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1.
Science ; 385(6713): eadm6869, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39236186

ABSTRACT

Optical imaging plays a central role in biology and medicine but is hindered by light scattering in live tissue. We report the counterintuitive observation that strongly absorbing molecules can achieve optical transparency in live animals. We explored the physics behind this observation and found that when strongly absorbing molecules dissolve in water, they can modify the refractive index of the aqueous medium through the Kramers-Kronig relations to match that of high-index tissue components such as lipids. We have demonstrated that our straightforward approach can reversibly render a live mouse body transparent to allow visualization of a wide range of deep-seated structures and activities. This work suggests that the search for high-performance optical clearing agents should focus on strongly absorbing molecules.


Subject(s)
Optical Imaging , Animals , Mice , Light , Optical Imaging/methods , Refractometry , Scattering, Radiation , Water/chemistry , Skin , Muscles
2.
Sci Rep ; 14(1): 20774, 2024 09 06.
Article in English | MEDLINE | ID: mdl-39237580

ABSTRACT

Type 2 diabetes mellitus (T2DM) is a prevalent health challenge faced by countries worldwide. In this study, we propose a novel large language multimodal models (LLMMs) framework incorporating multimodal data from clinical notes and laboratory results for diabetes risk prediction. We collected five years of electronic health records (EHRs) dating from 2017 to 2021 from a Taiwan hospital database. This dataset included 1,420,596 clinical notes, 387,392 laboratory results, and more than 1505 laboratory test items. Our method combined a text embedding encoder and multi-head attention layer to learn laboratory values, and utilized a deep neural network (DNN) module to merge blood features with chronic disease semantics into a latent space. In our experiments, we observed that integrating clinical notes with predictions based on textual laboratory values significantly enhanced the predictive capability of the unimodal model in the early detection of T2DM. Moreover, we achieved an area greater than 0.70 under the receiver operating characteristic curve (AUC) for new-onset T2DM prediction, demonstrating the effectiveness of leveraging textual laboratory data for training and inference in LLMs and improving the accuracy of new-onset diabetes prediction.


Subject(s)
Diabetes Mellitus, Type 2 , Electronic Health Records , Diabetes Mellitus, Type 2/epidemiology , Humans , Taiwan/epidemiology , Neural Networks, Computer , Female , Male , ROC Curve , Middle Aged , Cohort Studies , Deep Learning , Databases, Factual
3.
Mitochondrion ; : 101954, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39245194

ABSTRACT

We rigorously assessed a comprehensive association testing framework for heteroplasmy, employing both simulated and real-world data. This framework employed a variant allele fraction (VAF) threshold and harnessed multiple gene-based tests for robust identification and association testing of heteroplasmy. Our simulation studies demonstrated that gene-based tests maintained an appropriate type I error rate at α = 0.001. Notably, when 5 % or more heteroplasmic variants within a target region were linked to an outcome, burden-extension tests (including the adaptive burden test, variable threshold burden test, and z-score weighting burden test) outperformed the sequence kernel association test (SKAT) and the original burden test. Applying this framework, we conducted association analyses on whole-blood derived heteroplasmy in 17,507 individuals of African and European ancestries (31 % of African Ancestry, mean age of 62, with 58 % women) with whole genome sequencing data. We performed both cohort- and ancestry-specific association analyses, followed by meta-analysis on both pooled samples and within each ancestry group. Our results suggest that mtDNA-encoded genes/regions are likely to exhibit varying rates in somatic aging, with the notably strong associations observed between heteroplasmy in the RNR1 and RNR2 genes (p < 0.001) and advance aging by the Original Burden test. In contrast, SKAT identified significant associations (p < 0.001) between diabetes and the aggregated effects of heteroplasmy in several protein-coding genes. Further research is warranted to validate these findings. In summary, our proposed statistical framework represents a valuable tool for facilitating association testing of heteroplasmy with disease traits in large human populations.

4.
Zhongguo Gu Shang ; 37(7): 670-5, 2024 Jul 25.
Article in Chinese | MEDLINE | ID: mdl-39104067

ABSTRACT

OBJECTIVE: To investigate the clinical effect of anterior cervical discectomy and fusion (ACDF) in the treatment of cervical spondylosis of vertebral artery type(CSA). METHODS: The clinical data of 42 patients with CSA from January 2020 to January 2022 were retrospectively analyzed. There were 25 males and 17 females, aged from 30 to 74 years old with an average of (53.9±11.0) years old. There were 18 cases with single-segment lesions, 17 cases with two-segment lesions, and 7 cases with three-segment lesions. The American Academy of Otolaryngology-Head and Neck Surgery's Hearing and Balance Committee score (CHE), the Neck Disability Index (NDI) and the cervical curvature Cobb angle were recorded before surgery and after surgery at 6 months. RESULTS: All 42 ACDF patients were followed up for 6 to 30 months with an average of (14.0±5.2) months. The operative time ranged from 95 to 220 min with an average of (160.38±36.77) min, the intraoperative blood loss ranged from 30 to 85 ml with an average of (53.60±18.98) ml. Tow patients had mild postoperative dysphagia, which improved with symptomatic treatment such as nebulized inhalation. CHE score decreased from (4.05±0.96) preoperatively to (2.40±0.70) at 6 months postoperatively (t=12.97, P<0.05). The number of improved vertigo at 6 months postoperatively was 38, with an improvement rate of 90.5%. NDI score was reduced from (34.43±8.04) preoperatively to (20.76±3.91) at 6 months postoperatively (t=11.83, P<0.05). The cervical curvature Cobb angle improved from (8.04±6.70)° preoperatively to (12.42±5.23)° at 6 months postoperatively (t=-15.96, P<0.05). CONCLUSION: The ACDF procedure has outstanding clinical efficacy in treating CSA. The operation can rapidly relieve patients' episodic vertigo symptoms by relieving bony compression and reconstructing cervical curvature. However, it is necessary to strictly grasp the indications for surgery and clarify the causes of vertigo in patients, and ACDF surgery is recommended for CSA patients for whom conservative treatment is ineffective.


Subject(s)
Cervical Vertebrae , Diskectomy , Spinal Fusion , Spondylosis , Vertebral Artery , Humans , Male , Female , Middle Aged , Diskectomy/methods , Spinal Fusion/methods , Spondylosis/surgery , Aged , Adult , Cervical Vertebrae/surgery , Vertebral Artery/surgery , Retrospective Studies , Treatment Outcome
5.
Environ Pollut ; 360: 124663, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39097257

ABSTRACT

Nanoplastics (NPs) are abundant in ocean environments, leading to environmental pollution and notable disruptions to the physiological functions of marine animals. To investigate the toxic effects of NPs on echinoderms, specifically sea cucumbers (Apostichopus japonicus), they were exposed to varying concentrations of NPs (0, 102, 104 particles/L) for 14 d. Subsequently, the 102 particles/L exposure group was purified for 35 d to elucidate the impact of both NPs exposure and purification on the intestinal bacteria structure and function. The results showed that the richness and variety of intestinal bacteria in sea cucumbers significantly reduced under NPs exposure, and then they could be restored to the pre-exposure treatment state after 35 d of purification. With the increase of NPs exposure concentration in the environment, the intestinal core bacteria gradually changed from Firmicutes and Proteobacteria to Pseudoalteromonas and Vibrio. The KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway database annotated that the gut microbiota of sea cucumbers was significantly downregulated in the glycosylation, carbohydratic and amino acid metabolic pathways (P < 0. 05), exogenous substance biodegradation and metabolism, DNA replication and repair pathways were significantly up-regulated (P < 0.05) under the exposure of NPs. In addition, nanoplastics exposure simplified the symbiotic network relationships of the gut bacteria, reduced the selective effect of host on the intestinal bacteria, and increased stochasticity. In conclusion, waterborne NPs can adversely affect the structure and function of sea cucumber intestinal bacteria, with these effects persisting for a duration. However, as the purification time lengthens, these adverse effects gradually diminish. This study aims to provide some theoretical basis for the biotoxic effects of NPs.

6.
Nat Commun ; 15(1): 6481, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39090118

ABSTRACT

The safety of energy storage devices is increasingly crucial due to the growing requirements for application under harsh conditions. Effective methods for enhancing robustness without compromising functionality are necessary. Here we present an impact-resistant, ready-to-use supercapacitor constructed from self-healable hydrogel electrolyte-infused lattice electrodes. Three-dimensional-printed carbon-coated silicon oxycarbide current collectors provide mechanical protection, with compressive stress, Young's modulus, and energy absorption up to 70.61 MPa, 2.75 GPa, and 92.15 kJ/m3, respectively. Commercially viable polyaniline and self-healable polyvinyl alcohol hydrogel are used as active coatings and electrolytes. I-wrapped package structured supercapacitor electrode exhibits a static specific capacitance of 585.51 mF/cm3 at 3 mA/cm3, with an energy density of 97.63 µWh/cm3 at a power density of 0.5 mW/cm3. It maintains operational integrity under extreme conditions, including post-impact with energy of 0.3 J/cm3, dynamic loading ranging from 0 to 18.83 MPa, and self-healing after electrolyte damage, demonstrating its promise for applications in extreme environments.

7.
Future Med Chem ; : 1-17, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39145469

ABSTRACT

Aim: Build a virtual screening model for ULK1 inhibitors based on artificial intelligence. Materials & methods: Build machine learning and deep learning classification models and combine molecular docking and biological evaluation to screen ULK1 inhibitors from 13 million compounds. And molecular dynamics was used to explore the binding mechanism of active compounds. Results & conclusion: Possibly due to less available training data, machine learning models significantly outperform deep learning models. Among them, the Naive Bayes model has the best performance. Through virtual screening, we obtained three inhibitors with IC50 of µM level and they all bind well to ULK1. This study provides an efficient virtual screening model and three promising compounds for the study of ULK1 inhibitors.


[Box: see text].

8.
Materials (Basel) ; 17(15)2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39124429

ABSTRACT

Room temperature drop hammer impact and compression after impact (CAI) experiments were conducted on carbon fiber-epoxy resin (CF/EP) composites to investigate the variation in impact load and absorbed energy, as well as to determine the residual compressive strength of CF/EP composites following impact damage. Industrial CT scanning was employed to observe the damage morphology after both impact and compression, aiding in the study of impact-damage and compression-failure mechanisms. The results indicate that, under the impact load, the surface of a CF/EP composite exhibits evident cratering as the impact energy increases, while cracks form along the length direction on the back surface. The residual compressive strength exhibits an inverse relationship with the impact energy. Impact damage occurring at an energy lower than 45 J results in end crushing during the compression of CF/EP composites, whereas energy exceeding 45 J leads to the formation of long cracks spanning the entire width of the specimen, primarily distributed symmetrically along the center of the specimen.

9.
Anal Chem ; 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39150895

ABSTRACT

Acyl-Coenzyme As (acyl-CoAs) are essential intermediates to incorporate carboxylic acids into the bioactive metabolic network across all species, which play important roles in lipid remodeling, fatty acids, and xenobiotic carboxylic metabolism. However, due to the poor liquid chromatographic behavior, the relatively low mass spectrometry (MS) sensitivity, and lack of authentic standards for annotation, the in-depth untargeted profiling of acyl-CoAs is challenging. We developed a chemical derivatization strategy of acyl-CoAs by employing 8-(diazomethyl) quinoline (8-DMQ) as the labeling reagent, which increased the detection sensitivity by 625-fold with good peak shapes. By applying the MS/MS fragmentation rules learned from the MS/MS spectra of 8-DMQ-acyl-CoA authentic standards, an 8-DMQ-acyl-CoA in silico mass spectral library containing 33,344 high-resolution tandem mass spectra of 8,336 acyl-CoA species was created. The in silico library facilitated the high-throughput and automatic annotation of acyl-CoA using multiple metabolomic data processing tools, such as NIST MS Search and MSDIAL. The feasibility of the in silico library in a complex sample was demonstrated by profiling endogenous acyl-CoAs in multiple organs of an aging mouse. 53 acyl-CoA species were annotated, including 12 oxidized fatty acyl-CoAs and 3 novel nonfatty acyl-CoAs. False positive annotations were further screened by developing an eXtreme Gradient Boosting (XGBoost) based retention time prediction model. The organ distribution and the aging dynamics of acyl-CoAs in a mouse model were discussed for the first time, which helped to elucidate the organ-specific function of acyl-CoAs and the role of different acyl-CoA species during aging.

10.
Nature ; 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39169185

ABSTRACT

Developmental myelination is a protracted process in the mammalian brain1. One theory for why oligodendrocytes mature so slowly posits that myelination may stabilize neuronal circuits and temper neuronal plasticity as animals age2-4. We tested this theory in the visual cortex, which has a well-defined critical period for experience-dependent neuronal plasticity5. During adolescence, visual experience modulated the rate of oligodendrocyte maturation in visual cortex. To determine whether oligodendrocyte maturation in turn regulates neuronal plasticity, we genetically blocked oligodendrocyte differentiation and myelination in adolescent mice. In adult mice lacking adolescent oligodendrogenesis, a brief period of monocular deprivation led to a significant decrease in visual cortex responses to the deprived eye, reminiscent of the plasticity normally restricted to adolescence. This enhanced functional plasticity was accompanied by a greater turnover of dendritic spines and coordinated reductions in spine size following deprivation. Furthermore, inhibitory synaptic transmission, which gates experience-dependent plasticity at the circuit level, was diminished in the absence of adolescent oligodendrogenesis. These results establish a critical role for oligodendrocytes in shaping the maturation and stabilization of cortical circuits and support the concept of developmental myelination acting as a functional brake on neuronal plasticity.

11.
Micromachines (Basel) ; 15(7)2024 Jun 28.
Article in English | MEDLINE | ID: mdl-39064354

ABSTRACT

In microfluidic systems, it is important to maintain flow stability to execute various functions, such as chemical reactions, cell transportation, and liquid injection. However, traditional flow sources, often bulky and prone to unpredictable fluctuations, limit the portability and broader application of these systems. Existing fluidic stabilizers, typically designed for specific flow sources, lack reconfigurability and adaptability in terms of the stabilization ratios. To address these limitations, a modular and standardized stabilizer system with tunable stabilization ratios is required. In this work, we present a Lego-like modular microfluidic stabilizer system, which is fabricated using 3D printing and offers multi-level stabilization combinations and customizable stabilization ratios through the control of fluidic RC constants, making it adaptable to various microfluidic systems. A simplified three-element circuit model is used to characterize the system by straightforwardly extracting the RC constant without intricate calculations of the fluidic resistance and capacitance. By utilizing a simplified three-element model, the stabilizer yields two well-fitted operational curves, demonstrating an R-square of 0.95, and provides an optimal stabilization ratio below 1%. To evaluate the system's effectiveness, unstable input flow at different working frequencies is stabilized, and droplet generation experiments are conducted and discussed. The results show that the microfluidic stabilizer system significantly reduces flow fluctuations and enhances droplet uniformity. This system provides a new avenue for microfluidic stabilization with a tunable stabilization ratio, and its plug-and-play design can be effectively applied across diverse applications to finely tune fluid flow behaviors in microfluidic devices.

12.
Antioxidants (Basel) ; 13(7)2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39061914

ABSTRACT

A 70-day feeding experiment was performed to investigate the effects of dietary vitamin E at different addition levels (0, 100, 200, and 400 mg/kg) on the growth, collagen content, antioxidant capacity, and expressions of genes related to the transforming growth factor beta (TGF-ß)/Sma- and Mad-related protein (SMAD) signaling pathway in sea cucumbers (Apostichopus japonicus). The results showed that the A. japonicus in the group with 200 mg/kg vitamin E exhibited significantly higher growth rates, hydroxyproline (Hyp) and type III collagen contents, and superoxide dismutase (SOD) activity, as well as the upregulation of genes related to Tenascin, SMAD1, and TGF-ß. Additionally, the A. japonicus in the group with 100 mg/kg vitamin E exhibited significantly higher body-wall indexes, denser collagen arrangements, improved texture quality, higher activities of glutathione peroxidase (GSH-Px) and peroxidase (POD), as well as the upregulation of genes related to collagen type I alpha 2 chain (COL1A2), collagen type III alpha 1 chain (COL3A1), and Sp-Smad2/3 (SMAD2/3). In contrast, the A. japonicus in the group with 400 mg/kg vitamin E showed a decrease in the growth rates, reduced Hyp contents, increased type I collagen contents, collagen fiber aggregation and a harder texture, along with the downregulation of genes related to the TGF-ß/SMAD signaling pathway. Furthermore, the A. japonicus in the group with 400 mg/kg exhibited oxidative stress, reflected by the lower activities of SOD, GSH-Px, and POD. These results indicated that A. japonicus fed diets with the addition of 100-200 mg/kg vitamin E had improved collagen retention and texture quality by increasing the activities of antioxidant enzymes and the expressions of genes in the TGF-ß/SMAD signaling pathway. However, the excessive addition of vitamin E (400 mg/kg) induced oxidative stress, which could increase the collagen degradation and fibrosis and pose a threat to the growth and texture quality of A. japonicus.

13.
Neuron ; 112(15): 2486-2502, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39002543

ABSTRACT

One key function of the brain is to control our body's movements, allowing us to interact with the world around us. Yet, many motor behaviors are not innate but require learning through repeated practice. Among the brain's motor regions, the cortico-basal ganglia circuit is particularly crucial for acquiring and executing motor skills, and neuronal activity in these regions is directly linked to movement parameters. Cell-type-specific adaptations of activity patterns and synaptic connectivity support the learning of new motor skills. Functionally, neuronal activity sequences become structured and associated with learned movements. On the synaptic level, specific connections become potentiated during learning through mechanisms such as long-term synaptic plasticity and dendritic spine dynamics, which are thought to mediate functional circuit plasticity. These synaptic and circuit adaptations within the cortico-basal ganglia circuitry are thus critical for motor skill acquisition, and disruptions in this plasticity can contribute to movement disorders.


Subject(s)
Basal Ganglia , Learning , Motor Skills , Neuronal Plasticity , Basal Ganglia/physiology , Neuronal Plasticity/physiology , Learning/physiology , Humans , Animals , Motor Skills/physiology , Cerebral Cortex/physiology , Neural Pathways/physiology , Motor Cortex/physiology
14.
Biology (Basel) ; 13(7)2024 Jul 03.
Article in English | MEDLINE | ID: mdl-39056689

ABSTRACT

To screen for immune indicators closely related to disease resistance, two species of sea urchin susceptible to black mouth disease (Strongylocentrotus intermedius, S. intermedius ♀ × Heliocidaris crassispina ♂) and three species of sea urchin resistant to black mouth disease (H. crassispina, H. crassispina ♀ × S. intermedius ♂ and Mesocentrotus nudus) were artificially infected with the black mouth pathogen Vibrio echinoideorum. The phagocytosis-related immune indices of the five sea urchin species were compared at different time points post-infection. The results demonstrated that the parameters such as apoptotic rate of phagocytes, mean contribution value (MCV) of single effective phagocyte on Acid Phosphatase (ACP), Reactive Oxygen Species (ROS), and Total Antioxidant Capacity (T-AOC) of the five sea urchin species first increased and then decreased after infection. The key time points were 3 h to 6 h and 48 h post-infection when the black mouth disease-resistant and susceptible sea urchins demonstrated differences. At 3 h or 6 h post-infection, the up-regulation folds in MCV of ACP, ROS and T-AOC of black mouth disease-resistant sea urchins were considerably higher than that of the susceptible sea urchins. At 6 h post-infection, the apoptosis rate and the phagocytic index (PI) of the black mouth disease-resistant sea urchins were significantly higher than those of the susceptible sea urchins (p < 0.05). At 48 h post-infection, the necrosis rate of phagocytes, MCV of ACP and MCV of ROS of the black mouth disease-resistant sea urchins were significantly lower than those of the susceptible sea urchins (p < 0.05). The apoptosis and necrosis rate of phagocytes, PI, and MCV on ACP, ROS may be used as indicators of disease resistance in sea urchins. Disease resistance standards in immune indices can be summarized as phagocytosis increases greatly in the early infection stage and decreases timely to a normal level after killing the pathogen in a short period.

15.
Genome Biol ; 25(1): 198, 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39075536

ABSTRACT

Single-cell multi-omics data reveal complex cellular states, providing significant insights into cellular dynamics and disease. Yet, integration of multi-omics data presents challenges. Some modalities have not reached the robustness or clarity of established transcriptomics. Coupled with data scarcity for less established modalities and integration intricacies, these challenges limit our ability to maximize single-cell omics benefits. We introduce scCross, a tool leveraging variational autoencoders, generative adversarial networks, and the mutual nearest neighbors (MNN) technique for modality alignment. By enabling single-cell cross-modal data generation, multi-omics data simulation, and in silico cellular perturbations, scCross enhances the utility of single-cell multi-omics studies.


Subject(s)
Single-Cell Analysis , Single-Cell Analysis/methods , Humans , Computer Simulation , Genomics/methods , Software , Computational Biology/methods , Multiomics
16.
Commun Biol ; 7(1): 923, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39085477

ABSTRACT

The emergence of single-cell Hi-C (scHi-C) technology has provided unprecedented opportunities for investigating the intricate relationship between cell cycle phases and the three-dimensional (3D) structure of chromatin. However, accurately predicting cell cycle phases based on scHi-C data remains a formidable challenge. Here, we present scHiCyclePred, a prediction model that integrates multiple feature sets to leverage scHi-C data for predicting cell cycle phases. scHiCyclePred extracts 3D chromatin structure features by incorporating multi-scale interaction information. The comparative analysis illustrates that scHiCyclePred surpasses existing methods such as Nagano_method and CIRCLET across various metrics including accuracy (ACC), F1 score, Precision, Recall, and balanced accuracy (BACC). In addition, we evaluate scHiCyclePred against the previously published CIRCLET using the dataset of complex tissues (Liu_dataset). Experimental results reveal significant improvements with scHiCyclePred exhibiting improvements of 0.39, 0.52, 0.52, and 0.39 over the CIRCLET in terms of ACC, F1 score, Precision, and Recall metrics, respectively. Furthermore, we conduct analyses on three-dimensional chromatin dynamics and gene features during the cell cycle, providing a more comprehensive understanding of cell cycle dynamics through chromatin structure. scHiCyclePred not only offers insights into cell biology but also holds promise for catalyzing breakthroughs in disease research. Access scHiCyclePred on GitHub at https:// github.com/HaoWuLab-Bioinformatics/ scHiCyclePred .


Subject(s)
Cell Cycle , Chromatin , Deep Learning , Single-Cell Analysis , Single-Cell Analysis/methods , Chromatin/metabolism , Chromatin/chemistry , Humans , Computational Biology/methods
17.
ACS Biomater Sci Eng ; 10(8): 4839-4854, 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39079050

ABSTRACT

Intervertebral disc degeneration (IVDD) is a prevalent chronic condition causing spinal pain and functional impairment. This study investigates the role of extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUCMSCs) in regulating IVDD. Using RNA-seq, we analyzed differential expressions of lncRNA and miRNA in nucleus pulposus tissues from various mouse groups. We identified key regulatory molecules, MALAT1 and miRNA-138-5p, which contribute to IVDD. Further experiments demonstrated that MALAT1 can up-regulate SLC7A11 expression by competitively binding to miR-138-5p, forming a MALAT1/miR-138-5p/SLC7A11 coexpression regulatory network. This study elucidates the molecular mechanism by which hUCMSC-derived EVs regulate IVDD and could help develop novel therapeutic strategies for treating this condition. Our findings demonstrate that hUCMSCs-EVs inhibit ferroptosis in nucleus pulposus cells, thereby improving IVDD. These results highlight the therapeutic potential of hUCMSCs-EVs in ameliorating the development of IVDD, offering significant scientific and clinical implications for new treatments.


Subject(s)
Extracellular Vesicles , Intervertebral Disc Degeneration , Mesenchymal Stem Cells , MicroRNAs , RNA, Long Noncoding , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Intervertebral Disc Degeneration/therapy , Intervertebral Disc Degeneration/genetics , Intervertebral Disc Degeneration/metabolism , Intervertebral Disc Degeneration/pathology , Humans , Mesenchymal Stem Cells/metabolism , Animals , Extracellular Vesicles/metabolism , Extracellular Vesicles/genetics , Mice , Nucleus Pulposus/metabolism , Nucleus Pulposus/pathology , Umbilical Cord/cytology , Umbilical Cord/metabolism , Male , Mice, Inbred C57BL , Gene Expression Regulation , Ferroptosis/genetics
18.
PeerJ ; 12: e17677, 2024.
Article in English | MEDLINE | ID: mdl-38974410

ABSTRACT

Background: The study aims to evaluate the diagnostic efficacy of contrast-enhanced ultrasound (CEUS) and shear-wave elastography (SWE) in detecting small malignant breast nodules in an effort to inform further refinements of the Breast Imaging Reporting and Data System (BI-RADS) classification system. Methods: This study retrospectively analyzed patients with breast nodules who underwent conventional ultrasound, CEUS, and SWE at Gongli Hospital from November 2015 to December 2019. The inclusion criteria were nodules ≤ 2 cm in diameter with pathological outcomes determined by biopsy, no prior treatments, and solid or predominantly solid nodules. The exclusion criteria included pregnancy or lactation and low-quality images. Imaging features were detailed and classified per BI-RADS. Diagnostic accuracy was assessed using receiver operating characteristic curves. Results: The study included 302 patients with 305 breast nodules, 113 of which were malignant. The diagnostic accuracy was significantly improved by combining the BI-RADS classification with CEUS and SWE. The combined approach yielded a sensitivity of 88.5%, specificity of 87.0%, positive predictive value of 80.0%, negative predictive value of 92.8%, and accuracy of 87.5% with an area under the curve of 0.877. Notably, 55.8% of BI-RADS 4A nodules were downgraded to BI-RADS 3 and confirmed as benign after pathological examination, suggesting the potential to avoid unnecessary biopsies. Conclusion: The integrated use of the BI-RADS classification, CEUS, and SWE enhances the accuracy of differentiating benign and malignant small breast nodule, potentially reducing the need for unnecessary biopsies.


Subject(s)
Breast Neoplasms , Contrast Media , Elasticity Imaging Techniques , Ultrasonography, Mammary , Humans , Female , Elasticity Imaging Techniques/methods , Retrospective Studies , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Middle Aged , Adult , Ultrasonography, Mammary/methods , Aged , Sensitivity and Specificity , ROC Curve , Breast/diagnostic imaging , Breast/pathology
19.
Nat Commun ; 15(1): 5989, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39013867

ABSTRACT

Single-cell sequencing is a crucial tool for dissecting the cellular intricacies of complex diseases. Its prohibitive cost, however, hampers its application in expansive biomedical studies. Traditional cellular deconvolution approaches can infer cell type proportions from more affordable bulk sequencing data, yet they fall short in providing the detailed resolution required for single-cell-level analyses. To overcome this challenge, we introduce "scSemiProfiler", an innovative computational framework that marries deep generative models with active learning strategies. This method adeptly infers single-cell profiles across large cohorts by fusing bulk sequencing data with targeted single-cell sequencing from a few rigorously chosen representatives. Extensive validation across heterogeneous datasets verifies the precision of our semi-profiling approach, aligning closely with true single-cell profiling data and empowering refined cellular analyses. Originally developed for extensive disease cohorts, "scSemiProfiler" is adaptable for broad applications. It provides a scalable, cost-effective solution for single-cell profiling, facilitating in-depth cellular investigation in various biological domains.


Subject(s)
Single-Cell Analysis , Single-Cell Analysis/methods , Humans , Deep Learning , Computational Biology/methods , Gene Expression Profiling/methods , Supervised Machine Learning
20.
World J Clin Cases ; 12(21): 4483-4490, 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39070817

ABSTRACT

BACKGROUND: Renal stones ranging 20-40 mm are very common in China. Although no large-sample clinical studies have confirmed the clinical efficacy and safety of this method, there is also a lack of comparative data with traditional treatment. AIM: To investigate the clinical efficacy of flexible ureteroscopy (FURS) and percutaneous nephrolithotomy (PCNL) by postoperative stone clearance and changes in soluble vascular cell adhesion molecule 1 (sVCAM-1) and kidney injury molecule 1 (KIM-1) levels in patients with large kidney stones (> 2 cm in diameter). METHODS: This single-center observational study was performed at a Chinese hospital between January 1, 2021, and October 30, 2023. All 250 enrolled patients were diagnosed with large kidney stones (> 2 cm) and divided into a FURS group (n = 145) and a PCNL group (n = 105) by the surgical method. The FURS group was treated with flexible ureteroscopy and the PCNL group was treated with percutaneous nephrolithotomy. The operation time, time to palinesthesia, intraoperative blood loss, drop in hemoglobin, length of hospital stay, stone clearance rate, and complications were recorded in the two groups. Preoperative and postoperative serum sVCAM-1 levels, erythrocyte sedimentation rate (ESR), urine KIM-1 levels, preoperative and postoperative pain visual analog scale (VAS) and Wisconsin Stone Quality of Life Questionnaire (WISQOL) scores were also documented. RESULTS: All 250 eligible patients completed the follow-up. There were no significant differences in baseline characteristics between the two groups (P > 0.05). The operation time in the FURS group was significantly greater than that in the PCNL group. The time to ambulation, intraoperative blood loss, decrease in hemoglobin, and length of hospital stay were significantly lower in the FURS group than in the PCNL group. The FURS group also had a significantly higher stone clearance rate and a lower incidence of postoperative complications. There was no significant difference in antibiotic use between the groups. Postoperative serum sVCAM-1 levels, urine KIM-1 levels, and VAS scores were lower in the FURS group than in the PCNL group, but postoperative ESR and WISQOL scores were greater in the FURS group than in the PCNL group. CONCLUSION: FURS demonstrated superior clinical efficacy in treating large kidney stones (> 2 cm in diameter) compared PCNL. It not only improved the postoperative stone clearance rate and reduced complications and recovery time but also positively affected serum SCM-1, ESR, and urine KIM-1 levels, subsequent improvement of patient quality of life.

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