Baricitinib protects ICIs-related myocarditis by targeting JAK1/STAT3 to regulate Macrophage polarization.

PURPOSE: The emergence of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, but these drugs can also cause severe immune-related adverse effects (irAEs), including myocarditis. Researchers have become interested in exploring ways to mitigate this side effect, and one promising avenue is the use of baricitinib, a Janus kinase inhibitor known to have anti-inflammatory properties. This study aimed to examine the potential mechanism by which baricitinib in ICIs-related myocarditis. METHODS: To establish an ICIs-related myocarditis model, BALB/c mice were administered murine cardiac troponin I (cTnI) peptide and anti-mouse programmed death 1 (PD-1) antibodies. Subsequently, baricitinib was administered to the mice via intragastric administration. Echocardiography, HE staining, and Masson staining were performed to evaluate myocardial functions, inflammation, and fibrosis. Immunofluorescence was used to detect macrophages in the cardiac tissue of the mice.In vitro experiments utilized raw264.7 cells to induce macrophage polarization using anti-PD-1 antibodies. Different concentrations of baricitinib were applied to assess cell viability, and the release of pro-inflammatory cytokines was measured. The activation of the JAK1/STAT3 signaling pathway was evaluated through western blot analysis. RESULTS: Baricitinib demonstrated its ability to improve cardiac function and reduce cardiac inflammation, as well as fibrosis induced by ICIs. Mechanistically, baricitinib treatment promoted the polarization of macrophages towards the M2 phenotype. In vitro and in vivo experiments showed that anti-PD-1 promoted the release of inflammatory factors. However, treatment with baricitinib significantly inhibited the phosphorylation of JAK1 and STAT3. Additionally, the use of RO8191 reversed the effects of baricitinib, further confirming our findings. CONCLUSION: Baricitinib demonstrated its potential as a protective agent against ICIs-related myocarditis by modulating macrophage polarization. These findings provide a solid theoretical foundation for the development of future treatments for ICIs-related myocarditis.

Left atrial reservoir longitudinal strain and its incremental value to the left ventricular global longitudinal strain in predicting anthracycline-induced cardiotoxicity.

BACKGROUND: Left ventricular global longitudinal strain (LVGLS) has been recommended by current guidelines for diagnosing anthracycline-induced cardiotoxicity. However, little is known about the early changes in left atrial (LA) morphology and function in this population. Our study aimed to evaluate the potential usefulness of LA indices and their incremental value to LVGLS with three-dimensional echocardiography (3DE) in the early detection of subclinical cardiotoxicity in patients with lymphoma receiving anthracycline. METHODS: A total of 80 patients with diffuse large B-cell lymphoma who received six cycles of anthracycline-based treatment were enrolled. Echocardiography was performed at baseline (T0), after four cycles (T1), and after the completion of six cycles of chemotherapy (T2). Left ventricular ejection fraction (LVEF), LVGLS, LA volumes, LA emptying fraction (LAEF), LA active emptying fraction (LAAEF), and LA reservoir longitudinal strain (LASr) were quantified with 3DE. Left atrioventricular global longitudinal strain (LAVGLS) was calculated as the sum of peak LASr and the absolute value of peak LVGLS (LAVGLS = LASr+|LVGLS|). LV cardiotoxicity was defined as a new LVEF reduction by ≥10 percentage points to an LVEF of ≤50%. RESULTS: Fourteen (17.5%) patients developed LV cardiotoxicity at T2. LA volumes, LAEF, and LAAEF remained stable over time. Impairment of LASr (28.35 ± 5.03 vs. 25.04 ± 4.10, p < .001), LVGLS (-22.77 ± 2.45 vs. -20.44 ± 2.62, p < .001), and LAVGLS (51.12 ± 5.63 vs. 45.61 ± 5.22, p < .001) was observed by the end of the fourth cycle of chemotherapy (T1). Statistically significant declines in LVEF (61.30 ± 4.73 vs. 57.08 ± 5.83, p < .001) were only observed at T2. The relative decrease in LASr (ΔLASr), LVGLS (ΔLVGLS), and LAVGLS (ΔLAVGLS) from T0 to T1 were predictors of LV cardiotoxicity. A ΔLASr of >19.75% (sensitivity, 71.4%; specificity, 87.9%; area under the curve (AUC), .842; p < .001), a ΔLVGLS of >13.19% (sensitivity, 78.6%; specificity, 74.2%; AUC, .763; p < .001), and a ΔLAVGLS of >16.80% (sensitivity, 78.6%; specificity, 93.9%; AUC, .905; p < .001) predicted subsequent LV cardiotoxicity at T2, with the AUC of ΔLAVGLS significantly larger than that of ΔLVGLS (.905 vs. .763, p = .027). Compared to ΔLVGLS, ΔLAVGLS showed improved specificity (93.9% vs. 74.2%, p = .002) and maintained sensitivity in predicting LV cardiotoxicity. CONCLUSIONS: LASr could predict anthracycline-induced LV cardiotoxicity with excellent diagnostic performance. Incorporating LASr into LVGLS (LAVGLS) led to a significantly improved specificity and maintained sensitivity in predicting LV cardiotoxicity.

Coronary hemodynamic simulation study.

In this paper, a two-way fluid-structure coupling model is developed to simulate and analyze the hemodynamic process based on dynamic coronary angiography, and examine the influence of different hemodynamic parameters on coronary arteries in typical coronary stenosis lesions. Using the measured FFR pressure data of a patient, the pressure-time function curve is fitted to ensure the accuracy of the boundary conditions. The average error of the simulation pressure results compared to the test data is 6.74%. In addition, the results related to blood flow, pressure contour and wall shear stress contour in a typical cardiac cycle are obtained by simulation analysis. These results are found to be in good agreement with the laws of the real cardiac cycle, which verifies the rationality of the simulation. In conclusion, based on the modeling and hemodynamic simulation analysis process of dynamic coronary angiography, this paper proposes a method to assist the analysis and evaluation of coronary hemodynamic and functional parameters, which has certain practical significance.

Cardiac magnetic resonance-based layer-specific strain in immune checkpoint inhibitor-associated myocarditis.

AIMS: To assess the different imaging characteristics between corticosteroid-sensitive (CS) and corticosteroid-refractory (CR) immune checkpoint inhibitor-associated myocarditis (ICIaM) with cardiac magnetic resonance (CMR) and the potential CMR parameters in the early detection of CR ICIaM. METHODS AND RESULTS: Thirty-five patients diagnosed with ICIaM and 30 age and gender-matched cancer patients without a history of ICI treatment were enrolled. CMR with contrast was performed within 2 days of clinical suspicion. Left ventricular ejection fraction (LVEF) and late gadolinium enhancement (LGE) were assessed by CMR. LV sub-endocardial (GLSendo) and sub-epicardial (GLSepi) global longitudinal strains were quantified by offline feature tracking analysis. CS and CR ICIaM were defined based on the trend of Troponin I and clinical course during corticosteroid treatment. All 35 patients presented with non-fulminant symptoms upon initial assessment. Twenty patients (57.14%) were sensitive, and 15 (42.86%) were refractory to corticosteroids. Compared with controls, 22 patients (62.86%) with ICIaM developed LGE. LVEF decreased in CR ICIaM compared with the CS group and controls. GLSendo (-14.61 ± 2.67 vs. -18.50 ± 2.53, P < 0.001) and GLSepi (-14.75 ± 2.53 vs. -16.68 ± 2.05, P < 0.001) significantly increased in patients with CR ICIaM compared with the CS ICIaM. In patients with CS ICIaM, although GLSepi (-16.68 ± 2.05 vs. -19.31 ± 1.80, P < 0.001) was impaired compared with the controls, GLSendo was preserved. There was no difference in CMR parameters between LGE-positive and negative groups. LVEF, GLSendo, and GLSepi were predictors of CR ICIaM. When LVEF, GLSendo, and GLSepi were included in multivariate analysis, only GLSendo remained an independent predictor of CR ICIaM (OR: 2.170, 95% CI: 1.189-3.962, P = 0.012). A GLSendo of ≥-17.10% (sensitivity, 86.7%; specificity, 80.0%; AUC, 0.860; P < 0.001) could predict CR ICIaM in the ICIaM cohort. Kaplan-Meier analysis showed that in patients with impaired GLSendo of ≥-17.10%, cardiovascular adverse events (CAEs) occurred much earlier than in patients with preserved GLSendo of <-17.10% (Log-rank test P = 0.017). CONCLUSIONS: CR and CS ICIaM demonstrated different functional and morphological characteristics in different myocardial layers. An impaired GLSendo could be a helpful parameter in early identifying corticosteroid-refractory individuals in the ICIaM population.

Effects of Wind-Water Erosion and Topographic Factor on Soil Properties in the Loess Hilly Region of China.

Wind and water erosion processes can lead to soil degradation. Topographic factors also affect the variation of soil properties. The effect of topographic factors on soil properties in regions where wind and water erosion simultaneously occur remains complicated. To address this effect, we conducted this study to determine the relationships between the changes in wind-water erosion and soil properties in different topographic contexts. We collected soil samples from conical landforms with different slope characteristics and positions in the wind-water erosion crisscross region of China. We examined the soil 137Cs inventory, soil organic carbon (SOC), total nitrogen (TN), soil particles, soil water content (SWC), and biomass. 137Cs was applied to estimate soil erosion. The results show that the soil erosion rate followed the order of northwest slope > southwest slope > northeast slope > southeast slope. The soil erosion rate on the northwest slope was about 12.06-58.47% higher than on the other. Along the slopes, the soil erosion rate decreased from the upper to the lower regions, and was 65.65% higher at the upper slope than at the lower one. The change in soil erosion rate was closely related to soil properties. The contents of SOC, TN, clay, silt, SWC, and biomass on the northern slopes (northwest and northeast slopes) were lower than those on the southern slopes (southeast and southwest slopes), and they were lower at the upper slope than at the lower one. Redundancy analysis showed that the variation in soil properties was primarily affected by the slope aspect, and less affected by soil erosion, accounting for 56.1% and 30.9%, respectively. The results demonstrate that wind-water erosion accelerates the impact of topographic factors on soil properties under slope conditions. Our research improves our understanding of the mechanisms of soil degradation in gully regions where wind and water erosion simultaneously occur.

Nuclear ATR lysine-tyrosylation protects against heart failure by activating DNA damage response.

Dysregulated amino acid increases the risk for heart failure (HF) via unclear mechanisms. Here, we find that increased plasma tyrosine and phenylalanine levels are associated with HF. Increasing tyrosine or phenylalanine by high-tyrosine or high-phenylalanine chow feeding exacerbates HF phenotypes in transverse aortic constriction and isoproterenol infusion mice models. Knocking down phenylalanine dehydrogenase abolishes the effect of phenylalanine, indicating that phenylalanine functions by converting to tyrosine. Mechanistically, tyrosyl-tRNA synthetase (YARS) binds to ataxia telangiectasia and Rad3-related gene (ATR), catalyzes lysine tyrosylation (K-Tyr) of ATR, and activates the DNA damage response (DDR) in the nucleus. Increased tyrosine inhibits the nuclear localization of YARS, inhibits the ATR-mediated DDR, accumulates DNA damage, and elevates cardiomyocyte apoptosis. Enhancing ATR K-Tyr by overexpressing YARS, restricting tyrosine, or supplementing tyrosinol, a structural analog of tyrosine, promotes YARS nuclear localization and alleviates HF in mice. Our findings implicate facilitating YARS nuclear translocation as a potential preventive and/or interfering measure against HF.

Conversion of Polyethylene to High-Yield Fuel Oil at Low Temperatures and Atmospheric Initial Pressure.

The transformation of waste plastics into fuels via energy-efficient and low-cost pyrolysis could incentivize better waste plastic management. Here, we report pressure-induced phase transitions in polyethylene, which continue to heat up without additional heat sources, prompting the thermal cracking of plastics into premium fuel products. When the nitrogen initial pressure is increased from 2 to 21 bar, a monotonically increasing peak temperature is observed (from 428.1 °C to 476.7 °C). At 21 bar pressure under different atmosphere conditions, the temperature change driven by high-pressure helium is lower than that driven by nitrogen or argon, indicating that phase transition is related to the interaction between long-chain hydrocarbons and intercalated high-pressure medium layers. In view of the high cost of high-pressure inert gases, the promotion or inhibition effect of low-boiling hydrocarbons (transitioning into the gaseous state with increasing temperature) on phase transition is explored, and a series of light components are used as phase transition initiators to replace high-pressure inert gases to experiment. The reason that the quantitative conversion of polyethylene to high-quality fuel products is realized through the addition of 1-hexene at a set temperature of 340 °C and the initial atmospheric pressure. This discovery provides a method for recycling plastics by low energy pyrolysis. In addition, we envisage recovering some of the light components after plastic pyrolysis as phase change initiators for the next batch of the process. This method is able to reduce the cost of light hydrocarbons or high-pressure gas insertion, reduce heat input, and improve material and energy utilization.

Tripartite motif 25 ameliorates doxorubicin-induced cardiotoxicity by degrading p85α.

Doxorubicin (DOX)-based chemotherapy is widely used to treat malignant tumors; however, the cardiotoxicity induced by DOX restricts its clinical usage. A therapeutic dose of DOX can activate ubiquitin-proteasome system. However, whether and how ubiquitin-proteasome system brings out DOX-induced cardiotoxicity remains to be investigated. Here we conducted a proteomics analysis of a DOX-induced cardiotoxicity model to screen the potentially ubiquitination-related molecules. Dysregulated TRIM25 was found to contribute to the cardiotoxicity. In vivo and in vitro cardiotoxicity experiments revealed that TRIM25 ameliorated DOX-induced cardiotoxicity. Electron microscopy and endoplasmic reticulum stress markers revealed that TRIM25 mitigated endoplasmic reticulum stress and apoptosis in DOX-induced cardiomyocytes. Mechanistically, the Co-immunoprecipitation assays and CHX pulse-chase experiment determined that TRIM25 affected p85α stability and promoted its ubiquitination and degradation. This leads to increase of nuclear translocation of XBP-1s, which mitigates endoplasmic reticulum stress. These findings reveal that TRIM25 may have a therapeutic role for DOX-induced cardiotoxicity.

Protective Effect of Crocin on Immune Checkpoint Inhibitors-Related Myocarditis Through Inhibiting NLRP3 Mediated Pyroptosis in Cardiomyocytes via NF-κB Pathway.

Purpose: Immune checkpoint inhibitors (ICIs)-related myocarditis is now one of the most critical immune-related adverse effects (irAEs) in tumor immunotherapy, which has raised great concern in cardio-oncology. The pathogenesis involved in cardiac injury remains elusive. Crocin, the main component of saffron, has shown distinct functions in cardioprotective and anti-inflammation properties. We therefore aimed to investigate the potential effect of crocin on the protection of ICIs-related myocarditis and its underlying molecular mechanism. Methods: We immunized the BALB/c mice with murine cardiac troponin I (cTnI) peptide and additionally gave anti-mouse programmed death 1 (PD-1) to induce the mouse model of ICIs-related myocarditis. Mice were treated with crocin at different dosages. In vitro, HL-1 cells were pre-incubated with crocin at different concentrations and then stimulated with lipopolysaccharide (LPS). Myocardial contractile functions, myocardial inflammation and fibrosis, and myocardial injury were assessed. The expressions of pyroptosis-related proteins and nuclear factor-κB (NF-κB) pathway were evaluated. Results: Crocin treatment could partially reverse the ICIs-related myocarditis in terms of improving heart function, ameliorating inflammation and fibrosis in the myocardium, and alleviating myocardial injury. Mechanistically, ICIs administration significantly activated pyrin domain-containing protein 3 (NLRP3) inflammasome in cardiomyocytes. Crocin treatments significantly downregulated the expression of NLRP3, cleaved gasdermin D (GSDMD), cleaved caspase1, interleukin-1ß (IL-1ß), and IL-18. Besides, crocin inhibited the activation of NF-κB pathway, which performed as reducing the phosphorylation of p-NF-kappa-B inhibitor-α (p-IκBα), degradation of IκBα, phosphorylation of p65 and p65 DNA binding activity both in vivo and in vitro. Conclusion: By reversing the pyroptosis in cardiomyocytes, crocin treatment in a mouse model exerted great potential to aid in the prevention of ICIs-related myocarditis from a novel target.

Right Ventricular Ejection Fraction Assessed by Three-Dimensional Echocardiography Is Associated with Long-Term Adverse Clinical Cardiac Events in Patients with Anthracycline-Induced Cardiotoxicity.

BACKGROUND: Patients with cancer treated with chemotherapy are at risk for cardiovascular toxicity. Global longitudinal strain has been reported to play important roles in predicting cardiovascular adverse events (CAEs) in patients treated with anthracycline. In addition to various left ventricular indicators, the authors hypothesized that right ventricular (RV) parameters might be associated with CAEs related to anthracycline treatment. METHODS: In this retrospective study, 96 patients diagnosed with diffuse large B-cell lymphoma who received chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab) were studied using three-dimensional transthoracic echocardiography. Baseline demographic data and oncologic and echocardiographic parameters were analyzed. The main outcome was the proportion of patients with grade 3 to 5 CAEs. The association of all three-dimensional transthoracic echocardiographic parameters with long-term CAEs was analyzed using Cox proportional-hazard analysis. RESULTS: Over a median follow-up period of 6.1 years (range, 4.9-7.6 years) after the completion of anthracycline chemotherapy, 18 of 96 patients (19%) experienced CAEs. Percentage changes (%Δ) in left ventricular global longitudinal strain (LVGLS), global circumferential strain, RV ejection fraction (RVEF), and RV end-systolic volume were associated with CAEs (P < .05). A relative reduction of RVEF (hazard ratio, 0.847; 95% CI, 0.785-0.915; P < .001) was the strongest associated factor for CAEs. An increase in CAEs was also observed in patients with impaired %ΔLVGLS > 15% and impaired %ΔRVEF > 12.7% compared with those with impaired %ΔLVGLS > 15% and impaired %ΔRVEF < 12.7% (P = .032). CONCLUSIONS: Three-dimensional echocardiography-based assessments of %ΔRVEF and %Δ in RV end-systolic volume were significantly associated with CAEs in patients with lymphoma treated with anthracycline chemotherapy.

Catalytic Pyrolysis of Polyethylene for the Selective Production of Monocyclic Aromatics over the Zinc-Loaded ZSM-5 Catalyst.

The transformation of waste plastics into value-added aromatics could incentivize better waste plastic management. The reported studies had low selectivity for monocyclic aromatics because more polycyclic aromatic hydrocarbons and carbon residues were generated. The effects of temperature, pressure, and catalyst on monocyclic aromatic selectivity were explored using a central composite design (CCD) followed by the response surface methodology (RSM) at a high ramp rate of 15 °C/min. The liquid product yield and selectivity to aromatic hydrocarbons were enhanced by regulating the acidic properties of the catalyst and processing parameters. The proportion of monocyclic aromatics in the liquid product was up to 90%, and the yield of monocyclic aromatics based on the reactant mass was 51% at the optimized condition. The carbon deposit production was low (only approximately 1%), which allowed higher liquid yields. In addition, the coupling mechanism of multiple factors on the depolymerization/aromatization reactions was proposed. This conversion of polyethylene into high-yield monocyclic aromatics provides a viable plastic recycling approach.

Pyrolysis of long chain hydrocarbon-based plastics via self-exothermic effects: The origin and influential factors of exothermic processes.

Converting plastic wastes into value-added products through energy-efficient pyrolysis is essential, and it requires lower pyrolysis temperatures and shorter processing times than that of other processes. An exothermic phenomenon was observed during the process high-pressure polyethylene pyrolysis. It was proven for the first time that the exotherm is caused by a pressure-induced phase transition, in which colossal heat release can be driven by relatively small pressures. A large temperature change (> 100 °C) leads to the deep cracking of polyethylene, although the set temperature is far lower than the required temperature for thermal cracking. Importantly, the heat input stops immediately when the set temperature is reached; thus, the external heating time is short. Polyethylene can be completely converted into liquid products in ~90 wt% yield and with a small number of gases. The self-exothermic phase transition only occurs within a certain range of material thickness, which is related to the corresponding phase behavior. In the self-exothermic pyrolysis process, with an increase in the thickness of polyethylene, the proportion of low-value olefins in oil products decreases gradually, while alkanes, isoalkanes and aromatics show an increasing trend, making the product composition closer to the fuel standard. This work provides a viable approach for plastic recycling at low pyrolysis temperatures and short external heating times with the help of a self-exothermic phase transition in the absence of a catalyst.

Identification of early cardiac dysfunction and heterogeneity after pressure and volume overload in mice by high-frequency echocardiographic strain imaging.

Object: Aortic stenosis and regurgitation are clinically important conditions characterized with different hypertrophic types induced by pressure or volume overload, respectively, but with comparable cardiac function in compensated stage. Speckle-tracking based strain imaging has been applied to assess subtle alterations in cardiac abnormality, but its application in differentiating these two types of ventricular hypertrophy is still sparse. Here, we performed strain imaging analysis of cardiac remodeling in these two loading conditions. Methods: C57BL/6J mice were subjected to transverse aortic constriction (TAC)-induced pressure overload or aortic regurgitation (AR)-induced volume overload. Conventional echocardiography and strain imaging were comprehensively assessed to detect stimulus-specific alterations in TAC and AR hearts. Results: Conventional echocardiography did not detect significant changes in left ventricular systolic (ejection fraction and fractional shortening) and diastolic (E/E') function in either TAC or AR mice. On the contrary, global strain analysis revealed global longitudinal strain and strain rate were remarkably impaired in TAC while preserved in AR mice, although global radial, and circumferential strain and strain rate were significantly reduced in both models. Regional strain analysis in the long axis demonstrated that longitudinal strain and strain rate in all or most segments were decreased in TAC but maintained or slightly dented in AR mice, while radial strain and strain rate indicated overt decline in both models. Moreover, decreased radial and circumferential strain and strain rate were observed in most segments of TAC and AR mice in the short axis. Conclusion: Strain imaging is superior to conventional echocardiography to detect subtle changes in myocardial deformation, with longitudinal strain and strain rate indicating distinct functional changes in pressure versus volume overload myocardial hypertrophy, making it potentially an advanced approach for early detection and differential diagnosis of cardiac dysfunction.

Case Series of Steroid-Resistant Immune Checkpoint Inhibitor Associated Myocarditis: A Comparative Analysis of Corticosteroid and Tofacitinib Treatment.

Background: Immune checkpoint inhibitor (ICI)-associated myocarditis is an uncommon and potentially fatal immune-related adverse event (irAE). Although corticosteroids are recommended as the first-line treatment by current guidelines, patients still have variable responses to it, and the guidelines vary significantly in terms of treatment strategies. Objectives: In this study, we performed a retrospective analysis of ICI-associated myocarditis in our hospital to propose a new comparative analysis to aid individualized treatment. Methods: We reviewed detailed records of 24 patients with confirmed ICI-associated myocarditis in our hospital from July 1, 2019, to April 1, 2021. Although all the cases in our study received recommended initial corticosteroid treatment according to the guidelines, different responses to corticosteroid were observed during the process of subsequent corticosteroid tapering. Basing on troponin cardiac troponin T rebound during corticosteroid tapering, we propose a new classification analysis of ICI-associated myocarditis that included two subgroups: corticosteroid-sensitive (n = 8) and corticosteroid-resistant group (n = 16). Results: Compared with corticosteroid-sensitive patients, larger doses of corticosteroid, longer period of treatment, and higher mortality rate were found in corticosteroid-resistant patients. Corticosteroid-resistant patients were characterized by more prominent ptosis, muscle weakness, elevated cardiac biomarkers, creatine kinase, and hepatic enzymes levels than that in the corticosteroid-sensitive patients. Tofacitinib (5 mg twice a day) was used in 11 corticosteroid-resistant patients, with seven patients recovered from ICI-associated myocarditis, showing a promising therapeutic effect. Conclusion: Our group analysis of corticosteroid responsiveness in patients with ICI-associated myocarditis may help clinicians to apply individualized treatment in this high-risk cohort. In addition, tofacitinib could provide clinical benefits when used early in the corticosteroid-resistant patients and may provide a new option for the treatment of ICI-associated myocarditis.

Release and sedimentation behaviors of biochar colloids in soil solutions.

The release of biochar colloids considerably affects the stability of biochar in environment. Currently, information on the release behavior and suspension stability of biochar colloids in real soil solutions is scarce. In this study, 20 soils were collected from different districts in China and the release behavior of biochar colloids and their suspension stability in soil solutions were systematically examined. The results showed that both pyrolysis temperature and biomass source had important effects on the formation of biochar colloids in soil solutions. The formation amount of biochar colloids from low pyrolysis temperatures (400 °C) (average amount of 9.33-16.41 mg/g) were significantly higher than those from high pyrolysis temperatures (700 °C) (average amount of less than 2 mg/g). The formation amount of wheat straw-derived biochar colloids were higher than those of rice straw-derived biochar colloids probably due to the higher O/C ratio in wheat-straw biochar. Further, biochar colloidal formation amount was negatively correlated with comprehensive effect of dissolved organic carbon, Fe and Al in soil solutions. The sedimentation curve of biochar colloids in soil solutions is well described by an exponential model and demonstrated high suspension stability. Around 40% of the biochar colloids were maintained in the suspension at the final sedimentation equilibrium. The settling efficiency of biochar colloids was positively correlated with comprehensive effect of the ionic strength and K, Ca, Na, and Mg contents in soil solutions. Our findings help promote a deeper understanding of biochar loss and stability in the soil-water environment.

Hyperprogressive disease in patients with advanced renal cell carcinoma: a new pattern of post-treatment cancer behavior.

Renal cell carcinoma (RCC) is among the most common cancers of the genitourinary system. Once RCC has progressed to a high tumor stage, surgery is no longer the optimal option, and treatment with drugs is more suitable. However, a proportion of patients with advanced RCC (aRCC) experience accelerated progression following targeted therapy or immunotherapy, a condition known as hyperprogressive disease (HPD). There is a growing body of literature that recognizes the importance of HPD. In the present review, thousands of studies that describe a variety of treatments for aRCC were identified in PubMed, Web of Science, and Cochrane Library and analyzed to establish the severity of clinical outcomes. Therefore, we managed to perform a review related to HPD of aRCC in these databases. It was found that 7~74% of patients advanced into progressive disease, 0~45% of patients died during post-treatment assessment, possibly due to fatal HPD. However, risk factors, mechanisms, and predictive factors are still not entirely clear. It is suggested that combination therapies might play a pivotal role in preventing HPD. Additional light needs to be shed on customization of therapies for aRCC after more data is collected and analyzed for HPD.

Incentive mechanism to promote corn stalk return sustainably in Henan, China.

Corn stalk return (CSR) can manage agricultural residues on the spot to avoid field open burning and protect the environment. However, the implementation of this measure encounters reluctance from farmers which hinders its sustainability. This study combined the economic (cost) and technical (return amount, crushing quality, and decomposition of corn stalk) aspects to examine the factors affecting farmers' willingness to participate in the CSR by using a logistic regression model. The level of willingness to accept (WTA) compensation and its determinants were analyzed by using a tobit model. Based on the survey of 925 farmers, this study found the likelihood of farmers' participation in CSR will be decreased when CSR has high machinery cost, an excessive amount of stalk, poor quality of crushing, and slow decomposing rate. The farmers' WTA for CSR was estimated at about 711 Chinese Yuan (RMB) per ha annually, much higher than the current compensation level of 75-225 RMB per ha in Henan. Farmers were willing to be compensated more because of the high cost and slow decomposing rate. The issues in economic and technical sides should attract more attention, and the compensation should be increased and the technical problems should be solved to stimulate farmers' willingness of CSR. By providing a fuller understanding of farmers' CSR behavior, this study can serve as a reference for the Chinese government to develop and implement better policies.

Release and stability of water dispersible biochar colloids in aquatic environments: Effects of pyrolysis temperature, particle size, and solution chemistry.

Pathways for the physical disintegration of biochar (BC) and the release of water dispersible BC colloids (WDBC) have received much attention due to their unique impacts on carbon loss and contaminant. However, the current understanding of the mechanisms involved in WDBC formation and associated influencing factors is rather limited. This study systematically explored the effects of pyrolysis temperature, initial particle size, and solution chemistry on WDBC formation in aqueous solutions and examined the formation and colloidal stability of WDBC in natural solutions. Results showed that pyrolysis temperature determined the abrasion resistance of pyrolyzed BC, and the submicron fragment rate decreased in the order 400 °C (BC400) > 700 °C (BC700) > 200 °C (BC200). The WDBC yield decreased in the order BC400 (77.5-331 mg g-1) > BC700 (33.5-173 mg g-1) > BC200 (16.8-125 mg g-1) depending on BC size at a solution ionic strength (IS) ≤ 1 mM, which was positively correlated with the submicron fragment rate of bulk BC. With the exception of BC200, increasing IS (0.1-20 mM) and decreasing pH (3.0-10.0) significantly inhibited WDBC yield. Release and sedimentation dominated the WDBC formation processes with the former being more susceptible to solution chemistry. Derjaguin-Landau-Verwey-Overbeek interactions properly explained the effect of IS on WDBC from BC400 and BC700, while the steric resistance of abundant dissolved organic carbon on BC200 was mainly responsible for the high formation of WDBC at high IS (20-50 mM). WDBC had high colloidal stability and could form and stabilize well in natural surface waters and soil solutions, suggesting the relevant risk of long-distance migration of WDBC in environments. These findings represent new knowledge regarding the physical decomposition and the fate of BC in the environment.