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The hierarchical packaging of chromatin fibers plays a critical role in gene regulation. The 30-nm chromatin fibers, a central-level structure bridging nucleosomal arrays to higher-order organizations, function as the first level of transcriptional dormant chromatin. The dynamics of 30-nm chromatin fiber play a crucial role in biological processes related to DNA. Here, we report a 3.6-angstrom resolution cryogenic electron microscopy structure of H5-bound dodecanucleosome, i.e., the chromatin fiber reconstituted in the presence of linker histone H5, which shows a two-start left-handed double helical structure twisted by tetranucleosomal units. An atomic structural model of the H5-bound chromatin fiber, including an intact chromatosome, is built, which provides structural details of the full-length linker histone H5, including its N-terminal domain and an HMG-motif-like C-terminal domain. The chromatosome structure shows that H5 binds the nucleosome off-dyad through a three-contact mode in the chromatin fiber. More importantly, the H5-chromatin structure provides a fine molecular basis for the intra-tetranucleosomal and inter-tetranucleosomal interactions. In addition, we systematically validated the physiological functions and structural characteristics of the tetranucleosomal unit through a series of genetic and genomic studies in Saccharomyces cerevisiae and in vitro biophysical experiments. Furthermore, our structure reveals that multiple structural asymmetries of histone tails confer a polarity to the chromatin fiber. These findings provide structural and mechanistic insights into how a nucleosomal array folds into a higher-order chromatin fiber with a polarity in vitro and in vivo.
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Protozoa play a pivotal role in the microbial cycle, and ciliated protozoan grazing habits are associated with dimethyl sulfide (DMS) cycle. Many studies have explored the impacts of nanoplastics (NPs) and microplastics (MPs) on ecotoxicological effects of ciliates. However, limited research exists on NPs and MPs influences on the production of organic sulfur compounds. The impact of NPs and MPs on the production of dimethyl sulfoxide (DMSO) and carbonyl sulfide (COS) remains unclear. Therefore, we examined the impacts of three concentrations (1 × 105, 5 × 105, and 1 × 106 items/mL) of polystyrene (PS) NPs (50 nm) and MPs (1 and 5 µm) on the ecotoxicology and DMS/dimethylsulfoniopropionate (DMSP)/DMSO/COS production in the ciliate Uronema marinum. NPs and MPs exposure were found to reduce the abundance, growth rate, volume, and biomass of U. marinum. Additionally, NPs and MPs increased the superoxide anion radical (O2Ëâ) production rates and malondialdehyde (MDA) contents (24 h), leading to a decline in glutathione (GSH) content and an ascend in superoxide dismutase (SOD) activity to mitigate the effects of reactive oxygen species (ROS). Exposure to PS NPs and MPs decreased the ingestion rates of algae by 7.5-14.4%, resulting in decreases in DMS production by 56.8-85.4%, with no significant impact on DMSO production. The results suggest a distinct pathway for the production of DMSO or COS compared to DMS. These findings help us to understand the NPs and MPs impacts on the marine ecosystem and organic sulfur compound yield, potentially influencing the global climate.
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This article is concerned about fixed-time (FT) synchronization of spatiotemporal networks (STNs) with the Robin boundary condition. Above all, a switching-type FT stability theorem and an integral inequality are established, which provide a novel theoretical tool for the rigorous analysis of FT control in STNs. Subsequently, three kinds of nontrivial power-law controllers are developed which are separately acted on the interior, the boundary, and the whole of the spatial domain. Based on these control schemes and Lyapunov-like method, several flexible criteria are obtained to achieve FT synchronization of STNs, and the upper bound of the synchronization time is explicitly estimated. Note that, the derived results here are also perfectly applicable to STNs with Neumann or Dirichlet boundary condition. Several illustrate examples are presented at final to confirm the developed controllers and criteria.
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Respiratory pathogens pose significant challenges to public health, demanding efficient diagnostic methods. This study presents an integrated microfluidic chip for the simultaneous detection of multiple respiratory pathogens. The chip integrates magnetic bead-based nucleic acid extraction and purification, acoustic streaming-driven mixing, liquid equalization, and multiplex PCR amplification with in situ fluorescence detection. Nucleic acid extraction takes only 12 min, yielding results comparable to commercial kits. Efficient mixing of magnetic beads is achieved through a combination of designed micropillars and bubble-trapping array structures. The micropillars maintain the aqueous phase in the mixing chamber, while the bubble-trapping arrays enable stable formation of bubbles, serving as a micromixer under the acoustic field. To prevent cross-contamination, an oil-encapsulated water droplet system is incorporated throughout nucleic acid extraction and PCR amplification. This assay displays remarkable multiplex analysis capability on a single chip, enabling the simultaneous detection of 12 common respiratory pathogens with a low detection limit of 10 copies/µL. Moreover, this method demonstrates excellent practical applicability in clinical nasal samples. Compared to many microfluidic chip-based molecular biology methods, the assay exhibits comparable or superior multipathogen analysis capability, sensitivity, and speed, completing the sample-to-answer process in approximately 70 min. This integrated microfluidic device offers a promising multiplex molecular diagnosis platform for on-site simultaneous detection of multiple pathogens.
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Endosomal Toll-like receptors (eTLRs) are essential for the sensing of non-self through RNA and DNA detection. Here, using spatiotemporal analysis of vesicular dynamics, super-resolution microscopy studies, and functional assays, we show that endomembrane defects associated with the deficiency of the small GTPase Rab27a cause delayed eTLR ligand recognition, defective early signaling, and impaired cytokine secretion. Rab27a-deficient neutrophils show retention of eTLRs in amphisomes and impaired ligand internalization. Extracellular signal-regulated kinase (ERK) signaling and ß2-integrin upregulation, early responses to TLR7 and TLR9 ligands, are defective in Rab27a deficiency. CpG-stimulated Rab27a-deficient neutrophils present increased tumor necrosis factor alpha (TNF-α) secretion and decreased secretion of a selected group of mediators, including interleukin (IL)-10. In vivo, CpG-challenged Rab27a-null mice show decreased production of type I interferons (IFNs) and IFN-γ, and the IFN-α secretion defect is confirmed in Rab27a-null plasmacytoid dendritic cells. Our findings have significant implications for immunodeficiency, inflammation, and CpG adjuvant vaccination.
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BACKGROUND: Acute appendicitis (AA) is the most common cause of acute abdomen in children. Anesthesia significantly influences the surgical treatment of AA in children, making the scientific and effective selection of anesthetics crucial. AIM: To assess the clinical effect of atropine (ATR) in combination with remifentanil (REMI) in children undergoing surgery for AA. METHODS: In total, 108 cases of pediatric AA treated between May 2020 and May 2023 were selected, 58 of which received ATR + REMI [research group (RG)] and 50 who received REMI [control group (CG)]. Comparative analyses were conducted on the time to loss of eyelash reflex, pain resolution time, recovery time from anesthesia, incidence of adverse events (AEs; respiratory depression, hypoxemia, bradycardia, nausea and vomiting, and hypotension), intraoperative responses (head shaking, limb activity, orientation recovery, safe departure time from the operating room), hemodynamic parameters [oxygen saturation (SPO2), mean arterial pressure, heart rate, and respiratory rate], postoperative sedation score (Ramsay score), and pain level [the Face, Legs, Activity, Cry, Consolability (FLACC) Behavioral Scale]. RESULTS: Compared with the CG, the RG showed significantly shorter time to loss of eyelash reflex, pain resolution, recovery from anesthesia, and safe departure from the operating room. Furthermore, the incidence rates of overall AEs (head shaking, limb activity, etc.) were lower, and influences on intraoperative hemodynamic parameters and stress response indexes were fewer. The Ramsay score at 30 min after extubation and the FLACC score at 60 min after extubation were significantly lower in the RG than in the CG. CONCLUSION: ATR + REMI is superior to REMI alone in children undergoing AA surgery, with a lower incidence of AEs, fewer influences on hemodynamics and stress responses, and better post-anesthesia recovery.
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BACKGROUND: A polymorphism in the fat mass and obesity-associated gene (FTO) is linked to enhanced neural sensitivity to food-cues and attenuated ghrelin suppression. Risk allele carriers regain more weight than non-carriers after bariatric surgery. It remains unclear how FTO variation affects brain function and ghrelin following surgery. METHODS: Resting-state functional magnetic resonance imaging (RS-fMRI) and cue-reactivity fMRI with high-/low-caloric food-cues were performed at pre-surgery and 1-, 6-, and 12-months post-surgery to examine brain function in 16 carriers with one copy of the rs9939609 A allele (AT) and 26 non-carriers (TT). Behavioral assessments up to five years post-surgery were also conducted. RESULTS: AT relative to TT group had smaller BMI-loss at 12 to 60 months post-surgery and lower resting-state activity in posterior cingulate cortex following LSG (group-by-time interaction effects). Meanwhile, AT relative to TT group showed greater food-cue responses in dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC) and insula (group effects). There were negative associations of weight-loss with ghrelin and greater activation in DLPFC, DMPFC and insula in AT but not TT group. CONCLUSION: These findings indicate that FTO variation is associated with the evolution of ghrelin signaling and brain function after bariatric surgery, which might hinder weight-loss.
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Dimethyl sulfide (DMS) is a prevalent volatile organic sulfur compound relevant to the global climate. Ecotoxicological effects of nano- and microplastics (NPs and MPs) on phytoplankton, zooplankton, and bacteria have been investigated by numerous studies. Yet, the influences of NPs/MPs on dimethylated sulfur compounds remains understudied. Herein, we investigated the impacts of polystyrene (PS) NPs/MPs (80 nm, 1 µm, and 10 µm) on zooplankton grazing, chlorophyll a (Chl a) concentration, bacterial community, dimethylsulfoniopropionate (DMSP), and DMS production in the microcosms. Our findings revealed that rotifer grazing increased the production of DMS in the absence of NPs/MPs but did not promote DMS production when exposed to NPs/MPs. The ingestion rates of the rotifer and copepod exposed to NPs/MPs at high concentrations were significantly reduced. NPs/MPs exposure significantly decreased DMS levels in the treatments with rotifers compared to the animal controls. In the bacterial microcosms, smaller NPs/MPs sizes were more detrimental to Chl a concentrations compared to larger sizes. The study revealed a stimulatory effect on Chl a concentrations, DMSPd concentrations, and bacterial abundances when exposed to 10 µm MP with low concentrations. The effects of NPs/MPs on DMS concentrations were both dose- and size-dependent, with NPs showing greater toxicity compared to larger MPs. NPs/MPs led to changes in bacterial community compositions, dependent on both dosage and size. NPs caused a notable decrease in the alpha diversities and richness of bacteria compared to MPs. These results provide insights into the influences of NPs/MPs on food webs, and subsequently organic sulfur compounds cycles.
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INTRODUCTION: Rheumatoid arthritis (RA) combined with hashimoto thyroiditis (HT) is an important cause of various fatal comorbidities of RA. There is no precise conclusion about the cause of this disease. METHODS: Peripheral blood and synovial tissue were collected from healthy participants, patients with RA, and patients with both RA and HT. Immunofluorescence staining and Pearson correlation analysis were used to detect the levels of γδTCR and the correlation between IL-17 and p-STAT3, respectively. ELISA, chemiluminescence assays, qRT-PCR and Western blot were performed to detect the levels of IgG, IgM, IFN-γ, IL-1ß, TNF-α, Tg-Ab, Tpo-Ab, IL-17, IL-2, p-SATA3, and STAT3, respectively. RESULTS: There was increased proportion of γδT cells, IL-17, and p-STAT3 levels in RA and HT patients. IL-17 was positively correlated with p-STAT3. γδT cells significantly promoted the expression of IgG, Tg-Ab, Tpo-Ab, and IL-17. When γδT and human fibroblast-like synoviocytes (FLSs) were co-cultured, the levels of IL-2, IFN-γ, IL-1ß, TNF-α, and IL-17 were increased, and the IL-17/STAT3 signaling pathway was activated. When IL-17-silenced γδT cells and STAT3-silenced FLSs were co-cultured, the levels of IL-1ß and TNF-α in FLSs were significantly decreased. Furthermore, when STAT3-silenced FLSs were added to the co-culture medium of B cells and γδT cells, the levels of IL-1ß and TNF-α were also decreased significantly. CONCLUSION: γδT cells induced RA directly or by stimulating B cells to activate STAT3 through IL-17.
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Akkermansia muciniphila and Faecalibacterium prausnitzii are next-generation probiotics, which has been reported to protect disease and effectively utilize various carbohydrates (starch and pectin) as nutrients for growth. Atemoya exhibiting fruity flavor, which is suitable for enhancing aroma and attenuating unpleasant taste caused by the koji metabolites. Results indicated that malic acid was increased (from 42.4 to 70.1 mg/100 g) in fermented Atemoya-Amazake. In addition, fermented Atemoya-Amazake elevated growthes in A. muciniphila and F. prausnitzii. Similarly, the populations of Parabacteroides (5.7 fold) and Akkermansia (1.66 fold) were elevated by fermented Atemoya-Amazake treatment in an in vitro simulated gastrointestinal system compared to the control group. Results revealed that fermented Atemoya-Amazake modulated the intestinal microbiota through increasing the production of short-chain fatty acids (exhibiting anti-pathogenic activity) for 2.1, 2.5, 2.6, and 2.1 folds in acetic acid, propionic acid, isobutyric acid, and butyric acid, respectively; suggesting this fermented Atemoya-Amazake could be applied in intestinal protection.
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Background: Thyroid hormones (THs) have been found that it is closely associated with the onset and progression of non-alcoholic fatty liver disease (NAFLD). However, the current study could not verify the intrinsic relationship between thyroid hormones and NAFLD, which requires further research. Methods: The searches of studies reported both TH level in serum and NAFLD were performed in PubMed, Web of Science, Cochrane Library, and Embase databases. We combined an overall meta-analysis with a dose-response meta-analysis to assess the correlation and dose-response relationship between thyroid function levels and the risk of NAFLD. Results: Overall, 10 studies were included with a total of 38,425 individuals. We found that the non-linear dose-response model showed that for every 1 ng/dL increase in FT4, the risk of NAFLD was reduced by 10.56% (p=0.003). The odds ratios (ORs) for NAFLD with high free triiodothyronine (FT3) exposure compared to those with low FT3 were 1.580 (95% CI 1.370 to 1.830, I2 = 0.0%, p<0.001) in the overall meta-analysis. The continuous variable meta-analysis indicated that individuals with high levels of TSH (SMD=1.32, 95% CI 0.660 to 1.970, p<0.001) had significantly higher levels of liver fibrosis than those with low levels. Conclusions: Our findings only validate that there is a correlation between the occurrence of NAFLD and abnormal levels of THs, and it is expected that more observational studies will still be conducted in the future to further demonstrate the relationship between thyroid hormones and NAFLD. Trial registration: Registered number in PROSPERO: CRD42023405052.
Subject(s)
Non-alcoholic Fatty Liver Disease , Thyroid Gland , Humans , Non-alcoholic Fatty Liver Disease/blood , Thyroid Function Tests , Thyroid Gland/physiopathology , Thyroid Hormones/blood , Triiodothyronine/bloodABSTRACT
The cell wall serves as the primary barrier against the entry of heavy metal ions into cells. However, excessive accumulation of heavy metals within plants can lead to alterations in the spatial structure and physical properties of the cell wall, thereby affecting the capacity of plants to capture heavy metals. Proline (Pro) is involved in the synthesis of the cell wall, modulating the stability and integrity of its structure. Extensins, core proteins that maintain the cell wall structure, are proline/hydroxyproline-rich glycoproteins that contain the characteristic sequence Ser-[Pro]3-5. They act as intermediates in the regulation of biological processes such as cell wall synthesis, assembly, and signal transduction, typically forming a network structure of cell wall proteins through cross-linking with pectin. This network is essential for the self-assembly expansion of the plant cell wall and plays an indispensable role in cell wall stress signal transduction through its interaction with intracellular signalling molecules. However, the mechanisms by which Pro affects the synthesis of cell wall structural proteins, cell wall assembly, and the sensing of cell wall stress under heavy metal stress remain unclear. This review, from the perspectives of biochemistry and molecular biology, comprehensively elaborates on the impact of Pro and Pro-rich proteins on the structure and function of the cell wall. These findings emphasize the mechanism by which Pro enhances the ability of the cell wall to capture heavy metals, providing new research ideas for the use of genetic engineering to manipulate cell wall synthesis and repair, thereby reducing the phytotoxicity of heavy metals.
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Salvia miltiorrhiza ethanol-extracted polysaccharide (SMEP) and thymopentin (TP5) have been proved with strong immunomodulatory activity, and T cells subsets play pivotal roles in the inhibition of solid tumors growth. In the present study, the structure of SMEP was further identified via methylation and nuclear magnetic resonance spectra, and the immunomodulatory activity in combination with TP5 was investigated via evaluating T cell subsets spatial distributions in tumor-bearing mice, finally the cellular status of solid tumor cells was analyzed. The results revealed that SMEP was a neutral heteropolysaccharide using (1 â 4)-α-D-Glcp and (2 â 1)-ß-D-Fruf as the main chain, along with branched chains of (1 â 6)-α-D-Galp. The SMEP+TP5 treatments could effectively promote the differentiation and improve the specific recognition capacity of CD4+ T cells in tumor-bearing mice, thereby activate tumor-infiltrating CD8+ T cells to exert cytotoxic effects, finally promoting the tumor cells apoptosis via blocking cell cycle at G0/G1 phase, which might be relevant with suppression of Wnt/ß-catenin signaling pathway. These findings highlighted the potential of SMEP as an immunoadjuvant for patients bearing immune-deficiency related diseases, and provided data support for the functional researches of T cell subsets in tumor immunity.
Subject(s)
Antigens, CD19 , Immunotherapy, Adoptive , Humans , Antigens, CD19/immunology , Treatment Outcome , Immunotherapy, Adoptive/methods , Recurrence , Male , Female , Receptors, Chimeric Antigen , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/immunology , AdultABSTRACT
The quality of surimi, widely used in processed seafood, is compromised by freeze-thaw cycles, leading to protein denaturation and oxidative degradation. The objective of this study is to explore the effects of adding natural whey peptide hydrolysate (WPH) on the myofibrillar proteins of repeatedly freeze-thawed surimi. Results indicated surimi treated with 15% WPH exhibited only a 128% increase in surface hydrophobicity and a maximum peroxide value of 7.84 µg/kg, significantly lower than the control group. Additionally, salt-soluble protein content, emulsification activity, and stability decreased with the increase in freeze-thaw cycles. With a 15% WPH offering the most significant protective effect, evidenced by reductions of only 25.02%, 42.52% and 37.02% in salt-soluble protein content, emulsification activity, and stability, respectively. These outcomes demonstrate that WPH effectively reduces protein denaturation during repeated freeze-thaw processes. Future research should explore the molecular mechanisms underlying WPH's protective effects and evaluate their applicability in other food systems.
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Babesia is a tick-transmitted parasite that infects wild and domestic animals, causes babesiosis in humans, and is an increasing public health concern. Here, we investigated the prevalence and molecular characteristics of Babesia infections in the rodents in Southeastern Shanxi, China. Small rodents were captured, and the liver and spleen tissues were used for Babesia detection using traditional PCR and sequencing of the partial 18S rRNA gene. The analysis revealed that 27 of 252 small rodents were positive for Babesia, with an infection rate of 10.71%. The infection rates in different sexes and rodent tissues were not statistically different, but those in different rodent species, habitats, and sampling sites were statistically different. The highest risk of Babesia infection was observed in Niviventer confucianus captured from the forests in Huguan County. Forty-three sequences from 27 small rodents positive for Babesia infection were identified as Babesia microti, including 42 sequences from 26 N. confucianus, and one sequence from Apodemus agrarius. Phylogenetic analysis showed that all sequences were clustered together and had the closest genetic relationship with Babesia microti strains isolated from Rattus losea and N. confucianus in China, and belonged to the Kobe-type, which is pathogenic to humans. Compared to other Kobe-type strains based on the nearly complete 18S rRNA gene, the sequences obtained in this study showed the difference by 1-3 bp. Overall, a high prevalence of Babesia microti infection was observed in small rodents in Southeastern Shanxi, China, which could benefit us to take the implementation of relevant prevention and control measures in this area.
Subject(s)
Babesia microti , Babesiosis , Phylogeny , RNA, Ribosomal, 18S , Rodentia , Animals , Babesia microti/genetics , Babesia microti/isolation & purification , China/epidemiology , Babesiosis/epidemiology , Babesiosis/parasitology , Prevalence , Rodentia/parasitology , RNA, Ribosomal, 18S/genetics , Female , Male , Rodent Diseases/epidemiology , Rodent Diseases/parasitologyABSTRACT
BACKGROUND AND AIM: The incidence of rectal neuroendocrine tumors (R-NETs) has increased in recent years. However, the predictors of lymph node (LN) metastasis and clinical outcomes, particularly following endoscopic treatment, remain unclear. Our study aims to elucidate the potential risk factors for LN metastasis and the clinical outcomes of patients undergoing endoscopic resection in R-NETs. METHODS: A total of 128 patients with R-NETs were retrospectively identified from a single center between June 2012 and December 2021. Risk factors for LN metastasis in R-NETs were analyzed using multivariate analysis. Additionally, the clinical outcomes of endoscopic resections in patients with R-NETs were assessed. RESULTS: In our study, 128 patients with R-NETs were retrospectively analyzed. The risk factors for LN metastasis determined by multivariate analysis were tumor size and patient age at diagnosis. Among the 111 patients treated with endoscopic resection and with tumor margin records available, 92 underwent endoscopic submucosal dissection (ESD) and 19 underwent conventional endoscopic mucosal resection (EMR). There was no significant difference between the two groups regarding the positive rates of basal tumor margin and lateral tumor margin. Furthermore, 64 patients who underwent endoscopic resection for R-NETs were successfully followed up (range, 1.64-76.71 months), during which only one patient developed local recurrence. CONCLUSION: Tumor size and age at diagnosis were predictors for LN metastasis of R-NETs. Both ESD and EMR are alternative techniques with a favorable prognosis for R-NETs, even in cases with positive resection margins. However, due to the relatively small number of patients undergoing EMR and missing data in follow-up protocols, definitive conclusions require further large-scale studies.
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Ultralong room-temperature phosphorescence (RTP) and thermally activated delayed fluorescence (TADF) materials provide exciting opportunities for the rational design of persistent luminescence owing to their long-lived excitons. However, conventional rare-earth-based all-inorganic emitters involve high cost and harsh synthesis conditions, and purely organic systems may require complicated synthesis routes and tedious purification. Therefore, it is highly desirable to develop a cost-effective and easily manufacturable method for achieving color-tunable RTP-TADF with a long afterglow. Herein, we demonstrate a rational strategy to introduce different anions (Cl-, Br- and OAc- ions) into a Zn-based metal-organic scaffold, which can improve the crystal rigidity and achieve a well-balanced RTP-TADF. Both theoretical and experimental studies have demonstrated that the adjustment of different anions can effectively modulate the spin-orbit coupling (SOC) and the energy gap of singlet-triplet states (ΔEST) and then tailor the afterglow lifetime. Moreover, we prepared dye-doped metal-organic hybrid glasses with remarkable potential for the color-tunable afterglow. Therefore, this work not only provides a new horizon for modulating crystal and glass states with color/lifetime-tunable persistent luminescence, but also contributes to optical information storage and anti-counterfeiting technology.
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The design and development of new large-capacity and selective materials for extracting rare precious metals via electronic waste is practically essential. In this paper, a new efficient UiO-66-NCS has been obtained as a consequence of the modification of the classical Zr-MOF (UiO-66-NH2), and its ability to recover gold has been investigated. These batch results adequately illustrated that UiO-66-NCS exhibited good adsorption capacity (675.5 mg g-1) and exceptional selectivity. In addition, UiO-66-NCS achieved faster adsorption equilibrium times of about 120 min. Adsorption kinetics and isotherms demonstrated that the pseudo-second-order adsorption scheme and a Langmuir-type procedure were shown by the adsorption of Au(III) on UiO-66-NCS. Characterized by pH effect experiments, TEM, XRD, and XPS, the adsorption of UiO-66-NCS with Au(III) relies on coordination, which further results in reduction, and the generated Au(0) is uniformly dispersed in the MOF. The adsorbent has considerable advantages for cyclic regeneration. Finally, DFT fitting results showed that the adsorption binding energy of UiO-66-NCS with [AuCl4]- was -8.63 kcal mol-1 for the adsorption process. UiO-66-NCS is likely to be an ideal substance for gold recovery.