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1.
Int Immunopharmacol ; 140: 112835, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39088917

ABSTRACT

In recent years, researchers have focused on studying the mechanism of sepsis-induced immunosuppression, but there is still a lack of suitable animal models that accurately reflect the process of sepsis-induced immunosuppression. The aim of this study was to evaluate the immune status at various stages in a model of sepsis-induced secondary pneumonia and to demonstrate whether pyroptosis is one of the modes of immune cell death in sepsis. Firstly, we established a sepsis model in C57BL/6J mice using cecal ligation and puncture (CLP). The surviving mice were treated with a 40 µL suspension of P.aeruginosa (Pa) under anesthesia on day 4 post-CLP to establish a sepsis-induced secondary pneumonia model. Secondly, routine blood tests, serum ALT and PCT levels, gross lung specimens, and H&E staining of the lung and liver tissues were used to assess the successful establishment of this model. Serum levels of TNF-α and IL-6, the CD4+/CD8+ratio in blood, H&E staining of the spleen, and immunohistochemistry of CD4 and CD8 in the spleen were detected to evaluate the immune status of the model mice. Finally, the expression levels of pyroptosis-related proteins in the spleen were detected by Western blot. The expression of GSDMD was assessed using immunohistochemistry, and pyroptosis was directly observed through transmission electron microscopy. The experimental results above confirmed the successful construction of the model for sepsis-induced secondary pneumonia, demonstrating its ability to reflect sepsis-induced immunosuppression. Moreover, the expression of pyroptosis-related proteins, immunohistochemical GSDMD, and transmission electron microscopy of the spleen showed that pyroptosis was one of the modes of immune cell death in sepsis.

2.
Front Cell Infect Microbiol ; 14: 1407064, 2024.
Article in English | MEDLINE | ID: mdl-39119295

ABSTRACT

Background & aims: HBV infection initiates autoimmune responses, leading to autoantibody generation. This research explores the role of autoantibodies in HBV-related Acute-on-Chronic Liver Failure (ACLF), offering novel perspectives for clinical management. Method: We applied immunoprecipitation and iTRAQ techniques to screen for autoantibodies in serum from HBV-related cirrhosis patients and conducted detection with conformation- stabilizing ELISA in a cohort of 238 HBV-infected individuals and 49 health controls. Our results were validated in a retrospective cohort comprising 106 ACLF patients and further assessed through immunohistochemical analysis in liver tissues from an additional 10 ACLF cases. Results: Utilizing iTRAQ, we identified Argonaute1-3 autoantibodies (AGO-Abs) in this research. AGO2-Abs notably increased in cirrhosis, decompensation, and further in ACLF, unlike AGO1-Abs and AGO3-Abs. This reflects disease severity correlation. Logistic regression and COX models confirmed AGO2-Abs as independent prognostic indicators for decompensated liver cirrhosis (DLC) and ACLF. In the ROC analysis, AGO2-Abs showed significant diagnostic value for predicting 28- and 90-day mortality (AUROC = 0.853 and 0.854, respectively). Furthermore, combining AGO2-Abs with the Child-Pugh, MELD, and AARC scores significantly improved their predictive accuracy (P < 0.05). Kaplan-Meier analysis showed poorer survival for AGO2-Abs levels above 99.14µg/ml. These findings were supported by a retrospective validation cohort. Additionally, immunohistochemistry revealed band-like AGO2 expression in periportal liver areas, with AGO2-Abs levels correlating with total bilirubin, indicating a potential role in exacerbating liver damage through periportal functions. Conclusions: AGO2-Abs is a robust biomarker for predicting the mortality of patients with HBV-related ACLF.


Subject(s)
Acute-On-Chronic Liver Failure , Argonaute Proteins , Autoantibodies , Biomarkers , Liver Cirrhosis , Humans , Acute-On-Chronic Liver Failure/mortality , Acute-On-Chronic Liver Failure/immunology , Female , Male , Biomarkers/blood , Liver Cirrhosis/mortality , Liver Cirrhosis/immunology , Autoantibodies/blood , Autoantibodies/immunology , Middle Aged , Adult , Retrospective Studies , Prognosis , Hepatitis B virus/immunology , Liver/pathology , Hepatitis B/complications , Hepatitis B/mortality , Hepatitis B/immunology , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/mortality , Hepatitis B, Chronic/immunology , ROC Curve
3.
BMC Microbiol ; 24(1): 239, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961321

ABSTRACT

BACKGROUND: The gut microbiota significantly influences the health and growth of red-spotted grouper (Epinephelus akaara), a well-known commercial marine fish from Fujian Province in southern China. However, variations in survival strategies and seasons can impact the stability of gut microbiota data, rendering it inaccurate in reflecting the state of gut microbiota. Which impedes the effective enhancement of aquaculture health through a nuanced understanding of gut microbiota. Inspired by this, we conducted a comprehensive analysis of the gut microbiota of wild and captive E. akaara in four seasons. RESULTS: Seventy-two E. akaara samples were collected from wild and captive populations in Dongshan city, during four different seasons. Four sections of the gut were collected to obtain comprehensive information on the gut microbial composition and sequenced using 16S rRNA next-generation Illumina MiSeq. We observed the highest gut microbial diversity in both captive and wild E. akaara during the winter season, and identified strong correlations with water temperature using Mantel analysis. Compared to wild E. akaara, we found a more complex microbial network in captive E. akaara, as evidenced by increased abundance of Bacillaceae, Moraxellaceae and Enterobacteriaceae. In contrast, Vibrionaceae, Clostridiaceae, Flavobacteriaceae and Rhodobacteraceae were found to be more active in wild E. akaara. However, some core microorganisms, such as Firmicutes and Photobacterium, showed similar distribution patterns in both wild and captive groups. Moreover, we found the common community composition and distribution characteristics of top 10 core microbes from foregut to hindgut in E. akaara. CONCLUSIONS: Collectively, the study provides relatively more comprehensive description of the gut microbiota in E. akaara, taking into account survival strategies and temporal dimensions, which yields valuable insights into the gut microbiota of E. akaara and provides a valuable reference to its aquaculture.


Subject(s)
Bacteria , Gastrointestinal Microbiome , RNA, Ribosomal, 16S , Seasons , Animals , Gastrointestinal Microbiome/genetics , RNA, Ribosomal, 16S/genetics , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , China , Ecosystem , Phylogeny , Aquaculture , Bass/microbiology , High-Throughput Nucleotide Sequencing , Sequence Analysis, DNA , DNA, Bacterial/genetics , Biodiversity
4.
Article in English | MEDLINE | ID: mdl-38995864

ABSTRACT

Background: Puerperal infection is one of the four main causes of maternal mortality. A giant intrauterine mass caused by puerperal infection is a rare form of infection. The delay in treatment may result in the removal of the uterus. Case Presentation: We report a case of a large intrauterine mass resulting from puerperal infection, in which the uterus was salvaged through antibiotic treatment and curettage. The patient was a 27-year-old female, who presented with a large intrauterine mass, accompanied by fever and abdominal pain 35 days after vaginal delivery. The large intrauterine mass was ultimately pathologically confirmed to be necrotic smooth muscle tissue instead of residual pregnancy tissue. Conclusion: In most cases, the intrauterine mass after pregnancy is residual pregnancy tissue. Early identification and management are critical to ensure a good prognosis for patients. Obstetricians and pregnant women should be fully aware of the hazards of puerperal infections.

5.
Int J Pharm ; 662: 124496, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39033943

ABSTRACT

Chemo-photodynamic synergistic therapy (CPST) holds tremendous promise for treating cancers. Unfortunately, existing CPST applications suffer from complex synthetic procedures, low drug co-loading efficiency, and carrier-related toxicity. To address these issues, we have developed a supramolecular carrier-free self-sensitized nanoassemblies by co-assembling podophyllotoxin (PTOX) and chlorin e6 (Ce6) to enhance CPST efficiency against tumors. The nanoassemblies show stable co-assembly performance in simulative vivo neural environment (∼150 nm), with high co-loading ability for PTOX (72.2 wt%) and Ce6 (27.8 wt%). In vivo, the nanoassemblies demonstrate a remarkable ability to accumulate at tumor sites by leveraging the enhanced permeability and retention (EPR) effect. The disintegration of nanoassemblies following photosensitizer bioactivation triggered by the acidic tumor environment effectively resolves the challenge of aggregation-caused quenching (ACQ) effect. Upon exposure to external light stimulation, the disintegrated nanoassemblies not only illuminate cancer cells synergistically but also exert a more potent antitumor effect when compared with PTOX and Ce6 administered alone. This self-sensitized strategy represents a significant step forward in CPST, offering a unique co-delivery paradigm for clinic cancer treatment.

6.
G3 (Bethesda) ; 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39047060

ABSTRACT

The Nepetoideae, a subfamily of Lamiaceae (mint family), is rich in aromatic plants, many of which are sought after for their use as flavours and fragrances or for their medicinal properties. Here we present genome assemblies for two species in Nepetiodeae: Drepanocaruym sewerzowii and Marmoritis complanata. Both assemblies were generated using Oxford Nanopore Q20+ reads with contigs anchored to nine pseudomolecules that resulted in 335 Mb and 305 Mb assemblies, respectively, and BUSCO scores above 95% for both the assembly and annotation. We furthermore provide a species tree for the Lamiaceae using only genome derived gene models, complementing existing transcriptome and marker-based phylogenies.

7.
Circulation ; 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39056171

ABSTRACT

BACKGROUND: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. RNA-binding proteins are identified as regulators of cardiac disease; DDX5 (dead-box helicase 5) is a master regulator of many RNA processes, although its function in heart physiology remains unclear. METHODS: We assessed DDX5 expression in human failing hearts and a mouse HF model. To study the function of DDX5 in heart, we engineered cardiomyocyte-specific Ddx5 knockout mice. We overexpressed DDX5 in cardiomyocytes using adeno-associated virus serotype 9 and performed transverse aortic constriction to establish the murine HF model. The mechanisms underlined were subsequently investigated using immunoprecipitation-mass spectrometry, RNA-sequencing, alternative splicing analysis, and RNA immunoprecipitation sequencing. RESULTS: We screened transcriptome databases of murine HF and human dilated cardiomyopathy samples and found that DDX5 was significantly downregulated in both. Cardiomyocyte-specific deletion of Ddx5 resulted in HF with reduced cardiac function, an enlarged heart chamber, and increased fibrosis in mice. DDX5 overexpression improved cardiac function and protected against adverse cardiac remodeling in mice with transverse aortic constriction-induced HF. Furthermore, proteomics revealed that DDX5 is involved in RNA splicing in cardiomyocytes. We found that DDX5 regulated the aberrant splicing of Ca2+/calmodulin-dependent protein kinase IIδ (CamkIIδ), thus preventing the production of CaMKIIδA, which phosphorylates L-type calcium channel by serine residues of Cacna1c, leading to impaired Ca2+ homeostasis. In line with this, we found increased intracellular Ca2+ transients and increased sarcoplasmic reticulum Ca2+ content in DDX5-depleted cardiomyocytes. Using adeno-associated virus serotype 9 knockdown of CaMKIIδA partially rescued the cardiac dysfunction and HF in Ddx5 knockout mice. CONCLUSIONS: These findings reveal a role for DDX5 in maintaining calcium homeostasis and cardiac function by regulating alternative splicing in cardiomyocytes, identifying the DDX5 as a potential target for therapeutic intervention in HF.

8.
Biomaterials ; 311: 122691, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38996673

ABSTRACT

Acoustic holography (AH), a promising approach for cell patterning, emerges as a powerful tool for constructing novel invitro 3D models that mimic organs and cancers features. However, understanding changes in cell function post-AH remains limited. Furthermore, replicating complex physiological and pathological processes solely with cell lines proves challenging. Here, we employed acoustical holographic lattice to assemble primary hepatocytes directly isolated from mice into a cell cluster matrix to construct a liver-shaped tissue sample. For the first time, we evaluated the liver functions of AH-patterned primary hepatocytes. The patterned model exhibited large numbers of self-assembled spheroids and superior multifarious core hepatocyte functions compared to cells in 2D and traditional 3D culture models. AH offers a robust protocol for long-term in vitro culture of primary cells, underscoring its potential for future applications in disease pathogenesis research, drug testing, and organ replacement therapy.


Subject(s)
Hepatocytes , Holography , Liver , Hepatocytes/cytology , Hepatocytes/metabolism , Animals , Liver/cytology , Holography/methods , Mice , Acoustics , Cells, Cultured , Spheroids, Cellular/cytology , Mice, Inbred C57BL
9.
Front Plant Sci ; 15: 1387951, 2024.
Article in English | MEDLINE | ID: mdl-38903422

ABSTRACT

Balancing the biomass requirements of different functions for the purpose of population reproduction and persistence can be challenging for alpine plants due to extreme environmental stresses from both above- and below-ground sources. The presence of ecosystem engineers in alpine ecosystems effectively alleviates microenvironmental stresses, hence promoting the survival and growth of other less stress-tolerant species. However, the influence of ecosystem engineers on plant resource allocation strategies remains highly unexplored. In this study, we compared resource allocation strategies, including biomass accumulation, reproductive effort (RE), root fraction (RF), as well as relationships between different functions, among four alpine plant species belonging to Gentianaceae across bare ground, tussock grass-, cushion-, and shrub-engineered microhabitats. Shrub-engineered microhabitats exerted the strongest effects on regulating plant resource allocation patterns, followed by tussock grass- and cushion-engineered microhabitats. Additionally, apart from microhabitats, population background and plant life history also significantly influenced resource allocation strategies. Generally, plants established within engineered microhabitats exhibited higher biomass accumulation, as well as increased flower, leaf and stem production. Furthermore, individuals within engineered microhabitats commonly displayed lower RF, indicating a greater allocation of resources to above-ground functions while reducing allocation to root development. RE of annual plants was significantly higher than that of perennial plants. However, individuals of annual plants within engineered microhabitats showed lower RE compared to their counterparts in bare ground habitats; whereas perennial species demonstrated similar RE between microhabitat types. Moreover, RE was generally independent of plant size in bare-ground habitats but exhibited size-dependency in certain populations for some species within specific engineered microhabitat types. However, size-dependency did exist for absolute reproductive and root biomass allocation in most of the cases examined here. No trade-offs were observed between flower mass and flower number, nor between leaf mass and leaf number. The capacity of ecosystem engineers to regulate resource allocation strategies in associated plants was confirmed. However, the resource allocation patterns resulted synergistically from the ecosystem engineering effects, population environmental backgrounds, and plant life history strategies. In general, such regulations can improve individual survival and reproductive potential, potentially promoting population persistence in challenging alpine environments.

10.
J Innate Immun ; 16(1): 354-366, 2024.
Article in English | MEDLINE | ID: mdl-38852581

ABSTRACT

INTRODUCTION: Inactivated parapoxvirus ovis (iPPVO) exerts strong immunomodulatory effects on innate immune cells, making it an attractive therapeutic candidate. However, little is known about the signaling pathways that are involved in iPPVO-induced immune responses. METHODS: In this study, we systematically analyzed how different types of dendritic cells (DCs) react to iPPVO (Zylexis, strain D1701) in both BALB/c and C57BL/6 mice by flow cytometry and ELISAs, and investigated which signaling pathway is related to DC activation by Western blotting and protein profiling. RESULTS: We demonstrated that bone marrow-derived conventional DCs (BM-cDCs) and bone marrow-derived plasmacytoid DCs (BM-pDCs) matured and secreted type I interferons in response to Zylexis stimulation in both mouse strains. Similarly, Zylexis promoted the secretion of IL-12/23p40 and TNF by pDCs. However, IL-12/23p40 and TNF secretion by cDCs were induced in BALB/c mice but not in C57BL/6 mice. Analyzing the underlying signaling pathways revealed that iPPVO-induced maturation of cDCs was Toll-like receptor 9 (TLR9) independent, while the maturation of pDCs partially depended on the TLR9 pathway. Moreover, the production of proinflammatory cytokines by cDCs and the secretion of IFN-α/ß by pDCs partially depended on the TLR9 pathway in both mouse strains. Therefore, other signaling pathways seem to participate in the response of DCs to iPPVO, supported by protein profiling. CONCLUSION: Our data provide useful insights into the diversity of iPPVO sensors and their varying effects across different strains and species.


Subject(s)
Dendritic Cells , Mice, Inbred BALB C , Mice, Inbred C57BL , Parapoxvirus , Signal Transduction , Toll-Like Receptor 9 , Animals , Dendritic Cells/immunology , Mice , Parapoxvirus/immunology , Toll-Like Receptor 9/metabolism , Cells, Cultured , Immunity, Innate , Bone Marrow Cells/immunology , Mice, Knockout , Poxviridae Infections/immunology , Female , Vaccines, Inactivated/immunology , Species Specificity , Virus Inactivation
11.
Biomaterials ; 311: 122681, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38944968

ABSTRACT

Cell-laden bioprinting is a promising biofabrication strategy for regenerating bioactive transplants to address organ donor shortages. However, there has been little success in reproducing transplantable artificial organs with multiple distinctive cell types and physiologically relevant architecture. In this study, an omnidirectional printing embedded network (OPEN) is presented as a support medium for embedded 3D printing. The medium is state-of-the-art due to its one-step preparation, fast removal, and versatile ink compatibility. To test the feasibility of OPEN, exceptional primary mouse hepatocytes (PMHs) and endothelial cell line-C166, were used to print hepatospheroid-encapsulated-artificial livers (HEALs) with vein structures following predesigned anatomy-based printing paths in OPEN. PMHs self-organized into hepatocyte spheroids within the ink matrix, whereas the entire cross-linked structure remained intact for a minimum of ten days of cultivation. Cultivated HEALs maintained mature hepatic functions and marker gene expression at a higher level than conventional 2D and 3D conditions in vitro. HEALs with C166-laden vein structures promoted endogenous neovascularization in vivo compared with hepatospheroid-only liver prints within two weeks of transplantation. Collectively, the proposed platform enables the manufacture of bioactive tissues or organs resembling anatomical architecture, and has broad implications for liver function replacement in clinical applications.


Subject(s)
Bioprinting , Hepatic Veins , Hepatocytes , Liver , Neovascularization, Physiologic , Printing, Three-Dimensional , Spheroids, Cellular , Animals , Bioprinting/methods , Hepatocytes/cytology , Mice , Spheroids, Cellular/cytology , Liver/cytology , Liver Transplantation , Liver, Artificial , Tissue Engineering/methods , Tissue Scaffolds/chemistry , Cell Line , Mice, Inbred C57BL , Male
12.
J Colloid Interface Sci ; 672: 161-169, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-38838625

ABSTRACT

Intelligent shape memory polymer can be potentially used in manufacturing implantable devices that enables a benign variation of implant dimensions with the external stimuli, thus effectively lowering insertion forces and evading associated risks. However, in surgical implantation, biomaterials-associated infection has imposed a huge burden to healthcare system that urgently requires an efficacious replacement of antibiotic usages. Preventing the initial attachment and harvesting a biocidal function upon native surfaces may be deemed as a preferable strategy to tackle the issues of bacterial infection. Herein, a functionalized polylactic acid (PLA) composite membrane assembled with graphene (GE, a widely used photothermal agent) was fabricated through a blending process and then polydimethylsiloxane utilized as binders to pack hydrophobic SiO2 tightly onto polymer surface (denoted as PLA-GE/SiO2). Such an active platform exhibited a moderate shape-memory performance upon near-infrared (NIR) light stimulation, which was feasible for programmed deformation and shape recovery. Particularly stirring was that PLA-GE/SiO2 exerted a pronounced bacteria-killing effect under NIR illumination, 99.9 % of E. coli and 99.8 % of S. aureus were effectively eradicated in a lean period of 5 min. Furthermore, the obtained composite membrane manifested excellent antiadhesive properties, resulting in a bacteria-repelling efficacy of up to 99 % for both E. coli and S. aureus species. These findings demonstrated the potential value of PLA-GE/SiO2 as a shape-restorable platform in "kill&repel" integration strategy, further expanding its applications for clinical anti-infective treatment.


Subject(s)
Anti-Bacterial Agents , Escherichia coli , Graphite , Microbial Sensitivity Tests , Polyesters , Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Escherichia coli/drug effects , Staphylococcus aureus/drug effects , Polyesters/chemistry , Polyesters/pharmacology , Graphite/chemistry , Graphite/pharmacology , Silicon Dioxide/chemistry , Silicon Dioxide/pharmacology , Surface Properties , Membranes, Artificial , Particle Size , Bacterial Adhesion/drug effects , Polymers/chemistry , Polymers/pharmacology , Infrared Rays , Dimethylpolysiloxanes/chemistry , Dimethylpolysiloxanes/pharmacology
13.
Noncoding RNA ; 10(3)2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38921831

ABSTRACT

Fibrotic liver features excessive deposition of extracellular matrix (ECM), primarily produced from "activated" hepatic stellate cells (HSCs). While targeting human HSCs (hHSCs) in fibrosis therapeutics shows promise, the overall understanding of hHSC activation remains limited, in part because it is very challenging to define the role of human long non-coding RNAs (lncRNAs) in hHSC activation. To address this challenge, we identified another cell type that acts via a diverse gene network to promote fibrogenesis. Then, we identified the lncRNAs that were differentially regulated in activated hHSCs and the other profibrotic cell. Next, we conducted concurrent analysis to identify those lncRNAs that were specifically involved in fibrogenesis. We tested and confirmed that transdifferentiation of vascular smooth muscle cells (VSMCs) represents such a process. By overlapping TGFß-regulated lncRNAs in multiple sets of hHSCs and VSMCs, we identified a highly selected list of lncRNA candidates that could specifically play a role in hHSC activation. We experimentally characterized one human lncRNA, named CARMN, which was significantly regulated by TGFß in all conditions above. CARMN knockdown significantly reduced the expression levels of a panel of marker genes for hHSC activation, as well as the levels of ECM deposition and hHSC migration. Conversely, gain of function of CARMN using CRISPR activation (CRISPR-a) yielded the completely opposite effects. Taken together, our work addresses a bottleneck in identifying human lncRNAs that specifically play a role in hHSC activation and provides a framework to effectively select human lncRNAs with significant pathophysiological role.

14.
Nat Nanotechnol ; 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849544

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the dysfunction and progressive death of cerebral and spinal motor neurons. Preliminary epidemiological research has hinted at a relationship between environmental risks and the escalation of ALS, but the underlying reasons remain mostly mysterious. Here we show that nanosize polystyrene plastics (PS) induce ALS-like symptoms and illustrate the related molecular mechanism. When exposed to PS, cells endure internal oxidative stress, which leads to the aggregation of TAR DNA-binding protein 43 kDa (TDP-43), triggering ALS-like characteristics. In addition, the oxidized heat shock protein 70 fails to escort TDP-43 back to the nucleus. The cytoplasmic accumulation of TDP-43 facilitates the formation of a complex between PS and TDP-43, enhancing the condensation and solidification of TDP-43. These findings are corroborated through in silico and in vivo assays. Altogether, our work illustrates a unique toxicological mechanism induced by nanoparticles and provides insights into the connection between environmental pollution and neurodegenerative disorders.

15.
Acta Pharm Sin B ; 14(6): 2716-2731, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38828148

ABSTRACT

Lipogenesis is often highly upregulated in breast cancer brain metastases to adapt to intracranial low lipid microenvironments. Lipase inhibitors hold therapeutic potential but their intra-tumoral distribution is often blocked by the blood‒tumor barrier (BTB). BTB activates its Wnt signaling to maintain barrier properties, e.g., Mfsd2a-mediated BTB low transcytosis. Here, we reported VCAM-1-targeting nano-wogonin (W@V-NPs) as an adjuvant of nano-orlistat (O@V-NPs) to intensify drug delivery and inhibit lipogenesis of brain metastases. W@V-NPs were proven to be able to inactivate BTB Wnt signaling, downregulate BTB Mfsd2a, accelerate BTB vesicular transport, and enhance tumor accumulation of O@V-NPs. With the ability to specifically kill cancer cells in a lipid-deprived environment with IC50 at 48 ng/mL, W@V-NPs plus O@V-NPs inhibited the progression of brain metastases with prolonged survival of model mice. The combination did not induce brain edema, cognitive impairment, and systemic toxicity in healthy mice. Targeting Wnt signaling could safely modulate the BTB to improve drug delivery and metabolic therapy against brain metastases.

16.
Front Psychol ; 15: 1379391, 2024.
Article in English | MEDLINE | ID: mdl-38863671

ABSTRACT

The alteration of consciousness during shamanic rituals is both a physical and mystical phenomenon. It involves psychological and spiritual experiences. Through ritual practices, shamans can connect with archetype within the collective unconscious, utilizing trance-inducing techniques for "hallucinatory exploration". This study surveyed 75 participants to investigate the impact of prototype symbols in Shamanistic rituals on participants' consciousness states focusing on Jungian psychology's concept of archetype. The results indicate that archetype symbols in shamanic rituals can significantly influence participants' conscious state, leading them to experience a conscious dissolution of the self. Furthermore, archetype symbols have different effects at the stages of consciousness change. In particular, during the "Visionary Restructuralization" stage, archetype symbols, such as patterns, masks, totems and music, brought participants' consciousness to a peak and caused significant changes to it. These findings suggest that the metaphoric function of archetype symbols plays a crucial role in rituals. Archetype symbols connect the individual to the collective unconscious through visual images and symbolic imagery. They prompt the participants to experience emotional resonances that transcend individual experiences and affect their state of consciousness.

18.
Pain Ther ; 13(4): 865-881, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38805167

ABSTRACT

INTRODUCTION: Patients frequently suffer from debilitating chronic postsurgical pain (CPSP) subsequent to thoracoscopic surgery. The impact of postoperative dexmedetomidine infusion on CPSP remains elusive. This study aimed to scrutinize the effect of dexmedetomidine on both 1-year incidence of CPSP and the quality of recovery after thoracoscopic pulmonary nodule surgery. METHODS: This retrospective analysis encompassed clinical and follow-up data from 1148 patients undergoing thoracoscopic pulmonary nodule surgery at our institution between September 2021 and August 2022. Depending on whether dexmedetomidine was infused intravenously or not on the first night after surgery, patients were stratified into the dexmedetomidine group or the control group, with propensity score matching applied to harmonize baseline characteristics. Comparative analysis sought to delineate distinctions of CPSP and recovery quality 1 year after surgery. RESULTS: Following propensity score matching, a cohort of 258 patients in each group underwent analysis. Comparisons after matching revealed no statistically significant disparities in 1-year CPSP incidence [76/258 (29.5%) versus 78/258 (30.2%), P = 0.847], moderate-to-severe pain occurrence [17/76 (22.4%) versus 22/78 (28.2%), P = 0.405], neuropathic pain occurrence [11/76 (14.5%) versus 11/78 (14.1%), P = 0.948], and postoperative recovery quality assessed by 12-Item Short Form Health Survey (SF-12) score (113.1 [107.2, 116.0] versus 113.0 [107.4, 116.0], P = 0.328). Multivariate logistic regression analysis encompassing the entire cohort identified being female [odds ratio (OR) 2.10, 95% confidence interval (CI) 1.59-2.79, P < 0.001) and postoperative rescue analgesia (OR 1.47, 95% CI 1.09-1.96, P = 0.010) as risk factors for CPSP, while intraoperative fentanyl dosage (OR 0.92, 95% CI 0.87-0.98, P = 0.006) emerged as a protective factor. CONCLUSION: The prolonged administration of dexmedetomidine did not yield discernible amelioration in either 1-year CPSP or the recovery quality after thoracoscopic surgery. Noteworthy risk factors for CPSP encompassed female sex, postoperative rescue analgesia, and diminished fentanyl dosage intraoperatively.

19.
Ann Bot ; 134(2): 325-336, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38720433

ABSTRACT

BACKGROUND AND AIMS: There are intrinsic conflicts between signalling to mutualists and concealing (camouflaging) from antagonists. Like animals, plants also use camouflage as a defence against herbivores. However, this can potentially reduce their attractiveness to pollinators. METHODS: Using Fritillaria delavayi, an alpine camouflaged plant with inter-population floral colour divergence, we tested the influence of floral trait differences on reproduction. We conducted pollination experiments, measured floral morphological characteristics, estimated floral colours perceived by pollinators, analysed floral scent and investigated reproductive success in five populations. KEY RESULTS: We found that the reproduction of F. delavayi depends on pollinators. Under natural conditions, a flower-camouflaged population had 100 % fruit set and similar seed set to three out of four yellow-flowered populations. Bumblebees are important pollinators in the visually conspicuous yellow-flowered populations, whereas flies are the only pollinator in the flower-camouflaged population, visiting flowers more frequently than bumblebees. The camouflaged flowers cannot be discriminated from the rock background as perceived by pollinators, but may be located by flies through olfactory cues. CONCLUSIONS: Collectively, our results demonstrate that the flower-camouflaged population has different reproductive traits from the visually conspicuous yellow-flowered populations. A pollinator shift from bumblebees to flies, combined with high visitation frequency, compensates for the attractiveness disadvantage in camouflaged plants.


Subject(s)
Flowers , Fritillaria , Pollination , Reproduction , Pollination/physiology , Animals , Flowers/physiology , Flowers/anatomy & histology , Reproduction/physiology , Bees/physiology , Fritillaria/physiology , Diptera/physiology , Color , Fruit/physiology , Biological Mimicry/physiology , Pigmentation/physiology
20.
Nutr Diabetes ; 14(1): 26, 2024 05 16.
Article in English | MEDLINE | ID: mdl-38755177

ABSTRACT

PURPOSE: The study was designed to investigate the occurrence and risk factors of malnutrition in diabetic foot ulcers (DFU) patients and examine the association between malnutrition and length of stay (LOS). METHODS: This observational study included DFU hospitalized patients in two campuses of a hospital from January 2021 to June 2023. The diagnosis standard of malnutrition was established by using the Global Leadership Initiative on Malnutrition (GLIM) criteria. Patients were followed up to ascertain the length of hospitalization, and hospital stays longer than 17 days were considered as prolonged LOS. To explore the risk factors of malnutrition and the association between malnutrition and LOS, univariate and multivariate logistic regression analyses were performed. RESULTS: Overall 219 DFU patients were enrolled, malnutrition was identified in 38.36% of patients according to GLIM criteria, and 92 patients (42%) were recognized as prolonged LOS. Logistic regression analyses showed that BMI (P <0.001), Alb (P = 0.002), HbA1c (P <0.001), ulcer infection (P <0.001), LOS (P = 0.010), and ABI (P = 0.024) were independent risk factors for malnutrition. Besides, malnutrition by GLIM criteria was closely related to prolonged LOS and malnourished DFU patients were 2.857 times (95% CI, 1.497-5.450; P = 0.001) likely to present prolonged LOS than that of normal nutrition. CONCLUSION: Malnutrition was considered to be extremely prevalent in DFU patients and was associated with approximately three times higher likelihood of prolonged LOS. Implementing and disseminating the diagnostic criteria during routine practice is crucial, given the predictive efficacy of GLIM criteria.


Subject(s)
Diabetic Foot , Length of Stay , Malnutrition , Humans , Malnutrition/epidemiology , Diabetic Foot/epidemiology , Male , Risk Factors , Female , Middle Aged , Aged , Nutritional Status
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