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1.
Oncoimmunology ; 13(1): 2373530, 2024.
Article in English | MEDLINE | ID: mdl-38979545

ABSTRACT

TCRαß+ CD4- CD8- double-negative T (DNT) cells are minor populations in peripheral blood, and their roles have mostly been discussed in inflammation and autoimmunity. However, the functions of DNT cells in tumor microenvironment remain to be elucidated. We investigated their characteristics, possible origins and functions in colorectal cancer tissues as well as their corresponding tumor-draining lymph nodes. We found a significant enrichment of DNT cells in tumor tissues compared with their corresponding lymph nodes, especially in tumors with lower T cell infiltration. T cell receptor (TCR) sequence analysis of CD4+ T, CD8+ T and DNT cells indicated that TCR sequences detected in DNT cells were found in CD8+ T cells, but rarely in CD4+ T cells, suggesting that a part of DNT cells was likely to be originated from CD8+ T cells. Through a single-cell transcriptomic analysis of DNT cells, we found that a DNT cell cluster, which showed similar phenotypes to central memory CD8+ T cells with low expression of effector and exhaustion markers, revealed some specific gene expression patterns, including higher GZMK expression. Moreover, in flow cytometry analysis, we found that DNT cells lost production of cytotoxic mediators. These findings imply that DNT cells might function as negative regulators of anti-tumor immune responses in tumor microenvironment.


Subject(s)
Colorectal Neoplasms , Lymph Nodes , Tumor Microenvironment , Humans , Colorectal Neoplasms/immunology , Colorectal Neoplasms/pathology , Lymph Nodes/immunology , Lymph Nodes/pathology , Tumor Microenvironment/immunology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Male , Female , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Aged , Receptors, Antigen, T-Cell/metabolism , Receptors, Antigen, T-Cell/genetics , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Middle Aged
3.
Front Psychol ; 15: 1340769, 2024.
Article in English | MEDLINE | ID: mdl-38962223

ABSTRACT

Introduction: Ethical voice is a valuable ethical behavior that enables organizations to promptly recognize and rectify unethical issues and practices, thus preventing severe dilemmas and crises. Despite its importance, the extant literature has yet to fully explore the impact of a leader's ethical voice on subordinate outcomes. This study bridges this gap by integrating social identity theory and social exchange theory to scrutinize the process by which a leader's ethical voice affects subordinate task performance. Methods: We employ a serial mediation model to explore the mechanisms by which a leader's ethical voice enhances subordinates' task performance. Our theoretical framework is empirically validated using a dataset that includes 449 subordinate-leader pairings from Chinese enterprises. Results: The survey results demonstrate that a leader's ethical voice has a significant positive impact on subordinate task performance. Subordinate identification with leader and leader-member exchange not only individually mediate the effects of a leader's ethical voice on subordinate task behavior but also jointly serve as a chain-mediated mechanism in the influence of a leader's ethical voice on subordinate task behavior. Discussion: These findings illuminate the substantial effects that ethical leadership behaviors exert on employee performance and offer fresh perspectives on the intricate dynamics that govern this influence.

4.
Elife ; 122024 Jul 04.
Article in English | MEDLINE | ID: mdl-38963411

ABSTRACT

Precise developmental timing control is essential for organism formation and function, but its mechanisms are unclear. In C. elegans, the microRNA lin-4 critically regulates developmental timing by post-transcriptionally downregulating the larval-stage-fate controller LIN-14. However, the mechanisms triggering the activation of lin-4 expression toward the end of the first larval stage remain unknown. We demonstrate that the transmembrane transcription factor MYRF-1 is necessary for lin-4 activation. MYRF-1 is initially localized on the cell membrane, and its increased cleavage and nuclear accumulation coincide with lin-4 expression timing. MYRF-1 regulates lin-4 expression cell-autonomously and hyperactive MYRF-1 can prematurely drive lin-4 expression in embryos and young first-stage larvae. The tandem lin-4 promoter DNA recruits MYRF-1GFP to form visible loci in the nucleus, suggesting that MYRF-1 directly binds to the lin-4 promoter. Our findings identify a crucial link in understanding developmental timing regulation and establish MYRF-1 as a key regulator of lin-4 expression.


Subject(s)
Caenorhabditis elegans Proteins , Caenorhabditis elegans , Gene Expression Regulation, Developmental , MicroRNAs , Transcription Factors , Caenorhabditis elegans/genetics , Caenorhabditis elegans/metabolism , Caenorhabditis elegans/growth & development , Animals , Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans Proteins/genetics , MicroRNAs/metabolism , MicroRNAs/genetics , Transcription Factors/metabolism , Transcription Factors/genetics , Promoter Regions, Genetic , Transcription, Genetic , Membrane Proteins/metabolism , Membrane Proteins/genetics , Cell Nucleus/metabolism
5.
Ann Hematol ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38955826

ABSTRACT

We aimed to evaluate if circulating plasma cells (CPC) detected by flow cytometry could add prognostic value of R2-ISS staging. We collected the electronic medical records of 336 newly diagnosed MM patients (NDMM) in our hospital from January 2017 to June 2023. The median overall survival (OS) for patients and R2-ISS stage I-IV were not reached (NR), NR, 58 months and 53 months, respectively. There was no significant difference in OS between patients with stage I and patients with stage II (P = 0.309) or between patients with stage III and patients with stage IV (P = 0.391). All the cases were re-classified according to R2-ISS stage and CPC numbers ≥ 0.05% (CPC high) or<0.05% (CPC low) into four new risk groups: Group 1: R2-ISS stage I + R2-ISS stage II and CPC low, Group 2: R2-ISS stage II and CPC high + R2-ISS stage III and CPC low, Group 3: R2-ISS stage III and CPC high + R2-ISS stage IV and CPC low, Group 4: R2-ISS stage IV and CPC high. The median OS were NR, NR, 57 months and 32 months. OS of Group 1 was significantly longer than that of Group 2 (P = 0.033). OS in Group 2 was significantly longer than that of Group 3 (P = 0.007). OS in Group 3 was significantly longer than that of Group 4 (P = 0.041). R2-ISS staging combined with CPC can improve risk stratification for NDMM patients.

6.
Neurosci Bull ; 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38907786

ABSTRACT

Autism Spectrum Disorders (ASDs) are reported as a group of neurodevelopmental disorders. The structural changes of brain regions including the hippocampus were widely reported in autistic patients and mouse models with dysfunction of ASD risk genes, but the underlying mechanisms are not fully understood. Here, we report that deletion of Trio, a high-susceptibility gene of ASDs, causes a postnatal dentate gyrus (DG) hypoplasia with a zigzagged suprapyramidal blade, and the Trio-deficient mice display autism-like behaviors. The impaired morphogenesis of DG is mainly caused by disturbing the postnatal distribution of postmitotic granule cells (GCs), which further results in a migration deficit of neural progenitors. Furthermore, we reveal that Trio plays different roles in various excitatory neural cells by spatial transcriptomic sequencing, especially the role of regulating the migration of postmitotic GCs. In summary, our findings provide evidence of cellular mechanisms that Trio is involved in postnatal DG morphogenesis.

7.
Molecules ; 29(11)2024 May 28.
Article in English | MEDLINE | ID: mdl-38893417

ABSTRACT

A nanocomposite of multi-walled carbon nanotubes (MWCNTs) decorated with molybdenum dioxide (MoO2) nanoparticles is fabricated through the reduction of phosphomolybdic acid hydrate on functionalized MWCNTs in a hydrogen-argon (10%) atmosphere in a tube furnace. The MoO2/MWCNTs composite is proposed as an anodic modification material for microbial fuel cells (MFCs). MWCNTs have outstanding physical and chemical peculiarities, with functionalized MWCNTs having substantially large electroactive areas. In addition, combined with the exceptional properties of MoO2 nanoparticles, the synergistic advantages of functionalized MWCNTs and MoO2 nanoparticles give a MoO2/MWCNTs anode a large electroactive area, excellent electronic conductivity, enhanced extracellular electron transfer capacity, and improved nutrient transfer capability. Finally, the power harvesting of an MFC with the MoO2/MWCNTs anode is improved, with the MFC showing long-term repeatability of voltage and current density outputs. This exploratory research advances the fundamental application of anodic modification to MFCs, simultaneously providing valuable guidance for the use of carbon-based transition metal oxide nanomaterials in high-performance MFCs.

8.
Lancet Infect Dis ; 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38878787

ABSTRACT

Avian influenza virus continues to pose zoonotic, epizootic, and pandemic threats worldwide, as exemplified by the 2020-23 epizootics of re-emerging H5 genotype avian influenza viruses among birds and mammals and the fatal jump to humans of emerging A(H3N8) in early 2023. Future influenza pandemic threats are driven by extensive mutations and reassortments of avian influenza viruses rooted in frequent interspecies transmission and genetic mixing and underscore the urgent need for more effective actions. We examine the changing global epidemiology of human infections caused by avian influenza viruses over the past decade, including dramatic increases in both the number of reported infections in humans and the spectrum of avian influenza virus subtypes that have jumped to humans. We also discuss the use of advanced surveillance, diagnostic technologies, and state-of-the-art analysis methods for tracking emerging avian influenza viruses. We outline an avian influenza virus-specific application of the One Health approach, integrating enhanced surveillance, tightened biosecurity, targeted vaccination, timely precautions, and timely clinical management, and fostering global collaboration to control the threats of avian influenza viruses.

9.
BMC Plant Biol ; 24(1): 414, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38760680

ABSTRACT

BACKGROUND: Variations in hydraulic conductivity may arise from species-specific differences in the anatomical structure and function of the xylem, reflecting a spectrum of plant strategies along a slow-fast resource economy continuum. Spruce (Picea spp.), a widely distributed and highly adaptable tree species, is crucial in preventing soil erosion and enabling climate regulation. However, a comprehensive understanding of the variability in anatomical traits of stems and their underlying drivers in the Picea genus is currently lacking especially in a common garden. RESULTS: We assessed 19 stem economic properties and hydraulic characteristics of 17 Picea species grown in a common garden in Tianshui, Gansu Province, China. Significant interspecific differences in growth and anatomical characteristics were observed among the species. Specifically, xylem hydraulic conductivity (Ks) and hydraulic diameter exhibited a significant negative correlation with the thickness to span ratio (TSR), cell wall ratio, and tracheid density and a significant positive correlation with fiber length, and size of the radial tracheid. PCA revealed that the first two axes accounted for 64.40% of the variance, with PC1 reflecting the trade-off between hydraulic efficiency and mechanical support and PC2 representing the trade-off between high embolism resistance and strong pit flexibility. Regression analysis and structural equation modelling further confirmed that tracheid size positively influenced Ks, whereas the traits DWT, D_r, and TSR have influenced Ks indirectly. All traits failed to show significant phylogenetic associations. Pearson's correlation analysis demonstrated strong correlations between most traits and longitude, with the notable influence of the mean temperature during the driest quarter, annual precipitation, precipitation during the wettest quarter, and aridity index. CONCLUSIONS: Our results showed that xylem anatomical traits demonstrated considerable variability across phylogenies, consistent with the pattern of parallel sympatric radiation evolution and global diversity in spruce. By integrating the anatomical structure of the stem xylem as well as environmental factors of origin and evolutionary relationships, our findings provide novel insights into the ecological adaptations of the Picea genus.


Subject(s)
Climate , Picea , Wood , Xylem , Picea/anatomy & histology , Picea/physiology , Picea/growth & development , Wood/anatomy & histology , Xylem/anatomy & histology , Xylem/physiology , China , Species Specificity , Plant Stems/anatomy & histology , Plant Stems/physiology , Plant Stems/growth & development
10.
Article in English | MEDLINE | ID: mdl-38775884

ABSTRACT

Emodin has been proven to have weight-reducing and lipid-lowering effects. In order to make emodin play a better anti-obesity role, we designed and developed an emodin loaded dissolving microneedle patch, in which emodin existed in the form of emodin-polyvinylpyrrolidone co-precipitate (Emodin-PVP). Meanwhile, polydopamine (PDA) was added to the microneedle patch (PDA-Emodin-PVP-MN) for photothermal-enhanced chemotherapy of obesity. The average weight of the patch was 0.1 ± 0.05 g and the drug loading was 0.37 ± 0.031 mg. After 5 min of NIR irradiation (808 nm, 0.6 W/cm2), the rat abdominal temperature could reach 48 ℃, and the cumulative release of emodin reached 96.25%. The diffusion coefficient of emodin in the in vitro agar diffusion experiment was 249.27 mm2 h-1. No obvious toxicity was observed in hemolysis test, CCK-8 assay and microscopic histopathological analysis. The patch significantly reduced the percent of body weight ( P < 0.01), lipid-body ratio ( P < 0.001), serum FFAs ( P < 0.01) and the cell volume of peritesticular adipose tissue in the high-fat diet induced obese rats, indicating the patch had good anti-obesity effect. The mechanism of action may be related to the up-regulation of HSL and LPL protein levels in rat peritesticular adipose tissue.

11.
Front Mol Neurosci ; 17: 1365978, 2024.
Article in English | MEDLINE | ID: mdl-38660385

ABSTRACT

Non-coding RNAs (ncRNAs) play essential regulatory functions in various physiological and pathological processes in the brain. To systematically characterize the ncRNA profile in cortical cells, we downloaded single-cell SMART-Seq v4 data of mouse cerebral cortex. Our results revealed that the ncRNAs alone are sufficient to define the identity of most cortical cell types. We identified 1,600 ncRNAs that exhibited cell type specificity, even yielding to distinguish microglia from perivascular macrophages with ncRNA. Moreover, we characterized cortical layer and region specific ncRNAs, in line with the results by spatial transcriptome (ST) data. By constructing a co-expression network of ncRNAs and protein-coding genes, we predicted the function of ncRNAs. By integrating with genome-wide association studies data, we established associations between cell type-specific ncRNAs and traits related to neurological disorders. Collectively, our study identified differentially expressed ncRNAs at multiple levels and provided the valuable resource to explore the functions and dysfunctions of ncRNAs in cortical cells.

12.
Pestic Biochem Physiol ; 201: 105893, 2024 May.
Article in English | MEDLINE | ID: mdl-38685255

ABSTRACT

Potato virus Y (PVY) is one of the most important pathogens in the genus Potyvirus that seriously harms agricultural production. Copper (Cu), as a micronutrient, is closely related to plant immune response. In this study, we found that foliar application of Cu could inhibit PVY infection to some extent, especially at 7 days post inoculation (dpi). To explore the effect of Cu on PVY infection, transcriptome sequencing analysis was performed on PVY-infected tobacco with or without Cu application. Several key pathways regulated by Cu were identified, including plant-pathogen interaction, inorganic ion transport and metabolism, and photosynthesis. Moreover, the results of virus-induced gene silencing (VIGS) assays revealed that NbMLP423, NbPIP2, NbFd and NbEXPA played positive roles in resistance to PVY infection in Nicotiana benthamiana. In addition, transgenic tobacco plants overexpressing NtEXPA11 showed increased resistance to PVY infection. These results contribute to clarify the role and regulatory mechanism of Cu against PVY infection, and provide candidate genes for disease resistance breeding.


Subject(s)
Copper , Disease Resistance , Nicotiana , Plant Diseases , Potyvirus , Nicotiana/virology , Nicotiana/genetics , Potyvirus/physiology , Copper/pharmacology , Plant Diseases/virology , Disease Resistance/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression Profiling , Plants, Genetically Modified/virology , Gene Expression Regulation, Plant , Transcriptome
13.
Bioorg Chem ; 147: 107328, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38583248

ABSTRACT

Discovering novel NDM-1 inhibitors is an urgent task for treatment of 'superbug' infectious diseases. In this study, we found that naturally occurring houttuynin and its sulfonate derivatives might be effective NDM-1 inhibitors with novel mechanism, i.e. the attribute of partially covalent inhibition of sulfonate derivatives of houttuynin against NDM-1. Primary structure-activity relationship study showed that both the long aliphatic side chain and the warhead of aldehyde group are vital for the efficiency against NDM-1. The homologs with longer chains (SNH-2 to SNH-5) displayed stronger inhibitory activities with IC50 range of 1.1-1.5 µM, while the shorter chain the weaker inhibition. Further synergistic experiments in cell level confirmed that all these 4 compounds (at 32 µg/mL) recovered the antibacterial activity of meropenem (MER) against E. coli BL21/pET15b-blaNDM-1.


Subject(s)
Anti-Bacterial Agents , Dose-Response Relationship, Drug , Escherichia coli , Microbial Sensitivity Tests , Structure-Activity Relationship , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Escherichia coli/drug effects , Escherichia coli/enzymology , Molecular Structure , beta-Lactamases/metabolism , beta-Lactamase Inhibitors/pharmacology , beta-Lactamase Inhibitors/chemistry , beta-Lactamase Inhibitors/chemical synthesis , Biological Products/pharmacology , Biological Products/chemistry , Biological Products/chemical synthesis , Humans , Escherichia coli Proteins
15.
J Appl Genet ; 65(2): 367-373, 2024 May.
Article in English | MEDLINE | ID: mdl-38418803

ABSTRACT

Since its initial identification, the Forkhead Box P2 gene (FOXP2) has maintained its singular status as the archetypal monogenic determinant implicated in Mendelian forms of human speech and language impairments. Despite the passage of two decades subsequent to its discovery, extant literature remains disproportionately sparse with regard to case-specific instances and loci of mutational perturbations. The objective of the current investigation centers on furnishing an enriched delineation of both its clinical manifestations and its mutational heterogeneity. Clinical phenotypes and peripheral blood samples were assiduously amassed from familial subjects. Whole-exome sequencing and Sanger sequencing methodologies were deployed for the unambiguous identification of potential genetic variants and for corroborating their co-segregation within the family pedigree. An exhaustive review of published literature focusing on patients manifesting speech and language disorders consequent to FOXP2 genetic anomalies was also undertaken. The investigation yielded the identification of a novel heterozygous variant, c.661del (p.L221Ffs*41), localized within the FOXP2 gene in the proband, an inheritance from his symptomatic mother. The proband presented with an array of symptoms, encompassing dysarthric speech, deficits in instruction comprehension, and communicative impediments. In comparison, the mother exhibited attenuated symptoms, including rudimentary verbalization capabilities punctuated by pronounced stuttering and dysarthria. A comprehensive analysis of articles archived in the Human Gene Mutation Database (HGMD) classified under "DM" disclosed the existence of 74 patients inclusive of the subjects under current examination, sub-divided into 19 patients with null variants, 5 patients with missense variants, and 50 patients with gross deletions or complex genomic rearrangements. A conspicuous predominance of delayed speech, impoverished current verbal abilities, verbal comprehension deficits, and learning difficulties were observed in patients harboring null or missense FOXP2 variants, as compared to their counterparts with gross deletions or complex rearrangements. Developmental delays, hypotonia, and craniofacial aberrations were exclusive to the latter cohort. The elucidated findings augment the existing corpus of knowledge on the genetic architecture influencing both the proband and his mother within this specified familial context. Of critical importance, these discoveries furnish a robust molecular framework conducive to the prenatal diagnostic evaluations of prospective progeny within this familial lineage.


Subject(s)
Language Disorders , Speech , Humans , China , Forkhead Transcription Factors/genetics , Language Disorders/genetics , Mutation
16.
Zhongguo Zhong Yao Za Zhi ; 49(2): 487-497, 2024 Jan.
Article in Chinese | MEDLINE | ID: mdl-38403324

ABSTRACT

This study aims to explore the anti-inflammatory, vasodilation, and cardioprotective effects of the intestinal absorption liquids containing Xinshubao Tablets or single herbs, and to elucidate the potential mechanism based on network pharmacology. Western blot was then conducted to validate the expression changes of core proteins. Lipopolysaccharide(LPS)-stimulated RAW264.7 cells were used to observe the anti-inflammatory effect. The vasodilation activity was examined by the microvessel relaxation assay in vitro. Oxygen-glucose deprivation(OGD)-induced H9c2 cells were used to investigate the cardioprotective effect. The chemical components were retrieved from Herb databases and composition of Xinshubao Tablets drug-containing intestinal absorption solution. Drug targets were retrieved from SwissTargetPrediction databases. GeneCards was searched for the targets associated with the anti-inflammatory, vasodilation, and cardioprotective effects. The common targets shared by the drug and the effects were used to establish the protein-protein interaction(PPI) network, from which the core targets were obtained. Finally, the core targets were imported into Cytoscape 3.9.1 for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analyses. The anti-inflammatory experiment showed that both Xinshubao Tablets and the single herbs constituting this formula had anti-inflammatory effects. Curcumae Radix had the strongest inhibitory effect on the production of tumor necrosis factor-α(TNF-α), and Salviae Miltiorrhizae Radix et Rhizoma had the strongest inhibitory effect on the generation of interleukin-6(IL-6). Xinshubao Tablets, Curcumae Radix, and Crataegi Fructus had vasodilation effect, and Crataegi Fructus had the strongest effect. Xinshubao Tablets, Salviae Miltiorrhizae Radix et Rhizoma, Acanthopanacis Senticosi Radix et Rhizoma seu Caulis, and Paeoniae Radix Alba had cardioprotective effects, and Salviae Miltiorrhizae Radix et Rhizoma had the strongest cardioprotective effect. Network pharmacology results demonstrated that except the whole formula, Salviae Miltiorrhizae Radix et Rhizoma had the most components with anti-inflammatory effect, and Curcumae Radix had the most components with vasodilation and cardioprotective effects, followed by Salviae Miltiorrhizae Radix et Rhizoma. The nitric oxide synthase 3(NOS3) was predicted as the core target for the anti-inflammatory, vasodilation, and cardioprotective effects. Western blot results showed that Xinshubao Tablets significantly up-regulated the expression of NOS3 in OGD-induced H9c2 cells. GO enrichment analysis showed that the effects were mainly related to lipid exported from cell, regulation of blood pressure, and inflammatory response. KEGG pathway enrichment predicted AGE-RAGE and HIF-1 signaling pathways as the key pathways.


Subject(s)
Drugs, Chinese Herbal , Drugs, Chinese Herbal/chemistry , Network Pharmacology , Vasodilation , Rhizome/chemistry , Plant Roots/chemistry , Tumor Necrosis Factor-alpha , Medicine, Chinese Traditional
17.
World J Clin Cases ; 12(4): 721-728, 2024 Feb 06.
Article in English | MEDLINE | ID: mdl-38322695

ABSTRACT

BACKGROUND: Total knee arthroplasty (TKA) is recognized as the most effective surgical intervention for relieving pain and improving joint mobility and deformity in patients with knee osteoarthritis and other synovial diseases. The application of accelerated postoperative rehabilitation (enhanced recovery after surgery) has demonstrated its efficacy in improving patient outcomes, and early postoperative joint function exercise has become a key prognostic factor in knee replacement. The unexpected appearance of limb pain and swelling hindered the patient's tendency for early mobilization, leading in prolonged hospitalization, delayed functional recovery and negative psychological responses. AIM: To investigate the impact of incorporating programmed pain nursing with collaborative nursing on elderly patients undergoing knee replacement surgery. METHODS: A retrospective analysis was conducted on a cohort of 116 patients who underwent TKA at our hospital between July 2019 and July 2021. The patients were divided into two groups: A control group (n = 58) receiving programmatic nursing, and an observed group (n = 58) receiving programmed nursing combined with a collaborative nursing model. A pain management team consisting of attending physicians, head nurses, and responsible nurses was established. Outcome measures included visual analogue scale (VAS) scores, activities of daily living (ADL) scale scores, and functional scores. RESULTS: The ADL scores of patients in both groups exhibited a continuous increase. However, there was no statistically significant difference in the ADL scores between the two groups at 48 h and the 7th d post-surgery (P > 0.05). Upon reexamination at the 3rd mo, the observation group demonstrated higher ADL scores compared to the control group (67.48 ± 14.69 vs 59.40 ± 16.06, P < 0.05). The VAS scores of both groups significantly decreased, with no significant difference observed between the groups at each time point (P > 0.05). The functional status of patients in both groups exhibited a gradual increase prior to intervention and at the 1st, 2nd, and 3rd month following discharge (P < 0.05). There was no statistically significant difference in knee joint function scores between the two groups at the 1st month after discharge (47.52 vs 45.81, P > 0.05). However, the knee joint function scores of patients in the observation group were significantly higher than those in the control group at the 2nd (59.38 vs 53.19, P < 0.05) and 3rd month (71.92 vs 64.34, P < 0.05) following discharge. CONCLUSION: The utilization of programmed pain nursing in conjunction with collaborative nursing for out-of-hospital care of TKA patients has demonstrated favorable outcomes, encompassing pain reduction, enhanced prognosis, and improved nursing quality for patients.

18.
Sci Bull (Beijing) ; 69(10): 1458-1471, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38402028

ABSTRACT

Synaptic dysfunction is a core component of the pathophysiology of schizophrenia. However, the genetic risk factors and molecular mechanisms related to synaptic dysfunction are still not fully understood. The Stonin 2 (STON2) gene encodes a major adaptor for clathrin-mediated endocytosis (CME) of synaptic vesicles. In this study, we showed that the C-C (307Pro-851Ala) haplotype of STON2 increases the susceptibility to schizophrenia and examined whether STON2 variations cause schizophrenia-like behaviors through the regulation of CME. We found that schizophrenia-related STON2 variations led to protein dephosphorylation, which affected its interaction with synaptotagmin 1 (Syt1), a calcium sensor protein located in the presynaptic membrane that is critical for CME. STON2307Pro851Ala knockin mice exhibited deficits in synaptic transmission, short-term plasticity, and schizophrenia-like behaviors. Moreover, among seven antipsychotic drugs, patients with the C-C (307Pro-851Ala) haplotype responded better to haloperidol than did the T-A (307Ser-851Ser) carriers. The recovery of deficits in Syt1 sorting and synaptic transmission by acute administration of haloperidol effectively improved schizophrenia-like behaviors in STON2307Pro851Ala knockin mice. Our findings demonstrated the effect of schizophrenia-related STON2 variations on synaptic dysfunction through the regulation of CME, which might be attractive therapeutic targets for treating schizophrenia-like phenotypes.


Subject(s)
Schizophrenia , Synaptic Transmission , Synaptotagmin I , Animals , Female , Humans , Male , Mice , Antipsychotic Agents/pharmacology , Antipsychotic Agents/therapeutic use , Endocytosis/drug effects , Gene Knock-In Techniques , Genetic Predisposition to Disease , Haloperidol/pharmacology , Haplotypes , Phosphorylation , Protein Transport , Schizophrenia/metabolism , Schizophrenia/genetics , Synapses/metabolism , Synapses/drug effects , Synaptic Transmission/drug effects , Synaptic Vesicles/metabolism , Synaptotagmin I/metabolism , Synaptotagmin I/genetics
19.
Mol Pharm ; 21(3): 1364-1381, 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38291993

ABSTRACT

Immunotherapy has emerged as a promising approach for cancer treatment, and the use of microRNAs (miRNAs) as therapeutic agents has gained significant attention. In this study, we investigated the effectiveness of immunotherapy utilizing miRNA34a and Jurkat T cells in inducing cell death in non-small-cell lung cancer cells, specifically A549 cells. Moreover, we explored the impact of Jurkat T cell activation and miRNA34a delivery using iron oxide nanorods (IONRs) on the killing of cancer cells. A549 cells were cocultured with both activated and inactivated Jurkat T cells, both before and after the delivery of miRNA34a. Surprisingly, our results revealed that even inactive Jurkat T cells were capable of inducing cell death in cancer cells. This unexpected observation suggested the presence of alternative mechanisms by which Jurkat T cells can exert cytotoxic effects on cancer cells. We stimulated Jurkat T cells using anti-CD3/CD28 and analyzed their efficacy in killing A549 compared to that of the inactive Jurkat T cells in conjunction with miRNA34a. Our findings indicated that the activation of Jurkat T cells significantly enhanced their cytotoxic potential against cancer cells compared to their inactive counterparts. The combined treatment of A549 cells with activated Jurkat T cells and miRNA34a demonstrated the highest level of cancer cell death, suggesting a synergistic effect between Jurkat T cell activation and miRNA therapy. Besides the apoptosis mechanism for the Jurkat T cells' cytotoxic effects on A549 cells, we furthermore investigated the ferroptosis pathway, which was found to have an impact on the cancer cell killing due to the presence of miRNA34a and IONRs as the delivery agent inside the cancer cells.


Subject(s)
Antineoplastic Agents , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , MicroRNAs , Humans , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/therapy , T-Lymphocytes, Cytotoxic , Lung Neoplasms/genetics , Lung Neoplasms/therapy , Jurkat Cells , MicroRNAs/genetics , Immunotherapy/methods
20.
Skin Res Technol ; 30(1): e13550, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38174801

ABSTRACT

OBJECTIVE: To summarize and analysis the application of biologic agents in patients with psoriasis in the real world. METHODS: Relying on collected data from June 2020 to September 2021 in the database of China Psoriasis Standardized Diagnosis and Treatment Center, 2529 cases of psoriasis patients treated with biologic agents in 188 different tertiary hospitals across China were retrospective analyzed. The collected information mainly includes demographic data (age, gender, psoriasis history), curative effectiveness of used biologics drug withdrawal and its reason. According to the collected information, condition of the usage for each category of biologics and influencing factor of biologics replacement were analyzed. RESULT: A total of 2529 patients were analyzed, which included 1626 male (64.29%) and 903 female (35.71%) with an average age of 42.12 ± 14.70 (17 âˆ¼ 85) years old; 2336 (92.37%) patients were aged from 19 to 60 years old. Within these patients, 2362 of them (93.40%) had a psoriasis area and severity index (PASI) score, and 1776 of these patients had moderate to severe cases (75.19%). According to the patient's self-evaluation of the past efficacy of biological agents, secukinumab was chosen by the most people to have the highest efficacy (1140 cases, 93.60%). The main reason for the withdrawal of secukinumab is that the disease is already well controlled at the time of withdrawal (67 cases, 38.95%); for TNF- α inhibitor is the poor curative effect; for ustekinumab and ixekizumab were the non-affordable price. CONCLUSIONS: In the current biotherapy of psoriasis in China, the efficacy of secukinumab is thought by most people to be the highest. Secukinumab is the first choice when the needs of changing biologics appear.


Subject(s)
Biological Products , Psoriasis , Humans , Male , Female , Adult , Middle Aged , Aged, 80 and over , Young Adult , Antibodies, Monoclonal/therapeutic use , Biological Products/therapeutic use , Retrospective Studies , Ustekinumab/therapeutic use , Psoriasis/drug therapy , Severity of Illness Index , Treatment Outcome
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