Association between dietary magnesium intake and muscle mass among hypertensive population: evidence from the National Health and Nutrition Examination Survey.

BACKGROUND: Magnesium is critical for musculoskeletal health. Hypertensive patients are at high risk for magnesium deficiency and muscle loss. This study aimed to explore the association between magnesium intake and muscle mass in patients with hypertension. METHODS: In this population-based cross-sectional study, 10,279 U.S. hypertensive adults aged 20 years or older were derived from the National Health and Nutrition Examination Survey in 1999-2006 and 2011-2018. Magnesium (Mg) intake from diet and supplements was assessed using 24-hour diet recalls. Muscle mass was evaluated by appendicular skeletal muscle mass index (ASMI, total ASM in kilograms [kg] divided by square of height in meters [m2]). The association of Mg intake with ASMI was estimated using weighted multivariable-adjusted linear regression models and restricted cubic splines. RESULTS: Dose-response analyses showed a positive linear correlation between dietary Mg intake and ASMI. Every additional 100 mg/day in dietary Mg was associated with 0.04 kg/m2 (95% confidence interval [CI] 0.02-0.06 kg/m2) higher ASMI. The ASMI in participants who met the recommended dietary allowance (RDA) for dietary Mg was 0.10 kg/m2 (95% CI 0.04-0.16 kg/m2) higher than those whose dietary Mg was below estimated average requirement (EAR). However, the relationship of Mg intake from supplements with ASMI was not identified. CONCLUSION: Higher level of dietary Mg intake rather than Mg supplements was associated with more muscle mass in U.S. adults with hypertension, which highlights the importance of meeting the recommended levels for dietary Mg intake.

Assessing the impact of gait speed on gait stability using multi-scale entropy fused with plantar pressure signals.

Introduction: Walking speed can affect gait stability and increase the risk of falling. Methods: In this study, we design a device to measure the distribution of the plantar pressure to investigate the impact of the walking speed on the stability of the human gait and movements of the body. We fused the entropy acquired at multiple scales with signals of the plantar pressure to evaluate the effects of the walking speed on the stability of the human gait. We simultaneously collected data on the motion-induced pressure from eight plantar regions to obtain the fused regional pressure. To verify their accuracy, we obtained data on the plantar pressure during walking by using the force table of the Qualisys system. We then extracted the peak points and intervals of the human stride from pressure signals fused over three regions, and analyzed the mechanics of their regional fusion by using the regional amplitude-pressure ratio to obtain the distribution of the plantar pressure at an asynchronous walking speed. Furthermore, we introduced multi-scale entropy to quantify the complexity of the gait and evaluate its stability at different walking speeds. Results: The results of experiments showed that increasing the speed from 2 to 6 km/h decreased the stability of the gait, with a 26.7% increase in the amplitude of pressure in the region of the forefoot. The hindfoot and forefoot regions were subjected to the minimal pressure at a speed of 2 km/h, while the most consistent stress was observed in regions of the forefoot, midfoot, and hindfoot. Moreover, the curve of entropy at a speed of 2 km/h exhibited a slow decline at a small scale and high stability at a large scale. Discussion: The multi-scale entropy increased the variation in the stability of the synchronous velocity of walking compared with the sample entropy and the analysis of regional fusion mechanics. Multi-scale entropy can thus be used to qualitatively assess the relationship between the speed and stability of the gait, and to identify the most stable gait speed that can ensure gait stability and posture control.

High Accuracy Prediction of PROTAC Complex Structures.

The design of PROteolysis-TArgeting Chimeras (PROTACs) requires bringing an E3 ligase into proximity with a target protein to modulate the concentration of the latter through its ubiquitination and degradation. Here, we present a method for generating high-accuracy structural models of E3 ligase-PROTAC-target protein ternary complexes. The method is dependent on two computational innovations: adding a "silent" convolution term to an efficient protein-protein docking program to eliminate protein poses that do not have acceptable linker conformations and clustering models of multiple PROTACs that use the same E3 ligase and target the same protein. Results show that the largest consensus clusters always have high predictive accuracy and that the ensemble of models can be used to predict the dissociation rate and cooperativity of the ternary complex that relate to the degrading activity of the PROTAC. The method is demonstrated by applications to known PROTAC structures and a blind test involving PROTACs against BRAF mutant V600E. The results confirm that PROTACs function by stabilizing a favorable interaction between the E3 ligase and the target protein but do not necessarily exploit the most energetically favorable geometry for interaction between the proteins.

Discovery and Structural Characterization of Small Molecule Binders of the Human CTLH E3 Ligase Subunit GID4.

Targeted protein degradation (TPD) strategies exploit bivalent small molecules to bridge substrate proteins to an E3 ubiquitin ligase to induce substrate degradation. Few E3s have been explored as degradation effectors due to a dearth of E3-binding small molecules. We show that genetically induced recruitment to the GID4 subunit of the CTLH E3 complex induces protein degradation. An NMR-based fragment screen followed by structure-guided analog elaboration identified two binders of GID4, 16 and 67, with Kd values of 110 and 17 µM in vitro. A parallel DNA-encoded library (DEL) screen identified five binders of GID4, the best of which, 88, had a Kd of 5.6 µM in vitro and an EC50 of 558 nM in cells with strong selectivity for GID4. X-ray co-structure determination revealed the basis for GID4-small molecule interactions. These results position GID4-CTLH as an E3 for TPD and provide candidate scaffolds for high-affinity moieties that bind GID4.

SENP1 protects cisplatin-induced AKI by attenuating apoptosis through regulation of HIF-1α.

BACKGROUND: Acute kidney injury is a clinical syndrome with both high morbidity and mortality. However, the underlying molecular mechanism of AKI is still largely unknown. The role of SENP1 in AKI is unclear, while one of its substrates, HIF-1α possesses nephroprotective effect in AKI. Herein, this study aimed to reveal the role of SENP1/HIF-1α axis in AKI by using both cell and animal models. METHODS: We investigated the effects of AKI on SENP1 expression using clinical samples, and cisplatin-induced AKI model based on mice or HK-2 cells. The influence of SENP1 knockdown or over-expression on cisplatin-induced AKI was studied in vitro and in vivo. Following the exploration of the change in HIF-1α expression brought by AKI, the synergistic effects of SENP1 knockdown and HIF-1α over-expression on AKI were examined. RESULTS: The results showed the up-regulation of SENP1 in clinical specimens, as well as cell and animal models. The knockdown or over-expression of SENP1 in HK-2 cells could promote or inhibit AKI through regulating cell apoptosis, respectively. Moreover, SENP1+/- mice suffered from much more serious AKI compared with mice in wild type group. Furthermore, we found that HIF-1α over-expression could attenuate the promoted cell apoptosis as well as AKI induced by SENP1 knockdown. CONCLUSIONS: we showed that SENP1 provided protection for kidney in AKI via regulating cell apoptosis and through the regulation of HIF-1α. This study could benefit for the understanding of the pathogenesis of AKI and provide potential therapeutic target for AKI treatment.

In-center Nocturnal Hemodialysis Reduced the Circulating FGF23, Left Ventricular Hypertrophy, and All-Cause Mortality: A Retrospective Cohort Study.

Fibroblast growth factor 23(FGF23) is the most important biomarker and pathogenic factor in Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). In the moderate and severe stages of chronic renal failure, abnormally elevated circulating FGF23 can lead to some complications, including myocardial hypertrophy, which is positively correlated with all-cause mortality. However, the circulating FGF23 level of different hemodialysis modalities, the underlying essential regulatory factors, and potential clinical benefits remain to be elucidated. In this retrospective cohort study, 90 in-center nocturnal hemodialysis (INHD) and 90 matched conventional hemodialysis (CHD) patients were enrolled. The complete blood count, intact FGF23(iFGF23), calcium, phosphorus, PTH, and other biochemical and echocardiographic parameters of INHD and CHD patients were collected and analyzed at 1-year follow-up. The all-cause mortality was recorded during the 7-year follow-up. Furthermore, the regulatory factors of iFGF23 and its association with echocardiographic parameters and mortality were investigated by multivariate regression. The levels of iFGF23 and serum phosphate in patients undergoing INHD were significantly lower than those in patients undergoing CHD. The left ventricular volume index (LVMI) in patients with INHD was significantly attenuated and positively correlated with the drop of serum iFGF23. The INHD group had reduced all-cause mortality compared to the CHD group. Multivariate analysis showed that iFGF23 was positively correlated with serum calcium, serum phosphorus, and calcium-phosphate product. The calcium-phosphate product is an independent determining factor of serum iFGF23. Compared with the CHD group, the INHD group presented with a significantly reduced circulating iFGF23 level, which was closely associated with attenuation of left ventricular hypertrophy, but INHD reduced all-cause mortality in an FGF23 independent manner.

The microprotein Nrs1 rewires the G1/S transcriptional machinery during nitrogen limitation in budding yeast.

Commitment to cell division at the end of G1 phase, termed Start in the budding yeast Saccharomyces cerevisiae, is strongly influenced by nutrient availability. To identify new dominant activators of Start that might operate under different nutrient conditions, we screened a genome-wide ORF overexpression library for genes that bypass a Start arrest caused by absence of the G1 cyclin Cln3 and the transcriptional activator Bck2. We recovered a hypothetical gene YLR053c, renamed NRS1 for Nitrogen-Responsive Start regulator 1, which encodes a poorly characterized 108 amino acid microprotein. Endogenous Nrs1 was nuclear-localized, restricted to poor nitrogen conditions, induced upon TORC1 inhibition, and cell cycle-regulated with a peak at Start. NRS1 interacted genetically with SWI4 and SWI6, which encode subunits of the main G1/S transcription factor complex SBF. Correspondingly, Nrs1 physically interacted with Swi4 and Swi6 and was localized to G1/S promoter DNA. Nrs1 exhibited inherent transactivation activity, and fusion of Nrs1 to the SBF inhibitor Whi5 was sufficient to suppress other Start defects. Nrs1 appears to be a recently evolved microprotein that rewires the G1/S transcriptional machinery under poor nitrogen conditions.

Elevated growth and biomass along temperate forest edges.

Fragmentation transforms the environment along forest edges. The prevailing narrative, driven by research in tropical systems, suggests that edge environments increase tree mortality and structural degradation resulting in net decreases in ecosystem productivity. We show that, in contrast to tropical systems, temperate forest edges exhibit increased forest growth and biomass with no change in total mortality relative to the forest interior. We analyze >48,000 forest inventory plots across the north-eastern US using a quasi-experimental matching design. At forest edges adjacent to anthropogenic land covers, we report increases of 36.3% and 24.1% in forest growth and biomass, respectively. Inclusion of edge impacts increases estimates of forest productivity by up to 23% in agriculture-dominated areas, 15% in the metropolitan coast, and +2% in the least-fragmented regions. We also quantify forest fragmentation globally, at 30-m resolution, showing that temperate forests contain 52% more edge forest area than tropical forests. Our analyses upend the conventional wisdom of forest edges as less productive than intact forest and call for a reassessment of the conservation value of forest fragments.

Identification and optimization of molecular glue compounds that inhibit a noncovalent E2 enzyme-ubiquitin complex.

Pharmacological control of the ubiquitin-proteasome system (UPS) is of intense interest in drug discovery. Here, we report the development of chemical inhibitors of the ubiquitin-conjugating (E2) enzyme CDC34A (also known as UBE2R1), which donates activated ubiquitin to the cullin-RING ligase (CRL) family of ubiquitin ligase (E3) enzymes. A FRET-based interaction assay was used to screen for novel compounds that stabilize the noncovalent complex between CDC34A and ubiquitin, and thereby inhibit the CDC34A catalytic cycle. An isonipecotamide hit compound was elaborated into analogs with ~1000-fold increased potency in stabilizing the CDC34A-ubiquitin complex. These analogs specifically inhibited CDC34A-dependent ubiquitination in vitro and stabilized an E2~ubiquitin thioester reaction intermediate in cells. The x-ray crystal structure of a CDC34A-ubiquitin-inhibitor complex uncovered the basis for analog structure-activity relationships. The development of chemical stabilizers of the CDC34A-ubiquitin complex illustrates a general strategy for de novo discovery of molecular glue compounds that stabilize weak protein interactions.

PKD2 gene variants in Chinese patients with autosomal dominant polycystic kidney disease.

PKD2 gene variants account for 4.5% to 20% of patients with autosomal dominant polycystic kidney disease (ADPKD). Little is known about the clinical characteristics of PKD2 variants in Chinese patients with ADPKD. Herein, we performed a comprehensive search for variants of PKD2 gene in 44 Chinese ADPKD pedigrees and a total of 37 variants were identified. Of these 37 variants, 18 were nonsense variants, 10 frameshift variants, 4 missense variants, and 5 splice site variants. 11/37 variants were detected for the first time. The median age at diagnosis was 30.5 years, and positive family history was detected in 77.27% patients, liver cysts in 68.18%, hypertension in 45.45%, nephrolithiasis in 31.82%, macro-hematuria in 22.73%, and proteinuria in 13.63%. The level of estimated glomerular filtration rate in 8/39 patients were blow 60 ml/min/1.73m2 . 11/17 patients were classified as rapid progression by Mayo Clinic classification. The end stage renal disease (ESRD) events were reported in 9/22 pedigrees, and the presence of nephrolithiasis and macro-hematuria were significantly associated with ESRD in the pedigrees with PKD2 variants. The identified variants and clinical features will facilitate the early diagnosis and prognosis prediction in Chinese ADPKD patients with PKD2 variants.

Hyperoxalemia Leads to Oxidative Stress in Endothelial Cells and Mice with Chronic Kidney Disease.

INTRODUCTION: Cardiovascular disease is the most common cause of morbidity and mortality in patients with ESRD. In addition to phosphate overload, oxalate, a common uremic toxin, is also involved in vascular calcification in patients with ESRD. The present study investigated the role and mechanism of hyperoxalemia in vascular calcification in mice with uremia. METHODS: A uremic atherosclerosis (UA) model was established by left renal excision and right renal electrocoagulation in apoE-/- mice to investigate the relationship between oxalate loading and vascular calcification. After 12 weeks, serum and vascular levels of oxalate, vascular calcification, inflammatory factors (TNF-α and IL-6), oxidative stress markers (malondialdehyde [MDA], and advanced oxidation protein products [AOPP]) were assessed in UA mice. The oral oxalate-degrading microbe Oxalobacter formigenes (O. formigenes) was used to evaluate the effect of a reduction in oxalate levels on vascular calcification. The mechanism underlying the effect of oxalate loading on vascular calcification was assessed in cultured human aortic endothelial cells (HAECs) and human aortic smooth muscle cells (HASMCs). RESULTS: Serum oxalate levels were significantly increased in UA mice. Compared to the control mice, UA mice developed more areas of aortic calcification and showed significant increases in aortic oxalate levels and serum levels of oxidative stress markers and inflammatory factors. The correlation analysis showed that serum oxalate levels were positively correlated with the vascular oxalate levels and serum MDA, AOPP, and TNF-α levels, and negatively correlated with superoxide dismutase activity. The O. formigenes intervention decreased serum and vascular oxalate levels, while did not improve vascular calcification significantly. In addition, systemic inflammation and oxidative stress were also improved in the O. formigenes group. In vitro, high concentrations of oxalate dose-dependently increased oxidative stress and inflammatory factor expression in HAECs, but not in HASMCs. CONCLUSIONS: Our results indicated that hyperoxalemia led to the systemic inflammation and the activation of oxidative stress. The reduction in oxalate levels by O. formigenes might be a promising treatment for the prevention of oxalate deposition in calcified areas of patients with ESRD.

Genomic driven factors enhance biocatalyst-related cellulolysis potential in anaerobic digestion.

Anaerobic digestion (AD) is a promising technology to recover bioenergy from biodegradable biomass, including cellulosic wastes. Through a few fractionation/separation techniques, cellulose has demonstrated its potential in AD, but the performance of the process is rather substrate-specific, as cellulolysis bacteria are sensitive to the enzyme-substrate interactions. Cellulosome is a self-assembled enzyme complex with many functionalized modules in the bacteria which has been gradually studied, however the genomic fingerprints of the culture-specific cellulosome in AD are relatively unclear especially under processing conditions. To clarify the key factors affecting the cellulosome induced cellulolysis, this review summarized the most recent publications of AD regarding the fates of cellulose, sources and functional genes of cellulosome, and omics methods for functional analyses. Different processes for organic treatment including applying food grinds in sewer, biomass valorization, cellulose fractionation, microaeration, and enzymatic hydrolysis enhanced fermentation, were highlighted to support the sustainable development of AD technology.

Prognosis of Diabetic Peripheral Neuropathy via Decomposed Digital Volume Pulse from the Fingertip.

Diabetic peripheral neuropathy (DPN) is a very common neurological disorder in diabetic patients. This study presents a new percussion-based index for predicting DPN by decomposing digital volume pulse (DVP) signals from the fingertip. In this study, 130 subjects (50 individuals 44 to 89 years of age without diabetes and 80 patients 37 to 86 years of age with type 2 diabetes) were enrolled. After baseline measurement and blood tests, 25 diabetic patients developed DPN within the following five years. After removing high-frequency noise in the original DVP signals, the decomposed DVP signals were used for percussion entropy index (PEIDVP) computation. Effects of risk factors on the incidence of DPN in diabetic patients within five years of follow-up were tested using binary logistic regression analysis, controlling for age, waist circumference, low-density lipoprotein cholesterol, and the new index. Multivariate analysis showed that patients who did not develop DPN in the five-year period had higher PEIDVP values than those with DPN, as determined by logistic regression model (PEIDVP: odds ratio 0.913, 95% CI 0.850 to 0.980). This study shows that PEIDVP can be a major protective factor in relation to the studied binary outcome (i.e., DPN or not in diabetic patients five years after baseline measurement).

Functional characterization of a PROTAC directed against BRAF mutant V600E.

The RAF family kinases function in the RAS-ERK pathway to transmit signals from activated RAS to the downstream kinases MEK and ERK. This pathway regulates cell proliferation, differentiation and survival, enabling mutations in RAS and RAF to act as potent drivers of human cancers. Drugs targeting the prevalent oncogenic mutant BRAF(V600E) have shown great efficacy in the clinic, but long-term effectiveness is limited by resistance mechanisms that often exploit the dimerization-dependent process by which RAF kinases are activated. Here, we investigated a proteolysis-targeting chimera (PROTAC) approach to BRAF inhibition. The most effective PROTAC, termed P4B, displayed superior specificity and inhibitory properties relative to non-PROTAC controls in BRAF(V600E) cell lines. In addition, P4B displayed utility in cell lines harboring alternative BRAF mutations that impart resistance to conventional BRAF inhibitors. This work provides a proof of concept for a substitute to conventional chemical inhibition to therapeutically constrain oncogenic BRAF.

[A retrospective study on risk factors for prognosis of children with sepsis].

OBJECTIVE: To explore the risk factors that may affect the prognosis of sepsis in children. METHODS: A retrospective study was conducted. Septic children who aged 28 days to 18 years old admitted to the department of critical care medicine of Xi'an Children's Hospital from January 2018 to May 2019 were enrolled. The general demographic data and clinical indicators within 8 hours after admission were collected, and the 28-day mortality was the end point. The differences of the indexes between the survival and the dead children were compared, and the risk factors of prognosis by binary Logistic regression analysis were analyzed. The predictive value of related risk factors on the prognosis was verified by receiver operating characteristic (ROC) curve. RESULTS: A total of 165 children with sepsis were selected, 75 died in 28-days with a 28-day mortality of 45.45%. Compared with the survival group, the alanine aminotransferase (ALT), aspertate aminotransferase (AST), serum creatinine (SCr), creatine kinase isoenzyme (CK-MB), lactate (Lac) and procalcitonin (PCT) in the dead group significantly increased [ALT (U/L): 404.99±88.26 vs. 181.64±35.17, AST (U/L): 453.37±35.37 vs. 210.69±92.50, SCr (µmol/L): 156.46±105.65 vs. 54.32±25.46, CK-MB (U/L): 244.86±53.68 vs. 97.29±19.11, Lac (mmol/L): 5.55±1.66 vs. 2.49±1.29, PCT (ng/L): 35.55±15.87 vs. 18.66±4.91, all P < 0.01], while platelet count (PLT), serum ionized calcium concentration (iCa2+) significantly decreased [PLT (×109/L): 81.49±29.53 vs. 165.43±97.81, iCa2+ (mmol/L): 0.89±0.16 vs. 1.84±0.14, both P < 0.01]. There was no significant difference in gender, age, prothrombin time (PT), activated partial thromboplastin time (APTT), albumin (ALB) and blood urea nitrogen (BUN) between the two groups. Binary Logistic regression analysis showed that Lac, SCr and PCT were the risk factors for the prognosis of children with sepsis [odds ratio (OR) and 95% confidence interval (95%CI) were 2.18 (1.22-3.09), 2.01 (1.00-2.07), 1.14 (1.07-1.21), respectively, all P < 0.01], while PLT and iCa2+ were protective factors [OR and 95%CI were 0.95 (0.93-0.98), 0.32 (0.12-0.42), respectively, both P < 0.01]. Further ROC curve analysis showed that Lac, PCT and SCr were all of predictive value for the prognosis of children with sepsis, and the area under ROC curve (AUC) was 0.881, 0.864, 0.711, respectively (all P < 0.01); the combined predicted AUC of Lac, SCr, PCT, PLT and iCa2+ influencing factors was as high as 0.981, with the sensitivity of 97.6%, and the specificity of 98.7%. CONCLUSIONS: Lac, PCT and SCr are independent risk factors for the prognosis of children with sepsis.

Effect of Sheng Xue Ning Tablets on Renal Anemia in Patients Subject to Maintenance Hemodialysis and Safety Evaluation: A Multi-setting Prospective Randomized Study.

This study compared Sheng Xue Ning (SXN) tablets with ferrous succinate (FS) tablets in terms of their efficacy for the treatment of iron-deficient renal anemia and safety in patients subject to maintenance hemodialysis (MHD). A total of 94 patients undergoing MHD were randomly assigned to an experiment group (receiving oral SXN tablets, SXN group) and a control group (orally given FS tablets, FS group) and followed up for 12 weeks. Erythropoietin (EPO) was used in both groups. The efficacy was assessed by detecting the subsequent changes in hemoglobin (Hb), serum iron (SI), SF and transferrin saturation (TSAT). At the 12th week, Hb and TSAT levels in both groups were significantly increased compared to those in the screening period (P<0.05). However, no significant difference in Hb and TSAT was found between the two groups. The average weekly EPO dosage used was lower in SXN group than in FS group (P<0.05) at the 10th week and the 12th week. Our study showed that SXN tablets can effectively ameliorate renal anemia and keep iron metabolism stable in MHD patients, and its efficacy is virtually close to that of FS tablets. Meanwhile, SXN tablets can reduce the dosage of EPO and have a good safety profile.

SOCS3 protects against neonatal necrotizing enterocolitis via suppressing NLRP3 and AIM2 inflammasome activation and p65 nuclear translocation.

BACKGROUND: Necrotizing enterocolitis (NEC) is an acquired disorder of mucosal damage characterized by the diffuse or local necrosis of the intestine. The suppressor of cytokine signaling 3 (SOCS3) has been demonstrated to possess anti-inflammatory action in gastritis, ulcerative colitis and other inflammatory diseases. The present study aims to explore the effects of SOCS3 on LPS-induced colonic cell model of NEC, and investigate the underlying mechanisms. METHODS: Expression of SOCS3 in tissue samples of NEC and LPS-induced enterocytes were evaluated by real-time quantitative PCR (RT-qPCR). Western blotting and enzyme-linked immunosorbent assay (ELISA) were applied to examine the effect of SOCS3 on inflammatory molecules. Co-immunoprecipitation assay were devoted to explore the relation between SOCS3 and TLR4. RESULTS: We proved that SOCS3 was expressed at a low level in tissue samples of NEC and LPS-induced enterocytes, and LPS inhibited SOCS3 expression via JAK2/STAT3 pathway. Overexpression of SOCS3 weaken the LPS-induced inflammatory response in FHC and CACO2 cells. Moreover, SOCS3 downregulates proinflammatory cytokines by targeting TLR4, thus mediating the p65 nuclear translocation, and the activation of NLR family pyrin domain containing 3/absent in melanoma-2 (NLRP3/AIM2) inflammasome, ultimately reveals its anti-inflammatory effects. CONCLUSIONS: Taken together, our data revealed that LPS inhibited SOCS3 expression via JAK2/STAT3 pathway, and SOCS3 protects enterocytes against NEC through mediating p65 nuclear translocation and NLRP3/AIM2 inflammasome activation in a TLR4 dependent manner.

Spatiotemporal tracking of carbon emissions and uptake using time series analysis of Landsat data: A spatially explicit carbon bookkeeping model.

Reducing terrestrial carbon emissions to the atmosphere requires accurate measuring, reporting and verification of land surface activities that emit or sequester carbon. Many carbon accounting practices in use today provide only regionally aggregated estimates and neglect the spatial variation of pre-disturbance forest conditions and post-disturbance land cover dynamics. Here, we present a spatially explicit carbon bookkeeping model that utilizes a high-resolution map of aboveground biomass and land cover dynamics derived from time series analysis of Landsat data. The model produces estimates of carbon emissions/uptake with model uncertainty at Landsat resolution. In a case study of the Colombian Amazon, an area of 47 million ha, the model estimated total emissions of 3.97 ± 0.71 Tg C yr-1 and uptake by regenerating forests of 1.11 ± 0.23 Tg C yr-1 2001-2015, with an additional 45.1 ± 7.99 Tg of carbon remaining in the form of woody products, decomposing slash and charcoal at the end of 2015 (estimates provided with ±95% confidence intervals). Total emissions attributed to the study period (including carbon not yet released) is 6.97 ± 1.24 Tg C yr-1. The presented model is based on recent technological advancements in the field of remote sensing to achieve spatially explicit modeling of carbon emissions and uptake associated with land surface changes and post-disturbance landscapes that is compliant with international reporting criteria.