ABSTRACT
Given China's prohibition on the utilization of antibiotics as feed additives in 2020, we aim to investigate nutrition additives that are both efficient and safe. Lactobacillus, a well-recognized beneficial probiotic, has explicitly been investigated for its effects on health status of the host and overall impact on food industry. To evaluate effects of Lactobacillus plantarum (LW) supplementation on broiler chicken, we conducted comprehensive multi-omics analysis, growth performance evaluation, RT-qPCR analysis, and immunofluorescence. The findings revealed that LW supplementation resulted in a substantial progress in growth performance (approximately 205 g increase in final body weight in comparison to the control group (p < 0.01)). Additionally, LW exhibited promising potential for enhancing antioxidant properties of serum and promoting gut integrity and growth as evidenced by improved antioxidant indices (p < 0.01), intestinal villus morphology (p < 0.01), and enhanced gut barrier function (p < 0.01). Meanwhile, the multi-omics analysis, including 16S rRNA sequencing and liquid chromatography-tandem mass spectrometry, revealed an enrichment of beneficial microbes in the gut of broilers that were supplemented with LW, while simultaneously depleting harmful microorganisms. Moreover, a noteworthy modification was observed in gut metabolic profiling subsequent to the execution of the probiotic strategy. Specifically, variations were noticed in the levels of metabolites and metabolic pathways such as parathyroid hormone synthesis, inflammatory mediator regulation of TRP channels, oxidative phosphorylation, and mineral absorption. Taken together, our findings validate that LW administration produces valuable effects on the health and growth performance of broilers owing to its capability to boost the gut microbiota homeostasis and intestinal metabolism. Present findings signify the potential of LW as a dietary additive to promote growth and development in broiler chickens.
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Acute myeloid leukemia (AML) can manifest as de novo AML (dn-AML) or secondary AML (s-AML), with s-AML being associated with inferior survival and distinct genomic characteristics. The underlying reasons for this disparity remain to be elucidated. In this multicenter study, next-generation sequencing (NGS) was employed to investigate the mutational landscape of AML in 721 patients from June 2020 to May 2023.Genetic mutations were observed in 93.34% of the individuals, with complex variations (more than three gene mutations) present in 63.10% of them. TET2, ASXL1, DNMT3A, TP53 and SRSF2 mutations showed a higher prevalence among older individuals, whereas WT1 and KIT mutations were more commonly observed in younger patients. BCOR, BCORL1, ZRSR2, ASXL1 and SRSF2 exhibited higher mutation frequencies in males. Additionally, ASXL1, NRAS, PPMID, SRSF2, TP53 and U2AF1 mutations were more common in patients with s-AML, which PPM1D was more frequently associated with therapy-related AML (t-AML). Advanced age and hyperleukocytosis independently served as adverse prognostic factors for both types of AML; however, s-AML patients demonstrated a greater number of monogenic adverse prognostic factors compared to dn-AML cases (ASXL1, PPM1D, TP53 and U2AF1 in s-AML vs. FLT3, TP53 and U2AF1 in dn-AML). Age and sex-related gene mutations suggest epigenetic changes may be key in AML pathogenesis. The worse prognosis of s-AML compared to dn-AML could be due to the older age of s-AML patients and more poor-prognosis gene mutations. These findings could improve AML diagnosis and treatment by identifying potential therapeutic targets and risk stratification biomarkers.
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Non-invasive neuroimaging has revealed specific network-based resting-state dynamics in the human brain, yet the underlying neurophysiological mechanism remains unclear. We employed intracranial electroencephalography to characterize local field potentials within the default mode network (DMN), frontoparietal network (FPN), and salience network (SN) in 42 participants. We identified stronger within-network phase coherence at low frequencies (θ and α band) within the DMN, and at high frequencies (γ band) within the FPN. Hidden Markov modeling indicated that the DMN exhibited preferential low frequency phase coupling. Phase-amplitude coupling (PAC) analysis revealed that the low-frequency phase in the DMN modulated the high-frequency amplitude envelopes of the FPN, suggesting frequency-dependent characterizations of intrinsic brain networks at rest. These findings provide intracranial electrophysiological evidence in support of the network model for intrinsic organization of human brain and shed light on the way brain networks communicate at rest.
ABSTRACT
Informed by the interaction of person-affect-cognition-execution (I-PACE) theory, the present studies examined the association between peer rejection, peer popularity, and social media addiction (SMA) at both between-person and within-person levels. Two distinct processes, the fear-driven/compensation-seeking process and the reward-driven process were explored. In Study 1, using a cross-sectional sample of high school students (N = 318), both processes were supported via different cognitive mediators. Support for the fear-driven/compensation-seeking process was demonstrated by finding that avoidance expectancy was a significant cognitive mediator between peer-nominated rejection and SMA. In turn, the reward-driven process was supported by the significant mediation of reward expectancy between peer-nominated popularity and SMA. In Study 2, using ecological momentary assessment with college students (N = 54), we found the fear-driven/compensation-seeking process partially supported through both between-person and within-person mediations. Specifically, negative affect and social media craving were two affective mediators that linked peer rejection and addictive social media use behaviors. On the other hand, the reward-driven process was predominantly supported by within-person mediations, in which positive affect and social media craving were found to be mediators of the relationship between peer popularity and addictive social media use behaviors. The results underscore that adolescents experiencing rejection tend to use social media to avoid negative feelings and compensate for interpersonal deficits, while adolescents experiencing popularity tend to use social media to maintain positive feelings and gain social rewards. Implications for the assessment, case formulation, and treatment of SMA in counseling practice are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
ABSTRACT
Chimeric antigen receptor (CAR) T cell therapy shows promise in treating malignant tumors. However, the use of human epidermal growth factor receptor-2 (HER2) CAR-T cells carries the risk of severe toxicity, including cytokine release syndrome, due to their "on-target off-tumor" recognition of HER2. Enhancing the quality and functionality of HER2 CARs could greatly improve the therapeutic potential of CAR-T cells. In this study, we developed a novel anti-HER2 monoclonal antibody, Ab8, which targets domain III of HER2, distinct from the domain IV recognition of trastuzumab. Although two anti-HER2 mAbs induced similar levels of antibody-dependent cellular cytotoxicity, trastuzumab-based CAR-T cells exhibited potent antitumor activity against HER2-positive cancer cells. In conclusion, our findings provide scientific evidence that antibody recognition of the membrane-proximal domain promotes the anti-tumor response of HER2-specific CAR-T cells.
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Hepatocellular carcinoma (HCC), a highly lethal solid tumor, has shown responsiveness to ferroptosis inducers, presenting new avenues in cancer treatment. Our study focuses on the roles of STAT3 and Nf-κB in regulating ferroptosis, particularly their interaction in this process. Using HepG2 cells, we employed specific inhibitors (Stattic for STAT3 and Bay11-7082 for Nf-κB) and a ferroptosis inducer, SSPH I, to dissect their collective impact on ferroptosis. Our findings reveal that inhibiting STAT3 and Nf-κB enhances ferroptosis and cytotoxicity induced by SSPH I. This is mechanistically linked to alterations in iron metabolism-related proteins and GPX4 resulting from SSPH I action, which consequently triggers a STAT3-dependent activation of Nf-κB. The inhibition of STAT3 and Nf-κB led to increased intracellular ROS, MDA, and Fe2+, along with significant GSH depletion, thereby intensifying lipid peroxidation and iron overload in HepG2 cells. This study offers a deeper understanding of the ferroptosis mechanisms in HCC. It highlights the therapeutic potential of targeting STAT3 and Nf-κB pathways to enhance the efficacy of ferroptosis-based treatments.
Subject(s)
Ferroptosis , Liver Neoplasms , NF-kappa B , STAT3 Transcription Factor , Signal Transduction , Humans , Ferroptosis/drug effects , Hep G2 Cells , STAT3 Transcription Factor/metabolism , NF-kappa B/metabolism , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/drug therapy , Signal Transduction/drug effects , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/drug therapy , Sulfones/pharmacology , Nitriles/pharmacology , Reactive Oxygen Species/metabolism , Cyclic S-Oxides/pharmacology , Lipid Peroxidation/drug effectsABSTRACT
A heavy rainstorm struck Henan, China, in July 2021. Previous studies have indicated that natural disasters have a wide range of psychological sequelae, but little research has been done on the psychological effects of floods specifically. This study aimed to track the mental health trajectories of flood victims over time and identify associated protective and risk factors. People living in the areas most impacted by the flood (N = 376) were surveyed at four different time points: 3 weeks, 1 month, 2 months, and 3 months post-flood. Latent growth mixture modeling was utilized to delineate longitudinal patterns of depression, anxiety, and posttraumatic stress disorder (PTSD). Least absolute shrinkage and selection operator logistic regression, a supervised machine-learning approach, was employed to discern predictors among 49 assessed variables at both contextual and personal levels. Results revealed three classes of PTSD (resilience, recovery, moderate symptoms) and anxiety (resilience, chronicity, recovery) trajectories, along with two classes of depression trajectories (resilience, chronicity). Key factors predicting resilience in mental health included personality traits, media consumption habits, pre-existing health conditions at the individual level, and asset loss and ongoing adversities at the contextual level. In spite of the widespread impact of the flood, most victims displayed resilience in the face of adversity. Identifying critical factors across various psychological symptoms offers valuable insights for both pre-disaster preparation and post-disaster trans-diagnostic psychological interventions.
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BACKGROUND: Prenatal depression is associated with adverse health outcomes for both mothers and their children. The worldwide COVID-19 pandemic has presented new risks and challenges for expectant mothers. The aims of the study were to investigate the underlying mechanism between COVID-19 risk perception of Chinese pregnant women and their prenatal depressive symptoms and potential protective factors such as family sense of coherence (FSOC). METHOD: A total of 181 Chinese pregnant women (Mage = 31.40 years, SD = 3.67, ranged from 23 to 43) participated in an online survey from April 22 to May 16, 2020. Risk perception and negative emotions (fear and anxiety) related with COVID-19, FSOC, and prenatal depressive symptoms were assessed. RESULTS: The experience of maternal COVID-19 related negative emotion fully mediated the positive relationship between COVID-19 risk perception and prenatal depressive symptoms of pregnant women (ß = 0.12, 95% CI [0.06, 0.19]). When confronting COVID-19 related fear and anxiety, expectant mothers from higher coherent families experienced a significantly lower level of prenatal depressive symptoms. CONCLUSIONS: Contextual negative emotional experience was demonstrated to explain how risk perception impacts depressive symptoms during severe public health crisis for pregnant women. FSOC may be a psychological resource protecting pregnant women from experiencing adverse psychological outcomes during COVID-19 pandemic.
ABSTRACT
The olfactory tubercle (TUB), also called the tubular striatum, receives direct input from the olfactory bulb and, along with the nucleus accumbens, is one of the two principal components of the ventral striatum. As a key component of the reward system, the ventral striatum is involved in feeding behavior, but the vast majority of research on this structure has focused on the nucleus accumbens, leaving the TUB's role in feeding behavior understudied. Given the importance of olfaction in food seeking and consumption, olfactory input to the striatum should be an important contributor to motivated feeding behavior. Yet the TUB is vastly understudied in humans, with very little understanding of its structural organization and connectivity. In this study, we analyzed macrostructural variations between the TUB and the whole brain and explored the relationship between TUB structural pathways and feeding behavior, using body mass index (BMI) as a proxy in females and males. We identified a unique structural covariance between the TUB and the periaqueductal gray (PAG), which has recently been implicated in the suppression of feeding. We further show that the integrity of the white matter tract between the two regions is negatively correlated with BMI. Our findings highlight a potential role for the TUB-PAG pathway in the regulation of feeding behavior in humans.
Subject(s)
Feeding Behavior , Olfactory Tubercle , Periaqueductal Gray , Humans , Male , Female , Feeding Behavior/physiology , Adult , Periaqueductal Gray/physiology , Olfactory Tubercle/physiology , Magnetic Resonance Imaging/methods , Young Adult , Neural Pathways/physiologyABSTRACT
In patients on maintenance hemodialysis (MHD), vascular calcification (VC) is an independent predictor of cardiovascular disease (CVD), which is the primary cause of death in chronic kidney disease (CKD). The main component of VC in CKD is the vascular smooth muscle cells (VSMCs). VC is an ordered, dynamic activity. Under the stresses of oxidative stress and calcium-phosphorus imbalance, VSMCs undergo osteogenic phenotypic transdifferentiation, which promotes the formation of VC. In addition to traditional epigenetics like RNA and DNA control, post-translational modifications have been discovered to be involved in the regulation of VC in recent years. It has been reported that the process of osteoblast differentiation is impacted by catalytic histone or non-histone arginine methylation. Its function in the osteogenic process is comparable to that of VC. Thus, we propose that arginine methylation regulates VC via many signaling pathways, including as NF-B, WNT, AKT/PI3K, TGF-/BMP/SMAD, and IL-6/STAT3. It might also regulate the VC-related calcification regulatory factors, oxidative stress, and endoplasmic reticulum stress. Consequently, we propose that arginine methylation regulates the calcification of the arteries and outline the regulatory mechanisms involved.
Subject(s)
Arginine , Vascular Calcification , Animals , Humans , Arginine/metabolism , Methylation , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/pathology , Oxidative Stress , Signal Transduction , Vascular Calcification/metabolism , Vascular Calcification/pathologyABSTRACT
BACKGROUND: The immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is crucial for preventing infections and relapse and enhancing graft-versus-tumor effects. B cells play an important role in humoral immunity and immune regulation, but their reconstitution after allo-HSCT has not been well studied. METHODS: In this study, we analyzed the dynamics of B cells in 252 patients who underwent allo-HSCT for 2 years and assessed the impact of factors on B-cell reconstitution and their correlations with survival outcomes, as well as the development stages of B cells in the bone marrow and the subsets in the peripheral blood. RESULTS: We found that the B-cell reconstitution in the bone marrow was consistent with the peripheral blood (p = 0.232). B-cell reconstitution was delayed by the male gender, age >50, older donor age, the occurrence of chronic and acute graft-versus-host disease, and the infections of fungi and cytomegalovirus. The survival analysis revealed that patients with lower B cells had higher risks of death and relapse. More importantly, we used propensity score matching to obtain the conclusion that post-1-year B-cell reconstitution is better in females. Meanwhile, using mediation analysis, we proposed the age-B cells-survival axis and found that B-cell reconstitution at month 12 posttransplant mediated the effect of age on patient survival (p = 0.013). We also found that younger patients showed more immature B cells in the bone marrow after transplantation (p = 0.037). CONCLUSION: Our findings provide valuable insights for optimizing the management of B-cell reconstitution and improving the efficacy and safety of allo-HSCT.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Female , Humans , Male , Transplantation, Homologous , Hematopoietic Stem Cell Transplantation/adverse effects , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control , Graft vs Host Disease/epidemiology , B-Lymphocytes , RecurrenceABSTRACT
Vascular calcification is a major risk factor for cardiovascular disease mortality, with a significant prevalence in chronic kidney disease (CKD). Pharmacological inhibition of histone acetyltransferase has been proven to protect against from vascular calcification. However, the role of Histone Deacetylase 2 (HDAC2) and molecular mechanisms in vascular calcification of CKD remains unknown. An in vivo model of CKD was established using mouse fed with a high adenine and phosphate diet, and an in vitro model was produced using human aortic vascular smooth muscle cells (VSMCs) stimulated with ß-glycerophosphate (ß-GP). HDAC2 expression was found to be reduced in medial artery of CKD mice and ß-GP-induced VSMCs. Overexpression of HDAC2 attenuated OPN and OCN upregulation, α-SMA and SM22α downregulation, and calcium deposition in aortas of CKD. The in vitro results also demonstrated that ß-GP-induced osteogenic differentiation was inhibited by HDAC2. Furthermore, we found that HDAC2 overexpression caused an increase in LC3II/I, a decrease in p62, and an induction of autophagic flux. Inhibition of autophagy using its specific inhibitor 3-MA blocked HDAC2's protective effect on osteogenic differentiation in ß-GP-treated VSMCs. Taken together, these results suggest that HDAC2 may protect against vascular calcification by the activation of autophagy, laying out a novel insight for the molecular mechanism in vascular calcification of CKD.
Subject(s)
Glycerophosphates , Renal Insufficiency, Chronic , Vascular Calcification , Humans , Animals , Mice , Histone Deacetylase 2/genetics , Osteogenesis , AutophagyABSTRACT
Deleted in breast cancer 1 (DBC1) is a human nuclear protein that modulates the activities of various proteins involved in cell survival and cancer progression. Oxidized form of nicotinamide adenine dinucleotide (NAD+) is suggested to bind to the Nudix homology domains (NHDs) of DBC1, thereby regulating DBC1-Poly (ADP-ribose) polymerase 1 (PARP1) interactions, resulting in the restoration of DNA repair. Using Nuclear Magnetic Resonance (NMR) and Isothermal Titration Calorimetry (ITC), we confirmed NAD+ and its precursor nicotinamide mononucleotide (NMN) both bind the NHD domain of DBC1 (DBC1354-396). NAD+ likely interacts with DBC1354-396 through hydrogen bonding, with a binding affinity (8.99 µM) nearly twice that of NMN (17.0 µM), and the key binding sites are primarily residues E363 and D372, in the agreement with Molecular Docking experiments. Molecular Dynamics (MD) simulation further demonstrated E363 and D372's anchoring role in the binding process. Additional mutagenesis experiments of E363 and D372 confirmed their critical involvement of ligand-protein interactions. These findings lead to a better understanding of how NAD+ and NMN regulate DBC1, thereby offering insights for the development of targeted therapies and drug research focused on DBC1-associated tumors.
Subject(s)
DNA Repair , NAD , Humans , NAD/metabolism , Molecular Docking Simulation , Cell Survival , Binding SitesABSTRACT
To address the lightweight and real-time issues of coal sorting detection, an intelligent detection method for coal and gangue, Our-v8, was proposed based on improved YOLOv8. Images of coal and gangue with different densities under two diverse lighting environments were collected. Then the Laplacian image enhancement algorithm was proposed to improve the training data quality, sharpening contours and boosting feature extraction; the CBAM attention mechanism was introduced to prioritize crucial features, enhancing more accurate feature extraction ability; and the EIOU loss function was added to refine box regression, further improving detection accuracy. The experimental results showed that Our-v8 for detecting coal and gangue in a halogen lamp lighting environment achieved excellent performance with a mean average precision (mAP) of 99.5%, was lightweight with FLOPs of 29.7, Param of 12.8, and a size of only 22.1 MB. Additionally, Our-v8 can provide accurate location information for coal and gangue, making it ideal for real-time coal sorting applications.
ABSTRACT
BACKGROUND: Medial vascular calcification is commonly identified in chronic kidney disease (CKD) patients and seriously affects the health and life quality of patients. This study aimed to investigate the effects of protein arginine methyltransferase 3 (PRMT3) on vascular calcification induced by CKD. METHODS: A mice model of CKD was established with a two-step diet containing high levels of calcium and phosphorus. Vascular smooth muscle cells (VSMCs) were subjected to ß-glycerophosphate (ß-GP) treatment to induce the osteogenic differentiation as an in vitro CKD model. RESULTS: PRMT3 was upregulated in VSMCs of medial artery of CKD mice and ß-GP-induced VSMCs. The inhibitor of PRMT3 (SGC707) alleviated the vascular calcification and inhibited the glycolysis of CKD mice. Knockdown of PRMT3 alleviated the ß-GP-induced osteogenic transfomation of VSMCs by the repression of glycolysis. Next, PRMT3 interacted with hypoxia-induced factor 1α (HIF-1α), and the knockdown of PRMT3 downregulated the protein expression of HIF-1α by weakening its methylation. Gain of HIF-1α reversed the PRMT3 depletion-induced suppression of osteogenic differentiation and glycolysis of VSMCs. CONCLUSION: The inhibitory role of PRMT3 depletion was at least mediated by the regulation of glycolysis upon repressing the methylation of HIF-1α.
Subject(s)
Glycerophosphates , Renal Insufficiency, Chronic , Vascular Calcification , Animals , Humans , Mice , Hypoxia , Osteogenesis/genetics , Protein-Arginine N-Methyltransferases/genetics , Renal Insufficiency, Chronic/genetics , Vascular Calcification/etiologyABSTRACT
To keep pace with the demands of semiconductor integration technology, a semiconductor device should offer a small footprint. Here, we demonstrate a compact electro-optic modulator by controlling the spatial distribution of carrier density in indium tin oxide (ITO). The proposed structure is mainly composed of a symmetrical metal electrode layer, calcium fluoride dielectric layer, and an ITO propagating layer. The carrier density on the surface of the ITO exhibits a periodical distribution when the voltage is applied on the electrode, which greatly enhances the interaction between the surface plasmon polaritons (SPPs) and the ITO. This structure can not only effectively improve the modulation depth of the modulator, but also can further reduce the device size. The numerical results indicate that when the length, width, and height of the device are 14 µm, 5 µm, and 8 µm, respectively, the modulation depth can reach 37.1 dB at a wavelength of 3.66 µm. The structure can realize a broadband modulation in theory only if we select a different period of the electrode corresponding to the propagating wavelength of SPPs because the modulator is based on the scattering effect principle. This structure could potentially have high applicability for optoelectronic integration, optical communications, and optical sensors in the future.
ABSTRACT
Background: Epilepsy monitoring requires simulating seizure-inducing conditions which frequently causes discomfort to epilepsy monitoring unit (EMU) patients. COVID-19 hospital restrictions added another layer of stress during hospital admissions. The purpose of this pilot study was to provide evidence that live virtual Clinically Designed Improvisatory Music (CDIM) brings relief to EMU patients for their psychological distress. Methods: Five persons with epilepsy (PWEs) in the EMU during the COVID-19 lockdown participated in the study (average age ± SD = 30.2 ± 6 years). Continuous electroencephalogram (EEG) and electrocardiogram (EKG) were obtained before, during, and after live virtual CDIM. CDIM consisted of 40 minutes of calming music played by a certified clinical music practitioner (CMP) on viola. Post-intervention surveys assessed patients' emotional state on a 1-10 Likert scale. Alpha/beta power spectral density ratio was calculated for each subject across the brain and was evaluated using one-way repeated analysis of variance, comparing 20 minutes before, during, and 20 minutes after CDIM. Post-hoc analysis was performed using paired t-test at the whole brain level and regions with peak changes. Results: Patients reported enhanced emotional state (9 ± 1.26), decrease in tension (9.6 ± 0.49), decreased restlessness (8.6 ± 0.80), increased pleasure (9.2 ± 0.98), and likelihood to recommend (10 ± 0) on a 10-point Likert scale. Based on one-way repeated analysis of variance, alpha/beta ratio increased at whole-brain analysis (F3,12 = 5.01, P = 0.018) with a peak in midline (F3,12 = 6.63, P = 0.0068 for Cz) and anterior medial frontal region (F3,12 = 6.45, P = 0.0076 for Fz) during CDIM and showed a trend to remain increased post-intervention. Conclusion: In this pilot study, we found positive effects of CDIM as reported by patients, and an increased alpha/beta ratio with meaningful electroencephalographic correlates due to the calming effects in response to CDIM. Our study provides proof of concept that live virtual CDIM offered demonstrable comfort with biologic correlations for patients admitted in the EMU during the COVID-19 pandemic.
ABSTRACT
SARS-CoV-2 is spread through exhaled breath of infected individuals. A fundamental question in understanding transmission of SARS-CoV-2 is how much virus an individual is exhaling into the environment while they breathe, over the course of their infection. Research on viral load dynamics during COVID-19 infection has focused on internal swab specimens, which provide a measure of viral loads inside the respiratory tract, but not on breath. Therefore, the dynamics of viral shedding on exhaled breath over the course of infection are poorly understood. Here, we collected exhaled breath specimens from COVID-19 patients and used RTq-PCR to show that numbers of exhaled SARS-CoV-2 RNA copies during COVID-19 infection do not decrease significantly until day 8 from symptom-onset. COVID-19-positive participants exhaled an average of 80 SARS-CoV-2 viral RNA copies per minute during the first 8 days of infection, with significant variability both between and within individuals, including spikes over 800 copies a minute in some patients. After day 8, there was a steep drop to levels nearing the limit of detection, persisting for up to 20 days. We further found that levels of exhaled viral RNA increased with self-rated symptom-severity, though individual variation was high. Levels of exhaled viral RNA did not differ across age, sex, time of day, vaccination status or viral variant. Our data provide a fine-grained, direct measure of the number of SARS-CoV-2 viral copies exhaled per minute during natural breathing-including 312 breath specimens collected multiple times daily over the course of infection-in order to fill an important gap in our understanding of the time course of exhaled viral loads in COVID-19.
ABSTRACT
Chimeric antigen receptor (CAR)-modified natural killer (NK) cells are recognized as promising immunotherapeutic agents for cancer treatment. However, the efficacy and trafficking of CAR-NK cells in solid tumors are hindered by the complex barriers present in the tumor microenvironment (TME). We have developed a novel strategy that utilizes living CAR-NK cells as carriers to deliver anticancer drugs specifically to the tumor site. We also introduce a time-lapse method for evaluating the efficacy and tumor specificity of CAR-NK cells using a two-photon microscope in live mouse models and three-dimensional (3D) tissue slide cultures. Our results demonstrate that CAR-NK cells exhibit enhanced antitumor immunity when combined with photosensitive chemicals in both in vitro and in vivo tumor models. Additionally, we have successfully visualized the trafficking, infiltration, and accumulation of drug-loaded CAR-NK cells in deeply situated TME using non-invasive intravital two-photon microscopy. Our findings highlight that tumor infiltration of CAR-NK cells can be intravitally monitored through the two-photon microscope approach. In conclusion, our study demonstrates the successful integration of CAR-NK cells as drug carriers and paves the way for combined cellular and small-molecule therapies in cancer treatment. Furthermore, our 3D platform offers a valuable tool for assessing the behavior of CAR cells within solid tumors, facilitating the development and optimization of immunotherapeutic strategies with clinical imaging approaches.
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In lithium-ion batteries (LIBs), the stabilized capacities of transition metal compound anodes usually exhibit higher values than their theoretical values due to the interfacial charge storage, the formation of reversible electrolyte-derived surface layer, or interfacial magnetization. But the effectively utilizing the mechanisms to achieve novel anodes is rarely explored. Herein, a novel nanosized cobalt ditelluride (CoTe2 ) anodes with ultra-high capacity and long term stability is reported. Electrochemical tests show that the lithium storage capacity of the best sample reaches 1194.7 mA h g-1 after 150 cycles at 0.12 A g-1 , which increases by 57.8% compared to that after 20 cycles. In addition, the sample offers capacities of 546.6 and 492.1 mA h g-1 at 0.6 and 1.8 A g-1 , respectively. During cycles, CoTe2 particles (average size 20 nm) are gradually pulverized into the smaller nanoparticles (<3 nm), making the magnetization more fully due to the larger contact area of Co/Li2 Te interface, yielding an increased capacity. The negative capacity fading is observed, and verified by ex situ structural characterizations and in situ electrochemical measurements. The proposed strategy can be further extended to obtain other high-performance ferromagnetic metal based electrodes for energy storage applications.