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1.
Artigo em Inglês | MEDLINE | ID: mdl-38621188

RESUMO

We thoroughly investigated the anharmonic lattice dynamics and microscopic mechanisms of the thermal and electronic transport characteristics in orthorhombic o-CsCu5S3 at the atomic level. Taking into account the phonon energy shifts and the wave-like tunneling phonon channel, we predict an ultralow κL of 0.42 w/mK at 300 K with an extremely weak temperature dependence following ∼T-0.33. These findings agree well with experimental values along with the parallel to the Bridgman growth direction. The κL in o-CsCu5S3 is suppressed down to the amorphous limit, primarily due to the unconventional Cu-S bonding induced by the p-d hybridization antibonding state coupled with the stochastic oscillation of Cs atoms. The nonstandard temperature dependence of κL can be traced back to the critical or dominant role of wave-like tunneling of phonon contributions in thermal transport. Moreover, the p-d hybridization of Cu(3)-S bonding results in the formation of a valence band with "pudding-mold" and high-degeneracy valleys, ensuring highly efficient electron transport characteristics. By properly adjusting the carrier concentration, excellent thermoelectric performance is achieved with a maximum thermoelectric conversion efficiency of 18.4% observed at 800 K in p-type o-CsCu5S3. Our work not only elucidates the anomalous electronic and thermal transport behavior in the copper-based chalcogenide o-CsCu5S3 but also provides insights for manipulating its thermal and electronic properties for potential thermoelectric applications.

2.
Med Biol Eng Comput ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38622437

RESUMO

Mandibular defect repair has always been a clinical challenge, facing technical bottleneck. The new materials directly affect technological breakthroughs in mandibular defect repair field. Our aim is to fabricate a scaffold of advanced biomaterials for repairing of small mandibular defect. Therefore, a novel dual-channel scaffold consisting of silk fibroin/collagen type-I/hydroxyapatite (SCH) and polycaprolactone/hydroxyapatite (PCL/HA) was fabricated by cryogenic 3D printing technology with double nozzles. The mechanical properties and behaviors of the dual-channel scaffold were investigated by performing uniaxial compression, creep, stress relaxation, and ratcheting experiments respectively. The experiments indicated that the dual-channel scaffold was typical non-linear viscoelastic consistent with cancellous tissue; the Young's modulus of this scaffold was 60.1 kPa. Finite element analysis (FEA) was employed performing a numerical simulation to evaluate the implantation effect in mandible. The stress distribution of the contact area between scaffold and defect was uniform, the maximum Mises stress of cortical bone and cancellous bone in defect area were 54.520 MPa and 3.196 MPa, and the maximum displacement of cortical bone and cancellous bone in defect area were 0.1575 mm and 0.1555 mm respectively, which distributed in the incisor region. The peak maximum Mises stress experienced by the implanted scaffold was 3.128 × 10-3 MPa, and the maximum displacement was 6.453 × 10-2 mm distributed near incisor area. The displacement distribution of the scaffold was consistent with that of cortical and cancellous bone. The scaffold recovered well when the force applied on it disappeared. Above all, the dual-channel scaffold had excellent bio-mechanical properties in implanting mandible, which provides a new idea for the reconstruction of irregular bone defects in the mandible and has good clinical development prospects.

3.
Front Endocrinol (Lausanne) ; 15: 1365350, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628586

RESUMO

Background: Thyroid-associated ophthalmopathy (TAO) is the most prevalent autoimmune orbital condition, significantly impacting patients' appearance and quality of life. Early and accurate identification of active TAO along with timely treatment can enhance prognosis and reduce the occurrence of severe cases. Although the Clinical Activity Score (CAS) serves as an effective assessment system for TAO, it is susceptible to assessor experience bias. This study aimed to develop an ensemble deep learning system that combines anterior segment slit-lamp photographs of patients with facial images to simulate expert assessment of TAO. Method: The study included 156 patients with TAO who underwent detailed diagnosis and treatment at Shanxi Eye Hospital Affiliated to Shanxi Medical University from May 2020 to September 2023. Anterior segment slit-lamp photographs and facial images were used as different modalities and analyzed from multiple perspectives. Two ophthalmologists with more than 10 years of clinical experience independently determined the reference CAS for each image. An ensemble deep learning model based on the residual network was constructed under supervised learning to predict five key inflammatory signs (redness of the eyelids and conjunctiva, and swelling of the eyelids, conjunctiva, and caruncle or plica) associated with TAO, and to integrate these objective signs with two subjective symptoms (spontaneous retrobulbar pain and pain on attempted upward or downward gaze) in order to assess TAO activity. Results: The proposed model achieved 0.906 accuracy, 0.833 specificity, 0.906 precision, 0.906 recall, and 0.906 F1-score in active TAO diagnosis, demonstrating advanced performance in predicting CAS and TAO activity signs compared to conventional single-view unimodal approaches. The integration of multiple views and modalities, encompassing both anterior segment slit-lamp photographs and facial images, significantly improved the prediction accuracy of the model for TAO activity and CAS. Conclusion: The ensemble multi-view multimodal deep learning system developed in this study can more accurately assess the clinical activity of TAO than traditional methods that solely rely on facial images. This innovative approach is intended to enhance the efficiency of TAO activity assessment, providing a novel means for its comprehensive, early, and precise evaluation.


Assuntos
Aprendizado Profundo , Oftalmopatia de Graves , Humanos , Oftalmopatia de Graves/diagnóstico por imagem , Qualidade de Vida , Órbita , Dor
4.
ACS Med Chem Lett ; 15(4): 518-523, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38628793

RESUMO

Small-molecule inhibitors targeting programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) interactions can compensate for the shortcomings of antibody-based inhibitors and have attracted considerable attention, some of which have already entered clinical trials. Herein, based on our previous study on small-molecule PD-L1 inhibitors, we reported a series of 8-(o-tolyl)quinazoline derivatives by the skeleton merging strategy. Homogenous time-resolved fluorescence (HTRF) assay against PD-1/PD-L1 interaction identified compound A5, which showed the most potent inhibition with an IC50 value of 23.78 nM. Meanwhile, based on the results of HTRF assay, the structure-activity relationships (SARs) of the tail were focused on. Cell-based PD-1/PD-L1 blockade assay further revealed that A5 significantly blocked the PD-1/PD-L1 interaction at 1.1 µM in the co-culture system of Jurkat-NFAT-PD-1 cells and Hep3B-OS8-hPD-L1 cells with no significant cytotoxicity on Jurkat cells. Moreover, the proposed binding mode of A5 was investigated by a docking analysis. These results indicate that compound A5 is a promising lead compound that deserves further investigation.

5.
IEEE Comput Graph Appl ; PP2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630562

RESUMO

Caricature generation aims to translate portrait photos into caricatures with exaggerated and hand-drawn artistic styles. Previous methods faced challenges in creating diverse and meaningful exaggeration effects, yielding unsatisfactory and uncontrollable results. To overcome this, we proposed ETCari, a novel weakly supervised exaggeration transfer network. ETCari enables the learning of diverse exaggeration caricature styles from various artists, better meeting individual customization requirements and achieving diversified exaggeration while retaining identity features. Specifically, we use the thin-plate spline control point deformation field as the ground truth, serving as the loss for weakly supervised learning to address the challenge of no labels. We convert input to an intermediate modality for domain adaptation, training a teacher model. Subsequently, we perform cross-modal knowledge distillation to train the student model, simplifying preprocessing during inference and avoiding the impact of face parser errors. Experiments on the WebCaricature dataset demonstrate that ETCari effectively performs exaggeration transfer, generating appealing caricatures.

6.
Med Image Anal ; 95: 103164, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38615431

RESUMO

Blessed by vast amounts of data, learning-based methods have achieved remarkable performance in countless tasks in computer vision and medical image analysis. Although these deep models can simulate highly nonlinear mapping functions, they are not robust with regard to the domain shift of input data. This is a significant concern that impedes the large-scale deployment of deep models in medical images since they have inherent variation in data distribution due to the lack of imaging standardization. Therefore, researchers have explored many domain generalization (DG) methods to alleviate this problem. In this work, we introduce a Hessian-based vector field that can effectively model the tubular shape of vessels, which is an invariant feature for data across various distributions. The vector field serves as a good embedding feature to take advantage of the self-attention mechanism in a vision transformer. We design paralleled transformer blocks that stress the local features with different scales. Furthermore, we present a novel data augmentation method that introduces perturbations in image style while the vessel structure remains unchanged. In experiments conducted on public datasets of different modalities, we show that our model achieves superior generalizability compared with the existing algorithms. Our code and trained model are publicly available at https://github.com/MedICL-VU/Vector-Field-Transformer.

8.
Cell Commun Signal ; 22(1): 212, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566100

RESUMO

The pathogenesis of Parkinson's disease (PD) is strongly associated with neuroinflammation, and type I interferons (IFN-I) play a crucial role in regulating immune and inflammatory responses. However, the specific features of IFN in different cell types and the underlying mechanisms of PD have yet to be fully described. In this study, we analyzed the GSE157783 dataset, which includes 39,024 single-cell RNA sequencing results for five PD patients and six healthy controls from the Gene Expression Omnibus database. After cell type annotation, we intersected differentially expressed genes in each cell subcluster with genes collected in The Interferome database to generate an IFN-I-stimulated gene set (ISGs). Based on this gene set, we used the R package AUCell to score each cell, representing the IFN-I activity. Additionally, we performed monocle trajectory analysis, and single-cell regulatory network inference and clustering (SCENIC) to uncover the underlying mechanisms. In silico gene perturbation and subsequent experiments confirm NFATc2 regulation of type I interferon response and neuroinflammation. Our analysis revealed that microglia, endothelial cells, and pericytes exhibited the highest activity of IFN-I. Furthermore, single-cell trajectory detection demonstrated that microglia in the midbrain of PD patients were in a pro-inflammatory activation state, which was validated in the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model as well. We identified transcription factors NFATc2, which was significantly up-regulated and involved in the expression of ISGs and activation of microglia in PD. In the 1-Methyl-4-phenylpyridinium (MPP+)-induced BV2 cell model, the suppression of NFATc2 resulted in a reduction in IFN-ß levels, impeding the phosphorylation of STAT1, and attenuating the activation of the NF-κB pathway. Furthermore, the downregulation of NFATc2 mitigated the detrimental effects on SH-SY5Y cells co-cultured in conditioned medium. Our study highlights the critical role of microglia in type I interferon responses in PD. Additionally, we identified transcription factors NFATc2 as key regulators of aberrant type I interferon responses and microglial pro-inflammatory activation in PD. These findings provide new insights into the pathogenesis of PD and may have implications for the development of novel therapeutic strategies.


Assuntos
Interferon Tipo I , Neuroblastoma , Doença de Parkinson , Camundongos , Animais , Humanos , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Doenças Neuroinflamatórias , Células Endoteliais/metabolismo , NF-kappa B/metabolismo , Análise de Célula Única , Camundongos Endogâmicos C57BL
9.
Artigo em Inglês | MEDLINE | ID: mdl-38557975

RESUMO

INTRODUCTION: Tegoprazan (TPZ), a potassium-competitive acid blocker, exerts a strong acid-suppression effect and a rapid onset of action. However, research on TPZ-amoxicillin (TA) dual treatment is limited. Here, we compared the safety and efficacy of TPZ-amoxicillin dual treatment and TPZ, bismuth potassium citrate, amoxicillin, and clarithromycin (TBAC) quadruple therapy in patients newly diagnosed with H. pylori infection over a 14-day treatment period. METHODS: A total of 236 patients newly diagnosed with H. pylori were enrolled in this multi-center, prospective, open-label, and randomized controlled study. Patients randomly received either TA dual or TBAC quadruple therapy. The incidence of adverse reactions and treatment compliance were recorded and then analyzed. RESULTS: The intention-to-treat analysis revealed that H. pylori-eradication rates were 83.9% (95% confidence interval [CI] 78.2%-91.3%) and 81.4% (95% CI 74.2%-88.5%) for the TA and TBAC groups, respectively, with no statistically significant difference between them (P = 0.606). The per-protocol analysis revealed that the H. pylori-eradication rates were 88.3% and 84.8% for the TA and TBAC groups, respectively (P = 0.447). The incidence of adverse reactions was significantly lower in the TA group than in the TBAC group (4.2% vs. 15.3%, P = 0.004). Moreover, the TA group demonstrated substantially higher treatment compliance than the TBAC group (94.1% vs. 89.0%, P = 0.020). CONCLUSION: The TA dual therapy successfully eradicated H. pylori with a high eradication rate and a low incidence of adverse reactions. Therefore, this treatment is recommended as an alternative course for patients newly diagnosed with H. pylori infection.

10.
Biotechnol Lett ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607604

RESUMO

Biofuel production from lignocellulose feedstocks is sustainable and environmentally friendly. However, the lignocellulosic pretreatment could produce fermentation inhibitors causing multiple stresses and low yield. Therefore, the engineering construction of highly resistant microorganisms is greatly significant. In this study, a composite functional chimeric cellulosome equipped with laccase, versatile peroxidase, and lytic polysaccharide monooxygenase was riveted on the surface of Saccharomyces cerevisiae to construct a novel yeast strain YI/LVP for synergistic lignin degradation and cellulosic ethanol production. The assembly of cellulosome was assayed by immunofluorescence microscopy and flow cytometry. During the whole process of fermentation, the maximum ethanol concentration and cellulose conversion of engineering strain YI/LVP reached 8.68 g/L and 83.41%, respectively. The results proved the availability of artificial chimeric cellulosome containing lignin-degradation enzymes for cellulosic ethanol production. The purpose of the study was to improve the inhibitor tolerance and fermentation performance of S. cerevisiae through the construction and optimization of a synergistic lignin-degrading enzyme system based on cellulosome.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38593404

RESUMO

The cell plasma membrane is a two-dimensional, fluid mosaic material composed of lipids and proteins that create a semipermeable barrier defining the cell from its environment. Compared with soluble proteins, the methodologies for the structural and functional characterization of membrane proteins are challenging. An emerging tool for studies of membrane proteins in mammalian systems is a "plasma membrane on a chip," also known as a supported lipid bilayer. Here, we create the "plant-membrane-on-a-chip,″ a supported bilayer made from the plant plasma membranes of Arabidopsis thaliana, Nicotiana benthamiana, or Zea mays. Membrane vesicles from protoplasts containing transgenic membrane proteins and their native lipids were incorporated into supported membranes in a defined orientation. Membrane vesicles fuse and orient systematically, where the cytoplasmic side of the membrane proteins faces the chip surface and constituents maintain mobility within the membrane plane. We use plant-membrane-on-a-chip to perform fluorescent imaging to examine protein-protein interactions and determine the protein subunit stoichiometry of FLOTILLINs. We report here that like the mammalian FLOTILLINs, FLOTILLINs expressed in Arabidopsis form a tetrameric complex in the plasma membrane. This plant-membrane-on-a-chip approach opens avenues to studies of membrane properties of plants, transport phenomena, biophysical processes, and protein-protein and protein-lipid interactions in a convenient, cell-free platform.

12.
J Med Chem ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38588467

RESUMO

The increased remodeling of the extracellular matrix (ECM) in pulmonary fibrosis (PF) generates bioactive ECM fragments called matricryptins, which include elastin-derived peptides (EDPs). The interaction between EDPs and their receptors, including elastin-binding protein (EBP), plays a crucial role in exacerbating fibrosis. Here, we present LXJ-02 for the first time, a novel ultralong-acting inhibitor that disrupts the EDPs/EBP peptide-protein interaction, promoting macrophages to secrete matrix metalloproteinase-12 (MMP-12), and showing great promise as a stable peptide. MMP-12 has traditionally been implicated in promoting inflammation and fibrosis in various acute and chronic diseases. However, we reveal a novel role of LXJ-02 that activates the macrophage-MMP-12 axis to increase MMP-12 expression and degrade ECM components like elastin. This leads to the preventing of PF while also improving EDP-EBP interaction. LXJ-02 effectively reverses PF in mouse models with minimal side effects, holding great promise as an excellent therapeutic agent for lung fibrosis.

13.
Chem Sci ; 15(14): 5192-5200, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38577355

RESUMO

Layered transition metal oxides (NaxTMO2) possess attractive features such as large specific capacity, high ionic conductivity, and a scalable synthesis process, making them a promising cathode candidate for sodium-ion batteries (SIBs). However, NaxTMO2 suffer from multiple phase transitions and Na+/vacancy ordering upon Na+ insertion/extraction, which is detrimental to their electrochemical performance. Herein, we developed a novel cathode material that exhibits an abnormal P2-type structure at a stoichiometric content of Na up to 1. The cathode material delivers a reversible capacity of 108 mA h g-1 at 0.2C and 97 mA h g-1 at 2C, retaining a capacity retention of 76.15% after 200 cycles within 2.0-4.3 V. In situ diffraction studies demonstrated that this material exhibits an absolute solid-solution reaction with a low volume change of 0.8% during cycling. This near-zero-strain characteristic enables a highly stabilized crystal structure for Na+ storage, contributing to a significant improvement in battery performance. Overall, this work presents a simple yet effective approach to realizing high Na content in P2-type layered oxides, offering new opportunities for high-performance SIB cathode materials.

14.
Microbiol Spectr ; : e0183923, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564670

RESUMO

Solid organ transplantation is a crucial treatment for patients who have reached the end stage of heart, lung, kidney, or liver failure. However, the likelihood of developing cancer post-transplantation increases. Additionally, primary malignant tumors remain a major obstacle to the long-term survival of transplanted organs. Therefore, it is essential to investigate effective therapies that can boost the immune system's ability to combat cancer and prevent allograft rejection. We established a mouse orthotopic liver tumor model and conducted allogeneic heterotopic heart transplantation. Various treatments were administered, and survival curves were generated using the Kaplan-Meier method. We also collected graft samples and measured inflammatory cytokine levels in the serum using an inflammatory array. The specificity of the histochemical techniques was tested by staining sections. We administered a combination therapy of phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR) dual inhibitor BEZ235 and Lactobacillus rhamnosus HN001 to primary liver cancer model mice with cardiac allografts. Consistent with our prior findings, L. rhamnosus HN001 alleviated the intestinal flora imbalance caused by BEZ235. Our previous research confirmed that the combination of BEZ235 and L. rhamnosus HN001 significantly prolonged cardiac transplant survival. IMPORTANCE: We observed that the combination of phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR) dual inhibitor BEZ235 and Lactobacillus rhamnosus HN001 notably prolonged cardiac transplant survival while also inhibiting the progression of primary liver cancer. The combination therapy was efficacious in treating antitumor immunity and allograft rejection, as demonstrated by the efficacy results. We also found that this phenomenon was accompanied by the regulation of inflammatory IL-6 expression. Our study presents a novel and effective therapeutic approach to address antitumor immunity and prevent allograft rejection.

15.
Exp Hematol Oncol ; 13(1): 43, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637863

RESUMO

Chimeric antigen receptors (CAR) are engineered fusion proteins that target T-cells to specific surface antigens of tumor cells to generate effective anti-tumor responses. CAR T-cell therapy is playing an increasingly important role in the treatment of relapsed/refractory B-cell malignancies (R/R BCM). Attempting to make CAR T-cells safer and more effective in treating R/R BCM, various novel engineered CAR T-cell agents are currently in the research and development or clinical trial stages. We have summarized here the latest reports on the novel CAR T-cell therapies for R/R BCM presented at the 2023 ASH Annual Meeting as well as the latest updates in related clinical trials.

16.
J Extracell Vesicles ; 13(4): e12429, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38576241

RESUMO

Osteoporosis (OP) is a systematic bone disease characterized by low bone mass and fragile bone microarchitecture. Conventional treatment for OP has limited efficacy and long-term toxicity. Synthetic biology makes bacterial extracellular vesicle (BEVs)-based therapeutic strategies a promising alternative for the treatment of OP. Here, we constructed a recombinant probiotics Escherichia coli Nissle 1917-pET28a-ClyA-BMP-2-CXCR4 (ECN-pClyA-BMP-2-CXCR4), in which BMP-2 and CXCR4 were overexpressed in fusion with BEVs surface protein ClyA. Subsequently, we isolated engineered BEVs-BMP-2-CXCR4 (BEVs-BC) for OP therapy. The engineered BEVs-BC exhibited great bone targeting in vivo. In addition, BEVs-BC had good biocompatibility and remarkable ability to promote osteogenic differentiation of BMSCs. Finally, the synthetic biology-based BEVs-BC significantly prevented the OP in an ovariectomized (OVX) mouse model. In conclusion, we constructed BEVs-BC with both bone-targeting and bone-forming in one-step using synthetic biology, which provides an effective strategy for OP and has great potential for industrialization.


Assuntos
Vesículas Extracelulares , Osteoporose , Animais , Camundongos , Vesículas Extracelulares/metabolismo , Osteogênese , Osteoporose/terapia , Transdução de Sinais , Biologia Sintética
17.
Biotechnol J ; 19(4): e2300557, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38581092

RESUMO

The halogenase-based catalysis is one of the most environmentally friendly methods for the synthesis of halogenated products, among which flavin-dependent halogenases (FDHs) have attracted great interest as one of the most promising biocatalysts due to the remarkable site-selectivity and wide substrate range. However, the complexity of constructing the NAD+-NADH-FAD-FADH2 bicoenzyme cycle system has affected the engineering applications of FDHs. In this work, a coenzyme self-sufficient tri-enzyme fusion was constructed and successfully applied to the continuous halogenation of L-tryptophan. SpFDH was firstly identified derived from Streptomyces pratensis, a highly selective halogenase capable of generating 6-chloro-tryptophan from tryptophan. Then, using gene fusion technology, SpFDH was fused with glucose dehydrogenase (GDH) and flavin reductase (FR) to form a tri-enzyme fusion, which increased the yield by 1.46-fold and making the coenzymes self-sufficient. For more efficient halogenation of L-tryptophan, a continuous halogenation bioprocess of L-tryptophan was developed by immobilizing the tri-enzyme fusion and attaching it to a continuous catalytic device, which resulted in a reaction yield of 97.6% after 12 h reaction. An FDH from S. pratensis was successfully applied in the halogenation and our study provides a concise strategy for the preparation of halogenated tryptophan mediated by multienzyme cascade catalysis.


Assuntos
Halogenação , Triptofano , Coenzimas , Oxirredutases/genética , Oxirredutases/metabolismo , Flavinas/metabolismo
18.
Front Public Health ; 12: 1368508, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601491

RESUMO

Background: Alzheimer's disease (AD) is increasingly recognized as a pressing global public health issue, demanding urgent development of scientific AD management strategies. In recent years, the proportion of AD patients in Intensive Care Units (ICU) has been on the rise. Simultaneously, the use of mechanical ventilation (MV) is becoming more prevalent among this specific patient group. Considering the pathophysiological characteristics of AD, the application of MV in AD patients may lead to different outcomes. However, due to insufficient research data, the significant impact of MV on the prognosis of AD patients in the ICU remains unclear. Therefore, we conducted this study to comprehensively evaluate the potential influence of MV on the survival rate of AD patients in the ICU. Methods: We obtained data from the MIMIC-IV database for patients diagnosed with AD. Using propensity score matching (PSM), we paired patients who received MV treatment with those who did not receive treatment. Next, we conducted Cox regression analysis to evaluate the association between MV and in-hospital mortality, 7-day mortality, 28-day mortality, 90-day mortality, 4-year mortality, length of hospital stay, and ICU stay. Results: The data analysis involved a cohort of 641 AD patients spanning from 2008 to 2019, inclusive. Following a 1:2 propensity score matching (PSM) procedure, 300 patients were successfully paired, comprising 123 individuals who underwent MV treatment and 177 who did not. MV demonstrated an association with an elevated risk of in-hospital mortality (HR 5.782; 95% CI 2.981-11.216; p < 0.001), 7-day mortality (HR 6.353; 95% CI 3.014-13.392; p < 0.001), 28-day mortality (HR 3.210; 95% CI 1.977-5.210; p < 0.001), 90-day mortality (HR 2.334; 95% CI 1.537-3.544; p < 0.001), and 4-year mortality (HR 1.861; 95% CI 1.370-2.527; p < 0.001). Furthermore, it was associated with a prolonged length of ICU stay [3.6(2.2,5.8) vs. 2.2(1.6,3.7); p = 0.001]. In the subgroup analysis, we further confirmed the robustness of the results obtained from the overall population. Additionally, we observed a significant interaction (p-interaction <0.05) between age, admission type, aspirin use, statin use, and the use of MV. Conclusion: In patients with AD who are receiving treatment in the ICU, the use of MV has been linked to higher short-term, medium-term, and long-term mortality rates, as well as prolong ICU stays. Therefore, it is crucial to break away from conventional thinking and meticulously consider both the medical condition and personal preferences of these vulnerable patients. Personalized treatment decisions, comprehensive communication between healthcare providers and patients, formulation of comprehensive treatment plans, and a focus on collaboration between the ICU and community organizations become imperative.


Assuntos
Doença de Alzheimer , Respiração Artificial , Humanos , Estudos Retrospectivos , Doença de Alzheimer/terapia , Cuidados Críticos/métodos , Unidades de Terapia Intensiva
19.
Wound Repair Regen ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602090

RESUMO

An argon-based low-temperature plasma jet (LTPJ) was used to treat chronically infected wounds in Staphylococcus aureus-laden mice. Based on physicochemical property analysis and in vitro antibacterial experiments, the effects of plasma parameters on the reactive nitrogen and oxygen species (RNOS) content and antibacterial capacity were determined, and the optimal treatment parameters were determined to be 4 standard litre per minute and 35 W. Additionally, the plasma-treated activation solution had a bactericidal effect. Although RNOS are related to the antimicrobial effect of plasma, excess RNOS may be detrimental to wound remodelling. In vivo studies demonstrated that medium-dose LTPJ promoted MMP-9 expression and inhibited bacterial growth during the early stages of healing. Moreover, LTPJ increased collagen deposition, reduced inflammation, and restored blood vessel density and TGF-ß levels to normal in the later stages of wound healing. Therefore, when treating chronically infected wounds with LTPJ, selecting the medium dose of plasma is more advantageous for wound recovery. Overall, our study demonstrated that low-temperature plasma jets may be a potential tool for the treatment of chronically infected wounds.

20.
Dev Dyn ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38481039

RESUMO

BACKGROUND: Disruption of ALX4 causes autosomal dominant parietal foramina and autosomal recessive frontonasal dysplasia with alopecia, but the mechanisms involving ALX4 in craniofacial and other developmental processes are not well understood. Although mice carrying distinct mutations in Alx4 have been previously reported, the perinatal lethality of homozygous mutants together with dynamic patterns of Alx4 expression in multiple tissues have hindered systematic elucidation of the cellular and molecular mechanisms involving Alx4 in organogenesis and disease pathogenesis. RESULTS: We report generation of Alx4f/f conditional mice and show that tissue-specific Cre-mediated inactivation of Alx4 in cranial neural crest and limb bud mesenchyme, respectively, recapitulated craniofacial and limb developmental defects as found in Alx4-null mice but without affecting postnatal survival. While Alx4-null mice that survive postnatally exhibited dorsal alopecia, mice lacking Alx4 function in the neural crest lineage exhibited a highly restricted region of hair loss over the anterior skull whereas mice lacking Alx4 in the cranial mesoderm lineage exhibited normal hair development, suggesting that Alx4 plays partly redundant roles in multiple cell lineages during hair follicle development. CONCLUSION: The Alx4f/f mice provide a valuable resource for systematic investigation of cell type- and stage-specific function of ALX family transcription factors in development and disease.

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