Evaluating the impact of ecological factors on the quality and habitat distribution of Lonicera japonica Flos using HPLC and the MaxEnt model.

Introduction: The quality of traditional Chinese medicine is based on the content of their secondary metabolites, which vary with habitat adaptation and ecological factors. This study focuses on Lonicera japonica Flos (LJF), a key traditional herbal medicine, and aims to evaluate how ecological factors impact its quality. Methods: We developed a new evaluation method combining high-performance liquid chromatography (HPLC) fingerprinting technology and MaxEnt models to assess the effects of ecological factors on LJF quality. The MaxEnt model was used to predict suitable habitats for current and future scenarios, while HPLC was employed to analyze the contents of key compounds. We also used ArcGIS for spatial analysis to create a quality zoning map. Results: The analysis identified 21 common chromatographic peaks, with significant variations in the contents of Hyperoside, Rutin, Chlorogenic acid, Cynaroside, and Isochlorogenic acid A across different habitats. Key environmental variables influencing LJF distribution were identified, including temperature, precipitation, and elevation. The current suitable habitats primarily include regions south of the Yangtze River. Under future climate scenarios, suitable areas are expected to shift, with notable expansions in southern Gansu, southeastern Tibet, and southern Liaoning. The spatial distribution maps revealed that high-quality LJF is predominantly found in central and southern Hebei, northern Henan, central Shandong, central Sichuan, southern Guangdong, and Taiwan. Discussion: The study indicates that suitable growth areas can promote the accumulation of certain secondary metabolites in plants, as the accumulation of these metabolites varies. The results underscore the necessity of optimizing quality based on cultivation practices. The integration of HPLC fingerprinting technology and the MaxEnt model provides valuable insights for the conservation and cultivation of herbal resources, offering a new perspective on evaluating the impact of ecological factors on the quality of traditional Chinese medicines.

Association between the perceived built environment and health behaviors in older adults: a cross-sectional study from Beijing, China.

BACKGROUND: Under the background of the increasing trend of population aging, the health and quality of life of older adults have become the focus of social concern. As an important part of older adults' daily life, the design and configuration of the built environment may positively or negatively affect older adults' health behaviors. Therefore, this study aims to explore the relationship between older adults' perceived built environments and health behaviors, which is the association between perceived built environments and older adults' physical activity (PA) and social interactions. This is important for optimizing the community built environment and improving the quality of life of older adults. METHODS: In this study, a questionnaire was surveyed on 916 Chinese older adults aged 60 and above. The questionnaire was used to collect demographic information and social interaction from the participants, and the Physical Activity Neighborhood Environment Scale (PANES) and the Physical Activity Scale for the Elderly (PASE) were used to assess older adults' subjective perceptions of the built environment in their neighborhoods and their levels of PA, respectively. In data analysis, ANOVA and chi-square tests were used to compare the significance of differences between groups, and multiple linear regression model were used to estimate the association between older adults' perceived characteristics of the built environment and their PA and social interaction. RESULTS: After controlling for confounders such as gender, age, BMI, and education level, the multiple linear regression model showed that perceived destination accessibility, neighborhood infrastructure, aesthetic qualities, and neighborhood environment indices were significantly correlated with PA (ß = 0.083 ~ 0.095, P < 0.05) and social interaction (ß = 0.087 ~ 0.144, P < 0.05) among older adults. In addition, neighborhood safety (ß = -0.084, P < 0.05), social environment (ß = 0.091, P < 0.01), and street connectivity (ß = 0.112, P < 0.001) were also strongly associated with older adults' social interaction. CONCLUSIONS: Different perceived built environment attributes are correlated with the health behaviors of Chinese older adults to different degrees. This finding helps to guide community planning and construction, provides an empirical basis for improving health behaviors of older adults, and provides an important reference for building healthy communities for older adults and realizing comprehensive healthy development of older adults. TRIAL REGISTRATION: There was no trial registration for this study, but the study was approved by the Institutional Review Board of Tsinghua University (No. THU0120230196).

Single-cell analysis of the survival mechanisms of fratricidal CAR-T targeting of T cell malignancies.

Chimeric antigen receptor T (CAR-T) cell therapy targeting T cell tumors still faces many challenges, one of which is its fratricide due to the target gene expressed on CAR-T cells. Despite this, these CAR-T cells can be expanded in vitro by extending the culture time and effectively eliminating malignant T cells. However, the mechanisms underlying CAR-T cell survival in cell subpopulations, the molecules involved, and their regulation are still unknown. We performed single-cell transcriptome profiling to investigate the fratricidal CAR-T products (CD26 CAR-Ts and CD44v6 CAR-Ts) targeting T cells, taking CD19 CAR-Ts targeting B cells from the same donor as a control. Compared with CD19 CAR-Ts, fratricidal CAR-T cells exhibit no unique cell subpopulation, but have more exhausted T cells, fewer cytotoxic T cells, and more T cell receptor (TCR) clonal amplification. Furthermore, we observed that fratricidal CAR-T cell survival was accompanied by target gene expression. Gene expression results suggest that fratricidal CAR-T cells may downregulate their human leukocyte antigen (HLA) molecules to evade T cell recognition. Single-cell regulatory network analysis and suppression experiments revealed that exhaustion mediated by critical regulatory factors may contribute to fratricidal CAR-T cell survival. Together, these data provide valuable and first-time insights into the survival of fratricidal CAR-T cells.

Evaluation of the environmental factors influencing the quality of Astragalus membranaceus var. mongholicus based on HPLC and the Maxent model.

BACKGROUND: In recent years, global climate change in tandem with increased human activity has resulted in habitat degradation or the migration of rare medicinal plants, potentially impacting the quality of medicinal herbs. Astragalus membranaceus var. mongholicus is a valuable bulk medicinal material in Northwest China. As the demand for this medicinal herb continues to increase in both domestic and international markets, ensuring the sustainable development of high-quality Astragali Radix is important. In this study, the maximum entropy (Maxent) model was applied, thereby incorporating 136 distribution records, along with 39 environmental factors of A. membranaceus var. mongholicus, to assess the quality zonation and potential distribution of this species in China under climate change. RESULTS: The results showed that the elevation, annual mean temperature, precipitation of wettest month, solar radiation in June, and mean temperature of warmest quarter were the critical environmental factors influencing the accumulation of astragaloside IV and Astragalus polysaccharide in A. membranaceus var. mongholicus. Among the twelve main environmental variables, annual mean temperature, elevation, precipitation of the wettest month, and solar radiation in November were the four most important factors influencing the distribution of A. membranaceus var. mongholicus. In addition, ecological niche modelling revealed that highly suitable habitats were mainly located in central and western Gansu, eastern Qinghai, northern Shaanxi, southern Ningxia, central Inner Mongolia, central Shanxi, and northern Hebei. However, the future projections under climate change suggested a contraction of these suitable areas, shifting towards northeastern high-latitude and high-elevation mountains. CONCLUSIONS: The findings provide essential insights for developing adaptive strategies for A. membranaceus var. mongholicus cultivation in response to climate change and can inform future research on this species. By considering the identified environmental factors and the potential impacts of the predicted climate changes, we can visualize the regional distribution of high-quality Radix Astragali and develop conservation strategies to protect and restore its suitable habitats.

Influences of crop diversification on yield, resource use efficiency, and environmental footprint in farmland landscapes in intensive farming.

Enhancing crop diversification in intensive fields has the potential to increase crop yield and reduce environmental footprint. However, these relationships at the landscape scale remained unclear in intensive farming. Addressing this gap, this paper aims to elucidate how crop yield, resources use efficiency (RUE), and environmental footprint (EF) vary with crop diversification levels in the North China Plain. Management practices, including crop pattern, field size, and agronomic inputs, were collected for 421 landscapes of 1 × 1 km subplots using Sentinel-2 and Landsat-8 images and survey. The results showed that, at the landscape scale, energy and fertilizer contributed over 53 %, and 37 % of the carbon footprint, respectively. N fertilizer constituted >98 % of the nitrogen footprint. P fertilizer accounted for over 80 %, while electricity comprised >13 % of the phosphorus footprint. Compared with simplified landscapes, diversified landscapes exhibited several significant features: 1) 56 % reduction of the area ratio of winter wheat-summer maize double crop pattern (WM), 2) a significant decrease in field size, 3) the decreased use of total NPK fertilizers at 32 %, 30 %, and 30 %, respectively, 4) the increased inputs of irrigation water, diesel, electricity, pesticide and labour at 21 %, 19 %, 21 %, 77 %, and 92 %, respectively. Although yield could be reduced at 33 % when transforming simplified landscapes into moderately diversified ones, they increased with the further promotion of crop diversification. Thus, the diversified landscapes could achieve a balance in yield, RUE, and EF to enhance sustainability, whereas simplified landscapes can similarly achieve a balance to benefit productivity. We emphasize the viable potential of diversified landscapes to enhance sustainable agricultural development by optimizing crop composition. This analysis offers pioneering evidence of landscape-scale agronomic and environmental performances of crop diversification.

Survey data on livelihoods and inputs and outputs of crop production in Quzhou county on the North China Plain.

Farmers' decisions on crop choice, management practices, and livelihood strategies are essential to agricultural sustainability. This data article describes three datasets on crop production in Quzhou, a county in the central part of North China Plain. The three datasets cover different scales. The village dataset assembles basic data on all 342 villages of Quzhou county, including information on population, land area, crop grown, labour, irrigation and markets. Data was sourced from the yearbook data of 2017 and a village cadres survey in 2018. The village dataset was used to create a village typology from which 35 villages belonging to seven village types (five for each type) were selected for stratified random sampling to collect information on farm characteristics and cropping practices. We surveyed these 35 villages, interviewing fifteen farmer households per village (525 in total) in 2020. The interviewees represented two farm management models: smallholder farms and business farms. The resulting household dataset provides farm-level data, including demographic data of farming decision-makers and the number of household members, land use and machinery resources, crop production management practices, and government subsidies. The crop-level dataset was derived from the household survey and included input-output inventories for each crop grown during one year on each field greater than 1/30th ha (1/2 mu) on the 525 surveyed farms within a year. This dataset comprises information on cropping practices in 1352 fields. The three datasets provide a basis for analyses on cropping practices and sustainability attributes of farms and crops in a typical agricultural county on the North China Plain.

Improvement in the quality and productivity of Codonopsis pilosula seedlings by dazomet soil fumigation.

Dazomet is a dry powder formulation that releases toxic gas containing methyl isothiocyanate, which controls soil-borne pests and weeds, improving crop yields when applied to moist soils. To explore the efficacy of dazomet fumigation in the cultivation of the perennial herb Codonopsis pilosula, four typical cultivars (G1, G2, W1 and TCK) in Gansu Province were selected for seedling cultivation after soil fumigation (F) by dazomet, and non-fumigated soil was used as a control (CK). The experiments took 2 years to complete. The functional diversity of the soil enzymes and microorganisms, seedling emergence and physiological characteristics, and the quality and yield of Codonopsis seedlings and Radix were assessed. The results showed that the seed emergence rate, seedling re-green rate and several antioxidant enzymatic activities improved in the treatments involving soil fumigation with dazomet, and membrane lipid peroxidation in the seedlings decreased. On average, compared with those of the respective controls, the root viability and yield of the seedlings of the tested cultivars also increased by 34.87% and 42.4%, respectively, and the incidence of root rot in the seedlings was reduced by 83.9%, compared with their respective controls. After harvest, the yield increased by 23.9%, the incidence of root rot decreased by 61.3%, increase in yield and a 61.3% reduction in incidence, and the medicinal materials were determined to be safe and residue-free. The effects of fumigation were cultivar-specific and were especially prominent in G2. Therefore, soil fumigation with dazomet could improve the quality and productivity of Codonopsis pilosula seedlings. Taken together, these findings suggest that when herbs are bred by seedling transplantation, especially cultivars of good quality but poor resistance or species with rare germplasm resources, soil fumigation provides a way to improve cultivation effectiveness and, more importantly, ensures the probability of successfully breeding the species.

Objectively measured the impact of ambient air pollution on physical activity for older adults.

BACKGROUND: Air pollution poses a significant health risk to the human population, especially for vulnerable groups such as the elderly, potentially discouraging their engagement in physical activity. However, there is a lack of sufficient objective and longitudinal data in current research on how air pollution affects physical activity among older adults. With these gaps, we aimed to explore the relationship between air pollution and objective measurement-based physical activity among older adults by engaging in a longitudinal study design. METHODS: A total of 184 older adults were recruited from three cities with varying levels of air quality. Mean daily minutes of physical activity were measured with 7 consecutive days of accelerometer monitoring (ActiGraph GT3X-BT). Corresponding air pollution data including daily PM2.5 (µg/m3), PM10 (µg/m3) and air quality index (AQI) were sourced from the China National Environmental Monitoring Centre at monitor locations close to older adults' addresses. Associations between air quality and physical activity were estimated using a fixed effect model, adjusting for average daytime temperature, rain, age and weight. RESULTS: AQI and PM2.5 were observed to exhibit significant, inverse, and linear associations with mean daily walk steps, minutes of light physical activity (LPA), moderate physical activity (MPA) and moderate-to-vigorous physical activity (MVPA) in the single variable models. A one-level increase in AQI corresponded to a decline in 550.04 steps (95% [CI] = -858.97, -241.10; p < 0.001), 10.43 min (95% [CI] = -17.07, -3.79; p < 0.001), 4.03 min (95% [CI] = -7.48, -0.59; p < 0.001) and 4.16 min (95% [CI] = -7.77, -0.56; p < 0.001) in daily walking steps, LPA, MPA, and MVPA, respectively. A one-level increase in PM2.5 correlated with a decline in daily walk steps, LPA, MPA and MVPA by 361.85 steps (95% [CI] = -516.53, -207.16; p < 0.001), 8.97 min (95% [CI] = -12.28, -5.66; p < 0.001), 3.73 min (95% [CI] = -5.46, -2.01; p < 0.001,) and 3.79 min (95% [CI] = -5.59, -1.98; p < 0.001), respectively. However, PM10 displayed a significant negative association exclusively with LPA, with one-level increase in PM10 resulting in a 3.7-minute reduction in LPA (95% [CI] = -6.81, -0.59, p < 0.05). CONCLUSION: Air pollution demonstrates an inverse association with physical activity levels among older adults, potentially discouraging their engagement in physical activity. Different air quality indicators may exert varying impacts on physical activity. Future studies are warranted to enhance policy interventions aimed at reducing air pollution and promoting physical activity.

Non-Hermitian metagrating for perfect absorption of elastic waves.

Beyond the fashion of Hermitian physics, non-Hermiticity has inspired, most recently, a surge of nontrivial principles and significant applications in both open quantum and classical systems characterized by gain or loss. However, research on elastic wave manipulation is still predominantly focused on conservative Hermitian systems, overlooking the energy interaction with the environment. The unavoidable energy loss, originating from the inherent material properties, is normally ignored. Additionally, most existing materials for elastic wave absorption suffer from complex configurations, sophisticated designs, and large volumes. Achieving highly efficient absorption properties in advanced artificial materials with ultrathin size and easy fabrication is still a challenge. This work proposes a design strategy based on non-Hermitian modulation to address such a challenge. The proposed non-Hermitian metagrating (NHMG), featured with the subwavelength unit cell, achieves the perfect absorption of elastic waves under specific low-loss conditions. The loss-induced non-Hermitian effects for perfect absorption are theoretically elucidated and a design framework is established in the NHMG with irregular and arbitrary shapes. The robust performance of omnidirectional and perfect absorption capabilities with respect to the boundary shape, rotation angle, and wave source location is numerically and experimentally verified. Consequently, a cloaking device based on the NHMG is further designed to avoid arbitrary-shaped targets being detected. Our study enriches the ways to elastic wave manipulation in non-Hermitian materials and provides an ultra-compact solution for wave absorption in engineering applications.

Uptake and elimination of methylsiloxanes in hens after oral exposure: Implication for risk estimation.

Methylsiloxanes are accumulated easily in aquatic organisms and may pose potential risks. However, available information on their uptake and accumulation in terrestrial species remains scarce. This study investigated the uptake, elimination and accumulation of eight typical methylsiloxanes in hens after a single oral exposure. At 1440 min after oral exposure, methylsiloxanes were mainly accumulated in kidney, liver and ovary, representing for 29.5 %, 20.4 % and 17.4 % of the summed methylsiloxanes in all tissues, respectively; all investigated chemicals were also detected in brains and unformed yolks. We found much higher mass uptake fractions (MUFs) of cyclic (27.5-66.5 %) than linear chemicals (9.9-17.3 %) by hens via this exposure, and the observed MUFs of individual cyclic congeners were comparable to the higher values of those reported for rats or fish previously. However, the metabolic half-life (t1/2) of these chemicals in hen tissues were in the range of 1.04-57.5 h based on kinetic analyses, indicating higher clearances in comparison with those reported for fish and rats. More research is needed on the metabolic mechanism of these chemicals in hens. Our findings provide important information for further understanding of transportation and transformation of these chemicals in terrestrial organisms and the associated potential risks.

EBV-Encoded MicroRNA-BART17-3p Targets DDX3X and Promotes EBV Infection in EBV-Associated T/Natural Killer-Cell Lymphoproliferative Diseases.

Background: Epstein-Barr virus (EBV) persistently infects T/natural killer (NK) cells causing an array of refractory EBV-associated T/NK-cell lymphoproliferative disorders. EBV-encoded microRNAs are important regulators for EBV latent infection and tumorigenesis. However, the roles of most EBV microRNAs in EBV-infected T/NK cells remain poorly understood. Methods: On the basis of a search of the doRiNA database and the BiBiServ2-RNAhybrid website, we predicted that EBV-miR-BART17-3p targeted DDX3X, and we verified the hypothesis by dual-luciferase reporter assay and cell function experiments. In addition, we collected 50 EBV-positive T-, B-, and NK-cell samples from the peripheral blood of EBV-positive cases to examine the role of EBV-miR-BART17-3p in the disease. Results: We found that EBV-miR-BART17-3p directly targeted DDX3X and downregulated DDX3X expression. By analyzing EBV-positive cell samples from cell lines and patients, we found that EBV-miR-BART17-3p was highly expressed only in EBV-positive NK cells and that the overexpression was significantly related to high EBV loads in EBV-infected NK cells. Furthermore, we found that EBV-miR-BART17-3p downregulated the RIG-I-like receptor antiviral pathway and promoted the expression of EBV-encoded proteins in EBV-infected NK cells by targeting DDX3X. Conclusions: Our study showed that EBV-miR-BART17-3p was abundantly expressed in EBV-infected NK cells and inhibited the important antivirus immune responses of hosts by targeting DDX3X of the RIG-I-like receptor pathway. These findings could help us gain insights into the pathogenic mechanisms underlying EBV-associated T/NK-cell lymphoproliferative disorders and find the potential therapeutic target.

Case Report: Fatal cytomegalovirus pneumonia after CAR-T cell therapy in the long-term follow-up.

Introduction: The rapidly developed CAR-T cell therapy has a unique profile of side effects, which perhaps has not been totally realized and understood, especially the late-phase toxicity. CMV is prevalent world-wide and establishes a life-long latency infection. It can lead to life-threatening complications in immunocompromised host, and little is known about CMV disease in patients after CAR-T cell therapy. Here, we report a patient who developed possible CMV-pneumonia three months after anti-CD19 and anti-CD22 CAR-T cell therapy for relapsed B-ALL, contributing to the understanding of severe side-effects mediated by virus infection or reactivation in patients receiving CAR-T cell infusion. Case presentation: A 21-year old male patient with relapsed B-ALL received anti-CD19/22 CAR-T cell therapy, and achieved complete remission 2 weeks after the infusion. However, three months later, the patient was hospitalized again with a 10-day history of fever and cough and a 3-day history of palpitations and chest tightness. He was diagnosed with possible CMV pneumonia. Under treatment with antiviral medicine (ganciclovir/penciclovir), intravenous gamma globulin and methylprednisolone and the use of BiPAP ventilator, his symptoms improved, but after removing penciclovir his symptoms went out of control, and the patient died of respiratory failure 22 days after admission. Conclusion: CMV infection/reactivation can occur in patients long after receiving anti-CD19/22 CAR-T cell therapy, and induce fatal pneumonia, which reminds us of the late side effects associated with immunosuppression after CAR-T cell infusion.

Functional diversification and dynamics of CAR-T cells in patients with B-ALL.

Understanding of cellular evolution and molecular programs of chimeric antigen receptor-engineered (CAR)-T cells post-infusion is pivotal for developing better treatment strategies. Here, we construct a longitudinal high-precision single-cell transcriptomic landscape of 7,578 CAR-T cells from 26 patients with B cell acute lymphoblastic leukemia (B-ALL) post-infusion. We molecularly identify eight CAR-T cell subtypes, including three cytotoxic subtypes with distinct kinetics and three dual-identity subtypes with non-T cell characteristics. Remarkably, long-term remission is coincident with the dominance of cytotoxic subtypes, while leukemia progression is correlated with the emergence of subtypes with B cell transcriptional profiles, which have dysfunctional features and might predict relapse. We further validate in vitro that the generation of B-featured CAR-T cells is induced by excessive tumor antigen stimulation or suppressed TCR signaling, while it is relieved by exogenous IL-12. Moreover, we define transcriptional hallmarks of CAR-T cell subtypes and reveal their molecular changes along computationally inferred cellular evolution in vivo. Collectively, these results decipher functional diversification and dynamics of peripheral CAR-T cells post-infusion.

Farmers perceive diminishing ecosystem services, but overlook dis-services in intensively used agricultural landscapes in the North China Plain.

The UN sustainable development goals ask countries to advance sustainable production methods in agriculture. While the need for a transition to sustainable agricultural production is widely felt, there is little insight into local stakeholders' perceptions regarding agroecosystem (dis)services in areas with intensive production methods. The North China Plain is an agricultural production area with intensive production systems and simplified agricultural landscapes. We conducted a survey with 267 farmers in Quzhou county in the North China Plain in 2020 to measure the perceived level of agroecosystem (dis)services supply and the changes therein between 2015 and 2020. We analyzed which explanatory factors were associated with farmers' perceptions. Provisioning services were at a high level, while the regulating and supporting ecosystem services were considered to be in low supply, as evidenced by low scores for the presence of natural enemies and earthworms, and for natural habitats such as hedgerows and windbreaks. Most of the participants did not perceive dis-services from agriculture. Differences in perception between villages with contrasting biophysical and socio-economic conditions highlight the relevance of contextualized policy development for agricultural landscape composition and configuration to manage ecosystem (dis)services.

A New Method of Extracting Polygonatum sibiricum Polysaccharide with Antioxidant Function: Ultrasound-Assisted Extraction-Deep Eutectic Solvents Method.

Polygonatum sibiricum Polysaccharide (PsP) with antioxidant function is the main active component of Polygonatum sibiricum (P.sibiricum). The currently poor extraction yield and extraction methods of PsP cannot meet the application of that in food industrial production. In this research, an ultrasound-assisted extraction-deep eutectic solvents (UAE-DESs) method, which has never been used in the PsP industry, was first used to extract PsP. The extraction conditions were optimized by the response surface method (RSM). Both the extraction yield and antioxidant function were simultaneously considered during the optimization process. The indicators of PsP's level and antioxidant activity in vitro were used to present the extraction yield of the UAE-DESs method, the purity, and the antioxidant effect of PsP. Under the optimal conditions, which included a liquid-solid ratio of 26:1 (mL:g), extraction temperature of 80 °C, ultrasonic time of 51 min, and ultrasonic power of 82 W, the PsP extraction yield could reach (43.61 ± 0.09)%, which was obviously higher than single DESs (33.81%) and UAE (5.83%), respectively, and the PsP appeared favorably antioxidant function. This research proposed an efficient extraction method for PsP, filled the basic research gap, and further improved the development of PsP as a dietary supplement with antioxidant function in the food industry.

Occurrence and potential release of heavy metals in female underwear manufactured in China: Implication for women's health.

Underwear is a potential source of women's exposure to heavy metals owing to its direct contact with the skin, especially the skin of the vagina and vulva, which has a strong absorptive capacity. However, information regarding the prevalence of metals in female underwear, and its potential hazards, remains scarce. In the present study, we examined the concentrations and potential release of Cr, Co, Ni, Cu, As, Cd, Sb, and Pb in brassieres and briefs manufactured in China. We detected higher levels of Pb and moderate levels of other metals, relative to the metal levels reported for other textiles in the literature. Cu, As, Ni and Cd, had higher migration rates (MRs) from the underwear, with medians of 100%, 100%, 30.1%, and 20.7%, respectively. The median MRs of the other metals were in the range 1.07%-15.7%. On the whole, the total and extractable concentrations of these metals differed by item and fabric type. The pollution of raw materials and the use of chemical additives containing metals commonly contributed to the metals in the underwear. On the basis of the exposure estimation, the non-carcinogenic risks posed by the underwear metals were acceptable, but the carcinogenic risks from the metals in 5.18% of brassiere samples exceeded the acceptable level.

Revealing the impact of CD70 expression on the manufacture and functions of CAR-70 T-cells based on single-cell transcriptomics.

BACKGROUND: Chimeric antigen receptor-modified T cells (CAR T-cells) have shown exhilarative clinical efficacy for hematological malignancies. However, a shared antigen pool between healthy and malignant T-cells remains a concept to be technically and clinically explored for CAR T-cell therapy in T-cell cancers. No guidelines for engineering CAR T-cells targeting self-expressed antigens are currently available. METHOD: Based on anti-CD70 CAR (CAR-70) T-cells, we constructed CD70 knock-out and wild-type CAR (CAR-70KO and CAR-70WT) T-cells and evaluated their manufacturing and anti-tumor capability. Single-cell RNA sequencing and TCR sequencing were performed to further reveal the underlying differences between the two groups of CAR T-cells. RESULTS: Our data showed that the disruption of target genes in T-cells before CAR transduction advantaged the expansion and cell viability of CAR T-cells during manufacturing periods, as well as the degranulation, anti-tumor efficacy, and proliferation potency in response to tumor cells. Meanwhile, more naïve and central memory phenotype CAR+ T-cells, with higher TCR clonal diversity, remained in the final products in KO samples. Gene expression profiles revealed a higher activation and exhaustion level of CAR-70WT T-cells, while signaling transduction pathway analysis identified a higher level of the phosphorylation-related pathway in CAR-70KO T-cells. CONCLUSION: This study evidenced that CD70 stimulation during manufacturing process induced early exhaustion of CAR-70 T-cells. Knocking-out CD70 in T-cells prevented the exhaustion and led to a better-quality CAR-70 T-cell product. Our research will contribute to good engineering CAR T-cells targeting self-expressed antigens.