SARS-CoV-2 N protein-induced Dicer, XPO5, SRSF3, and hnRNPA3 downregulation causes pneumonia.

Though RNAi and RNA-splicing machineries are involved in regulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, their precise roles in coronavirus disease 2019 (COVID-19) pathogenesis remain unclear. Herein, we show that decreased RNAi component (Dicer and XPO5) and splicing factor (SRSF3 and hnRNPA3) expression correlate with increased COVID-19 severity. SARS-CoV-2 N protein induces the autophagic degradation of Dicer, XPO5, SRSF3, and hnRNPA3, inhibiting miRNA biogenesis and RNA splicing and triggering DNA damage, proteotoxic stress, and pneumonia. Dicer, XPO5, SRSF3, and hnRNPA3 knockdown increases, while their overexpression decreases, N protein-induced pneumonia's severity. Older mice show lower expression of Dicer, XPO5, SRSF3, and hnRNPA3 in their lung tissues and exhibit more severe N protein-induced pneumonia than younger mice. PJ34, a poly(ADP-ribose) polymerase inhibitor, or anastrozole, an aromatase inhibitor, ameliorates N protein- or SARS-CoV-2-induced pneumonia by restoring Dicer, XPO5, SRSF3, and hnRNPA3 expression. These findings will aid in developing improved treatments for SARS-CoV-2-associated pneumonia.

A brief review of current treatment options for osteoarthritis including disease-modifying osteoarthritis drugs (DMOADs) and novel therapeutics.

Osteoarthritis (OA) is a chronic disorder caused by degenerative changes in articular cartilage, which are mainly manifests as degeneration of cartilage, subchondral bone remodeling, as well as synovial inflammation. Over the next few decades, OA and its burden will continue to increase worldwide, posing a major public health challenge for the foreseeable future. Treatment for OA includes non-pharmacological, pharmacological, and surgical treatments. Existing conservative treatments and joint surgery can only alleviate the symptoms and cannot be cured, so new therapies for OA are urgently needed. Since advances in the understanding of OA pathophysiology, researchers have identified some potential therapeutic targets against degeneration of cartilage, subchondral bone remodeling and synovial inflammation, enabling development of the disease-modifying OA drugs (DMOADs). Additionally, a number of new technologies are also being investigated for treating OA, such as RNA interference (RNAi), CRISPR/Cas9 and PROTAC. The goal of this review is to describe the current development status of DMOADs and to discuss the potential of emerging therapeutic approaches for treating OA, thus providing a reference for OA treatments.

Marker selection strategies for circulating tumor DNA guided by phylogenetic inference.

Motivation: Blood-based profiling of tumor DNA ("liquid biopsy") has offered great prospects for non-invasive early cancer diagnosis, treatment monitoring, and clinical guidance, but require further advances in computational methods to become a robust quantitative assay of tumor clonal evolution. We propose new methods to better characterize tumor clonal dynamics from circulating tumor DNA (ctDNA), through application to two specific questions: 1) How to apply longitudinal ctDNA data to refine phylogeny models of clonal evolution, and 2) how to quantify changes in clonal frequencies that may be indicative of treatment response or tumor progression. We pose these questions through a probabilistic framework for optimally identifying maximum likelihood markers and applying them to characterizing clonal evolution. Results: We first estimate a distribution over plausible clonal lineage models, using bootstrap samples over pre-treatment tissue-based sequence data. We then refine these lineage models and the clonal frequencies they imply over successive longitudinal samples. We use the resulting framework for modeling and refining tree distributions to pose a set of optimization problems to select ctDNA markers to maximize measures of utility capturing ability to solve the two questions of reducing uncertain in phylogeny models or quantifying clonal frequencies given the models. We tested our methods on synthetic data and showed them to be effective at refining distributions of tree models and clonal frequencies so as to minimize measures of tree distance relative to the ground truth. Application of the tree refinement methods to real tumor data further demonstrated their effectiveness in refining a clonal lineage model and assessing its clonal frequencies. The work shows the power of computational methods to improve marker selection, clonal lineage reconstruction, and clonal dynamics profiling for more precise and quantitative assays of tumor progression. Availability: https://github.com/CMUSchwartzLab/Mase-phi.git. Contact: russells@andrew.cmu.edu.

Catalytic Hydrogenolysis by Atomically Dispersed Iron Sites Embedded in Chemically and Redox Non-innocent N-Doped Carbon.

Atomically dispersed first-row transition metals embedded in nitrogen-doped carbon materials (M-N-C) show promising performance in catalytic hydrogenation but are less well-studied for reactions with more complex mechanisms, such as hydrogenolysis. Their ability to catalyze selective C-O bond cleavage of oxygenated hydrocarbons such as aryl alcohols and ethers is enhanced with the participation of ligands directly bound to the metal ion as well as longer-range contributions from the support. In this article, we describe how Fe-N-C catalysts with well-defined local structures for the Fe sites catalyze C-O bond hydrogenolysis. The reaction is facilitated by the N-C support. According to spectroscopic analyses, the as-synthesized catalysts contain mostly pentacoordinated FeIII sites, with four in-plane nitrogen donor ligands and one axial hydroxyl ligand. In the presence of 20 bar of H2 at 170-230 °C, the hydroxyl ligand is lost when N4FeIIIOH is reduced to N4FeII, assisted by the H2 chemisorbed on the support. When an alcohol binds to the tetracoordinated FeII sites, homolytic cleavage of the O-H bond is accompanied by reoxidation to FeIII and H atom transfer to the support. The role of the N-C support in catalytic hydrogenolysis is analogous to the behavior of chemically and redox-non-innocent ligands in molecular catalysts based on first-row transition metal ions and enhances the ability of M-N-Cs to achieve the types of multistep activations of strong bonds needed to upgrade renewable and recycled feedstocks.

Association between weekend catch-up sleep and depressive symptoms in American adults: Finding from NHANES 2017-2020.

BACKGROUND: The effect of weekend catch-up sleep (WCS) on depressive symptoms is inconsistent among different populations, with limited evidence in Americans. Therefore, we aimed to investigate the association between WCS and depressive symptoms in American adults. METHODS: We recruited 7719 participants from the National Health and Nutrition Examination Survey (NHANES) 2017-2020. Information on sleep duration and depressive symptoms were assessed by several self-reported questions and Patient Health Questionnaire-9 (PHQ-9), respectively. Then, WCS duration was calculated as weekend sleep duration minus weekday sleep duration, and WCS was further defined as WCS duration >0 h. Survey designed regression analyses were used to assess the association of WCS and depressive symptoms. RESULTS: In fully adjusted multivariate logistic regression models, the odds ratio (95 % confidence interval) for depressive symptoms and the ß (95 % confidence interval) for PHQ-9 score in response to WCS were 0.746 (0.462, 1.204; P = 0.218) and -0.429 (-0.900, 0.042; P = 0.073), respectively. Besides, the smooth relationship presented L-shaped, and only WCS duration of 0-2 h was statistically significantly associated with depressive symptoms or PHQ-9 score. Subgroup analyses showed that the negative associations were stronger among men, adults younger than 65 years, and those with short weekday sleep duration (P for interaction <0.05). LIMITATIONS: The cross-sectional design limits the capability for causal relationship between WCS and depressive symptoms. CONCLUSIONS: This study suggests that moderate WCS is associated with reduced odds of depressive symptoms, which provides additional epidemiological evidence for the effects of sleep on depressive symptoms.

Neutrophil Targeting Platform Reduces Neutrophil Extracellular Traps for Improved Traumatic Brain Injury and Stroke Theranostics.

Traumatic brain injuries (TBI) and stroke are major causes of morbidity and mortality in both developing and developed countries. The complex and heterogeneous pathophysiology of TBI and cerebral ischemia-reperfusion injury (CIRI), in addition to the blood-brain barrier (BBB) resistance, is a major barrier to the advancement of diagnostics and therapeutics. Clinical data showed that the severity of TBI and stroke is positively correlated with the number of neutrophils in peripheral blood and brain injury sites. Furthermore, neutrophil extracellular traps (NETs) released by neutrophils correlate with worse TBI and stroke outcomes by impairing revascularization and vascular remodeling. Therefore, targeting neutrophils to deliver NETs inhibitors to brain injury sites and reduce the formation of NETs can be an optimal strategy for TBI and stroke therapy. Herein, the study designs and synthesizes a reactive oxygen species (ROS)-responsive neutrophil-targeting delivery system loaded with peptidyl arginine deiminase 4 (PAD4) inhibitor, GSK484, to prevent the formation of NETs in brain injury sites, which significantly inhibited neuroinflammation and improved neurological deficits, and improved the survival rate of TBI and CIRI. This strategy may provide a groundwork for the development of targeted theranostics of TBI and stroke.

Upregulation of CELSR1 expression promotes ovarian cancer cell proliferation, migration, and invasion.

Cadherin epidermal growth factor and laminin-G seven-pass G-type receptor 1 (CELSR1) is a planar cell polarity protein involved in the transmission of directional cues to align either individual cells within an epithelial sheet or multicellular clusters. CELSR1 has been suggested to play a role in glioma, breast cancer, and chronic lymphocytic leukemia development; however, whether it has a role in the pathogenesis of ovarian cancer remains unknown. The aim of this study was to determine the role of CELSR1 in ovarian cancer and elucidate its underlying molecular mechanisms. By analyzing gene expression data downloaded from the Cancer Genome Atlas database, we found that CELSR1 expression was upregulated in ovarian cancer tissues compared to that in normal ovarian tissues. High CELSR1 expression levels were associated with poor prognosis in patients with ovarian cancer. Cell proliferation, scratch, and transwell assays revealed that CELSR1 promoted the proliferation, migration, and invasion of ovarian cancer cells in vitro. In addition, transcriptome sequencing analysis revealed that CELSR1 knockdown in T29H cells resulted in the dysregulation of the expression of 1320 genes. Further analysis revealed that genes involved in proliferation- and migration-associated signaling pathways were regulated by CELSR1. Our study demonstrates that CELSR1 is highly expressed in ovarian cancer cells and regulates their proliferation and migration, suggesting its potential as a diagnostic marker and therapeutic target.

Mutual communication between radiosensitive and radioresistant esophageal cancer cells modulates their radiosensitivity.

Radiotherapy is an important treatment modality for patients with esophageal cancer; however, the response to radiation varies among different tumor subpopulations due to tumor heterogeneity. Cancer cells that survive radiotherapy (i.e., radioresistant) may proliferate, ultimately resulting in cancer relapse. However, the interaction between radiosensitive and radioresistant cancer cells remains to be elucidated. In this study, we found that the mutual communication between radiosensitive and radioresistant esophageal cancer cells modulated their radiosensitivity. Radiosensitive cells secreted more exosomal let-7a and less interleukin-6 (IL-6) than radioresistant cells. Exosomal let-7a secreted by radiosensitive cells increased the radiosensitivity of radioresistant cells, whereas IL-6 secreted by radioresistant cells decreased the radiosensitivity of radiosensitive cells. Although the serum levels of let-7a and IL-6 before radiotherapy did not vary significantly between patients with radioresistant and radiosensitive diseases, radiotherapy induced a more pronounced decrease in serum let-7a levels and a greater increase in serum IL-6 levels in patients with radioresistant cancer compared to those with radiosensitive cancer. The percentage decrease in serum let-7a and the percentage increase in serum IL-6 levels at the early stage of radiotherapy were inversely associated with tumor regression after radiotherapy. Our findings suggest that early changes in serum let-7a and IL-6 levels may be used as a biomarker to predict the response to radiotherapy in patients with esophageal cancer and provide new insights into subsequent treatments.

Hypotension and cognitive impairment among the elderly: Evidence from the CLHLS.

BACKGROUND: While high blood pressure has been linked to cognitive impairment, the relationship between low blood pressure, especially hypotension, and cognitive impairment has not been well studied. Therefore, this study aimed to assess the prevalence of hypotension and cognitive impairment in the seniors of China, and the association between hypotension and cognitive function impairment. METHODS: The data was derived from the 2018 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Systolic blood pressures (SBP) and diastolic blood pressures (DBP) were measured by objective examination. The Chinese version of the Mini-Mental State Examination (CMMSE) was used to evaluate the cognitive impairment of the elderly. Generalized linear models were conducted to evaluate the association of hypotension with cognitive impairment. RESULTS: The prevalence of hypotension and cognitive impairment in the Chinese elderly were 0.76% and 22.06%, respectively. Participants with hypotension, lower SBP, and lower DBP, had odds ratios of 1.62, 1.38, and 1.48 for cognitive impairment, respectively. Besides, the CMMSE scores decreased by 2.08, 0.86, and 1.08 in the elderly with hypotension, lower SBP, and DBP, compared with those with non-hypotension, higher SBP, and DBP, respectively. Subgroup analyses showed that the association of cognitive impairment with hypotension was stronger in Chinese elderly who had decreased activity of daily living. Moreover, there was statistical evidence of a nonlinear dose-response relationship of SBP and DBP with cognitive impairment (Pnonlinear < 0.05). CONCLUSION: Hypotension was a potential risk factor for cognitive impairment of the Chinese elderly, especially for those having decreased activity of daily living. Blood pressure management should be conducted to prevent them from cognitive impairment.

A Co-based nitrogen-doped lignin carbon catalyst with high stability and wide operating window for rapid degradation of antibiotics.

Co-based catalysts play a crucial role in the activation of peroxymonosulfate (PMS) for degradation contaminants. However, the practical application of such catalysts is hindered by challenges like the self-aggregation of Co nanoparticles and leaching of Co2+. In this study, the Co-based catalyst Co-N/C@CL was synthesized from carboxymethylated lignin obtained by grafting abundant carboxymethyl groups into alkali lignin, in which the presence of these carboxymethyl groups enhanced its water solubility and allowed the formation of stable macromolecular complexes with Co2+. This catalyst exhibited a high specific surface area (521.8 m2·g-1) and a uniform distribution of Co nanoparticles. Consequently, the Co-N/C@CL/PMS system could completely remove 20 ppm tetracycline (TC) in 2 min at a rate of 2.404 min-1. Experimental results and DFT calculations revealed that the synergistic effect of lignin carbon and Co NPs accelerated the cleavage and electron transfer of OO bonds, thus promoting the formation of 1O2, OH and SO4-, with 1O2 emerging as the predominant contributor. Moreover, Co-N/C@CL displayed excellent cycling stability and low Co2+ leaching. This work not only provides a feasible strategy for the preparation of highly active and stable Co-based carbon materials but also offers a promising catalyst for the efficient degradation of TC.

Small cytosolic double-stranded DNA represses cyclic GMP-AMP synthase activation and induces autophagy.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is a major mediator of inflammation following stimulation with >45 bp double-stranded DNA (dsDNA). Herein, we identify a class of ∼20-40 bp small cytosolic dsDNA (scDNA) molecules that compete with long dsDNA (200-1,500 bp herring testis [HT]-DNA) for binding to cGAS, thus repressing HT-DNA-induced cGAS activation. The scDNA promotes cGAS and Beclin-1 interaction, releasing Rubicon, a negative regulator of phosphatidylinositol 3-kinase class III (PI3KC3), from the Beclin-1-PI3KC3 complex. This leads to PI3KC3 activation and induces autophagy, causing degradation of STING and long cytosolic dsDNA. Moreover, DNA damage decreases, and autophagy inducers increase scDNA levels. scDNA transfection and treatment with autophagy inducers attenuate DNA damage-induced cGAS activation. Thus, scDNA molecules serve as effective brakes for cGAS activation, preventing excessive inflammatory cytokine production following DNA damage. Our findings may have therapeutic implications for cytosolic DNA-associated inflammatory diseases.

Zinc Vacancy Promotes Photo-Reforming Lignin Model to H2 Evolution and Value-Added Chemicals Production.

Lignin, rich in ß-O-4 bonds and aromatic structure, is a renewable and potential resource for value-added chemicals and promoting H2 evolution. However, direct photo-reforming lignin remains a huge challenge due to its recalcitrant structure. Herein, a collaborative strategy is proposed by dispersing Pt on zinc-vacancy-riched ZnIn2 S4 (Pt/VZn -ZIS) for revealing the effect of lignin structure during photo-reforming process with lignin models. And a series of theoretical calculations and experimental results show that lignin model substances with more nucleophilic group structures will have a stronger tendency to occur the photo-reforming reactions. In addition, benefiting of Pt-S electronic channel is formed by occupying Pt atom onto zinc vacancies in ZnIn2 S4 , which can effectively reduce the energy barrier of H2 evolution and accompany the selective oxidation of lignin model from Cα-OH to Cα = O under simulated sunlight. The natural lignin is used to further demonstrate this selective oxidation mechanism. The presented work demonstrates the photo-reforming lignin model mechanism and the influence of lignin-structure during the process of photo-reforming.

Ligustrazine Nanoparticle Hitchhiking on Neutrophils for Enhanced Therapy of Cerebral Ischemia-Reperfusion Injury.

Ischemic stroke is a refractory disease that endangers human health and safety owing to cerebral ischemia. Brain ischemia induces a series of inflammatory reactions. Neutrophils migrate from the circulatory system to the site of cerebral ischemia and accumulate in large numbers at the site of inflammation across the blood-brain barrier. Therefore, hitchhiking on neutrophils to deliver drugs to ischemic brain sites could be an optimal strategy. Since the surface of neutrophils has a formyl peptide receptor (FPR), this work modifies a nanoplatform surface by the peptide cinnamyl-F-(D)L-F-(D)L-F (CFLFLF), which can specifically bind to the FPR receptor. After intravenous injection, the fabricated nanoparticles effectively adhered to the surface of neutrophils in peripheral blood mediated by FPR, thereby hitchhiking with neutrophils to achieve higher accumulation at the inflammatory site of cerebral ischemia. In addition, the nanoparticle shell is composed of a polymer with reactive oxygen species (ROS)-responsive bond breaking and is encased in ligustrazine, a natural product with neuroprotective properties. In conclusion, the strategy of hitching the delivered drugs to neutrophils in this study could improve drug enrichment in the brain, thereby providing a general delivery platform for ischemic stroke or other inflammation-related diseases.

Projection of Premature Cancer Mortality in Hunan, China, Through 2030: Modeling Study.

BACKGROUND: The United Nations Sustainable Development Goals for 2030 include reducing premature mortality from noncommunicable diseases by one-third. Although previous modeling studies have predicted premature mortality from noncommunicable diseases, the predictions for cancer and its subcategories are less well understood in China. OBJECTIVE: The aim of this study was to project premature cancer mortality of 10 leading cancers in Hunan Province, China, based on various scenarios of risk factor control so as to establish the priority for future interventions. METHODS: We used data collected between 2009 and 2017 from the Hunan cancer registry annual report as empirical data for projections. The population-attributable fraction was used to disaggregate cancer deaths into parts attributable and unattributable to 10 risk factors: smoking, alcohol use, high BMI, diabetes, physical inactivity, low vegetable and fruit intake, high red meat intake, high salt intake, and high ambient fine particulate matter (PM2.5) levels. The unattributable deaths and the risk factors in the baseline scenario were projected using the proportional change model, assuming constant annual change rates through 2030. The comparative risk assessment theory was used in simulated scenarios to reflect how premature mortality would be affected if the targets for risk factor control were achieved by 2030. RESULTS: The cancer burden in Hunan significantly increased during 2009-2017. If current trends for each risk factor continued to 2030, the total premature deaths from cancers in 2030 would increase to 97,787 in Hunan Province, and the premature mortality (9.74%) would be 44.47% higher than that in 2013 (6.74%). In the combined scenario where all risk factor control targets were achieved, 14.41% of premature cancer mortality among those aged 30-70 years would be avoided compared with the business-as-usual scenario in 2030. Reductions in the prevalence of diabetes, high BMI, ambient PM2.5 levels, and insufficient fruit intake played relatively important roles in decreasing cancer premature mortality. However, the one-third reduction goal would not be achieved for most cancers except gastric cancer. CONCLUSIONS: Existing targets on cancer-related risk factors may have important roles in cancer prevention and control. However, they are not sufficient to achieve the one-third reduction goal in premature cancer mortality in Hunan Province. More aggressive risk control targets should be adopted based on local conditions.

Simultaneous Oxidative Cleavage of Lignin and Reduction of Furfural via Efficient Electrocatalysis by P-Doped CoMoO4.

Electrochemical oxidative lignin cleavage and coupled 2-furaldehyde reduction provide a promising approach for producing high-value added products. However, developing efficient bifunctional electrocatalysts with noble-metal-like activity still remains a challenge. Here, an efficient electrochemical strategy is reported for the selective oxidative cleavage of Cα -Cß bonds in lignin into aromatic monomers by tailoring the electronic structure through P-doped CoMoO4 spinels (99% conversion, highest monomer selectivity of 56%). Additionally, the conversion and selectivity of 2-furaldehyde reduction to 2-methyl furan reach 87% and 73%, respectively. In situ Fourier transform infrared and density functional theory analysis reveal that an upward shift of the Ed upon P-doping leads to an increase in the antibonding level, which facilitates the Cα -Cß adsorption of the lignin model compounds, thereby enhancing the bifunctional electrocatalytic activity of the active site. This work explores the potential of a spinel as a bifunctional electrocatalyst for the oxidative cracking of lignin and the reductive conversion of small organic molecules to high-value added chemicals via P-anion modulation.

Selective Production of 1,2-Propanediol or 1,3-Propanediol from Glycerol Hydrogenolysis over Transition Metal Doped Pt/TiO2.

Selective hydrogenolysis of biomass-derived glycerol to propanediol is important for producing high value-added chemicals from renewable resources but faces a huge challenge. Here we report a transition metal doped Pt/TiO2 catalyst with incorporated Cr, Mo, or W oxides, which exhibits the selective formation of 1,2-propanediol or 1,3-propanediol with a yield from 51.2% to 82.5% toward glycerol hydrogenolysis. In situ experimental studies verify that the surrounding CrOx decreases the hydrogenating ability of Pt, leading to the formation of 1,2-propanediol, while the MoOx or WOx brings the Brønsted acid, giving 1,3-propanediol. This modification based on the catalyst compositions alters the reaction pathway with a different adsorption and bond scission mechanism, which can be extended to other sustainable catalytic systems.

Association between dietary inflammatory index and oral cancer risk: A systematic review and dose-response meta-analysis.

Background: Dietary inflammatory index (DII) has been suggested to be associated with oral cancer risk. However, a quantitative comprehensive assessment of the dose-response relationship has not been reported. We performed a meta-analysis to clarify the risk of oral cancer with DII. Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science databases for relevant articles published up to 1 March 2022. Fixed- or random-effects models were utilized to estimate the pooled odds ratio (OR) of oral cancer with DII, as appropriate. Restricted cubic splines were used to model the dose-response relationship. Results: We included five case-control studies involving 1,278 cases and 5,137 controls in the meta-analysis. Risk of oral cancer was increased by 135% with the highest versus lowest DII level [OR: 2.35, 95% confidence interval (CI): 1.88-2.94], and 79% with higher versus lower DII level (OR: 1.79, 95% CI: 1.49-2.15). We found no evidence of a nonlinear dose-response association of DII with oral cancer (pnon-linearity = 0.752), and the risk was increased by 17% (OR: 1.17, 95% CI: 1.05-1.30) with 1 unit increment in DII score. Conclusion: This meta-analysis suggested that a higher DII score was associated with increased risk of oral cancer. Therefore, reducing pro-inflammatory components and promoting anti-inflammatory components of diet may be effective in the prevention of oral cancer.

[Pathogenesis of Psoriatic Pruritus].

Pruritus is a common symptom of most primary skin diseases and some systemic diseases. Despite the high incidence of pruritus in patients with psoriasis,the specific pathogenesis is complex and unclear. The occurrence and development of skin pruritus in psoriasis patients involve the joint participation of nervous,immune,endocrine,and vascular systems.This article reviews the mediators related to the pathogenesis of pruritus in psoriasis,aiming to improve the understanding of itching symptoms and the treatment of pruritus.

Decoupled temperature and pressure hydrothermal synthesis of carbon sub-micron spheres from cellulose.

The temperature and pressure of the hydrothermal process occurring in a batch reactor are typically coupled. Herein, we develop a decoupled temperature and pressure hydrothermal system that can heat the cellulose at a constant pressure, thus lowering the degradation temperature of cellulose significantly and enabling the fast production of carbon sub-micron spheres. Carbon sub-micron spheres can be produced without any isothermal time, much faster compared to the conventional hydrothermal process. High-pressure water can help to cleave the hydrogen bonds in cellulose and facilitate dehydration reactions, thus promoting cellulose carbonization at low temperatures. A life cycle assessment based on a conceptual biorefinery design reveals that this technology leads to a substantial reduction in carbon emissions when hydrochar replacing fuel or used for soil amendment. Overall, the decoupled temperature and pressure hydrothermal treatment in this study provides a promising method to produce sustainable carbon materials from cellulose with a carbon-negative effect.