ABSTRACT
Introduction: Proliferative diabetic retinopathy (PDR) is a common diabetes complication, significantly impacting vision and quality of life. Previous studies have suggested a potential link between arginine pathway metabolites and diabetic retinopathy (DR). Connective tissue growth factor (CTGF) plays a role in the occurrence and development of fibrovascular proliferation (FVP) in PDR patients. However, the relationship between arginine pathway metabolites and FVP in PDR remains undefined. This study aimed to explore the correlation between four arginine pathway metabolites (arginine, asymmetric dimethylarginine[ADMA], ornithine, and citrulline) and the severity of FVP in PDR patients. Methods: In this study, plasma and aqueous humor samples were respectively collected from 30 patients with age-related cataracts without diabetes mellitus (DM) and from 85 PDR patients. The PDR patients were categorized as mild-to-moderate or severe based on the severity of fundal FVP. The study used Kruskal-Wallis test to compare arginine, ADMA, ornithine, and citrulline levels across three groups. Binary logistic regression identified risk factors for severe PDR. Spearman correlation analysis assessed associations between plasma and aqueous humor metabolite levels, and between ADMA and CTGF levels in aqueous humor among PDR patients. Results: ADMA levels in the aqueous humor were significantly greater in patients with severe PDR than in those with mild-to-moderate PDR(P=0.0004). However, the plasma and aqueous humor levels of arginine, ornithine, and citrulline did not significantly differ between mild-to-moderate PDR patients and severe PDR patients (P>0.05). Binary logistic regression analysis indicated that the plasma (P=0.01) and aqueous humor (P=0.006) ADMA levels in PDR patients were risk factors for severe PDR. Furthermore, significant correlations were found between plasma and aqueous humor ADMA levels (r=0.263, P=0.015) and between aqueous humor ADMA and CTGF levels (r=0.837, P<0.001). Conclusion: Elevated ADMA levels in plasma and aqueous humor positively correlate with the severity of FVP in PDR, indicating ADMA as a risk factor for severe PDR.
Subject(s)
Aqueous Humor , Arginine , Diabetic Retinopathy , Humans , Arginine/analogs & derivatives , Arginine/blood , Arginine/metabolism , Male , Female , Diabetic Retinopathy/metabolism , Diabetic Retinopathy/pathology , Diabetic Retinopathy/blood , Middle Aged , Aqueous Humor/metabolism , Risk Factors , Aged , Severity of Illness Index , Ornithine/blood , Ornithine/metabolism , Ornithine/analogs & derivatives , Citrulline/blood , Citrulline/metabolism , Biomarkers/blood , Biomarkers/metabolism , Connective Tissue Growth Factor/metabolism , Connective Tissue Growth Factor/bloodABSTRACT
The study assessed a co-processing system segregating food waste (FW) with different impurities into liquid (slurry) and solid fractions and treated using anaerobic digestion (AD) and pyrolysis (Py), respectively, which is defined as ADCo-Py. Biomethane potential tests showed higher methane yield from the FW slurry fraction (572.88 mL/gVSFW) compared to the whole FW (294.37 mL/gVSFW). Pyrolyzing the FW solid fraction reduced nitrogen compounds in bio-oil by 62 % compared to the whole FW. The energy balance and economic feasibility of ADCo-Py were compared with stand-alone AD, Py, and AD integrated with incineration (ADCo-INC). While all systems required extra energy, stand-alone Py and ADCo-INC needed 3.8 and 2.8 times more energy than ADCo-Py, respectively. Techno-economic analysis favored ADCo-Py, with a net present value (NPV) of $15 million and an internal rate of return (IRR) of 34 %. These findings highlighted FW separation as a promising approach, aligning with energy and economic goals in sustainable FW management.
Subject(s)
Refuse Disposal , Waste Management , Food Loss and Waste , Food , Incineration , Methane , Anaerobiosis , BioreactorsABSTRACT
Accurately identifies the cellular composition of complex tissues, which is critical for understanding disease pathogenesis, early diagnosis, and prevention. However, current methods for deconvoluting bulk RNA sequencing (RNA-seq) typically rely on matched single-cell RNA sequencing (scRNA-seq) as a reference, which can be limiting due to differences in sequencing distribution and the potential for invalid information from single-cell references. Hence, a novel computational method named SCROAM is introduced to address these challenges. SCROAM transforms scRNA-seq and bulk RNA-seq into a shared feature space, effectively eliminating distributional differences in the latent space. Subsequently, cell-type-specific expression matrices are generated from the scRNA-seq data, facilitating the precise identification of cell types within bulk tissues. The performance of SCROAM is assessed through benchmarking against simulated and real datasets, demonstrating its accuracy and robustness. To further validate SCROAM's performance, single-cell and bulk RNA-seq experiments are conducted on mouse spinal cord tissue, with SCROAM applied to identify cell types in bulk tissue. Results indicate that SCROAM is a highly effective tool for identifying similar cell types. An integrated analysis of liver cancer and primary glioblastoma is then performed. Overall, this research offers a novel perspective for delivering precise insights into disease pathogenesis and potential therapeutic strategies.
Subject(s)
Gene Expression Profiling , Software , Animals , Mice , Gene Expression Profiling/methods , Single-Cell Analysis/methods , Sequence Analysis, RNA/methodsABSTRACT
The use of glycols is seen in various industries and occupations. In the past few decades, the health implications of inhalable glycols have gained public attention. Inhalable glycols may cause adverse health effects, especially for workers in occupations receiving frequent exposure and consumers of glycol-based daily products. Our previous work highlighted the rapid accumulation of formaldehyde and glycolaldehyde in fog juice, thus proposing the occurrence of glycol autoxidation. However, the fundamentals of glycol autoxidation remained unclear and unexplored. Our goal is to investigate the autoxidation of common glycols during indoor storage. Carbonyls were quantified using liquid chromatography-mass spectrometry (LC-MS), and peroxides from autoxidation were monitored via iodometry and UV-Vis spectrometry. The impact of certain factors such as the water mixing ratio and antioxidants (vitamin C) was also investigated. Formation of aldehydes in many glycols was weekly monitored, such as e-cigarette juice and triethylene glycol (TEG). Occurrence of autoxidation was confirmed by the increase in the total peroxide concentration. Additionally, we highlighted the dependence of the carbonyl formation rate on the TEG-water mixing ratio, demonstrating the complex role of water in glycol autoxidation. We have also tested the effectiveness of vitamin C and made suggestions for minimizing the formation of toxic carbonyls in consumer products.
Subject(s)
Electronic Nicotine Delivery Systems , Humans , Polyethylene Glycols , Peroxides , Weather , Ascorbic Acid , WaterABSTRACT
Diabetic microangiopathy is a typical and severe problem in diabetics, including diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, and diabetic cardiomyopathy. Patients with type 2 diabetes and diabetic microvascular complications have significantly elevated levels of Asymmetric dimethylarginine (ADMA), which is an endogenous inhibitor of nitric oxide synthase (NOS). ADMA facilitates the occurrence and progression of microvascular complications in type 2 diabetes through its effects on endothelial cell function, oxidative stress damage, inflammation, and fibrosis. This paper reviews the association between ADMA and microvascular complications of diabetes and elucidates the underlying mechanisms by which ADMA contributes to these complications. It provides a new idea and method for the prevention and treatment of microvascular complications in type 2 diabetes.
Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Angiopathies , Diabetic Nephropathies , Diabetic Retinopathy , Humans , Diabetes Mellitus, Type 2/complications , Diabetic Nephropathies/pathology , Diabetic Angiopathies/epidemiology , Diabetic Retinopathy/complicationsABSTRACT
Offshore wind power, with accelerated declining levelized costs, is emerging as a critical building-block to fully decarbonize the world's largest CO2 emitter, China. However, system integration barriers as well as system balancing costs have not been quantified yet. Here we develop a bottom-up model to test the grid accommodation capabilities and design the optimal investment plans for offshore wind power considering resource distributions, hourly power system simulations, and transmission/storage/hydrogen investments. Results indicate that grid integration barriers exist currently at the provincial level. For 2030, optimized offshore wind investment levels should be doubled compared with current government plans, and provincial allocations should be significantly improved considering both resource quality and grid conditions. For 2050, offshore wind capacity in China could reach as high as 1500 GW, prompting a paradigm shift in national transmission structure, favoring long-term storage in the energy portfolio, enabling green hydrogen production in coastal demand centers, resulting in the world's largest wind power market.
ABSTRACT
PURPOSE: This paper aimed to assess the diagnostic utility of a newly developed gene-based technology-nanopore targeted sequencing (NTS) in suspected endophthalmitis patients. METHODS: This retrospective study included 43 patients (44 eyes) with suspected endophthalmitis. NTS was applied along with microbiological culture to detect unknown pathogens in intraocular fluid samples. The diagnostic utility of NTS was mainly evaluated from three aspects, including the positivity rate of bacterial/fungal presence, diagnostic turnaround time and the frequency of change in treatment based on etiology test results. Non-parametric, two-sided Wilcoxon rank sum test, the McNemar's test and the kappa statistic were used for statistical comparisons. RESULTS: NTS showed significant advantages over traditional culture in positivity rates and diagnostic time (P < 0.001, kappa = 0.082; Z = -5.805, P < 0. 001). As regards antibiotic strategy, 17 patients (39.53%) and 5 patients (11.63%) underwent medication change following NTS and culture results respectively (P < 0.001, kappa = 0.335). With reasonable use of antibiotic and surgical intervention, most patients responded favorably, judged by significantly improved visual acuity (Z = -4.249, P < 0.001). The mean duration of hospitalization was 8.49 ± 2.45 days (range, 1-16 days). CONCLUSION: The high efficiency feature of NTS in pathogen detection renders it a valuable supplementary to traditional culture. Additionally, it has facilitated patients' management for the early and precise diagnosis of endophthalmitis.
Subject(s)
Endophthalmitis , Eye Infections, Bacterial , Nanopores , Humans , Retrospective Studies , Endophthalmitis/etiology , Aqueous Humor/microbiology , Anti-Bacterial Agents/therapeutic use , Eye Infections, Bacterial/microbiologyABSTRACT
Aerosol optical properties play an important role in affecting direct aerosol radiative forcing (DARF). However, DARF estimation is still uncertain due to the complexity of aerosol optical properties. Therefore, in this study, the spatiotemporal distributions of aerosol properties and their effects on DARF in China from 2004 to 2020 are investigated using the Santa Barbara DISORT Atmospheric Radiative Transfer (SBDART) model. The results show that the aerosol optical parameters vary greatly and change with seasonal regularity, which is greatly affected by human activities. The control variable method was employed on aerosol optical properties for better estimation of DARF. Single scattering albedo (SSA) has the greatest effect on DARF, followed by aerosol optical depth (AOD) and the asymmetric factor (ASY) among the seven examined stations in China. The average DARF decreases by 4.2 % when the SSA increases by 0.3 % but increases by 34.7 % when the SSA decreases by 3 % in mainland China. When the AOD changes from -60 to +60 %, DARF changes from -54.7 % to +58.4 %. The variation in DARF is between -3 % and +3 % when the ASY varies from -30 % to +30 %. The instability in DARF resulted from the complicated and volatile nature of aerosol optical properties in the region; the aerosol optical properties are greatly affected by the aerosol types and relative humidity. The results of this study have important reference significance for understanding the variation of DARF and formulating pollution prevention and control policies in the region.
Subject(s)
Air Pollutants , Humans , Air Pollutants/analysis , China , Aerosols/analysisABSTRACT
Artificial fog is commonly employed in the entertainment industry and indoor household celebrations. The fog is generated from glycol-based solvents, which can also be found in e-cigarettes and personal care products. Although potential health impacts of glycol inhalation are frequently cited by studies of e-cigarette smoking, the dynamics and the chemical composition of glycol-based aerosols have never been studied systematically. The objective of this work is to investigate the impact of glycol-based aerosol on indoor air quality. Specifically, we targeted artificial fogs generated with common glycols, including propylene glycol (PG) and triethylene glycol (TEG). With the aid of a novel aerosol collecting and monitoring instrument setup, we obtained time-resolved aerosol profiles and their chemical compositions in an experimental room. Artificial fog has given rise to a significant amount of ultra-fine particulate matter, demonstrating its negative impact on indoor air quality. Additionally, we found a high concentration (9.75 mM) of formaldehyde and other carbonyls in fog machine fluids stored for months. These compounds are introduced to the indoor air upon artificial fog application. We propose that carbonyls have accumulated from the oxidative decomposition of glycols, initiated by OH radicals and singlet oxygens (1 O2 ) and likely sustained by autooxidation. Oxidation of glycols by indoor oxidants has never been reported previously. Such chemical processes can represent an unrecognized source of toxic carbonyl compounds which is also applicable to other glycol-based solvents.
Subject(s)
Air Pollutants , Air Pollution, Indoor , Electronic Nicotine Delivery Systems , Aerosols , Air Pollutants/analysis , Air Pollution, Indoor/analysis , Formaldehyde/analysis , Glycols/analysis , Oxidants , Particulate Matter , Propylene Glycol/analysis , Solvents , WeatherABSTRACT
Parthenolide (PTL) is a natural compound with anti-inflammatory and antioxidant properties and is an active ingredient extracted from the medicinal plant Tanacetum parthenium. ACT001 is derived from parthenolide and is a fumarate form of dimethylaminomylide (DMAMCL). Its effect is equivalent to that of PTL, but it is more stable in plasma and has lower acquisition costs. Related reports indicate that NLRP3-mediated neuroinflammation is involved in the progression of Parkinson's disease (PD). In our research, we explored whether ACT001 alleviates NLRP3-mediated neuroinï¬ammation in PD mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Our results revealed that ACT001 reduces movement impairment and cognitive deï¬cit in PD mice. In addition, it alleviates dopaminergic neurodegeneration in the nigrostriatal pathway and inhibits oxidative stress, the inflammatory response and activation of the NLRP3 inflammasome in the midbrain of MPTP-induced PD mice. Moreover, it attenuates microglial activation in the nigrostriatal pathway. Overall, our study showed that ACT001 alleviates NLRP3-mediated neuroinï¬ammation in PD mice induced by MPTP.
Subject(s)
Behavior, Animal/drug effects , Cytokines/drug effects , Inflammasomes/drug effects , Inflammation/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/drug effects , Parkinsonian Disorders/metabolism , Sesquiterpenes, Guaiane/pharmacology , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine , Animals , Catalase/drug effects , Catalase/metabolism , Circadian Rhythm/drug effects , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Corpus Striatum/pathology , Cytokines/metabolism , Dopaminergic Neurons/drug effects , Dopaminergic Neurons/metabolism , Dopaminergic Neurons/pathology , Inflammasomes/metabolism , Inflammation/physiopathology , Malondialdehyde/metabolism , Mice , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Oxidative Stress/drug effects , Parkinsonian Disorders/physiopathology , Substantia Nigra/drug effects , Substantia Nigra/metabolism , Substantia Nigra/pathology , Superoxide Dismutase/drug effects , Superoxide Dismutase/metabolism , Tyrosine 3-Monooxygenase/metabolismABSTRACT
Sperm cells of seed plants have lost their motility and are transported by the vegetative pollen tube cell for fertilization, but the extent to which they regulate their own transportation is a long-standing debate. Here we show that Arabidopsis lacking two bHLH transcription factors produces pollen without sperm cells. This abnormal pollen mostly behaves like the wild type and demonstrates that sperm cells are dispensable for normal pollen tube development.
Subject(s)
Arabidopsis/physiology , Pollen Tube/cytology , Pollen/physiology , Pollination , Arabidopsis/cytology , Arabidopsis/genetics , Arabidopsis Proteins/physiology , Basic Helix-Loop-Helix Transcription Factors/physiology , Mutation , Pollen/cytology , Pollen/genetics , Pollen Tube/genetics , Pollen Tube/growth & developmentABSTRACT
During the angiosperm (flowering-plant) life cycle, double fertilization represents the hallmark between diploid and haploid generations [1]. The success of double fertilization largely depends on compatible communication between the male gametophyte (pollen tube) and the maternal tissues of the flower, culminating in precise pollen tube guidance to the female gametophyte (embryo sac) and its rupture to release sperm cells. Several important factors involved in the pollen tube reception have been identified recently [2-6], but the underlying signaling pathways are far from being understood. Here, we report that a group of female-specific small proteins, early nodulin-like proteins (ENODLs, or ENs), are required for pollen tube reception. ENs are featured with a plastocyanin-like (PCNL) domain, an arabinogalactan (AG) glycomodule, and a predicted glycosylphosphatidylinositol (GPI) anchor motif. We show that ENs are asymmetrically distributed at the plasma membrane of the synergid cells and accumulate at the filiform apparatus, where arriving pollen tubes communicate with the embryo sac. EN14 strongly and specifically interacts with the extracellular domain of the receptor-like kinase FERONIA, localized at the synergid cell surface and known to critically control pollen tube reception [6]. Wild-type pollen tubes failed to arrest growth and to rupture after entering the ovules of quintuple loss-of-function EN mutants, indicating a central role of ENs in male-female communication and pollen tube reception. Moreover, overexpression of EN15 by the endogenous promoter caused disturbed pollen tube guidance and reduced fertility. These data suggest that female-derived GPI-anchored ENODLs play an essential role in male-female communication and fertilization.
Subject(s)
Arabidopsis Proteins/genetics , Arabidopsis/physiology , Gene Expression Regulation, Plant , Pollen Tube/physiology , Arabidopsis/genetics , Arabidopsis/growth & development , Arabidopsis Proteins/classification , Arabidopsis Proteins/metabolism , Organ Specificity , Phylogeny , Pollen Tube/growth & development , Signal TransductionABSTRACT
Successful sexual reproduction in animals and plants requires communication between male and female gametes. In flowering plants, unlike in animals, eggs and sperm cells are enclosed in multicellular embryo sacs and pollen grains, respectively; guided growth of the pollen tube into the ovule is necessary for fertilization. Pollen tube guidance requires accurate perception of ovule-emitted guidance cues by the receptors in pollen tubes. Although several ovule-secreted peptides controlling pollen tube guidance have recently been identified, i.e., maize EGG APPARATUS1 (EA1), Torenia LURE1/LURE2, and Arabidopsis CRP810_1/AtLURE1, little is known about the receptors. Here, we identified two receptor-like kinase (RLK) genes preferentially expressed in Arabidopsis pollen tubes, Lost In Pollen tube guidance 1 (LIP1) and 2 (LIP2), which are involved in guidance control of pollen tubes. LIP1 and LIP2 were anchored to the membrane in the pollen tube tip region via palmitoylation, which was essential for their guidance control. Simultaneous inactivation of LIP1 and LIP2 led to impaired pollen tube guidance into micropyle and significantly reduced attraction of pollen tubes toward AtLURE1. Our results suggest that LIP1 and LIP2 represent essential components of the pollen tube receptor complex to perceive the female signal AtLURE1 for micropylar pollen tube guidance.