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1.
Eur J Pediatr ; 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39093423

ABSTRACT

Mycoplasma pneumoniae pneumonia (MPP) is a common respiratory tract infection disease in children. To date, there have been few studies on the relationship between cytological changes in bronchoalveolar lavage fluid (BALF) and clinical features. The objective of this study is to investigate the correlation between changes in the proportion of cell classifications in BALF and the clinical features in children with severe MPP (SMPP). In total, the study included 64 children with SMPP requiring bronchoalveolar lavage who were admitted to our hospital between March and September 2022 (study group) and 11 children with bronchial foreign bodies without co-infection (control group), who were admitted during the same period. The proportion of cell classifications in BALF was determined by microscopic examination after performing Wright-Giemsa staining. Patients were grouped according to different clinical characteristics, and between-group comparisons were made regarding the variations in the proportion of cell classifications in BALF. The levels of blood routine neutrophil percentage (GRA%), C-reactive protein, D-dimer and lactate dehydrogenase in the study group were higher than those in the control group (P < 0.05). There were differences in the GRA% and macrophage percentage in the BALF between the two groups (P < 0.05). The GRA% and blood lymphocyte percentage were associated with pleural effusion. Multiple indicators correlated with extrapulmonary manifestations (P < 0.05). Moreover, the percentage of lymphocytes in the BALF correlated with pleural effusion, extrapulmonary manifestations and refractory MPP (RMPP) (P < 0.05). Logistic regression showed that BALF lymphocytes were protective factors for RMPP, while serum amyloid A and extrapulmonary manifestations were risk factors (P < 0.05). CONCLUSION: The BALF of children with SMPP is predominantly neutrophilic. A lower percentage of lymphocytes is related to a higher incidence of pleural effusion, extrapulmonary manifestations and progression to RMPP, as well as a longer length of hospitalisation. WHAT IS KNOWN: • Mycoplasma pneumonia in children is relatively common in clinical practice. Bronchoalveolar lavage (BAL) is a routine clinical procedure. WHAT IS NEW: However, there are relatively few studies focusing on the cytomorphological analysis of cells in BAL fluid.

2.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(8): 982-987, 2024 Aug 10.
Article in Chinese | MEDLINE | ID: mdl-39097284

ABSTRACT

OBJECTIVE: To study the molecular basis for a proband with A subtype B of the ABO blood group and explore the influence of amino acid variant on the activity of glycosyltransferase (GT). METHODS: A proband who had presented at the First Affiliated Hospital of Zhengzhou University on July 2, 2020 was selected as the study subject. Serological identification of the ABO blood groups of the proband and her family members were performed by gel card and test tube methods. The ABO gene of the proband was identified by PCR-sequence specific primers (PCR-SSP) and DNA sequencing. A 3D molecular homologous model was constructed to predict the impact of the variant on the stability of α-(1→3)-D-N-acetylgalactosamine transferase (GTA). RESULTS: The red blood cells of the proband, her mother and two younger brothers showed weak agglutination with anti-A and strong agglutination with anti-B. The sera showed 1~2+ agglutination with Ac and no agglutination with Bc. Based on the serological characteristics, the proband was identified as AwB subtype. Pedigree analysis suggested that the variant was inherited from her mother. The blood group of the proband was identified as A223B type by PCR-SSP. ABO gene sequencing analysis showed that the proband has harbored heterozygous variants of c.297A>G, c.467C>T, c.526C>G, c.657C>T, c.703G>A, c.796C>A, c.803G>C, c.930G>A and c.1055insA. Based on the results of clone sequencing, it was speculated that the genotype was ABO*A223/ABO*B.01. There were c.467C>T and c.1055insA variants compared with ABO*A1.01, and c.1055insA variant compared with ABO*A1.02. Homologous modeling showed that the C-terminal of A223 GT was significantly prolonged, and the local amino acids and hydrogen bond network have changed. CONCLUSION: Above results revealed the molecular genetics mechanism of A223B subtype. The c.1055insA variant carried by the proband may affect the enzymatic activity of GTA and ultimately lead to weakening of A antigen.


Subject(s)
ABO Blood-Group System , Pedigree , Humans , ABO Blood-Group System/genetics , Female , Male , Adult , N-Acetylgalactosaminyltransferases/genetics , Genotype , Blood Grouping and Crossmatching
3.
Hell J Nucl Med ; 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39097808

ABSTRACT

Fibroblast activation protein inhibitor (FAPI) positron emission tomography/computed tomography (PET/CT) is a multimodal imaging technique that combines PET and CT, utilizing FAP inhibitors as radiotracers. Fibroblast activation protein, a serine protease highly expressed in many epithelial tumor-associated fibroblasts, plays a crucial role in tumor stroma formation and remodeling. Through the detection of FAP expression, FAPI PET/CT facilitates the diagnosis and staging of both benign and malignant pulmonary tumors. In contrast to traditional fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT focusing on glucose metabolism, FAPI PET/CT offers benefits such as enhanced specificity, reduced background noise, accelerated imaging speed, and decreased radiation exposure. This review provides an overview of the progress in applying FAPI PET/CT and 18F-FDG PET/CT in pulmonary malignancies and discusses current challenges and future prospects.

4.
Int J Cardiol ; 415: 132446, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39147279
5.
Chem Sci ; 15(32): 12889-12899, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39148796

ABSTRACT

The capsular polysaccharide (CPS) is a major virulence factor of the pathogenic Acinetobacter baumannii and a promising target for vaccine development. However, the synthesis of the 1,2-cis-2-amino-2-deoxyglycoside core of CPS remains challenging to date. Here we develop a highly α-selective ZnI2-mediated 1,2-cis 2-azido-2-deoxy chemical glycosylation strategy using 2-azido-2-deoxy glucosyl donors equipped with various 4,6-O-tethered groups. Among them the tetraisopropyldisiloxane (TIPDS)-protected 2-azido-2-deoxy-d-glucosyl donor afforded predominantly α-glycoside (α : ß = >20 : 1) in maximum yield. This novel approach applies to a wide acceptor substrate scope, including various aliphatic alcohols, sugar alcohols, and natural products. We demonstrated the versatility and effectiveness of this strategy by the synthesis of A. baumannii K48 capsular pentasaccharide repeating fragments, employing the developed reaction as the key step for constructing the 1,2-cis 2-azido-2-deoxy glycosidic linkage. The reaction mechanism was explored with combined experimental variable-temperature NMR (VT-NMR) studies and mass spectroscopy (MS) analysis, and theoretical density functional theory calculations, which suggested the formation of covalent α-C1GlcN-iodide intermediate in equilibrium with separated oxocarbenium-counter ion pair, followed by an SN1-like α-nucleophilic attack most likely from separated ion pairs by the ZnI2-activated acceptor complex under the influence of the 2-azido gauche effect.

6.
Drug Test Anal ; 2024 Aug 17.
Article in English | MEDLINE | ID: mdl-39152891

ABSTRACT

The effective implementation of drug precursor legislation has driven the innovation and design of new alternative substances. The application of 1,3-dicarbonyl precursors as alternative precursors for the synthesis of 1-phenyl-2-propanone (P2P) and 3,4-methylenedioxyphenyl-2-propanone (MDP2P) has created new challenges to legal control. Their 1,3-dicarbonyl structure allows the precursors to exist as an equilibrium mixture of the tautomeric diketo and keto-enolic forms during the nuclear magnetic resonance (NMR) analysis. In this study, the keto-enol tautomerism of four 1,3-dicarbonyl drug pre-precursors, α-phenylacetoacetamide (APAA), methyl α-phenylacetoacetate (MAPA), ethyl α-phenylacetoacetate (EAPA), and methyl 2-(benzo[d][1,3]dioxol-5-yl)-3-oxobutanoate (MAMDPA) were investigated through NMR. One-dimensional (1D) and 2D NMR were combined to assign signals for the diketo and keto-enolic tautomers. Results showed that the keto-enol tautomerism was solvent-dependent but was also influenced by the substituent present in the molecule. Further, the analysis results indicated that majority of substances existed mainly in the diketo form. The enol-keto equilibrium constant (Keq) was stable in dimethyl sulfoxide-d6 and chloroform-d, while unstable for some compounds in acetone-d6 and deuterated methanol. The presence of impurities in the seized sample may disrupt the equilibrium between keto-enol tautomers in 1,3-dicarbonyl precursors. After the optimization of several key quantitative parameters, a quantitative NMR method for the quantification of 1,3-dicarbonyl drug precursors were also developed to facilitate their quantitative analysis. This is the first study to investigate the keto-enol tautomerism and quantification of 1,3-dicarbonyl drug precursors by NMR, providing a new approach for structure analysis and quantification of new precursor analogues.

7.
PeerJ ; 12: e17838, 2024.
Article in English | MEDLINE | ID: mdl-39157771

ABSTRACT

Purpose: The aim of this study was to identify factors associated with difficult video laryngoscopy in obese patients. Methods: A total of 579 obese patients undergoing elective laparoscopic weight loss surgery were intubated with a single-lumen endotracheal tube using a video laryngoscopy under general anesthesia, and the patients were divided into two groups based on the Cormack-Lehane classification (difficult video laryngoscopy defined as ≥ 3): the easy video laryngoscopy group and the difficult video laryngoscopy group. Record the general condition of the patient, bedside testing indicators related to the airway, Cormack-Lehane classification during intubation, and intubation failure rate. Results: The findings of this study show that the incidence of difficult video laryngoscopy in obese patients is 4.8%. Multivariate logistic regression analysis indicated that body mass index was significantly associated with difficult video laryngoscopy (OR = 1.082, 95% CI [1.033-1.132], P < 0.001). Conclusion: For Chinese obese patients without known difficult airways, the incidence of difficult video laryngoscopy is 4.8%. Body mass index is associated factors for the occurrence of difficult video laryngoscopy, with an increased risk observed as body mass index rise.


Subject(s)
Body Mass Index , Intubation, Intratracheal , Laryngoscopy , Obesity , Humans , Laryngoscopy/methods , Laryngoscopy/adverse effects , Male , Female , Prospective Studies , Obesity/surgery , Intubation, Intratracheal/methods , Intubation, Intratracheal/adverse effects , Middle Aged , Adult , China/epidemiology , Laparoscopy/methods , Risk Factors , Preoperative Care/methods , Video Recording , Anesthesia, General
8.
PLoS One ; 19(8): e0308343, 2024.
Article in English | MEDLINE | ID: mdl-39110699

ABSTRACT

BACKGROUND: Metabolic score for insulin resistance (METS-IR) is a surrogate index to estimate insulin sensitivity. The aim of this study was to examine the association between METS-IR and regression to normoglycemia in Chinese adults with prediabetes. METHODS: A total of 15,415 Chinese adults with prediabetes defined by their fasting blood glucose were included in this retrospective study. The association between METS-IR and regression to normoglycemia from prediabetes was evaluated using the Cox proportional hazards regression model. A Cox proportional hazards regression with cubic spline function was performed to explore the nonlinear association between METS-IR and regression to normoglycemia. Kaplan-Meier curves was used to describe the probability of regression to normoglycemia from prediabetes. RESULTS: In multivariate Cox proportional hazards regression analyses, the increase in METS-IR was independently associated with a reduced probability of regression to normoglycemia from prediabetes (all p < 0.01 in models 1-3). A nonlinear association between METS-IR and the probability of regression to normoglycemia was observed, with an inflection point of 49.3. The hazard ratio on the left side of the inflection point was 0.965 (95% CI 0.953-0.976). Subgroup analyses demonstrated the robustness of our findings. CONCLUSION: This study demonstrated a negative and nonlinear association between METS-IR and regression to normoglycemia in Chinese adults with prediabetes. When METS-IR is below 49.3, reducing METS-IR could significantly increase the probability of regression to normoglycemia from prediabetes.


Subject(s)
Blood Glucose , Insulin Resistance , Prediabetic State , Humans , Prediabetic State/epidemiology , Prediabetic State/metabolism , Male , Female , Retrospective Studies , Middle Aged , Adult , Blood Glucose/metabolism , Blood Glucose/analysis , China/epidemiology , Proportional Hazards Models , Aged , Asian People , East Asian People
9.
Zhongguo Zhong Yao Za Zhi ; 49(14): 3887-3893, 2024 Jul.
Article in Chinese | MEDLINE | ID: mdl-39099362

ABSTRACT

In this study, a mouse model of premature ovarian failure(POF) was constructed by injecting D-galactose(200 mg·kg~(-1)) into the back of the neck for 6 weeks. The mice were randomly divided into a normal group(group N), a model group(group M), and a Qiwei Guibao Granules group(group A, 12.87 g·kg~(-1)). Starting from the 11th day of modeling, group A was treated with Qiwei Guibao Granules by gavage for 32 days, while group M and group N were given equal volume of saline. Metabolomics analysis was used to explore the mechanism of action of Qiwei Guibao Granules in the treatment of POF. The results showed that compared with group N, the group M exhibited decreased wet weight of bilateral ovaries, increased levels of LH and FSH in serum, and significantly decreased levels of E_2 and PROG. After treatment with Qiwei Guibao Granules, compared with the group M, the group A showed a significant increase in the wet weight of bilateral ovaries, a significant decrease in the levels of FSH and LH in serum, and a significant increase in the level of E_2. Metabolomics analysis revealed 55 differential metabolites identified between group N and group M(14 upregulated and 41 downregulated compared with group N) and 82 differential metabolites identified between group M and group A(56 upregulated and 26 downregulated compared with group M), with 5 metabolites showing consistent changes between the group N vs group M. After excluding these 5 metabolites, 77 metabolites that changed after intervention with Qiwei Guibao Granules were focused on. These mainly involved histidine metabolism, glycine, serine, and threonine metabolism, and glycerophospholipid metabolism. Among them, carnosine, 1-methyl-L-histidine, imidazoleacetic acid, choline, L-threonine, beta-hydroxypyruvic acid, phosphatidylcholine, and glycerol-3-phosphate were the major differential metabolites in these three metabolic pathways. Therefore, Qiwei Guibao Granules may exert therapeutic effects on POF mice by regulating amino acid metabolism and lipid metabolism in the mouse body.


Subject(s)
Drugs, Chinese Herbal , Metabolomics , Primary Ovarian Insufficiency , Animals , Female , Primary Ovarian Insufficiency/drug therapy , Primary Ovarian Insufficiency/metabolism , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/pharmacology , Mice , Humans , Ovary/drug effects , Ovary/metabolism , Disease Models, Animal
10.
Sci Rep ; 14(1): 18588, 2024 08 10.
Article in English | MEDLINE | ID: mdl-39127740

ABSTRACT

True morels (Morchella) are globally renowned medicinal and edible mushrooms. White mold disease caused by fungi is the main disease of Morchella, which has the characteristics of wide incidence and strong destructiveness. The disparities observed in the isolation rates of different pathogens indicate their varying degrees of host adaptability and competitive survival abilities. In order to elucidate its potential mechanism, this study, the pathogen of white mold disease from Dafang county, Guizhou Province was isolated and purified, identified as Pseudodiploöspora longispora by morphological, molecular biological and pathogenicity tests. Furthermore, high-quality genome of P. longisporus (40.846 Mb) was assembled N50 of 3.09 Mb, predicts 7381 protein-coding genes. Phylogenetic analysis of single-copy homologous genes showed that P. longispora and Zelopaecilomyces penicillatus have the closest evolutionary relationship, diverging into two branches approximately 50 (44.3-61.4) MYA. Additionally, compared with the other two pathogens causing Morchella disease, Z. penicillatus and Cladobotryum protrusum, it was found that they had similar proportions of carbohydrate enzyme types and encoded abundant cell wall degrading enzymes, such as chitinase and glucanase, indicating their important role in disease development. Moreover, the secondary metabolite gene clusters of P. longispora and Z. penicillatus show a high degree of similarity to leucinostatin A and leucinostatin B (peptaibols). Furthermore, a gene cluster with synthetic toxic substance Ochratoxin A was also identified in P. longispora and C. protrusum, indicating that they may pose a potential threat to food safety. This study provides valuable insights into the genome of P. longispora, contributing to pathogenicity research.


Subject(s)
Genome, Fungal , Genomics , Phylogeny , Genomics/methods , Ascomycota/genetics , Ascomycota/pathogenicity , Ascomycota/isolation & purification , Evolution, Molecular , Fungal Proteins/genetics
11.
Biomed Chromatogr ; : e5969, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-39126348

ABSTRACT

This study aimed to explore the pharmacodynamics and mechanisms of different processing methods of Ligustrum lucidum Ait. (LLA) in addressing kidney-yin deficiency (KYD). Forty-eight Sprague-Dawley rats were divided into eight groups based on their weight. The KYD model was established by intragastric administration of levothyroxine sodium. Each group was administered the corresponding treatment for 15 consecutive days. The general condition of the rats during the treatment period was observed. In addition, the levels of cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), and the ratio of cAMP to cGMP in the serum of rats from different groups were measured. Serum samples were analyzed using the ultra-performance liquid chromatography (UPLC)-Orbitrap Fusion MS technique for metabolomics analysis. Compared with the model group, the general condition of the rats in the wine-steamed L. lucidum group (WL) and salt-steamed L. lucidum group (SSL) groups showed significant improvement. The serum levels of cAMP, cGMP, and the cAMP-to-cGMP ratio tended to return to normal. Metabolic analysis identified 38 relevant biomarkers and revealed 3 major metabolic pathways: phenylalanine, tyrosine, and tryptophan biosynthesis; phenylalanine metabolism; and sphingolipid metabolism. The different processing methods of LLA demonstrated therapeutic effects on KYD in rats, likely related to the restoration of disturbed metabolism by adjusting the levels of endogenous metabolites in the kidney. The SSL demonstrated significantly superior effects compared with the other four types of LLA processed products.

12.
RSC Adv ; 14(33): 24165-24174, 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39101063

ABSTRACT

Hyperuricemia, characterized by elevated uric acid levels and subsequent crystal deposition, contributing to conditions such as gout, cardiovascular events, and kidney injury, poses a significant health threat, particularly in developed countries. Current drug options for treatment are limited, with safety concerns, leading to suboptimal therapeutic outcomes in symptomatic hyperuricemia patients and a lack of pharmaceutical interventions for asymptomatic cases. Distinguishing from the previous drug design strategies, we directly target uric acid, the pathological molecule of hyperuricemia, resulting in a pyrimidine derivative capable of increasing the solubility and excretion of uric acid by forming a complex with it. Its prodrug showed an anti-hyperuricemia activity comparable to benzbromarone and a favorable safety profile in vivo. Our finding provides a strategy purely based on organic chemistry to address the largely unmet therapeutic needs on novel anti-hyperuricemia drugs.

13.
Polymers (Basel) ; 16(15)2024 Jul 28.
Article in English | MEDLINE | ID: mdl-39125171

ABSTRACT

Human physical activity monitoring plays a crucial role in promoting personalized health management. In this work, inspired by an ancient Chinese belt, a belt-type wearable sensor (BWS) based on a triboelectric nanogenerator (TENG) is presented to monitor daily movements and collect the body motion mechanical energy. The developed BWS consists of a soft silicone sheet and systematically connected sensing units made from triboelectric polymer materials including polytetrafluoroethylene (PTFE) and polyamide (PA). A parameter study of the sensing units is firstly conducted to optimize the structure of BWS. The experimental studies indicate that the parameter-optimized BWS unit achieves a maximum output voltage of 47 V and a maximum current of 0.17 µA. A BWS with five sensing units is manufactured to record body movements, and it is able to distinguish different physical activities including stillness, walking, running, jumping, normal breathing, cessation of breathing, and deep breathing. In addition, the developed BWS successfully powers electronic devices including a smartphone, digital watch, and LED lights. We hope this work provides a new strategy for the development of wearable self-powered intelligent devices.

14.
Phytother Res ; 38(8): 4151-4167, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39136618

ABSTRACT

Despite active clinical trials on the use of Oleandrin alone or in combination with other drugs for the treatment of solid tumors, the potential synergistic effect of Oleandrin with radiotherapy remains unknown. This study reveals a new mechanism by which Oleandrin targets ATM and ATR kinase-mediated radiosensitization in lung cancer. Various assays, including clonogenic, Comet, immunofluorescence staining, apoptosis and Cell cycle assays, were conducted to evaluate the impact of oleandrin on radiation-induced double-strand break repair and cell cycle distribution. Western blot analysis was utilized to investigate alterations in signal transduction pathways related to double-strand break repair. The efficacy and toxicity of the combined therapy were assessed in a preclinical xenotransplantation model. Functionally, Oleandrin weakens the DNA damage repair ability and enhances the radiation sensitivity of lung cells. Mechanistically, Oleandrin inhibits ATM and ATR kinase activities, blocking the transmission of ATM-CHK2 and ATR-CHK1 cell cycle checkpoint signaling axes. This accelerates the passage of tumor cells through the G2 phase after radiotherapy, substantially facilitating the rapid entry of large numbers of inadequately repaired cells into mitosis and ultimately triggering mitotic catastrophe. The combined treatment of Oleandrin and radiotherapy demonstrated superior inhibition of tumor proliferation compared to either treatment alone. Our findings highlight Oleandrin as a novel and effective inhibitor of ATM and ATR kinase, offering new possibilities for the development of clinical radiosensitizing adjuvants.


Subject(s)
Ataxia Telangiectasia Mutated Proteins , Cardenolides , DNA Damage , Lung Neoplasms , Ataxia Telangiectasia Mutated Proteins/metabolism , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/radiotherapy , Animals , Cardenolides/pharmacology , DNA Damage/drug effects , Cell Line, Tumor , Mice , Radiation Tolerance/drug effects , Signal Transduction/drug effects , Apoptosis/drug effects , Radiation-Sensitizing Agents/pharmacology , Mice, Nude , Xenograft Model Antitumor Assays , DNA Repair/drug effects , Cell Proliferation/drug effects , A549 Cells
15.
Alzheimers Res Ther ; 16(1): 179, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-39127661

ABSTRACT

BACKGROUND: Microglial activation has been suggested to be involved in the pathogenesis of depression and Alzheimer's disease (AD). Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is a marker of microglial activation. The purpose of this study was to investigate the interrelationships of cerebrospinal fluid (CSF) sTREM2, AD pathology, as well as minimal depressive symptoms (MDSs), and cognition. METHODS: A total of 545 non-demented individuals from the Alzheimer's Disease Neuroimaging Initiative cohort were included in our study. The average age of the total population was 72.6 years and the percentage of females was 42.6%. Linear regression models were conducted to investigate the linear relationships of MDSs with CSF sTREM2, AD pathology, cognition, and brain structure. Mediation models and structural equation models (SEM) were conducted to examine whether CSF sTREM2 mediated the relationships of MDSs with AD pathology and cognition. RESULTS: Results revealed that individuals with MDSs had lower CSF sTREM2 levels than normal controls. Linear regression showed that MDSs were linearly associated with CSF sTREM2 (PFDR = 0.012) and amyloid biomarkers (PFDR < 0.05), as well as cognitive scores (PFDR < 0.05) and hippocampal volume (PFDR = 0.003). Mediation analyses revealed that CSF sTREM2 mediated the association between MDSs and amyloid pathology, with the mediating proportions ranging from 6.030 to 18.894%. However, SEM failed to reveal that MDS affected cognition through CSF amyloid pathology and CSF sTREM2. CONCLUSIONS: MDSs are associated with amyloid pathology and cognition. CSF sTREM2 may potentially be an intervenable target between depression and AD pathology.


Subject(s)
Alzheimer Disease , Depression , Membrane Glycoproteins , Receptors, Immunologic , Humans , Female , Male , Membrane Glycoproteins/cerebrospinal fluid , Aged , Alzheimer Disease/cerebrospinal fluid , Alzheimer Disease/pathology , Depression/cerebrospinal fluid , Biomarkers/cerebrospinal fluid , Cognition/physiology , Aged, 80 and over , Cohort Studies , Brain/pathology , Brain/diagnostic imaging , Amyloid beta-Peptides/cerebrospinal fluid , Middle Aged
16.
Neuropharmacology ; 259: 110115, 2024 Aug 11.
Article in English | MEDLINE | ID: mdl-39137872

ABSTRACT

Immune cells and interleukins play a crucial role in female-specific pain signaling. Interleukin 16 (IL-16) is a cytokine primarily associated with CD4+ T cell function. While previous studies have demonstrated the important role of spinal CD4+ T cells in neuropathic pain, the specific contribution of IL-16 to neuropathic pain remains unclear. In this study, by using a spinal nerve ligation (SNL)-induced neuropathic pain mice model, we found that SNL induced an increase in IL-16 mRNA levels, which persisted for a longer duration in female mice compared to male mice. Immunofluorescence analysis further confirmed enhanced IL-16- and CD4-positive signals in the spinal dorsal horn following SNL surgery in female mice. Knockdown of spinal IL-16 by siRNA or inhibition of CD4 by FGF22-IN-1, a CD4 inhibitor, attenuated established mechanical and thermal pain hypersensitivity induced by SNL. Furthermore, female mice injected with IL-16 intrathecally exhibited significant spontaneous pain, mechanical and thermal hyperalgesia, all of which could be alleviated by FGF22-IN-1 or a CD3 antibody. Additionally, IL-16 induced astrocyte activation but not microglial activation in the spinal dorsal horn of female mice. Meanwhile, astrocyte activation could be suppressed by the CD3 antibody. These results provide compelling evidence that IL-16 promotes astrocyte activation via CD4 on CD3+ T cells, which is critical for maintaining neuropathic pain in female mice.

17.
Talanta ; 280: 126713, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39167936

ABSTRACT

Metal-organic frameworks (MOFs) hold great promise as advanced chemical sensing materials due to their high surface area and tunable surface chemistry. However, due to the inherent conductivity, building a highly sensitive MOFs-based gas sensor for real-time monitoring hazardous gas operated at room temperature (RT) is still a huge challenge. Herein, an in-situ anchoring strategy is proposed to construct a 1D-0D core-shell heterostructure by integrating silver nanowires (AgNWs) with highly conductivity and Zn-MOF with high specific surface area. The incorporation of AgNWs establishes a highly conductive network architecture to facilitate rapid charge transport while preventing the Zn-MOF nanoparticles from agglomeration, ensuring an effective transmission highway for target gas molecules. Meanwhile, the Zn-MOF nanoparticles induce remarkable absorption capacity and contribute high gas response. By strategically amalgamating the inherent distinctive virtues of the individual components and capitalizing on the synergistic benefits arising from the composite, the sensors hinged upon the refined AgNWs@Zn-MOF (A@Z) heterostructure unveiled remarkable response value of 27 to 20 ppm ethanol at RT, accompanied by a low detection limit of 1 ppm. Moreover, the A@Z sensor further showcases superior selectivity and repeatability. This work offers a fresh standpoint for the fabrication of MOF-based heterostructures, fostering advancements in diverse applications.

18.
Nat Prod Bioprospect ; 14(1): 48, 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39158647

ABSTRACT

Recently the FDA conducted a risk investigation and labeled the Boxed Warning for all BCMA- and CD19-directed CAR-T cell therapy, so does it mean that the public must take risk of secondary cancer to receive cell therapy? Here, without lentivirus and professional antigen presenting cell application, a novel tumor-specific T-cell therapy was successfully developed only by co-culturing MHC+ cancer cells and Naïve-T cells under the CD28 co-stimulatory signals. These tumor-specific T-cells could be separated through cell size and abundantly produced from peripheral blood, and would spontaneously attack target cells that carrying the same tumor antigen while avoiding others in vitro test. Moreover, it markedly decreased 90% tumor nodules companying with greatly improving overall survival (76 days vs 30 days) after twice infusion back to mice. This work maximally avoided the risks of secondary cancer and non-specific killing, and might open a revolutionary beginning of natural tumor-specific T-cell therapy.

19.
Chem Sci ; 15(32): 12957-12963, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39148766

ABSTRACT

Concurrent near-infrared-II (NIR-II) fluorescence imaging (FLI) and photoacoustic imaging (PAI) holds tremendous potential for effective disease diagnosis owing to their combined benefits and complementary features, in particular on the basis of a single molecule. However, the simultaneous guarantee of high-quality NIR-II FLI and PAI is recognized to be challenging impeded by the competitive photophysical processes at the molecular level. Herein, a simple organic fluorophore, namely T-NSD, is finely engineered with facile synthetic procedures through delicately modulating the rigidity and electron-withdrawing ability of the molecular acceptor. The notable advantages of fabricated T-NSD nanoparticles include a large Stokes shift, intense fluorescence emission in the NIR-II region, and anti-quenching properties in the aggregated states, which eventually enable the implementation of dual-modal NIR-II FLI/PAI in a 4T1 tumor-xenografted mouse model with reliable performance and good biocompatibility. Overall, these findings present a simple strategy for the construction of NIR-II optical agents to allow multimodal disease diagnosis.

20.
ACS Nano ; 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39146501

ABSTRACT

As a host for exchange bias (EB), van der Waals (vdW) magnetic materials have exhibited intriguing and distinct functionalities from conventional magnetic materials. The EB in most vdW systems is far below room temperature, which poses a challenge for practical applications. Here, by using Kerr microscopy, we demonstrate a record-high blocking temperature that approaches room temperature and a huge positive EB field that nears 2 kOe at 100 K in naturally oxidized two-dimensional (2D) vdW ferromagnetic Fe3GaTe2 nanoflakes. Moreover, we realized a reversible manipulation of both the presence/absence and positive/negative signs of EB via a training magnetic field without multiple field cooling processes. Thus, our study clearly reveals the robust, sizable, and sign-tunable EB in vdW magnetic materials up to near room temperature, thereby establishing Fe3GaTe2 as an emerging room-temperature-operating vdW material and paving the way for designing practical 2D spintronic devices.

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