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Although lithium-sulfur (Li-S) batteries have long been touted as next-generation energy storage devices, the rampant dendrite growth at the anode side and sluggish redox kinetics at the cathode side drastically impede their practical application. Herein, a dual-functional fibrous skeleton implanted with single-atom Co-N

Northern peatlands with large organic nitrogen (N) storage have the potential to be N2 O hotspots under climate warming, elevated N deposition, and vegetation composition change caused by climate change. However, the interactions of these three factors and the primary controls on N2 O fluxes in peatlands are not well-known. Here, the three factors were manipulated in a boreal bog in western Newfoundland, Canada for 5 years. We found that warming mitigated the positive N effect on N2 O fluxes in the mid-growing season under intact vegetation owing to the increase of available N uptake by vegetation and less N for N2 O production. In contrast, warming strengthened the N effect on N2 O fluxes in the early growing season under the absence of graminoids or shrubs, which could be attributed to the increase of available carbon and nitrogen for N2 O production. It should be noted that these effects were not observed under the condition of low carbon availability. In addition, gross primary production was found as a critical control on N2 O fluxes under N addition. Our findings emphasize that the interaction of abiotic (warming and elevated nitrogen deposition) and biotic factors (vegetation composition change) on N2 O fluxes should be taken into account in order to project N2 O fluxes in peatland ecosystems accurately.

Single atom catalysts have received widespread attention for their fascinating performance in terms of metal atom efficiency as well as their unique catalysis mechanisms comparing to conventional catalysts. Here, we prepared a high-performance catalyst of single-Cu-atom-decorated boron nitride nanofibers (BNNF-Cu) via a facile calcination method for the first time. The as-prepared catalyst shows excellent catalytic activity and good stability for converting different nitro compounds into their corresponding amines both with and without photoexcitation. By combined studies using synchrotron radiation analysis, high-resolution high-angle annular dark-field transmission electron microscopy studies and DFT calculation, dispersion and coordination of Cu atoms as well as their catalytic mechanisms are explored. The BNNF-Cu catalyst is found to have a record high turn-over frequency comparing to previously reported nonprecious-metal-based catalysts. While the performance of the BNNF-Cu catalyst is only of the middle range level among the state-of-the-art precious-metal-based catalysts, due to the much lower cost of the BNNF-Cu catalyst, its cost-efficiency is the highest among these catalysts. This work provides a new choice of support material which can promote the development of single atoms catalysts.

Mosses dominate the understory of black spruce forest, and changes in moss community composition and functional traits may influence many important ecosystem processes, particularly paludification due to accumulation of peat (mainly Sphagnum). To understand performance and fitness of ground-cover mosses in early forest succession following clearcutting, we investigated photosynthetic traits in Sphagnum and three feathermoss species (i.e., Hylocomium, Ptilium, and Pleurozium) coexisting in mature stands and decade-old black spruce harvest blocks. The results showed that all of these mosses have a significantly higher light saturation point at the harvested plots than the forested plots. Feathermosses at the harvested plots all underwent a reduction in quantum efficiency, chlorophyll b content, and chlorophylls:carotenoids ratio related to photoinhibition, particularly Pleurozium, which experienced a significant decrease in maximum net photosynthesis. In contrast, Sphagnum showed a significant increase in maximum gross photosynthesis, dark respiration, and the ratio of chlorophyll a:b at the harvested plots compared with the forested plots. The distinctive responses of moss photosynthetic traits indicate the potential proliferation of Sphagnum and decrease of feathermosses, and thus consequent peat accumulation. Our results emphasize the importance of the photosynthetic traits of moss as indicators of postharvest conditions for enhancing understory vegetation management to maintain and improve productivity of black spruce.

Light use efficiency (LUE) is a critical parameter to estimate the gross primary production (GPP) for terrestrial ecosystems from remotely sensed data. Only a few studies have estimated the LUE for boreal peatlands and none has calculated the LUE for a drained boreal peatland due to the limited availability of direct measurement of GPP and absorbed photosynthetically active radiation (APAR), which are required to calculate the LUE. In this study, we used eddy covariance (EC) measurement of GPP and APAR at a drained peatland pasture and an adjacent boreal bog to calculate the LUE. The pasture had a significantly higher LUE (0.034 ± 0.0109 mol mol-1) than the bog (0.028 ± 0.098 mol mol-1). The LUE showed significant year-to-year variation at the pasture, but not at the bog. The LUE variation strongly correlated with air temperature and water table depth at both sites, but did not correlate well with vapor pressure deficit. This study indicates that agricultural drainage significantly alters the LUE of boreal peatlands and that the drained peatlands need to be considered separately in LUE-based models for northern peatlands. Moreover, a longer period of study is needed to fully understand the temporal dynamics of LUE in natural peatlands.

The shortage of lithium resources is promoting the development of cost-efficient battery candidates, especially aqueous rechargeable batteries (ARBs) with high safety and power density. Copper hexa...

Peatlands are known as N2O sinks or low N2O sources due to nitrogen (N) limitation. However, climate warming and N deposition can modulate this limitation, and little is known about the combinative effects of them on N2O emission from boreal peatlands. In this study, experimental warming and N fertilization treatments were conducted at a boreal peatland in western Newfoundland, Canada. Contrary to previous studies on permafrost peatland and alpine meadows, the effect of warming treatment on N2O flux was not detectable during the growing seasons of 2015 and 2016. The N fertilization treatment significantly increased the N2O flux by 1.61 nmol m−2 s−1 due to increased N availability. Noticeably, warming reduced the effect of N fertilization treatment on N2O flux with high significance in the middle growing season of 2015. This can be attributed to low N availability caused by stimulated vegetation growth in the warming treatment. In addition, the results showed that total nitrogen was the main control on N2O emission under N fertilization, while dissolved organic carbon was the main driver under the combined treatment of warming and N fertilization. Due to elevated N2O emissions under N deposition/fertilization, the contribution of N2O to global warming and ozone depletion should not be ignored.

Aims To assess the expression of epithelial-mesenchymal transition (EMT) regulators in follicular thyroid tumours. Methods and results The expression of E-cadherin (E-CAD) and transcription factors TWIST, SLUG and SNAIL in follicular thyroid tumours was examined by immunohistochemistry in tissue samples, including 18 follicular adenomas (FA), 12 minimally invasive follicular thyroid carcinomas (MI-FTC), 16 widely invasive follicular thyroid carcinomas (WI-FTC), 10 poorly differentiated follicular thyroid carcinomas (PDTC) and six anaplastic thyroid carcinomas (ATC). Metastatic tumour tissues from six of these cases were also examined. The results showed an increasing expression trend of EMT regulators in a panel of follicular tumour cases with a spectrum of morphological subtypes from low- to high-risk malignancy. The expression of EMT regulators was higher in the WI-FTC, PDTC and ATC groups but focal and lower in the FA and MI-FTC groups. Different expression intensity of E-CAD and EMT regulators at the tumour centre part and the invasive front (IF) was observed. The loss of E-CAD and expression of EMT regulators was significantly correlated with distant metastasis and vascular invasion (VI) in the well-differentiated follicular carcinoma (WD-FTC), and six tumours of metastatic sites also showed variables positive for EMT regulators. The disease-free survival analysis showed an apparent relationship between the expression of EMT regulators and the tumour disease-free outcomes in WD-FTC. Conclusions Our study supported the role of EMT in the development of follicular thyroid carcinoma and indicated that EMT regulatory proteins may play an important role in WD-FTC that are widely invasive and exhibit distant metastasis.

Unit Commitment (UC) is an important problem in power system operations. It is traditionally scoped for 24 hours with one-hour time intervals. To improve system flexibility by accommodating the increasing net-load variability, sub-hourly UC has been suggested. Such a problem is larger and more complicated than hourly UC because of the increased number of periods and reduced unit ramping capabilities per period. The computational burden is further exacerbated for systems with large numbers of virtual transactions leading to dense transmission constraints matrices. Consequently, the state-of-the-art and practice method, branch-and-cut (B&C), suffers from poor performance. In this paper, our recent Surrogate Absolute-Value Lagrangian Relaxation (SAVLR) is enhanced by embedding ordinal-optimization concepts for a drastic reduction in subproblem solving time. Rather than formally solving subproblems by using B&C, subproblem solutions that satisfy SAVLR’s convergence condition are obtained by modifying solutions from previous iterations or solving crude subproblems. All virtual transactions are included in each subproblem to reduce major changes in solutions across iterations. A parallel version is also developed to further reduce the computation time. Testing on MISO’s large cases demonstrates that our ordinal-optimization embedded approach obtains near-optimal solutions efficiently, is robust, and provides a new way on solving other MILP problems.

Standardized programmed death-ligand 1 (PD-L1) assessment in non-small cell lung cancer (NSCLC) is challenging, owing to inter-observer variability among pathologists and the use of different antibodies. There is a strong demand for the development of an artificial intelligence (AI) system to obtain high-precision scores of PD-L1 expression in clinical diagnostic scenarios. We developed an AI system using whole slide images (WSIs) of the 22c3 assay to automatically assess the tumor proportion score (TPS) of PD-L1 expression based on a deep learning (DL) model of tumor detection. Tests were performed to show the diagnostic ability of the AI system in the 22c3 assay to assist pathologists and the reliability of the application in the SP263 assay. A robust high-performance DL model for automated tumor detection was devised with an accuracy and specificity of 0.9326 and 0.9641, respectively, and a concrete TPS value was obtained after tumor cell segmentation. The TPS comparison test in the 22c3 assay showed strong consistency between the TPS calculated with the AI system and trained pathologists (R = 0.9429-0.9458). AI-assisted diagnosis test confirmed that the repeatability and efficiency of untrained pathologists could be improved using the AI system. The Ventana PD-L1 (SP263) assay showed high consistency in TPS calculations between the AI system and pathologists (R = 0.9787). In conclusion, a high-precision AI system is proposed for the automated TPS assessment of PD-L1 expression in the 22c3 and SP263 assays in NSCLC. Our study also indicates the benefits of using an AI-assisted system to improve diagnostic repeatability and efficiency for pathologists.

Peatlands store a large amount of organic carbon and are vulnerable to climate change and human disturbances. However, ecosystem-scale peatland models often do not explicitly simulate the decrease in peat substrate quality, i.e., decomposability or the dynamics of decomposers during peat decomposition, which are key controls in determining peat carbon's response to a changing environment. In this paper, we incorporated the tracking of each year's litter input (a cohort) and controls of microbial processes into the McGill Wetland Model (MWMmic) to address this discrepancy. Three major modifications were made: (1) the simple acrotelm-catotelm decomposition model in MWM was changed into a time-aggregated cohort model, to track the decrease in peat quality with decomposition age; (2) microbial dynamics: growth, respiration and death were incorporated into the model and decomposition rates are regulated by microbial biomass; and (3) vertical and horizontal transport of the dissolved organic carbon (DOC) were added and used to regulate the growth of microbial biomass. MWMmic was evaluated against measurements from the Mer Bleue peatland, a raised ombrotrophic bog located in southern Ontario, Canada. The model was able to replicate microbial and DOC dynamics, while at the same time reproduce the ecosystem-level CO2 and DOC fluxes. Sensitivity analysis with MWMmic showed increased peatland resilience to perturbations compared to the original MWM, because of the tracking of peat substrate quality. The analysis revealed the most important parameters in the model to be microbial carbon use efficiency (CUE) and turnover rate. Simulated microbial adaptation with those two physiological parameters less sensitive to disturbances leads to a significantly larger peat C loss in response to warming and water table drawdown. Thus, the rarely explored peatland microbial physiological traits merit further research. This work paves the way for further model development to examine important microbial controls on peatland's biogeochemical cycling.

Metastatic tumors (MTs) may show different characteristics of the immune microenvironment from primary tumors (PTs) in non-small cell lung cancer (NSCLC). The heterogeneity of immune markers in metastatic NSCLC and its associated factors has not been well demonstrated. In this study, 64 surgically resected specimens of paired PTs and MTs were obtained from 28 patients with NSCLC. Multiplex immunofluorescence (mIF; panel including programmed death-ligand 1 (PD-L1), Cytokeratin, CD8, and CD68) was performed on whole sections. The heterogeneity of the immune contexture of PD-L1 expression, infiltrating lymphocytes, and immune-to-tumor cell distances was quantified via digital image analysis. In a quantitative comparison of MTs and corresponding PTs, MTs showed higher PD-L1 expression levels, lower density of CD8+ cytotoxic T lymphocytes (CTLs), and longer spatial distance between CTLs and tumor cells. Subgroup analysis, which associated clinical factors, revealed that the heterogeneity of immune markers was more obvious in extrapulmonary, metachronous, and treated MTs, while fewer differences were observed in intrapulmonary, synchronous, and untreated MTs. In particular, MTs showed significantly higher PD-L1 expression and lower lymphocyte infiltration in metastatic NSCLC with EGFR mutations. Prognosis analysis showed that an increased density of CD8+ CTLs in MTs was associated with better overall survival (OS). Therefore, significant discrepancies in PD-L1 expression and lymphocyte infiltration in metastatic NSCLC are most likely associated with temporal heterogeneity with a history of anti-treatment and correlated with EGFR mutations. The detection of immune markers in re-obtained metastatic specimens may be required for immunotherapy prediction in these patients with metastatic NSCLC.

For neoadjuvant therapy in patients with non-small cell lung cancer, the major pathologic response of primary tumors may be an assessable and reliable surrogate measure of survival. Few studies have examined the pathologic evaluation of metastatic lymph node responses and their prognostic significance. This retrospective study enrolled 336 patients with non-small cell lung cancer (squamous cell carcinoma, n = 216; adenocarcinoma, n = 120) treated with neoadjuvant therapy including chemotherapy (n = 316) and targeted therapy (adenocarcinoma, n = 20). The treatment response of the primary tumor and lymph node metastases (LNM) were pathologically assessed according to the multidisciplinary recommendations of the International Association for the Study of Lung Cancer. The relationship of overall survival (OS) and disease-free survival (DFS) with the responses of the primary tumor or LNM was analyzed. The optimal cutoff value of the residual viable tumor (%RVT) of the primary tumor was 12% for both OS (P < 0.001) and DFS (P < 0.001). The pathologic assessment identified LNM in 208 patients. The optimal %RVT cutoff value in LNM was 8% for both OS (P = 0.003) and DFS (P < 0.001). The Spearman's rank correlation coefficient between primary tumors and corresponding LNM was 0.487 for %RVT (P < 0.001), which indicated a positive correlation. On multivariable analysis, an RVT of the primary tumor ≤12% was an independent prognostic factor for improved OS (P = 0.024), whereas an RVT of LNM ≤ 8% was an independent prognostic factor for increased DFS (P = 0.018). Furthermore, in the neoadjuvant chemotherapy group, the optimal %RVT cutoff values for OS in patients with squamous cell carcinoma and adenocarcinoma in the primary tumor were 12% and 58%, respectively. Considering its convenience and operability in clinical application, a 10% threshold RVT value can be used for prognostic evaluation of LNM and primary tumors of squamous cell carcinoma histology; further studies are needed to confirm the optimal cutoff value for primary tumors of adenocarcinoma.

AimsThis study aimed to validate the application of combined multiplex immunofluorescence (mIF) and digital image analysis (DIA) in formalin-fixed and paraffin-embedded tissues for the quantitative assessment of programmed death-ligand 1(PD-L1) and immune cells (ICs) in non-small cell lung cancer (NSCLC).MethodsFifty resected samples of NSCLC were sequentially stained with a DNA-tagged mIF (panel including PD-L1, CKpan, CD8, CD68 and 4′,6-diamidino-2-phenylindole (DAPI)) and conventional immunohistochemistry (cIHC). The assessment of cell density and consistency of tumour proportion score (TPS) via DIA were compared with those by pathologists.ResultsA strong correlation in the cell population of immune markers was obtained between mIF and cIHC (for PD-L1: R=0.9304, CKpan: R=0.8231, CD8: R=0.9314 and CD68: R=0.8366) within 95% limits of agreement. The continuous TPS calculated using mIF was highly consistent with the IHC staining results which were evaluated by pathologists (R=0.9362). However, in the comparison of TPS using interval variables, a poor agreement was obtained at a cut-off of 1% (κ=0.197), whereas excellent agreement was achieved at cut-offs of 50% (κ=0.908) and 5% (κ=0.823). DIA on mIF showed that PD-L1 commonly colocalised with CD68+ macrophages and CD8+ cytotoxic cells were closer to PD-L1-/CK+ tumour cells (TCs) than to PD-L1+/CK+ TCs in spatial distribution.ConclusionsA combination of mIF and DIA is useful for the quantification of PD-L1 expression and IC populations in NSCLC. Further validation of TPS at a cut-off of 1% and assay harmonisation is essential for translating this method in a diagnostic setting.

Increasing number in global COVID-19 cases demands for mathematical model to analyze the interaction between the virus dynamics and the response of innate and adaptive immunity. Here, based on the assumption of a weak and delayed response of the innate and adaptive immunity in SARS-CoV-2 infection, we constructed a mathematical model to describe the dynamic processes of immune system. Integrating theoretical results with clinical COVID-19 patients' data, we classified the COVID-19 development processes into three typical modes of immune responses, correlated with the clinical classification of mild & moderate, severe and critical patients. We found that the immune efficacy (the ability of host to clear virus and kill infected cells) and the lymphocyte supply (the abundance and pool of na��ve T and B cell) play important roles in the dynamic process and determine the clinical outcome, especially for the severe and critical patients. Furthermore, we put forward possible treatment strategies for the three typical modes of immune response. We hope our results can help to understand the dynamical mechanism of the immune response against SARS-CoV-2 infection, and to be useful for the treatment strategies and vaccine design., 18 pages, 5 figures

Peatlands are impacted by climate and land-use changes, with feedback to warming by acting as either sources or sinks of carbon. Expert elicitation combined with literature review reveals key drivers of change that alter peatland carbon dynamics, with implications for improving models. The carbon balance of peatlands is predicted to shift from a sink to a source this century. However, peatland ecosystems are still omitted from the main Earth system models that are used for future climate change projections, and they are not considered in integrated assessment models that are used in impact and mitigation studies. By using evidence synthesized from the literature and an expert elicitation, we define and quantify the leading drivers of change that have impacted peatland carbon stocks during the Holocene and predict their effect during this century and in the far future. We also identify uncertainties and knowledge gaps in the scientific community and provide insight towards better integration of peatlands into modelling frameworks. Given the importance of the contribution by peatlands to the global carbon cycle, this study shows that peatland science is a critical research area and that we still have a long way to go to fully understand the peatland-carbon-climate nexus.

This study is based on a unique direct selling method in the health food and cosmetics market. We build a supply chain consisted of one supplier and one retailer and utilize a game theory model to study it. The supplier owns superior power and can set the price and commission rate, whereas the retailer can determine the quality of value-added service. To maintain social welfare, the government may limit the commission rate set by the supplier. We find that the government’s regulation might make the supply chain’s social and economic performance better off or worse off, depending on a consumer’s preference to value-added services. Additionally, we provide a cost-sharing contract between supplier and salespeople to achieve supply chain coordination. Our study provides applicable insights for each supply chain player and political guidance for the government.

Vegetation degradation, due to climate change and human activities, changes the biomass, vegetation species composition, and soil nutrient input sources and thus affects soil nutrient cycling and enzyme activities. However, few studies have focused on the responses of soil nutrients and enzymes to vegetation degradation in high-altitude wet meadows. In this study, we examined the effects of vegetation degradation on soil nutrients (soil organic carbon, SOC; total nitrogen, TN; total phosphorus, TP) and enzyme activities (i.e., urease, catalase, amylase) in an alpine meadow in the eastern margin of the Qinghai-Tibet Plateau. Four different levels of degradation were defined in terms of vegetation density and composition: primary wet meadow (CK), lightly degraded (LD), moderately degraded (MD), and heavily degraded (HD). Soil samples were collected at depth intervals of 0–10, 10–20, 20–40, 40–60, 60–80, and 80–100 cm to determine soil nutrient levels and enzyme activities. The results showed that SOC, TN, catalase and amylase significantly decreased with degradation level, while TP and urease increased with degradation level (P P P P P P

Boreal peatland Sphagnum may be affected by climate warming and elevated nitrogen availability directly and indirectly via altering vascular plant interaction. Here, we used a field experiment of nitrogen addition, warming, and vascular plant removal to investigate the effects of these factors on Sphagnum in a Canadian blanket boreal peatland. We revealed that significant effects of warming and nitrogen addition on Sphagnum were regulated by vascular plant interaction. The intense competition of vascular plants accelerated an adverse effect of warming on Sphagnum, while facilitation of vascular plants reduced detrimental losses of the Sphagnum due to high dose of nitrogen addition and both warming and the nitrogen addition. These findings indicate the crucial role of vascular plants in regulating the effects of environmental changes on existing Sphagnum in boreal peatlands.

Lithium-rich, manganese-based layered oxides are considered one of the most valuable cathode materials for the next generation of high-energy density lithium-ion batteries (LIBs) for their high specific capacity and low cost. However, their practical implementation in LIBs is hindered by the rapid voltage/capacity decay on cycling and the long-standing contradictions between redox kinetics and volumetric energy density due to their poor calendaring compatibility. Herein, a coherent near-zero-strain interphase is constructed on the grain boundaries of cathode secondary particles by infusing LiAlO2 material through the reactive infiltration method (RIM). Theoretical calculations, multi-scale characterizations, and electrochemical tests show that this coherent interphase with near-zero-strain feature upon electrochemical (de)lithiation inhibits volume changes of the lattice and structural degradation of cathode primary particles during cycling. More importantly, the ionically conductive LiAlO2 nanolayer infiltrated in the grain boundaries of cathode secondary particles can not only promote the rapid Li+ migration and act as a barrier to protect the material from the corrosion of the electrolyte but also effectively improve the mechanical strength of the cathode secondary particles. Collectedly, the LiAlO2-infiltrated cathode materials display superior electrochemical cyclability, enhanced rate capability, and industrial calendaring performance, marking a significant step toward commercial implementation.

AIM: The heterogeneity of PD-L1 status between core needle biopsies (CNBs) from one tumor was not well studied before. The current study attempts to find out the best index using multiple core biopsies from one tumor which can better reflect the actual PD-L1 status. METHODS: Random CNB was performed in surgical specimens from 170 consecutive Non-Small Cell Lung Cancer (NSCLC) samples. 51 cases (41 cases with PD-L1 positive and 10 cases with PD-L1 negative) and 216 matched CNBs were analyzed by DAKO 22C3 PharmDx Link 48 Autostainer. The PD-L1 status was compared between the surgical specimens and matched CNBs. RESULTS: The heterogeneity of PD-L1 status between CNBs from one tumor was observed in 56.1% PD-L1 positive cases. Different tumor proportion score (TPS) statistical forms with regard to the highest, mean, median, weighted average TPS, as well as TPS showed by the longest biopsy specimen and the biopsy with most tumor volume were compared. At a cutoff of 1%, the concordance rates were 94.1%, 88.2%, 90.2%, 86.3%, 86.3% and 86.3%; At a cutoff of 50%, the concordance rates were 92.2%, 86.3%, 84.3%, 82.4%, 82.4% and 86.3%, respectively. The CNB with the highest TPS can best represent PD-L1 status estimated by whole surgical specimen.CONCLUSIONS: The highest TPS among the multiple biopsies is a robust evaluation of the PD-L1 status, but not mean TPS, at the 1% and 50% cutoffs.

Sodium-ion batteries (SIBs) have been considered as one of the most promising secondary battery techniques for large-scale energy storage applications. However, developing appropriate electrode materials that can satisfy the demands of long-term cycling and high energy/power capabilities remains a challenge. Herein, a fluorine modulation strategy is reported that can trigger highly active exposed crystal facets in anatase TiO

Sub-hourly Unit Commitment (UC) problems have been suggested as a way to improve power system efficiency. Such problems, however, are much more difficult than hourly UC problems. This is not just because of the increased number of period to consider, but also because of much reduced unit ramping capabilities leading to more complicated convex hulls. As a result, state-of-the-art and practice methods such as branch-and-cut suffer from poor performance. In this paper, our recent Surrogate Absolute-Value Lagrangian Relaxation (SAVLR) method, which overcame major difficulties of standard Lagrangian Relaxation, is enhanced by synergistically incorporating the concept of Ordinal Optimization (OO). By using OO, solving subproblems becomes much faster. Testing of Midcontinent ISO (MISO)’s problem with 15 minutes as the time interval over 36 hours involving about 1,100 units and 15000 virtuals demonstrates that the new method obtains near-optimal solutions efficiently and significantly outperforms branch-and-cut.

Northern peatlands have sequestered a huge amount of carbon through exceptionally low microbial activity which is partly attributed to their nutrient-poor conditions. Evergreen shrubs, a dominant species in ombrotrophic bogs, adapt to this nutrient-poor condition by developing organic nutrient acquisition strategies, mediated by ericoid mycorrhizal association. However, the mycorrhizal symbionts together with nutrient cycling have been omitted in peatland models, precluding our ability to simulate the significance of nutrient limitation in peatlands following environmental changes. To address this issue, we further developed the well-established peatland model MWM by incorporating a mechanistic mycorrhizal fungi model and both nitrogen and phosphorus cycles. The new model was adopted to simulate the fertilization effect on peatlands and evaluated against measurements from the long-term fertilization experiments at Mer Bleue, a raised ombrotrophic bog located in southern Ontario, Canada. The model successfully reproduced the observed dramatic changes with fertilization in mycorrhizal performance, vegetation composition and carbon cycle. Greater availability of inorganic nutrients diminished the role of mycorrhizal fungi in plant nutrient uptake. More assimilated carbon was allocated to shrub growth, which then inhibited the growth of sphagnum moss and ultimately posed a threat to the carbon-sequestration capacity of peatlands. Therefore, mycorrhizal activities, which have been overlooked in past peatland studies, could play a significant role in understanding how peatlands respond to increased nutrient deposition in the future.

We observed BL Lac in the B, V, R, and I bands with an 85 cm telescope on nine nights from 2019 September 18 to 2019 December 6. More than 2300 data points were collected. All intraday light curves were examined for variations by using the most reliable power-enhanced F-test and the ANOVA test, and intraday variability was found on five nights. Thanks to our high precision and high temporal resolution data, two key discoveries were made in the following analyses. (1) In addition to the strong bluer-when-brighter behavior on most nights, we observed a color reversal that is rarely found in BL Lac objects. This indicates that there are two different energy distributions of injected electrons on this night. (2) The object traced clockwise loops on the color–magnitude diagrams on one night. These are the first intraday spectral hysteresis loops reported in the optical bands in this object, suggesting interband time lags. We estimated the interband lags by using the ZDCF, ICCF, and JAVELIN, and found the variations in the V and R band lagged that in the B band by about 16 and 18 minutes, respectively. Such optical time lags are expected if the acceleration timescale is much shorter than the cooling timescale.

The rainfall amount and the frequency of extreme rainfall events have been predicted to increase in the Qinghai-Tibetan Plateau during the growing season. These changes will likely affect ecosystem processes, including those that control nitrogen (N) cycling and storage; however, the direction of the changes remains unclear. In this study, we experimentally altered the amount and frequency of precipitation events during the growing season (May through October) at an alpine wetland in the Qinghai-Tibetan Plateau. The treatments included ambient rain (CK) plus 25 mm of extra water for each irrigation event but with different irrigation frequency, i.e., weekly (DF1), biweekly (DF2), every three weeks (DF3) and every four weeks (DF4). During the growing season, the N2O flux showed a large seasonal variation. Compared with the treatment of natural rainfall events, the increase in the rainfall amount promoted the N2O emission flux. As the frequency of rainfall events increased, the aboveground biomass increased significantly from 85.82 g·m−2 to 245.79 g·m−2, and the accumulated N2O emissions first increased and then decreased; we observed the peak of the N2O flux at the DF2 rainfall frequency. We also found the significant linear relationships between soil N2O flux, nitrate nitrogen, and microbial biomass nitrogen content. Furthermore, among the soil microbial factors, higher rainfall frequency (DF1) significantly reduced the relative abundance of the original dominant species (Alphaproteobacteria) in the studied wetland soil. Our results indicate that alpine wetlands are highly sensitive to increased precipitation variability and high frequencies of extreme rainfall events could significantly reduce N2O emission. Future precipitation patterns could weaken the contribution rate of wetland N2O emission to the global warming.

We measured year-round landscape-scale methane (CH4) flux in a boreal bog from May 2014 to April 2016 using the eddy covariance technique. The objectives of the study were to investigate the controls on CH4 flux at different periods of the growing season and to quantify the annual CH4 flux budget. The daily average growing season water table (WT) ranged from -0.33 to −0.08 m in 2014 and from −0.36 to −0.08 m in 2015. Strong seasonal variability in the daily average CH4 fluxes was observed in both 2014 and 2015, ranging from near zero before May to a peak of above 20 nmol m−2 s−1 in the middle-late August in 2014 and in the early-middle September in 2015. Soil temperature at 50 cm and water table exerted interactive impact on the seasonal variation in the daily average growing season CH4 flux in both years. Soil temperature at 1 cm was negatively related to CH4 flux when water table dropped more than 0.25 m below the peat surface in 2015 growing season, suggesting that the seasonal variation in CH4 flux was dominated by the variation due to CH4 oxidation. During the non-growing season, the daily variation in CH4 fluxes was mostly related to friction velocity in both years. In addition, daily average CH4 flux was linearly related to net ecosystem exchange of CO2 (NEE) when daily NEE was negative (i.e., days with CO2 uptake larger than ecosystem respiration), but there was no correlation between them when NEE was positive (days with ecosystem respiration dominated over CO2 uptake) during the growing season. We found that this boreal bog acted as a small CH4 source of 3.7 ± 0.9 g CH4 m−2 from May 2014 to April 2015 and 3.1 ± 0.9 g CH4 m−2 from May 2015 to April 2016. These values were at the lower end of the range of CH4 emission rates reported for boreal peatlands. Non-growing season CH4 emissions accounted for 41% (the first study year) and 39% (the second study year) of the annual emissions, highlighting the importance of non-growing season CH4 emissions in estimating the annual CH4 budget and the feedback to climate.

This study focuses on how product substitutability, electronic word-of-mouth (e-WOM), and market size affect equilibrium myopic and far-sighted pricing strategies in a two-period duopoly market. Th...

Refurbishment and quality recovery, as two important strategies of reverse logistics, have been widely used for consumer durables, especially consumer electronics. This trend is driven by manufactu...

This paper aims to explore manufacturers horizontal information sharing strategy under competition. The model framework is based on a two-echelon supply chain composed of one upstream supplier and two downstream manufacturers with asymmetric capacity constraint. Analysis of the model establishes manufacturers’ information sharing strategies under different conditions and shows how supplier’s pricing decision can shape manufacturers’ information sharing incentives.

Peatlands on the Tibetan Plateau play crucial roles in regional carbon cycling but faced serious degradation in recent decades, and hydrological restoration is being conducted to regain their ecosystem function. However, how restoration affects the environmental controls on carbon processes of these unique ecosystems remains unclear, and the role of vegetation community in regulating carbon processes in response to the restoration is unknown. A long dam was built at the outlet of a large shallow lake on the plateau in order to evaluate the effects of hydrological restoration on the carbon sequestration of the world’s largest alpine peatlands. The carbon dioxide (CO2) and methane (CH4) fluxes from three widely distributed peatland communities, i.e., Kobresia pusilla, Carex enervis, and Carex muliensis commuities, were investigated immediately before and after restoration. The water table rising as a consequence of restoration, at least temporarily, decreased the carbon consumption rate (plant respiration plus soil decomposition) for each unit of carbon fixation by plants, which is community dependent. However, a positive relationship between temperature sensitivity of ecosystem respiration (Reco) and optimal water table for respiration implies a positive feedback between water table rising and warming on Reco. Meanwhile, the dominant factor explaining the variance of Reco shifted from soil temperature (explained 56%) to water table (explained 68%) after restoration. Water table rising enhanced the CH4 emissions by 3–12 times, with significantly different changes in CH4 flux over a standard variation in water table level among the communities. Temperature was excluded while only water table and vegetation type were included in the model to predict CH4 fluxes after restoration in contrast to before. We argue that the shift of driving environmental factors and the role of vegetation community are essential in evaluating the effects of hydrological restoration on carbon cycling of Plateau peatlands, particularly during the transitional period.

Despite the many studies about peatland development and carbon dynamics in China, especially for Zoige peatlands on the eastern edge of the Tibetan Plateau, few apply modeling as an effective approach to study peatland development. In order to fill up the knowledge gaps of China alpine peatland development and to provide a comparison with previous research, we studied the Zoige peatlands in Holocene with a modeling approach. Simulated results were obtained by the Holocene peatland model (HPM). Driving data was reconstructed based on paleoclimate studies. Model calibration and performance index validation were done by comparing the model output with literature data about peat age depth. Based on our results, the peat cohort mass mean accumulation rate was 0.45 mm year−1 (ranging from 0.38 to 0.50 mm year−1). The mean C accumulation rate was about 0.026 kg C m−2 year−1 (ranging from 0.023 to 0.029 kg C m−2 year−1), with a peak accumulation rate around 7 ka to 6 ka BP during the Holocene. The peat depth was 5.38 m (ranging from 4.6 to 5.99 m). The total peat storage in Zoige was about 1.76 Pg (ranging from 1.58 to 2.29 pg), and the carbon stock was estimated as 0.432 pg C (ranging from 0.348 to 0.479 pg C) in Zoige peatlands during the Holocene. After model calibration and validation, simulated results indicated that peat development and carbon accumulation were controlled by variation of water table depth (WTD). Simulated results indicated that the Zoige peatlands are the most important component of peatlands in China in terms of carbon stock. Though HPM lacks in driving data of temperature and incomplete climate factors, its limitations in the parameter setting should not offset the added value of the modeling approach in improving our understanding of peatland carbon and their controlling factor dynamics at the long-term scales in the Zoige region where there are very few studies so far.

Net ecosystem exchange of carbon dioxide (NEE) and its components, gross primary productivity (GPP) and ecosystem respiration (ER), were compared between a bog and an abandoned peatland pasture within the same peatland complex in western Newfoundland, Canada. Measurements based on the eddy covariance technique from April 2014 to April 2016 were used to examine the influence of agricultural management and abandonment on peatland carbon dioxide (CO2) exchange. NEE, GPP and ER at both sites showed pronounced seasonal variation, peaking near the middle growing season. The maximum net CO2 uptake rate of −28.61 μmol m−2 s−1 and emission rate of 14.39 μmol m−2 s−1 at the pasture were significantly higher than those at the bog (−9.67 μmol m−2 s−1 and 5.50 μmol m−2 s−1, respectively). Daytime average GPP was related to photosynthetic photon flux density and air temperature and the nighttime average ER decreased with soil water content, but increased with surface soil temperature for both sites. Annual NEE of the pasture (−128 ± 60 g C m−2 yr−1 in 2014–15 and −124 ± 56 g C m−2 yr−1 in 2015–16) was considerably larger than that of the bog (−46 ± 36 g C m−2 yr−1 in 2014–15). GPP of 1086 ± 141 g C m−2 yr−1 in 2014–15 and 982 ± 123 g C m−2 yr−1 in 2015–16 and ER of 957 ± 129 g C m−2 yr−1 in 2014–15 and 858 ± 112 g C m−2 yr−1 in 2015–16 at the pasture were approximately twice the magnitude of the corresponding fluxes at the bog. The difference in GPP between the bog and pasture was mainly related to their different aboveground biomass. Higher ER at the pasture was probably related to its lower water table depth, greater substrate availability and higher autotrophic respiration. Unlike previous findings that managed peatlands are large CO2 emitters, our results suggest that abandoned peatland pastures can function like natural grasslands and sequester considerable amounts of CO2 from the atmosphere.

Aims Cyclin D1, generally considered to be absent in chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL), has been reported in the proliferation centres (PCs) of recent CLL/SLL cases. Cyclin D1 immunostaining in CLL/SLL may lead to diagnostic confusion. The objective of this study was to identify the types of stained cells and the impact on diagnosis. Methods Cyclin D1 expression was assessed by immunostaining samples from 46 cases of CLL/SLL. CD68 and double immunostaining with CD20/CyclinD1, CD68/CyclinD1, and CD163/CyclinD1 were then performed in cases of CLL/SLL positive for cyclinD1 in the PCs. Results Dim-positive cyclin D1 staining in randomly scattered cells in the CLL/SLLs were observed in 38/46 cases (82.6%). In five (10.9%) cases, more than 50 cyclin D1-positive cells per high-power field were detected within the PCs in CLL/SLL with weak to moderate intensity. Double immunochemical staining in these cases showed that cyclin D1 in these positive cells was mostly co-expressed with CD68 and CD163 and the cells were negative for CD20. Conclusions The cyclin D1-positive CLL/SLL cells in this study were mostly histiocytes. The expression of cyclin D1 by histiocytes may mimic cyclin D1+ CLL/SLL; thus, the recognition of cyclin D1 expression by non-lymphoid cells in lymphoma is important.

Aqueous Ca2+ ion battery (ACIB) is known as a promising candidate for large-scale grid storage due to its low cost, high performance and safety. However, the large ion size of Ca2+ (1.00 A) limits the ability of Ca2+ to (de)intercalate in the host structure. In this report, hierarchical Ca-birnessite with ultrathin and intertwined nanosheets structure converted from Mn3O4 nanowall arrays (NWAs) was successfully fabricated via an electro-conversion method, showing a fast surface faraday reaction as well as favorable Ca2+ storage kinetics and properties. When tested in ACIB, the electro-converted Ca-birnessite (ECCB) electrode exhibits an excellent specific capacity of 175 mAh g − 1 at 0.1 A g − 1, high rate performance (89 mAh g − 1 at 2 A g − 1) and long cycling stability (83.2% retention after 2000 cycles at 1 A g − 1). A kinetic analysis indicates that the reaction mechanism is dominated by surface-limited capacitance. Moreover, we constructed a balanced 1.9 V full cell of ECCB//PI, which delivers a reversible capacity of 42.1 mAh g − 1 at 0.2 A g − 1 and an energy density of 30.56 Wh kg−1 at power density of 143.4 W kg−1. Furthermore, the full cell shows an excellent cycling stability with almost no capacity decay after 1500 cycles at 1 A g − 1. This work offers a new strategy for designing high performance cathodes for aqueous calcium ion battery.

Background: As of early August 2021, more than 190 million people have developed coronavirus disease (COVID-19), a pandemic that has killed approximately 4 million people. Caused by acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19 exhibited a highly variable clinical course, ranging from a high proportion of asymptomatic and mild infections to severe and fatal disease. However, the immunological determinants underlying the heterogeneity of COVID-19 remain to be fully elucidated. Methods: To systemically analyze the immunopathogenesis of COVID-19, a multicompartment mathematical model based on both immunological principles and COVID-19-related work performed by the scientific community was built to illustrate the dynamics of host immunity after SARS-CoV-2 infection. We used ordinary differential equations (ODEs) to simulate the time-dependent functions of immunologic variations in the four compartments, which were draining lymph nodes, peripheral blood, lung and distant lymph nodes and spleen. Our model consisted of equations for 109 immunologic variations, which contained 223 parameters. K was used to characterize the adequacy of the SARS-CoV-2-specific naïve T/B cell pool; K I represented the hill coefficient of antigen-presenting cell (APC) differentiation. Further, we used method of pseudo landscape to visualize the effect of APC capacity and the SARS-CoV-2-specific naïve T/B cell pool on clinical outcomes. Results: Based on both immunologic knowledge and extensive COVID-19-related work performed by the scientific community, we constructed a knowledge-driven mathematical model that incorporated SARS-CoV-2 infection, bacterial infection, leukocyte chemotaxis, innate immunity and adaptive immunity. The model simulated and predicted the different trajectories of the viral load, bacterial load, immune cells, cytokines and infected epithelial cells in patients with different severities. A higher viral load and longer virus-shedding period were observed in patients with higher severity, along with an increase in SARS-CoV-2-infected lung epithelial cells. The trajectories of both peripheral blood IL-6 and lymphocytes predicted COVID-19 outcomes. Based on the distribution, trafficking and differentiation of immune cells after SARS-CoV-2 infection, we proposed that early-stage lymphopenia is related to lymphocyte chemotaxis. The delayed initiation of both innate and adaptive immunity resulted in elevated SARS-CoV-2 shedding and was a pivotal cause of COVID-19 severity. Spatiotemporally, viral shedding and postviral bacterial infection evoked stronger innate immunity. Viral shedding could be restrained by the rapid initiation of APC, antibody-secreting cell (ASC) and cytotoxic T cell (CTL). Moreover, our model predicted that the insufficient SARS-CoV-2-specific naïve T/B cell pools and inactive APC caused a series of chain reactions, including viral shedding, bacterial infection, sepsis and cytokine storms. Finally, pseudopotential analysis revealed that a high state characterized by severe bacterial infections and cytokine storms was a stable attractor for patients with insufficient SARS-CoV-2-specific naïve T/B cells and inactive APC (Figure 1). Conclusion: Overall, our analysis provided a comprehensive view of the dynamics of host immunity after SARS-CoV-2 infection and highlighted that the antigen-specific naïve T/B cell pool and APC ability may essentially determine COVID-19 heterogeneity from an immunological standpoint. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Birnessite MnO2 is a promising cathode material for aqueous Mg-ion batteries due to its layered structure with large interlayer distance. However, the two-dimensional growth mode of birnessite induces nanosheet morphology with preferred growth of inactive (001) planes with sluggish ion transport kinetics. In this work, a high Mg content birnessite with hierarchical nanowall arrays morphology is prepared by in situ electro-conversion using spinel Mn3O4 nanowall arrays. The electro-conversion Mg-birnessite (ECMB) nanowall arrays are assembled by ultrasmall nanosheets with reduced (001) planes but increased active (010) planes, affording enriched open intercalation channels and shortened Mg2+ diffusion length. Consequently, the ECMB cathode exhibits a large specific reversible capacity of about 255.1 mAh g−1 at a current density of 200 mA g−1, and outstanding cycling stability with 73.6% capacity retention after 3000 cycles. Finally, a 2.2 V aqueous full cell is constructed by using ECMB as positive electrode and polyimide as negative electrode, which achieves a high energy density of 65.2 Wh kg−1 at a power density of 96 W kg−1. This work demonstrates effective crystal plane modulation for Mg-birnessite to achieve superior Mg2+ storage in aqueous batteries.

Building energy consumption accounts for nearly 40% of global energy consumption, HVAC (Heating, Ventilating, and Air Conditioning) systems are the major building energy consumers, and as one type of HVAC systems, the heat pump air conditioning system, which is more energy-efficient compared to the traditional air conditioning system, is being more widely used to save energy. However, in northern China, extreme climatic conditions increase the cooling and heating load of the heat pump air conditioning system and accelerate the aging of the equipment, and the sensor may detect drifted parameters owing to climate change. This non-linear drifted parameter increases the false alarm rate of the fault detection and the need for unnecessary troubleshooting. In order to overcome the impact of the device aging and the drifted parameter, a Kalman filter and SPC (statistical process control) fault detection method are introduced in this paper. In this method, the model parameter and its standard variance can be estimated by Kalman filter based on the gray model and the real-time data of the air conditioning system. Further, by using SPC to construct the dynamic control limits, false alarm rate is reduced. And this paper mainly focuses on the cold machine failure in the component failure and its soft fault detection. This approach has been tested on a simulation model of the “Sino-German Energy Conservation Demonstration Center” building heat pump air-conditioning system in Shenyang, China, and the results show that the Kalman filter and SPC fault detection method is simple and highly efficient with a low false alarm rate, and it can deal with the difficulties caused by the extreme environment and the non-linear influence of the parameters, and what's more, it provides a good foundation for dynamic fault diagnosis and fault prediction analysis.

Background: T cell receptor(TCR)-engineered T cell therapy, by replacing the antigen recognition domain of TCR with an antibody-derived Fab fragment, is another active field of cellular immunotherapy for cancer. We previously developed a human anti-CD19 antibody (ET190L1), and found that ET190L1-TCR-T cells maintained comparable anti-tumor potency with less cytokine release to CD28-costimulated ET190L1-CAR and CD137-based CTL019 T cells (Cell Discov. 2018 Nov 20;4:62.). ET019003-T cells are novel anti-CD19 γδ TCR-T cells generated based on ET190L1-TCR-T cells by adding an independent chimeric signaling receptor(CSR) to further promote T cell activation and reduce cytokine release (Figure 1A). We report outcomes for adult patients with relapsed or refractory diffuse large B-cell lymphoma (RR DLBCL) treated with ET019003-T cells. Methods: Our first-in-human, single-center, phase 1 study (NCT04014894) was designed to evaluate the safety and efficacy of ET019003-T cells in patients with CD19 + malignancies, of whom 8 with RR DLBCL are reported here. Eligible patients must have (1) histologically confirmed DLBCL; (2) CD19 + on malignant cells by IHC; (3) refractory disease as defined in the SCHOLAR-1 study, or recurrent disease within 6 months or at least 2 times after CR; (4) prior therapy including an anti-CD20 monoclonal antibody and an anthracycline. Patients with CNS lymphoma were eligible. Bridging therapy wasn't allowed after apheresis. Cyclophosphamide 250 mg/m 2 on day -5 and fludarabine 25 mg/m 2 on day -5 to -3 were used as the conditioning regimen. Planned dose levels were 2, 4x10 6 TCR+T cells/kg, and repeated infusions were allowed. Primary objectives were incidence of adverse events (AEs) and overall response rate(ORR). CRS and neurotoxicity were graded using the ASTCT criteria, and other AEs using CTCAE v5.0. Response was assessed per Lugano Criteria (Cheson 2014). Results: 8 pts (median age 50, range 33-71) received infusion of ET019003-T cells (6 at 2x10 6/kg, and 2 at 4x10 6/kg) and were included in the study analysis. Patient enrollment was ceased in June, 2020. Pt1 had primary CNS lymphoma, and 62.5% had stage 4 disease against Ann Arbor staging. MYC/BCL2/BCL6 triple expression was detected in 50% of pts, and double expression in 25%. Pts had received a median of 4.5 (range 2-8) prior lines of treatment, and 37.5% received prior PD-1 inhibitors, and 62.5% had primary refractory disease. 3 pts (37.5%) experienced grade 1 CRS that resolved spontaneously; 1(pt2) developed grade 3 neurotoxicity (dose-limiting toxicity), manifested by confusion, barylalia, tremor and agitation, which occurred after CRS and responded to corticosteroids. The most common AE was neutropenia (100%), and 62.5% were related to conditioning regimen; other hematologic AEs included thrombocytopenia (37.5%) and anemia (12.5%). Pt8 had pulmonary infection on day 15, and pt1 experienced viral encephalitis at 18 months, and both were manageable. As of July 20, 2021, median follow-up after infusion was 15 months (range 2-24.7). 6 pts(75%) achieved a clinical response, and 5(62.5%) reached CR, of whom 80% kept ongoing CR (all at 18+ months). 3 pts received a second infusion, pt5 for consolidation therapy after CR, and pt2 and pt7 for salvage therapy after disease progression, but response wasn't observed (Figure 1B). Pt1 with primary CNS lymphoma got continuing CR, without CRS or neurotoxicity (Figure 1C). The rate of overall survival, progression-free survival, and duration of response at 12 months was 87.5%, 62.5% and 66.7%, respectively. ET019003 cells showed striking peak expansion during 10-20 days post infusion as measured as ET019003+ cells per milliliter of PB by flow cytometry and copies per microgram of genomic DNA by qPCR, but poor expansion was observed in the second infusions (Figure 1D). ET019003 cells were detectable in cerebrospinal fluid of pt1, and continued to be detectable at 12+ months in PB of pt3 and pt5. Serum cytokine levels increased mildly post-infusion, except elevated IL-6 (>10 folds of upper limit of normal) in 3 pts (pt1 with a high baseline level, coinciding with onset of CRS and neurotoxicity of pt2, and concurrent with pulmonary infection of pt8). Conclusion: These data suggest ET019003-T cells had a good safety profile and could induce durable remission in patients with RR DLBCL, even with primary CNS lymphoma. γ/δ TCR-T cells may present a potential therapeutic option for these patients. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background ： Chimeric antigen receptor (CAR) T cells targeting CD19 have achieved great clinical responses in patients with relapsed or refractory acute B lymphoblastic leukemia (R/R B-ALL). However, severe adverse events such as cytokine release syndrome (CRS) and neurotoxicity restrict it to further application. Tocilizumab against human interleukin-6 (IL-6) receptor is a common treatment for CAR-T cell therapy associated cytokine release syndrome. Corticosteroids are used when remission is not reached after the application of tocilizumab as well as neurotoxicity occurs, according to the guidance. However, their suitable timing still remains unclear when taking their efficacy and side effects into consideration. Methods: From January 2016 to July 2020, in our phase 1/2 clinical trials (NCT02965092、NCT04008251), 55 patients with R/R B-ALL were enrolled and injected with anti-CD19 CAR-T cells. Clinical laboratory tests on day 0、4、7、10、14、21、28 after infusion as well as endpoints、adverse events and treatment were recorded. CRS and neurotoxicity were graded according to American Society for Transplantation and Cellular Therapy (ASTCT)，and infection severity was classified as mild, moderate, severe, life-threatening, or fatal. (Young et al. Biol Blood Marrow Transplant 2016; 22:359-70.) Patients were assigned to four cohorts based on the fold change of IL-6 and the use of Tocilizumab. We defined fold change as the ratio of peak before Tocilizumab given to baseline in Tocilizumab group and the ratio of peak within 28 days to baseline in non- Tocilizumab group. According to the statistics, two groups were separated into high level (fold change over 5) and low level (fold change below 5), respectively. Wilcoxon tests、Log-rank tests and Fisher's exact tests were used to analyze statistics in GraphPad Prism 9. Results: During the observation period of 28-day-postinfusion, the use of Tocilizumab or corticosteroids did not significantly reduce the response rate or increase infectious risk (P>0.99, P=0.052). Doing a median follow-up of 7 months, the use of corticosteroids was significantly associated with shorter overall survival (OS) and progression-free survival (PFS), while it did not appear when Tocilizumab was applied alone. In addition, significantly fold change of IL-6, IL-10 were observed among subjects suffering cytokine release syndrome before the use of Tocilizumab or corticosteroids and higher levels of TNF-α were observed in 3 subjects with mild neurotoxicity (P=0.0002, P In high level group, patients treated with Tocilizumab had mild CRS limiting to grade 1-2, with shorter duration of CRS (median=5) than non-Tocilizumab (median=6) , though it is without significant difference (P=0.874). In low level group, the use of Tocilizumab is associated with shorter PFS（P=0.0275）as well as severe cytokine release syndrome. Two patients developed grade 4 CRS after infusing Tocilizumab，with apparently increased level of IL-10 (fold change=200) or IFN-γ (fold change=114.24). Neurotoxicity occurred in four patients in Tocilizumab group, and their IL-6 levels increased significantly after treatment, reaching an average peak of 1000pg/ml (157-22001.9). No neurotoxicity were observed in non-Tocilizumab group. Conclusion: Our study demonstrate that severe and persistent CRS could be avoided by applying Tocilizumab when IL-6 has increased over 5-fold from baseline. Tocilizumab is not recommended to use with little change of IL-6 because it fails to suppress the inflammatory response, and may trigger the activation of other cytokines and accelerate the progress of disease recurrence in patients. Although corticosteroids were associated with relapse, we still suggested that corticosteroids should be administrated to antagonize neurotoxicity with symptoms and significantly increased IL-6 levels after the infusion of Tocilizumab. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.