ABSTRACT
Mercury (Hg), especially methylmercury (MeHg), accumulation in rice grain due to rice paddy possessing conditions conducive to Hg methylation has led to human Hg exposure through consumption of rice-based daily meals. In addition to being a food staple, rice is widely used as a raw material to produce a vast variety of processed food products. Little is known about Hg levels in snacking rice-food products and potential Hg exposure from consumption of them, besides previous studies on infant rice cereals. Aiming to provide complementary information for a more complete assessment on Hg exposure risk originated from Hg-containing rice, this study determined total Hg (THg) and MeHg levels in 195 rice-containing and rice-free processed food products covering all major types of snack foods marketed in China and the estimated daily intake (EDI) of dietary Hg from the consumption of these foods. The results clearly showed THg and MeHg contents in rice-containing foods were significantly higher than rice-free products, suggesting the transfer of Hg and MeHg from the rice to the end products, even after manufacturing processes. Moreover, significant positive correlations were observed between THg, MeHg, or MeHg/THg ratio and rice content for samples containing multiple grains as ingredients, further indicating the deciding role of rice for Hg levels in the end food products. Although the EDI of THg and MeHg via rice-based food products were relatively low compared to the reference dose, it should be considered these snacking food products would contribute additive Hg intake outside of the daily regular meals.
Subject(s)
Dietary Exposure , Food Contamination , Mercury , Methylmercury Compounds , Oryza , Oryza/chemistry , Mercury/analysis , Food Contamination/analysis , China , Methylmercury Compounds/analysis , Dietary Exposure/analysis , Dietary Exposure/statistics & numerical data , Humans , Risk AssessmentABSTRACT
BACKGROUND: Acceleration of aging is a major challenge in public health. Previous studies have focused on the associations between specific types of exercise or overall levels of physical activity with accelerated aging, with less attention given to the weekly exercise patterns. OBJECTIVE: To explore the relationship between weekly exercise patterns and acceleration of aging among American adults. METHODS: We extracted data from the 2015-2018 National Health and Nutrition Examination Survey (NHANES), involving 9850 participants aged ≥20 with comprehensive records on exercise and phenotypic age. Hierarchical clustering categorized participants into three groups based on weekly exercise time and days: cluster 1 (Rare or No Exercise), cluster 2 (Moderate Frequency, Moderate Duration) and cluster 3 (Moderate Frequency, Long Duration). Acceleration of aging was defined as the phenotypic age advance >0. RESULTS: After full adjustment, weekly exercise time and days showed the significant non-linear negative correlation with accelerated aging. The risk of accelerated aging was lowest when weekly exercise days reached five and the weekly exercise time reached three hours. Both cluster 2 and cluster 3 were significantly negatively correlated with acceleration of aging. No significant differences were observed in the association with accelerated aging between cluster 2 and cluster 3. CONCLUSIONS: These findings highlight the importance of targeted exercise programs for healthy aging. They also emphasize the need for public health initiatives to integrate regular physical activity into daily routines to improve the longevity and well-being of American adults.
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In the realm of photovoltaic research, 2D transition metal carbides (MXenes) have gained significant interest due to their exceptional photoelectric capabilities. However, the instability of MXenes due to oxidation has a direct impact on their practical applications. In this work, the oxidation process of Nb2CTx MXene in aqueous systems is methodically simulated at the atomic level and nanosecond timescales, which elucidates the structural variations influenced by the synergistic effects of water and dissolved oxygen, predicting a transition from metal to semiconductor with 44% C atoms replaced by O atoms in Nb2CTx. Moreover, Nb2CTx with varying oxidation degrees is utilized as electron transport layers (ETLs) in perovskite solar cells (PSCs). Favorable energy level alignments with superior electron transfer capability are achieved by controlled oxidation. By further exploring the composites of Nb2CTx to its derivatives, the strong interaction of the nano-composites is demonstrated to be more effective for electron transport, thus the corresponding PSC achieves a better performance with long-term stability compared with the widely used ETLs like SnO2. This work unravels the oxidation dynamics of Nb2CTx and provides a promising approach to designing ETL by exploiting MXenes to their derivatives for photovoltaic technologies.
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Background: Sleep disturbances are widespread but usually overlooked health risk factors for coronavirus disease 2019 (COVID-19). We aimed to investigate the influence of pre-existing sleep disturbances on the susceptibility, severity, and long-term effects of COVID-19. Methods: We searched PubMed, Web of Science, and Embase for relevant articles from inception to October 27, 2023 and updated at May 8, 2024. Sleep disturbances included obstructive sleep apnea (OSA), insomnia, abnormal sleep duration, night-shift work, and any other sleep disturbances. Outcomes were COVID-19 susceptibility, hospitalization, mortality, and long COVID. The effect sizes were pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). This study is registered with PROSPERO (CRD42024503518). Findings: A total of 48 observational studies (n = 8,664,026) were included. Pre-existing sleep disturbances increased the risk of COVID-19 susceptibility (OR = 1.12, 95% CI 1.07-1.18), hospitalization (OR = 1.25, 95% CI 1.15-1.36), mortality (OR = 1.45, 95% CI 1.19-1.78), and long COVID (OR = 1.36 95% CI 1.17-1.57). Subgroup analysis showed that younger individuals with sleep disturbances were associated with higher susceptibility and hospitalization and a lower risk of mortality than older individuals. Males with sleep disturbances were associated with higher mortality. For specific sleep disturbances, the susceptibility and hospitalization of COVID-19 were associated with OSA, abnormal sleep duration, and night-shift work; mortality of COVID-19 was linked to OSA; risk of long COVID was related to OSA, abnormal sleep duration and insomnia. Interpretation: Pre-existing sleep disturbances, especially OSA, increased the risk of COVID-19 susceptibility, hospitalization, mortality, and long COVID. Age and sex played important roles in the effect of sleep disturbances on COVID-19. Funding: The National Natural Science Foundation of China and the Key Laboratory of Respiratory Diseases of Liaoning Province.
ABSTRACT
While many countries employed digital contact tracing to contain the spread of SARS-CoV-2, the contribution of cospace-time interaction (i.e., individuals who shared the same space and time) to transmission and to super-spreading in the real world has seldom been systematically studied due to the lack of systematic sampling and testing of contacts. To address this issue, we utilized data from 2230 cases and 220,878 contacts with detailed epidemiological information during the Omicron outbreak in Beijing in 2022. We observed that contact number per day of tracing for individuals in dwelling, workplace, cospace-time interactions, and community settings could be described by gamma distribution with distinct parameters. Our findings revealed that 38% of traced transmissions occurred through cospace-time interactions whilst control measures were in place. However, using a mathematical model to incorporate contacts in different locations, we found that without control measures, cospace-time interactions contributed to only 11% (95%CI: 10%-12%) of transmissions and the super-spreading risk for this setting was 4% (95%CI: 3%-5%), both the lowest among all settings studied. These results suggest that public health measures should be optimized to achieve a balance between the benefits of digital contact tracing for cospace-time interactions and the challenges posed by contact tracing within the same setting.
Subject(s)
COVID-19 , Contact Tracing , SARS-CoV-2 , Contact Tracing/methods , Humans , COVID-19/transmission , COVID-19/epidemiology , SARS-CoV-2/isolation & purification , China/epidemiology , Disease Outbreaks , Models, TheoreticalABSTRACT
Drought is one of the most common environmental stressors that severely threatens plant growth, development, and productivity. B2 (2,4-dichloroformamide cyclopropane acid), a novel plant growth regulator, plays an essential role in drought adaptation, significantly enhancing the tolerance of Carex breviculmis seedlings. Its beneficial effects include improved ornamental value, sustained chlorophyll content, increased leaf dry weight, elevated relative water content, and enhanced root activity under drought conditions. B2 also directly scavenges hydrogen peroxide and superoxide anion contents while indirectly enhancing the activities of antioxidant enzymes (superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase) to detoxify reactive oxygen species (ROS) oxidative damage. Transcriptome analysis demonstrated that B2 activates drought-responsive transcription factors (AP2/ERF-ERF, WRKY, and mTERF), leading to significant upregulation of genes associated with phenylpropanoid biosynthesis (HCT, POD, and COMT). Additionally, these transcription factors were found to suppress the degradation of starch. B2 regulates phytohormone signaling related-genes, leading to an increase in abscisic acid contents in drought-stressed plants. Collectively, these findings offer new insights into the intricate mechanisms underlying C. breviculmis' resistance to drought damage, highlighting the potential application of B2 for future turfgrass establishment and management with enhanced drought tolerance.
Subject(s)
Droughts , Plant Growth Regulators , Reactive Oxygen Species , Starch , Reactive Oxygen Species/metabolism , Plant Growth Regulators/metabolism , Starch/metabolism , Starch/biosynthesis , Gene Expression Regulation, Plant , Signal Transduction , Plant Proteins/metabolism , Plant Proteins/genetics , Propanols/metabolism , Transcription Factors/metabolism , Transcription Factors/genetics , Drought ResistanceABSTRACT
We investigated Alongshan virus infection in reindeer in northeastern China. We found that 4.8% of the animals were viral RNA-positive, 33.3% tested positive for IgG, and 19.1% displayed neutralizing antibodies. These findings suggest reindeer could serve as sentinel animal species for the epidemiologic surveillance of Alongshan virus infection.
Subject(s)
Antibodies, Viral , Reindeer , Animals , Reindeer/virology , China/epidemiology , Antibodies, Viral/blood , Antibodies, Neutralizing/blood , Bunyaviridae Infections/veterinary , Bunyaviridae Infections/epidemiology , Bunyaviridae Infections/virology , RNA, Viral , Immunoglobulin G/bloodABSTRACT
Benzene is the main environmental pollutant and risk factor of childhood leukemia and chronic benzene poisoning. Benzene exposure leads to hematopoietic stem and progenitor cell (HSPC) dysfunction and abnormal blood cell counts. However, the key regulatory targets and mechanisms of benzene hematotoxicity are unclear. In this study, we constructed a benzene-induced hematopoietic damage mouse model to explore the underlying mechanisms. We identified that Insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) was significantly reduced in benzene-exposed mice. Moreover, targeting IGF2BP1 effectively mitigated damages to hematopoietic function and hematopoietic molecule expression caused by benzene in mice. On the mechanics, by metabolomics and transcriptomics, we discovered that branched-chain amino acid (BCAA) metabolism and fatty acid oxidation were key metabolic pathways, and Branched-chain amino acid transaminase 1 (BCAT1) and Carnitine palmitoyltransferase 1a (CPT1A) were critical metabolic enzymes involved in IGF2BP1-mediated hematopoietic injury process. The expression of the above molecules in the benzene exposure population was also examined and consistent with animal experiments. In conclusion, targeting IGF2BP1 alleviated hematopoietic injury caused by benzene exposure, possibly due to the reprogramming of BCAA metabolism and fatty acid oxidation via BCAT1 and CPT1A metabolic enzymes. IGF2BP1 is a potential regulatory and therapeutic target for benzene hematotoxicity.
Subject(s)
Amino Acids, Branched-Chain , Benzene , Fatty Acids , Oxidation-Reduction , Animals , Benzene/toxicity , Amino Acids, Branched-Chain/metabolism , Fatty Acids/metabolism , Oxidation-Reduction/drug effects , Mice , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , Carnitine O-Palmitoyltransferase/metabolism , Carnitine O-Palmitoyltransferase/genetics , Male , Mice, Inbred C57BL , Hematopoietic Stem Cells/metabolism , Hematopoietic Stem Cells/drug effectsABSTRACT
Microplastics (MPs) have been found in the air, human nasal cavity, and lung, suggesting that the respiratory tract is one of the important exposure routes for MPs. The lung is a direct target organ for injury from inhaled MPs, but data on lung injury from longer-term exposure to environmental doses of MPs are limited, and the mechanisms remain unclear. Here, C57BL/6 J mice were treated with 5 µm polystyrene (PS)-MPs by intratracheal instillation (0.6, 3, and 15 mg/kg) for 60 days to establish MPs exposure model. We found that PS-MPs lead to increased collagen fibers and decreased lung barrier permeability and lung function in lung tissue. Mechanistically, the abundance of gram-negative bacteria in the pulmonary flora increased after inhalation of PS-MPs, causing lipopolysaccharide (LPS) release. The expression of Toll-like receptor 4 (TLR4), the key receptor of LPS, was increased, and ferroptosis occurred in lung tissue cells. Further in vitro intervention experiments were performed, pulmonary flora/TLR4-induced imbalance of lung iron homeostasis is an important mechanism of PS-MPs-induced lung injury. Our study provides new evidence for lung injury caused by environmental doses of MPs and strategies to prevent it through longer-term dynamic observation.
Subject(s)
Homeostasis , Iron , Lung , Mice, Inbred C57BL , Microplastics , Polystyrenes , Toll-Like Receptor 4 , Animals , Polystyrenes/toxicity , Mice , Lung/drug effects , Microplastics/toxicity , Toll-Like Receptor 4/metabolism , Homeostasis/drug effects , Iron/metabolism , Lung Injury/chemically induced , Inhalation Exposure/adverse effectsABSTRACT
An eight-week feeding trial was designed to assess which component of commensal Bacillus siamensis LF4 can mitigate SBM-induced enteritis and microbiota dysbiosis in spotted seabass (Lateolabrax maculatus) based on TLRs-MAPKs/NF-кB signaling pathways. Fish continuously fed low SBM (containing 16 % SBM) and high SBM (containing 40 % SBM) diets were used as positive (FM group) and negative (SBM group) control, respectively. After feeding high SBM diet for 28 days, fish were supplemented with B. siamensis LF4-derived whole cell wall (CW), cell wall protein (CWP), lipoteichoic acid (LTA) or peptidoglycan (PGN) until 56 days. The results showed that a high inclusion of SBM in the diet caused enteritis, characterized with significantly (P < 0.05) decreased muscular thickness, villus height, villus width, atrophied and loosely arranged microvillus. Moreover, high SBM inclusion induced an up-regulation of pro-inflammatory cytokines and a down-regulation of occludin, E-cadherin, anti-inflammatory cytokines, apoptosis related genes and antimicrobial peptides. However, dietary supplementation with CW, LTA, and PGN of B. siamensis LF4 could effectively alleviate enteritis caused by a high level of dietary SBM. Additionally, CWP and PGN administration increased beneficial Cetobacterium and decreased pathogenic Plesiomonas and Brevinema, while dietary LTA decreased Plesiomonas and Brevinema, suggesting that CWP, LTA and PGN positively modulated intestinal microbiota in spotted seabass. Furthermore, CW, LTA, and PGN application significantly stimulated TLR2, TLR5 and MyD88 expressions, and inhibited the downstream p38 and NF-κB signaling. Taken together, these results suggest that LTA and PGN from B. siamensis LF4 could alleviate soybean meal-induced enteritis and microbiota dysbiosis in L. maculatus, and p38 MAPK/NF-κB pathways might be involved in those processes.
Subject(s)
Animal Feed , Bacillus , Diet , Dysbiosis , Enteritis , Fish Diseases , Gastrointestinal Microbiome , Glycine max , Lipopolysaccharides , Peptidoglycan , Teichoic Acids , Animals , Fish Diseases/immunology , Animal Feed/analysis , Enteritis/veterinary , Enteritis/immunology , Enteritis/microbiology , Dysbiosis/veterinary , Dysbiosis/immunology , Bacillus/physiology , Bacillus/chemistry , Gastrointestinal Microbiome/drug effects , Diet/veterinary , Glycine max/chemistry , Lipopolysaccharides/pharmacology , Teichoic Acids/pharmacology , Peptidoglycan/pharmacology , Peptidoglycan/administration & dosage , Bass/immunology , Probiotics/pharmacology , Probiotics/administration & dosage , Dietary Supplements/analysis , Random AllocationABSTRACT
Despite identifying El Niño events as a factor in dengue dynamics, predicting the oscillation of global dengue epidemics remains challenging. Here, we investigate climate indicators and worldwide dengue incidence from 1990 to 2019 using climate-driven mechanistic models. We identify a distinct indicator, the Indian Ocean basin-wide (IOBW) index, as representing the regional average of sea surface temperature anomalies in the tropical Indian Ocean. IOBW is closely associated with dengue epidemics for both the Northern and Southern hemispheres. The ability of IOBW to predict dengue incidence likely arises as a result of its effect on local temperature anomalies through teleconnections. These findings indicate that the IOBW index can potentially enhance the lead time for dengue forecasts, leading to better-planned and more impactful outbreak responses.
Subject(s)
Dengue , Epidemics , Humans , Climate Models , Dengue/epidemiology , El Nino-Southern Oscillation , Incidence , Indian Ocean , Hot TemperatureABSTRACT
Decabromodiphenyl ether (BDE-209) has been universally detected in environmental media and animals, but its damage to ovarian function and mechanism is still unclear, and melatonin has been shown to improve mammalian ovarian function. This study aimed to investigate the toxic effects of BDE-209 on the ovary and tried to improve ovarian function with melatonin. Herein, BDE-209 was administered orally to female SD rats for 60 days. Enzyme-linked immunosorbent assay, HE staining, transcriptome analysis, qPCR and immunohistochemical staining were used to explore and verify the potential mechanism. We found that BDE-209 exposure had effects on the ovary, as shown by abnormal changes in the estrous cycle, hormone levels and ovarian reserve function in rats, while increasing the proportion of collagen fibres in ovarian tissue. In terms of mechanism, cuproptosis, a form of cell death, was identified to play a crucial role in BDE-209-induced ovarian dysfunction, with the phenotype manifested as copper salt accumulation in ovary, downregulation of glutathione pathway metabolism and copper transfer molecule (ATP7A/B), and upregulation of FDX1, lipoic acid pathway (LIAS, LIPT1), pyruvate dehydrogenase complex components (DLAT, PDHB, PDHA1), and copper transfer molecule (SLC31A1). Furthermore, possible interventions were explored. Notably, a supplement with melatonin has a repair effect on the damage to ovarian function by reversing the gene expression of cuproptosis-involved molecules. Overall, this study revealed that cuproptosis is involved in BDE-209-induced ovarian damage and the beneficial effect of melatonin on ovarian copper damage, providing evidence for the prevention and control of female reproductive damage induced by BDE-209.
Subject(s)
Halogenated Diphenyl Ethers , Melatonin , Ovary , Rats, Sprague-Dawley , Animals , Melatonin/pharmacology , Female , Halogenated Diphenyl Ethers/toxicity , Ovary/drug effects , Ovary/metabolism , Rats , Protective Agents/pharmacology , Environmental Pollutants/toxicityABSTRACT
Strigolactones (SLs) are plant hormones that regulate several key agronomic traits, including shoot branching, leaf senescence, and stress tolerance. The artificial regulation of SL biosynthesis and signaling has been considered as a potent strategy in regulating plant architecture and combatting the infection of parasitic weeds to help improve crop yield. DL1b is a previously reported SL receptor inhibitor molecule that significantly promotes shoot branching. Here, we synthesized 18 novel compounds based on the structure of DL1b. We performed rice tillering activity assay and selected a novel small molecule, C6, as a candidate SL receptor inhibitor. In vitro bioassays demonstrated that C6 possesses various regulatory functions as an SL inhibitor, including inhibiting germination of the root parasitic seeds Phelipanche aegyptiaca, delaying leaf senescence and promoting hypocotyl elongation of Arabidopsis. ITC analysis and molecular docking experiments further confirmed that C6 can interact with SL receptor proteins, thereby interfering with the binding of SL to its receptor. Therefore, C6 is considered a novel SL receptor inhibitor with potential applications in plant architecture control and prevention of root parasitic weed infestation.
Subject(s)
Arabidopsis , Esters , Heterocyclic Compounds, 3-Ring , Lactones , Naphthalenes , Molecular Docking Simulation , Carboxylic AcidsABSTRACT
Objective: To investigate the effectiveness of a multimodal deep learning model in predicting tumor budding (TB) grading in rectal cancer (RC) patients. Materials and methods: A retrospective analysis was conducted on 355 patients with rectal adenocarcinoma from two different hospitals. Among them, 289 patients from our institution were randomly divided into an internal training cohort (n = 202) and an internal validation cohort (n = 87) in a 7:3 ratio, while an additional 66 patients from another hospital constituted an external validation cohort. Various deep learning models were constructed and compared for their performance using T1CE and CT-enhanced images, and the optimal models were selected for the creation of a multimodal fusion model. Based on single and multiple factor logistic regression, clinical N staging and fecal occult blood were identified as independent risk factors and used to construct the clinical model. A decision-level fusion was employed to integrate these two models to create an ensemble model. The predictive performance of each model was evaluated using the area under the curve (AUC), DeLong's test, calibration curve, and decision curve analysis (DCA). Model visualization Gradient-weighted Class Activation Mapping (Grad-CAM) was performed for model interpretation. Results: The multimodal fusion model demonstrated superior performance compared to single-modal models, with AUC values of 0.869 (95% CI: 0.761-0.976) for the internal validation cohort and 0.848 (95% CI: 0.721-0.975) for the external validation cohort. N-stage and fecal occult blood were identified as clinically independent risk factors through single and multivariable logistic regression analysis. The final ensemble model exhibited the best performance, with AUC values of 0.898 (95% CI: 0.820-0.975) for the internal validation cohort and 0.868 (95% CI: 0.768-0.968) for the external validation cohort. Conclusion: Multimodal deep learning models can effectively and non-invasively provide individualized predictions for TB grading in RC patients, offering valuable guidance for treatment selection and prognosis assessment.
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Fe3Al is a good magnetic loss absorber for microwave absorption. However, due to the relatively high density and poor impedance matching ratio, the potential of Fe3Al cannot be fully released. Herein, a dielectric loss absorber of carbon nanotubes (CNTs) is coupled with Fe3Al to form Fe3Al/CNTs composite absorbers. CNTs are randomly tangled and coated on the surface of the Fe3Al flakes, forming a connecting conductive network. By carefully tuning the content of CNTs, the optimized Fe3Al/CNTs composite absorber with 1.5% of CNTs can combine both magnetic loss and dielectric loss mechanisms, thus achieving an impedance matching ratio close to 1 while keeping strong attenuation for enhanced microwave absorption. As a result, an effective absorption bandwidth (RL ≤ -10 dB) of 4.73 GHz at a thickness of 2 mm is achieved.
ABSTRACT
Nanoplatforms with high Mn2+ coordination can display efficient T1 magnetic resonance imaging (MRI) contrast enhancement. Herein, an earth gravity-like method for enhanced interaction between Ferritin (Fn) and Mn2+ by the growth of platinum nanoparticles (PNs) in Fn's cage structure via a biomineralization method is first proposed. Fn has good biocompatibility and can provide a suitable growth site for PNs. PNs with negative charge have certain attraction to Mn2+ with positive charge, improving Fn's loading capacity of Mn2+ by attraction force; and thus, achieving efficient MRI contrast enhancement. In addition, PNs can be applied for efficient photothermal therapy (PTT) under near infrared ray (NIR) irradiation. Systemic delivery of this nanoplatform shows obvious MRI contrast enhancement and tumor progression inhibition after NIR irradiation, as well as no obvious side effects. Therefore, this nanoplatform has the potential to contribute to nanotheranostic for clinical transformation.
Subject(s)
Contrast Media , Ferritins , Magnetic Resonance Imaging , Manganese , Metal Nanoparticles , Photothermal Therapy , Platinum , Platinum/chemistry , Platinum/pharmacology , Photothermal Therapy/methods , Animals , Magnetic Resonance Imaging/methods , Ferritins/chemistry , Ferritins/metabolism , Metal Nanoparticles/chemistry , Metal Nanoparticles/therapeutic use , Manganese/chemistry , Humans , Mice , Contrast Media/chemistry , Infrared Rays , Cell Line, Tumor , Mice, Inbred BALB C , Neoplasms/therapy , Neoplasms/diagnostic imaging , Neoplasms/metabolism , Mice, NudeABSTRACT
Chimeric antigen receptor (CAR) T-cell therapies are increasingly adopted as a commercially available treatment for hematologic and solid tumor cancers. As CAR-T therapies reach more patients globally, the cryopreservation and banking of patients' leukapheresis materials is becoming imperative to accommodate intra/inter-national shipping logistical delays and provide greater manufacturing flexibility. This study aims to determine the optimal temperature range for transferring cryopreserved leukapheresis materials from two distinct types of controlled rate freezing systems, Liquid Nitrogen (LN2)-based and LN2-free Conduction Cooling-based, to the ultracold LN2 storage freezer (≤-135 °C), and its impact on CAR T-cell production and functionality. Presented findings demonstrate that there is no significant influence on CAR T-cell expansion, differentiation, or downstream in-vitro function when employing a transfer temperature range spanning from -30 °C to -80 °C for the LN2-based controlled rate freezers as well as for conduction cooling controlled rate freezers. Notably, CAR T-cells generated from cryopreserved leukapheresis materials using the conduction cooling controlled rate freezer exhibited suboptimal performance in certain donors at transfer temperatures lower than -60 °C, possibly due to the reduced cooling rate of lower than 1 °C/min and extended dwelling time needed to reach the final temperatures within these systems. This cohort of data suggests that there is a low risk to transfer cryopreserved leukapheresis materials at higher temperatures (between -30 °C and -60 °C) with good functional recovery using either controlled cooling system, and the cryopreserved materials are suitable to use as the starting material for autologous CAR T-cell therapies.
Subject(s)
Cryopreservation , Immunotherapy, Adoptive , Leukapheresis , T-Lymphocytes , Cryopreservation/methods , Leukapheresis/methods , Humans , T-Lymphocytes/cytology , T-Lymphocytes/immunology , Immunotherapy, Adoptive/methods , Receptors, Chimeric Antigen , Temperature , Freezing , Cell Culture Techniques/methodsABSTRACT
Due to the annual increase in its production and consumption in occupational environments, the adverse blood outcomes caused by benzene are of concern. However, the mechanism of benzene-induced hematopoietic damage remains elusive. Here, we report that benzene exposure causes hematopoietic damage in a dose-dependent manner and is associated with disturbances in gut microbiota-long chain fatty acids (LCFAs)-inflammation axis. C57BL/6J mice exposed to benzene for 45 days were found to have a significant reduction in whole blood cells and the suppression of hematopoiesis, an increase in Bacteroides acidifaciens and a decrease in Lactobacillus murinus. Recipient mice transplanted with fecal microbiota from benzene-exposed mice showed potential for hematopoietic disruption, LCFAs, and interleukin-5 (IL-5) elevation. Abnormally elevated plasma LCFAs, especially palmitoleic acid (POA) exacerbated benzene-induced immune-inflammation and hematopoietic damage via carnitine palmitoyltransferase 2 (CPT2)-mediated disorder of fatty acid oxidation. Notably, oral administration of probiotics protects the mice against benzene-induced hematopoietic toxicity. In summary, our data reveal that the gut microbiota-POA-IL-5 axis is engaged in benzene-induced hematopoietic damage. Probiotics might be a promising candidate to prevent hematopoietic abnormalities from benzene exposure.
Subject(s)
Fatty Acids, Monounsaturated , Gastrointestinal Microbiome , Interleukin-5 , Animals , Mice , Mice, Inbred C57BL , Benzene/toxicity , Fatty Acids , InflammationABSTRACT
Nickel oxide (NiOx) has been limited in use as a hole transport layer for its low conduction, surface defects, and redox reactions with the perovskite layer. To address these issues, the incorporation of zwitterion L-tryptophan (Trp) is proposed at the NiOx/Trp interface. The carboxyl group of Trp effectively passivates the surface positive defects of NiOx, thereby improving its optical and electrical properties. The ammonium group of Trp not only passivates negative defects but modulates the growth of the perovskite layer, resulting in an improved perovskite film quality. Furthermore, the Trp layer acts as a buffer layer, suppressing adverse interfacial reactions between the perovskite and NiOx. Consequently, perovskite solar cells with 1.56 and 1.68 eV absorbers achieve the champion power conversion efficiency (PCE) of 23.79% and 20.41%, respectively. Moreover, the unencapsulated devices demonstrate excellent long-term stability, retaining above 80% of the initial PCE value after 1600 h of storage in the air with a humidity of 50-60%.