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Deep eutectic solvent (DES) has caught widely attention of researchers in biomass pretreatment. As a highly efficient surfactant, cetyltrimethylammonium bromide (CTAB) was expected to be used for synthesizing new DESs with additional functions in pretreatment. In this work, an efficient pretreatment method using a mixture of CTAB and lactic acid (LA) as a novel functional DES was established to improve enzymatic digestion efficiency of rice husk (RH). The results showed that DES CTAB:LA effectively removed lignin (51.5%) and xylan (79.9%) and the enzymatic hydrolysis activity of CTAB:LA-treated RH was 5 times that of RH. Then, a series of characterization demonstrated that a substantial accessibility increased, a hydrophobicity and lignin surface area decreased, and great surface morphology alternation were observed on the treated RH, which explained the increase in enzymatic hydrolysis efficiency. Overall, the discovery of more functional DESs might be motivated and biorefinery pretreatment processes might be greatly promoted.
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Biochar is getting increasing consideration for eco-friendly soil amendment and environmental remediation. Once added to the soil, biochar would undergo the natural ageing process, affecting its physicochemical properties and, as a result, the adsorption and immobilization of pollutants in the water and soil. To evaluate the high/low temperature pyrolyzed biochar performance on complex contaminants and the effect of climate ageing, the batch experiments were conducted on the adsorption of the pollutants of antibiotics sulfapyridine (SPY) and a typical coexisting heavy metal Cu2+ as one or binary system on low/high pyrolytic temperature biochars before and after the simulated tropical climate and frigid climate region ageing treatment. The results showed that high-temperature ageing could enhance the SPY adsorption in biochar-amended soil. The SPY sorption mechanism was fully elucidated, and the result confirmed that H-bonding was the dominant role in biochar-amended soil, and π-π electron-donor-acceptor (EDA) interaction and micro-pore filling was another factor for SPY adsorption. This study could lead to the conclusion that low-temperature pyrolytic biochar is a better option for sulfonamide-Cu(II) contaminated soil remediation in tropical regions.
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Kiwifruit (Actinidia chinensis) is commonly covered by fruit hairs (trichomes) that affect kiwifruit popularity in the commercial market. However, it remains largely unknown which gene mediates trichome development in kiwifruit. In this study, we analyzed two kiwifruit species, A. eriantha (Ae) with long, straight, and bushy trichomes and A. latifolia (Al) with short, distorted, and spare trichomes, by second- and third-generation RNA sequencing. Transcriptomic analysis indicated that the expression of the NAP1 gene, a positive regulator of trichome development, was suppressed in Al compared with that in Ae. Additionally, the alternative splicing of AlNAP1 produced two short transcripts (AlNAP1-AS1 and AlNAP1-AS2) lacking multiple exons, in addition to a full-length transcript of AlNAP1-FL. The defects of trichome development (short and distorted trichome) in Arabidopsis nap1 mutant were rescued by AlNAP1-FL but not by AlNAP1-AS1. AlNAP1-FL gene does not affect trichome density in nap1 mutant. The qRT-PCR analysis indicated that the alternative splicing further reduces the level of functional transcripts. These results indicated that the short and distorted trichomes in Al might be caused by the suppression and alternative splicing of AlNAP1. Together, we revealed that AlNAP1 mediates trichome development and is a good candidate target for genetic modification of trichome length in kiwifruit.
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Actinidia , Arabidopsis , Transcriptoma , Actinidia/genética , Tricomas/metabolismo , Frutas/genética , Processamento Alternativo , Arabidopsis/genética , Regulação da Expressão Gênica de PlantasRESUMO
Pseudomonas syringae pv. actinidiae (Psa) causes bacterial canker of kiwifruit with heavy economic losses. However, little is known about the pathogenic genes of Psa. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas-mediated genome editing technology has dramatically facilitated the characterization of gene function in various organisms. However, CRISPR genome editing could not be efficiently employed in Psa due to lacking homologous recombination repair. The base editor (BE) system, which depends on CRISPR/Cas, directly induces single nucleoside C to T without homology recombination repair. Here, we used dCas9-BE3 and dCas12a-BE3 systems to create substitutions of C to T and to convert CAG/CAA/CGA codons to stop codons (TAG/TAA/TGA) in Psa. The dCas9-BE3 system-induced single C-to-T conversion frequency of 3 to 10 base positions ranged from 0% to 100%, with a mean of 77%. The dCas12a-BE3 system-induced single C-to-T conversion frequency of 8 to 14 base positions in the spacer region ranged from 0% to 100%, with a mean of 76%. In addition, a relatively saturated Psa gene knockout system covering more than 95% of genes was developed based on dCas9-BE3 and dCas12a-BE3, which could knock out two or three genes at the same time in the Psa genome. We also found that hopF2 and hopAO2 were involved in the Psa virulence of kiwifruit. The HopF2 effector can potentially interact with proteins such as RIN, MKK5, and BAK1, while the HopAO2 effector can potentially interact with the EFR protein to reduce the host's immune response. In conclusion, for the first time, we established a PSA.AH.01 gene knockout library that may promote research on elucidating the gene function and pathogenesis of Psa.
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Actinidia , Pseudomonas syringae , Edição de Genes , Doenças das Plantas/microbiologia , Técnicas de Inativação de Genes , Actinidia/genéticaRESUMO
From a porous structure perspective, the one-stage de novo synthesis method and impregnation method were applied to synthesize Ag(I) ion-containing ZIF-8 samples. With the de novo synthesis method, Ag(I) ions could be located inside micropores or adsorbed on the external surface of the ZIF-8 by selecting AgNO3 in water or Ag2CO3 in ammonia solution as precursors, respectively. The ZIF-8 confining Ag(I) ion exhibited a much lower constant releasing rate than the Ag(I) ion adsorbed on the ZIF-8 surface in artificial seawater. As such, strong diffusion resistance in association with the confinement effect is contributed by ZIF-8's micropore. On the other hand, the release of Ag(I) ions adsorbed on the external surface was diffusion limited. Therefore, the releasing rate would reach a maximum not increasing with Ag(I) loading in the ZIF-8 sample.
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Hyperuricemia is a prevalent disease worldwide that is characterized by elevated urate levels in the blood owing to purine metabolic disorders, which can result in gout and comorbidities. To facilitate the treatment of hyperuricemia through the uricolysis, we engineered a probiotic Escherichia coli Nissle 1917 (EcN) named EcN C6 by inserting an FtsP-uricase cassette into an "insulated site" located between the uspG and ahpF genes. Expression of FtsP-uricase in this insulated region did not influence the probiotic properties or global gene transcription of EcN but strongly increased the enzymatic activity for urate degeneration, suggesting that the genome-based insulated system is an ideal strategy for EcN modification. Oral administration of EcN C6 successfully alleviated hyperuricemia, related symptoms and gut microbiota in a purine-rich food-induced hyperuricemia rat model and a uox-knockout mouse model. Together, our study provides an insulated site for heterologous gene expression in EcN strain and a recombinant EcN C6 strain as a safe and effective therapeutic candidate for hyperuricemia treatment.
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An anterior cruciate ligament (ACL) tear is a common musculoskeletal injury with a high incidence. Traditional diagnosis employs magnetic response imaging (MRI), physical testing, or other clinical examination, which relies on complex and expensive medical instruments, or individual doctoral experience. Herein, we propose a wearable displacement sensing system based on a grating-structured triboelectric stretch sensor to diagnose the ACL injuries. The stretch sensor exhibits a high resolution (0.2 mm) and outstanding robustness (over 1,000,000 continuous operation cycles). This system is employed in clinical trial to diagnose ACL injuries. It measures the displacement difference between the affected leg and the healthy leg during Lachman test. And when such a difference is greater than 3 mm, the ACL is considered to be at risk for injury or tear. Compared with the gold standard of arthroscopy, the consistency rate of this wearable diagnostic system reached about 85.7%, which is higher than that of the Kneelax3 arthrometer (78.6%) with a large volume. This shows that the wearable system possesses the feasibility to supplement and improve existing arthrometers for facile diagnosing ACL injuries. It may take a promising step for wearable healthcare.
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Organic field effect transistor (OFET) devices are one of the most popular candidates for the development of biochemical sensors due to their merits of being flexible and highly customizable for low-cost large-area manufacturing. This review describes the key points in constructing an extended-gate type OFET (EGOFET) biochemical sensor with high sensitivity and stability. The structure and working mechanism of OFET biochemical sensors are described firstly, emphasizing the importance of critical material and device engineering to higher biochemical sensing capabilities. Next, printable materials used to construct sensing electrodes (SEs) with high sensitivity and stability are presented with a focus on novel nanomaterials. Then, methods of obtaining printable OFET devices with steep subthreshold swing (SS) for high transconductance efficiency are introduced. Finally, approaches for the integration of OFETs and SEs to form portable biochemical sensor chips are introduced, followed by several demonstrations of sensory systems. This review will provide guidelines for optimizing the design and manufacturing of OFET biochemical sensors and accelerating the movement of OFET biochemical sensors from the laboratory to the marketplace.
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The re-emerging mpox (formerly monkeypox) virus (MPXV), a member of Orthopoxvirus genus together with variola virus (VARV) and vaccinia virus (VACV), has led to public health emergency of international concern since July, 2022. Inspired by the unprecedent success of coronavirus disease 2019 (COVID-19) mRNA vaccines, the development of a safe and effective mRNA vaccine against MPXV is of high priority. Based on our established lipid nanoparticle (LNP)-encapsulated mRNA vaccine platform, we rationally constructed and prepared a panel of multicomponent MPXV vaccine candidates encoding different combinations of viral antigens including M1R, E8L, A29L, A35R and B6R. In vitro and in vivo characterization demonstrated that two immunizations of all mRNA vaccine candidates elicit a robust antibody response as well as antigen specific Th1-biased cellular response in mice. Importantly, the penta- and tetra-component vaccine candidates AR-MPXV5 and AR-MPXV4a showed superior capability of inducing neutralizing antibodies as well as of protecting from VACV challenge in mice. Our study provides critical insights to understand the protection mechanism of MPXV infection and direct evidence supporting further clinical development of these multicomponent mRNA vaccine candidates.
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Recently, increasing studies have shown that the functional properties of proteins, including emulsifying properties, antioxidant properties, solubility, and thermal stability, can be improved through glycation reaction under controlled reaction conditions. The use of glycated proteins to stabilize hydrophobic active substances and to explore the gastrointestinal fate of the stabilized hydrophobic substances has also become the hot spot. Therefore, in this review, the effects of glycation on the structure and function of food proteins and the physical stability and oxidative stability of protein-stabilized oil/water emulsions were comprehensively summarized and discussed. Also, this review sheds lights on the in vitro digestion characteristics and edible safety of emulsion stabilized by glycated protein. It can further serve as a research basis for understanding the role of structural features in the emulsification and stabilization of glycated proteins, as well as their utilization as emulsifiers in the food industry.
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Background: Differences in bronchial microbiota composition have been found to be associated with asthma; however, it is still unclear whether these findings can be applied to recurrent wheezing in infants especially with aeroallergen sensitization. Objectives: To determine the pathogenesis of atopic wheezing in infants and to identify diagnostic biomarkers, we analyzed the bronchial bacterial microbiota of infants with recurrent wheezing and with or without atopic diseases using a systems biology approach. Methods: Bacterial communities in bronchoalveolar lavage samples from 15 atopic wheezing infants, 15 non-atopic wheezing infants, and 18 foreign body aspiration control infants were characterized using 16S rRNA gene sequencing. The bacterial composition and community-level functions inferred from between-group differences from sequence profiles were analyzed. Results: Both α- and ß-diversity differed significantly between the groups. Compared to non-atopic wheezing infants, atopic wheezing infants showed a significantly higher abundance in two phyla (Deinococcota and unidentified bacteria) and one genus (Haemophilus) and a significantly lower abundance in one phylum (Actinobacteria). The random forest predictive model of 10 genera based on OTU-based features suggested that airway microbiota has diagnostic value for distinguishing atopic wheezing infants from non-atopic wheezing infants. PICRUSt2 based on KEGG hierarchy (level 3) revealed that atopic wheezing-associated differences in predicted bacterial functions included cytoskeleton proteins, glutamatergic synapses, and porphyrin and chlorophyll metabolism pathways. Conclusion: The differential candidate biomarkers identified by microbiome analysis in our work may have reference value for the diagnosis of wheezing in infants with atopy. To confirm that, airway microbiome combined with metabolomics analysis should be further investigated in the future.
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Brônquios , Sons Respiratórios , Humanos , Lactente , Projetos Piloto , RNA Ribossômico 16S , BactériasRESUMO
BACKGROUND: Chemotherapy (CT) is central to the treatment of triple negative breast cancer (TNBC), but drug toxicity and resistance place strong restrictions on treatment regimes. Fasting sensitizes cancer cells to a range of chemotherapeutic agents and also ameliorates CT-associated adverse effects. However, the molecular mechanism(s) by which fasting, or short-term starvation (STS), improves the efficacy of CT is poorly characterized. METHODS: The differential responses of breast cancer or near normal cell lines to combined STS and CT were assessed by cellular viability and integrity assays (Hoechst and PI staining, MTT or H2DCFDA staining, immunofluorescence), metabolic profiling (Seahorse analysis, metabolomics), gene expression (quantitative real-time PCR) and iRNA-mediated silencing. The clinical significance of the in vitro data was evaluated by bioinformatical integration of transcriptomic data from patient data bases: The Cancer Genome Atlas (TCGA), European Genome-phenome Archive (EGA), Gene Expression Omnibus (GEO) and a TNBC cohort. We further examined the translatability of our findings in vivo by establishing a murine syngeneic orthotopic mammary tumor-bearing model. RESULTS: We provide mechanistic insights into how preconditioning with STS enhances the susceptibility of breast cancer cells to CT. We showed that combined STS and CT enhanced cell death and increased reactive oxygen species (ROS) levels, in association with higher levels of DNA damage and decreased mRNA levels for the NRF2 targets genes NQO1 and TXNRD1 in TNBC cells compared to near normal cells. ROS enhancement was associated with compromised mitochondrial respiration and changes in the metabolic profile, which have a significant clinical prognostic and predictive value. Furthermore, we validate the safety and efficacy of combined periodic hypocaloric diet and CT in a TNBC mouse model. CONCLUSIONS: Our in vitro, in vivo and clinical findings provide a robust rationale for clinical trials on the therapeutic benefit of short-term caloric restriction as an adjuvant to CT in triple breast cancer treatment.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Neoplasias de Mama Triplo Negativas , Animais , Camundongos , Humanos , Dieta Redutora , Espécies Reativas de Oxigênio , ObesidadeRESUMO
l-Heptopyranoses are important components of bacterial polysaccharides and biological active secondary metabolites like septacidin (SEP), which represents a group of nucleoside antibiotics with antitumor, antifungal, and pain-relief activities. However, little is known about the formation mechanisms of those l-heptose moieties. In this study, we deciphered the biosynthetic pathway of the l,l-gluco-heptosamine moiety in SEPs by functional characterizing four genes and proposed that SepI initiates the process by oxidizing the 4'-hydroxyl of l-glycero-α-d-manno-heptose moiety of SEP-328 (2) to a keto group. Subsequently, SepJ (C5 epimerase) and SepA (C3 epimerase) shape the 4'-keto-l-heptopyranose moiety by sequential epimerization reactions. At the last step, an aminotransferase SepG installs the 4'-amino group of the l,l-gluco-heptosamine moiety to generate SEP-327 (3). An interesting phenomenon is that the SEP intermediates with 4'-keto-l-heptopyranose moieties exist as special bicyclic sugars with hemiacetal-hemiketal structures. Notably, l-pyranose is usually converted from d-pyranose by bifunctional C3/C5 epimerase. SepA is an unprecedented monofunctional l-pyranose C3 epimerase. Further in silico and experimental studies revealed that it represents an overlooked metal dependent-sugar epimerase family bearing vicinal oxygen chelate (VOC) architecture.
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Keratoconus (KC) is a noninflammatory ectatic disease characterized by progressive thinning and an apical cone-shaped protrusion of the cornea. In recent years, more and more researchers have been committed to automatic and semi-automatic KC detection based on corneal topography. However, there are few studies about the severity grading of KC, which is particularly important for the treatment of KC. In this work, we propose a lightweight KC grading network (LKG-Net) for 4-level KC grading (Normal, Mild, Moderate, and Severe). First of all, we use depth-wise separable convolution to design a novel feature extraction block based on the self-attention mechanism, which can not only extract rich features but also reduce feature redundancy and greatly reduce the number of parameters. Then, to improve the model performance, a multi-level feature fusion module is proposed to fuse features from the upper and lower levels to obtain more abundant and effective features. The proposed LKG-Net was evaluated on the corneal topography of 488 eyes from 281 people with 4-fold cross-validation. Compared with other state-of-the-art classification methods, the proposed method achieves 89.55% for weighted recall (W_R), 89.98% for weighted precision (W_P), 89.50% for weighted F1 score (W_F1) and 94.38% for Kappa, respectively. In addition, the LKG-Net is also evaluated on KC screening, and the experimental results show the effectiveness.
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Hydrogen peroxide (H2O2) is an indispensable basic reagent in various industries, such as textile bleach, chemical synthesis, and environmental protection. However, it is challenging to prepare H2O2 in a green, safe, simple and efficient way under ambient conditions. Here, we found that H2O2 could be synthesized using a catalytic pathway only by contact charging a two-phase interface at room temperature and normal pressure. Particularly, under the action of mechanical force, electron transfer occurs during physical contact between polytetrafluoroethylene particles and deionized water/O2 interfaces, inducing the generation of reactive free radicals (·OH and ·O2-), and the free radicals could react to form H2O2, yielding as high as 313 µmol L-1 h-1. In addition, the new reaction device could show long-term stable H2O2 production. This work provides a novel method for the efficient preparation of H2O2, which may also stimulate further explorations on contact-electrification-induced chemistry process.
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Herein we present a nickel-catalyzed regio- and enantioselective ring opening reaction of 3,4-epoxy amides and esters with aromatic amines as nucleophiles. This method features high regiocontrol, diastereospecific SN2 reaction pathway, broad substrate scope, and mild reaction conditions, furnishing a wide range of γ-amino acid derivatives in a highly enantioselective manner. Notably, the selective nucleophilic attack to the C-4 position of epoxides is controlled by the directing effect of the pendant carbonyl group.
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Contact-electro-catalysis (CEC) has been recently proposed for the effective degradation of methyl orange, but the reactivity of catalysts in the CEC process needs further investigation. Here, we have used dielectric films, such as fluorinated ethylene propylene (FEP), modified by inductively coupled plasma (ICP) etching with argon, to replace the previously employed micro-powder due to their potential scalability, facile recycling process, and possible lower generation of secondary pollution. It has been found that ICP creates cone-like micro/nano structures on the surface, and thus changes the contact angle and specific surface area. The value of the contact angle varies non-linearly with etching time and attains a maximum after 60 seconds of etching. Concurrently, an increased electron transfer is observed, as well as an enhanced degradation efficiency, thus suggesting a special role of the surface structure. Finally, KPFM measurements show a lower electron affinity at the summit of the nanocones. This observation suggests that the structures are endowed with higher charge transfer ability. In addition, this film-based CEC has been observed in several polymer materials, such as PET, PTFE, and PVC. We view this work as a stepping stone to develop CEC into scalable applications, based on film technologies.
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Medicinal fungi are beneficial to human health and it reduces the risk of chronic diseases. Triterpenoids are polycyclic compounds derived from the straight-chain hydrocarbon squalene, which are widely distributed in medicinal fungi. Triterpenoids from medicinal fungal sources possess diverse bioactive activities such as anti-cancer, immunomodulatory, anti-inflammatory, anti-obesity. This review article describes the structure, fermentation production, biological activities, and application of triterpenoids from the medicinal fungi including Ganoderma lucidum, Poria cocos, Antrodia camphorata, Inonotus obliquus, Phellinus linteus, Pleurotus ostreatus, and Laetiporus sulphureus. Besides, the research perspectives of triterpenoids from medicinal fungi are also proposed. This paper provides useful guidance and reference for further research on medicinal fungi triterpenoids.
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BACKGROUND: Genetic factors play an important role in prostate cancer (PCa) susceptibility. OBJECTIVE: To discover common genetic variants contributing to the risk of PCa in men of African ancestry. DESIGN, SETTING, AND PARTICIPANTS: We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Common genotyped and imputed variants were tested for their association with PCa risk. Novel susceptibility loci were identified and incorporated into a multiancestry polygenic risk score (PRS). The PRS was evaluated for associations with PCa risk and disease aggressiveness. RESULTS AND LIMITATIONS: Nine novel susceptibility loci for PCa were identified, of which seven were only found or substantially more common in men of African ancestry, including an African-specific stop-gain variant in the prostate-specific gene anoctamin 7 (ANO7). A multiancestry PRS of 278 risk variants conferred strong associations with PCa risk in African ancestry studies (odds ratios [ORs] >3 and >5 for men in the top PRS decile and percentile, respectively). More importantly, compared with men in the 40-60% PRS category, men in the top PRS decile had a significantly higher risk of aggressive PCa (OR = 1.23, 95% confidence interval = 1.10-1.38, p = 4.4 × 10-4). CONCLUSIONS: This study demonstrates the importance of large-scale genetic studies in men of African ancestry for a better understanding of PCa susceptibility in this high-risk population and suggests a potential clinical utility of PRS in differentiating between the risks of developing aggressive and nonaggressive disease in men of African ancestry. PATIENT SUMMARY: In this large genetic study in men of African ancestry, we discovered nine novel prostate cancer (PCa) risk variants. We also showed that a multiancestry polygenic risk score was effective in stratifying PCa risk, and was able to differentiate risk of aggressive and nonaggressive disease.
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For eutrophic water bodies, potassium permanganate is an effective pre-oxidant to remove algae and its residue in water treatment sludge. Recycling water treatment sludge in concrete is an environmentally friendly and high-value utilization measure. However, little research has been done on the effect of manganese-rich drinking water sludge ash (DWSA) on concrete. The effect of water-binder ratio (w/b) on strength, shrinkage and microstructural characteristics of concrete containing DWSA was investigated, and the structural behavior was explained from a nanoscale perspective. The results show that recycling 10â¯% DWSA in concrete improved the strength and shrinkage resistance of the samples. Reducing the w/b effectively increased the strength of DWSA-modified concrete and reduced the shrinkage deformation. The paste with high w/b had higher contents of non-evaporated water and calcium hydroxide, as well as higher reaction degree of DWSA. Nanoscale characterization shows that reducing the w/b reduced the volume fraction of pore and unhydrated phases in the matrix and increased the proportion of high-density C-S-H. Meanwhile, reducing the w/b also reduced the interfacial transition zone width of DWSA-modified concrete. Recycling DWSA in concrete effectively reduced the total carbon footprint and cost of the mixture. The combined application of reducing the w/b and incorporating DWSA effectively improved the economic and environmental benefits of concrete material. For the concrete modified with 10â¯% DWSA (w/bâ¯=â¯0.3), its cost and carbon emissions are reduced by 14â¯%-21â¯% and 19â¯%-25â¯% compared with the reference sample, respectively. Overall, this study reveals the action mechanism of DWSA in cement system at different w/b from nanoscale perspective, and gives a new insight on determining the optimal w/b in full-scale application of DWSA concrete.