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1.
Bioresour Technol ; 396: 130420, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38336213

RESUMO

An integrated process for the co-production of cellulosic ethanol and microalgal biomass by fixing CO2 generated from bioethanol fermentation is proposed. Specifically, over one-fifth of the fermentative carbon was converted into high-purity CO2 during ethanol production. The optimal concentration of 4 % CO2 was identified for the growth and metabolism of Chlorella sp. BWY-1. A multiple short-term intermittent CO2 supply system was established to efficiently fix and recycle the waste CO2. Using this system, economical co-production of cellulosic ethanol by Zymomonas mobilis and microalgal biomass in biogas slurry wastewater was achieved, resulting in the production of ethanol at a rate of 0.4 g/L/h and a fixed fermentation CO2 of 3.1 g/L/d. Moreover, the amounts of algal biomass and chlorophyll a increased by over 50 % and two-fold, respectively. Through techno-economic analysis, the integrated process demonstrated its cost-effectiveness for cellulosic ethanol production. This study presents an innovative approach to a low-carbon circular bioeconomy.

2.
Sci Adv ; 10(7): eadl1299, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363846

RESUMO

Reservoir computing is a powerful neural network-based computing paradigm for spatiotemporal signal processing. Recently, physical reservoirs have been explored based on various electronic devices with outstanding efficiency. However, the inflexible temporal dynamics of these reservoirs have posed fundamental restrictions in processing spatiotemporal signals with various timescales. Here, we fabricated thin-film transistors with controllable temporal dynamics, which can be easily tuned with electrical operation signals and showed excellent cycle-to-cycle uniformity. Based on this, we constructed a temporal adaptive reservoir capable of extracting temporal information of multiple timescales, thereby achieving improved accuracy in the human-activity-recognition task. Moreover, by leveraging the former computing output to modify the hyperparameters, we constructed a closed-loop architecture that equips the reservoir computing system with temporal self-adaptability according to the current input. The adaptability is demonstrated by accurate real-time recognition of objects moving at diverse speed levels. This work provides an approach for reservoir computing systems to achieve real-time processing of spatiotemporal signals with compound temporal characteristics.

3.
Nat Commun ; 15(1): 1132, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326298

RESUMO

The exponential growth of various complex images is putting tremendous pressure on storage systems. Here, we propose a memristor-based storage system with an integrated near-storage in-memory computing-based convolutional autoencoder compression network to boost the energy efficiency and speed of the image compression/retrieval and improve the storage density. We adopt the 4-bit memristor arrays to experimentally demonstrate the functions of the system. We propose a step-by-step quantization aware training scheme and an equivalent transformation for transpose convolution to improve the system performance. The system exhibits a high (>33 dB) peak signal-to-noise ratio in the compression and decompression of the ImageNet and Kodak24 datasets. Benchmark comparison results show that the 4-bit memristor-based storage system could reduce the latency and energy consumption by over 20×/5.6× and 180×/91×, respectively, compared with the server-grade central processing unit-based/the graphics processing unit-based processing system, and improve the storage density by more than 3 times.

4.
Inorg Chem ; 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38374612

RESUMO

A family of rare-earth complexes [RE(III) = Y, La, Gd, Tb, Dy, and Er] with doubly reduced dibenzo[a,e]cyclooctatetraene (DBCOT) has been synthesized and structurally characterized. X-ray diffraction analysis confirms that all products of the [RE(DBCOT)(THF)4][RE(DBCOT)2] composition consist of the anionic sandwich [RE(DBCOT)2]- and the cationic counterpart [RE(DBCOT)(THF)4]+. Within the sandwich, two elongated π decks are slightly bent toward the metal center (avg. 7.3°) with a rotation angle of 35.9-37.6°. The RE(III) ion is entrapped between the central eight-membered rings of DBCOT2- in a η8 fashion. The trends in the RE-COT bond lengths are consistent with the variations of the ionic radii of RE(III) centers. The 1H NMR spectra of the diamagnetic Y(III) and La(III) analogues illustrate the distinct solution behavior for the cationic and anionic parts in this series. Magnetic measurements for the Dy analogue reveal single-molecule magnetism, which was rationalized by considering the effect of crystal-field splitting for both building units analyzed by electronic structure calculations.

5.
ACS Synth Biol ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38377538

RESUMO

The advancement of metabolic engineering and synthetic biology has promoted in-depth research on the nonmodel microbial metabolism, and the potential of nonmodel organisms in industrial biotechnology is becoming increasingly evident. The nonmodel organism Pseudomonas chlororaphis is a safe plant growth promoting bacterium for the production of phenazine compounds; however, its application is seriously hindered due to the lack of an effective gene expression precise regulation toolkit. In this study, we constructed a library of 108 promoter-5'-UTR (PUTR) and characterized them through fluorescent protein detection. Then, 6 PUTRs with stable low, intermediate, and high intensities were further characterized by report genes lacZ encoding ß-galactosidase from Escherichia coli K12 and phzO encoding PCA monooxygenase from P. chlororaphis GP72 and thus developed as a static gene expression regulation system. Furthermore, the stable and high-intensity expressed PMOK_RS0128085UTR was fused with the LacO operator to construct an IPTG-induced plasmid, and a self-induced plasmid was constructed employing the high-intensity PMOK_RS0116635UTR regulated by cell density, resulting in a dynamic gene expression regulation system. In summary, this study established two sets of static and dynamic regulatory systems for P. chlororaphis, providing an effective toolkit for fine-tuning gene expression and reprograming the metabolism flux.

6.
Cardiovasc Diabetol ; 23(1): 73, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365751

RESUMO

BACKGROUND: Stress hyperglycemia ratio (SHR) has recently been recognized as a novel biomarker that accurately reflects acute hyperglycemia status and is associated with poor prognosis of heart failure. We evaluated the relationship between SHR and clinical outcomes in patients with severe aortic stenosis receiving transcatheter aortic valve replacement (TAVR). METHODS: There were 582 patients with severe native aortic stenosis who underwent TAVR consecutively enrolled in the study. The formula used to determine SHR was as follows: admission blood glucose (mmol/L)/(1.59×HbA1c[%]-2.59). The primary endpoint was defined as all-cause mortality, while secondary endpoints included a composite of cardiovascular mortality or readmission for heart failure, and major adverse cardiovascular events (MACE) including cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke. Multivariable Cox regression and restricted cubic spline analysis were employed to assess the relationship between SHR and endpoints, with hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 3.9 years, a total of 130 cases (22.3%) of all-cause mortality were recorded. Results from the restricted cubic spline analysis indicated a linear association between SHR and all endpoints (p for non-linearity > 0.05), even after adjustment for other confounding factors. Per 0.1 unit increase in SHR was associated with a 12% (adjusted HR: 1.12, 95% CI: 1.04-1.21) higher incidence of the primary endpoint, a 12% (adjusted HR: 1.12, 95% CI: 1.02-1.22) higher incidence of cardiovascular mortality or readmission for heart failure, and a 12% (adjusted HR: 1.12, 95% CI: 1.01-1.23) higher incidence of MACE. Subgroup analysis revealed that SHR had a significant interaction with diabetes mellitus with regard to the risk of all-cause mortality (p for interaction: 0.042). Kaplan-Meier survival analysis showed that there were significant differences in the incidence of all endpoints between the two groups with 0.944 as the optimal binary cutoff point of SHR (all log-rank test: p < 0.05). CONCLUSIONS: Our study indicates linear relationships of SHR with the risk of all-cause mortality, cardiovascular mortality or readmission for heart failure, and MACE in patients with severe aortic stenosis receiving TAVR after a median follow-up of 3.9 years. Patients with an SHR exceeding 0.944 had a poorer prognosis compared to those with lower SHR values.


Assuntos
Estenose da Valva Aórtica , Insuficiência Cardíaca , Hiperglicemia , Substituição da Valva Aórtica Transcateter , Humanos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Prognóstico , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Estudos Prospectivos , Resultado do Tratamento , Hiperglicemia/diagnóstico , Fatores de Risco
7.
Small ; : e2309476, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38348999

RESUMO

Complex wound repair due to tumor recurrence and infection following tumor resection presents significant clinical challenges. In this study, a bifunctional nanocomposite immune hydrogel dressing, SerMA-LJC, is developed to address the issues associated with repairing infected damaged tissues and preventing tumor recurrence. Specifically, the immune dressing is composed of methacrylic anhydride-modified sericin (SerMA) and self-assembled nanoparticles (LJC) containing lonidamine (Lon), JQ1, and chlorine e6 (Ce6). In vitro and in vivo experiments demonstrate that the nanocomposite hydrogel dressing can trigger immunogenic cell death (ICD) and has a potent anti-tumor effect. Moreover, this dressing can mitigate the acidic microenvironment of tumor cells and suppress the overexpression of PD-L1 on the tumor cell surface, thereby altering the immunosuppressive tumor microenvironment and augmenting the anti-tumor immune response. Further, the RNA sequencing analysis revealed that the hydrogel dressing significantly impacts pathways associated with positive regulation of immune response, apoptotic process, and other relevant pathways, thus triggering a potent anti-tumor immune response. More importantly, the dressing generates a substantial amount of reactive oxygen species (ROS), which can effectively kill Staphylococcus aureus and promote infectious wound healing. In conclusion, this dual-function nanocomposite immune hydrogel dressing exhibits promise in preventing tumor recurrence and promoting infectious wound healing.

8.
Br J Cancer ; 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355839

RESUMO

BACKGROUND: We aimed to redefine Immune checkpoint inhibitors (ICIs)-responsive "hot" TME and develop a corresponding stratification model to maximize ICIs-efficacy in Hepatocellular Carcinoma (HCC). METHODS: Hypoxic scores were designed, and the relevance to immunotherapy responses were validated in pan-cancers through single cell analysis. Multi-omics analysis using the hypoxic scores and immune infiltrate abundance was performed to redefine the ICIs-responsive TME subtype in HCC patients from TCGA (n = 363) and HCCDB database (n = 228). The immune hypoxic stress index (IHSI) was constructed to stratify the ICIs-responsive TME subtype, with exploring biological mechanism in vitro and in vivo. MRI-radiomics models were built for clinical applicability. RESULTS: The hypoxic scores were lower in the dominant cell-subclusters of responders in pan-cancers. The higher immune infiltrate-normoxic (HIN) subtype was redefined as the ICIs-responsive TME. Stratification of the HIN subtype using IHSI effectively identified ICIs-responders in Melanoma (n = 122) and urological cancer (n = 22). TRAF3IP3, the constituent gene of IHSI, was implicated in ICIs-relevant "immune-hypoxic" crosstalk by stimulating MAVS/IFN-I pathway under normoxic condition. MRI-radiomics models assessing TRAF3IP3 with HIF1A expression (AUC > 0.80) screened ICIs-Responders in HCC cohort (n = 75). CONCLUSION: The hypoxic-immune stratification redefined ICIs-responsive TME and provided MRI-Radiomics models for initial ICIs-responders screening, with IHSI facilitating further identification.

9.
J Funct Biomater ; 15(2)2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38391890

RESUMO

Since chondrocytes are highly vulnerable to oxidative stress, an anti-oxidative bioink combined with 3D bioprinting may facilitate its applications in cartilage tissue engineering. We developed an anti-oxidative bioink with methacrylate-modified rutin (RTMA) as an additional bioactive component and glycidyl methacrylate silk fibroin as a biomaterial component. Bioink containing 0% RTMA was used as the control sample. Compared with hydrogel samples produced with the control bioink, solidified anti-oxidative bioinks displayed a similar porous microstructure, which is suitable for cell adhesion and migration, and the transportation of nutrients and wastes. Among photo-cured samples prepared with anti-oxidative bioinks and the control bioink, the sample containing 1 mg/mL of RTMA (RTMA-1) showed good degradation, promising mechanical properties, and the best cytocompatibility, and it was selected for further investigation. Based on the results of 3D bioprinting tests, the RTMA-1 bioink exhibited good printability and high shape fidelity. The results demonstrated that RTMA-1 reduced intracellular oxidative stress in encapsulated chondrocytes under H2O2 stimulation, which results from upregulation of COLII and AGG and downregulation of MMP13 and MMP1. By using in vitro and in vivo tests, our data suggest that the RTMA-1 bioink significantly enhanced the regeneration and maturation of cartilage tissue compared to the control bioink, indicating that this anti-oxidative bioink can be used for 3D bioprinting and cartilage tissue engineering applications in the future.

10.
J Trace Elem Med Biol ; 83: 127413, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38387427

RESUMO

BACKGROUND: Iodine excess (IE) intake leads to lymphocyte dysfunction and contributes to autoimmune thyroiditis (AIT). Abnormal thyroid function is associated with adverse cardiovascular events, endothelial dysfunction is often an early pathophysiological feature in most cardiovascular disease. However, the relationship between iodine and the cardiovascular system is currently unclear. Therefore, the aim of this study was to investigate the effects of IE on endothelial function in mouse model. METHODS: A total of 24 NOD.H-2h4 mice were randomly divided into different groups. A sodium iodide (NaI) group supplied with 0.05% NaI water for 8 weeks. Serum levels of tumor necrosis factors α (TNFα), interleukin-6 (IL-6) and C-reactive Protein (CRP), as well as endothelin-1 (ET-1), von Willebrand factor (VWF) and thrombomodulin (THBD) were detected by Elisa. In addition, the mRNA and protein expression of these genes were measured by RT-PCR and Western blotting. RESULTS: Here, we found the urinary iodine concentration (UIC) was higher in the NaI group compared to the control group. Serum levels of ET-1, VWF, and THBD were also significantly lower in the NaI group, however, CRP serum levels are significantly increased. In aorta, the mRNA and protein expression of ET-1, VWF, THBD were downregulated, however, the expression of IL-6, CRP and TNFα mRNA and protein were upregulated in the NaI group. A correlation analysis showed negative correlation between UIC with ET-1, VWF, and THBD, similarly, negative correlation between CRP with THBD was observed. In addition, positive correlations between UIC with CRP. CONCLUSION: Collectively, in the NOD.H-2h4 mice, IE supplementation had a suppressive effect on endothelial function, and this inhibition maybe due to the increase expression of inflammatory cytokines.

11.
Aging (Albany NY) ; 16(3): 2989-3006, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38329438

RESUMO

BACKGROUND: Growing experimental evidence indicates that cognitive impairment is linked to neuroinflammation. Minocycline (MINO), an antibiotic known for its anti-inflammatory, has shown promise in alleviating cognitive impairment. Nonetheless, the exact mechanism through which MINO improves cognitive impairment is not yet understood. METHODS: A neuroinflammatory model was establish by utilizing lipopolysaccharide. The assessment of mice's cognitive and learning abilities was conducted through the MWM and Y-maze tests. The evaluation of hippocampal neuronal injury and microglial activation were achieved by performing HE staining and IHC, respectively. To evaluate BV2 cell viability and apoptosis, the CCK-8 and Hoechst 33342/PI staining assays were employed. In order to assess the protein and RNA expression levels of NLRP3, caspase-1, IL-1ß, IL-18, Iba-1, and Bcl2/Bax, WB and RT-qPCR were utilized. Additionally, the inhibitory effect of MINO on apoptosis by targeting the NLRP3/caspase-1 pathway was investigated using Nigericin. RESULTS: MINO was effective in reducing the time it took for mice to escape from the test, increasing the number of platforms they crossed, and mitigating damage to the hippocampus while also suppressing microglial activation and the expression of Iba-1 in a neuroinflammatory model caused by LPS. Furthermore, MINO improved the viability of BV2 cell and reduced apoptosis. It also had the effect of reducing the expression levels of NLRP3/Caspase-1, IL-1ß, IL-18, and BAX, while upregulating the expression of Bcl2. Additionally, MINO was found to downregulate the NLRP3 expression, which is specifically activated by nigericin. CONCLUSION: The protective effect of MINO relies on the crucial involvement of the NLRP3/caspase-1 pathway.


Assuntos
Disfunção Cognitiva , Proteína 3 que Contém Domínio de Pirina da Família NLR , Camundongos , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Lipopolissacarídeos/toxicidade , Minociclina/farmacologia , Minociclina/uso terapêutico , Interleucina-18 , Caspase 1/metabolismo , Nigericina , Proteína X Associada a bcl-2 , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo
12.
J Sci Food Agric ; 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38348948

RESUMO

BACKGROUND: Obesity has been demonstrated as a risk factor that seriously affects health. Insoluble dietary fiber (IDF), as a major component of dietary fiber, has positive effects on obesity, inflammation and diabetes. RESULTS: In this study, complex IDF was prepared using 50% enoki mushroom IDF, 40% carrot IDF, and 10% oat IDF. The effects and potential mechanism of complex IDF on obesity were investigated in C57BL/6 mice fed a high-fat diet. The results showed that feeding diets containing 5% complex IDF for 8 weeks significantly reduced mouse body weight, epididymal lipid index, and ectopic fat deposition, and improved mouse liver lipotoxicity (reduced serum levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase), fatty liver, and short-chain fatty acid composition. High-throughput sequencing of 16S rRNA and analysis of fecal metabolomics showed that the intervention with complex IDF reversed the high-fat-diet-induced dysbiosis of gut microbiota, which is associated with obesity and intestinal inflammation, and affected metabolic pathways, such as primary bile acid biosynthesis, related to fat digestion and absorption. CONCLUSION: Composite IDF intervention can effectively inhibit high-fat-diet-induced obesity and related symptoms and affect the gut microbiota and related metabolic pathways in obesity. Complex IDF has potential value in the prevention of obesity and metabolic syndrome. © 2024 Society of Chemical Industry.

13.
Natl Sci Rev ; 11(3): nwae031, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38410826

RESUMO

Carbyne, an elusive sp-hybridized linear carbon allotrope, has fascinated chemists and physicists for decades. Due to its high chemical reactivity and extreme instability, carbyne was much less explored in contrast to the sp2-hybridized carbon allotropes such as graphene. Herein, we report the on-surface synthesis of polyynic carbon chains by demetallization of organometallic polyynes on the Au(111) surface; the longest one observed consists of ∼60 alkyne units (120 carbon atoms). The polyynic structure of carbon chains with alternating triple and single bonds was unambiguously revealed by bond-resolved atomic force microscopy. Moreover, an atomically precise polyyne, C14, was successfully produced via tip-induced dehalogenation and ring-opening of the decachloroanthracene molecule (C14Cl10) on a bilayer NaCl/Au(111) surface at 4.7 K, and a band gap of 5.8 eV was measured by scanning tunnelling spectroscopy, in a good agreement with the theoretical HOMO-LUMO gap (5.48 eV).

14.
J Immunol Res ; 2024: 6622950, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38314088

RESUMO

Our research addresses the critical environmental issue of a fine particulate matter (PM2.5), focusing on its association with the increased infection risks. We explored the influence of PM2.5 on human beta-defensin 1 (HBD1), an essential peptide in mucosal immunity found in the airway epithelium. Using C57BL/6J mice and human bronchial epithelial cells (HBE), we examined the effects of PM2.5 exposure followed by Pseudomonas aeruginosa (P. aeruginosa) infection on HBD1 expression at both mRNA and protein levels. The study revealed that PM2.5's toxicity to epithelial cells and animals varies with time and concentration. Notably, HBE cells exposed to PM2.5 and P. aeruginosa showed increased bacterial invasion and decreased HBD1 expression compared to the cells exposed to P. aeruginosa alone. Similarly, mice studies indicated that combined exposure to PM2.5 and P. aeruginosa significantly reduced survival rates and increased bacterial invasion. These harmful effects, however, were alleviated by administering exogenous HBD1. Furthermore, our findings highlight the activation of MAPK and NF-κB pathways following PM2.5 exposure. Inhibiting these pathways effectively increased HBD1 expression and diminished bacterial invasion. In summary, our study establishes that PM2.5 exposure intensifies P. aeruginosa invasion in both HBE cells and mouse models, primarily by suppressing HBD1 expression. This effect can be counteracted with exogenous HBD1, with the downregulation mechanism involving the MAPK and NF-κB pathways. Our study endeavors to elucidate the pathogenesis of lung infections associated with PM2.5 exposure, providing a novel theoretical basis for the development of prevention and treatment strategies, with substantial clinical significance.


Assuntos
NF-kappa B , beta-Defensinas , Humanos , Camundongos , Animais , NF-kappa B/metabolismo , beta-Defensinas/genética , beta-Defensinas/metabolismo , Camundongos Endogâmicos C57BL , Pulmão/patologia , Material Particulado/efeitos adversos
15.
Kidney Med ; 6(2): 100760, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38304582

RESUMO

Rationale & Objective: This study describes the epidemiology, characteristics, and clinical outcomes of patients with focal segmental glomerulosclerosis (FSGS)-attributed kidney failure in the US Renal Data System (USRDS) during 2008-2018, and health care resource utilization and costs among those with Medicare-linked data. Study Design: This was a retrospective cohort study. Setting & Population: Patients with FSGS-attributed kidney failure in the USRDS were enrolled in the study. Outcomes: The outcomes were as follows: Prevalence and incidence, clinical and demographic characteristics, time to kidney transplant or death, health care resource utilization, and direct health care costs. Analytical Approach: Patients with FSGS as the primary cause of kidney failure were followed from USRDS registration (index date) until death or data end. Prevalence and incidence were calculated per 1,000,000 US persons. Patient characteristics at index and treatment modalities during follow-up were described. Time to kidney transplant or death was assessed with Kaplan-Meier and competing risk analyses. Health care resource utilization and costs were reported among patients with 1 year Medicare Part A+B coverage postindex, including (Medicare Coverage subgroup) or excluding (1-year Medicare Coverage subgroup) those who died. Results: The FSGS cohort and Medicare Coverage and 1-year Medicare Coverage subgroups included 25,699, 6,340, and 5,575 patients, respectively. Mean annual period prevalence and incidence rates of FSGS-attributed kidney failure were 87.6 and 7.5 per 1,000,000 US persons, respectively. Initial treatment for most patients was in-center hemodialysis (72.1%), whereas 7.3% received kidney transplant. Accounting for competing risk of death, year 1 and 5 kidney transplant rates were 15% and 34%, respectively. In the Medicare Coverage and 1-year Medicare Coverage subgroups, 76.6% and 74.2% required inpatient admission, 69.9% and 67.3% visited the emergency room, and mean monthly health care costs were $6,752 and $5,575 in the year postindex, respectively. Limitations: Drug costs may be underestimated because Medicare Part D coverage was not required; kidney acquisition costs were not available. Conclusions: FSGS-attributed kidney failure is associated with substantial clinical and economic burden, prompting the need for novel therapies for FSGS to delay kidney failure.


This study of patients in the US Renal Data System observed increasing prevalence and fluctuating incidence of focal segmental glomerulosclerosis (FSGS)-attributed kidney failure from 2008 to 2018. Patients experienced a high clinical burden, including more than 3 years of treatment with dialysis, one-third receiving a kidney transplant, and one-third dying during follow-up. In the first year after US Renal Data System registration, three-quarters of patients with Medicare coverage required hospitalization, and more than two-thirds visited the emergency room. The total annual health care costs were >$68,000 per patient with FSGS-attributed kidney failure, underscoring the high economic burden of this disorder and the treatments required to sustain life. Novel therapies for FSGS are needed to delay or ideally prevent the need dialysis and transplantation after kidney failure.

16.
Sci Rep ; 14(1): 124, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167930

RESUMO

To explore the relationship between miR-373 and the occurrence and development of colorectal cancer. Additionally, it aims to predict the potential cellular signaling pathways and regulatory mechanisms in which miR-373 may be involved and provides a theoretical basis and experimental evidence for the clinical application of miR-373 as a potential biomarker, molecular target, and prognostic indicator in colorectal cancer. Real-time quantitative PCR is used to analyze the expression of miR-373 in human colorectal cancer cell lines and normal human colonic epithelial cells. Further validation of the differential expression of miR-373 in colorectal cancer cell lines is being performed. Biological functions such as cell proliferation, invasion and apoptosis are being detected by MTT, CCK-8, transwell, cell cycle analysis, and flow cytometry experiments to verify the changes in the biological behavior of colon cancer cells after overexpression and interference of miR-373 in SW-480 cells and to explore the effects of miR-373 on cell proliferation, invasion, and apoptosis in colon cancer cells. Proteomic analysis is being conducted on proteins extracted from miR-373 overexpressing SW480 cells, and mass spectrometry is used for protein identification. GO, KEGG, and enrichment analysis are being employed to analyze the significantly differentially expressed proteins. The expression levels of pathway-related proteins are being verified using Western blot. Overexpression of miR-373 increased the invasive and metastatic ability of SW-480 cells; knockdown of miR-373 decreased the invasive and metastatic ability of SW-480 cells. However, there was no statistically significant effect on cell proliferation and apoptosis in SW-480 cells. Proteomic analysis identified 78 differentially expressed proteins based on fold change (FC) > 1.2 and P < 0.05. Annotation of differentially changed proteins revealed that the MAPK signaling pathway, PI3K-Akt signaling pathway, and FAK signaling pathway may play crucial roles in the migration and invasion of colorectal cancer. Western blot analysis showed that overexpression of miR-373 significantly increased the levels of p-ERK1/2 in SW480 cells. miR-373 may activate the ERK/MAPK signaling pathway to promote the invasion and migration of colorectal cancer cells.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , MicroRNAs , Humanos , Sistema de Sinalização das MAP Quinases/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteômica , Linhagem Celular Tumoral , Movimento Celular/genética , Neoplasias do Colo/patologia , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia
17.
Anal Chem ; 96(5): 2008-2021, 2024 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-38276876

RESUMO

Nontargeted lipidomics using liquid chromatography-tandem mass spectrometry can detect thousands of molecules in biological samples. However, the annotation of unknown oxidized lipids is limited to the structures present in libraries, restricting the analysis and interpretation of experimental data. Here, we describe Doxlipid, a computational tool for oxidized lipid annotation that predicts a dynamic MS/MS library for every experiment. Doxlipid integrates three key simulation algorithms to predict libraries and covers 32 subclasses of oxidized lipids from the three main classes. In the evaluation, Doxlipid achieves very high prediction and characterization performance and outperforms the current oxidized lipid annotation methods. Doxlipid, combined with a molecular network, further annotates unknown chemical analogs in the same reaction or pathway. We demonstrate the broad utility of Doxlipid by analyzing oxidized lipids in ferroptosis hepatocellular carcinoma, tissue samples, and other biological samples, substantially advancing the discovery of biological pathways at the trace oxidized lipid level.


Assuntos
Lipídeos , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Lipídeos/análise , Cromatografia Líquida/métodos , Algoritmos , Simulação por Computador
18.
Foods ; 13(2)2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38254527

RESUMO

Egg products after thermal treatment possess a unique flavor and are favored by consumers. In this study, the key aroma-active compounds of egg yolk products and their formation mechanism during thermal treatment were investigated. The volatile aroma compounds in egg yolks were monitored using an electronic nose, gas chromatography-mass spectrometry (GC-MS) and gas chromatography-olfactometry-mass spectrometry (GC-O-MS), and the lipid molecular species were explored using ultra-high-performance liquid chromatography- mass spectrometry with a Q-Exactive HF-X Orbitrap (UPLC-Q-Exactive HF-X). A total of 68 volatile compounds were identified. Boiled eggs mainly derived their flavor from hexanal, 2-pentyl-furan, 2-butanone, 3-methyl-butanal and heptane. Meanwhile, fried eggs relied mainly on 14 compounds, the most important of which were 2-ethyl-3-methyl-pyrazine, 3-ethyl-2,5-dimethyl-pyrazine, 2-ethyl-3,5-dimethyl-pyrazine, nonanal and 2,3-diethyl-5-methyl-pyrazine, providing a baked and burnt sugar flavor. A total of 201 lipid molecules, belonging to 21 lipid subclasses, were identified in egg yolks, and 13 oxidized lipids were characterized using a molecular network. Phosphoethanolamines (PEs) containing polyunsaturated fatty acids were the primary flavor precursors contributing to the development of egg yolks' flavor, participating in lipid oxidation reactions and the Maillard reaction and regulating the production of aldehydes and pyrazine compounds. This study provides reference and guidance for the development of egg yolk flavor products.

19.
J Anim Sci Biotechnol ; 15(1): 13, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38281954

RESUMO

BACKGROUND: Dairy cows are at high risk of fatty liver disease in early lactation, but current preventative measures are not always effective. Cows with fatty liver have lower circulating branched-chain amino acid (BCAA) concentrations whereas cows with high circulating BCAA levels have low liver triglyceride (TG). Our objective was to determine the impact of BCAA and their corresponding ketoacids (branched-chain ketoacids, BCKA) on production performance and liver TG accumulation in Holstein cows in the first 3 weeks postpartum. METHODS: Thirty-six multiparous Holstein cows were used in a randomized block design experiment. Cows were abomasally infused for the first 21 d postpartum with solutions of 1) saline (CON, n = 12); 2) BCA (67 g valine, 50 g leucine, and 34 g isoleucine, n = 12); and 3) BCK (77 g 2-ketovaline calcium salt, 57 g 2-ketoleucine calcium salt, and 39 g 2-ketoisoleucine calcium salt, n = 12). All cows received the same diet. Treatment effects were determined using PROC GLIMMIX in SAS. RESULTS: No differences were detected for body weight, body condition score, or dry matter intake averaged over the first 21 d postpartum. Cows receiving BCK had significantly lower liver TG concentrations compared to CON (6.60% vs. 4.77%, standard error of the mean (SEM) 0.49) during the first 3 weeks of lactation. Infusion of BCA increased milk yield (39.5 vs. 35.3 kg/d, SEM 1.8), milk fat yield (2.10 vs. 1.69 kg/d, SEM 0.08), and lactose yield (2.11 vs. 1.67 kg/d, SEM 0.07) compared with CON. Compared to CON, cows receiving BCA had lower plasma glucose (55.0 vs. 59.2 mg/dL, SEM 0.86) but higher ß-hydroxybutyrate (9.17 vs. 6.00 mg/dL, SEM 0.80). CONCLUSIONS: Overall, BCAA supplementation in this study improved milk production, whereas BCKA supplementation reduced TG accumulation in the liver of fresh cows.

20.
Kidney Med ; 6(2): 100759, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38282694

RESUMO

Rationale & Objective: This study describes the epidemiology, characteristics, and outcomes of patients with immunoglobulin A nephropathy (IgAN)-attributed kidney failure in the US Renal Data System (USRDS) from 2008 to 2018, including health care resource utilization and costs among patients with Medicare-linked data. Study Design: Retrospective cohort study. Setting & Population: Patients with IgAN-attributed kidney failure in the USRDS. Outcomes: Prevalence/incidence, clinical/demographic characteristics, time to kidney transplant, and health care resource utilization and costs. Analytical Approach: Patients with IgAN as primary cause of kidney failure (IgAN cohort) were followed from USRDS registration (index date) until data end/death. Prevalence/incidence were calculated per 1,000,000 US persons. Demographic and clinical characteristics at index and treatment modality during follow-up were summarized. Time from index to kidney transplant was assessed using Kaplan-Meier and competing risk analyses. Health care resource utilization and health care costs were reported among patients with 1 year Medicare Part A+B coverage postindex, including or excluding those who died (Medicare Coverage and 1-year Medicare Coverage subgroups, respectively). Results: The IgAN cohort, Medicare Coverage, and 1-year Medicare Coverage subgroups included 10,101, 1,696, and 1,510 patients, respectively. Mean annual period prevalence and incidence of IgAN-attributed kidney failure were 39.3 and 2.9 per 1,000,000 US persons, respectively. Initial treatment was in-center hemodialysis (63.1%) or kidney transplant (15.1%). Year 1 and 5 kidney transplant rates were 5% and 17%, respectively, accounting for competing risk of death. In the Medicare Coverage and 1-year Medicare Coverage subgroups, 74.4% and 72.3%, respectively, required inpatient admission, 67.3% and 64.4%, respectively, visited the emergency room, and mean total health care costs were $6,293 (SD: $6,934) and $5,284 ($3,455), respectively, per-patient-per-month in the year postindex. Limitations: Drug costs may be underestimated as Medicare Part D coverage was not required; kidney acquisition costs were unavailable. Conclusions: IgAN-attributed kidney failure is associated with substantial clinical and economic burdens. Novel therapies for IgAN that delay kidney failure are needed.


This study of patients in the United States Renal Data System (USRDS) observed fluctuating incidence and increasing prevalence of immunoglobulin A nephropathy (IgAN)-attributed kidney failure from 2008 to 2018. Patients experienced a high clinical burden, with 63% receiving in-center dialysis and over 15% receiving transplantation as initial therapy. In the first year after USRDS registration, nearly three-quarters of patients with Medicare coverage required hospitalization, and around two-thirds visited the emergency room. The total annual health care costs were >$63,000 per patient with IgAN-attributed kidney failure, underscoring the high economic burden of this disorder and currently available treatments. Novel therapies for IgAN are needed to delay or prevent the need for costly dialysis and transplantation after kidney failure.

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