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1.
CNS Neurosci Ther ; 30(7): e14828, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38946709

ABSTRACT

OBJECTIVE: Wallerian degeneration (WD) of the middle cerebellar peduncles (MCPs) following pontine infarction is a rare secondary degenerative neurological condition. Due to its infrequency, there is limited research on its characteristics. METHODS: This study aims to present three cases of WD of MCPs following pontine infarction and to analyze the prognosis, clinical manifestations, and neuroimaging features by amalgamating our cases with previously reported ones. RESULTS: The cohort consisted of 25 cases, comprising 18 men and 7 women aged 29 to 77 years (mean age: 66.2 years). The majority of patients (94%) exhibit risk factors for cerebrovascular disease, with hypertension being the primary risk factor. Magnetic resonance imaging (MRI) can detect WD of MCPs within a range of 21 days to 12 months following pontine infarction. This degeneration is characterized by bilateral symmetric hyperintensities on T2/FLAIR-weighted images (WI) lesions in the MCPs. Moreover, restricted diffusion, with hyperintensity on diffusion-weighted imaging (DWI) and low apparent diffusion coefficient (ADC) signal intensity may be observed as early as 21 days after the infarction. Upon detection of WD, it was observed that 20 patients (80%) remained asymptomatic during subsequent clinic visits, while four (16%) experienced a worsening of pre-existing symptoms. CONCLUSIONS: These findings underscore the importance of neurologists enhancing their understanding of this condition by gaining fresh insights into the neuroimaging characteristics, clinical manifestations, and prognosis of individuals with WD of bilateral MCPs.


Subject(s)
Brain Stem Infarctions , Middle Cerebellar Peduncle , Pons , Wallerian Degeneration , Humans , Male , Female , Middle Aged , Aged , Adult , Wallerian Degeneration/diagnostic imaging , Wallerian Degeneration/pathology , Pons/diagnostic imaging , Pons/pathology , Brain Stem Infarctions/diagnostic imaging , Middle Cerebellar Peduncle/diagnostic imaging , Middle Cerebellar Peduncle/pathology , Magnetic Resonance Imaging , Neuroimaging/methods
2.
Front Immunol ; 15: 1391848, 2024.
Article in English | MEDLINE | ID: mdl-38983856

ABSTRACT

Background: For Rheumatoid Arthritis (RA), a long-term chronic illness, it is essential to identify and describe patient subtypes with comparable goal status and molecular biomarkers. This study aims to develop and validate a new subtyping scheme that integrates genome-scale transcriptomic profiles of RA peripheral blood genes, providing a fresh perspective for stratified treatments. Methods: We utilized independent microarray datasets of RA peripheral blood mononuclear cells (PBMCs). Up-regulated differentially expressed genes (DEGs) were subjected to functional enrichment analysis. Unsupervised cluster analysis was then employed to identify RA peripheral blood gene expression-driven subtypes. We defined three distinct clustering subtypes based on the identified 404 up-regulated DEGs. Results: Subtype A, named NE-driving, was enriched in pathways related to neutrophil activation and responses to bacteria. Subtype B, termed interferon-driving (IFN-driving), exhibited abundant B cells and showed increased expression of transcripts involved in IFN signaling and defense responses to viruses. In Subtype C, an enrichment of CD8+ T-cells was found, ultimately defining it as CD8+ T-cells-driving. The RA subtyping scheme was validated using the XGBoost machine learning algorithm. We also evaluated the therapeutic outcomes of biological disease-modifying anti-rheumatic drugs. Conclusions: The findings provide valuable insights for deep stratification, enabling the design of molecular diagnosis and serving as a reference for stratified therapy in RA patients in the future.


Subject(s)
Arthritis, Rheumatoid , Gene Expression Profiling , Transcriptome , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/diagnosis , Humans , Antirheumatic Agents/therapeutic use , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Biomarkers , CD8-Positive T-Lymphocytes/immunology
3.
iScience ; 27(6): 109880, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38952686

ABSTRACT

Amygdala serves as a highly cellular, heterogeneous brain region containing excitatory and inhibitory neurons and is involved in the dopamine and serotoninergic neuron systems. An increasing number of studies have revealed the underpinned mechanism mediating social hierarchy in mammal and vertebrate, however, there are rare studies conducted on how amygdala on social hierarchy in poultry. In this study, we conducted food competition tests and determined the social hierarchy of the rooster. We performed cross-species analysis with mammalian amygdala, and found that cell types of human and rhesus monkeys were more closely related and that of chickens were more distant. We identified 26 clusters and divided them into 10 main clusters, of which GABAergic and glutamatergic neurons were associated with social behaviors. In conclusion, our results provide to serve the developmental studies of the amygdala neuron system and new insights into the underpinned mechanism of social hierarchy in roosters.

4.
Phys Med Biol ; 69(14)2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38959913

ABSTRACT

Objective. Follow-up computed tomography angiography (CTA) is necessary for ensuring occlusion effect of endovascular coiling. However, the implanted metal coil will introduce artifacts that have a negative spillover into radiologic assessment.Method. A framework named ReMAR is proposed in this paper for metal artifacts reduction (MARs) from follow-up CTA of patients with coiled aneurysms. It employs preoperative CTA to provide the prior knowledge of the aneurysm and the expected position of the coil as a guidance thus balances the metal artifacts removal performance and clinical feasibility. The ReMAR is composed of three modules: segmentation, registration and MAR module. The segmentation and registration modules obtain the metal coil knowledge via implementing aneurysms delineation on preoperative CTA and alignment of follow-up CTA. The MAR module consisting of hybrid convolutional neural network- and transformer- architectures is utilized to restore sinogram and remove the artifact from reconstructed image. Both image quality and vessel rendering effect after metal artifacts removal are assessed in order to responding clinical concerns.Main results. A total of 137 patients undergone endovascular coiling have been enrolled in the study: 13 of them have complete diagnosis/follow-up records for end-to-end validation, while the rest lacked of follow-up records are used for model training. Quantitative metrics show ReMAR significantly reduced the metal-artifact burden in follow-up CTA. Qualitative ranks show ReMAR could preserve the morphology of blood vessels during artifact removal as desired by doctors.Significance. The ReMAR could significantly remove the artifacts caused by implanted metal coil in the follow-up CTA. It can be used to enhance the overall image quality and convince CTA an alternative to invasive follow-up in treated intracranial aneurysm.


Subject(s)
Artifacts , Computed Tomography Angiography , Endovascular Procedures , Metals , Humans , Endovascular Procedures/instrumentation , Image Processing, Computer-Assisted/methods , Follow-Up Studies , Female
5.
Medicine (Baltimore) ; 103(27): e38756, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38968488

ABSTRACT

Physical exercise requires integrated autonomic and cardiovascular adjustments to maintain homeostasis. We aimed to observe acute posture-related changes in blood pressure, and apply a portable noninvasive monitor to measure the heart index for detecting arrhythmia among elite participants of a 246-km mountain ultra-marathon. Nine experienced ultra-marathoners (8 males and 1 female) participating in the Run Across Taiwan Ultra-marathon in 2018 were enrolled. The runners' Heart Spectrum Blood Pressure Monitor measurements were obtained in the standing and supine positions before and immediately after the race. Their high-sensitivity troponin T and N-terminal proB-type natriuretic peptide levels were analyzed 1 week before and immediately after the event. Heart rate was differed significantly in the immediate postrace assessment compared to the prerace assessment, in both the standing (P = .011; d = 1.19) and supine positions (P = .008; d = 1.35). Postural hypotension occurred in 4 (44.4%) individuals immediately postrace. In 3 out of 9 (33.3%) recruited finishers, the occurrence of premature ventricular complex signals in the standing position was detected; premature ventricular complex signal effect was observed in the supine position postrace in only 1 participant (11.1%). Premature ventricular complex signal was positively correlated with running speed (P = .037). Of the 6 individuals who completed the biochemical tests postrace, 2 (33.3%) had high-sensitivity troponin T and 6 (100%) had N-terminal proB-type natriuretic peptide values above the reference interval. A statistically significant increase was observed in both the high-sensitivity troponin T (P = .028; d = 1.97), and N-terminal proB-type natriuretic peptide (P = .028; d = 2.91) levels postrace compared to prerace. In conclusion, significant alterations in blood pressure and heart rate were observed in the standing position, and postexercise (postural) hypotension occurred among ultra-marathoners. The incidence of premature ventricular complexes was higher after the race than before.


Subject(s)
Autonomic Nervous System , Blood Pressure , Heart Rate , Marathon Running , Natriuretic Peptide, Brain , Troponin T , Humans , Female , Male , Autonomic Nervous System/physiology , Heart Rate/physiology , Marathon Running/physiology , Adult , Troponin T/blood , Middle Aged , Blood Pressure/physiology , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Taiwan , Ventricular Premature Complexes/physiopathology , Ventricular Premature Complexes/diagnosis , Hypotension, Orthostatic/physiopathology , Posture/physiology
6.
Heliyon ; 10(12): e32173, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38975162

ABSTRACT

A 19-year-old man presented with recurrent intermittent fever, progressive limbs weakness, numbness, and atrophy for 5 years. Biopsy of the sural nerve, spleen, lymph nodes, bone marrow and labial gland revealed that monomorphic small lymphoid cells infiltrated diffusely and that there was severe loss of large myelinated nerve fibers. Immunohistochemically, these cells were mainly CD8-positive T cells and were positive for CD3 and CD57. This patient was diagnosed as indolent CD8-positive T lymphoproliferative disorder (indolent CD8-positive T-LPD), emphasizing the need for a broad differential diagnosis under these conditions, and nerve biopsy should be performed.

7.
Am J Cancer Res ; 14(6): 2731-2754, 2024.
Article in English | MEDLINE | ID: mdl-39005680

ABSTRACT

Heterogeneity at biological and transcriptomic levels poses a challenge in defining and typing low-grade glioma (LGG), leading to a critical need for specific molecular signatures to enhance diagnosis, therapy, and prognostic evaluation of LGG. This study focused on fatty acid metabolism (FAM) related genes and prognostic features to investigate the mechanisms and treatment strategies for LGG cell metastasis and invasion. By screening 158 FAM-related genes and clustering 512 LGG samples into two subtypes (C1 and C2), differential gene expression analysis and functional enrichment were performed. The immune cell scores and prognosis were compared between the two subtypes, with C1 showing poorer outcomes and higher immune scores. A four-gene signature (PHEX, SHANK2, HOPX, and LGALS1) was identified and validated across different datasets, demonstrating a stable predictive effect. Cellular experiments confirmed the roles of LGALS1 and HOPX in promoting tumor cell proliferation, migration, and invasion, while SHANK2 exhibited a suppressive effect. This four-gene signature based on FAM-related genes offers valuable insights for understanding the pathogenesis and clinical management of LGG.

8.
Sci Rep ; 14(1): 15957, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38987376

ABSTRACT

We previously identified that serum EFNA1 and MMP13 were potential biomarker for early detection of esophageal squamous cell carcinoma. In this study, our aim is to explore the diagnostic value of serum EFNA1 and MMP13 for gastric cancer. We used enzyme-linked immunosorbent assay (ELISA) to detect the expression levels of serum EFNA1 and MMP13 in 210 GCs and 223 normal controls. The diagnostic value of EFNA1 and MMP13 was evaluated in an independent cohorts of GC patients and normal controls (n = 238 and 195, respectively). Receiver operating characteristics were used to calculate diagnostic accuracy. In training and validation cohorts, serum EFNA1 and MMP13 levels in the GC groups were significantly higher than those in the normal controls (P < 0.001). The area under the curve (AUC) of the combined detection of serum EFNA1 and MMP13 for GC was improved (0.794), compared with single biomarker used. Similar results were observed in the validation cohort. Importantly, the combined measurement of serum EFNA1 and MMP13 to detect early-stage GC also had acceptable diagnostic accuracy in training and validation cohort. Combined detection of serum EFNA1 and MMP13 could help identify early-stage GC, suggesting that it may be a promising tool for the early detection of GC.


Subject(s)
Biomarkers, Tumor , Matrix Metalloproteinase 13 , Stomach Neoplasms , Humans , Stomach Neoplasms/blood , Stomach Neoplasms/diagnosis , Biomarkers, Tumor/blood , Female , Male , Middle Aged , Matrix Metalloproteinase 13/blood , Aged , ROC Curve , Adult , Case-Control Studies , Early Detection of Cancer/methods
9.
Eur J Cancer ; 208: 114203, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38981314

ABSTRACT

PURPOSE: This study aims to investigate the underexplored prevalence of placebo-reported immune-related adverse events (irAEs) in immune checkpoint inhibitor (ICI) trials. METHODS: We searched public databases for randomized clinical trials (RCTs) involving ICI versus placebo treatments in patients with malignancies. Study characteristics and irAEs occurrences were extracted for meta-analyses using a random-effects model. MAIN OUTCOMES: Proportions of patients reported to experience any grade and grade 3 to 5 placebo irAEs; the risk ratio (RR) of reporting 'false' irAEs in the experiment arm (defined as 'false-irAE ratio', calculated by dividing the proportion of patients documented with irAEs in the placebo arm by that in the experimental arm). RESULTS: 47 RCTs with 30,119 patients were analyzed. The pooled proportion of patients reported to experience any grade and grade 3 to 5 irAEs among placebo participants was 22.85 % (17.33 %-29.50 %) and 3.40 % (2.35 %-4.63 %), respectively. The pooled proportion of placebo-treated patients who experienced serious irAEs was 0.67 % (0.03 %-1.91 %). Treatment discontinuation and death due to placebo irAEs occurred in 0.69 % (<0.01 %-1.30 %) and 0.12 % (<0.01 %-0.40 %) of patients, respectively. The false-irAE ratio for any grade and grade 3 to 5 irAEs were 0.49 and 0.28. The false-irAE ratio was significantly higher in RCTs with control arms of placebo plus non-immunotherapy than in those with placebo alone (any grade: 0.57 vs. 0.32, P < 0.001; grade 3 to 5: 0.36 vs. 0.12, P = 0.009). CONCLUSION: Our analyses of placebo-treated participants in ICI RCTs document the common occurrence of placebo irAEs. These findings are important for interpreting irAE profiles, avoiding inappropriate therapeutic interventions.

10.
Circ Arrhythm Electrophysiol ; 17(7): e012452, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39012929

ABSTRACT

BACKGROUND: Aging is one of the most potent risk determinants for the onset of atrial fibrillation (AF). Sirts (sirtuins) have been implicated in the pathogenesis of cardiovascular disease, and their expression declines with aging. However, whether Sirts involved in age-related AF and its underlying mechanisms remain unknown. The present study aims to explore the role of Sirts in age-related AF and delineate the underlying molecular mechanisms. METHODS: Sirt1 levels in the atria of both elderly individuals and aging rats were evaluated using quantitative real-time polymerase chain reaction and Western blot analysis. Mice were engineered to specifically knockout Sirt1 in the atria and right ventricle (Sirt1mef2c/mef2c). Various techniques, such as echocardiography, atrial electrophysiology, and protein acetylation modification omics were employed. Additionally, coimmunoprecipitation was utilized to substantiate the interaction between Sirt1 and RIPK1 (receptor-interacting protein kinase 1). RESULTS: We discerned that among the diverse subtypes of sirtuin proteins, only Sirt1 expression was significantly diminished in the atria of elderly people and aged rats. The Sirt1mef2c/mef2c mice exhibited an enlarged atrial diameter and heightened vulnerability to AF. Acetylated proteomics and cell experiments identified that Sirt1 deficiency activated atrial necroptosis through increasing RIPK1 acetylation and subsequent pseudokinase MLKL (mixed lineage kinase domain-like protein) phosphorylation. Consistently, necroptotic inhibitor necrosulfonamide mitigated atrial necroptosis and diminished both the atrial diameter and AF susceptibility of Sirt1mef2c/mef2c mice. Resveratrol prevented age-related AF in rats by activating atrial Sirt1 and inhibiting necroptosis. CONCLUSIONS: Our findings first demonstrated that Sirt1 exerts significant efficacy in countering age-related AF by impeding atrial necroptosis through regulation of RIPK1 acetylation, highlighting that the activation of Sirt1 or the inhibition of necroptosis could potentially serve as a therapeutic strategy for age-related AF.


Subject(s)
Atrial Fibrillation , Disease Models, Animal , Heart Atria , Mice, Knockout , Necroptosis , Receptor-Interacting Protein Serine-Threonine Kinases , Sirtuin 1 , Animals , Sirtuin 1/metabolism , Sirtuin 1/genetics , Acetylation , Heart Atria/metabolism , Heart Atria/pathology , Heart Atria/physiopathology , Receptor-Interacting Protein Serine-Threonine Kinases/metabolism , Receptor-Interacting Protein Serine-Threonine Kinases/genetics , Atrial Fibrillation/metabolism , Atrial Fibrillation/genetics , Atrial Fibrillation/physiopathology , Atrial Fibrillation/prevention & control , Atrial Fibrillation/pathology , Male , Humans , Rats , Aging/metabolism , Aging/pathology , Mice , Rats, Sprague-Dawley , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Signal Transduction , Age Factors , Aged , Mice, Inbred C57BL , Female
11.
Huan Jing Ke Xue ; 45(7): 4112-4121, 2024 Jul 08.
Article in Chinese | MEDLINE | ID: mdl-39022959

ABSTRACT

Clarifying the spatio-temporal evolution of the ecological environment quality of a watershed and its response to the natural environment and human factors are crucial for policy implementation in the ecological environment of the watershed. Using the Google earth engine(GEE) to establish a remote sensing ecological index (RSEI), the spatio-temporal changes in the ecological environment quality of the Huaihe River Basin from 2002 to 2022 were evaluated combined with trend analysis, variation coefficient, and Hurst index. The main driving factors of spatial differentiation of RSEI were explored using the geographic detector. The results showed that: ① In the past 21 years, RSEI of the Huaihe River Basin had generally improved, but it showed a gradual upward-downward trend. Overall, the area of poor and less poor grades decreased, the area of medium grades increased, and the area of good and excellent grades increased. The improved area accounted for 55.93%, and the degraded area accounted for 22.01%. ② In terms of spatial distribution, RSEI gradually deteriorated from east to west (except in the northwest and southwest marginal mountainous areas). The stability was better in the east and worse in the western and central areas. In the future, the ecological quality change in the basin was prone to be anti-sustainable and mainly improved. ③ Factor detection results showed that the spatial differentiation of RSEI in the basin was mainly driven by vegetation factors, followed by altitude. The interaction between two factors enhanced the driving force for RSEI spatial differentiation, in which the interaction between vegetation factor and elevation had the strongest driving force for RSEI spatial differentiation, reaching 86.3%.

12.
Int J Biol Macromol ; : 133767, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38986989

ABSTRACT

To address the increasing demand for sensitive and selective sample preparation methods for metal analysis; preconcentration of intended analyte from complex sample matrices before analysis is required to improve the performance of analysis instruments. In this study, we have engineered a sustainable and portable syringe-based hand-operable three-dimensionally (3D) printed sample pretreatment apparatus equipped with a replaceable bio-based thin- film metal sorbent. This device effectively addresses the challenges of sample matrix interference in metal analysis. A metal sorbent film composed of chitosan (CS) and polydopamine (PDA) leveraged the diverse functional groups in the CS/PDA matrix to significantly enhance the extraction efficiency for various metals. Our approach demonstrated excellent analytical performance, with coefficients of determination (R2) of 0.9982 for copper (Cu) and 0.996 for chromium (Cr). The method achieved low limits of detection (LOD) of 0.3 µg L-1 for Cr and 0.7 µg L-1 for Cu. Precision and practicality assessments using actual urine samples yielded satisfactory relative standard deviations (RSD%) ranging from of 1.6 %-8.5 % for both metals, indicating minimal interference from the sample matrix. Moreover, our approach exhibited robust performance even after seven consecutive extraction and desorption cycles, highlighting its sustainability and practical applicability for laboratory and on-site sample pretreatment.

13.
Nat Aging ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38987646

ABSTRACT

Emerging evidence suggests that neurological and other post-acute sequelae of COVID-19 can persist beyond or develop following SARS-CoV-2 infection. However, the long-term trajectories of cognitive change after a COVID-19 infection remain unclear. Here we investigated cognitive changes over a period of 2.5 years among 1,245 individuals aged 60 years or older who survived infection with the original SARS-CoV-2 strain in Wuhan, China, and 358 uninfected spouses. We show that the overall incidence of cognitive impairment among older COVID-19 survivors was 19.1% at 2.5 years after infection and hospitalization, evaluated using the Telephone Interview for Cognitive Status-40. Cognitive decline primarily manifested in individuals with severe COVID-19 during the initial year of infection, after which the rate of decline decelerated. Severe COVID-19, cognitive impairment at 6 months and hypertension were associated with long-term cognitive decline. These findings reveal the long-term cognitive trajectory of the disease and underscore the importance of post-infection cognitive care for COVID-19 survivors.

14.
Front Neurol ; 15: 1423956, 2024.
Article in English | MEDLINE | ID: mdl-38988601

ABSTRACT

Purpose: How cortical functional reorganization occurs after hearing loss in preschool children with congenital sensorineural hearing loss (CSNHL) is poorly understood. Therefore, we used resting-state functional MRI (rs-fMRI) to explore the characteristics of cortical reorganization in these patents. Methods: Sixty-three preschool children with CSNHL and 32 healthy controls (HCs) were recruited, and the Categories of Auditory Performance (CAP) scores were determined at the 6-month follow-up after cochlear implantation (CI). First, rs-fMRI data were preprocessed, and amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) were calculated. Second, whole-brain functional connectivity (FC) analysis was performed using bilateral primary auditory cortex as seed points. Finally, Spearman correlation analysis was performed between the differential ALFF, ReHo and FC values and the CAP score. Results: ALFF analysis showed that preschool children with CSNHL had lower ALFF values in the bilateral prefrontal cortex and superior temporal gyrus than HCs, but higher ALFF values in the bilateral thalamus and calcarine gyrus. And correlation analysis showed that some abnormal brain regions were weak negatively correlated with CAP score (p < 0.05). The ReHo values in the bilateral superior temporal gyrus, part of the prefrontal cortex and left insular gyrus were lower, whereas ReHo values in the bilateral thalamus, right caudate nucleus and right precentral gyrus were higher, in children with CSNHL than HCs. However, there was no correlation between ReHo values and the CAP scores (p < 0.05). Using primary auditory cortex (PAC) as seed-based FC further analysis revealed enhanced FC in the visual cortex, proprioceptive cortex and motor cortex. And there were weak negative correlations between the FC values in the bilateral superior temporal gyrus, occipital lobe, left postcentral gyrus and right thalamus were weakly negatively correlated and the CAP score (p < 0.05). Conclusion: After auditory deprivation in preschool children with CSNHL, the local functions of auditory cortex, visual cortex, prefrontal cortex and somatic motor cortex are changed, and the prefrontal cortex plays a regulatory role in this process. There is functional reorganization or compensation between children's hearing and these areas, which may not be conducive to auditory language recovery after CI in deaf children.

15.
Mol Metab ; : 101993, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39025297

ABSTRACT

OBJECTIVE: Proopiomelanocortin (POMC) neurons release potent anorexigenic neuropeptides, which suppress food intake and enhance energy expenditure via melanocortin receptors. Although the importance of central melanocortin in physiological regulation is well established, the underlying genetic mechanisms that define the functional identity of melanocortin neurons and maintain hypothalamic Pomc expression remain to be fully determined. In this study, we investigate the functional significance of Six3, a transcriptional regulator notably expressed in embryonic and adult mouse POMC neurons, in the regulation of hypothalamic Pomc expression and downstream physiological consequences. METHOD: We first evaluated the expression of Six3 in the developing and adult hypothalamus by double fluorescence in situ hybridization. Next, we assessed POMC immunoreactivity in mutant mice selectively lacking Six3 from Pomc-expressing neurons and quantified Pomc mRNA levels in a tamoxifen-inducible Six3 knockout mouse model activated at embryonic E9.5 days. We also determined glucose and insulin sensitivity, daily food intake, body composition and body weight in adult male and female mice lacking Six3 specifically from POMC neurons. Lastly, we assessed the physiological consequences of ablating Six3 from POMC neurons in adult mice. RESULTS: Six3 and Pomc were co-expressed in mouse hypothalamic neurons during development and adulthood. Mouse embryos deficient in Six3 showed reduced Pomc expression in the developing hypothalamus. Targeted deletion of Six3 specifically from POMC neurons resulted in decreased hypothalamic Pomc expression, increased daily food intake, enhanced glucose sensitivity and mild obesity in male but not in female mice. Finally, conditional removal of Six3 from POMC neurons in adult mice led to a reduction in hypothalamic POMC immunoreactivity with no significant effects in body weight or food intake. CONCLUSION: Altogether, our results demonstrate that Six3 plays an essential role in the early establishment of POMC neuron identity and the maintenance of physiological levels of hypothalamic Pomc expression. In addition, our study demonstrates that the functional significance of Six3 expression in POMC neurons is sexually dimorphic and age-dependent.

16.
Int J Surg ; 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38980664

ABSTRACT

BACKGROUND: We aimed to use preoperative computed tomography images to develop a radiomic nomogram to select patients who would benefit from spleen-preserving splenic hilar (No.10) lymphadenectomy (SPSHL). METHODS: A pooled analysis of three distinct prospective studies was performed. The splenic hilar lymph node (SHLN) ratio (sLNR) was established as the quotient of the number of metastatic SHLN to the total number of SHLN. Radiomic features reflecting the phenotypes of the primary tumor (RS1) and SHLN region (RS2) were extracted and used as predictive factors for sLNR. RESULTS: This study included 733 patients: 301 in the D2 group and 432 in the D2+No.10 group. The optimal sLNR cutoff value was set at 0.4, and the D2+No.10 group was divided into three groups: sLNR=0, sLNR≤0.4, and sLNR>0.4. Patients in the D2+No. 10 group were randomly divided into the training (n=302) and validation (n=130) cohorts. The AUCs value of the nomogram, including RS1 and RS2, were 0.952 in the training cohort and 0.888 in the validation cohort. The entire cohort was divided into three groups based on the nomogram scores: low, moderate and high SHLN metastasis burden groups (LMB, MMB and HMB, respectively). A similar 5-year OS rate was found between the D2 and D2+No. 10 groups in the LMB and HMB groups. In the MMB group, the 5-year OS of the D2+No. 10 group (73.4%) was significantly higher than that of the D2 group (37.6%) (P<0.001). CONCLUSIONS: The nomogram showed good predictive ability for distinguishing patients with various SHLN metastasis burdens. It can accurately identify patients who would benefit from SPSHL.

17.
Plant Phenomics ; 6: 0198, 2024.
Article in English | MEDLINE | ID: mdl-38939747

ABSTRACT

The pod and seed counts are important yield-related traits in soybean. High-precision soybean breeders face the major challenge of accurately phenotyping the number of pods and seeds in a high-throughput manner. Recent advances in artificial intelligence, especially deep learning (DL) models, have provided new avenues for high-throughput phenotyping of crop traits with increased precision. However, the available DL models are less effective for phenotyping pods that are densely packed and overlap in in situ soybean plants; thus, accurate phenotyping of the number of pods and seeds in soybean plant is an important challenge. To address this challenge, the present study proposed a bottom-up model, DEKR-SPrior (disentangled keypoint regression with structural prior), for in situ soybean pod phenotyping, which considers soybean pods and seeds analogous to human people and joints, respectively. In particular, we designed a novel structural prior (SPrior) module that utilizes cosine similarity to improve feature discrimination, which is important for differentiating closely located seeds from highly similar seeds. To further enhance the accuracy of pod location, we cropped full-sized images into smaller and high-resolution subimages for analysis. The results on our image datasets revealed that DEKR-SPrior outperformed multiple bottom-up models, viz., Lightweight-OpenPose, OpenPose, HigherHRNet, and DEKR, reducing the mean absolute error from 25.81 (in the original DEKR) to 21.11 (in the DEKR-SPrior) in pod phenotyping. This paper demonstrated the great potential of DEKR-SPrior for plant phenotyping, and we hope that DEKR-SPrior will help future plant phenotyping.

18.
Biochem Pharmacol ; : 116404, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38945279

ABSTRACT

Methicillin-resistant Staphylococcus aureus (MRSA), a notorious bacterium with high drug resistance and easy recurrence after surgery, has posed significant clinical treatment challenges. In the current scarcity of new antibiotics, the identification of adjuvants to existing antibiotics is a promising approach to combat infections caused by multidrug-resistant Gram-positive bacteria. The in vitro synergy test, which included a MIC assay, time-kill curve, antimicrobial susceptibility testing, and live/dead bacteria staining assay, revealed that laurocapram, a widely used chemical transdermal enhancer, could potentiate the antibacterial activity of cephalosporins against MRSA. In vitro, laurocapram combined with cefixime showed an excellent synergistic activity against MRSA (FICI = 0.28 ±â€¯0.00). In addition, the combination of laurocapram and cefixime may inhibited the formation of MRSA biofilm and caused cell membrane damage. Following that, we discovered that combining laurocapram with cefixime could alleviate the symptoms of mice in the MRSA skin infection model and the MRSA pneumonia model. In conclusion, laurocapram is a promising and low-cost antibacterial adjuvant, providing a new strategy for further exploring the use of lower doses of cephalosporins to combat MRSA infection.

19.
Sci Total Environ ; 945: 174121, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38901593

ABSTRACT

The widespread use of surfactants raise challenges to biological wastewater treatment. Anaerobic ammonium oxidation (anammox) process has the potential to treat wastewater containing anionic surfactants, but the response of anammox consortia at the molecular level under long-term exposure is unclear. Using high-throughput sequencing and gene quantification, combined with molecular docking, the effect of sodium dodecyl sulfonate (SDS) on anammox consortia were investigated. Levels of reactive oxygen species (ROS) might be lower than the threshold of oxidative damage, while the increase of lactate dehydrogenase (LDH) represented the cell membrane damage. Decreased abundance of functional genes (hdh, hzsA and nirS) indicated the decrease of the anammox bacterial abundance. Trace amounts of N-acyl homoserine lactone (AHL, C6-HSL, C8-HSL and C12-HSL) contained in influent could induce endogenous quorum sensing (QS), which could regulate the correlation between functional bacteria to optimize the microbial community and strengthen the resistance of anammox consortia to SDS. In addition, the proliferation of disinfectant resistance genes might increase the environmental pathogenicity of sewage discharge. This work highlights the potential response mechanism of anammox consortium to surfactants and provides a universal microbial-friendly bioenhancement strategy based on QS.


Subject(s)
Quorum Sensing , Surface-Active Agents , Waste Disposal, Fluid , Surface-Active Agents/metabolism , Waste Disposal, Fluid/methods , Wastewater/microbiology , Oxidation-Reduction , Anaerobiosis , Ammonium Compounds/metabolism , Molecular Docking Simulation , Microbial Consortia/physiology
20.
ACS Sens ; 9(6): 3433-3443, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38872232

ABSTRACT

The development of a portable, low-cost sensor capable of accurately detecting H2S gas in exhaled human breath at room temperature is highly anticipated in the fields of human health assessment and food spoilage evaluation. However, achieving outstanding gas sensing performance and applicability for flexible room-temperature operation with parts per billion H2S gas sensors still poses technical challenges. To address this issue, this study involves the in situ growth of MoS2 nanosheets on the surface of In2O3 fibers to construct a p-n heterojunction. The In2O3@MoS2-2 sensor exhibits a high response of 460.61 to 50 ppm of H2S gas at room temperature, which is 19.5 times higher than that of the pure In2O3 sensor and 322.1 times higher than that of pure MoS2. The In2O3@MoS2-2 also demonstrates a minimum detection limit of 3 ppb and maintains a stable response to H2S gas even after being bent 50 times at a 60° angle. These exceptional gas sensing properties are attributed to the increase in oxygen vacancies and chemisorbed oxygen on In2O3@MoS2-2 nanofibers as well as the formation of the p-n heterojunction, which modulates the heterojunction barrier. Furthermore, in this study, we successfully applied the In2O3@MoS2-2 sensor for oral disease and detection of food spoilage conditions, thereby providing new design insights for the development of portable exhaled gas sensors and gas sensors for evaluating food spoilage conditions at room temperature.


Subject(s)
Breath Tests , Hydrogen Sulfide , Limit of Detection , Molybdenum , Temperature , Humans , Hydrogen Sulfide/analysis , Breath Tests/methods , Breath Tests/instrumentation , Molybdenum/chemistry , Disulfides/chemistry , Indium/chemistry , Sulfides/chemistry
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