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1.
Elife ; 122024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38652107

RESUMO

Organisms utilize gene regulatory networks (GRN) to make fate decisions, but the regulatory mechanisms of transcription factors (TF) in GRNs are exceedingly intricate. A longstanding question in this field is how these tangled interactions synergistically contribute to decision-making procedures. To comprehensively understand the role of regulatory logic in cell fate decisions, we constructed a logic-incorporated GRN model and examined its behavior under two distinct driving forces (noise-driven and signal-driven). Under the noise-driven mode, we distilled the relationship among fate bias, regulatory logic, and noise profile. Under the signal-driven mode, we bridged regulatory logic and progression-accuracy trade-off, and uncovered distinctive trajectories of reprogramming influenced by logic motifs. In differentiation, we characterized a special logic-dependent priming stage by the solution landscape. Finally, we applied our findings to decipher three biological instances: hematopoiesis, embryogenesis, and trans-differentiation. Orthogonal to the classical analysis of expression profile, we harnessed noise patterns to construct the GRN corresponding to fate transition. Our work presents a generalizable framework for top-down fate-decision studies and a practical approach to the taxonomy of cell fate decisions.


Assuntos
Diferenciação Celular , Redes Reguladoras de Genes , Diferenciação Celular/genética , Animais , Hematopoese/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Desenvolvimento Embrionário/genética , Transdiferenciação Celular/genética , Humanos
2.
Traffic Inj Prev ; : 1-7, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38656921

RESUMO

OBJECTIVE: Young drivers aged 24 and below are at heightened risks of being influenced by their route familiarity levels. This study aims to compare prevalences of crash culpability, crash configurations and risky driver behaviors among newly licensed young drivers when they are driving on roads with different route familiarity levels. METHODS: Based on the road traffic crash and violation data in Yunnan Province of China from January 2017 through December 2019, we classified drivers' different route familiarity levels by utilizing spatial distance away from residence-based method, including driving on high route familiarity (HRF) and low route familiarity (LRF) roads. Prevalence ratios were estimated using generalized estimating equation log-binomial regression models. RESULTS: We identified 12016 newly licensed young drivers driving on HRF roads and 2189 drivers on LRF roads. Within 48 months of licensure, young drivers on LRF roads were more likely to be at fault for their motor vehicle crashes than those on HRF roads. Young drivers on LRF roads were more likely to be with failure to obey traffic control device, with failure to yield right of way, wrong way driving, backing unsafely and improper parking compared with those on HRF roads. Drivers on LRF roads were less likely to be inattentive and driving with unsafe speed and following too closely compared with those on HRF roads. CONCLUSIONS: Several basic aspects of targeted countermeasures can be put forward. Visual impacts such as rectangular rapid-flashing beacon (RRFB) can be used in order to prevent wrong way driving on the tourist roadways. Arranging safety talks and programs in colleges and universities and technical interventions like Advanced Driver Assistance Systems (ADAS) can be used to reduce young drivers' driving distraction and overconfidence. It is recommended that the driving schools can use these research findings to include in licensure program to make young drivers more aware of the various factors that expose them to crash risks so that more defensive driving may be needed under different situations, and this can also help build the graduated driving licensure (GDL) programme in China.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38594563

RESUMO

To elucidate the effects of long-term (20 years) afforestation with different woody plant species on the soil microenvironment in coal gangue polymetallic contaminated areas. This study analyzed the soil physicochemical properties, soil enzyme activities, soil ionophore, bacterial community structure, soil metabolite, and their interaction relationships at different vertical depths. Urease, sucrase, and acid phosphatase activities in the shallow soil layers increased by 4.70-7.45, 3.83-7.64, and 3.27-4.85 times, respectively, after the restoration by the four arboreal plant species compared to the plant-free control soil. Additionally, it reduced the content of available elements in the soil and alleviated the toxicity stress for Cd, Ni, Co, Cr, As, Fe, Cu, U, and Pb. After the long-term restoration of arboreal plants, the richness and Shannon indices of soil bacteria significantly increased by 4.77-23.81% and 2.93-7.93%, respectively, broadening the bacterial ecological niche. The bacterial community structure shaped by different arboreal plants exhibited high similarity, but the community similarity decreased with increasing vertical depth. Soils Zn, U, Sr, S, P, Mg, K, Fe, Cu, Ca, Ba, and pH were identified as important influencing factors for the community structure of Sphingomonas, Pseudarthrobacter, Nocardioides, and Thiobacillus. The metabolites such as sucrose, raffinose, L-valine, D-fructose 2, 6-bisphosphate, and oxoglutaric acid were found to have the greatest effect on the bacterial community in the rhizosphere soils for arboreal plants. The results of the study demonstrated that long-term planting for woody plants in gangue dumps could regulate microbial abundance and symbiotic patterns through the accumulation of rhizosphere metabolites in the soil, increase soil enzyme activity, reduce heavy metal levels, and improve the soil environment in coal gangue dumps.

4.
Cancer Cell ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38518774

RESUMO

Emerging as the most potent and durable combinational immunotherapy, dual anti-PD-1 and CTLA-4 immune checkpoint blockade (ICB) therapy notoriously increases grade 3-5 immune-related adverse events (irAEs) in patients. Accordingly, attempts to improve the antitumor potency of anti-PD-1+CTLA-4 ICB by including additional therapeutics have been largely discouraged due to concerns of further increasing fatal toxicity. Here, we screened ∼3,000 Food and Drug Administration (FDA)-approved drugs and identified clofazimine as a potential third agent to optimize anti-PD-1+CTLA-4 ICB. Remarkably, clofazimine outperforms ICB dose reduction or steroid treatment in reversing lethality of irAEs, but unlike the detrimental effect of steroids on antitumor efficacy, clofazimine potentiates curative responses in anti-PD-1+CTLA-4 ICB. Mechanistically, clofazimine promotes E2F1 activation in CD8+ T cells to overcome resistance and counteracts pathogenic Th17 cells to abolish irAEs. Collectively, clofazimine potentiates the antitumor efficacy of anti-PD-1+CTLA-4 ICB, curbs intractable irAEs, and may fill a desperate clinical need to improve patient survival.

5.
Biochem Genet ; 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316654

RESUMO

Despite many studies on papillary thyroid carcinoma (PTC) in the past few decades, some critical and significant genes remain undiscovered. To explore genes that may play crucial roles in PTC, a detailed analysis of the expression levels, mutations, and clinical significance of Kallikrein-related peptidases (KLKs) family genes in PTC was undertaken to provide new targets for the precise treatment of the disease. A comprehensive analysis of KLK family genes was performed using various online tools, such as GEPIA, Kaplan-Meier Plotter, LinkedOmics, GSCA, TIMER, and Cluego. KLK7, KLK10, and KLK11 were critical factors of KLK family genes. Then, functional assays were carried out on KLK7/10/11 to determine their proliferation, migration, and invasion capabilities in PTC. The mRNA expression levels of KLK7, KLK10, KLK11, and KLK13 were significantly elevated in thyroid carcinoma, while KLK1, KLK2, KLK3 and KLK4 mRNA levels were decreased compared to normal tissues. Correlations between KLK2/7-12/15 expression levels and tumor stage were also observed in thyroid carcinoma. Survival analysis demonstrated that KLK4/5/7/9-12/14 was associated with overall survival in patients with thyroid cancer. Not only were KLK genes strongly associated with cancer-related pathways, but also KLK7/10/11 was associated with immune-cell infiltration. Finally, silencing KLK7/10/11 impaired human papillary thyroid carcinoma cells' growth, migration ability, and invasiveness. The increased expression of KLK7, KLK10, and KLK11 may serve as molecular markers to identify PTC patients. KLK7, KLK10, and KLK11 could be potential prognostic indicators and targets for precision therapy against PTC.

6.
Arch Endocrinol Metab ; 68: e210541, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38394156

RESUMO

Objective: As the most prevalent type of thyroid malignancy, papillary thyroid carcinoma (PTC) accounts for over 80% of all thyroid cancers. Circular RNAs (circRNAs) have been found to regulate multiple cancers, including PTC. Materials and methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to analyse RNA and protein levels. Fluorescence in situ hybridization (FISH) was used to detect the distribution of the target genes. Functional experiments and animal experiments were implemented to analyse the biological functions of target genes in vitro and in vivo. Luciferase reporter, RNA pulldown, RNA binding protein immunoprecipitation (RIP) and mRNA stability assays were used to probe the underlying mechanisms. Results: CircSEMA6Awas found to be upregulated in PTC tissues and cells, and its circular structure was verified. CircSEMA6A promotes PTC cell migration and invasion. Moreover, circSEMA6A functions as a competing endogenous RNA (ceRNA) to upregulate proline rich and Gla domain 4 (PRRG4) expression by sponging microRNA-520h (miR-520h). CircSEMA6A recruits ELAV1 to stabilize PRRG4 mRNA and drives PTC progression via PRRG4. Conclusion: CircSEMA6A upregulates PRRG4 by targeting miR-520h and recruiting ELAVL1 to affect the invasion and migration of PTC cells, offering insight into the molecular mechanisms of PTC.


Assuntos
MicroRNAs , Neoplasias da Glândula Tireoide , Animais , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/patologia , Hibridização in Situ Fluorescente , Proliferação de Células/genética , Linhagem Celular Tumoral , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias da Glândula Tireoide/patologia
7.
Chemosphere ; 351: 141265, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38246497

RESUMO

Plant enrichment and tolerance to heavy metals are crucial for the phytoremediation of coal gangue mountain. However, understanding of how plants mobilize and tolerate heavy metals in coal gangue is limited. This study conducted potted experiments using Setaria viridis as a pioneer remediation plant to evaluate its tolerance to coal gangue, its mobilization and enrichment of metals, and its impact on the soil environment. Results showed that the addition of 40% gangue enhanced plant metal and oxidative stress resistance, thereby promoting plant growth. However, over 80% of the gangue inhibited the chlorophyll content, photoelectron conduction rate, and biomass of S. viridis, leading to cellular peroxidative stress. An analysis of metal resistance showed that endogenous S in coal gangue promoted the accumulation of glutathione, plant metal chelators, and non-protein thiols, thereby enhancing its resistance to metal stress. Setaria viridis cultivation affected soil properties by decreasing nitrogen, phosphorus, conductivity, and urease and increasing sucrase and acid phosphatase in the rhizosphere soil. In addition, S. viridis planting increased V, Cr, Ni, As, and Zn in the exchangeable and carbonate-bound states within the gangue, effectively enriching Cd, Cr, Fe, S, U, Cu, and V. The increased mobility of Cd and Pb was correlated with a higher abundance of Proteobacteria and Acidobacteria. Heavy metals, such as As, Fe, V, Mn, Ni, and Cu, along with environmental factors, including total nitrogen, total phosphorus, urease, and acid phosphatase, were the primary regulatory factors for Sphingomonas, Gemmatimonas, and Bryobacter. In summary, S. viridis adapted to gangue stress by modulating antioxidant and elemental enrichment systems and regulating the release and uptake of heavy metals through enhanced bacterial abundance and the recruitment of gangue-tolerant bacteria. These findings highlight the potential of S. viridis for plant enrichment in coal gangue areas and will aid the restoration and remediation of these environments.


Assuntos
Metais Pesados , Setaria (Planta) , Poluentes do Solo , Cádmio/farmacologia , Setaria (Planta)/metabolismo , Carvão Mineral , Urease , Metais Pesados/análise , Plantas/metabolismo , Fósforo/farmacologia , Bactérias/metabolismo , Enxofre/farmacologia , Solo , Fosfatase Ácida , Nitrogênio/farmacologia , Poluentes do Solo/análise
9.
BMC Vet Res ; 20(1): 2, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172782

RESUMO

BACKGROUND: Pregnancy toxemia is a common disease, which occurs in older does that are pregnant with multiple lambs in the third trimester. Most of the sick goats die within a few days, which can seriously impact the economic benefits of goat breeding enterprises. The disease is believed to be caused by malnutrition, stress, and other factors, that lead to the disorder of lipid metabolism, resulting in increased ketone content, ketosis, ketonuria, and neurological symptoms. However, the changes in gut microbes and their metabolism in this disease are still unclear. The objective of this experiment was to evaluate the effect of toxemia of pregnancy on the fecal microbiome and metabolomics of does. RESULTS: Eight pregnant does suspected of having toxemia of pregnancy (PT group) and eight healthy does during the same pregnancy (NC group) were selected. Clinical symptoms and pathological changes at necropsy were observed, and liver tissue samples were collected for pathological sections. Jugular venous blood was collected before morning feeding to detect biochemical indexes. Autopsy revealed that the liver of the pregnancy toxemia goat was enlarged and earthy yellow, and the biochemical results showed that the serum levels of aspartate aminotransferase (AST) and ß-hydroxybutyric acid (B-HB) in the PT group were significantly increased, while calcium (Ca) levels were significantly reduced. Sections showed extensive vacuoles in liver tissue sections. The microbiome analysis found that the richness and diversity of the PT microbiota were significantly reduced. Metabolomic analysis showed that 125 differential metabolites were screened in positive ion mode and enriched in 12 metabolic pathways. In negative ion mode, 100 differential metabolites were screened and enriched in 7 metabolic pathways. CONCLUSIONS: Evidence has shown that the occurrence of pregnancy toxemia is related to gut microbiota, and further studies are needed to investigate its pathogenesis and provide research basis for future preventive measures of this disease.


Assuntos
Doenças das Cabras , Microbiota , Pré-Eclâmpsia , Doenças dos Ovinos , Toxemia , Feminino , Gravidez , Ovinos , Animais , Pré-Eclâmpsia/veterinária , Cabras/metabolismo , Toxemia/veterinária , Metaboloma , Metabolômica , Carneiro Doméstico/metabolismo , RNA Ribossômico 16S
10.
Water Res ; 249: 120924, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38029486

RESUMO

To offset the imperfections of higher cost and emission of CO2 greenhouse gas in heterotrophic denitrification (HDN) as well as longer start-up time in autotrophic denitrification (ADN), we synergized the potential ternary electron donors of organic carbon source, thiosulfate and zero-valent iron (Fe0) to achieve efficient mixotrophic denitrification (MDN) of oligotrophic secondary effluent. When the influent chemical oxygen demand to nitrogen (COD/N) ratio ascended gradually in the batch operation with sufficient sulfur to nitrogen (S/N) ratio, the MDN with thiosulfate and Fe0 added achieved the highest TN removal for treating simulated and authentic secondary effluents. The external carbon is imperative for initiating MDN, while thiosulfate is indispensable for promoting TN removal efficiency. Although Fe0 hardly donated electrons for denitrification, the suitable circumneutral environment for denitrification was implemented by OH- released from Fe0 corrosion, which neutralized H+generated during thiosulfate-driven ADN. Meanwhile, Fe0 corrosion consumed the dissolved oxygen (DO) and created the low DO environment suitable for anoxic denitrification. This process was further confirmed by the continuous flow operation for treating authentic secondary effluent. The TN removal efficiency achieved its maximum under the combination condition of influent COD/N ratio of 3.1-3.5 and S/N ratio of 2.0-2.1. Whether in batch or continuous flow operation, the coordination of thiosulfate and Fe0 maintained the dominance of Thiobacillus for ADN, with the dominant heterotrophic denitrifiers (e.g., Plasticicumulans, Terrimonas, Rhodanobacter and KD4-96) coexisting in MDN system. The interaction insights of ternary electron donors in MDN established a pathway for realizing high-efficiency nitrogen removal of secondary effluent.


Assuntos
Desnitrificação , Tiossulfatos , Elétrons , Carbono , Reatores Biológicos , Nitratos/metabolismo , Processos Autotróficos , Nitrogênio
11.
Water Res ; 249: 120909, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38006788

RESUMO

Sludge hydrolysate, the byproduct generated during sludge hydrothermal treatment (HT), is a potential carbon source for biological denitrification. However, the refractory organic matters and the nutrient substances are unfavorable to the nitrogen removal. In this study, effects of HT conditions on the hydrolysate properties, and the hydrolysate compositions optimization via red soil (RS) filtration were investigated. At HT temperature of 160-220 °C and reaction time of 1-4 h, the highest dissolution rate of organics from sludge to hydrolysate achieved 70.1 %, while the acetic acid dominated volatile fatty acids (VFAs) was no more than 5.0 % of the total organic matter content. The NH4+-N and dissolved organic nitrogen (DON) were the main nitrogen species in hydrolysate. When the hydrolysate was filtered by RS, the high molecular weight organic matters, DON, NH4+ and PO43- were effectively retained by RS, while VFAs and polysaccharide favorable for denitrification were kept in the filtrate. When providing same COD as the carbon source, the filtrate group (Fi-Group) introduced lower concentrations of TN and humic substances but higher content of VFAs. This resulted in TN removal rate (57.0 %) and denitrification efficiency (93.6 %) in Fi-Group higher than those in hydrolysate group (Hy-Group), 39.4 % and 83.7 %, respectively. It is noticeable that both Hy- and Fi- Groups up-regulated most of denitrification functional genes, and increased the richness and diversity of denitrifying bacteria. Also, more denitrifying bacteria genera appeared, and their relative abundance increased significantly from 3.31 % in Control to 21.15 % in Hy- Group and 31.31 % in Fi-Group. This indicates that the filtrate is a more suitable carbon source for denitrification than hydrolysate. Moreover, the pH rose from 4.6 ± 0.14 to 6.5 ± 0.05, and the organic carbon, TN, TP and cation exchange capacity (CEC) of RS increased as well after being filtered, implying that the trapped compounds may have the potential to improve soil quality. This study provides a new insight for hydrolysate application according to its composition characteristics, and helps make the most use of wasted sludge.


Assuntos
Reatores Biológicos , Esgotos , Esgotos/química , Fermentação , Desnitrificação , Carbono , Solo , Bactérias , Ácidos Graxos Voláteis , Nitrogênio
12.
Int J Biol Macromol ; 254(Pt 1): 127614, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37884231

RESUMO

An emerging research focus is the role of m6A modifications in mediating the post-transcriptional regulation of mRNA during mammalian development. Recent evidence suggests that m6A methyltransferases and demethylases play critical roles in skeletal muscle development. Ythdf2 is a m6A "reader" protein that mediates mRNA degradation in an m6A-dependent manner. However, the specific function of Ythdf2 in skeletal muscle development and the underlying mechanisms remain unclear. Here, we observed that Ythdf2 expression was significantly upregulated during myogenic differentiation, whereas Ythdf2 knockdown markedly inhibited myoblast proliferation and differentiation. Combined analysis of high-throughput sequencing, Co-IP, and RIP assay revealed that Ythdf2 could bind to m6A sites in STK11 mRNA and form an Ago2 silencing complex to promote its degradation, thereby regulating its expression and consequently, the AMPK/mTOR pathway. Furthermore, STK11 downregulation partially rescued Ythdf2 knockdown-induced impairment of proliferation and myogenic differentiation by inhibiting the AMPK/mTOR pathway. Collectively, our results indicate that Ythdf2 mediates the decay of STK11 mRNA, an AMPK activator, in an Ago2 system-dependent manner, thereby driving skeletal myogenesis by suppressing the AMPK/mTOR pathway. These findings further enhance our understanding of the molecular mechanisms underlying RNA methylation in the regulation of myogenesis and provide valuable insights for conducting in-depth studies on myogenesis.


Assuntos
Proteínas Quinases Ativadas por AMP , Serina-Treonina Quinases TOR , Animais , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Estabilidade de RNA , Desenvolvimento Muscular/genética , Mamíferos/genética
13.
Eur J Med Chem ; 265: 116062, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38128235

RESUMO

Photocaged proteolysis-targeting chimeras (PROTACs), which employ light as a stimulus to control protein degradation, have recently garnered considerable attention as both powerful chemical tools and a promising therapeutic strategy. However, the poor penetration depth of traditionally used ultraviolet light and the deficiency of alternative caging positions have restricted their applications in biological systems. By installing a diverse array of photocaged groups, with excitation wavelengths ranging from 365 nm to 405 nm, onto different positions of cereblon (CRBN) and Von Hippel-Lindau (VHL)-recruiting Brd4 degraders, we conducted the first comprehensive study on visible-light-activatable photocaged PROTACs to the best of our knowledge. We found the A2, A4 and B3 positions to be most effective at regulating the activity of the degraders, and to provide the resulting molecules (9-12 and 17) as potent visible-light-controlled degraders in live cells.


Assuntos
Proteínas Nucleares , Proteína Supressora de Tumor Von Hippel-Lindau , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Proteólise , Luz , Ubiquitina-Proteína Ligases/metabolismo
14.
Water Res ; 250: 121013, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38118252

RESUMO

The ecological risk of tritiated wastewater into the environment has attracted much attention. Assessing the ecological risk of tritium-containing pollution is crucial by studying low-activity tritium exposure's environmental and biological effects on freshwater micro-environment and the enrichment potential of organically bound tritium (OBT) in microalgae and aquatic plants. The impact of tritium-contaminated wastewater on the microenvironment of freshwater systems was analyzed using microcosm experiments to simulate tritium pollution in freshwater systems. Low activity tritium pollution (105 Bq/L) induced differences in microbial abundance, with Proteobacteria, Bacteroidota, and Desulfobacterota occupying important ecological niches in the water system. Low activity tritium (105-107 Bq/L) did not affect the growth of microalgae and aquatic plants, but OBT was significantly enriched in microalgae and two aquatic plants (Pistia stratiotes, Spirodela polyrrhiza), with the enrichment coefficients of 2.08-3.39 and 1.71-2.13, respectively. At the transcriptional level, low-activity tritium (105 Bq/L) has the risk of interfering with gene expression in aquatic plants. Four dominant cyanobacterial strains (Leptolyngbya sp., Synechococcus elongatus, Nostoc sp., and Anabaena sp.) were isolated and demonstrated good environmental adaptability to tritium pollution. Environmental factors can modify the tritium accumulation potential in cyanobacteria and microalgae, theoretically enhancing food chain transfer.


Assuntos
Microalgas , Trítio/análise , Águas Residuárias , Poluição Ambiental/análise , Água Doce/análise
15.
Ying Yong Sheng Tai Xue Bao ; 34(11): 3114-3126, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37997423

RESUMO

Fluoroquinolone antibiotics (FQs) are one of the most widely used antibiotics, which are new pollutants with 'pseudo persistence' in the environment, causing great ecological risks. FQs could change the structure and function of microbial communities and affect nitrogen cycling mediated by microorganisms. Consequently, FQs would change the composition of various types of nitrogen in the environment and exert a significant impact on the global nitrogen cycling. We encapsulated the distribution of FQs in the environment and its impacts on nitrogen cycling mediated by microorganisms, explained the role of FQs in each key process of nitrogen cycling, aiming to provide an important reference for revealing the ecological effects of FQs. Generally, FQs could be detected in various environmental media, with significant differences in the concentration and types of FQs in different environments. Ofloxacin, norfloxacin, ciprofloxacin, and enrofloxacin are the four types of FQs with the highest detection frequency and concentration. The effect of FQs on nitrogen cycling deeply depends on typical characteristics of concentration and species. FQs mainly inhibit nitrification by reducing the abundance of amoA gene related to ammoxidation process and the abundance and composition of ammoxidation bacteria. FQs inhibits nitrification by reducing the abundance and composition of microbial communities. The denitrification process is mainly inhibited due to the reduction of the activity of related enzymes and the abundance of genes such as narG, nirS, norB, and nosZ genes, as well as the abundance and composition of denitrifying functional microorganisms. The process of anammox is restricted due to the reduction of the abundance, composition and hzo gene abundance of anaerobic anammox bacteria. FQs lead to the reduction of active nitrogen removal and the increase of N2O release in the environment, with further environmental problems such as water eutrophication and greenhouse effect. In the future, we should pay attention to the effects of low concentration FQs and complex antibiotics on the nitrogen cycling, and focus on the effects of FQs on the changes of nitrogen cycle-related microbial monomers and communities.


Assuntos
Fluoroquinolonas , Ciclo do Nitrogênio , Fluoroquinolonas/química , Antibacterianos/farmacologia , Antibacterianos/química , Poluição Ambiental , Nitrogênio , Desnitrificação
16.
Nat Commun ; 14(1): 7908, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38036533

RESUMO

Targeted proteasomal and autophagic protein degradation, often employing bifunctional modalities, is a new paradigm for modulation of protein function. In an attempt to explore protein degradation by means of autophagy we combine arylidene-indolinones reported to bind the autophagy-related LC3B-protein and ligands of the PDEδ lipoprotein chaperone, the BRD2/3/4-bromodomain containing proteins and the BTK- and BLK kinases. Unexpectedly, the resulting bifunctional degraders do not induce protein degradation by means of macroautophagy, but instead direct their targets to the ubiquitin-proteasome system. Target and mechanism identification reveal that the arylidene-indolinones covalently bind DCAF11, a substrate receptor in the CUL4A/B-RBX1-DDB1-DCAF11 E3 ligase. The tempered α, ß-unsaturated indolinone electrophiles define a drug-like DCAF11-ligand class that enables exploration of this E3 ligase in chemical biology and medicinal chemistry programs. The arylidene-indolinone scaffold frequently occurs in natural products which raises the question whether E3 ligand classes can be found more widely among natural products and related compounds.


Assuntos
Produtos Biológicos , Proteínas Culina , Oxindóis , Ligantes , Proteínas Culina/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteólise , Complexo de Endopeptidases do Proteassoma/metabolismo , Produtos Biológicos/farmacologia , Ubiquitinação
17.
Front Oncol ; 13: 1248830, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37869091

RESUMO

Papillary thyroid carcinoma (PTC) is the most common pathological type of thyroid malignancy and also has an excellent prognosis. Primary thyroid lymphoma (PTL) is rare and has a poor prognosis. The co-occurrence of both malignancies is extremely rare, and the preoperative diagnosis is rather difficult. We report the case of a patient with both PTC and PTL in the setting of Hashimoto's thyroiditis (HT). A 59-year-old female patient was referred to our department for progressive enlargement of the thyroid gland over a few months. The imaging results demonstrated an enlarged thyroid and a mass in the thyroid. Total thyroidectomy and bilateral central neck node dissection were conducted. The final diagnosis of the coexistence of thyroid diffuse large B cell lymphoma and PTC was confirmed by histopathology and immunohistochemistry. The patient received radiation therapy and six cycles of chemotherapy combined with targeted therapy, including rituximab, cyclophosphamide, doxorubicin, vindesine, and prednisone (R-CHOP). After 6 months of follow-up, neither tumor has recurred. It is important for physicians to keep PTL in mind for differential diagnosis in HT patients with sudden thyroid enlargement.

18.
Water Sci Technol ; 88(8): 1927-1943, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37906450

RESUMO

In this paper, molybdenum disulfide was grown on the surface of iron-containing tailings by hydrothermal method, and a series of highly efficient activated persulfate (PMS) iron-based catalysts were successfully prepared. The results show that in the CTM 1-200/PMS system, the additional ratio of tailings and the hydrothermal temperature have important effects on the catalyst. The catalyst prepared under the conditions of CT:MoS2 (molar ratio 1:1) and hydrothermal temperature of 200 °C (CTM 1-200) had the best degradation effect on BPA, and the degradation effect was increased by four times. The reason for the improvement of degradation efficiency is that the introduction of MoS2 accelerates the REDOX cycle between Fe(II)/Fe(III), and the reduction of Fe(III) is mainly related to Mo(IV), while the reduction capacity of S is relatively weak. Molybdenum disulfide/iron tailing composite material provides a way for tailings to solve the problem of water pollution.


Assuntos
Ferro , Molibdênio , Compostos Férricos , Peróxidos
19.
Ying Yong Sheng Tai Xue Bao ; 34(8): 2274-2284, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37681392

RESUMO

Sulfonamides (SAs) are the first broad-spectrum synthetic antimicrobial agents used in human health and veterinary medicine. The majority of SAs entering human body is discharged into aquatic environment in the form of parent material or metabolites. The residues of SAs and their metabolites in the aquatic environment and the development of drug resistance can be serious threats to ecosystems and human health. We summarized recent advances in the research of SAs. The main metabolite types of SAs and the distribution characteristics of metabolites in different aquatic environments were introduced. The ecotoxicology of SAs metabolites, especially the distribution and hazards of sulfonamide resistance genes (sul-ARGs), were discussed with emphasis. Finally, the future research works were proposed. This paper could provide basic information for further research on SAs.


Assuntos
Ecossistema , Ecotoxicologia , Humanos , Sulfanilamida , Sulfonamidas/toxicidade
20.
Water Res ; 245: 120569, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37683522

RESUMO

The sulfur autotrophic denitrification (SADN) process is an organic-free denitrification process that utilizes reduced inorganic sulfur compounds (RISCs) as the electron donor for nitrate reduction. It has been proven to be a cost-effective and environment-friendly approach to achieving carbon neutrality in wastewater treatment plants. However, there is no consensus on whether SADN can become a dominant denitrification process to treat domestic wastewater or industrial wastewater if organic carbon is desired to be saved. Through a comprehensive summary of the SADN process and extensive discussion of state-of-the-art SADN-based technologies, this review provides a systematic overview of the potential of the SADN process as a sustainable alternative for the heterotrophic denitrification (HD) process (organic carbons as electron donor). First, we introduce the mechanism of the SADN process that is different from the HD process, including its transformation pathways based on different RISCs as well as functional bacteria and key enzymes. The SADN process has unique theoretical advantages (e.g., economy and carbon-free, less greenhouse gas emissions, and a great potential for coupling with novel autotrophic processes), even if there are still some potential issues (e.g., S intermediates undesired production, and relatively slow growth rate of sulfur-oxidizing bacteria [SOB]) for wastewater treatment. Then we present the current representative SADN-based technologies, and propose the outlooks for future research in regards to SADN process, including implement of coupling of SADN with other nitrogen removal processes (e.g., HD, and sulfate-dependent anaerobic ammonium oxidation), and formation of SOB-enriched biofilm. This review will provide guidance for the future applications of the SADN process to ensure a robust-performance and chemical-saving denitrification for wastewater treatment.

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