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The influence of chimeric antigen receptor T (CAR-T) cell therapy on platelet function in relapsed/refractory (R/R) multiple myeloma (MM) has not been thoroughly investigated. Our cohort comprised fifty MM patients treated with CAR-T cells. The mean platelet closure time (PCT) induced by collagen/adenosine diphosphate (CADP) in peripheral blood was significantly prolonged before lymphodepletion (195.24 ± 11.740 s) and notably reduced post-CAR-T cell therapy (128.02 ± 5.60 s), with a statistically significant improvement (67.22, 95% CI 46.91-87.53, P < 0.001). This post-treatment PCT was not significantly different from that of healthy controls (10.64, 95% CI 1.11-22.40, P > 0.05). Furthermore, a pronounced enhancement in PCT was observed in patients with a response greater than partial remission (PR) following CAR-T cell infusion compared to pre-treatment values (P < 0.001). An extended PCT was also associated with a less favorable remission status. In patients with cytokine release syndrome (CRS) grades 0-2, those with a PCT over 240.5 s exhibited a shorter progression-free survival (PFS), with median PFS times of 10.2 months for the PCT > 240.5 s group versus 22.0 months for the PCT ≤ 240.5 s group. Multivariate analysis revealed that a PCT value exceeding 240.5 s is an independent prognostic factor for overall survival (OS) in R/R MM patients after CAR-T cell therapy. The study demonstrates that CAR-T cell therapy enhances platelet function in R/R MM patients, and PCT emerges as a potential prognostic biomarker for the efficacy of CAR-T cell therapy., (© 2024. The Author(s).)

Relapsed/refractory multiple myeloma patients with extramedullary disease (EMD) have unfavorable prognosis and lack effective therapy. Chimeric antigen receptor (CAR) T-cell activities in EMD have yet to be determined; how EMD-specific microenvironment influences the clinical outcomes of CAR T-cell therapy remains of great interest. In this prospective cohort study, patients with histologically confirmed extra-osseous EMD were enrolled and treated with combined anti-BCMA and anti-CD19 CAR T-cell therapy from May 2017 to September 2023. Thirty-one patients were included in the study. Overall response occurred in 90.3% of medullary disease and 64.5% of EMD (p = .031). Discrepancies in treatment response were noted between medullary and extramedullary diseases, with EMD exhibiting suboptimal and delayed response, as well as shortened response duration. With a median follow-up of 25.3 months, the median progression-free and overall survival were 5.0 and 9.7 months, respectively. Landmark analysis demonstrated that progression within 6 months post-infusion is strongly associated with an increased risk of death (HR = 4.58; p = .029). Compared with non-EMD patients, patients with EMD showed inferior survival outcomes. Unique CAR-associated local toxicities at EMD were seen in 22.6% patients and correlated with the occurrence and severity of systemic cytokine release syndrome. To the cutoff date, 65% treated patients experienced EMD progression, primarily in the form of BCMA + progression. The pretherapy EMD immunosuppressive microenvironment, characterized by infiltration of exhausted CD8 + T cells, was associated with inferior clinical outcomes. CAR T cells have therapeutic activity in relapsed/refractory EMD, but the long-term survival benefits may be limited. EMD-specific microenvironment potentially impacts treatment. Further efforts are needed to extend EMD remission and improve long-term outcomes., (© 2024 Wiley Periodicals LLC.)

Background: Some challenges still exist with single-target B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapies due to variable or negative BCMA expression, although they have yielded remarkable efficacy in relapsed or refractory multiple myeloma. We developed anti-BCMA/GPRC5D bispecific CARs to mitigate the limitations and potentiate the functions of CAR T cells., Methods: This single-arm, phase 1 trial was conducted at the Affiliated Hospital of Xuzhou Medical University (Xuzhou, China). The trial enrolled patients aged 18-75 years with relapsed or refractory multiple myeloma and an Eastern Cooperative Oncology Group performance status of 0-3. Anti-BCMA/GPRC5D bispecific CAR T cells were administered at 0·5 × 10 6 , 1·0 × 10 6 , 2·0 × 10 6 , and 4·0 × 10 6 CAR T cells per kg in the dose-escalation phase, with additional patients included at the dose selected for the dose-expansion phase. The primary endpoint was safety, which included dose-limiting toxicity and maximum tolerated dose. Activity was also evaluated as a secondary endpoint. The maximum tolerated dose was chosen for the dose-expansion phase. Safety and activity analyses were done in all patients who received anti-BCMA/GPRC5D bispecific CAR T cells as defined in the protocol. This trial is registered with ClinicalTrials.gov (NCT05509530) and is complete., Findings: Between Sept 1, 2022, and Nov 3, 2023, 24 patients were enrolled and underwent apheresis. Three patients were excluded after apheresis (two patients discontinued due to rapid disease progression and one patient was withdrawn because of failed manufacture of CAR T cells), so 21 patients were infused with anti-BCMA/GPRC5D bispecific CAR T cells. Median follow-up was 5·8 months (IQR 5·2-6·7). Median age was 62 years (IQR 56-67). Eight (38%) patients were male, and 13 (62%) female. All patients were Chinese. At the 4·0 × 10 6 CAR T cells per kg dose, two patients had dose-limiting toxicities, of whom one died of subarachnoid haemorrhage (which was not considered to be related to the study treatment). The maximum tolerated dose was identified as 2·0 × 10 6 CAR T cells per kg. The most common grade 3 or worse adverse events were haematological toxicities in 19 (90%) patients (except lymphopenia). 15 (71%) patients had cytokine release syndrome, of which all cases were grade 1 or 2. One case of grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in a patient who received 4·0 × 10 6 CAR T cells per kg. No ICANS or grade 3 or worse organ toxicities were observed in patients who received 0·5-2·0 × 10 6 CAR T cells per kg. The overall response rate was 86% (18 of 21 patients), with 13 (62%) patients having a complete response or better, and 17 (81%) patients having measurable residual disease negativity. Of the 12 patients who received 2·0 × 10 6 CAR T cells per kg (three in the dose-escalation phase and an addition nine in the dose-expansion phase), the overall response rate was 92% (11 of 12 patients) with nine (75%) patients having a complete response or better., Interpretation: Anti-BCMA/GPRC5D bispecific CAR T cells show a good safety profile and encouraging activity in patients with relapsed or refractory multiple myeloma., Funding: National Natural Science Foundation of China., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests AHC is a founding member of Shanghai YaKe Biotechnology, a biotechnology company focusing on research and development of tumour cellular immunotherapy. YZ and SP are employed by Shanghai YaKe Biotechnology. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Trailing parents, a distinct group emerging from China's rapid social change and urbanization, are experiencing migration in old age, posing challenges for their social adaptation. Existing research has mainly focused on the hardships faced by this group, but few studies have focused on how they cope with change and achieve some degree of successful social adaptation. This study aimed to understand the coping and social adaptation process of trailing parents in China., Methods: This study used a qualitative research approach. A total of 24 trailing parents were invited to participate in a semi-structured interview and share their experiences and efforts to cope with the many challenges. Kumpfer's resilience framework was used as the theoretical framework for the study design, data collection, and data analysis., Results: This study identified several intra-family and community stressors that trailing parents may face when moving to a new environment and uncovered five key resilience characteristics that may be triggered or fostered in the presence of these stressors, including physical fitness, psychological stability, open-mindedness, learning ability, and nurturing hobbies. Individuals with resilience traits have been observed to engage in positive cognitive processing and transform the new environment. Consistent with Kumpfer's resilience framework, this study revealed the dynamics of the stressors faced by trailing parents in the new environments, the role of resilience characteristics, and the critical influence of social support in shaping the interplay between the individual and the environment that enabled them to adapt positively., Conclusions: This study highlights the importance of fostering resilience traits and leveraging positive coping mechanisms to facilitate a smoother adaptation process for trailing parents. Meanwhile, there is an urgent need to focus on creating opportunities that strengthen their social support networks., (© 2024. The Author(s).)

Background: Peripheral T-cell lymphomas (PTCL) are an aggressive group of mature T-cell neoplasms, often associated with poor outcomes, in part, due to frequent relapsed/refractory disease. The objective of this study was to assess the prognostic impact of disease progression within 24 months (POD24) on overall survival (OS) for patients diagnosed with PTCL., Methods: A retrospective analysis was conducted on a cohort of patients with newly diagnosed PTCL who underwent chemotherapy at the Affiliated Hospital of Xuzhou Medical University between January 2010 and September 2021. Prognostic assessment was limited to patients who were evaluable for POD24., Results: Records were reviewed for 106 patients with PTCL, of whom 66 patients experienced POD24 (referred to as the POD24 group) and 40 patients did not experience POD24 (referred to as the no POD24 group). Significant differences were observed between the POD24 group and the no POD24 group in regard to clinical stage, Eastern Cooperative Oncology Group (ECOG) performance status (PS), International Prognostic Index (IPI) score, lactate dehydrogenase (LDH) levels, β2-microglobulin (β2-MG) levels, prealbumin and albumin levels. Patients in the POD24 group had a significant shorter median OS compared to the no POD24 group (11.9 months vs not reached, respectively; P  < 0.001). Non response (NR) to treatment and POD24 were identified as independent negative prognostic factors for survival in patients with PTCL., Conclusion: POD24 is a prognostic factor associated with unfavorable outcomes in patients with PTCL and can be used to identify high-risk patients and guide treatment decisions.

Despite the high therapeutic response achieved with B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapy in relapsed and refractory multiple myeloma (R/R MM), primary resistance and relapse exist with single-target immunotherapy. Here, we design bispecific BC19 CAR T cells targeting BCMA/CD19 and evaluate antimyeloma activity in vitro and in vivo. Preclinical results indicate that BC19 CAR specifically recognize target antigens, and BC19 CAR T cells mediate selective killing of BCMA or CD19-positive cancer cells. BC19 CAR T cells also exhibit potent antigen-specific anti-tumor activity in xenograft mouse models. We conduct an open-label, single-arm, phase I/II study of BC19 CAR T cells in 50 patients with R/R MM (ChiCTR2000033567). The primary endpoint was safety. BC19 CAR T cells are well tolerated with grade 3 or higher cytokine release syndrome in 8% of patients and grade 1 neurotoxic events in 4% of patients, which meet the pre-specified primary endpoint. Secondary endpoints include overall response rate (92%), median progression-free survival (19.7 months), median overall survival (19.7 months) and median duration of response (not reached). Our study demonstrates that bispecific BC19 CAR T cells are feasible, safe and effective in treating patients with R/R MM., (© 2024. The Author(s).)

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) B-cell acute lymphoblastic leukemia (B-ALL). We present a retrospective study of 67 patients with R/R B-ALL who received anti-CD19 CAR T-cell therapy, 41 (61.2%) patients received G-CSF (G-CSF group), while 26 (38.8%) did not (non-G-CSF group). Patients had similar duration of grade 3-4 neutropenia between the two groups. The incidences of CRS and NEs were higher in G-CSF group, while no differences in severity were found. Further stratified analysis showed that the incidence and severity of CRS were not associated with G-CSF administration in patients with low bone marrow (BM) tumor burden. None of the patients with low BM tumor burden developed NEs. However, there was a significant increase in the incidence of CRS after G-CSF administration in patients with high BM tumor burden. The duration of CRS in patients who used G-CSF was longer. There were no significant differences in response rates at 1 and 3 months after CAR T-cell infusion, as well as overall survival (OS) between the two groups. In conclusion, our results showed that G-CSF administration was not associated with the incidence or severity of CRS in patients with low BM tumor burden, but the incidence of CRS was higher after G-CSF administration in patients with high BM tumor burden. The duration of CRS was prolonged in G-CSF group. G-CSF administration was not associated with the efficacy of CAR T-cell therapy., (© 2024. The Author(s).)

As the electron transport layer in quantum dot light-emitting diodes (QLEDs), ZnO suffers from excessive electrons that lead to luminescence quenching of the quantum dots (QDs) and charge-imbalance in QLEDs. Therefore, the interplay between ZnO and QDs requires an in-depth understanding. In this study, DFT and COSMOSL simulations are employed to investigate the effect of sulfur atoms on ZnO. Based on the simulations, thiol ligands (specifically 2-hydroxy-1-ethanethiol) to modify the ZnO nanocrystals are adopted. This modification alleviates the excess electrons without causing any additional issues in the charge injection in QLEDs. This modification strategy proves to be effective in improving the performance of red-emitting QLEDs, achieving an external quantum efficiency of over 23% and a remarkably long lifetime T 95 of >12 000 h at 1000 cd m -2 . Importantly, the relationship between ZnO layers with different electronic properties and their effect on the adjacent QDs through a single QD measurement is investigated. These findings show that the ZnO surface defects and electronic properties can significantly impact the device performance, highlighting the importance of optimizing the ZnO-QD interface, and showcasing a promising ligand strategy for the development of highly efficient QLEDs., (© 2023 Wiley‐VCH GmbH.)

Maintaining animal gut health through modulating the gut microbiota is a constant need when antibiotics are not used in animal feed during the food animal production process. Prebiotics is regarded as one of the most promising antibiotic alternatives for such purpose. As an attractive prebiotic, the role and mechanisms of neoagarooligosaccharides (NAOS) in promoting animal growth and gut health have not been elucidated. In this study, we first cloned and expressed marine bacterial β-agarase in yeast to optimize the NAOS preparation and then investigated the role and the underlying mechanisms of the prepared NAOS in improving chicken gut health and function. The marine bacterial β-agarase PDE13B was expressed in Pichia pastoris GS115 and generated even-numbered NAOS. Dietary the prepared NAOS promoted chicken growth and improved intestinal morphology, its barrier, and digestion capabilities, and absorption function. Metagenomic analysis indicated that NAOS modulated the chicken gut microbiota structure and function, and microbial interactions, and promoted the growth of spermidine-producing bacteria especially Faecalibacterium. Through integration of gut metagenome, gut content metabolome, and gut tissue transcriptome, we established connections among NAOS, gut microbes, spermidine, and chicken gut gene expression. The spermidine regulation of genes related to autophagy, immunity, and inflammation was further confirmed in chicken embryo intestinal epithelium cells. We also verified that NAOS can be utilized by Faecalibacterium prausnitzii to grow and produce spermidine in in vitro experiments. Collectively, we provide a systematic investigation of the role of NAOS in regulating gut health and demonstrate the microbial spermidine-mediated mechanism involved in prebiotic effects of NAOS, which lays foundation for future use of NAOS as a new antibiotic alternative in animal production., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The concept of high entropy is considered promising to enhance electromagnetic wave absorption properties. However, preparing high-entropy sulfides with unique structures for high-performance electromagnetic absorption remains a challenge. In this study, hierarchical porous flower-like dual-phase sulfides were designed with increased entropy and fabricated using a versatile approach. The porous flower configuration enhanced the scattering of electromagnetic waves and the impedance-matching characteristics. Additionally, the effect of high entropy induced diverse defects that were favorable for electromagnetic wave dissipation in dual-phase sulfides. The design of the dual-phase structure generated strong interface polarization, and the composition and content of the phases exhibited clear changes with the increase in the number of metal elements. Interestingly, apparent lattice distortions, defects, and shear strains were directly observed near the dual-phase interface of millerite (102) and pyrite (220) planes, facilitating the occurrence of dipole polarization. Consequently, the developed dual-phase high-entropy sulfide exhibited outstanding microwave absorption properties. The minimum reflection loss value of (FeCoNiCuZn)S was -45.8 dB at a thickness of 1.5 mm, and the optimal effective absorption bandwidth was 3.8 GHz at a thickness of 1.4 mm thickness. Thus, the design of high-entropy sulfides brings meaningful guidance for tuning the wave absorption properties in sulfides.

Importance: The improvement of chicken growth performance is one of the major concerns for the poultry industry. Gut microbes are increasingly evidenced to be associated with chicken physiology and metabolism, thereby influencing chicken growth and development. Here, through integrated multi-omics analyses, we showed that chickens from the same line differing in their body weight were very different in their gut microbiota structure and host-microbiota crosstalk; microbes in high body weight (HBW) chickens contributed to chicken growth by regulating the gut function and homeostasis. We also verified that a specific bacterial consortium consisting of isolates from the HBW chickens has the potential to be used as chicken growth promoters. These findings provide new insights into the potential links between gut microbiota and chicken phenotypes, shedding light on future manipulation of chicken gut microbiota to improve chicken growth performance., Competing Interests: The authors declare no conflict of interest.

The development of hyperuricemia (HUA) and gout is associated with dysbiosis of the gut microbiota. Quercetin can reduce serum uric acid levels and thus alleviate HUA by modulating the gut microbiota. However, the detailed mechanisms involved in this process are not fully understood. Here, we showed that quercetin significantly reduced the serum uric acid level in a chicken HUA model by altering the chicken cecal microbiota structure and function and increasing the abundance of Lactobacillus aviarius. An L. aviarius strain, CML180, was isolated from the quercetin-treated chicken gut microbiota. Strain characterization indicated that quercetin promoted the growth of L. aviarius CML180 and increased its adhesion, hydrophobicity, and co-aggregation abilities. Gavage of live L. aviarius CML180 to a mouse model of HUA-established by adenosine and potassium oxonate-reduced the serum uric acid level and alleviated HUA. The ability of L. aviarius CML180 to decrease the level of uric acid was due to its degradation of purine nucleosides, which are the precursors for uric acid production. A nucleoside hydrolase gene, nhy69, was identified from the genome of L. aviarius CML180, and the resulting protein, Nhy69, exhibited strong purine nucleoside-hydrolyzing activity at mesophilic temperature and neutral pH conditions. These findings provide mechanistic insights into the potential of quercetin to treat HUA or gout diseases via a specific gut microbe., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Class I flextensional transducers cannot form broadband characteristics because of the deep valley between their first- and second-order response curves. This valley arises from the sound pressure cancellation produced by the vibration in different areas of the shell. This paper examines the cause of the deep valley by analyzing the three-dimensional equivalent radiated sound field of the transducer. By solving the three-dimensional vibration equation of the shell of revolution and reducing its dimensionality, it can be concluded that its vibration state is related to the positive and negative curvatures in both main directions. Therefore, a variable-curvature shell class I flextensional transducer is proposed, and the second-order vibration of the transducer is changed by the variable-curvature structure composed of positive and negative Gaussian curvature surfaces. The proposed transducer avoids sound pressure cancellation and achieves broadband characteristics. After optimization, a transducer prototype is fabricated, and a pool test is conducted. The test results show that the transducer couples the first three vibration modes, attaining broadband characteristics with an in-band fluctuation of less than 8 dB and a bandwidth of more than 5.4 kHz in the axial and circumferential directions., (© 2023 Acoustical Society of America.)

Artificial neural networks are prone to suffer from catastrophic forgetting. Networks trained on something new tend to rapidly forget what was learned previously, a common phenomenon within connectionist models. In this work, we propose an effective and efficient continual learning framework using random theory, together with Bayes' rule, to equip a single model with the ability to learn streaming data. The core idea of our framework is to preserve the performance of old tasks by guiding output weights to stay in a region of low error while encountering new tasks. In contrast to the existing continual learning approaches, our main contributions concern (1) closed-formed solutions with detailed theoretical analysis; (2) training continual learners by one-pass observation of samples; (3) remarkable advantages in terms of easy implementation, efficient parameters, fast convergence, and strong task-order robustness. Comprehensive experiments under popular image classification benchmarks, FashionMNIST, CIFAR-100, and ImageNet, demonstrate that our methods predominately outperform the extensive state-of-the-art methods on training speed while maintaining superior accuracy and the number of parameters, in the class incremental learning scenario. Code is available at https://github.com/toil2sweet/CRNet.

A new simple Pt(ii) terpyridyl salt that shows reversible response towards acetonitrile and irreversible response towards methanol has been reported, accompanied with the colorimetric/luminescent changing from red to yellow. Experimentally and theoretically, the spectroscopic change derives from the hydrogen bonds between crystal water in the Pt(ii) terpyridyl salt and external organic molecules, and the different strength of hydrogen bond leads either reversible or irreversible stimuli-response. Furthermore, this Pt(ii) terpyridyl salt has been on one hand applied as a probe for sensing acetonitrile in water solution, with high selectivity, good reversibility, proper sensitivity and fast response rate, and on the other hand as advanced anticounterfeiting materials. The current study provides a new approach to acquire and design either reversible or irreversible stimuli-responsive luminescent materials., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Background: Ginkgo biloba extract (GBE) is evidenced to be effective in the prevention and alleviation of metabolic disorders, including obesity, diabetes and fatty liver disease. However, the role of GBE in alleviating fatty liver hemorrhagic syndrome (FLHS) in laying hens and the underlying mechanisms remain to be elucidated. Here, we investigated the effects of GBE on relieving FLHS with an emphasis on the modulatory role of GBE in chicken gut microbiota., Results: The results showed that GBE treatment ameliorated biochemical blood indicators in high-fat diet (HFD)-induced FLHS laying hen model by decreasing the levels of TG, TC, ALT and ALP. The lipid accumulation and pathological score of liver were also relieved after GBE treatment. Moreover, GBE treatment enhanced the antioxidant activity of liver and serum by increasing GSH, SOD, T-AOC, GSH-PX and reducing MDA, and downregulated the expression of genes related to lipid synthesis (FAS, LXRα, GPAT1, PPARγ and ChREBP1) and inflammatory cytokines (TNF-α, IL-6, TLR4 and NF-κB) in the liver. Microbial profiling analysis revealed that GBE treatment reshaped the HFD-perturbed gut microbiota, particularly elevated the abundance of Megasphaera in the cecum. Meanwhile, targeted metabolomic analysis of SCFAs revealed that GBE treatment significantly promoted the production of total SCFAs, acetate and propionate, which were positively correlated with the GBE-enriched gut microbiota. Finally, we confirmed that the GBE-altered gut microbiota was sufficient to alleviate FLHS by fecal microbiota transplantation (FMT)., Conclusions: We provided evidence that GBE alleviated FLHS in HFD-induced laying hens through reshaping the composition of gut microbiota. Our findings shed light on mechanism underlying the anti-FLHS efficacy of GBE and lay foundations for future use of GBE as additive to prevent and control FLHS in laying hen industry., (© 2023. The Author(s).)

Despite surpassing lung cancer as the most frequently diagnosed cancer, female breast cancer (BC) still lacks rapid detection methods for screening that can be implemented on a large scale in practical clinical settings. However, urine is a readily available biofluid obtained non-invasively and contains numerous volatile organic metabolites (VOMs) that offer valuable metabolic information concerning the onset and progression of diseases. In this work, a rapid method for analysis of VOMs in urine by using high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS) coupled with dynamic purge injection. A simple pretreatment process of urine samples by adding acid and salt was employed for efficient VOM sampling, and the numbers of metabolites increased and the detection sensitivity was improved after the acid (HCl) and salt (NaCl) addition. The established mass spectrometry detection method was applied to analyze a set of training samples collected from a local hospital, including 24 breast cancer patients and 27 healthy controls. Statistical analysis techniques such as principal component analysis, partial least squares discriminant analysis, and the Mann-Whitney U test were used, and nine VOMs were identified as differential metabolites. Finally, acrolein, 2-pentanone, and methyl allyl sulfide were selected to build a metabolite combination model for distinguishing breast cancer patients from the healthy group, and the achieved sensitivity and specificity were 92.6% and 91.7%, respectively, according to the receiver operating characteristic curve analysis. The results demonstrate that this technology has potential to become a rapid screening tool for breast cancer, with significant room for further development.

The present study aimed to determine the clinical characteristics of cytopenia in patients with relapsed and refractory B-cell non-Hodgkin lymphoma (B-NHL) who were treated with chimeric antigen receptor T-cell (CAR-T) therapy. Thus, a total of 63 patients with relapsed and refractory B-NHL who underwent CAR-T therapy between March 2017 and October 2021 were retrospectively selected for analysis. Neutropenia, anemia and thrombocytopenia at grade ≥3 occurred in 48 (76.19%), 16 (25.39%) and 15 (23.80%) cases, respectively. The results of a multivariate analysis demonstrated that the baseline absolute neutrophil count (ANC) and hemoglobin concentration were independent risk factors for grade ≥3 cytopenia. A total of 3 patients died early and were therefore excluded from the present study. Furthermore, cell recovery was examined at day +28 after infusion; 21 patients (35%) did not recover from cytopenia and 39 patients (65%) recovered. A multivariate analysis demonstrated that the baseline ANC <2.29×10 9 /l, baseline hemoglobin <114.50 g/l and baseline IL-6 >21.43 pg/l were independent risk factors affecting hemocyte recovery. In conclusion, patients with relapsed and refractory B-NHL exhibited an increased incidence of grade ≥3 hematologic toxicity following CAR-T cell therapy, while baseline blood cell and IL-6 levels are independent risk factors for hemocyte recovery., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2023, Spandidos Publications.)

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., Competing Interests: Declaration of Competing Interests The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

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 × 10 6 /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.

Introduction: Chimeric antigen receptor (CAR) T cell therapy has achieved unprecedented efficacy recently. However, the factors related to responses and durable remission are elusive. This study was to investigate the impact of pre-lymphodepletion (pre-LD) absolute lymphocyte count (ALC) on CAR T cell therapy outcomes., Methods: We conducted a retrospective study of 84 patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) who underwent CAR T cell treatment at the Affiliated Hospital of Xuzhou Medical University between March 1,2016 and December 31, 2021. The enrolled patients were divided into high group and low group according to the optimal cutoff value of pre-LD ALC. The Kaplan-Meier analyses was used to calculate survival curves. The Cox proportional hazards model was used for univariate and multivariate analysis to assess the prognostic factors., Results: The ROC showed that the optimal cutoff value of pre-LD ALC was 1.05 x 10 9 /L. The overall response (defined as partial response or complete response) rate was significantly higher in patients with a high pre-LD ALC (75% versus 52.08%; P=0.032). Patients with a low pre-LD ALC had significantly inferior overall survival (OS) and progression-free survival (PFS) compared with those having a high pre-LD ALC (median OS, 9.6 months versus 45.17 months [P=0.008]; median PFS, 4.07 months versus 45.17 months [P= 0.030]). Meanwhile, low pre-LD ALC is an independent risk factor for PFS and OS., Discussion: The data suggested that pre-LD ALC may serve as a helpful indicator to predict the outcomes of CAR T cell therapy in patients with R/R DLBCL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lu, Zhu, Liu, Wang, Sun, Cheng, Yan, Cao, Sang, Zhu, Li, Sun, Zheng, Xu and Li.)

Background: Chimeric antigen receptor - T (CAR-T) cell therapy has shown remarkable efficacy in patients with relapsed/refractory multiple myeloma (R/R MM). However, a subset of patients still experienced progression or relapse, and the predictors of prognosis are little known. We analyzed the inflammatory markers before CAR-T cell infusion, to clarify their correlation with survival and toxicity., Methods: This study involved 109 R/R MM patients who received CAR-T therapy between June 2017 and July 2021. Inflammatory markers, including ferritin, c-reactive protein (CRP), and interleukin-6 (IL-6) before CAR-T cell infusion were detected and then categorized by quartiles. Adverse events and clinical outcomes were compared between patients with upper quartile of inflammatory markers and patients with lower three quartiles of inflammatory markers. An inflammatory prognostic index (InPI) based on these three inflammatory markers was developed in this study. Patients were divided into 3 groups according to the InPI score, progression-free survival (PFS) and overall survival (OS) were compared among the groups. In addition, we explored the correlation between cytokine release syndrome (CRS) and pre-infusion inflammatory markers., Results: We found that the pre-infusion high ferritin (hazard ratio [HR], 3.382; 95% confidence interval [CI], 1.667 to 6.863; P = .0007), high CRP (HR, 2.043; 95% CI, 1.019 to 4.097; P = .044), and high IL-6 (HR, 3.298; 95% CI, 1.598 to 6.808; P = .0013) were significantly associated with inferior OS. The formula of the InPI score was based on the HR value of these 3 variables. Three risk groups were formed: (good, 0 to 0.5 point; intermediate, 1 to 1.5 points; poor, 2 to 2.5 points). Median OS for patients with good, intermediate, and poor InPI was not reached, 24 months, and 4 months, respectively, and median PFS was 19.1 months, 12.3 months, and 2.9 months, respectively. In the cox proportional hazards model, poor InPI remained an independent prognostic factor for PFS and OS. Pre-infusion ferritin was negatively associated with CAR T-cell expansion normalized to baseline tumor burden. Spearman correlation analysis showed that pre-infusion ferritin and IL-6 levels positively correlated with the grade of CRS ( P = .0369 and P = .0117, respectively). The incidence of severe CRS was higher in patients with high IL-6 compared with patients with low IL-6 (26% vs . 9%, P = .0405). Pre-infusion ferritin, CRP and IL-6 were positively correlated with each peak values within the first month after infusion., Conclusions: Our results suggest that patients with elevated inflammation markers before CAR-T cell infusion are more likely to have poor prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Jie, Nian, Wang, Wang, Ma, Jiang, Wu, Qiao, Chen, Cao, Yan, Shi, Cheng, Zhu, Sang, Li, Chen, Xu and Li.)

Phytoremediation is considered an effective method for indoor air pollution control. The removal rate and mechanism of benzene in air by two plants, Tradescantia zebrina Bosse and Epipremnum aureum (Linden ex André) G. S. Bunting, were investigated through fumigation experiments under the condition of plant hydroponics culturing. Results showed that the plant removal rates increased with increase in benzene concentration in air. When the benzene concentration in air was set at 432.25-1314.75 mg·m -3 , the removal rates of T. zebrina and E. aureum ranged from 23.05 ± 3.07 to 57.42 ± 8.28 mg·kg -1 ·h -1 FW and from 18.82 ± 3.73 to 101.58 ± 21.20 mg·kg -1 ·h -1 FW, respectively. The removal capacity was positively related to the transpiration rate of plants, indicating that gas exchange rate could be a key factor for the evaluation of removal capacity. There existed fast reversible transport of benzene on air-shoot interface and root-solution interface. After shoot exposure to benzene for 1 h, downward transport was the dominant mechanism in the removal of benzene in air by T. zebrina, while in vivo fixation was the dominant mechanism at exposure time of 3 and 8 h. Within 1-8 h of shoot exposure time, in vivo fixation capacity was always the key factor affecting the removal rate of benzene in the air by E. aureum. Contribution ratio of in vivo fixation in the total benzene removal rate increased from 6.29 to 92.29% for T. zebrina and from 73.22 to 98.42% for E. aureum in the experimental conditions. Reactive oxygen species (ROS) burst induced by benzene exposure was responsible for the contribution ratio change of different mechanisms in the total removal rate, which also was verified by the change of activities of antioxidant enzymes (CAT, POD, and SOD). Transpiration rate and antioxidant enzyme activity could be considered parameters to evaluate the plant removal ability to benzene and to screen plants for establishment of plant-microbe combination technology., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In quantum dot light-emitting diodes (QLEDs), even seemingly with interfacial exciton quenching between quantum dots (QDs) and the electron transport layer (ETL) limiting the device efficiency, the internal quantum efficiency of such QLEDs approaches 100%. Therefore, it is a puzzle that QLEDs exhibit high performance although they suffer from interfacial exciton quenching. In this work, we solve this puzzle by identifying the cause of the interfacial exciton quenching. By analyzing the optical characteristics of pristine and encapsulated QD-ETL films, the interfacial exciton quenching in the pristine QD-ETL film is attributed to O 2 -induced charge transfer. We further investigate the charge transfer mechanism and its effect on the performance of QLEDs. Finally, we show the photodegradation of the pristine QD-ETL film under UV irradiation. Our work bridges interfacial exciton quenching and high performance in hybrid QLEDs and highlights the significance of encapsulation in QLEDs.

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 (R 2  = 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/mm 3 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/mm 3 , 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., Competing Interests: Declaration of competing interest The authors declared that they have no conflict of interest., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Type IV flextensional transducers do not have broadband characteristics due to the deep valley between their first- and second-order response curves arising from the sound pressure cancellation produced by the vibration in different areas of the shell. In this paper, the cause of the deep valley is examined by analyzing the equivalent radiated sound field of the transducer. Simplifying the three-dimensional vibration equation to a two-dimensional equation shows that the vibration state of the shell is related to the positive and negative curvature. Therefore, a variable-shell flextensional transducer with a negative curvature is proposed, which changes the second-order vibration of the transducer by introducing a negative curvature structure. The transducer avoids acoustic pressure cancellation, achieves broadband characteristics, and has continuous high efficiency in the frequency band. After optimization, a prototype of the transducer is fabricated and a pool test is completed. The test results show that the transducer realizes the coupling of the first three vibration mode, forming a broad band with an in-band fluctuation of less than 8 dB at 1200-5600 Hz, and the efficiencies of the first to third resonance peaks are 30.2 %, 16.6 %, and 9.4 %, respectively.

Encouraging response has been achieved in relapsed/refractory (R/R) B-cell lymphoma treated by chimeric antigen receptor T (CAR-T) cells. The efficacy and safety of CAR-T cells in central nervous system lymphoma (CNSL) are still elusive. Here, we retrospectively analyzed 15 patients with R/R secondary CNSL receiving CD19-specific CAR-T cell-based therapy. The patients were infused with CD19, CD19/CD20 or CD19/CD22 CAR-T cells following a conditioning regimen of cyclophosphamide and fludarabine. The overall response rate was 73.3% (11/15), including 9 (60%) with complete remission (CR) and 2 (13.3%) with partial remission (PR). During a median follow-up of 12 months, the median progression-free survival (PFS) was 4 months, and the median overall survival (OS) was 9 months. Of 12 patients with systemic tumor infiltration, 7 (58.3%) achieved CR in CNS, and 5 (41.7%) achieved CR both systemically and in CNS. Median DOR for CNS and systemic disease were 8 and 4 months, respectively. At the end point of observation, of the 7 patients achieved CNS disease CR, one was still alive with sustained CR of CNS disease and systemic disease. The other 6 died of systemic progression. Of the 15 patients, 11 (73.3%) experienced grades 1-2 CRS, and no patient had grades 3-4 CRS. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 3 (20%) patients, including 1 (6.6%) with grade 4 ICANS. All the CRS or ICANS were manageable. The CD19-specific CAR-T cell-based therapy appeared to be a promising therapeutic approach in secondary CNSL, based on its antitumor effects and an acceptable side effect profile, meanwhile more strategies are needed to maintain the response., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Yan, Wang, Qi, Hu, Li, Cao, Zhang, Xiao, Shi, Xia, Ma, Qiao, Li, Pan, Qi, Cheng, Sun, Zhu, Sang, Li, Li, Zheng, Zhao, Liang, Huang and Xu.)

Purpose: A combination of anti-B-cell maturation antigen (BCMA) and anti-CD19 chimeric antigen receptor (CAR) T cells induced high response rates in patients with relapsed or refractory (R/R) multiple myeloma (MM), but long-term outcomes have not been assessed yet., Patients and Methods: In this single-arm, phase II trial, patients with R/R MM received a combination of anti-BCMA CAR T cells and anti-CD19 CAR T cells at a dose of 1 × 10 6 cells/kg, after receiving a conditioning chemotherapy consisting of cyclophosphamide and fludarabine. The overall response, long-term outcomes, and safety were assessed, as were their associations with clinical and disease characteristics., Results: Of 69 enrolled patients, 62 received the combined infusion of anti-BCMA and anti-CD19 CAR T cells with a median follow-up of 21.3 months. The overall response rate was 92% (57/62), and complete response or better was observed in 37 patients (60%). Minimal residual disease-negativity was confirmed in 77% (43/56) of the patients with available minimal residual disease detection. The estimated median duration of response was 20.3 months (95% CI, 9.1 to 31.5). The median progression-free survival was 18.3 months (95% CI, 9.9 to 26.7), and the median overall survival was not reached. Patients with extramedullary disease had significantly inferior survival. Fifty-nine patients (95%) had cytokine release syndrome, with 10% grade 3 or higher. Neurotoxic events occurred in seven patients (11%), including 3% grade 3 or higher. Late adverse effects were rare, except for B-cell aplasia, hypogammaglobulinemia, and infections., Conclusion: The combination of anti-BCMA and anti-CD19 CAR T cells induced durable response in patients with R/R MM, with a median progression-free survival of 18.3 months and a manageable long-term safety profile.

Electrophoretic deposition (EPD) is a facile technique to deposit quantum dots (QDs) films, which can be used as the color conversion layers for display applications. To better understand the EPD process, researchers have built many models of the EPD process. However, most of these models lack solid experimental support. Here, by adopting simple yet effective solvent engineering and well-designed experiments, this study proves the Cordelair-Greil model on EPD processes. Moreover, some supplements about this model are made according to practical experiments. The experimental verification of the Cordelair-Greil model is a solid step toward revealing the dynamics of the EPD process. Furthermore, the formation of cracks in EPD deposited QD films is prevented through solvent engineering. This work proves that besides modifying the intrinsic properties of QDs, solvent engineering is also a simple, effective, and low-cost way to study the EPD process and improve the QD film qualities deposited., (© 2022 Wiley-VCH GmbH.)

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., (© 2022 by The American Society of Hematology.)

In chickens, the effect of host genetics on the gut microbiota is not fully understood, and the extent to which the heritable gut microbes affect chicken metabolism and physiology is still an open question. Here, we explored the interactions among chicken genetics, the cecal microbiota and metabolites in breast muscle from ten chicken breeds in China. We found that different chicken breeds displayed distinct cecal microbial community structures and functions, and 15 amplicon sequence variants (ASVs) were significantly associated with host genetics through different genetic loci, such as those related to the intestinal barrier function. We identified five heritable ASVs significantly associated with 53 chicken muscle metabolites, among which the Megamonas probably affected lipid metabolism through the production of propionate. Our study revealed that the chicken genetically associated cecal microbes may have the potential to affect the bird's physiology and metabolism., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

This work demonstrated color-conversion layers of red and green quantum dots color filter for full-color display arrays. Ligands exchange using (3-glycidyloxypropyl) trimethoxysilane with epoxy functional groups to treat QDs in the liquid phase was performed for photolithography use. The combination of ligands of QDs with photo-initiator played a protective role on QDs. Moreover, the pixel size of green QDCF can be reduced to 50 μm, and a high optical density (OD) of 1.2 is realized.

Anti-CD30 CAR-T is a potent candidate therapy for relapsed/refractory (r/r) CD30+ lymphomas with therapy limitations, and the efficacy needed to be further improved. Herein a multi-center phase II clinical trial (NCT03196830) of anti-CD30 CAR-T treatment combined with PD-1 inhibitor in r/r CD30+ lymphoma was conducted. After a lymphocyte-depleting chemotherapy with fludarabine and cyclophosphamide, 4 patients in cohort 1 and 3 patients in cohort 2 received 10 6 /kg and 10 7 /kg CAR-T cells, respectively, and 5 patients in cohort 3 received 10 7 /kg CAR-T cells combined with anti-PD-1 antibody. The safety and the efficacy of CAR-T cell therapy were analyzed. Cytokine release syndrome (CRS) was observed in 4 of 12 patients, and only 1 patient (patient 9) experienced grade 3 CRS and was treated with glucocorticoid and tocilizumab. No CAR-T-related encephalopathy syndrome was observed. Only two patients in cohorts 2 and 3 experienced obviously high plasma levels of IL-6 and ferritin after CD30 CAR-T cell infusion. The overall response rate (ORR) was 91.7% (11/12), with 6 patients achieving complete remission (CR) (50%). In cohorts 1 and 2, 6 patients got a response (85.7%), with 2 patients achieving CR (28.6%). In cohort 3, 100% ORR and 80% CR were obtained in 5 patients without ≥3 grade CRS. With a median follow-up of 21.5 months (range: 3 - 50 months), the progression-free survival and the overall survival rates were 45 and 70%, respectively. Of the 11 patients who got a response after CAR-T therapy, 7 patients (63.6%) maintained their response until the end of follow-up. Three patients died last because of disease progression. Taken together, the combination of anti-PD-1 antibody showed an enhancement effect on CD30 CAR-T therapy in r/r CD30+ lymphoma patients with minimal toxicities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sang, Wang, Geng, Li, Li, Zhang, Zhou, Song, Sun, Yan, Li, Li, Li and Xu.)

Microplastics (MPs) coexist with other pollutants (such as heavy metals) in water, adversely impacting aquatic organisms, which might cause unpredictable ecological risks. This study aims to evaluate the effect of copper (Cu 2+ ) and polystyrene microplastics (PS-MPs) on antioxidant capacity, immune response and intestinal microbiota of Nile tilapia. Cu 2+ and PS-MPs co-exposure enhanced Cu 2+ bioaccumulation in the liver of fish compared with Cu 2+ -alone exposure. Fish exposed to PS-MPs and Cu 2+ displayed histopathologic alterations in the liver, intestine and gill. Exposure at low concentrations of Cu 2+ in the C0 and CP0 groups can improve antioxidant capacity and immune response, while oxidative damage and inflammation existed in the high concentration of Cu 2+ groups. Intestinal microbiota results showed that the diversity and structure were changed by Cu 2+ and PS-MPs exposure, and harmful bacterium even increased at high concentration of Cu 2+ and PS-MPs exposure groups. All in all, PS-MPs aggravate the accumulation of Cu 2+ and lead to perturbations in biological systems of Nile tilapia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Hemophagocytic lymphohistiocytosis (HLH) is an immune disorder with rapid progression and poor survival. Individual treatment strategy is restricted, due to the absence of precise stratification criteria. In this multicenter retrospective study, we aimed to develop a feasible prognostic model for adult HLH in China. A total of 270 newly diagnosed patients of adult HLH were retrieved from the Huaihai Lymphoma Working Group (HHLWG), of whom 184 from 5 medical centers served as derivation cohort, and 86 cases from 3 other centers served as validation cohort. X-Tile program and Maxstat analysis were used to identify optimal cutoff points of continuous variables; univariate and multivariate Cox analyses were used for variable selection, and the Kaplan-Meier curve was used to analyze the value of variables on prognosis. The C-index, Brier Score, and calibration curve were used for model validation. Multivariate analysis showed that age, creatinine, albumin, platelet, lymphocyte ratio, and alanine aminotransferase were independent prognostic factors. By rounding up the hazard ratios from 6 significant variables, a maximum of 9 points was assigned. The final scoring model of HHLWG-HPI was identified with four risk groups: low risk (≤3 pts), low-intermediate risk (4 pts), high-intermediate risk (5-6 pts), and high risk (≥7 pts), with 5-year overall survival rates of 68.5%, 35.2%, 21.3%, and 10.8%, respectively. The C-indexes were 0.796 and 0.758 in the derivation and validation cohorts by using a bootstrap resampling program. In conclusion, the HHLWG-HPI model provides a feasible and accurate stratification system for individualized treatment strategy in adult HLH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shen, Jin, Sun, Zhang, Chen, Hu, He, Wang, Liu, Zhang, Liu, Wang, Jiao, Miao, Gu, Wang, Wang, Shi, Ye, Zhu, Sun, Song, Xu, Yan, Sun, Cao, Li, Li, Wang, Huang, Xu and Sang.)

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 × 10 9 /L (range, 0.1 to 2.9× 10 9 /L). The optimal cutoff value of pre-LD ALC was 0.75 × 10 9 /L. Twenty-two patients (26%) had a low pre-LD ALC (<0.75 × 10 9 /L), and 63 patients (74%) had a high pre-LD ALC (≥0.75 × 10 9 /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., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to report., (Copyright © 2021. Published by Elsevier Inc.)

Systematic and dynamic humoral immune reconstitution is little-known for patients with relapsed/refractory (R/R) multiple myeloma (MM) who received anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy. We investigated the kinetics of B-cell, normal plasma cell, and immunoglobulin recovery in 40 patients who achieved ongoing response after anti-BCMA CAR T-cell therapy. All patients developed B-cell aplasia and the median duration of B-cell aplasia was 70 days (range, 23-270). The B-cell count reached its nadir on median day 7 and returned to baseline level on median day 97. BCMA+ cells in bone marrow turned undetectable on median day 28 (13-159) in 94.87% (37 of 39) of patients. Normal plasma cells in bone marrow were first redetected on median day 212. All patients developed a significant decrease in serum IgG, IgA, and IgM on median day 60. At year 1, recovery of serum IgG, IgM, and IgA was observed in 53.33% (8 of 15; non-IgG MM), 73.08% (19 of 26; non-IgM MM), and 23.81% (5 of 21;non-IgA MM) of the patients, respectively. Median time to IgG, IgM, and IgA recovery were days 386, 254, and not reached during follow-up, respectively. Virus-specific IgG levels decreased with loss of protection. Twenty-three of 40 (57.5%) patients had a total of 44 infection events. There were no infection-related deaths. These results reveal a 7-month aplasia of bone marrow normal plasma cells and longer period of hypogammaglobulinemia, suggesting a profound and lasting humoral immune deficiency after anti-BCMA CAR T-cell therapy, especially for IgA., (© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Early response could be obtained in most patients with relapsed or refractory B cell lymphoblastic leukemia (R/R B-ALL) treated with chimeric antigen receptor T-cell (CAR-T) therapy, but relapse occurs in some patients. There is no consensus on treatment strategy post CAR-T cell therapy. In this retrospective study of humanized CD19-targeted CAR-T cell (hCART19s) therapy for R/R B-ALL, we analyzed the patients treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) or received a second hCART19s infusion, and summarized their efficacy and safety. We retrospectively studied 28 R/R B-ALL patients treated with hCART19s in the Affiliated Hospital of Xuzhou Medical University from 2016 to 2020. After the first hCART19s infusion, 10 patients received allo-HSCT (CART+HSCT group), 7 patients received a second hCART19s infusion (CART2 group), and 11 patients did not receive HSCT or a second hCART19s infusion (CART1 group). The safety, efficacy, and long-term survival were analyzed. Of the 28 patients who received hCART19s treatment, 1 patient could not be evaluated for efficacy, and 25 (92.6%) achieved complete remission (CR) with 20 (74.7%) achieving minimal residual disease (MRD) negativity. Seven (25%) patients experienced grade 3-4 CRS, and one died from grade 5 CRS. No patient experienced ≥3 grade ICANS. The incidence of second CR is higher in the CART+HSCT group compared to the CART2 group (100% vs. 42.9%, p = 0.015). The median follow-up time was 1,240 days (range: 709-1,770). Significantly longer overall survival (OS) and leukemia-free survival (LFS) were achieved in the CART+HSCT group (median OS and LFS: not reached, p = 0.006 and 0.001, respectively) compared to the CART2 group (median OS: 482; median LFS: 189) and the CART1 group (median OS: 236; median LFS: 35). In the CART+HSCT group, the incidence of acute graft- versus -host disease (aGVHD) was 30% (3/10), and transplantation-related mortality was 30% (3/10). No chronic GVHD occurred. Multivariate analysis results showed that blasts ≥ 20% in the bone marrow and MRD ≥ 65.6% are independent factors for inferior OS and LFS, respectively, while receiving allo-HSCT is an independent factor associated with both longer OS and LFS. In conclusion, early allo-HSCT after CAR-T therapy can achieve long-term efficacy, and the adverse events are controllable., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Ma, Shen, Chen, Ma, Yan, Shi, Wang, Song, Sun, Cao, Cheng, Zhu, Sun, Li, Li, Zheng, Xu and Sang.)

Introduction: Chimeric antigen receptor T (CAR-T) cells are effective in treating hematological malignancies. However, in patients receiving CAR-T therapy, data characterizing cardiac disorders are limited., Methods: 126 patients with hematologic malignancies receiving CAR-T cell therapy were analyzed to determine the impact of CAR-T therapy on occurrence of cardiac disorders, including heart failure, arrhythmias, myocardial infarction, which were defined by the Common Terminology Criteria for Adverse Events (CTCAE). Parameters related to cardiac disorders were detected including myocardial enzyme, NT-proBNP and ejection fraction (EF). Cardiovascular (CV) events included decompensated heart failure (HF), clinically significant arrhythmias and CV death., Results: The median age of patients was 56 years (6 to 72 years). 58% patients were male, 62% had multiple myeloma, 20% had lymphoma and 18% had ALL. 33 (26%) patients had cardiac disorders, most of which were grade 1-2. 13 patients (10%) were observed with cardiac disorders grade 3-5, which comprised 5(4%) patients with new-onset HF, 2 (2%) patients with new-onset arrhythmias, 4 (3%) patients with the acute coronary syndrome, 1(1%) patient with myocardial infarction and 1(1%) patient with left ventricular systolic dysfunction. There were 9 CV events (7%) including 6 decompensated heart failure, 1 clinically significant arrhythmias and 2 CV deaths. Among the 33 patients with cardiac disorders, the patients with cardiac disorders CTCAE grade 3-5 had higher grade CRS (grade ≥ 3) than those with cardiac disorders CTCAE grade ≤ 2 ( P < 0.001). More patients with cardiac disorders CTCAE grade 3-5 were observed in the cohort who did not receive corticosteroids and/or tocilizumab therapy timely comparing with those who received corticosteroids and/or tocilizumab therapy timely ( P =0.0004)., Conclusions: Cardiac disorders CAR-T cell therapy were common and associated with occurrence of CRS. However, most cases were mild. For patients with CRS grade 3-5, timely administration of corticosteroids and/or tocilizumab can effectively prevent the occurrence and progression of cardiac disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Qi, Yan, Cheng, Chen, Wang, Wang, Cao, Zhang, Sang, Zhu, Sun, Li, Wu, Qiao, Fu, Zeng, Li, Zheng and Xu.)

Immunoglobulin D (IgD) multiple myeloma (MM) is a rare subtype of MM that carries a worse prognosis than non-IgD subtypes. Compared with non-IgD subtypes, IgD MM is associated with a shorter survival time. The application of chimeric antigen receptor (CAR) T-cell therapy for patients with relapsed or refractory multiple myeloma (R/R MM) has increasing evidence as an efficacious treatment. This study was designed to investigate efficacy and safety of chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory IgD MM (R/R IgD MM). In this single-arm, phase 2 trial, patients diagnosed with R/R IgD MM were infused with either a combination of anti-B-cell maturation antigen and anti-CD19 CAR T-cells or anti-CD19 CAR T-cells alone, with subsequent evaluation of therapeutic response and treatment-related toxicities. At the data cutoff date, 7 patients were enrolled in our study, and all patients achieved response based on the International Myeloma Working Group Uniform Response Criteria. Six patients achieved stringent complete remission (sCR) within 60 days after CAR T-cell infusion (median time 58 days, range 18 to 90 days), and 1 patient with extramedullary disease achieved minimal response (MR) at 30 days after infusion. Bone marrow minimal residual disease (MRD) negativity was achieved in all patients, and the median time to achieve MRD negativity was 22 days (range 14 to 60 days). The most common grade 3 to 4 treatment-related toxicities were hematological toxicities. All patients experienced cytokine release syndrome (CRS), although CAR T-cell-related neurotoxicity was not observed. In our study, CAR T-cell therapy showed encouraging efficacy in the patients with R/R IgD MM, achieving high rates of sCR and MRD negativity. Aside from CRS and prolonged hematologic toxicities, other adverse reactions were mild, suggesting that this is a well-tolerated treatment with a high therapeutic potential., (Copyright © 2020 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Clinical trials have confirmed that chimeric antigen receptor (CAR) T cell therapies are revolutionizing approaches for treating several relapsed or refractory hematological tumors. Cytokine release syndrome (CRS) is an adverse event with high incidence during CAR-T treatment. A further understanding of the characteristics and related risk factors of CRS is important for effective management. A total of 142 patients with relapsed or refractory acute lymphocyte leukemia (ALL), lymphoma, or multiple myeloma (MM) received lymphodepletion chemotherapy followed by infusion of CAR-T cells. The characteristics of CRS at different time points after treatment were monitored and risk factors were analyzed. The incidence of CRS for ALL, lymphoma, and multiple myeloma were 82%, 90%, and 90% respectively. Fever was observed on a median of day 3 for ALL, day 1 for lymphoma, and day 8.5 for MM after CAR-T cell infusion, and the duration was different between grade 1-2 CRS and grade 3-5 CRS. Disease types, peak concentration of IL-6, and CRP were associated with CRS. For patients with ALL, numbers of lymphoblast in bone marrow before lymphodepletion, peak concentration of IL-6, and CRP were independent risk factors of CRS. Clinical stage of lymphoma patients and high tumor burden in marrow of MM patients were independent risk factors of CRS. In conclusion, the characteristics and risk factors of CRS in different B-cell hematological tumors are different and should be managed individually during CAR-T cell therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yan, Zhang, Cao, Zhang, Liu, Huang, Cheng, Qiao, Wang, Wang, Gao, Shi, Sang, Zhu, Li, Sun, Wu, Qi, Li, Wang, Li, Liu, Zheng, Qian, Zhang and Xu.)

The formaldehyde dehydrogenase (FADH) activity in plants is essential to the removal of airborne formaldehyde (FA) by plants. A rapid and efficient method was established to assess the FADH activity in plants by analyzing the efficiencies of the extracts of fresh and enzyme-inactivated leaves to degrade FA, with the enzyme-inactivated leaves prepared by freezing with liquid nitrogen. The efficiencies of airborne FA dissipated by different plants were evaluated through the FA fumigation experiments using four selected plants, with the results analyzed against the calculated leaf FADH activities. Fresh and enzyme-inactivated leaf extracts degraded FA to different extents. The degradative efficiencies of leaf extracts were positively related to the initial FA test levels at 6-18 mg l -1 . The relative plant-leaf FADH activities formed the order of Chenopodium album L. > Atenia cordifolia > Plantain > Aloe, which was in line with the observed FA dissipating efficiencies of the plants exposed to 0.72 mg m -3 airborne FA for 24 h. Other dominant degrading mechanisms in plant leaves resulted in higher dissipating efficiencies of Plantain over that of Atenia cordifolia when exposed to 1.56 mg m -3 FA for 24 h. The established method could be applied to estimate the FADH activity in plants for assessment of the plant remediation efficiency of FA in air at lower concentrations.

Purpose: Anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy has demonstrated remarkable efficacy for refractory and relapsed diffuse large B cell lymphoma (R/R DLBCL). However, this therapy failed in nearly 25% patients mainly due to antigen loss. The authors performed a phase Ⅱ trial by coadministration of anti-CD19 and anti-CD20 CAR-T cells treatment for R/R DLBCL and evaluated its efficacy and toxicity., Methods: Totally 21 patients with DLBCL were enrolled in this study. The patients were conditioned with fludarabine and cyclophosphamide before the infusion of anti-CD19 and anti-CD20 CAR-T cells. Treatment response, toxicity, and persistence were monitored continuously., Results: Of the 21 patients received the treatment, the objective response rate (ORR) is 81.0% (95% confidence interval [CI], 58.1%-94.6%) with four cases of bulk (4/5) and one case of testis involvement; 52.4% (95% CI, 29.8%-74.3%) had a complete response (CR). Peak levels of anti-CD19 and anti-CD20 CAR cells were associated with response (P = .007 and .002). Grade 3-4 cytokine release syndrome (CRS) and neurologic events occurred in 28.5% and 9.5% patients, respectively. Median overall survival (OS) and progression-free survival (PFS) were 8.1 and 5.0 months, respectively. The maximum standard uptake value (SUVmax) of CD4/CD8 ratio before and after infusion were associated with responses, and the total lesion glycolysis (TLG) before infusion correlates with cytokines level., Conclusions: Coadministration of anti-CD19 and CD20 CAR-T cells therapy for DLBCL is feasible with manageable toxicity. Cytokine markers are related to toxicity and SUVmax could predict efficacy. This trial was registered at www.clinicaltrials.gov as NCT03207178., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Nowadays, there is an increasing demand of healthier plant calcium supplements. Moringa oleifera leaves (MOL) are rich in calcium and thus are promising candidates for developing efficient calcium supplements. Here, using fermentation-based approaches, we developed a Moringa oleifera leaf ferment (MOLF), which contents higher levels of calcium. The therapeutic potential of the MOLF was also examined both in vitro and in vivo. Nine lactic acid bacteria and four yeasts were tested for better fermentation of MOL. Calcium-deficient rats were used for evaluating the therapeutic effects of MOLF. The results of liquid fermentation showed that the mixture of Lactobacillus reuteri, Lactobacillus acidophilus , and Candida utilis elevated the content of MOL calcium most strikingly, with the content of calcium increased nearly 2.4-fold (from 2.08% to 4.90%). The resulting MOLF was then subjected to cell experiments and animal experiments. The results showed that calcium absorption in Caco-2 cells in MOLF group was higher than that in CaCl 2 group significantly. Interestingly, in calcium-deficient rats, MOLF treatment significantly increased the thickness of cortical bone, rat body weight, wet weight of the femur, and the femur bone density, whereas it decreased osteoclast numbers. These results indicate that microbial fermentation increased calcium bioavailability of MOL, promote the growth and development of calcium-deficient rats, bone calcium deposition, and bone growth; enhance bone strength; reduce bone resorption; and prevent calcium deficiency., Competing Interests: The authors declare that they have no conflict of interest., (© 2020 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Chimeric antigen receptor (CAR)-T cell therapy, a new immunotherapy for relapsed and refractory (R/R) hematologic malignancies, can be accompanied by adverse events, including coagulation disorders. Here, we performed a comprehensive analysis of coagulation parameters in 100 patients with R/R hematologic malignancies after receiving CAR-T cell therapy to illuminate the profiles of coagulation disorders and to facilitate the management of coagulation disorders. A high incidence of coagulation disorders was observed, including elevated D-dimer (50/100, 50%), increased fibrinogen degradation product (45/100, 45%), decreased fibrinogen (23/100, 23%), prolonged activated partial thromboplastin time (16/100, 16%), and prolonged prothrombin time (10/100, 10%). Coagulation disorders occurred mainly during day 6 to day 20 after CAR-T cell infusion. The changes in coagulation parameters were associated with high tumor burden in acute lymphoblastic leukemia, more lines of prior therapies, lower baseline platelet count, and especially cytokine release syndrome (CRS). Disseminated intravascular coagulation (DIC) was found in 7 patients with grade ≥3 CRS and indicated a poor prognosis. Our study suggests that coagulation disorders are manageable in most patients after CAR-T cell therapy. Coexistence of DIC and severe CRS is closely related to nonrelapsed deaths during the acute toxicity phase, and effective and timely treatment is the key to reduce nonrelapse mortality for patients with DIC and severe CRS., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Colloidal PbS quantum dots (QDs) are attractive for solution-processed thin-film optoelectronic applications. In particular, directly achieving QD thin-films by printing is a very promising method for low-cost and large-scale fabrication. The kinetics of QD particles during the deposition process play an important role in the QD film quality and their respective optoelectronic performance. In this work, the particle self-organization behavior of small-sized QDs with an average diameter of 2.88 ± 0.36 nm is investigated for the first time in situ during printing by grazing-incidence small-angle X-ray scattering (GISAXS). The time-dependent changes in peak intensities suggest that the structure formation and phase transition of QD films happen within 30 seconds. The stacking of QDs is initialized by a templating effect, and a face-centered cubic (FCC) film forms in which a superlattice distortion is also found. A body-centered cubic nested FCC stacking is the final QD assembly layout. The small size of the inorganic QDs and the ligand collapse during the solvent evaporation can well explain this stacking behavior. These results provide important fundamental understanding of structure formation of small-sized QD based films prepared via large-scale deposition with printing with a slot die coater.

Endometritis, an inflammatory response of the uterus tissue, is characterized by the production of inflammatory cytokines and migration of neutrophil (PMN) into the uterus tissue. Melatonin has been demonstrated to have anti-inflammatory and antioxidant effects. The purpose of this study was to investigate the protective effects of melatonin on lipopolysaccharide (LPS)-induced endometritis in mice. An endometritis model was induced by LPS and melatonin was given 1 h before LPS treatment. The results showed that melatonin inhibited LPS-induced pathologic changes, Myeloperoxidase (MPO) activity, and levels of interleukin-1 beta (IL-1β). Melatonin also inhibited LPS-induced thioredoxin-interacting protein (TXNIP)/NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome and nuclear factor kappa B (NF-κB) activation, reactive oxygen species (ROS) production, and endoplasmic reticulum (ER) stress. Furthermore, melatonin was found to increase AMPK activity. In conclusion, our results demonstrated that melatonin inhibited ER stress-associated TXNIP/NLRP3 inflammasome activation with a regulation of adenosine monophosphate activated protein kinase (AMPK) in LPS-induced endometritis. Melatonin may serve as a promising nutritional supplement for the treatment of endometritis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In addition to their hemostatic function, platelets play an important role in regulating the inflammatory response. The platelet NLRP3 inflammasome not only promotes interleukin-1β secretion, but was also found to be upregulated during platelet activation and thrombus formation in vitro However, the role of NLRP3 in platelet function and thrombus formation in vivo remains unclear. In this study, we aimed to investigate the role of NLRP3 in platelet integrin αIIbβ3 signaling transduction. Using NLRP3 -/- mice, we showed that NLRP3-deficient platelets do not have significant differences in expression of the platelet-specific adhesive receptors αIIbβ3 integrin, GPIba or GPVI; however, NLRP3 -/- platelets transfused into wild-type mice resulted in prolonged tail-bleeding time and delayed arterial thrombus formation, as well as exhibiting impaired spreading on immobilized fibrinogen and defective clot retraction, concomitant with decreased phosphorylation of c-Src, Syk and PLCγ2 in response to thrombin stimulation. Interestingly, addition of exogenous recombinant interleukin-1β reversed the defect in NLRP3 -/- platelet spreading and clot retraction, and restored thrombin-induced phosphorylation of c-Src/Syk/PLCγ2, whereas an anti-interleukin-1β antibody blocked spreading and clot retraction mediated by wild-type platelets. Using the direct NLRP3 inhibitor, CY-09, we demonstrated significantly reduced human platelet aggregation in response to threshold concentrations of collagen and ADP, as well as impaired clot retraction in CY-09-treated human platelets, supporting a role for NLRP3 also in regulating human platelet αIIbβ3 outside-in signaling. This study identifies a novel role for NLRP3 and interleukin-1β in platelet function, and provides a new potential link between thrombosis and inflammation, suggesting that therapies targeting NLRP3 or interleukin-1β might be beneficial for treating inflammation-associated thrombosis., (Copyright© 2018 Ferrata Storti Foundation.)