Genomic analysis reveals phylogeny of Zygophyllales and mechanism for water retention of a succulent xerophyte.

Revealing the genetic basis for stress-resistant traits in extremophile plants will yield important information for crop improvement. Zygophyllum xanthoxylum, an extant species of the ancient Mediterranean, is a succulent xerophyte that can maintain a favorable water status under desert habitats; however, the genetic basis of this adaptive trait is poorly understood. Furthermore, the phylogenetic position of Zygophyllales, to which Z. xanthoxylum belongs, remains controversial. In this study, we sequenced and assembled the chromosome-level genome of Z. xanthoxylum. Phylogenetic analysis showed that Zygophyllales and Myrtales form a separated taxon as a sister to the clade comprising fabids and malvids, clarifying the phylogenetic position of Zygophyllales at whole-genome scale. Analysis of genomic and transcriptomic data revealed multiple critical mechanisms underlying the efficient osmotic adjustment using Na+ and K+ as "cheap" osmolytes that Z. xanthoxylum has evolved through the expansion and synchronized expression of genes encoding key transporters/channels and their regulators involved in Na+/K+ uptake, transport, and compartmentation. It is worth noting that ZxCNGC1;1 (cyclic nucleotide-gated channels) and ZxCNGC1;2 constituted a previously undiscovered energy-saving pathway for Na+ uptake. Meanwhile, the core genes involved in biosynthesis of cuticular wax also featured an expansion and upregulated expression, contributing to the water retention capacity of Z. xanthoxylum under desert environments. Overall, these findings boost the understanding of evolutionary relationships of eudicots, illustrate the unique water retention mechanism in the succulent xerophyte that is distinct from glycophyte, and thus provide valuable genetic resources for the improvement of stress tolerance in crops and insights into the remediation of sodic lands.

Efficacy and safety of CD19-specific CAR T cell-based therapy in B-cell acute lymphoblastic leukemia patients with CNSL.

Few studies have described chimeric antigen receptor (CAR) T-cell therapy for patients with B-cell acute lymphoblastic leukemia (B-ALL) with central nervous system leukemia (CNSL) because of concerns regarding poor response and treatment-related neurotoxicity. Our study included 48 patients with relapsed/refractory B-ALL with CNSL to evaluate the efficacy and safety of CD19-specific CAR T cell-based therapy. The infusion resulted in an overall response rate of 87.5% (95% confidence interval [CI], 75.3-94.1) in bone marrow (BM) disease and remission rate of 85.4% (95% CI, 72.8-92.8) in CNSL. With a median follow-up of 11.5 months (range, 1.3-33.3), the median event-free survival was 8.7 months (95% CI, 3.7-18.8), and the median overall survival was 16.0 months (95% CI, 13.5-20.1). The cumulative incidences of relapse in BM and CNS diseases were 31.1% and 11.3%, respectively, at 12 months (P = .040). The treatment was generally well tolerated, with 9 patients (18.8%) experiencing grade ≥3 cytokine release syndrome. Grade 3 to 4 neurotoxic events, which developed in 11 patients (22.9%), were associated with a higher preinfusion disease burden in CNS and were effectively controlled under intensive management. Our results suggest that CD19-specific CAR T cell-based therapy can induce similar high response rates in both BM and CNS diseases. The duration of remission in CNSL was longer than that in BM disease. CD19 CAR T-cell therapy may provide a potential treatment option for previously excluded patients with CNSL, with manageable neurotoxicity. The clinical trials were registered at www.clinicaltrials.gov as #NCT02782351 and www.chictr.org.cn as #ChiCTR-OPN-16008526.

Physiological and transcriptomic analyses provide insight into thermotolerance in desert plant Zygophyllum xanthoxylum.

BACKGROUND: Heat stress has adverse effects on the growth and reproduction of plants. Zygophyllum xanthoxylum, a typical xerophyte, is a dominant species in the desert where summer temperatures are around 40 °C. However, the mechanism underlying the thermotolerance of Z. xanthoxylum remained unclear. RESULTS: Here, we characterized the acclimation of Z. xanthoxylum to heat using a combination of physiological measurements and transcriptional profiles under treatments at 40 °C and 45 °C, respectively. Strikingly, moderate high temperature (40 °C) led to an increase in photosynthetic capacity and superior plant performance, whereas severe high temperature (45 °C) was accompanied by reduced photosynthetic capacity and inhibited growth. Transcriptome profiling indicated that the differentially expressed genes (DEGs) were related to transcription factor activity, protein folding and photosynthesis under heat conditions. Furthermore, numerous genes encoding heat transcription shock factors (HSFs) and heat shock proteins (HSPs) were significantly up-regulated under heat treatments, which were correlated with thermotolerance of Z. xanthoxylum. Interestingly, the up-regulation of PSI and PSII genes and the down-regulation of chlorophyll catabolism genes likely contribute to improving plant performance of Z. xanthoxylum under moderate high temperature. CONCLUSIONS: We identified key genes associated with of thermotolerance and growth in Z. xanthoxylum, which provide significant insights into the regulatory mechanisms of thermotolerance and growth regulation in Z. xanthoxylum under high temperature conditions.

Associations of granulocyte colony-stimulating factor with toxicities and efficacy of chimeric antigen receptor T-cell therapy in relapsed or refractory multiple myeloma.

BACKGROUND AIMS: Few studies have reported the associations of granulocyte colony-stimulating factor (G-CSF) with cytokine release syndrome (CRS), neurotoxic events (NEs) and efficacy after chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory (R/R) multiple myeloma (MM). We present a retrospective study performed on 113 patients with R/R MM who received single anti-BCMA CAR T-cell, combined with anti-CD19 CAR T-cell or anti-CD138 CAR T-cell therapy. METHODS: Eight patients were given G-CSF after successful management of CRS, and no CRS re-occurred thereafter. Of the remaining 105 patients that were finally analyzed, 72 (68.6%) received G-CSF (G-CSF group), and 33 (31.4%) did not (non G-CSF group). We mainly analyzed the incidence and severity of CRS or NEs in two groups of patients, as well as the associations of G-CSF timing, cumulative dose and cumulative time with CRS, NEs and efficacy of CAR T-cell therapy. RESULTS: Both groups of patients had similar duration of grade 3-4 neutropenia, and the incidence and severity of CRS or NEs.There were also no differences in the incidence and severity of CRS or NEs between patients with the timing of G-CSF administration ≤3 days and those >3 days after CAR T-cell infusion. The incidence of CRS was greater in patients receiving cumulative doses of G-CSF >1500 µg or cumulative time of G-CSF administration >5 days. Among patients with CRS, there was no difference in the severity of CRS between patients who used G-CSF and those who did not. The duration of CRS in anti-BCMA and anti-CD19 CAR T-cell-treated patients was prolonged after G-CSF administration. There were no significant differences in the overall response rate at 1 and 3 months between the G-CSF group and the non-G-CSF group. CONCLUSIONS: Our results showed that low-dose or short-time use of G-CSF was not associated with the incidence or severity of CRS or NEs, and G-CSF administration did not influence the antitumor activity of CAR T-cell therapy.

Massive increases in C31 alkane on Zygophyllum xanthoxylum leaves contribute to its excellent abiotic stress tolerance.

BACKGROUND AND AIMS: Desert plants possess excellent water-conservation capacities to survive in extreme environments. Cuticular wax plays a pivotal role in reducing water loss through plant aerial surfaces. However, the role of cuticular wax in water retention by desert plants is poorly understood. METHODS: We investigated leaf epidermal morphology and wax composition of five desert shrubs from north-west China and characterized the wax morphology and composition for the typical xerophyte Zygophyllum xanthoxylum under salt, drought and heat treatments. Moreover, we examined leaf water loss and chlorophyll leaching of Z. xanthoxylum and analysed their relationships with wax composition under the above treatments. KEY RESULTS: The leaf epidermis of Z. xanthoxylum was densely covered by cuticular wax, whereas the other four desert shrubs had trichomes or cuticular folds in addition to cuticular wax. The total amount of cuticular wax on leaves of Z. xanthoxylum and Ammopiptanthus mongolicus was significantly higher than that of the other three shrubs. Strikingly, C31 alkane, the most abundant component, composed >71 % of total alkanes in Z. xanthoxylum, which was higher than for the other four shrubs studied here. Salt, drought and heat treatments resulted in significant increases in the amount of cuticular wax. Of these treatments, the combined drought plus 45 °C treatment led to the largest increase (107 %) in the total amount of cuticular wax, attributable primarily to an increase of 122 % in C31 alkane. Moreover, the proportion of C31 alkane within total alkanes remained >75 % in all the above treatments. Notably, the water loss and chlorophyll leaching were reduced, which was negatively correlated with C31 alkane content. CONCLUSION: Zygophyllum xanthoxylum could serve as a model desert plant for study of the function of cuticular wax in water retention because of its relatively uncomplicated leaf surface and because it accumulates C31 alkane massively to reduce cuticular permeability and resist abiotic stressors.

Factors associated with infection events after chimeric antigen receptor T-cell therapy for relapsed or refractory multiple myeloma.

OBJECTIVES: Chimeric antigen receptor (CAR) T-cell therapy is a new and effective method in relapsed or refractory (R/R) multiple myeloma (MM). This study was aimed to explore the risk factors of infection events. METHODS: We retrospectively analyzed 68 patients with R/R MM who received CAR T-cell therapy at the Affiliated Hospital of Xuzhou Medical University from June 2017 to June 2021.35 patients received anti-CD19 combined with anti-BCMA CAR T-cell therapy and 33 patients received anti-BCMA CAR T-cell therapy alone. RESULTS: Infection events in patients who received ≥4 prior lines of treatment or with grade 3-5 cytokines released syndrome (CRS) mainly occurred within 4 months after CAR T-cell infusion(CTI). The duration of infection-free survival was positively correlated with progression-free survival of patients with R/R MM (R2 = 0.962, p < 0.001) and the first infection event was closely accompanied by the disease relapse or progression. Treatment lines (p = 0.05), duration of ANC<500 cells/mm3 after CTI (p = 0.036), CRS grade (p = 0.007) and treatment response (p < 0.001) were the independent risk factors associated with infection for a multivariable model. The infection incidence was higher in patients with dual CAR T-cell therapy than with mono CAR T-cell therapy18 months after CTI although no statistic differences were observed within 18 months. CONCLUSIONS: Infections after CTI were closely associated with more lines of prior treatment, longer duration of ANC<500 cells/mm3, higher grade CRS and poor treatment response. Infections tended to occur in the early stage after CTI in patients with more lines of prior treatment and higher grade CRS.

Pretreatment neutrophil/lymphocyte ratio but not platelet/lymphocyte ratio has a prognostic impact in multiple myeloma.

BACKGROUND: We evaluated the prognostic significance of neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) in patients with multiple myeloma (MM). METHODS: In total, we retrospectively analyzed 315 newly diagnosed MM patients and calculated NLR and PLR from the complete blood count of the untreated patients. We further assessed the role of pretreatment NLR and PLR on overall survival (OS) and progression-free survival (PFS). RESULTS: Multiple myeloma patients with high NLR (≥2) experienced shorter OS (P=.02) and PFS (P=.01) compared with patients with low NLR (<2). Furthermore, among the patients with conventional chemotherapy, elderly patients, or patients with advanced stages, high NLR (≥2) was found to have a negative prognostic impact on OS and PFS. In the multivariate Cox analysis, we confirmed that the NLR was an independent prognostic factor for both OS and PFS (P=.000). But the differences in OS or PFS by PLR were not found in MM patients. CONCLUSIONS: Our study suggests that NLR not PLR can be acted as an independent prognostic factor for analyzing the clinical outcome of MM patients.

Safety risk assessment of subway shield construction under-crossing a river using CFA and FER.

Numerous subway projects are planned by China's city governments, and more subways can hardly avoid under-crossing rivers. While often being located in complex natural and social environments, subway shield construction under-crossing a river (SSCUR) is more susceptible to safety accidents, causing substantial casualties, and monetary losses. Therefore, there is an urgent need to investigate safety risks during SSCUR. The paper identified the safety risks during SSCUR by using a literature review and experts' evaluation, proposed a new safety risk assessment model by integrating confirmatory factor analysis (CFA) and fuzzy evidence reasoning (FER), and then selected a project to validate the feasibility of the proposed model. Research results show that (a) a safety risk list of SSCUR was identified, including 5 first-level safety risks and 38 second-level safety risks; (b) the proposed safety risk assessment model can be used to assess the safety risk of SSCUR; (c) safety inspection, safety organization and duty, quicksand layer, and high-pressure phreatic water were the high-level risks, and the onsite total safety risk was at the medium level; (d) management-type safety risks, environment-type safety risks, and personnel-type safety risks have higher expected utility values, and manager-type safety risks were expected have higher risk-utility values when compared to worker-type safety risks. The research can enrich the theoretical knowledge of SSCUR safety risk assessment and provide references to safety managers for conducting scientific and effective safety management on the construction site when a subway crosses under a river.

Production of copper nanoparticle-immobilized chitin nanofibers and their role in plant disease control.

Chitin is used in agriculture to improve crop production; however, its use is limited due to difficulties in its handling. A chitin nanofiber (CNF) overcomes this issue and, due to its elicitor activity, has great potential for crop protection. To expand CNF utilization, a copper nanoparticles-based antimicrobic CNF (CuNPs/CNF) was prepared using a chemical reduction method. The formation of CuNPs was confirmed via scanning electron microscopy. Thermogravimetric analysis revealed that the amount of CuNPs on the CNF was dose-dependent on the precursor salt, copper acetate. CuNPs endowed the CNF with strong antimicrobial activity against Alternaria brassicicola and Pectobacterium carotovorum. Moreover, the CuNPs/CNF reduced pathogen infection in cabbage. The antimicrobial activity and disease prevention of the CuNPs/CNF was increased compared to the corresponding CNF or commercial agrochemical Bordeaux treatment. These results indicate that CuNPs conferred antimicrobial activity on the CNF and increased the efficacy of plant disease protection.

Anti-G Protein-Coupled Receptor, Class C Group 5 Member D Chimeric Antigen Receptor T Cells in Patients With Relapsed or Refractory Multiple Myeloma: A Single-Arm, Phase â ¡ Trial.

PURPOSE: G protein-coupled receptor, class C group 5 member D (GPRC5D) is considered to be a promising surface target for multiple myeloma (MM) immunotherapy. Here, we report the efficacy and safety of anti-GPRC5D chimeric antigen receptor (CAR) T cells in patients with relapsed or refractory (R/R) MM. METHODS: This phase Ⅱ, single-arm study enrolled patients (18-70 years) with R/R MM. Lymphodepletion was performed before patients received 2 × 106/kg anti-GPRC5D CAR T cells. The primary end point was the proportion of patients who achieved an overall response. Safety was also evaluated in eligible patients. RESULTS: From September 1, 2021, to March 23, 2022, 33 patients were infused with anti-GPRC5D CAR T cells. At a median follow-up of 5.2 months (range, 3.2-8.9), the overall response rate was 91% (95% CI, 76 to 98; 30 of 33 patients), including 11 (33%) stringent complete responses, 10 (30%) complete responses, four (12%) very good partial responses, and five (15%) partial responses. Partial responses or better were observed in nine (100%) of nine patients with previous anti-B-cell maturation antigen (BCMA) CAR T-cell therapy, including two patients who had received repeated anti-BCMA CAR T-cell infusions with no responses at the last time. Grade 3 or higher hematologic toxicities were neutropenia (33 [100%]), anemia (17 [52%]), and thrombocytopenia (15 [45%]). Cytokine release syndrome occurred in 25 (76%) of 33 patients (all were grade 1 or 2), and neurotoxicities in three patients (one grade 2 and one grade 3 ICANSs and one grade 3 headache). CONCLUSION: Anti-GPRC5D CAR T-cell therapy showed an encouraging clinical efficacy and manageable safety profile in patients with R/R MM. For patients with MM that progressed after anti-BCMA CAR T-cell therapy or that is refractory to anti-BCMA CAR T cell, anti-GPRC5D CAR T-cell therapy might be a potential alternative option.

Co-workers' guanxi and construction workers' safety behavior: The mediating role of group identification.

The construction industry in China is characterized by higher safety risk, and construction workers' unsafe behaviors are one of the main causes of construction safety accidents, thus, designing scientific mechanisms that motivate and cultivate the construction workers to adopt safety behaviors becomes the key to the construction safety problem. Existing studies have examined some of the factors leading to workers' safety behavior (WSB) at the social, organizational, and individual levels, but ignore investigating the impact of co-workers' guanxi (CWG) on WSB. Thus, this research utilized exploratory factor analysis, confirmatory factor analysis, and structural equation modeling to examine the impact of CWG on WSB, and the mediating role of group identification (GI) in the relationship between CWG and WSB. Results show that CWG can directly or indirectly influence WSB, GI can exert a partial mediating effect on the relationship between CWG and GI. The research results enrich the research on c guanxi and causation of WSB, and provide a reference for project managers to carry out relationship-related safety management and industry regulations.

Emission Reduction Benefits and Economic Benefits of China's Pilot Policy on Carbon Emission Trading System.

As a market means to control nongreen behaviors of firms, the most expected incentive effect of the carbon emission trading system (CETS) is to achieve the dual economic and environmental effects. As a typical developing country, whether China's CETS has a positive incentive effect is significant to controlling greenhouse gas. Based on the quasinatural experiment of China's pilot policy on CETS in 2013, this study investigates its emission reduction and economic benefits using the difference-in-difference (DID) method. Then, the realization mechanism of CETS's incentive benefits is reversely studied with the idea that goals generate behavior. The results show that the following: (a) China's CETS has produced positive incentive effects of promoting both economic and emission reduction benefits. Furthermore, the results are still valid after using the instrumental variable to overcome the endogenous problem, placebo tests to eliminate sampling bias, and a series of robustness tests. (b) Further analysis shows that firms can choose to improve technology innovation and energy efficiency to get the positive incentive effects of CETS. (c) The incentive effects of CETS also have regional heterogeneity. The emission reduction and economic benefits are greater in provinces with deficient resource endowments and strict environmental law enforcement.

Value Proposition for Enabling Construction Project Innovation by Applying Building Information Modeling.

Building information modeling (BIM) is evolving as a digital infrastructure model for innovation in the construction field. The innovation-enabling potential of BIM has been highly neglected in the literature. This study explores the innovative potential of BIM, specifically its value in enabling construction innovation (CI). Through reflective research and a literature review, the relationship between BIM and CI is redefined, BIM-CI's value spectrum and underlying mechanisms are mapped and their required resources and activities are illustrated. The results indicate that different BIM applications provide various proinnovation environments wherein CI may flourish. Extra attention should be paid to BIM-enabled systematic collaborative innovation and digital innovation ecosystems with BIM as the core infrastructure that integrates the physical space with cyberspace to accelerate radical innovation. This study extends BIM management research by considering digital innovation and providing a new perspective for CI management theory and practice. The results will provide academics with a solid point of departure for developing relevant research and serve as a reference for practitioners who intend to utilize BIM for efficient innovation in construction projects.

A Simulation Study on the Processes of Intra-Group Informal Interaction Affecting Workers' Safety Behaviors.

The construction industry across the world is characterized by a high safety risk, and the occurrence of these safety accidents has led to substantial economic and social losses. The workers' unsafe behaviors are considered to be a main cause. Thus, recently, scholars in the construction industry have shifted their attention to the investigation of the influencing factors (or antecedents) and their impact on workers' safety behaviors (WSBs), hoping to provide insight into useful management policies. The existing literature has identified many society-level, cooperation-level, project-level, and individual-level concepts influencing WSB, but ignores the influence of intra-group informal interaction (IGII) on WSB. This study constructed a conceptual model for IGII, group knowledge sharing (GKS), and group identification (GI) to determine their influence on construction workers' safety behaviors, and then conducted simulation analysis using the software of NetLogo. The results show that IGII, GKS, and GI can positively influence workers' safety behaviors, and IGII can also positively influence WSB through GKS and GI. This study enriches the theoretical knowledge on the causation of construction workers' safety behaviors, provides references for project managers to carry out proper safety management, and offers a theoretic foundation for the formulation of industry regulations.

Exploring Technical Decision-Making Risks in Construction Megaprojects Using Grounded Theory and System Dynamics.

Technical decision-makings (TDMs) are a vital part of the decision-makings in construction megaprojects, facing high risks brought by technical complexity, dynamic environment, and subject cognition. Identifying technical decision-making risks (TDMRs) and exploring their interactions are important in megaproject management. Due to the high complexity of TDMs in megaprojects, TDMRs are complex and diverse. However, there is a lack of research on exploring the systematic TDMRs in megaprojects. To address this gap in knowledge, this paper aims to better understand the dynamic complexity of TDMRs in megaprojects by identifying the risks and exploring their interactions from a dynamic and systematic perspective. Grounded theory (GT) and system dynamics (SD) were adopted for this research. First, the GT was used to identify TDMRs in megaprojects and create a conceptual model depicting the relationships among TDMRs. Then, an SD model characterizing the causal structure of the TDMRs system in megaprojects is developed in both qualitative and quantitative manners. The developed model involves interrelationships among environmental risks, decision-making process risks, and decision-making execution process risks. After the validation of the model, a model simulation is conducted to predict the dynamic evolution process of the TDMRs. As a result, a multilayer risk list consisting of 42 index layer risk indicators, 13 field layer risk indicators, and 3 standard layer risk indicators is identified. The SD modeling results show that these multilevel TDMRs interact dynamically and have intricate influences on the total risk level of TDMs in megaprojects. The results of this study could be useful for decision-makers to identify and mitigate TDMRs in megaprojects.

Experimental Study of Energy Evolution at a Discontinuity in Rock under Cyclic Loading and Unloading.

Energy is often dissipated and released in the process of rock deformation and failure. To study the energy evolution of rock discontinuities under cyclic loading and unloading, cement mortar was used as rock material and a CSS-1950 rock biaxial rheological testing machine was used to conduct graded cyclic loading and unloading tests on Barton's standard profile line discontinuities with different joint roughness coefficients (JRCs). According to the deformation characteristics of the rock discontinuity sample, the change of internal energy is calculated and analyzed. The experimental results show that under the same cyclic stress, the samples harden with the increase in the number of cycles. With the increase of cyclic stress, the dissipated energy density of each stage gradually exceeds the elastic energy density and occupies a dominant position and increases rapidly as failure becomes imminent. In the process of increasing the shear stress step-by-step, the elastic energy ratio shows a downward trend, but the dissipated energy is contrary to it. The energy dissipation ratio can be used to characterize the internal damage of the sample under load. In the initial stage of fractional loading, the sample is in the extrusion compaction stage, and the energy dissipation ratio remains quasi-constant; then the fracture develops steadily, the damage inside the sample intensifies, and the energy dissipation ratio increases linearly (albeit at a low rate). When the energy storage limit is reached, the growth rate of energy dissipation ratio increases and changes when the stress level reaches a certain threshold. The increase of the roughness of rock discontinuity samples will improve their energy storage capacity to a certain extent.

Carbon Emission Factors Identification and Measurement Model Construction for Railway Construction Projects.

Carbon emissions have become a focus of political and academic concern in the global community since the launch of the Kyoto Protocol. As the largest carbon emitter, China has committed to reaching the carbon peak by 2030 and carbon neutrality by 2060 in the 75th United Nations High-level Meeting. The transport sector needs to be deeply decarbonized in China to achieve this goal. Previous studies have shown that the carbon emissions of the railway sector are small compared to highways, waterways, and civil aviation. However, these studies only consider the operation stage and do not consider the carbon emissions caused by large-scale railway infrastructure construction during the construction stage. As an essential source of carbon emissions and the focus of emissions reduction, the carbon emission of railway construction projects (RCPs) is in urgent need of relevant research. Based on a systematic literature review (SLR), this paper sorts out the carbon emission factors (CEFs) related to RCPs; combines semi-structured expert interviews to clarify the carbon emissions measurement boundary of RCPs; modifies and calibrates CEFs; constructs the carbon emission measurement model of RCPs including building material production stage, building material transportation stage, and construction stage; and conducts empirical analysis to validate carbon emission factors and measurement models. This study effectively complements the theoretical research on CEFs and measurement models in the construction stage of railway engineering and contributes to guiding the construction of low-carbon railways practically.

Disease resistance and growth promotion activities of chitin/cellulose nanofiber from spent mushroom substrate to plant.

Some studies have reported the method for treating the spent mushroom substrate (SMS). However, the effective use as a functional raw material based on properties of SMS remains a formidable challenge. In this study, we investigated the usefulness of SMS in agriculture to develop a new method for treating and utilizing it. First, we attempted to isolate chitin/cellulose nanofiber complex (CCNFC) from SMS using chemical pretreatment and mechanical fibrillation. The characterization results like SEM, FT-IR, and XRD showed that we successfully isolated the CCNFC from SMS. Second, we explored the biological activities of the CCNFC for its potential application as a functional agricultural nanomaterial. CCNFC water dispersion with low concentration (0.1 and 1 mg/mL) exhibited significant plant disease resistance and plant growth promotion activities. Our results suggested that SMS may provide a useful source of functional agricultural nanomaterial, which may contribute to treating and applying it in agriculture.

Absolute Lymphocyte Count Prior to Lymphodepletion Impacts Outcomes in Multiple Myeloma Patients Treated with Chimeric Antigen Receptor T Cells.

Chimeric antigen receptor (CAR) T cell therapy has shown unprecedented response rates in patients with relapsed/refractory (R/R) multiple myeloma (MM). However, the factors associated with immediate response and durable remission have not been fully elucidated. This study aimed to investigate the impact of prelymphodepletion (pre-LD) absolute lymphocyte count (ALC) on the outcomes of CAR T cell therapy and cytokine release syndrome (CRS). A receiver operating characteristic curve was used to determine the optimal cutoff value of pre-LD ALC. The correlation of pre-LD ALC with deep response (defined as very good partial response or better), CRS, and long-term outcomes was analyzed in 85 patients with R/R MM who received CAR T cell treatment. The median pre-LD ALC was 1.0 × 109/L (range, 0.1 to 2.9× 109/L). The optimal cutoff value of pre-LD ALC was 0.75 × 109/L. Twenty-two patients (26%) had a low pre-LD ALC (<0.75 × 109/L), and 63 patients (74%) had a high pre-LD ALC (≥0.75 × 109/L). The deep response rate was significantly higher in patients with a high pre-LD ALC compared with patients with a low pre-LD ALC (76% versus 41%; P = .002). Patients with a low pre-LD ALC had significantly inferior overall survival (OS) and progression-free survival (PFS) compared with those with a high pre-LD ALC (median OS, 15.4 months versus not reached [P < .001]; median PFS, 8.4 months versus 27.3 months [P < .001]). No correlation between pre-LD ALC and CRS was observed. Our data indicate that pre-LD ALC may be a useful indicator to predict the outcomes of CAR T cell therapy in patients with R/R MM. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Impact of glucocorticoids on short-term and long-term outcomes in patients with relapsed/refractory multiple myeloma treated with CAR-T therapy.

Background: Glucocorticoids (GCs) are often used to treat cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The effects of GCs on the efficacy of CAR-T cell treatment in relapsed/refractory multiple myeloma (RRMM) have not been fully established. We evaluated the impact of GCs on clinical outcomes of RRMM patients treated with CAR-T cells. Methods: This study involved RRMM patients treated with CAR-T cells at our center between June 2017 and December 2020. Patients were stratified into GC-used group (GC-group) and non-GC-used group (NGC-group). CRS or ICANS was graded on the basis of the American Society of Transplantation and Cellular Therapy consensus grading system. Response status was evaluated by the IMWG Uniform Response Criteria. The duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were calculated. Result: A total of 71 patients were included in this study. In the NGC group (40 patients), 34 (85%) had responses to CAR-T cell therapy, including 16 (40%) stringent complete response (sCR), seven (17.5%) complete response (CR), five (12.5%) very good partial response (VGPR), and six (15%) partial response (PR). The overall response rate (ORR) and complete response rate (CRR) in the NGC group were 85% and 57.5%. In the GC group (31 patients), 29 (93.5%) had responses, including 11 (35.5%) sCR, nine (29%) CR, two (6.4%) VGPR, and seven (22.6%) PR. Differences in ORR and CRR between the two groups were insignificant. The dose, duration, and timing of GCs did not affect ORR and CRR. At a median follow-up of 28.2 months, the median PFS was 20.4 months (95% CI, 7.9 to 32.9) while the median OS was 36.6 months (95% CI, 25.9 to 47.2) for the GC group. The median PFS and OS for the NGC group were 13.7 months (95% CI, 8.8 to 18.6) and 27.5 months (95% CI, 14.1 to 41.0). There were no significant differences in either PFS or OS between the GC group and the NGC group. Differences in median DOR for the patients with CR or better in the GC group and NGC group were not significant (p = 0.17). Earlier, prolonged use and high dose of GCs were not associated with any effects on either PFS or OS. Additionally, GCs had no effects on CAR-T cell proliferation. Conclusion: Administration of GCs, dose, timing, and duration does not influence the clinical efficacy of CAR-T cells in RRMM in this study.