A deep eutectic solvent (DES) formulated with tetramethylammonium hydroxide pentahydrate /urea (TMAH·5H2O/Urea) was designed for the first time to dissolve cellulose at room temperature. The optimized system, characterized by a 1:3 M ratio, demonstrates the capability to dissolve approximately 7.5 wt% cellulose, boasting a high degree of polymerization (DP = 526). Notably, both the pure DES and 4.0 wt% cellulose/TMAH·5H2O/Urea mixtures manifests low viscosity, establishing its potential as an effective spinning aid in fiber manufacturing. The structural analyses shows that the cellulose crystal type shifts from type I to type II form, accompanied by a reduction in both crystallinity and DP. A pivotal aspect of this research involves determining Kamlet-Taft parameters for TMAH·5H2O/Urea-DES with different molar ratios. The results reveal these solvate DESs exhibit the high hydrogen bond basicity, which enables them to easily form hydrogen bonds with hydroxyl groups of cellulose and demonstrate good cellulose solubility. In conclusion, this solvent system presents notable advantages, including straightforward synthesis procedures, low viscosity, and well cellulose solubility, paving the way for new approaches and techniques in cellulose utilization.
OBJECTIVE: Research the dose-response relationship between overall and certain types of exercise and cognitive function in older adults with Alzheimer's disease and dementia. DESIGN: Systemic and Bayesian Model-Based Network Meta-Analysis. METHODS: In our study, we analyzed data from randomized controlled trials investigating the effects of different exercises on cognitive outcomes in older adults with AD. We searched the Web of Science, PubMed, Cochrane Central Register of Controlled Trials, and Embase up to November 2023. Using the Cochrane Risk of Bias tool (Rob2) for quality assessment and R software with the MBNMA package for data analysis, we determined standard mean differences (SMDs) and 95% confidence intervals (95%CrI) to evaluate exercise's impact on cognitive function in AD. RESULTS: Twenty-seven studies with 2,242 AD patients revealed a nonlinear relationship between exercise and cognitive improvement in AD patients. We observed significant cognitive enhancements at an effective exercise dose of up to 1000 METs-min/week (SMDs: 0.535, SD: 0.269, 95% CrI: 0.023 to 1.092). The optimal dose was found to be 650 METs-min/week (SMDs: 0.691, SD: 0.169, 95% CrI: 0.373 to 1.039), with AE (Aerobic exercise) being particularly effective. For AE, the optimal cognitive enhancement dose was determined to be 660 METs-min/week (SMDs: 0.909, SD: 0.219, 95% CrI: 0.495 to 1.362). CONCLUSION: Nonlinear dose-response relationship between exercise and cognitive improvement in Alzheimer's disease, with the optimal AE dose identified at 660 METs-min/week for enhancing cognitive function in AD.
Alzheimer Disease , Bayes Theorem , Cognition , Network Meta-Analysis , Randomized Controlled Trials as Topic , Humans , Alzheimer Disease/psychology , Alzheimer Disease/therapy , Randomized Controlled Trials as Topic/methods , Cognition/physiology , Exercise Therapy/methods , Dementia/psychology , Dementia/therapy , Aged
Modulation of scattering in random lasers (RLs) by magnetic fields has attracted much attention due to its rich physical insights. We fabricate magnetic gain polymer optical fiber to generate RLs. From macroscopic experimental phenomena, with the increase of the magnetic field strength, the magnetic transverse photocurrent exists in disordered multiple scattering of RLs and the emission intensity of RLs decreases, which is the experimental observation of photonic Hall effect (PHE) and photonic magnetoresistance (PMR) in RLs. At the microscopic level, based on the field dependence theory of magnetic disorder in scattered nanoparticles and the replica symmetry breaking theory, the magnetic-induced transverse diffusion of photons reduces the scattering disorder, and then decreases the intensity fluctuation disorder of RLs. Our work establishes a connection between the above two effects and RLs, visualizes the influence of magnetic field on RL scattering at the microscopic level, which is crucial for the design of RLs.
The gut immune system embodies a complex interplay between the gut mucosal barrier, the host's immune cells, and gut microbiota. These components exist within a dynamic environment characterized by a variety of physical cues, e.g., compression, tension, shear stress, stiffness, and viscoelasticity. The physical cues can be modified under specific pathological conditions. Given their dynamic nature, comprehending the specific effects of these physical cues on the gut immune system is critical for pathological and therapeutic studies of intestinal immune-related diseases. This review aims to discuss how physical cues influence gut immunology by affecting the gut mucosal barrier, host immune cells, and gut microbiota, defining this concept as gut mechanoimmunology. This review seeks to highlight that an enhanced understanding of gut mechanoimmunology carries therapeutic implications, not only for intestinal diseases but also for extraintestinal diseases.
Advancement of the absorbent for CO2 capture is essential in optimizing the performance and reducing the negative environmental effects associated with this technology. Despite ammonia's promise as an absorbent, the volatility limits its practical application and creates potential environmental pollution. Therein, we assess various additives (amino acids, carbonates, and alkanolamines) for ammonia-based solvents using multi-stage circulation absorber from the viewpoints of aerosol emission, ammonia emission, and CO2 capture efficiency. Experimental findings reveal that ammonia volatilization can be inhibited by the protonation of free ammonia by carboxyl groups and the formation of hydrogen bonding between amino/hydroxyl groups and ammonia, with ammonia emission reduced by 21.7â¯%, aerosol emission reduced by 26.5â¯%, and CO2 capture efficiency increased to a maximum of 87.8â¯% under the condition of adding histidine. Moreover, the experiment highlights a positive correlation between total ammonia emission and aerosol concentration/diameter. Additionally, tests combining source abatement with water wash exhibit up to 50.5â¯% aerosol removal efficiency and up to 76.6â¯% ammonia removal efficiency. To further mitigate emissions, a comprehensive approach is proposed, achieving an 84.4â¯% reduction in ammonia emission and a 61.9â¯% reduction in aerosol emission. Finally, a method for recycling ammonia for desulfurization is suggested.
An FeN4 single-atom catalyst (SAC) embedded in a graphene matrix is considered an oxygen reduction reaction (ORR) catalyst for its good activity and durability, and decoration on the Fe active site can further modulate the performance of the FeN4 SAC. In this work, the axial heteroatom (L = P, S and Cl)-decorated FeN4 SAC (FeN4L) and pure FeN4 were comparatively studied using density functional theory (DFT) calculations. It was found that the rate-determining step (RDS) in the ORR on pure FeN4 is the reduction of OH to H2O in the last step with an overpotential of 0.58 V. However, the RDS of the ORR for the axial heteroatom-decorated FeN4L is the reduction of O2 to OOH in the first step. The axial P and S heteroatom-decorated FeN4P and FeN4S exhibit lower activity than pure FeN4 since the overpotentials of the ORR on FeN4P and FeN4S are 1.02 V and 1.09 V, respectively. Meanwhile, FeN4Cl exhibits the best activity towards the ORR since it possesses the lowest overpotential (0.51 V). The main reason is that the axial heteroatom decoration alleviates the adsorption of all the species in the whole ORR, thus modulating the free energy in every elementary reaction step. A volcano relationship between the d band center and the ORR activity can be determined among the axial heteroatom-decorated FeN4L SACs. The d band center of the Fe atom in various FeN4L SACs follows the order of FeN4 > FeN4Cl > FeN4S > FeN4P, whereas the overpotential of the ORR on various catalysts follows the order of FeN4Cl > FeN4 > FeN4S ≈ FeN4P. ΔG(*OH) is a simple descriptor for the prediction of the ORR activity of various axial heteroatom-decorated FeN4L, although the RDS in the ORR is either the first step or the last step. This paper provides a guide to the design and selection of the ORR over SACs with different axial heteroatom decorations, contributing to the rational design of more powerful ORR electrocatalysts and achieving advances in electrochemical conversion and storage devices.
OBJECTIVES: In this retrospective cohort study, we aimed to assess clinical effectiveness and viral clearance following the use of molnupiravir, azvudine and paxlovid in hospitalized patients with COVID-19 in China dominated by the omicron BA.5.2 and BF.7 subvariant of SARS-CoV-2. METHODS: Enrolled patients were assigned to the molnupiravir group or the azvudine group or the paxlovid group or the control group (not taking any antiviral drugs). The primary outcome of the cohort study was viral clearance and viral burden rebound after treatment and the secondary outcome was 28-day all-cause mortality. The four groups were propensity score-matched (1:1). We plotted viral load trends for each antiviral drug intervention using locally weighted regression (LOWESS) smoothed data. Multivariate logistic regression (stepwise algorithm) models were used to determine any risk factors for 28-day mortality. RESULTS: Of the 1537 patients receiving any treatment, 886 (57.6 %) received molnupiravir, 390 (25.4 %) received azvudine, 94 (6.1 %) received paxlovid, and 167 (10.9 %) did not use any antiviral drugs. Our data analysis showed that age (OR = 1.05, 95 % CI: 1.03-1.07, P < 0.001), Charlson comorbidty index (OR = 1.32, 95 % CI: 1.18-1.48, P < 0.001), severity of COVID-19 (P < 0.001), gamma globulin (OR = 2.04, 95 % CI: 1.03-3.99, P = 0.039) and corticosteroids use (OR = 2.3, 95 % CI: 1.19-4.69, P = 0.017) were independent prognostic factors for 28-day mortality in COVID-19 patients. After propensity score matching (PSM), the paxlovid recipients (OR = 0.22, 95 % CI: 0.05-0.83, P = 0.036) or azvudine recipients (OR = 0.27, 95 % CI: 0.07-0.91, P = 0.046) had lower 28-day mortality compared to their matched controls. Viral rebound occurred in the control group around days 9-16, while no viral rebound was found in any of the three oral antiviral groups. We found that molnupiravir group performed comparably in terms of the rate of nucleic acid conversion negative compared with the paxlovid group, while azvudine group performed slightly worse compared with the paxlovid group or molnupiravir group. CONCLUSIONS: In our retrospective cohort of hospitalized patients with COVID-19 during the wave of omicron strain, the molnupiravir, paxlovid and azvudine recipients showed a faster and more stable decrease in viral load and rare virus rebound in response to antiviral treatments when compared to the controls. The study supported that initiation treatment with paxlovid and azvudine was associated with significantly lower risk of all-cause death within 28 days.
One patient with rifampin-resistant tuberculosis underwent emergency left pneumonectomy and thoracic gauze packing for hemoptysis due to recurrent hemoptysis after transcatheter arterial embolization. Vital signs were maintained by mechanical ventilation and medication. Tracheotomy and anti-tuberculosis treatment were performed. After half a year of follow-up, the patient's condition was stable.
The biophysical properties of the extracellular matrix (ECM) play a pivotal role in modulating cancer progression via cell-ECM interactions. However, the biophysical properties specific to gastric cancer (GC) remain largely unexplored. Pertinently, GC ECM shows significantly heterogeneous metamorphoses, such as matrix stiffening and intricate restructuring. By combining collagen I and alginate, this study designs an in vitro biomimetic hydrogel platform to independently modulate matrix stiffness and structure across a physiological stiffness spectrum while preserving consistent collagen concentration and fiber topography. With this platform, this study assesses the impacts of matrix biophysical properties on cell proliferation, migration, invasion, and other pivotal dynamics of AGS. The findings spotlight a compelling interplay between matrix stiffness and structure, influencing both cellular responses and ECM remodeling. Furthermore, this investigation into the integrin/actin-collagen interplay reinforces the central role of integrins in mediating cell-ECM interactions, reciprocally sculpting cell conduct, and ECM adaptation. Collectively, this study reveals a previously unidentified role of ECM biophysical properties in GC malignant potential and provides insight into the bidirectional mechanical cell-ECM interactions, which may facilitate the development of novel therapeutic horizons.
PURPOSE: To develop a 3D, high-sensitivity CEST mapping technique based on the 3D stack-of-spirals (SOS) gradient echo readout, the proposed approach was compared with conventional acquisition techniques and evaluated for its efficacy in concurrently mapping of guanidino (Guan) and amide CEST in human brain at 3 T, leveraging the polynomial Lorentzian line-shape fitting (PLOF) method. METHODS: Saturation time and recovery delay were optimized to achieve maximum CEST time efficiency. The 3DSOS method was compared with segmented 3D EPI (3DEPI), turbo spin echo, and gradient- and spin-echo techniques. Image quality, temporal SNR (tSNR), and test-retest reliability were assessed. Maps of Guan and amide CEST derived from 3DSOS were demonstrated on a low-grade glioma patient. RESULTS: The optimized recovery delay/saturation time was determined to be 1.4/2 s for Guan and amide CEST. In addition to nearly doubling the slice number, the gradient echo techniques also outperformed spin echo sequences in tSNR: 3DEPI (193.8 ± 6.6), 3DSOS (173.9 ± 5.6), and GRASE (141.0 ± 2.7). 3DSOS, compared with 3DEPI, demonstrated comparable GuanCEST signal in gray matter (GM) (3DSOS: [2.14%-2.59%] vs. 3DEPI: [2.15%-2.61%]), and white matter (WM) (3DSOS: [1.49%-2.11%] vs. 3DEPI: [1.64%-2.09%]). 3DSOS also achieves significantly higher amideCEST in both GM (3DSOS: [2.29%-3.00%] vs. 3DEPI: [2.06%-2.92%]) and WM (3DSOS: [2.23%-2.66%] vs. 3DEPI: [1.95%-2.57%]). 3DSOS outperforms 3DEPI in terms of scan-rescan reliability (correlation coefficient: 3DSOS: 0.58-0.96 vs. 3DEPI: -0.02 to 0.75) and robustness to motion as well. CONCLUSION: The 3DSOS CEST technique shows promise for whole-cerebrum CEST imaging, offering uniform contrast and robustness against motion artifacts.
BACKGROUND: Because the cases are quite scarce, we aimed to review cases of foreign body impaction penetrating the neck through the esophagus to analyze the characteristics of these cases. The open surgery skills of the surgeon, the treatment procedure and the surgeons' experience in the rare diseases were analyzed. METHODS: We collected and analyzed all cases from 2015-2020 in our hospital. Surgical skills and procedures for fasting and anti-infection treatment were reviewed retrospectively. Follow-up was telephone communication. RESULTS: Our series included 15 cases. Tenderness in the pre-cervical site was a physical sign for screening. Thirteen cases underwent a lateral neck open surgery with the incision including the left side of neck and only two cases were incised from the right side of the neck. Pus was found 3 days after the impaction in one case, the shortest time observed in our series. The esophageal laceration was only sutured primarily in 5 cases (33.33%) among all fifteen cases. After sufficient drainage (average more than 9 days), antibiotic treatment and fasting (normally 2-3 weeks), patients gradually began to switch to solid foods from fluids after complete blood counts and confirmations from esophageal radiography result. No severe complications occurred, and all the patients have no swallowing dis-function and recovered well. CONCLUSION: Surgery should be performed as soon as possible after impaction. Lateral neck approach surgery and the therapeutic procedure described in this article are safe and effective treatments.
Esophagus , Foreign Bodies , Neck , Humans , Foreign Bodies/surgery , Male , Female , Adult , Retrospective Studies , Middle Aged , Esophagus/surgery , Neck/surgery , Young Adult , Adolescent , Aged
Objective: This retrospective study aims to identify risk factors for urogenic sepsis in patients with upper urinary tract stones following ureteral flexible lithotripsy (FURL). Additionally, we analyze the clinical characteristics of bacterial infections post-surgery. Methods: A total of 759 patients who underwent FURL at the Urology Department of Zunyi Medical University were included. Univariate and multivariate Logistic regression analyses were conducted to identify independent risk factors for urogenic sepsis post-FURL. The distribution of bacteria based on preoperative urine cultures was also analyzed. Statistical analysis was performed using R4.2.2 software. Results: Of the 759 patients, positive preoperative urine culture, urine nitrite positivity, urine white blood cell count (WBC) ≥ 200 cells/µL, residual stones, and neutrophil-to-lymphocyte ratio (NLR) were found to be independent risk factors for urogenic sepsis after FURL. Among the 164 patients with positive preoperative urine cultures, 32 developed urogenic sepsis post-surgery, with 68.75% having positive preoperative cultures. The leading pathogens causing postoperative urogenic sepsis were Escherichia coli (E. coli), Enterococcus faecium, Proteus mirabilis, and Klebsiella pneumoniae. The probabilities of progression to urogenic sepsis were as follows: E. coli 19% (n = 12), Enterococcus faecium 43% (n = 3), Proteus mirabilis 33.3% (n = 1), and Klebsiella pneumoniae 33.3% (n = 1). The ages of affected patients were 47.17 ± 13.2, 53.7, 41, and 79 years, respectively. Rates of comorbid diabetes were 36.4, 66.7, 50, 100%, with nitrite positivity rates at 72.7, 33.3, 50, 0%. Ten female patients were infected with E. coli, while patients infected with Klebsiella pneumoniae had an NLR of 7.62. Conclusion: Positive preoperative urine culture, urine nitrite positivity, urine WBC ≥ 200 cells/µL, residual stones, and NLR are independent risk factors for urogenic sepsis after FURL. Escherichia coli is the predominant pathogen post-FURL, with notable female prevalence and nitrite-positive urine in infections. Enterococcus faecium infections are associated with diabetes.
The gut microbiota is closely linked to atherosclerosis. However, the role of intestinal fungi, essential members of the complex microbial community, in atherosclerosis is poorly understood. Herein, we show that gut fungi dysbiosis is implicated in patients with dyslipidemia, characterized by higher levels of Candida albicans (C. albicans), which are positively correlated with plasma total cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels. Furthermore, C. albicans colonization aggravates atherosclerosis progression in a mouse model of the disease. Through gain- and loss-of-function studies, we show that an intestinal hypoxia-inducible factor 2α (HIF-2α)-ceramide pathway mediates the effect of C. albicans. Mechanistically, formyl-methionine, a metabolite of C. albicans, activates intestinal HIF-2α signaling, which drives increased ceramide synthesis to accelerate atherosclerosis. Administration of the HIF-2α selective antagonist PT2385 alleviates atherosclerosis in mice by reducing ceramide levels. Our findings identify a role for intestinal fungi in atherosclerosis progression and highlight the intestinal HIF-2α-ceramide pathway as a target for atherosclerosis treatment.
RATIONALE & OBJECTIVE: Light and heavy chain deposition disease (LHCDD) is a rare form of monoclonal immunoglobulin deposition disease (MIDD), and limited clinical data are available characterizing this condition. We described the clinicopathological characteristics and outcomes of LHCDD. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 13 patients with biopsy-proven LHCDD, diagnosed between January 2008 to December 2022, at two Chinese medical centers. FINDINGS: Among the 13 patients described, 6 were men and 7 were women, with a mean age of 52.6 ± 8.0 years. Patients presented with hypertension (76.9%), anemia (84.6%), elevated serum creatinine (84.6%, median serum creatinine 1.7 mg/dL), proteinuria (100%, average urine protein 3.0g/24h), nephrotic syndrome (30.8%) and microscopic hematuria (76.9%). Serum immunofixation electrophoresis showed monoclonal immunoglobulin for 11 (84.6%) patients. Serum free light chain (FLC) ratios were abnormal in 11 (84.6%) patients, and heavy/light chain (HLC) ratios were abnormal in 9 of 10 (90%) patients with available data. Five patients were diagnosed with multiple myeloma. A histological diagnosis of nodular mesangial sclerosis was made in 10 (76.9%) patients. Immunofluorescence demonstrated deposits of IgG subclass (γ-κ/γ-λ:4/3) in 7 patients, and IgA (α-κ/α-λ:2/3) in 5 patients. Six patients underwent IgG subclass staining (γ1/γ2/γ3:3/2/1). The deposits of IgD-κ were confirmed by mass spectrometry in 1 patient. Among 12 patients for whom data were available over a median of 26.5 months, 11 received chemotherapy, and 1 received conservative treatment. One patient died. Three (25%) patients progressed to kidney failure. Among the 9 patients evaluable for hematological and kidney disease progression, five (56%) had a hematologic response and one (11%) achieved improvement in kidney disease. LIMITATIONS: Retrospective descriptive study, limited number of patients, UPEP or UIFE missing for most patients. CONCLUSIONS: In this case series of LHCDD, light and heavy chain deposition in kidney tissues were most frequent with monoclonal IgG1-κ. Among patients with evaluable data, more than half had hematologic response but a kidney response was uncommon.
MAIN CONCLUSION: Genome-wide identification revealed 79 BpNAC genes belonging to 16 subfamilies, and their gene structures and evolutionary relationships were characterized. Expression analysis highlighted their importance in plant selenium stress responses. Paper mulberry (Broussonetia papyrifera), a deciduous arboreal plant of the Moraceae family, is distinguished by its leaves, which are abundant in proteins, polysaccharides, and flavonoids, positioning it as a novel feedstock. NAC transcription factors, exclusive to plant species, are crucial in regulating growth, development, and response to biotic and abiotic stress. However, extensive characterization of the NAC family within paper mulberry is lacking. In this study, 79 BpNAC genes were identified from the paper mulberry genome, with an uneven distribution across 13 chromosomes. A comprehensive, genome-wide analysis of BpNACs was performed, including investigating gene structures, promoter regions, and chromosomal locations. Phylogenetic tree analysis, alongside comparisons with Arabidopsis thaliana NACs, allowed for categorizing these genes into 16 subfamilies in alignment with gene structure and motif conservation. Collinearity analysis suggested a significant homologous relationship between the NAC genes of paper mulberry and those in Morus notabilis, Ficus hispida, Antiaris toxicaria, and Cannabis sativa. Integrating transcriptome data and Se content revealed that 12 BpNAC genes were associated with selenium biosynthesis. Subsequent RT-qPCR analysis corroborated the correlation between BpNAC59, BpNAC62 with sodium selenate, and BpNAC55 with sodium selenite. Subcellular localization experiments revealed the nuclear functions of BpNAC59 and BpNAC62. This study highlights the potential BpNAC transcription factors involved in selenium metabolism, providing a foundation for strategically breeding selenium-fortified paper mulberry.
Broussonetia , Gene Expression Regulation, Plant , Phylogeny , Plant Proteins , Selenium , Transcription Factors , Transcription Factors/genetics , Transcription Factors/metabolism , Broussonetia/genetics , Broussonetia/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Selenium/metabolism , Genome, Plant , Genome-Wide Association Study , Arabidopsis/genetics , Arabidopsis/metabolism , Stress, Physiological/genetics
INTRODUCTION: Tension-type headache (TTH) is common but challenging to manage due to limited effectiveness of conventional treatments. This study examines six complementary and alternative medicine (CAM) interventions through network meta-analysis to identify effective TTH management strategies. METHODS: We searched PubMed, Embase, Web of Science, Cochrane Library, OVID, CNKI, Wanfang, VIP, and CBM databases for randomized controlled trials on CAM for TTH treatment. Headache frequency and intensity were the primary outcomes. Methodological quality was evaluated on the basis of the Cochrane risk of bias tool. We used R software to conduct this Bayesian network meta-analysis. We used mean difference (MD) with 95% credible intervals (CI) to calculate the continuous outcomes and analyzed the percentages of the surface under the cumulative ranking (SUCRA) curve. RESULTS: In total, 32 randomized controlled trials (RCTs) with 2405 participants were analyzed. For reducing headache intensity, the network meta-analysis shows that acupuncture therapy combined with traditional Chinese medicine (AT_TCM), manual therapy (MT), psychological treatment (PT), and traditional Chinese medicine combined with acupuncture and manual therapy (TCM_AT_MT) are superior to Western medicine (WM). In the SUCRA curve, TCM_AT_MT is the best for reducing headache frequency (HF). CONCLUSIONS: This review, assessed as low-quality evidence by GRADE, cautiously suggests potential benefits of PT over other CAM interventions for TTH and indicates TCM_AT_MT might better reduce HF. It proposes that combining CAM interventions could enhance outcomes. Due to the preliminary nature of these findings, further high-quality RCTs are essential to confirm these suggestions and provide clearer clinical guidance. PROSPERO REGISTRATION NUMBER: CRD42021252073.
BACKGROUND: Microsatellite instability-high (MSI-H) has emerged as a significant biological characteristic of colorectal cancer (CRC). Studies reported that MSI-H CRC generally had a better prognosis than microsatellite stable (MSS)/microsatellite instability-low (MSI-L) CRC, but some MSI-H CRC patients exhibited distinctive molecular characteristics and experienced a less favorable prognosis. In this study, our objective was to explore the metabolic transcript-related subtypes of MSI-H CRC and identify a biomarker for predicting survival outcomes. METHODS: Single-cell RNA sequencing (scRNA-seq) data of MSI-H CRC patients were obtained from the Gene Expression Omnibus (GEO) database. By utilizing the copy number variation (CNV) score, a malignant cell subpopulation was identified at the single-cell level. The metabolic landscape of various cell types was examined using metabolic pathway gene sets. Subsequently, functional experiments were conducted to investigate the biological significance of the hub gene in MSI-H CRC. Finally, the predictive potential of the hub gene was assessed using a nomogram. RESULTS: This study revealed a malignant tumor cell subpopulation from the single-cell RNA sequencing (scRNA-seq) data. MSI-H CRC was clustered into two subtypes based on the expression profiles of metabolism-related genes, and ENO2 was identified as a hub gene. Functional experiments with ENO2 knockdown and overexpression demonstrated its role in promoting CRC cell migration, invasion, glycolysis, and epithelial-mesenchymal transition (EMT) in vitro. High expression of ENO2 in MSI-H CRC patients was associated with worse clinical outcomes, including increased tumor invasion depth (p = 0.007) and greater likelihood of perineural invasion (p = 0.015). Furthermore, the nomogram and calibration curves based on ENO2 showed potential prognosis predictive performance. CONCLUSION: Our findings suggest that ENO2 serves as a novel prognostic biomarker and is associated with the progression of MSI-H CRC.
Biomarkers, Tumor , Colorectal Neoplasms , Disease Progression , Microsatellite Instability , Phosphopyruvate Hydratase , Humans , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Colorectal Neoplasms/mortality , Colorectal Neoplasms/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Phosphopyruvate Hydratase/genetics , Phosphopyruvate Hydratase/metabolism , Prognosis , Female , Male , Gene Expression Regulation, Neoplastic , Epithelial-Mesenchymal Transition/genetics , Middle Aged , Nomograms , Single-Cell Analysis , DNA Copy Number Variations
Hepatic polypeptide nutrient solution (HP) is a mixture of hepatoprotective peptides derived from fresh porcine liver with various effects. However, the role and mechanisms of HP in nonalcoholic fatty liver disease (NAFLD) are still not well understood. We investigated the effects of HP NAFLD rats induced by high-cholesterol diet (HCD) and its underlying mechanisms. Rats were provided with HCD for 4 weeks and then received HP or metformin after 2 weeks of HCD feeding. The study found that HP reduced cholesterol and triglyceride levels in rats with NAFLD (all p < .05). Histopathological examination also showed that HP improved the liver lesions induced by the HCD diet. Furthermore, the oxidative stress and inflammatory responses of NAFLD rats treated with HP were also improved. In addition, it was discovered that HP triggered the activation of AMPK and decreased the expression of SREBP-1c and FAS while enhancing the expression of PPAR α and CPT-1 in liver. These findings indicated that HP might have therapeutic potential for NAFLD, possibly via activating AMPK signaling pathway.
BACKGROUND: Accurately predicting kidney outcomes in IgA nephropathy is crucial for clinical decision making. Insufficient use of longitudinal data in previous studies has limited the accuracy and interpretability of prediction models for failing to reflect the chronic nature of IgA nephropathy. This study aimed at establishing a multivariable dynamic deep learning model using comprehensive longitudinal data for the prediction of kidney outcomes in IgA nephropathy. METHODS: In this retrospective cohort study of 2,056 IgA nephropathy patients at 18 kidney centers, a total of 28,317 data points were collected by the sliding window method. Among them, 15,462 windows in a single center were randomly assigned to training (80%) and validation (20%) sets while 8797 windows in 18 kidney centers were assigned to an independently test set. Interpretable Multi-Variable Long Short-Term Memory (IMV-LSTM), a deep learning model, was implemented to predict kidney outcomes (kidney failure or 50% decline in kidney function) based on time-invariant variables measured at biopsy and time-variant variables measured during follow-up. Risk performance was evaluated using Kaplan-Meier analysis and the C statistic. Trajectory analysis was performed to assess the various trends of clinical variables during follow-up. RESULTS: The model achieved a higher C statistic (0.93; 95% CI, 0.92-0.95) on the test set than the XGBoost prediction model that we developed in a previous study using only baseline information (C statistic, 0.84; 95% CI, 0.80-0.88). Kaplan-Meier analysis showed that groups with lower predicted risks from the full model survived longer than groups with higher risks. Time-variant variables demonstrated higher importance scores than time-invariant variables. Within time-variant variables, more recent measurements showed higher importance scores. Further interpretation showed that certain trajectory groups of time-variant variables such as serum creatinine and urine protein were associated with elevated risks of adverse outcomes. CONCLUSIONS: In IgA nephropathy, a deep learning model can be used to accurately and dynamically predict kidney prognosis based on longitudinal data, and time-variant variables show strong ability to predict kidney outcome.
Flavonoids are crucial medicinal active ingredients in Ginkgo biloba. However, the effect of protein post-translational modifications (PTMs) on flavonoid biosynthesis remains poorly explored. Lysine acetylation, a reversible PTM, plays a crucial role in metabolic regulation. This study aims to investigate the potential role of acetylation in G. biloba flavonoid biosynthesis. Through comprehensive analysis of transcriptomes, metabolomes, proteomes, and acetylated proteins in different tissues, a total of 11,788 lysine acetylation sites were identified on 4324 acetylated proteins, including 89 acetylation sites on 23 proteins. Additionally, 128 types of differentially accumulated flavonoids were identified among tissues, and a dataset of differentially expressed genes related to the flavonoid biosynthesis pathway was constructed. Twelve (CHI, C3H1, ANR, DFR, CCoAOMT1, F3H1, F3H2, CCoAOMT2, C3H2, HCT, F3'5'H, and FG2) acetylated proteins that might be involved in flavonoid biosynthesis were identified. Specifically, we found that the modification levels of CCoAOMT1 and F3'5'H sites correlated with the catalytic production of homoeriodictyol and dihydromyricetin, respectively. Inhibitors of lysine deacetylase (trichostatin A, TSA) impacted total flavonoid content in different tissues and increased flavonoid levels in G. biloba roots. Treatment with TSA revealed that expression levels of GbF3'5'H and GbCCoAOMT1 in stems and leaves aligned with total flavonoid content variations, while in roots, expression levels of GbC3H2 and GbFG2 corresponded to total flavonoid content changes. Collectively, these findings reveal for the first time the important role of acetylation in flavonoid biosynthesis.
