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1.
Int J Rheum Dis ; 27(5): e15193, 2024 May.
Article in English | MEDLINE | ID: mdl-38742430

ABSTRACT

OBJECTIVE: Known for anti-inflammatory and antioxidant properties, flavonoid has phytoestrogenic effects, but it is unclear whether its role in hyperuricemia and metabolic syndrome (MetS) differs by gender. Moreover, given the strong association between hyperuricemia and MetS, we aimed to explore whether flavonoid is a protective factor for hyperuricemia, independently of MetS, in different genders. METHODS: Data for 2007-2010 and 2017-2018 were obtained from the National Health and Nutrition Examination Survey (NHANES) and the Food and Nutrient Database for Dietary Studies (FNDDS). To assess the association among flavonoid, hyperuricemia, and MetS, multivariate logistic regression and subgroup analyses were conducted. Besides, to investigate whether the association between flavonoid and hyperuricemia was independent of MetS, multivariate logistic regression models were further conducted to explore the association between flavonoid and MetS among females with hyperuricemia and to investigate the association between flavonoid and hyperuricemia among females after excluding MetS. RESULT: Among 5356 females, anthocyanin intake was inversely associated with the prevalence of hyperuricemia (Q4 vs. Q1: OR 0.49, 95% CI 0.31 to 0.76), and MetS (Q4 vs. Q1: OR 0.68, 95% CI 0.50 to 0.93). Furthermore, subgroup analyses showed the beneficial association between anthocyanin and hyperuricemia among females aged 40 to 59 years and menopausal. However, among 5104 males, no significant association was observed after adjustment for covariates (Q4 vs. Q1: OR 0.81, 95% CI 0.56 to 1.18). While in 372 females with hyperuricemia, no significant association was found between MetS and anthocyanin (Q4 vs. Q1: OR 0.88, 95% CI 0.31 to 2.49). Meanwhile, among 3335 females after excluding MetS, there was still a significant association between anthocyanin and a lower prevalence of hyperuricemia (Q4 vs. Q1: OR 0.38, 95% CI 0.17 to 0.85). CONCLUSION: Dietary anthocyanin is associated with a lower prevalence of hyperuricemia independently of MetS among females. Foods rich in anthocyanin should be emphasized for females, especially those aged 40 to 59 years and menopausal, which may be of potential significance in the prevention of hyperuricemia.


Subject(s)
Anthocyanins , Hyperuricemia , Metabolic Syndrome , Nutrition Surveys , Humans , Hyperuricemia/epidemiology , Hyperuricemia/blood , Hyperuricemia/diagnosis , Female , Metabolic Syndrome/epidemiology , Metabolic Syndrome/blood , Metabolic Syndrome/diagnosis , Prevalence , Adult , Middle Aged , Anthocyanins/administration & dosage , Sex Factors , Male , Risk Factors , Cross-Sectional Studies , United States/epidemiology , Protective Factors , Diet/adverse effects , Uric Acid/blood , Biomarkers/blood , Time Factors , Multivariate Analysis
2.
Liver Int ; 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38597373

ABSTRACT

BACKGROUND AND AIMS: Iron overload, oxidative stress and ferroptosis are associated with liver injury in alcohol-associated liver disease (ALD), however, the crosstalk among these regulatory pathways in ALD development is unclear. METHODS: ALD mouse model and general control of amino acid synthesis 5 like 1 (GCN5L1) liver knockout mice were generated to investigate the role of GCN5L1 in ALD development. Proteomic screening tests were performed to identify the key factors mediating GCN5L1 loss-induced ALD. RESULTS: Gene Expression Omnibus data set analysis indicates that GCN5L1 expression is negatively associated with ALD progression. GCN5L1 hepatic knockout mice develop severe liver injury and lipid accumulation when fed an alcohol diet. Screening tests identified that GCN5L1 targeted the mitochondrial iron transporter CISD1 to regulate mitochondrial iron homeostasis in ethanol-induced ferroptosis. GCN5L1-modulated CISD1 acetylation and activity were crucial for iron accumulation and ferroptosis in response to alcohol exposure. CONCLUSION: Pharmaceutical modulation of CISD1 activity is critical for cellular iron homeostasis and ethanol-induced ferroptosis. The GCN5L1/CISD1 axis is crucial for oxidative stress and ethanol-induced ferroptosis in ALD and is a promising avenue for novel therapeutic strategies.

3.
Antioxidants (Basel) ; 13(4)2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38671934

ABSTRACT

An 88-day feeding trial was conducted to evaluate the effects of dietary inosine 5'-monophosphate (5'-IMP) on the growth performance and salinity and oxidative stress resistance in the juvenile gibel carp CAS III (Carassius auratus gibelio; initial body weight: 7.48 g). Four isonitrogenous and isoenergetic diets containing exogenous 5'-IMP were formulated. P1, P2, P3 and P4 were diets containing 5'-IMP at four concentrations (0, 1, 2 and 4 g kg-1). The four diets were randomly allotted to triplicate tanks in a recirculating system. After the feeding trial, six fish per tank were netted randomly and placed into 12‱ saline water to test their response to salinity stress. The results indicated that the feed conversion rate was enhanced by dietary supplementation with 5'-IMP. The appetite, plasma neuropeptide Y level and feeding rate of the P3 group were lower than those in the control treatment group. Dietary supplementation with 5'-IMP improved the osmoregulatory adaptation of gibel carp under acute salinity stress. Six hours after the salinity stress treatment, in the dietary 5'-IMP treatment group, the plasma cortisol and K+ concentrations were lower and the Na+/K+-ATPase activity was greater than that in the control group. Dietary supplementation with 5'-IMP promoted the expression of the glucocorticoid receptors NKA-α1b and NKCC and retarded the expression of Hsp70 in P4-treated gill filaments and kidneys. Dietary supplementation with 5'-IMP resulted in a stable oxidative-stress-resistant phenotype characterized by increased levels of cellular antioxidants, including SOD, catalase, glutathione peroxidase, glutathione reductase and MPO. The above results of the current study demonstrate that supplementation of 5'-IMP can promote feed utilization and have positive influences on the salinity and oxidative stress resistance of gibel carp.

4.
Nat Commun ; 15(1): 3320, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38637525

ABSTRACT

Investigations into the compositional model of the Earth, particularly the atypical concentrations of volatile elements within the silicate portion of the early Earth, have attracted significant interest due to their pivotal role in elucidating the planet's evolution and dynamics. To understand the behavior of such volatile elements, an established 'volatility trend' has been used to explain the observed depletion of certain volatile elements. However, elements such as Se and Br remain notably over-depleted in the silicate Earth. Here we show the results from first-principles simulations that explore the potential for these elements to integrate into hcp-Fe through the formation of substitutional alloys, long presumed to be predominant constituents of the Earth's core. Based on our findings, the thermodynamic stability of these alloys suggests that these volatile elements might indeed be partially sequestered within the Earth's core. We suggest potential reservoirs for volatile elements within the deep Earth, augmenting our understanding of the deep Earth's composition.

5.
Environ Pollut ; 348: 123819, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38508368

ABSTRACT

Natural and anthropogenic pressures exert influence on ecosystem structure and function by affecting the physiology and behavior of organisms, as well as the trophic interactions within assemblages. Therefore, understanding how multiple stressors affect aquatic ecosystems can improve our ability to manage and protect these ecosystems and contribute to understanding fundamental ecological principles. Here, we conducted a mesocosm experiment to ascertain the individual and combined effects of multiple stressors on trophic interactions within species in freshwater ecosystems. Furthermore, we investigated how species respond to such changes by adapting their food resources. To mimic a realistic food web, we selected fish and shrimp as top predators, gastropods, zooplankton and zoobenthos as intermediate consumers, with producers (macrophytes, periphyton and phytoplankton) and detritus as basal resources. Twelve different treatments included a control, nutrient loading only, herbicide exposure only, and a combination of nutrient loading and herbicide exposure, each replicated under ambient temperature, constant warming and multiple heat waves to simulate environmental stressors. Our results demonstrated that antagonistic interactions between environmental stressors were widespread in trophic interactions, with a more pronounced and less intense impact observed for the high trophic level species. The responses of freshwater communities to environmental stressors are complex, involving direct effects on individual species as well as indirect effects through species interactions. Moreover, our results confirmed that the combinations of stressors, but not individual stressors, led to a shift to herbivory in top predators, indicating that multiple stressors can be more detrimental to organisms than individual stressors alone. These findings elucidate how changes in the resource utilization of species induced by environmental stressors can potentially influence species interactions and the structural dynamics of food webs in freshwater ecosystems.


Subject(s)
Food Chain , Herbicides , Animals , Ecosystem , Fresh Water , Fishes
6.
Chemosphere ; 354: 141497, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38452981

ABSTRACT

During the anammox process, mitigation of biomass washout to increase sludge retention is an important parameter of process efficiency. Signal molecular stimulants (SMS) initiate the sludge granulations controlled by programmed cell death (PCD) of microorganisms. In this study, the aerobic granular sludge (AGS), cell fragments, extracellular polymeric substances (EPS), and AGS process effluent were tested as SMS to identify their effect on anammox granulation. The results showed that the addition of SMS increased the nitrogen removal efficiency to varying degrees, whereas the addition of AGS process supernatant, as SMS, increased the ammonia removal efficiency up to 96%. The addition of SMS was also found to increase EPS production and contributed to sludge granulation. In this process, the proportion of PCD increased and both Gaiella and Denitratisoma abundance increased from 3.54% to 5.59%, and from 1.8% to 3.42%, respectively. In conclusion, PCD was found important to increase anaerobic ammonia oxidation performance through the granulation mechanism.


Subject(s)
Anaerobic Ammonia Oxidation , Sewage , Bioreactors , Ammonia , Nitrogen/metabolism , Apoptosis , Oxidation-Reduction
7.
Front Mol Biosci ; 11: 1329580, 2024.
Article in English | MEDLINE | ID: mdl-38516188

ABSTRACT

Preimplantation genetic testing for monogenic diseases (PGT-M) can be used to select embryos that do not develop disease phenotypes or carry disease-causing genes for implantation into the mother's uterus, to block disease transmission to the offspring, and to increase the birth rate of healthy newborns. However, the traditional PGT-M technique has some limitations, such as its time consumption, experimental procedural complexity, and the need for a complete family or reference embryo to construct the haplotype. In this study, proband-independent haplotyping based on NGS-based long-read sequencing (Phbol-seq) was used to effectively construct haplotypes. By targeting the mutation sites of single gene disease point mutations and small fragment deletion carriers, embryos carrying parental disease-causing mutations were successfully identified by linkage analysis. The efficiency of embryo resolution was then verified by classical Sanger sequencing, and it was confirmed that the construction of haplotype and SNP linkage analysis by Phbol-seq could accurately and effectively detect whether embryos carried parental pathogenic mutations. After the embryos confirmed to be nonpathogenic by Phbol-seq-based PGT-M and confirmed to have normal copy number variation by Phbol-seq-based PGT-A were transplanted into the uterus, gene detection in amniotic fluid of the implanted embryos was performed, and the results confirmed that Phbol-seq technology could accurately distinguish normal genotype embryos from genetically modified carrier embryos. Our results suggest that Phbol-seq is an effective strategy for accurately locating mutation sites and accurately distinguishing between embryos that inherit disease-causing genes and normal embryos that do not. This is critical for Phbol-seq-based PGT-M and could help more single-gene disease carriers with incomplete families, de novo mutations or suspected germline mosaicism to have healthy babies with normal phenotypes. It also helps to reduce the transmission of monogenic genetic diseases in the population.

8.
Plant Physiol Biochem ; 210: 108575, 2024 May.
Article in English | MEDLINE | ID: mdl-38554536

ABSTRACT

As natural dominant pigments, carotenoids and their derivatives not only contribute to fruit color and flavor quality but are regarded as phytochemicals beneficial to human health because of various bioactivities. Tomato is one of the most important vegetables as well as a main dietary source of carotenoids. So, it's of great importance to generate carotenoid-biofortified tomatoes. The carotenoid biosynthesis pathway is a network co-regulated by multiple enzymes and regulatory genes. Here, we assembled four binary constructs containing different combinations of four endogenous carotenoids metabolic-related genes, including SlORHis, SlDXS, SlPSY, and SlBHY by using a high efficiency multi-transgene stacking system and a series of fruit-specific promotors. Transgenic lines overexpression SlORHis alone, three genes (SlORHis/SlDXS/SlPSY), two genes (SlORHis/SlBHY), and all these four genes (SlORHis/SlDXS/SlPSY/SlBHY) were enriched with carotenoids to varying degrees. Notably, overexpressing SlORHis alone showed comparable effects with simultaneous overexpression of the key regulatory enzyme coding genes SlDXS, SlPSY, and SlORHis in promoting carotenoid accumulation. Downstream carotenoid derivatives zeaxanthin and violaxanthin were detected only in lines containing SlBHY. In addition, the sugar content and total antioxidant capacity of these carotenoids-enhanced tomatoes was also increased. These data provided useful information for the future developing of biofortified tomatoes with different carotenoid profiles, and confirmed a promising system for generation of nutrients biofortified tomatoes by multiple engineering genes stacking strategy.


Subject(s)
Carotenoids , Fruit , Plants, Genetically Modified , Solanum lycopersicum , Solanum lycopersicum/genetics , Solanum lycopersicum/metabolism , Carotenoids/metabolism , Plants, Genetically Modified/genetics , Fruit/genetics , Fruit/metabolism , Transgenes , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolism , Genes, Plant
9.
Biotechnol Biofuels Bioprod ; 17(1): 30, 2024 Feb 23.
Article in English | MEDLINE | ID: mdl-38395898

ABSTRACT

BACKGROUND: The recently discovered PcAA14A and B from white-rot basidiomycete Pycnoporus coccineus enriched our understanding of the oxidative degradation of xylan in fungi, however, the unusual mode of action of AA14 LPMOs has sparked controversy. The substrate specificity and functionality of AA14 LPMOs still remain enigmatic and need further investigation. RESULTS: In this study, a novel AA14 LPMO was characterized from the ascomycete Talaromyces rugulosus. TrAA14A has a broad substrate specificity with strong oxidative activity on pure amorphous cellulose and xyloglucan. It could simultaneously oxidize cellulose, xylan and xyloglucan in natural hemi/cellulosic substrate such as fibrillated eucalyptus pulp, and released native and oxidized cello-oligosaccharides, xylo-oligosaccharides and xyloglucan oligosaccharides from this substrate, but its cellulolytic/hemicellulolytic activity became weaker as the contents of xylan increase in the alkaline-extracted hemi/cellulosic substrates. The dual cellulolytic/hemicellulolytic activity enables TrAA14A to possess a profound boosting effect on cellulose hydrolysis by cellulolytic enzymes. Structure modelling of TrAA14A revealed that it exhibits a relatively flat active-site surface similar to the active-site surfaces in AA9 LPMOs but quite distinct from PcAA14B, despite TrAA14A is strongly clustered together with AA14 LPMOs. Remarkable difference in electrostatic potentials of L2 and L3 surfaces was also observed among TrAA14A, PcAA14B and NcLPMO9F. We speculated that the unique feature in substrate-binding surface might contribute to the cellulolytic/hemicellulolytic activity of TrAA14A. CONCLUSIONS: The extensive cellulolytic/hemicellulolytic activity on natural hemi/cellulosic substrate indicated that TrAA14A from ascomycete is distinctively different from previously characterized xylan-active AA9 or AA14 LPMOs. It may play as a bifunctional enzyme to decompose some specific network structures formed between cellulose and hemicellulose in the plant cell walls. Our findings shed new insights into the novel substrate specificities and biological functionalities of AA14 LPMOs, and will contribute to developing novel bifunctional LPMOs as the booster in commercial cellulase cocktails to efficiently break down the hemicellulose-cellulose matrix in lignocellulose.

10.
BMC Cardiovasc Disord ; 24(1): 35, 2024 01 06.
Article in English | MEDLINE | ID: mdl-38184523

ABSTRACT

BACKGROUND AND OBJECTIVE: Cardiac rehabilitation (CR) has been demonstrated to improve outcomes in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). However, the optimal CR initiation time and duration remain to be determined. This study aimed to explore the impact of the time factors on the CR outcomes in AMI patients who received PCI by the method of meta-regression analysis. METHODS: We searched five databases (PubMed, Embase, Cochrane Library, Web of Science and Google scholar) up to October 31, 2023. Meta-regression analysis was utilized to explore the impact of the time factors on the effect sizes. Subgroups with more than 3 studies were used for meta-regression analysis. RESULTS: Our analysis included 16 studies and a total of 1810 patients. The meta-regression analysis revealed that the initiation time and duration of CR had no significant impact on the occurrence of arrhythmia, coronary artery restenosis and angina pectoris. The initiation time and duration of CR also had no significant impact on the changes in left ventricular ejection fraction (LVEF, starting time: estimate = 0.160, p = 0.130; intervention time: estimate = 0.017, p = 0.149), left ventricular end-diastolic volume (LVEDV, starting time: estimate = - 0.191, p = 0.732; intervention time: estimate = - 0.033, p = 0.160), left ventricular end-systolic volume (LVESV, starting time: estimate = - 0.301, p = 0.464; intervention time: estimate = 0.015, p = 0.368) and 6-minute walk test (6MWT, starting time: estimate = - 0.108, p = 0.467; intervention time: estimate = 0.019, p = 0.116). CONCLUSION: Implementation of CR following PCI in patients with AMI is beneficial. However, in AMI patients, there is no significant difference in the improvement of CR outcomes based on different CR starting times within 1 month after PCI or different durations of the CR programs. It indicates that it is feasible for patients with AMI to commence CR within 1 month after PCI and continue long-term CR, but the time factors which impact CR are intricate and further clinical research is still needed to determine the optimal initiation time and duration of CR.


Subject(s)
Cardiac Rehabilitation , Myocardial Infarction , Percutaneous Coronary Intervention , Humans , Myocardial Infarction/diagnosis , Myocardial Infarction/therapy , Percutaneous Coronary Intervention/methods , Stroke Volume , Time Factors , Ventricular Function, Left
11.
Methods ; 222: 112-121, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38215898

ABSTRACT

Design of molecules for candidate compound selection is one of the central challenges in drug discovery due to the complexity of chemical space and requirement of multi-parameter optimization. Here we present an application scenario-oriented platform (ID4Idea) for molecule generation in different scenarios of drug discovery. This platform utilizes both library or rule based and generative based algorithms (VAE, RNN, GAN, etc.), in combination with various AI learning types (pre-training, transfer learning, reinforcement learning, active learning, etc.) and input representations (1D SMILES, 2D graph, 3D shape, binding site, pharmacophore, etc.), to enable customized solutions for a given molecular design scenario. Besides the usual generation followed screening protocol, goal-directed molecule generation can also be conducted towards predefined goals, enhancing the efficiency of hit identification, lead finding, and lead optimization. We demonstrate the effectiveness of ID4Idea platform through case studies, showcasing customized solutions for different design tasks using various input information, such as binding pockets, pharmacophores, and compound representations. In addition, remaining challenges are discussed to unlock the full potential of AI models in drug discovery and pave the way for the development of novel therapeutics.


Subject(s)
Drug Design , Drug Discovery , Binding Sites , Algorithms , Gene Library
12.
Int J Biol Macromol ; 260(Pt 1): 129504, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38228212

ABSTRACT

In this study, the novel auxiliary activity (AA) family 14 lytic polysaccharide monooxygenase (LPMO) SbAA14 from Sordaria brevicollis was successfully characterized. It was active against heteroxylan, xyloglucan and cellulose in ß-cellulose and released native oligosaccharides and corresponding C1- and/or C4-oxidized products. SbAA14 showed a branched chain preference, because partial removal of arabinosyl substituents from heteroxylan led to a decrease in activity. SbAA14 had synergistic effects with the debranching enzyme EpABF62C in an enzyme- and ascorbic acid-dependent manner. SbAA14 had synergistic effects with the GH10 endoxylanase EpXYN1, and the degree of synergy was greater with step-by-step addition than with simultaneous addition. SbAA14 could also synergize with Celluclast® 1.5 L on NaOH-pretreated wheat straw and on NaOH-pretreated and hydrogen peroxide-acetic acid (HPAC)-H2SO4-pretreated bamboo substrates. The greatest synergistic effect between SbAA14 and Celluclast® 1.5 L was observed for HPAC-H2SO4-200 mM pretreated bamboo, in which the degree of synergy reached approximately 1.61. The distinctive substrate preference of SbAA14 indicated that it is a novel AA14 LPMO that may act mainly on heteroxylan with numerous arabinosyl substituents between cellulose fibers rather than on recalcitrant xylan tightly associated with cellulose. These findings broaden the understanding of enigmatic AA14 LPMOs and provide new insights into the substrate specificities and biological functionalities of AA14 LPMOs in fungi.


Subject(s)
Glycoside Hydrolases , Lignin , Polysaccharides , Sordariales , Sodium Hydroxide , Cellulose , Mixed Function Oxygenases
13.
Rheumatol Ther ; 11(1): 51-60, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37930614

ABSTRACT

INTRODUCTION: Surgery is a risk factor for flares in people with gout. However, gout flares after endovascular interventional procedures are not well understood. The aim of this study was to evaluate the clinical features and risk factors for gout flare that develop during the postsurgical period including endovascular procedures. METHODS: We enrolled 222 patients with gout who developed postsurgical gout and 196 controls who had histories of gout but did not develop gout flares after surgery within 20 days. Clinical characteristics of patients who developed a postsurgical gout flare were compared with the controls. RESULTS: The rate of endovascular interventional procedures was higher (38.74% vs. 13.48%, P < 0.001) in the flare group than in the no-flare group and lower in orthopedic surgery (13.96% vs. 41.84%, P < 0.001). The Cox model showed that endovascular interventional procedures (HR, hazard ratio 1.752; 95% CI, confidence interval 1.126-2.724, P = 0.013) and presurgical uric acid levels of ≥ 7 mg/dl (HR 1.489; 95% CI 1.081-2.051, P = 0.015) were significantly associated with increased risks of postsurgical gout flare, and taking colchicine before surgery were significantly associated with decreased risk of postsurgical gout flare (HR 0.264; 95% CI 0.090-0.774, P = 0.015). There was no significant difference in the types of endovascular interventional procedures between the flare group and the no-flare group. CONCLUSIONS: Patients with a history of gout should be more alert to recurrence gout flares after endovascular interventional procedures. Adequate presurgical control of serum uric acid levels and/or prophylactic treatment with colchicine will help prevent gout flares during the postsurgical period.

14.
J Environ Manage ; 350: 119594, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-37995485

ABSTRACT

Microorganisms play a critical role in maintaining the delicate balance of ecosystem services. However, the assembly processes that shape microbial communities are vulnerable to a range of environmental stressors, such as climate change, eutrophication, and the use of herbicides. Despite the importance of these stressors, little is known about their cumulative impacts on microbial community assembly in aquatic ecosystems. To address this knowledge gap, we established 48 mesocosm experiments that simulated shallow lake ecosystems and subjected them to warming (including continuous warming (W) and heat waves (H)), glyphosate-based herbicides (G), and nutrient loading (E). Our study revealed that in the control group, both deterministic and stochastic processes codominated the assembly of microbial communities in water, whereas in sediment, the processes were primarily stochastic. Interestingly, the effects of multiple stress factors on assembly in these two habitats were completely opposite. Specifically, stressors promoted the dominance of stochastic processes in water but increased the importance of deterministic processes in sediment. Furthermore, warming amplified the effects of herbicides but exerted an opposite and stronger influence on assembly compared to nutrients, emphasizing the complexity of these mechanisms and the significance of considering multiple stressors. The interaction of some factors significantly affected assembly (p < 0.05), with the effects of WEG being most pronounced in water. Both water and sediment exhibited homogeneous assembly of microbial communities (mean NTI >0), but the phylogenetic clustering of microbial communities in water was more closely related (NTI >2). Our research revealed the response model of microbial community assembly in aquatic ecosystems to multiple environmental stresses, such as agricultural pollution, climate change, and eutrophication, and indicated that microbial community changes in sediment may be an important predictor of lake ecosystem development. This provides scientific evidence that better environmental management can reduce impacts on aquatic ecosystems under the threat of future warming.


Subject(s)
Herbicides , Microbiota , Ecosystem , Phylogeny , Eutrophication , Water
15.
J Chem Theory Comput ; 20(2): 799-818, 2024 Jan 23.
Article in English | MEDLINE | ID: mdl-38157475

ABSTRACT

Biomolecular simulations have become an essential tool in contemporary drug discovery, and molecular mechanics force fields (FFs) constitute its cornerstone. Developing a high quality and broad coverage general FF is a significant undertaking that requires substantial expert knowledge and computing resources, which is beyond the scope of general practitioners. Existing FFs originate from only a limited number of groups and organizations, and they either suffer from limited numbers of training sets, lower than desired quality because of oversimplified representations, or are costly for the molecular modeling community to access. To address these issues, in this work, we developed an AMBER-consistent small molecule FF with extensive chemical space coverage, and we provide Open Access parameters for the entire modeling community. To validate our FF, we carried out benchmarks of quantum mechanics (QM)/molecular mechanics conformer comparison and free energy perturbation calculations on several benchmark data sets. Our FF achieves a higher level of performance at reproducing QM energies and geometries than two popular open-source FFs, OpenFF2 and GAFF2. In relative binding free energy calculations for 31 protein-ligand data sets, comprising 1079 pairs of ligands, the new FF achieves an overall root-mean-square error of 1.19 kcal/mol for ΔΔG and 0.92 kcal/mol for ΔG on a subset of 463 ligands without bespoke fitting to the data sets. The results are on par with those of the leading commercial series of OPLS FFs.


Subject(s)
Benchmarking , Molecular Dynamics Simulation , Thermodynamics , Entropy , Proteins/chemistry , Ligands
16.
Animals (Basel) ; 13(23)2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38067073

ABSTRACT

Multiple stressors, including climate change, eutrophication, and pesticide contamination, are significant drivers of the decline in lake zoobenthos. Zoobenthos play a crucial role in aquatic ecosystems, impacting energy dynamics, nutrient cycling, and sediment degradation. However, these stressors have led to a decrease in the abundance and diversity of zoobenthos, resulting in notable changes in species composition and structure. Eutrophication typically increases zoobenthos abundance while reducing taxonomic diversity. Climate change, such as warming and heatwaves, also affects the zoobenthos community structure, with different species exhibiting varying levels of adaptability to temperature changes. Additionally, pesticides like imidacloprid have negative effects on the survival and growth of zoobenthos. However, the interactions between imidacloprid and other stressors remain understudied. Here, we used 48 mesocosms (2500 L) to simulate shallow lakes. We combined nutrient loading, sustained warming, and the imidacloprid pesticide to test how these stressors interactively influence the survival and community of zoobenthos. The experimental results demonstrate that elevated temperatures have a significant impact on aquatic benthic organisms under different treatment conditions. The increase in temperature led to a notable rise in species richness and α-diversity, primarily attributed to the stimulation of metabolic activities in zoobenthos, promoting their growth and reproduction. This finding underscores the potential influence of climate change on aquatic benthic ecosystems, particularly in terms of its promoting effect on α-diversity. However, it is essential to note that elevated temperatures also reduced ß-diversity among different sites, implying a potential trend toward homogenization in zoobenthos communities under warmer conditions. Moreover, this study revealed the interactive effects of multiple stressors on the diversity of aquatic benthic communities. Specifically, the pesticide imidacloprid's impact on zoobenthos is not isolated but demonstrates complex effects within various treatment interactions. In the presence of both temperature elevation and the addition of imidacloprid, the presence of imidacloprid appears to counteract the adverse effects of temperature elevation, resulting in increased species diversity. However, when imidacloprid coincides with nutrient input, it significantly affects α-diversity negatively. These findings highlight the complexity of zoobenthos responses to multiple stressors and how these factors influence both α-diversity and ß-diversity. They provide valuable insights for further research on the conservation and management of ecosystems.

17.
Microorganisms ; 11(11)2023 Nov 19.
Article in English | MEDLINE | ID: mdl-38004818

ABSTRACT

Bacteria in lake water bodies and sediments play crucial roles in various biogeochemical processes. In this study, we conducted a comprehensive analysis of bacterioplankton and sedimentary bacteria community composition and assembly processes across multiple seasons in 18 outdoor mesocosms exposed to three temperature scenarios. Our findings reveal that warming and seasonal changes play a vital role in shaping microbial diversity, species interactions, and community assembly disparities in water and sediment ecosystems. We observed that the bacterioplankton networks were more fragile, potentially making them susceptible to disturbances, whereas sedimentary bacteria exhibited increased stability. Constant warming and heatwaves had contrasting effects: heatwaves increased stability in both planktonic and sedimentary bacteria communities, but planktonic bacterial networks became more fragile under constant warming. Regarding bacterial assembly, stochastic processes primarily influenced the composition of planktonic and sedimentary bacteria. Constant warming intensified the stochasticity of bacterioplankton year-round, while heatwaves caused a slight shift from stochastic to deterministic in spring and autumn. In contrast, sedimentary bacteria assembly is mainly dominated by drift and remained unaffected by warming. Our study enhances our understanding of how bacterioplankton and sedimentary bacteria communities respond to global warming across multiple seasons, shedding light on the complex dynamics of microbial ecosystems in lakes.

18.
Biomacromolecules ; 24(11): 5394-5402, 2023 11 13.
Article in English | MEDLINE | ID: mdl-37870194

ABSTRACT

Intrinsic hemostasis is an innate body response to prevent bleeding based on the sol-gel transition of blood. However, it is often inadequate for exceptional situations, such as acute injury and coagulation disorders, which typically require immediate medical intervention. Herein, we report the preparation of an efficient hemostatic powder, composed of tannic acid (TA), poly(ethylene glycol) (PEG), and poly(d,l-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(d,l-lactide-co-glycolide) triblock copolymer (TB), for biomimetic hemostasis at the bleeding sites. TA has a high affinity for biomolecules and cells and can form coacervates with PEG driven by hydrogen bonding. TB enhances the mechanical strength and provides thermoresponsiveness. The hemostatic powder can rapidly transit into a physical and biodegradable seal on wet substrates under physiological conditions, demonstrating its promise for the generation of instant artificial clots. Importantly, this process is independent of the innate blood clotting process, which could benefit those with blood clotting disorders. This biomimetic hemostatic powder is an adaptive topical sealing agent for noncompressible and irregular wounds, which is promising for biomedical applications.


Subject(s)
Biomimetics , Hemostatics , Powders , Polylactic Acid-Polyglycolic Acid Copolymer , Polymers , Polyethylene Glycols/chemistry , Hemostatics/pharmacology
19.
ACS Macro Lett ; 12(11): 1437-1442, 2023 Nov 21.
Article in English | MEDLINE | ID: mdl-37819638

ABSTRACT

We report a rapid cross-linking strategy for the fabrication of polymer hydrogels based on a thiol-disulfide cascade reaction. Specifically, thiolated polymers (e.g., poly(ethylene glycol), hyaluronic acid, sodium alginate, poly(acrylic acid), and poly(methylacrylic acid)) can be cross-linked via the trigger of Ellman's reagent, resulting in the rapid formation of hydrogels over 20-fold faster than that via the oxidation in air. The gelation kinetics of hydrogels can be tuned by varying the polymer concentration and the molar ratio of Ellman's reagent and free thiols. The obtained hydrogels can be further functionalized with functional moieties (e.g., targeting ligands) for the selective adhesion of cells. This approach is applicable to various natural and synthetic polymers for the assembly of hydrogels with a minimized gelation time, which is promising for various biological applications.

20.
Plant J ; 116(6): 1737-1747, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37694805

ABSTRACT

Dicer-like (DCL) proteins are principal components of RNA silencing, a major defense mechanism against plant virus infections. However, their functions in suppressing virus-induced disease phenotypes remain largely unknown. Here, we identified a role for tomato (Solanum lycopersicum) DCL2b in regulating the wiry leaf phenotype during defense against tobacco mosaic virus (TMV). Knocking out SlyDCL2b promoted TMV accumulation in the leaf primordium, resulting in a wiry phenotype in distal leaves. Biochemical and bioinformatics analyses showed that 22-nt virus-derived small interfering RNAs (vsiRNAs) accumulated less abundantly in slydcl2b mutants than in wild-type plants, suggesting that SlyDCL2b-dependent 22-nt vsiRNAs are required to exclude virus from leaf primordia. Moreover, the wiry leaf phenotype was accompanied by upregulation of Auxin Response Factors (ARFs), resulting from a reduction in trans-acting siRNAs targeting ARFs (tasiARFs) in TMV-infected slydcl2b mutants. Loss of tasiARF production in the slydcl2b mutant was in turn caused by inhibition of miRNA390b function. Importantly, silencing SlyARF3 and SlyARF4 largely restored the wiry phenotype in TMV-infected slydcl2b mutants. Our work exemplifies the complex relationship between RNA viruses and the endogenous RNA silencing machinery, whereby SlyDCL2b protects the normal development of newly emerging organs by excluding virus from these regions and thus maintaining developmental silencing.


Subject(s)
Plant Viruses , Solanum lycopersicum , Tobacco Mosaic Virus , Tobacco Mosaic Virus/physiology , Solanum lycopersicum/genetics , Plant Viruses/genetics , RNA, Small Interfering/genetics , Indoleacetic Acids , Plant Leaves/genetics , Phenotype , Plant Diseases
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