , Sleep Quality , Depression/epidemiology , Depression/etiology , Depression/psychology , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/psychology , Anxiety/epidemiology , Anxiety/etiology , Anxiety/psychology , China/epidemiology
19.
World J Clin Cases ; 12(7): 1356-1364, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38524505

ABSTRACT

BACKGROUND: While most complications of cervical surgery are reversible, some, such as symptomatic postoperative spinal epidural hematoma (SEH), which generally occurs within 24 h, are associated with increased morbidity and mortality. Delayed neurological dysfunction is diagnosed in cases when symptoms present > 3 d postoperatively. Owing to its rarity, the risk factors for delayed neurological dysfunction are unclear. Consequently, this condition can result in irreversible neurological deficits and serious consequences. In this paper, we present a case of postoperative SEH that developed three days after hematoma evacuation. CASE SUMMARY: A 68-year-old man with an American Spinal Injury Association (ASIA) grade C injury was admitted to our hospital with neck pain and tetraplegia following a fall. The C3-C7 posterior laminectomy and the lateral mass screw fixation surgery were performed on the tenth day. Postoperatively, the patient showed no changes in muscle strength or ASIA grade. The patient experienced neck pain and subcutaneous swelling on the third day postoperatively, his muscle strength decreased, and his ASIA score was grade A. Magnetic resonance imaging showed hypointense signals on T1 weighted image (T1WI) and T2WI located behind the epidural space, with spinal cord compression. Emergency surgical intervention for the hematoma was performed 12 h after onset. Although hypoproteinemia and pleural effusion did not improve in the perioperative period, the patient recovered to ASIA grade C on day 30 after surgery, and was transferred to a functional rehabilitation exercise unit. CONCLUSION: This case shows that amelioration of low blood albumin and pleural effusion is an important aspect of the perioperative management of cervical surgery. Surgery to relieve the pressure on the spinal cord should be performed as soon as possible to decrease neurological disabilities.

20.
ACS Appl Mater Interfaces ; 16(13): 16653-16668, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38520338

ABSTRACT

Cancer metastasis and recurrence are closely associated with immunosuppression and a hypoxic tumor microenvironment. Chemodynamic therapy (CDT) and photothermodynamic therapy (PTT) have been shown to induce immunogenic cell death (ICD), effectively inhibiting cancer metastasis and recurrence when combined with immune adjuvants. However, the limited efficacy of Fenton's reaction and suboptimal photothermal effect present significant challenges for successfully inducing ICD through CDT and PTT. This paper described the synthesis and immunoantitumor activity of the novel iron-copper-doped folic acid carbon dots (CFCFB). Copper-doped folic acid carbon dots (Cu-FACDs) were initially synthesized via a hydrothermal method, using folic acid and copper gluconate as precursors. Subsequently, the nanoparticles CFCFB were obtained through cross-linking and self-assembly of Cu-FACDs with ferrocene dicarboxylic acid (FeDA) and 3-bromopyruvic acid (3BP). The catalytic effect of carbon dots in CFCFB enhanced the activity of the Fenton reaction, thereby promoting CDT-induced ICD and increasing the intracellular oxygen concentration. Additionally, 3BP inhibited cellular respiration, further amplifying the oxygen concentration. The photothermal conversion efficiency of CFCFB reached 55.8%, which significantly enhanced its antitumor efficacy through photothermal therapy. Immunofluorescence assay revealed that treatment with CFCFB led to an increased expression of ICD markers, including calreticulin (CRT) and ATP, as well as extracellular release of HMGB-1, indicating the induction of ICD by CFCFB. Moreover, the observed downregulation of ARG1 expression indicates a transition in the tumor microenvironment from an immunosuppressive state to an antitumor state following treatment with CFCFB. The upregulation of IL-2 and CD8 expression facilitated the differentiation of effector T cells, resulting in an augmented population of CD8+ T cells, thereby indicating the activation of systemic immune response.


Subject(s)
Nanoparticles , Neoplasms , Humans , Copper/pharmacology , CD8-Positive T-Lymphocytes , Iron/pharmacology , Carbon/pharmacology , Folic Acid/pharmacology , Neoplasms/drug therapy , Oxygen/pharmacology , Cell Line, Tumor , Tumor Microenvironment , Hydrogen Peroxide
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