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Mangrove wetlands are highly productive ecosystems in tropical and subtropical coastal zones, play crucial roles in water purification, biodiversity maintenance, and carbon sequestration. Recent years have seen the implementation of pond return initiatives, which have facilitated the gradual recovery of mangrove areas in China. However, the implications of these initiatives for soil aggregate stability, microbial community structure, and network interactions remain unclear. This study assesses the impacts of converting ponds to mangroves-both in natural and artificially restored settings-on soil aggregate stability and microbial networks at typical mangrove restoration sites along China's southeastern coast. Our observations confirmed our hypothesis that pond-to-mangrove conversions resulted in an increase in the proportion of large aggregates (>0.25â¯mm), improved soil aggregate structural stability, and increased carbon sequestration. However, mangrove recovery led to a decrease in the abundance and diversity of soil fungi communities. In terms of co-occurrence networks, naturally restored mangrove wetlands exhibited more nodes and edges. The naturally recovered mangrove wetlands demonstrated a higher level of community symbiosis compared to those that were manually restored. Conversely, bacterial networks showed a different pattern, with significant shifts in key taxa related to carbon sequestration functions. For instance, the proportion of bacterial Desulfobacterota and fungi Basidiomycota in natural recovery mangrove increased by 15.03â¯% and 7.82â¯%, respectively, compared with that in aquaculture ponds. Soil fungi and bacteria communities, as well as carbon sequestration by aggregates, were all positively correlated with soil total carbon content (Pâ¯<â¯0.05). Both bacterial and fungal communities contributed to soil aggregate stability. Our study highlights the complex relationships between soil microbial communities, aggregate stability, and the carbon cycle before and after land-use changes. These findings underscore the potential benefits of restoring mangrove wetlands, as such efforts can enhance carbon storage capacity and significantly contribute to climate change mitigation.
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Previous studies have predominantly explored the response mechanisms of constructed wetlands (CWs) to singular disturbances. In practical applications, CWs are frequently subject to multiple disturbances, resulting in complex interference mechanisms. Therefore, this study aims to select harmful algal blooms and microalga ZM-5 as disturbances to investigate the response mechanisms of CWs. Results revealed a dynamic pattern in COD removal efficiency of CWs, with fluctuations at 39.0 ± 6.2 % and 80.1 ± 4.7 % during the disturbances, followed by a recovery to approximately 65.7 ± 3.2 %. Additionally, the CWs exhibited a capacity for self-recovery and enhanced stability by selectively promoting specific microbial communities through the regulation of the genes responsible for indole-3-acetic acid (IAA) and vitamin production. Importantly, this study underscored the establishment of a resilient microbial community structure within CWs following multiple disturbances, characterized by a more interconnected microbial network. These findings shed light on the adaptive mechanisms of CWs in the face of complex environmental challenges.
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Humedales , Microalgas/metabolismo , Interacciones Microbianas , Análisis de la Demanda Biológica de Oxígeno , Floraciones de Algas Nocivas , Ácidos Indolacéticos/metabolismo , Biodegradación AmbientalRESUMEN
Objective: During in vitro fertilization-embryo transfer (IVF-ET) treatment, the reproductive endocrine regulatory mechanisms hold pivotal importance. Specifically, the serum estradiol (E 2) level during ovulation emerges as a critical factor influencing pregnancy outcomes. This retrospective study aimed to comprehensively compare two common clinical regimens based on the grouping of serum E 2 levels and the number of oocytes retrieved on the trigger day. Our objective was to evaluate the pregnancy outcomes in IVF-ET patients across different ovarian response groups, exploring the efficacy of the dual-trigger and single-trigger regimens to provide valuable insights for optimizing clinical strategies in the context of IVF-ET. Methods: A retrospective analysis was conducted on the clinical data of 2778 infertile patients who underwent ART (IVF/ICSI). Subsequently, a detailed statistical analysis was performed on 1032 patients following an antagonist regimen. Participants were categorized into single-trigger and dual-trigger groups based on real-world trigger protocols, considering different ovarian responses. Comprehensive statistical assessments were conducted on baseline characteristics, ovulation induction, and pregnancy outcomes. Results: Baseline characteristics and cycle parameters among the three patient groups (high ovarian response, normal response, and poor response) exhibited no significant differences between the dual-trigger and single-trigger regimen groups. Despite the dual-trigger regimen utilizing a significantly lower HCG dose, no notable discrepancies were observed in laboratory results and pregnancy outcomes (embryo transfer rate, pregnancy rate, and live birth rate) for normal and high responders. Remarkably, E 2 levels were higher in the dual-trigger group compared to the single-trigger group. In high and normal responders, the dual-trigger regimen demonstrated increased oocyte counts and oocyte acquisition rates, coupled with decreased transfer cancellation rates attributed to ovarian hyperstimulation syndrome (OHSS). Intriguingly, patients with a poor ovarian response experienced no graft cancellations due to OHSS prevention in either group. Conclusion: For patients with high and normal ovarian responses, the utilization of a dual-trigger regimen on the trigger day effectively mitigates the risk of OHSS. Our large sample study supports the substitutability of the dual-trigger regimen over the single-trigger regimen without compromising pregnancy outcomes. However, this conclusion is not applicable to patients with poor ovarian responses. The results of this study highlight the necessity of adopting a customized and individualized treatment approach that should be based on the patient's ovarian response. Additionally, recognizing the pivotal role of the endocrine environment in influencing pregnancy outcomes and the occurrence of OHSS, further exploration of the effects of different triggering regimens on endocrine parameters is warranted. Such investigations will contribute to enhancing the reproductive outcomes of IVF-ET technology.
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Brahma-related gene 1 (BRG1) has been implicated in the repair of DNA double-strand breaks (DSBs). Downregulation of BRG1 impairs DSBs repair leading to accumulation of double-stranded DNA (dsDNA). Currently, the role of BRG1 in diabetic cardiomyopathy (DCM) has not been clarified. In this study, we aimed to explore the function and molecular by which BRG1 regulates DCM using mice and cell models. We found that BRG1 was downregulated in the cardiac tissues of DCM mice and in cardiomyocytes cultured with high glucose and palmitic acid (HG/PA), which was accompanied by accumulation of dsDNA and activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. shRNA-mediated Brg1 knockdown aggravated DCM mice cardiac functions, enhanced dsDNA accumulation, cGAS-STING signaling activation, which induced inflammation and apoptosis. In addition, the results were further verified in HG/PA-treated primary neonatal rat cardiomyocytes (NRCMs). Overexpression of BRG1 in NRCMs yielded opposite results. Furthermore, a selective cGAS inhibitor RU.521 or STING inhibitor C-176 partially reversed the BRG1 knockdown-induced inflammation and apoptosis in vitro. In conclusion, our results demonstrate that BRG1 is downregulated during DCM in vivo and in vitro, resulting in cardiomyocyte inflammation and apoptosis due to dsDNA accumulation and cGAS-STING signaling activation. Therefore, targeting the BRG1-cGAS-STING pathway may represent a novel therapeutic strategy for improving cardiac function of patients with DCM.
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SARS-CoV-2 continues to threaten human health, antibody therapy is one way to control the infection. Because new SARS-CoV-2 mutations are constantly emerging, there is an urgent need to develop broadly neutralizing antibodies to block the viral entry into host cells. VNAR from sharks is the smallest natural antigen binding domain, with the advantages of small size, flexible paratopes, good stability, and low manufacturing cost. Here, we used recombinant SARS-CoV-2 Spike-RBD to immunize sharks and constructed a VNAR phage display library. VNAR R1C2, selected from the library, efficiently binds to the RBD domain and blocks the infection of ACE2-positive cells by pseudovirus. Next, homologous bivalent VNARs were constructed through the tandem fusion of two R1C2 units, which enhanced both the affinity and neutralizing activity of R1C2. R1C2 was predicted to bind to a relatively conserved region within the RBD. By introducing mutations at four key binding sites within the CDR3 and HV2 regions of R1C2, the affinity and neutralizing activity of R1C2 were significantly improved. Furthermore, R1C2 also exhibits an effective capacity of binding to the Omicron variants (BA.2 and XBB.1). Together, these results suggest that R1C2 could serve as a valuable candidate for preventing and treating SARS-CoV-2 infections.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , SARS-CoV-2 , Tiburones , Anticuerpos de Dominio Único , Glicoproteína de la Espiga del Coronavirus , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Animales , SARS-CoV-2/inmunología , Anticuerpos de Dominio Único/inmunología , Anticuerpos de Dominio Único/genética , Humanos , Tiburones/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , COVID-19/inmunología , COVID-19/virología , Sitios de Unión , Unión Proteica , Biblioteca de Péptidos , Células HEK293 , MutaciónRESUMEN
Diabetic cardiomyopathy (DCM), one of the most serious complications of diabetes mellitus, has become recognized as a cardiometabolic disease. In normoxic conditions, the majority of the ATP production (>95%) required for heart beating comes from mitochondrial oxidative phosphorylation of fatty acids (FAs) and glucose, with the remaining portion coming from a variety of sources, including fructose, lactate, ketone bodies (KB) and branched chain amino acids (BCAA). Increased FA intake and decreased utilization of glucose and lactic acid were observed in the diabetic hearts of animal models and diabetic patients. Moreover, the polyol pathway is activated, and fructose metabolism is enhanced. The use of ketones as energy sources in human diabetic hearts also increases significantly. Furthermore, elevated BCAA levels and impaired BCAA metabolism were observed in the hearts of diabetic mice and patients. The shift in energy substrate preference in diabetic hearts results in increased oxygen consumption and impaired oxidative phosphorylation, leading to diabetic cardiomyopathy. However, the precise mechanisms by which impaired myocardial metabolic alterations result in diabetes mellitus cardiac disease are not fully understood. Therefore, this review focuses on the molecular mechanisms involved in alterations of myocardial energy metabolism. It not only adds more molecular targets for the diagnosis and treatment, but also provides an experimental foundation for screening novel therapeutic agents for diabetic cardiomyopathy.
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Nanoplastics (NPs) in wastewaters may present a potential threat to biological nitrogen removal in constructed wetlands (CWs). Iron ions are pivotal in microbially mediated nitrogen metabolism, however, explicit evidence demonstrating the impact of NPs on nitrogen removal regulated by iron utilization and metabolism remains unclear. Here, we investigated how NPs disturb intracellular iron homeostasis, consequently interfering with the coupling mechanism between iron utilization and nitrogen metabolism in CWs. Results indicated that microorganisms affected by NPs developed a siderophore-mediated iron acquisition mechanism to compensate for iron loss. This deficiency resulted from NPs internalization limited the activity of the electron transport system and key enzymes involved in nitrogen metabolism. Microbial network analysis further suggested that NPs exposure could potentially trigger destabilization in microbial networks and impair effective microbial communication, and ultimately inhibit nitrogen metabolism. These adverse effects, accompanied by the dominance of Fe3+ over certain electron acceptors engaged in nitrogen metabolism under NPs exposure, were potentially responsible for the observed significant deterioration in nitrogen removal (decreased by 30 %). This study sheds light on the potential impact of NPs on intracellular iron utilization and offers a substantial understanding of the iron-nitrogen coupling mechanisms in CWs.
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Hierro , Nitrógeno , Humedales , Hierro/metabolismo , Nitrógeno/metabolismo , Eliminación de Residuos Líquidos , Aguas Residuales/química , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/toxicidadRESUMEN
Due to the low toxicity, biocompatibility and eco-friendliness, microorganisms have received a lot of attention for gold nanoparticles (AuNPs) synthesis. This work isolated a fungal strain capable of efficiently generating AuNPs from aerobic granular sludge, named XY3. Comparison of 18S rDNA sequence results showed that fungus XY3 belongs to Candida rugopelliculosa. AuNPs were synthesized by initiating an Au3+-induced stress response that prompted the reduction of Au3+ to Au0 by the fungus XY3. It is worth noting that the addition of nutritional substrates weakens the stress response induced by Au3+, resulting in a decrease in the yield of AuNPs. As evidenced by nystatin inhibition studies, the synthesis of AuNPs is based on biochemical reactions rather than purely physical changes. The XRD results suggested that XY3-secreted biomolecules were involved in the reduction of Au3+ and AuNPs synthesis. The results of the three variation patterns of reducing power, biomolecules, and AuNPs absorbance revealed that Au3+ reduction was mostly dependent on the reducing polysaccharides. In addition, extracellular proteins were shown to be involved in the synthesis of AuNPs, which is responsible for the uniform distribution of AuNPs. This work provided a wide and cost-effective seed source for AuNPs synthesis, and also offered a resourceful solution for residual sludge treatment of fungal type aerobic granular sludge.
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Due to the high salt content and pH value, the structure of saline-sodic soil was deteriorated, resulting in decreased soil fertility and inhibited soil element cycling. This, in turn, caused significant negative impacts on crop growth, posing a major challenge to global agriculture and food security. Despite numerous studies aimed at reducing the loss of plant productivity in saline-sodic soils, the knowledge regarding shifts in soil microbial communities and carbon/nitrogen cycling during saline-sodic soil improvement remains incomplete. Consequently, we developed a composite soil amendment to explore its potential to alleviate salt stress and enhance soil quality. Our findings demonstrated that the application of this composite soil amendment effectively enhanced microbial salinity resistance, promotes soil carbon fixation and nitrogen cycling, thereby reducing HCO3- concentration and greenhouse gas emissions while improving physicochemical properties and enzyme activity in the soil. Additionally, the presence of CaSO4 contributed to a decrease in water-soluble Na+ content, resulting in reduced soil ESP and pH by 14.64 % and 7.42, respectively. Our research presents an innovative approach to rehabilitate saline-sodic soil and promote ecological restoration through the perspective of elements cycles.
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Carbono , Suelo , Suelo/química , Álcalis , Ciclo del Nitrógeno , Nitrógeno , Carbón Orgánico/químicaRESUMEN
By virtue of the drug repurposing strategy, the anti-osteoporosis drug raloxifene was identified as a novel PPARγ ligand through structure-based virtual high throughput screening (SB-VHTS) of FDA-approved drugs and TR-FRET competitive binding assay. Subsequent structural refinement of raloxifene led to the synthesis of a benzothiophene derivative, YGL-12. This compound exhibited potent PPARγ modulation with partial agonism, uniquely promoting adiponectin expression and inhibiting PPARγ Ser273 phosphorylation by CDK5 without inducing the expression of adipongenesis associated genes, including PPARγ, aP2, CD36, FASN and C/EBPα. This specific activity profile resulted in effective hypoglycemic properties, avoiding major TZD-related adverse effects like weight gain and hepatomegaly, which were demonstrated in db/db mice. Molecular docking studies showed that YGL-12 established additional hydrogen bonds with Ile281 and enhanced hydrogen-bond interaction with Ser289 as well as PPARγ Ser273 phosphorylation-related residues Ser342 and Glu343. These findings suggested YGL-12 as a promising T2DM therapeutic candidate, thereby providing a molecular framework for the development of novel PPARγ modulators with an enhanced therapeutic index.
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PPAR gamma , Clorhidrato de Raloxifeno , Tiofenos , Ratones , Animales , PPAR gamma/metabolismo , Simulación del Acoplamiento Molecular , Reposicionamiento de MedicamentosRESUMEN
Non-classical secretory proteins are widely found in bacteria and have been extensively studied due to their important physiological roles. However, the relevant non-classical secretory mechanisms remain unclear. In this study, we found that oxalate decarboxylase (Bacm OxDC) from Bacillus mojavensis XH1 belongs to non-classical secretory proteins. Its N-terminus showed high hydrophilicity, which was different from the conventional signal peptide. The truncation test revealed that the deletion of the N-terminus affects the structure resulting in its inability to cross the cell membrane. Further studies verified that the exported peptide YydF played an important role in the secretion process of Bacm OxDC. Experimental results on the secretion mechanism indicated that Bacm OxDC bound to the exported peptide YydF and they are translocated to the cell membrane together, after which Bacm OxDC caused cell membrane relaxation for transmembrane secretion. Thereafter, three recombinant proteins were successfully secreted with certain enzymatic activity by fusing Bacm OxDC as a guide protein with various target proteins. To the best of our knowledge, this was the first time that non-classical secretion mechanism in bacteria has been analyzed. The novel discovery may provide a reference and broaden the horizons of the secretion pathway and expression regulation of proteins.
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Bacillus , Carboxiliasas , Carboxiliasas/química , Bacillus/genética , Bacillus/metabolismo , Bacillus subtilis/metabolismo , Señales de Clasificación de ProteínaRESUMEN
As wellknown persistent contaminants, polycyclic aromatic hydrocarbons (PAHs) and heterocyclic polyaromatic hydrocarbons (Heterocyclic PAHs)'s fates in cryogenic environments are remains uncertain. Herein, strain S01 was identified as Pseudomonas fluorescens, a novel bacterium tolerant to low temperature and capable of degrading PAHs and heterocyclic PAHs. Strain S01 exhibited growth at 5-40 â and degradation rate of mixed PAHs and heterocyclic PAHs reached 52% under low-temperature. Through comprehensive metabolomic, genomic, and transcriptomic analyses, we reconstructed the biodegradation pathway for PAHs and heterocyclic PAHs in S01 while investigating its response to low temperature. Further experiments involving deletion and replacement of methyl-accepting chemotaxis protein (MCP) confirmed its crucial role in enabling strain S01's adaptation to dual stress of low temperature and pollutants. Additionally, our analysis revealed that MCP was upregulated under cold stress which enhanced strain S01's motility capabilities leading to increased biofilm formation. The establishment of biofilm promoted preservation of distinct cellular membrane stability, thereby enhancing energy metabolism. Consequently, this led to heightened efficiency in pollutant degradation and improved cold resistance capabilities. Our findings provide a comprehensive understanding of the environmental fate of both PAHs and heterocyclic PAHs under low-temperature conditions while also shedding light on cold adaptation mechanism employed by strain S01.
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Contaminantes Ambientales , Hidrocarburos Policíclicos Aromáticos , Pseudomonas fluorescens , Hidrocarburos Policíclicos Aromáticos/metabolismo , Pseudomonas fluorescens/metabolismo , Quimiotaxis , Temperatura , Biodegradación Ambiental , Contaminantes Ambientales/metabolismoRESUMEN
Ubiquitin-specific protease 7 (USP7) is a promising prognostic and druggable target for cancer therapy. Inhibition of USP7 can activate the MDM2-P53 signaling pathway, thereby promoting cancer cell apoptosis. This study based on watvina molecular docking of virtual screening method and biological evaluation found the new USP7 inhibitors targeting catalytic active site. Three hits were screened from 3760 natural products and validated as USP7 inhibitors by enzymatic and kinetic assays. The IC50 values of scutellarein (Scu), semethylzeylastera (DML) and salvianolic acid C (SAC) were 3.017, 6.865 and 8.495 µM, respectively. Further, we reported that the hits could downregulate MDM2 and activate p53 signal pathway in HCT116 cells. Molecular dynamics simulation was used to investigate the binding mechanism of USP7 to Scu, the compound with the best performance, which formed stable contact with Val296, Gln297, Phe409, Tyr465 and Tyr514. These interactions are essential for maintaining the biological activity of Scu. Three natural products are suitable as lead compounds for the development of novel USP7 inhibitors, especially anti-colon cancer drugs.Communicated by Ramaswamy H. Sarma.
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The rapid screening of agricultural waste materials for capacitor preparation holds significant importance in comprehending the relationship between material properties and enhancing experimental efficiency. In this study, we developed two machine learning models to predict electrode material characteristics using 2997 data points extracted from 235 articles. The identification and influence of key features on prediction indices provide a theoretical foundation for subsequent practical preparation. Through regression analysis and index evaluation, corn straw emerged as the optimal material for capacitor preparation, leading us to propose a one-step activation and two-step modification approach to convert corn straw into porous biochar. By modifying biochar with Co(NO3)2·6H2O, the maximum electrode capacitance of porous carbon reached 732.6 F/g. Furthermore, the electrode exhibited exceptional cycle stability with a remaining capacitance of 96 % after 5000 cycles. The prepared symmetric capacitor demonstrated pseudocapacitance behavior with a capacitance of 183.15 F/g at a current density of 1.0 A/g, power density of 22 kW/kg, and energy density of 9.03 Wh/kg. Considering the increasing annual output of corn straw and its superior industrial application prospects compared to acid-, base-, or precious metal-based alternatives due to their cost-effectiveness and environmental friendliness, these findings highlight the potential practical value in utilizing modified corn straw biochar as an efficient energy storage electrode material.