Lignocellulosic biorefinery constitutes a critical pillar for transitioning the fossil-based industrial paradigm toward sustainability. However, in lignocellulosic biorefinery, cross-interference between cellulose, hemicellulose, and lignin persists throughout all steps. Effective regulation must extend beyond pretreatment across the entire process. Here, we develop a whole-process regulation strategy for corn stover. Mechanical fractionation homogenizes physical structure, yielding parenchyma-rich short fibers and vascular-bundle-dominant long fibers. For highly degradable short fibers, molecular control by methanol during steam explosion suppresses lignin condensation, followed by oxidative enhancement by carbon quantum dots during enzymatic hydrolysis, boosting cellulose conversion and facilitating mild lignin depolymerization for high-performance epoxy resins. For high-crystallinity long fibers, two-stage selective enzymatic hydrolysis preserves crystallinity to produce cellulose nanocrystals. Techno-economic analysis shows a 36.7% revenue increase over the unregulated baseline. This integrated approach embodies the concept of precision biorefinery: a transformative framework where whole-process regulation orchestrates multi-level heterogeneity-guided fractionation to enable full-component directed valorization, ensuring compatibility between biomass attributes, process, and product specifications. The concept and innovations have been industrially validated.

Rationale: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a critical syndrome with a mortality rate of up to 40%, and it is characterized by a prominent inflammatory cascade. The inflammasome and pyroptosis play crucial regulatory roles in regulating various inflammatory-related diseases by serving as pivotal signaling platforms for inflammatory responses and mediating the release of substantial quantities of inflammatory factors. Our previous studies confirmed that GC-1, a clinical-stage thyroid hormone analog, effectively mitigated pulmonary fibrosis by restoring mitochondrial function in epithelial cells. However, the potential effects of GC-1 on macrophage inflammasome assembly and pyroptosis in lung injury as well as the underlying mechanisms, remain unclear. Methods: The effects of GC-1 on lung injury, oxidative damage and inflammation were evaluated in two murine models of ALI (LPS- or HCl-induced models) by assessing lung pathology, the concentrations of IL-1β and IL-18 in BAL fluid, inflammasome and the levels of inflammasome- and pyroptosis-related proteins. Additionally, the impact of GC-1 on ROS-mediated inflammasome assembly and pyroptosis was investigated by examining ROS levels, Nrf2 signaling, and inflammasome adaptor protein ASC levels in mouse alveolar macrophages and human THP-1 macrophages treated with LPS and ATP. The Nrf2 inhibitor ML385 and the mitochondrial-ROS inhibitor Mito-TEMPO were used to further elucidate the effect of GC-1 on the Nrf2-p53-ASC pathway. Results: GC-1 significantly alleviated inflammation and lung injury in ALI model mice, as indicated by pulmonary pathology, inflammatory cytokine levels, ROS production and pyroptosis rates. Consistently, GC-1 inhibited ASC recruitment and oligomerization in macrophages, which suppressed the gasdermin D-mediated release of IL-1β and IL-18. These findings indicated a reduction in inflammasome assembly and pyroptosis initiation. Further research revealed that GC-1 may mitigate oxidative stress induced by mitochondrial damage through Nrf2 signaling, thereby inhibiting the expression of ROS-activated p53 and the target gene ASC. This protective effect of GC-1 could be reversed by ML385 and mimicked by Mito-TEMPO. Conclusions: This study presents a novel mechanism for treating ALI in which GC-1 inhibits macrophage ROS-mediated inflammasome assembly and pyroptosis through Nrf2-p53-ASC pathway. These findings highlight the promising potential of the use of GC-1 as an anti-inflammatory and antioxidant drug in the treatment of ALI/ARDS.

A simple and reliable total antioxidant capacity (TAC) assay is essential for food safety evaluation and human health monitoring. Herein, a trimetallic nanozyme (Fe3O4@Ag@Pt) was synthesized and exhibited OXD-, POD- and SOD-like activities, which could generate a synergistic catalytic system. Fe3O4@Ag@Pt can catalyze oxygen to produce various reactive oxygen intermediates, and the endogenous product H2O2 could be captured and further dissociated efficiently into •OH, due to its strong substrate binding affinity. Since antioxidants can compete with TMB and lead to an antioxidant concentration-dependent color change, a colormetric sensing platform was constructed with a detection limit of 1.97 μM, 5.06 μM, and 8.99 μM for GSH, AA and Trolox, respectively. The proposed Fe3O4@Ag@Pt based assay was suitably employed to quantify TAC in fruit samples, beverages and cells with the aid of spike recovery and reference method validation, which hold vast promise as an analytical platform for food safety and biomedical diagnosis.

Herein, Co- and Fe-based single-atom nanozymes (M/N-PC, M = Co or Fe) were successfully fabricated and their catalytic performances for patulin degradation were evaluated systematically. Co/N-PC, consisting of Co-N4 and nanoclusters sites, achieved a higher patulin degradation efficiency (99.4 %, within 60 min) than Fe/N-PC (only consisting of Fe-N5 sites). Synergistic interactions between Co-N4 and Co nanoclusters greatly enhanced electron density near the Fermi level in Co/N-PC, enabling its high catalytic performance. The degradation products of patulin exhibited negligible cytotoxicity. The M/N-PCs demonstrated good reusability, broad pH adaptability and high practical application potential for patulin degradation in apple juice. M/N-PC also exhibited high efficiency in degrading aflatoxin B1, deoxynivalenol and zearalenone (∼100 %, 10-40 min). This study provides in-depth insights into the relationship between metal active site structures in M/N-PCs and their catalytic properties for mycotoxin detoxification, offering guidance for the design of highly efficient single-atom nanozymes.

The dense structure of woody biomass leads to high-intensity pretreatment methods involving acids, alkalines, chemical reagents, or significant energy inputs. However, the fundamental causes of this phenomenon have not been correlated. This study investigates the application of salt-frost, a natural energy source, in combination with hydrothermal treatment to enhance enzymatic hydrolysis of poplar and to explore the correlation between the dense structure and the treatment intensity. Salt-frost pretreatment enhances poplar's porosity and substrate flowability, reducing water saturation by 5.2-10.1 % compared to untreated samples. Salt-frost reduces hydro-thermal severity by 84.0 %, significantly reducing levels of formic acid, 5-hydroxymethylfurfural, and furfural at 140 degrees C. The salt-frost treatment increased glucose hydrolysis yields by 147.0 %, achieving 5.68 g/L within 12 hours compared to untreated samples. It emphasizes the significant relationship between porous structure and treatment intensity. This study introduces an energy-efficient approach suitable for high-altitude regions, providing practical insights into the processing of woody biomass.

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by aberrant fibroblast activation and extracellular matrix deposition. Emerging evidence implicates mitochondrial dysfunction in IPF pathogenesis. Although CAMKK2 has been implicated in mitochondrial function associated with diabetic nephropathy, its role and underlying mechanisms in IPF remain unclear. This study aims to investigate the role of CAMKK2 in IPF. This study employed AAV-CAMKK2 mice, primary human/mouse lung fibroblasts, MRC-5 cells, and IPF patient samples. The CAMKK2 inhibitor (STO-609), shCAMKK2 and Flag-CAMKK2 overexpression plasmid were used to investigate the role of CAMKK2 in lung fibroblasts. Fibroblast activity was assessed by transwell migration, collagen contraction, and wound-healing assays. Mitochondrial function (ROS, mitochondrial membrane potential (MMP), ATP and oxygen consumption rate (OCR)) was measured by ROS assay, JC-1 assay, ATP assay and Seahorse assay. Mitochondrial dynamics (MFN1/MFN2, DRP1), PGC-1α, and p-T172AMPK were analyzed alongside fibrotic markers (FN1, COL1A1 and α-SMA) by Western blotting and RT-qPCR. The AMPK inhibitor (Compound C) and PGC-1α inhibitor (SR-18292) were used to investigate the role of AMPK and PGC-1α in this study. This study revealed that CAMKK2 expression was significantly downregulated in pulmonary fibrosis, concomitant with impaired mitochondrial function-related proteins (PGC-1α, MFN1and MFN2). In vitro experiments demonstrated that CAMKK2 inhibition or shCAMKK2 knockdown exacerbated fibroblast activation and extracellular matrix (ECM) production in both MRC-5 cells and primary mouse lung fibroblasts. Conversely, CAMKK2 overexpression attenuated TGF-β1-induced fibroblast activation and ECM deposition in MRC-5 cells and primary human lung fibroblasts. Further investigation established that CAMKK2 overexpression normalized mitochondrial morphology, enhanced MMP, ATP content and respiratory capacity to ameliorate mitochondrial dysfunction in TGF-β1–induced MRC-5 cells. Moreover, CAMKK2 upregulated mitochondrial fusion protein expression (MFN1 and MFN2) and suppressed fission (DRP1) in MRC-5 cells. Mechanistically, CAMKK2 regulated mitochondrial dynamics and OXPHOS function via the AMPK/PGC-1α pathway in TGF-β1–induced MRC-5 cells, as evidenced by rescued protein expression (MFN1 and MFN2), and reversal of these effects following AMPK or PGC-1α inhibition. In vivo studies showed that AAV-mediated CAMKK2 delivery significantly attenuated bleomycin-induced pulmonary fibrosis in mice. In summary, these findings collectively demonstrate that CAMKK2 regulated mitochondrial dynamics and OXPHOS function via AMPK/PGC-1α signaling pathway to alleviate pulmonary fibrosis in lung fibroblasts. Therefore, targeting CAMKK2 presents a novel and promising therapeutic strategy for the treatment of pulmonary fibrosis.

The impact of the COVID-19 pandemic on the takeaway dietary pattern has led to significant shifts in dietary patterns. However, the precise details of these changes and their associated environmental and nutritional consequences remain unrevealed. Here, we address this knowledge gap through the text mining of 299.25 million takeaway product consumption records. Taking Beijing as a case study, we estimated the comprehensive shift in food takeaway diets. Overall takeaway consumption trends in 7 food categories-dairy (-27.90%), meat (-34.98%), grain (-32.46%), eggs (-19.51%), fruit (-25.46%), seafood (-38.21%) and soybean (-13.16%)-experienced significant declines, while the intake of oil (15.64%) and sugar (16.04%) saw an increase. The overall environmental impact demonstrated a reduction, with declines observed in carbon footprint (-34.35%), nitrogen footprint (-33.95%), phosphorus footprint (-32.67%), water footprint (-32.84%), and land use (-33.18%) compared to pre-COVID levels. Our results reveal a decrease in environmental impacts and a simultaneous alleviation of nutritional imbalances in total within the early stages of the COVID-19 pandemic in the food takeaway industry. The findings contributed to understanding of shift in takeaway eating patterns caused by the pandemic, hold implications for environmental and nutritional consequences of takeaway diet patterns.

The study explored contamination characteristics, spatial distribution, varietal and seasonal differences, health risks, processing effects on STC residues, and the relationship between aflatoxin B1 (AFB1) and STC. A total of 1032 rice samples from 17 Chinese provinces were processed into brown and polished rice and analyzed using LC-MS/MS. Rice showed widespread STC pollution, with a maximum concentration of 23.8 μg/kg, and significant regional variations. Indica rice was more susceptible to STC than japonica rice, while the planting season had minimal impact. Risk assessment showed acceptable health risks overall, although high consumers faced potential threats. Hulling and polishing reduced STC levels, but residues remained in highly contaminated samples. The correlation between AFB1 and STC underscores the need for vigilance in monitoring and control. This research provides a scientific basis for food safety control measures.

The carbon emission trading scheme (CETS) facilitates efficacious resource allocation through the exchange of carbon emission quotas tailored to the specific needs of distinct entities. The growing significance of CETS in propelling corporate green innovation (GI) has emerged as a pivotal subject. Utilizing the double machine learning model to transcend the constraints of conventional approaches, this work assesses the influence and underlying mechanisms of CETS on GI, leveraging a dataset of Chinese listed firms spanning 2010 to 2022. The research findings reveal a positive correlation between corporate GI and CETS, with the CETS significantly fostering GI endeavors in corporate end governance. Mechanism testing corroborates that CETS augments corporate GI by heightening both internal and external pressures faced by corporates and providing incentives for them. Moreover, the innovation induced by this policy has displaced other innovation resources, manifesting a discernible crowding-out effect. Heterogeneity analysis highlights a stronger effect of CETS on GI within largescale, private, environmentally conscientious corporates and corporates in the eastern region.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disorder characterized by excessive scarring of lung tissue, predominantly affecting middle-aged and elderly populations. Oxidative stress plays a pivotal role in the pathogenesis of pulmonary fibrosis, disrupting redox homeostasis and driving fibrotic progression. Glutathione reductase (GSR), a key antioxidant enzyme, is essential for maintaining cellular glutathione (GSH) levels and mitigating oxidative damage. However, the specific involvement of GSR in IPF remains poorly understood. This study found that GSR levels were downregulated in IPF patients and mice treated with bleomycin (BLM). GSR knockdown enhanced epithelial-to-mesenchymal transition (EMT) in A549 cells and promoted the activation of MRC5 cells. Additionally, GSR depletion promoted cellular migration and senescence in both A549 and MRC5 cells. Mechanistically, silencing GSR in A549 and MRC5 cells led to a marked reduction in intracellular GSH levels, resulting in elevated reactive oxygen species (ROS) accumulation, thereby promoting the activation of the TGF-β/Smad2 signaling pathway. In conclusion, our findings demonstrate that GSR deficiency aggravates pulmonary fibrosis by impairing antioxidant defense mechanisms, promoting EMT, and activating fibroblasts through the TGF-β/Smad2 signaling. These findings suggest that GSR may be essential in reducing the fibrotic progression of IPF.

Abstract Many tumor types, including pancreatic adenocarcinomas, have dysregulated circadian rhythms. Here we show that the master regulator of circadian control, BMAL1, is overexpressed in pancreatic ductal adenocarcinoma (PDAC) relative to normal tissue and plays a role in protecting PDAC cells from recognition by the immune system. Using CRISPR-generated knockout (KO) cell lines, we evaluated the cells ability to create liver metastasis using a splenic metastasis assay and found that loss of Bmal1 KO abrograted metastasis. We hypothesized that could be through an immune mediated mechanism and evaluated the Bmal KO cells for their expression of cell surface MHCI. Remarkably loss of Bmal1 led to a significant increase in cell surface MHCI expression. This was due to a change in localization of the MHCI molecule. Proper localization of MHC1 is known to depend upon proteasome-generated peptides, and we found that loss of Bmal1 increased proteosomal activity. We used Cut and Run to demonstrate that Bmal1 binds directly to the promoters for core components of the proteosome. Taken together these studies implicate Bmal1 in regulating anti-tumor immunity in PDAC through its regulation of protesomal activity and MHC1 surface expression. This is a novel function for a circadian rhythm gene in PDAC biology. Citation Format: Orjola Prela, Lan Wang, Ching-Hua Shih, Juliana Cazarin de Menezes, Brian Altman, Paula M. Vertino, Chris R. Harris, Darren R. Carpizo. The circadian master regulator BMAL1 blocks immune cell recognition of pancreatic ductal adenocarcinomas by reducing proteasome activity and MHC1 cell surface localization [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C019.

Initial material characteristics were one of the decisive factors affecting the hydrothermal pretreatment of woody biomass with a dense structure. In this study, the effect of initial material particle size on poplar hydrothermal pretreatment and enzymatic hydrolysis was evaluated. The enzymatic hydrolysis yield and the accessibility of the enzymatic reaction were significantly increased with an initial material with an average particle size of initial material (D50) < 500 μm, because of the different pretreatment effects of initial material. SEM and compositional analysis indicated that the reduction of the initial particle size facilitated hydrothermal pretreatment with better depolymerization effects. The bulk density of D50 < 500 μm increased by 28.87

The non-dissolving strategy utilizes green steam explosion method to pretreat corn stover, and then directly blend it with PVA solution to fabricate a lignocellulose-based hydrogel, which avoids component separation, modification, and dissolution.

Hydroxide exchange membranes and ionomers (HEMs and HEIs) are crucial components to facilitate the flow of anion groups between the electrode in the electrochemical devices. HEMs consist of polymer backbones and cationic groups within the backbone chain or pendant side chain. The robustness of HEMs is critical to the long-term durability of devices. However, HEMs can be gradually degraded by the attack of hydroxide anion group and the oxidation reaction of radicals. In the past decades, many efforts have been made to mitigate the degradation by hydroxide attack with the utilization of ether-free backbones and stable cation groups. The radical attack to HEM is also detrimental to the cell durability, but rarely studied. Superoxide (O2 •-), hydroperoxyl (HOO•), hydroxyl (HO•) and hydrogen (H•) radicals have been demonstrated to form in-situ in the fuel cells and water electrolyzers. The formation of reactive oxygen species (ROS) is a common phenomenon as radicals were found to be generated in the presence of both platinum group metal (PGM) and PGM-free oxygen reduction reaction (ORR) catalysts in the fuel cells. The rapid oxidation of the backbones and cation groups for both phenyl-based (poly(arylene piperidinium)) and phenyl-free-based (polynorbornene) ionomer was also observed in the durability test of HEM electrolyzers. These results indicated that it is imperative to enhance the oxidative stability of HEM and HEI due to their vulnerability to free radical attacks under challenging electrochemical operating conditions, which can result in material degradation, undermining the long-term stability of HEM. In this work, an organic radical scavenger was incorporated into the polymer through a stable chemical bond. The radical scavenger can effectively capture radicals to inhibit the oxidation of the aryl ring to form the benzoate. The oxidative stability of designed HEM was enhanced, as 64.7% of strain, 64.2% of stress and 98.7% of conductivity were retained, while the membrane without radical scavenger moiety retained only 14.7% of strain, 46.7 of stress and 85.4% of conductivity. References Wang, J.; Zhao, Y.; Setzler, B. P.; Rojas-Carbonell, S.; Ben Yehuda, C.; Amel, A.; Page, M.; Wang, L.; Hu, K.; Shi, L.; Gottesfeld, S.; Xu, B.; Yan, Y. Poly(aryl piperidinium) membranes and ionomers for hydroxide exchange membrane fuel cells. Nat. Energy. 2019, 4, 392. Parrondo, J.; Wang, Z.; Jung, M.-S. J.; Ramani, V. Reactive oxygen species accelerate degradation of anion exchange membranes based on polyphenylene oxide in alkaline environments. Phys. Chem. Chem. Phys. 2016, 18 , 19705. Wierzbicki, S.; Douglin, J. C.; Singh, R. K.; Dekel, D. R.; Kruczała, K. Operando EPR Study of Radical Formation in Anion-Exchange Membrane Fuel Cells. ACS Catal. 2023, 13, 2744. Lindquist G, Gaitor J, Thompson W, Brogden V, Noonan K, Boettcher S. Oxidative instability of ionomers in hydroxide-exchange-membrane electrolyzers. ChemRxiv. 2023; doi:10.26434/chemrxiv-2023-7w3rz This content is a preprint and has not been peer-reviewed.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fatal, and aging-associated interstitial lung disease with a poor prognosis and limited treatment options, while the pathogenesis remains elusive. In this study, we found that the expression of nuclear receptor subfamily 2 group F member 2 (NR2F2), a member of the steroid thyroid hormone superfamily of nuclear receptors, was reduced in both IPF and bleomycin-induced fibrotic lungs, markedly in bleomycin-induced senescent epithelial cells. Inhibition of NR2F2 expression increased the expression of senescence markers such as p21 and p16 in lung epithelial cells, and activated fibroblasts through epithelial-mesenchymal crosstalk, inversely overexpression of NR2F2 alleviated bleomycin-induced epithelial cell senescence and inhibited fibroblast activation. Subsequent mechanistic studies revealed that overexpression of NR2F2 alleviated DNA damage in lung epithelial cells and inhibited cell senescence. Adenovirus-mediated Nr2f2 overexpression attenuated bleomycin-induced lung fibrosis and cell senescence in mice. In summary, these data demonstrate that NR2F2 is involved in lung epithelial cell senescence, and targeting NR2F2 may be a promising therapeutic approach against lung cell senescence and fibrosis.

The recalcitrance of plant cell walls poses significant challenges in pretreatment and enzymatic hydrolysis processes, hindering the conversion of lignocellulosic biomass into fermentable sugars. To elucidate the lignocellulosic recalcitrance characteristics of corn stover, this study investigated the anatomical and pore structure of the enzymatic residues from steam-exploded corn stover. The morphology identification of corn stover clarified that the enzymatic residues primarily consisted of sclerenchyma, accounting for 84.43 %. It was found that the sclerenchyma was characterized by a small cavity diameter (3-25 mu m) and thick wall (5-8 mu m). The surface area of the enzymatic residues increased significantly, while the median pore size decreased compared with the steam-exploded corn stover. The sclerenchyma is the main recalcitrant structure of enzymatic residues. The thick walls and small pores of sclerenchyma cells in enzymatic residues impeded cellulase's mass transfer and penetration, resulting in low distribution density and reduced accessibility. Based on the above analysis of lignocellulosic recalcitrance characteristics, the research findings offer crucial insights into lignocellulosic biomass pretreatment strategies and provide valuable suggestions for industrialization conversion processes.