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1.
Nat Commun ; 15(1): 4696, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38824133

ABSTRACT

Age-related microangiopathy, also known as small vessel disease (SVD), causes damage to the brain, retina, liver, and kidney. Based on the DNA damage theory of aging, we reasoned that genomic instability may underlie an SVD caused by dominant C-terminal variants in TREX1, the most abundant 3'-5' DNA exonuclease in mammals. C-terminal TREX1 variants cause an adult-onset SVD known as retinal vasculopathy with cerebral leukoencephalopathy (RVCL or RVCL-S). In RVCL, an aberrant, C-terminally truncated TREX1 mislocalizes to the nucleus due to deletion of its ER-anchoring domain. Since RVCL pathology mimics that of radiation injury, we reasoned that nuclear TREX1 would cause DNA damage. Here, we show that RVCL-associated TREX1 variants trigger DNA damage in humans, mice, and Drosophila, and that cells expressing RVCL mutant TREX1 are more vulnerable to DNA damage induced by chemotherapy and cytokines that up-regulate TREX1, leading to depletion of TREX1-high cells in RVCL mice. RVCL-associated TREX1 mutants inhibit homology-directed repair (HDR), causing DNA deletions and vulnerablility to PARP inhibitors. In women with RVCL, we observe early-onset breast cancer, similar to patients with BRCA1/2 variants. Our results provide a mechanistic basis linking aberrant TREX1 activity to the DNA damage theory of aging, premature senescence, and microvascular disease.


Subject(s)
DNA Damage , Exodeoxyribonucleases , Phosphoproteins , Animals , Exodeoxyribonucleases/genetics , Exodeoxyribonucleases/metabolism , Humans , Phosphoproteins/genetics , Phosphoproteins/metabolism , Mice , Recombinational DNA Repair , Phenotype , Mutation , Drosophila/genetics , Aging/genetics , Aging/metabolism , Female , Drosophila melanogaster/genetics , Male , Retinal Diseases , Vascular Diseases , Hereditary Central Nervous System Demyelinating Diseases
2.
Front Mol Biosci ; 11: 1391046, 2024.
Article in English | MEDLINE | ID: mdl-38841190

ABSTRACT

Dendritic cells (DCs) are involved in the initiation and maintenance of immune responses against malignant cells by recognizing conserved pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) through pattern recognition receptors (PRRs). According to recent studies, tumor cell-derived DNA molecules act as DAMPs and are recognized by DNA sensors in DCs. Once identified by sensors in DCs, these DNA molecules trigger multiple signaling cascades to promote various cytokines secretion, including type I IFN, and then to induce DCs mediated antitumor immunity. As one of the potential attractive strategies for cancer therapy, various agonists targeting DNA sensors are extensively explored including the combination with other cancer immunotherapies or the direct usage as major components of cancer vaccines. Moreover, this review highlights different mechanisms through which tumor-derived DNA initiates DCs activation and the mechanisms through which the tumor microenvironment regulates DNA sensing of DCs to promote tumor immune escape. The contributions of chemotherapy, radiotherapy, and checkpoint inhibitors in tumor therapy to the DNA sensing of DCs are also discussed. Finally, recent clinical progress in tumor therapy utilizing agonist-targeted DNA sensors is summarized. Indeed, understanding more about DNA sensing in DCs will help to understand more about tumor immunotherapy and improve the efficacy of DC-targeted treatment in cancer.

3.
Reprod Toxicol ; 128: 108634, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38851359

ABSTRACT

Vinorelbine is a commonly used drug to treat various malignancies, such as breast cancer, non-small cell lung cancer, and metastatic pleural mesothelioma. Its side effects include severe neutropenia, local phlebitis, gastrointestinal reactions, and neurotoxicity. In view of the scarcity of research on vinorelbine's reproductive toxicity, this study evaluated the impact of vinorelbine ditartrate, a commonly used form of vinorelbine, on oocyte maturation in vitro. Our investigation revealed that vinorelbine ditartrate had no effect on oocyte meiotic resumption. However, it did reduce the rate of first polar body extrusion, suggesting that it could significantly impede the meiotic maturation of oocytes. Vinorelbine ditartrate exposure was found to disturb the regular spindle assembly and chromosome alignment, leading to the continuous activation of the spindle assembly checkpoint (SAC) and a delayed activation of the anaphase-promoting complex/cyclosome (APC/C), ultimately causing aneuploidy in oocytes. Consequently, the administration of vinorelbine is likely to result in oocyte aneuploidy, which can be helpful in providing a drug reference and fertility guidance in a clinical context.

4.
Zool Res ; 45(3): 633-647, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38766746

ABSTRACT

Painful stimuli elicit first-line reflexive defensive reactions and, in many cases, also evoke second-line recuperative behaviors, the latter of which reflects the sensing of tissue damage and the alleviation of suffering. The lateral parabrachial nucleus (lPBN), composed of external- (elPBN), dorsal- (dlPBN), and central/superior-subnuclei (jointly referred to as slPBN), receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption. However, the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear. In this study, we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor ( NK1R) (lPBN NK1R) are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle, while elPBN neurons are dispensable for driving such reactions. Notably, lPBN NK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats. Lastly, both lPBN NK1R and elPBN neurons contribute to chemical irritant-induced nocifensive reactions. Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.


Subject(s)
Nociception , Parabrachial Nucleus , Animals , Parabrachial Nucleus/physiology , Mice , Nociception/physiology , Neurons/physiology , Pain/physiopathology , Male , Behavior, Animal/physiology
5.
New Phytol ; 243(1): 477-494, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38715078

ABSTRACT

Cultivated spinach (Spinacia oleracea) is a dioecious species. We report high-quality genome sequences for its two closest wild relatives, Spinacia turkestanica and Spinacia tetrandra, which are also dioecious, and are used to study the genetics of spinach domestication. Using a combination of genomic approaches, we assembled genomes of both these species and analyzed them in comparison with the previously assembled S. oleracea genome. These species diverged c. 6.3 million years ago (Ma), while cultivated spinach split from S. turkestanica 0.8 Ma. In all three species, all six chromosomes include very large gene-poor, repeat-rich regions, which, in S. oleracea, are pericentromeric regions with very low recombination rates in both male and female genetic maps. We describe population genomic evidence that the similar regions in the wild species also recombine rarely. We characterized 282 structural variants (SVs) that have been selected during domestication. These regions include genes associated with leaf margin type and flowering time. We also describe evidence that the downy mildew resistance loci of cultivated spinach are derived from introgression from both wild spinach species. Collectively, this study reveals the genome architecture of spinach assemblies and highlights the importance of SVs during the domestication of cultivated spinach.


Subject(s)
Domestication , Genome, Plant , Spinacia oleracea , Spinacia oleracea/genetics , Chromosomes, Plant/genetics , Phylogeny , Recombination, Genetic/genetics
6.
ACS Nano ; 2024 May 27.
Article in English | MEDLINE | ID: mdl-38801653

ABSTRACT

Stem cell therapies are gaining traction as promising treatments for a variety of degenerative conditions. Both clinical and preclinical studies of regenerative medicine are hampered by the lack of technologies that can evaluate the migration and behavior of stem cells post-transplantation. This study proposes an innovative method to longitudinally image in vivo human-induced pluripotent stem cells differentiated to retinal pigment epithelium (hiPSC-RPE) cells by multimodal photoacoustic microscopy, optical coherence tomography, and fluorescence imaging powered by ultraminiature chain-like gold nanoparticle cluster (GNC) nanosensors. The GNC exhibits an optical absorption peak in the near-infrared regime, and the 7-8 nm size in diameter after disassembly enables renal excretion and improved safety as well as biocompatibility. In a clinically relevant rabbit model, GNC-labeled hiPSC-RPE cells migrated to RPE degeneration areas and regenerated damaged tissues. The hiPSC-RPE cells' distribution and migration were noninvasively, longitudinally monitored for 6 months with exceptional sensitivity and spatial resolution. This advanced platform for cellular imaging has the potential to enhance regenerative cell-based therapies.

7.
Cell Rep ; 43(5): 114223, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38748879

ABSTRACT

Quorum sensing (QS) is a cell-to-cell communication mechanism mediated by small diffusible signaling molecules. Previous studies showed that RpfR controls Burkholderia cenocepacia virulence as a cis-2-dodecenoic acid (BDSF) QS signal receptor. Here, we report that the fatty acyl-CoA ligase DsfR (BCAM2136), which efficiently catalyzes in vitro synthesis of lauryl-CoA and oleoyl-CoA from lauric acid and oleic acid, respectively, acts as a global transcriptional regulator to control B. cenocepacia virulence by sensing BDSF. We show that BDSF binds to DsfR with high affinity and enhances the binding of DsfR to the promoter DNA regions of target genes. Furthermore, we demonstrate that the homolog of DsfR in B. lata, RS02960, binds to the target gene promoter, and perception of BDSF enhances the binding activity of RS02960. Together, these results provide insights into the evolved unusual functions of DsfR that control bacterial virulence as a response regulator of QS signal.


Subject(s)
Bacterial Proteins , Burkholderia cenocepacia , Coenzyme A Ligases , Gene Expression Regulation, Bacterial , Promoter Regions, Genetic , Quorum Sensing , Quorum Sensing/genetics , Burkholderia cenocepacia/pathogenicity , Burkholderia cenocepacia/genetics , Burkholderia cenocepacia/metabolism , Virulence , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Coenzyme A Ligases/metabolism , Coenzyme A Ligases/genetics , Animals , Signal Transduction , Fatty Acids, Monounsaturated/metabolism , Mice , Protein Binding , Lauric Acids/metabolism
8.
Sci Adv ; 10(20): eado1463, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38758782

ABSTRACT

A ketogenic diet (KD) is a high-fat, low-carbohydrate diet that leads to the generation of ketones. While KDs improve certain health conditions and are popular for weight loss, detrimental effects have also been reported. Here, we show mice on two different KDs and, at different ages, induce cellular senescence in multiple organs, including the heart and kidney. This effect is mediated through adenosine monophosphate-activated protein kinase (AMPK) and inactivation of mouse double minute 2 (MDM2) by caspase-2, leading to p53 accumulation and p21 induction. This was established using p53 and caspase-2 knockout mice and inhibitors to AMPK, p21, and caspase-2. In addition, senescence-associated secretory phenotype biomarkers were elevated in serum from mice on a KD and in plasma samples from patients on a KD clinical trial. Cellular senescence was eliminated by a senolytic and prevented by an intermittent KD. These results have important clinical implications, suggesting that the effects of a KD are contextual and likely require individual optimization.


Subject(s)
Cellular Senescence , Diet, Ketogenic , Mice, Knockout , Tumor Suppressor Protein p53 , Animals , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/genetics , Mice , Humans , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Cyclin-Dependent Kinase Inhibitor p21/genetics , AMP-Activated Protein Kinases/metabolism , Proto-Oncogene Proteins c-mdm2/metabolism , Male , Organ Specificity
9.
Infect Dis Ther ; 13(6): 1291-1313, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38720132

ABSTRACT

INTRODUCTION: Over the past decade, numerous studies have described the types of pathogens and their antibiotic resistance patterns in patients with burn injuries in China; however, the findings have generally been inconsistent. We conducted a literature search and meta-analysis to summarize the infection spectra and antimicrobial resistance patterns in patients with burn injuries. METHODS: We searched the PubMed, Embase, Web of Science, China National Knowledge Infrastructure, China Biomedical Literature, Wanfang, and Weipu databases for relevant articles published between January 2010 and December 2023. The DerSimonian-Laird random-effects model was used to estimate the proportions and 95% confidence intervals (CIs) of pathogens among Chinese patients with burn injuries. Meta-regression analyses were performed to explore differences in the proportions of pathogens among different subgroups and their resistance patterns. This study was registered with PROSPERO (CRD42024514386). RESULTS: The database searches yielded 2017 records; after removing duplicates and conducting initial screening, 219 articles underwent full-text screening. Ultimately, 60 studies comprising a total of 62,819 isolated strains reported the proportions of pathogens in patients with burn injuries and were included in this meta-analysis. Meta-analyses were conducted on 18 types of pathogens. The most common pathogens causing infections in Chinese patients with burn injuries were Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Staphylococcus epidermidis. Similar results were observed in the subgroup analysis focusing on wound infections. Since 2015, there has been a significant decrease in the proportion of Pseudomonas aeruginosa (R2 = 4.89%) and a significant increase in the proportion of Klebsiella pneumoniae (R2 = 9.60%). In terms of antibiotic resistance, there has been a significant decrease in the resistance of Staphylococcus aureus to multiple antibiotics and an increasing trend in the resistance of Klebsiella pneumoniae. CONCLUSIONS: We systematically summarized the epidemiological characteristics and antibiotic resistance patterns of pathogens among individuals suffering from burns in China, thus providing guidance for controlling wound infections and promoting optimal empirical antimicrobial therapy. The observed high levels of antibiotic resistance underscore the need for ongoing monitoring of antibiotic usage trends.

10.
Environ Sci Pollut Res Int ; 31(24): 35161-35172, 2024 May.
Article in English | MEDLINE | ID: mdl-38724846

ABSTRACT

Modern life is filled with radiofrequency electromagnetic radiation (RF-EMR) in various frequency bands, while the health risks are not clear. In this study, mice were whole-body exposed to 0.9/1.5/2.65 GHz radiofrequency radiation at 4 W/kg for 2 h per day for 4 weeks to investigate the emotional effects. It was found that the mice showed anxiety but no severe depression. The ELISA results showed a significant decrease in amino acid neurotransmitters (GABA, DA, 5-HT), although acetylcholine (ACH) levels were not significantly altered. Furthermore, Western blot results showed that BDNF, TrkB, and CREB levels were increased in the cerebral cortex, while NF-κB levels were decreased. In addition, pro-inflammatory factors (IL-6, IL-1ß, TNF-α) were significantly elevated, and anti-inflammatory factors (IL-4, IL-10) tended to decrease. In conclusion, multi-frequency electromagnetic radiation induces an inflammatory response through the CREB-BDNF-TrkB and NF-κB pathways in the cerebral cortex and causes a decrease in excitatory neurotransmitters, which ultimately causes anxiety in mice.


Subject(s)
Anxiety , Cerebral Cortex , Electromagnetic Radiation , Inflammation , Animals , Mice , Cerebral Cortex/radiation effects , Male , Brain-Derived Neurotrophic Factor/metabolism , NF-kappa B/metabolism
11.
Cell Death Dis ; 15(4): 253, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38594244

ABSTRACT

Mitochondria are important for the activation of endothelial cells and the process of angiogenesis. NDUFS8 (NADH:ubiquinone oxidoreductase core subunit S8) is a protein that plays a critical role in the function of mitochondrial Complex I. We aimed to investigate the potential involvement of NDUFS8 in angiogenesis. In human umbilical vein endothelial cells (HUVECs) and other endothelial cell types, we employed viral shRNA to silence NDUFS8 or employed the CRISPR/Cas9 method to knockout (KO) it, resulting in impaired mitochondrial functions in the endothelial cells, causing reduction in mitochondrial oxygen consumption and Complex I activity, decreased ATP production, mitochondrial depolarization, increased oxidative stress and reactive oxygen species (ROS) production, and enhanced lipid oxidation. Significantly, NDUFS8 silencing or KO hindered cell proliferation, migration, and capillary tube formation in cultured endothelial cells. In addition, there was a moderate increase in apoptosis within NDUFS8-depleted endothelial cells. Conversely, ectopic overexpression of NDUFS8 demonstrated a pro-angiogenic impact, enhancing cell proliferation, migration, and capillary tube formation in HUVECs and other endothelial cells. NDUFS8 is pivotal for Akt-mTOR cascade activation in endothelial cells. Depleting NDUFS8 inhibited Akt-mTOR activation, reversible with exogenous ATP in HUVECs. Conversely, NDUFS8 overexpression boosted Akt-mTOR activation. Furthermore, the inhibitory effects of NDUFS8 knockdown on cell proliferation, migration, and capillary tube formation were rescued by Akt re-activation via a constitutively-active Akt1. In vivo experiments using an endothelial-specific NDUFS8 shRNA adeno-associated virus (AAV), administered via intravitreous injection, revealed that endothelial knockdown of NDUFS8 inhibited retinal angiogenesis. ATP reduction, oxidative stress, and enhanced lipid oxidation were detected in mouse retinal tissues with endothelial knockdown of NDUFS8. Lastly, we observed an increase in NDUFS8 expression in retinal proliferative membrane tissues obtained from human patients with proliferative diabetic retinopathy. Our findings underscore the essential role of the mitochondrial protein NDUFS8 in regulating endothelial cell activation and angiogenesis.


Subject(s)
Angiogenesis , Proto-Oncogene Proteins c-akt , Humans , Mice , Animals , Proto-Oncogene Proteins c-akt/metabolism , Cell Movement , Human Umbilical Vein Endothelial Cells/metabolism , TOR Serine-Threonine Kinases/metabolism , RNA, Small Interfering/pharmacology , Lipids/pharmacology , Adenosine Triphosphate/pharmacology , Cell Proliferation/genetics , NADH Dehydrogenase/genetics , NADH Dehydrogenase/metabolism
12.
Diagnostics (Basel) ; 14(7)2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38611678

ABSTRACT

Bone metastasis has been reported in up to 70% of patients with advanced breast cancer. A total of 55.76% of skeletal metastases in women were derived from breast cancer. However, patients with bone metastasis from an occult primary breast cancer are a rare subset of patients. Here, we present the case of a 38-year-old woman who had sternum pain for 4 months. A whole-body PET-CT scan revealed that the FDG uptake of both the sternum and internal mammary node was significantly increased. The final diagnosis of occult breast cancer was established by immunohistochemical (IHC) staining, which is of great significance for identifying the origin of a metastatic tumor despite no visualized lesions of mammary glands.

13.
World Neurosurg ; 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38642836

ABSTRACT

BACKGROUND: Keyhole surgery has been widely used to clip various intracranial aneurysms. Here, the feasibility of microsurgical clipping of multiple intracranial aneurysms via the keyhole approach was further investigated. METHODS: The clinical data of 80 patients with multiple intracranial aneurysms treated with keyhole surgery were retrospectively analyzed. The patients included 25 males and 55 females, with an average age of 57.5 years. There were 13 patients with unruptured aneurysms, 67 patients with ruptured aneurysms (small aneurysms accounted for 52.2% of ruptured aneurysms), and a total of 198 aneurysms. A 4 cm incision and a bone hole of approximately 2.5 cm were used per craniotomy standards. Forty-eight cases were treated via the supraorbital keyhole approach, 45 cases via the pterional keyhole approach, and 3 cases via the interhemispheric keyhole approach. RESULTS: A bilateral and unilateral keyhole approach was applied in 18 and 62 cases, respectively. A total of 170 ipsilateral and 7 contralateral aneurysms were clipped. The complete clipping rate was 98.9%. During the follow-up period of 6-12 months after surgery, the Glasgow outcome scale score was 5 points in 74 cases, 4 points in 5 cases, and 3 points in 1 case. The prognosis was associated with the preoperative Hunt-Hess classification but not with the number of operative sides, the operation opportunity, or the number of clipped aneurysms. CONCLUSION: Early keyhole surgical clipping of multiple intracranial aneurysms is an effective treatment. Among ruptured aneurysms, small aneurysms are common and need attention and timely treatment.

14.
Vet Sci ; 11(4)2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38668443

ABSTRACT

Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) play key roles in regulating testosterone secretion and spermatogenesis in male mammals, respectively, and they maintain the fertility of male animals by binding to their corresponding receptors. We designed and prepared a recombinant LH receptor (LHR) subunit vaccine and a recombinant FSH receptor (FSHR) subunit vaccine and used male Sprague Dawley (SD) rats as a model to examine their effects on testicular development, spermatogenesis, and testosterone secretion in prepubertal and pubertal mammals. Both vaccines (LHR-DTT and FSHR-DTT) significantly decreased the serum testosterone level in prepubertal rats (p < 0.05) but had no effect on the testosterone secretion in pubertal rats; both vaccines decreased the number of cell layers in the seminiferous tubules and reduced spermatogenesis in prepubertal and pubertal rats. Subunit vaccine FSHR-DTT decreased the sperm density in the epididymis in both prepubertal and pubertal rats (p < 0.01) and lowered testicular index and sperm motility in pubertal rats (p < 0.05), whereas LHR-DTT only reduced the sperm density in the epididymis in pubertal rats (p < 0.05). These results indicate that the FSHR subunit vaccine may be a promising approach for immunocastration, but it still needs improvements in effectiveness.

15.
Biochem Biophys Res Commun ; 711: 149911, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38603832

ABSTRACT

Macrophages play a crucial role in host response and wound healing, with M2 polarization contributing to the reduction of foreign-body reactions induced by the implantation of biomaterials and promoting tissue regeneration. Electrical stimulation (ES) and micropatterned substrates have a significant impact on the macrophage polarization. However, there is currently a lack of well-established cell culture platforms for studying the synergistic effects of these two factors. In this study, we prepared a graphene free-standing substrate with 20 µm microgrooves using capillary forces induced by water evaporation. Subsequently, we established an ES cell culture platform for macrophage cultivation by integrating a self-designed multi-well chamber cell culture device. We observed that graphene microgrooves, in combination with ES, significantly reduce cell spreading area and circularity. Results from immunofluorescence, ELISA, and flow cytometry demonstrate that the synergistic effect of graphene microgrooves and ES effectively promotes macrophage M2 phenotypic polarization. Finally, RNA sequencing results reveal that the synergistic effects of ES and graphene microgrooves inhibit the macrophage actin polymerization and the downstream PI3K signaling pathway, thereby influencing the phenotypic transition. Our results demonstrate the potential of graphene-based microgrooves and ES to synergistically modulate macrophage polarization, offering promising applications in regenerative medicine.


Subject(s)
Electric Stimulation , Graphite , Macrophages , Graphite/chemistry , Macrophages/drug effects , Macrophages/metabolism , Animals , Mice , RAW 264.7 Cells , Cell Polarity/drug effects , Phosphatidylinositol 3-Kinases/metabolism , Signal Transduction
16.
Medicine (Baltimore) ; 103(14): e37676, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38579079

ABSTRACT

This study aimed to investigate factors associated with the clinical outcomes of patients who underwent pediatric liver transplantation (LT) and received enhanced recovery after surgery (ERAS) nursing. A cohort of 104 pediatric patients was studied at our hospital. Data on 8 indicators and 2 clinical outcomes, including length of hospital stay (LOS) and 30-day readmission rates, were collected. Linear and logistic regression analyses were employed to examine the associations of the 8 indicators with hospital-LOS and readmission risks, respectively. The predictive value of these indicators for the outcomes was determined using the receiver operating characteristic (ROC) curve, decision curve analysis, and importance ranking through the XGBoost method. A comprehensive model was developed to evaluate its predictive accuracy. Regression analyses identified donor age, donor gender, and intensive care unit (ICU)-LOS of recipients as significant predictors of hospital LOS (all P < .05), whereas no indicators were significantly associated with readmission risk. Further, ROC analysis revealed that 3 indicators provided superior prediction for 28-day hospital LOS compared to the median LOS of 18 days. ICU-LOS demonstrated the highest clinical net benefit for predicting 28-day hospital-LOS. Multivariable regression analysis confirmed the independent predictive value of donor age and ICU-LOS for the hospital-LOS (all ß > 0, all P < .05). Although the comprehensive model incorporating donor age and ICU-LOS showed stable predictive capability for hospital-LOS, its performance did not significantly exceed that of the individual indicators. In pediatric LT, hospital LOS warrants greater emphasis over readmission rates. Donor age and ICU-LOS emerged as independent risk factors associated with prolonged hospital LOS.


Subject(s)
Enhanced Recovery After Surgery , Liver Transplantation , Humans , Child , Prognosis , Risk Factors , Intensive Care Units , Length of Stay , Retrospective Studies
17.
Front Neurol ; 15: 1340284, 2024.
Article in English | MEDLINE | ID: mdl-38450066

ABSTRACT

Anti-IgLON5 disease is a recently discovered autoimmune encephalopathy with sleep disorder as a hallmark in the majority of reported cases. Additional neurological manifestations include bulbar dysfunction, gait problems, movement disorders, oculomotor abnormalities, and hyperexcitability of the nervous system. At present, an increasing number of publications have dealt with the course and possible treatment options for anti-IgLON5 disease, and its clinical spectrum has expanded wider and more heterogeneous. Here, we report a case of a 66-year-old female with cognitive impairment accompanied by slow reaction, impaired memory, and decreased orientation. A positive cerebral MRI change and serum and cerebrospinal fluid (CSF) antibodies against IgLON5 were found during the diagnostic course. Subsequently the patient received immunotherapy and was generally in good health with no new symptoms during follow-up. Early testing for IgLON5 antibodies should be considered in patients with atypical neurological symptoms such as cognitive impairment, slow reaction, or decreased orientation. In clinical practice, immunotherapy should be considered in all cases of anti-IgLON5 encephalopathies.

18.
Research (Wash D C) ; 7: 0343, 2024.
Article in English | MEDLINE | ID: mdl-38550777

ABSTRACT

Fut2-mediated α1,2-fucosylation is important for gut homeostasis, including the intestinal stem cell (ISC). The stemness of ISC declines with age, and aging-associated ISC dysfunction is closely related to many age-related intestinal diseases. We previously found intestinal epithelial dysfunction in some aged Fut2 knockout mice. However, how Fut2-mediated α1,2-fucosylation affects ISC aging is still unknown. On this basis, the herein study aims to investigate the role of Fut2-mediated α1,2-fucosylation in ISC aging. Aging models in ISC-specific Fut2 knockout mice were established. ISCs were isolated for proteomics and N-glycoproteomics analysis. ISC functions and mitochondrial functions were examined in mice and organoids. Ulex europaeus agglutinin I chromatography and site-directed mutagenesis were used to validate the key target fucosylated proteins of Fut2. As a result, Fut2 knockout impaired ISC stemness and promoted aging marker expression in aged mice. Proteomics analysis indicated mitochondrial dysfunction in Fut2 knockout ISC. More injured mitochondria, elevated levels of reactive oxygen species, and decreased levels of adenosine 5'-triphosphate (ATP) in Fut2 knockout ISC were found. Moreover, respiratory chain complex impairment and mitophagy dysfunction in Fut2 knockout ISC were further noted. Finally, Fut2 was demonstrated to regulate mitochondrial functions mainly by regulating the α1,2-fucosylation of N-acyl sphingosine amidohydrolase 2 (Asah2) and Niemann-Pick type C intracellular cholesterol transporter 1 (Npc1). In conclusion, this study demonstrated the substantial role of Fut2 in regulating ISC functions during aging by affecting mitochondrial function. These findings provide novel insights into the molecular mechanisms of ISC aging and therapeutic strategies for age-related intestinal diseases.

19.
Med Eng Phys ; 125: 104117, 2024 03.
Article in English | MEDLINE | ID: mdl-38508797

ABSTRACT

This study aims to establish an effective benign and malignant classification model for breast tumor ultrasound images by using conventional radiomics and transfer learning features. We collaborated with a local hospital and collected a base dataset (Dataset A) consisting of 1050 cases of single lesion 2D ultrasound images from patients, with a total of 593 benign and 357 malignant tumor cases. The experimental approach comprises three main parts: conventional radiomics, transfer learning, and feature fusion. Furthermore, we assessed the model's generalizability by utilizing multicenter data obtained from Datasets B and C. The results from conventional radiomics indicated that the SVM classifier achieved the highest balanced accuracy of 0.791, while XGBoost obtained the highest AUC of 0.854. For transfer learning, we extracted deep features from ResNet50, Inception-v3, DenseNet121, MNASNet, and MobileNet. Among these models, MNASNet, with 640-dimensional deep features, yielded the optimal performance, with a balanced accuracy of 0.866, AUC of 0.937, sensitivity of 0.819, and specificity of 0.913. In the feature fusion phase, we trained SVM, ExtraTrees, XGBoost, and LightGBM with early fusion features and evaluated them with weighted voting. This approach achieved the highest balanced accuracy of 0.964 and AUC of 0.981. Combining conventional radiomics and transfer learning features demonstrated clear advantages over using individual features for breast tumor ultrasound image classification. This automated diagnostic model can ease patient burden and provide additional diagnostic support to radiologists. The performance of this model encourages future prospective research in this domain.


Subject(s)
Breast Neoplasms , Radiomics , Humans , Female , Retrospective Studies , Ultrasonography, Mammary , Machine Learning , Breast Neoplasms/diagnostic imaging
20.
ACS Appl Mater Interfaces ; 16(13): 16724-16731, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38508864

ABSTRACT

Traditional metal materials used in electronic devices are often problematic due to issues like bending resistance, oxidation leading to failure, and environmental pollution. To address these challenges, microwave electronic devices are constantly casting around for metal substitute materials with additional characteristics such as flexibility, anticorrosive, and eco-friendly. However, finding suitable materials that are accessible for radiofrequency (RF) applications is a difficult yet promising task. Consequently, a high-performance metasurface antenna based on highly conductive graphene films for satellite communications is developed in this paper. The proposed graphene assembled films (GAFs) have a conductivity of up to 1.13 × 106 S/m. Simulation and measurement results confirm the excellent performance of the designed antenna. Comparative experiments are also conducted on salt spray and mechanical bending between GAF antenna patterns and copper foil counterparts, further demonstrating the outstanding flexible property and corrosion resistance performance of prepared GAFs.

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