CAR-redirected natural killer T cells demonstrate superior antitumor activity to CAR-T cells through multimodal CD1d-dependent mechanisms.

Human natural killer T (NKT) cells have been proposed as a promising cell platform for chimeric antigen receptor (CAR) therapy in solid tumors. Here we generated murine CAR-NKT cells and compared them with CAR-T cells in immune-competent mice. Both CAR-NKT cells and CAR-T cells showed similar antitumor effects in vitro, but CAR-NKT cells showed superior antitumor activity in vivo via CD1d-dependent immune responses in the tumor microenvironment. Specifically, we show that CAR-NKT cells eliminate CD1d-expressing M2-like macrophages. In addition, CAR-NKT cells promote epitope spreading and activation of endogenous T cell responses against tumor-associated neoantigens. Finally, we observed that CAR-NKT cells can co-express PD1 and TIM3 and show an exhaustion phenotype in a model of high tumor burden. PD1 blockade as well as vaccination augmented the antitumor activity of CAR-NKT cells. In summary, our results demonstrate the multimodal function of CAR-NKT cells in solid tumors, further supporting the rationale for developing CAR-NKT therapies in the clinic.

Truncated M13 phage for smart detection of E. coli under dark field.

BACKGROUND: The urgent need for affordable and rapid detection methodologies for foodborne pathogens, particularly Escherichia coli (E. coli), highlights the importance of developing efficient and widely accessible diagnostic systems. Dark field microscopy, although effective, requires specific isolation of the target bacteria which can be hindered by the high cost of producing specialized antibodies. Alternatively, M13 bacteriophage, which naturally targets E. coli, offers a cost-efficient option with well-established techniques for its display and modification. Nevertheless, its filamentous structure with a large length-diameter ratio contributes to nonspecific binding and low separation efficiency, posing significant challenges. Consequently, refining M13 phage methodologies and their integration with advanced microscopy techniques stands as a critical pathway to improve detection specificity and efficiency in food safety diagnostics. METHODS: We employed a dual-plasmid strategy to generate a truncated M13 phage (tM13). This engineered tM13 incorporates two key genetic modifications: a partial mutation at the N-terminus of pIII and biotinylation at the hydrophobic end of pVIII. These alterations enable efficient attachment of tM13 to diverse E. coli strains, facilitating rapid magnetic separation. For detection, we additionally implemented a convolutional neural network (CNN)-based algorithm for precise identification and quantification of bacterial cells using dark field microscopy. RESULTS: The results obtained from spike-in and clinical sample analyses demonstrated the accuracy, high sensitivity (with a detection limit of 10 CFU/µL), and time-saving nature (30 min) of our tM13-based immunomagnetic enrichment approach combined with AI-enabled analytics, thereby supporting its potential to facilitate the identification of diverse E. coli strains in complex samples. CONCLUSION: The study established a rapid and accurate detection strategy for E. coli utilizing truncated M13 phages as capture probes, along with a dark field microscopy detection platform that integrates an image processing model and convolutional neural network.

Nanoengineered Neutrophil as 19F-MRI Tracer for Alert Diagnosis and Severity A of Acute Lung Injury.

Acute lung injury (ALI) is a severe complication in clinical settings. Alert diagnosis and severity assessment of ALI is pivotal to ensure curative treatment and increase survival rates. However, the development of a precise ALI diagnostic strategy remains a pending task. Here, leveraging neutrophil's inflammation-homing and physiological barrier-navigating capability, a facile strategy is proposed for achieving targeted 19F-MRI detection of ALI based on the nanoengineered neutrophil internalized with perfluorocarbon nanoemulsion (Neu@PFC). The remodeling process poses a negligible impact on the neutrophil's inherent activation and transmigration functions. The migratory behavior of Neu@PFC toward pneumonia is confirmed in vivo using an LPS-induced ALI murine model. Direct intratracheal (i.t.) administration contributes to a vast deposition of Neu@PFC within the lung, allowing for real-time 19F-MRI visualization and the potential to predict progressive pneumonia. Furthermore, intravenous (i.v.) administration of Neu@PFC enables quantitative assessment of the extent of ALI due to the chemokine-guided neutrophil migration. This study not only provides a pathway to diagnose ALI, but also sheds light on the neutrophil recruitment and activation cues in different tissues and inflammatory conditions, which is a prerequisite for developing potential therapeutic approaches.

Progression of disease within 24 months (POD24) in multiple myeloma implicates poor prognosis and limitations of current prediction models for POD24.

Multiple myeloma (MM) is a common hematological malignancy, and its prognostic factors have been extensively studied. Progression of disease within 24 months (POD24) suggests a poor prognosis in many malignancies, but is rarely mentioned in MM. This study aimed to investigate the prognostic value of POD24 in MM and risk factors of POD24, and to evaluate the predictive value of existing MM prognostic models for POD24. The research retrospectively analyzed the clinical data of MM patients and found that the occurrence of POD24 is an independent prognostic factor affecting overall survival in MM, while non-transplantion and genetic abnormality are independent risk factors for the occurrence of POD24. The existing prognostic models are not effective in predicting POD24. Therefore, it's still necessary to explore a prognostic model that can predict POD24 more accurately.

SARS-CoV-2 spike protein induces the cytokine release syndrome by stimulating T cells to produce more IL-2.

Introduction: Cytokine release syndrome (CRS) is one of the leading causes of mortality in patients with COVID-19 caused by the SARS-CoV-2 coronavirus. However, the mechanism of CRS induced by SARS-CoV-2 is vague. Methods: Using spike protein combined with IL-2, IFN-γ, and TNF-α to stimulate human peripheral blood mononuclear cells (PBMCs) to secrete CRS-related cytokines, the content of cytokines in the supernatant was detected, and the effects of NK, T, and monocytes were analyzed. Results: This study shows that dendritic cells loaded with spike protein of SARS-CoV-2 stimulate T cells to release much more interleukin-2 (IL-2,) which subsequently cooperates with spike protein to facilitate PBMCs to release IL-1ß, IL-6, and IL-8. These effects are achieved via IL-2 stimulation of NK cells to release tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), as well as T cells to release IFN-γ Mechanistically, IFN-γ and TNF-α enhance the transcription of CD40, and the interaction of CD40 and its ligand stabilizes the membrane expression of toll-like receptor 4 (TLR4) that serves as a receptor of spike protein on the surface of monocytes. As a result, there is a constant interaction between spike protein and TLR4, leading to continuous activation of nuclear factor-κ-gene binding (NF-κB). Furthermore, TNF-α also activates NF-κB signaling in monocytes, which further cooperates with IFN-γ and spike protein to modulate NF-κB-dependent transcription of CRS-related inflammatory cytokines. Discussion: Targeting TNF-α/IFN-γ in combination with TLR4 may represent a promising therapeutic approach for alleviating CRS in individuals with COVID-19.

Oral antioxidant edaravone protects against cognitive deficits induced by chronic hypobaric hypoxia at high altitudes.

Chronic hypobaric hypoxia at high altitudes can impair cognitive functions, especially causing deficits in learning and memory, which require therapeutic intervention. Here, we showed that mice subjected to hypobaric hypoxia (simulating an altitude of 5000 m) for one month experienced significant cognitive impairment, accompanied by increased biomarker levels of oxidative stress in the brain and blood. Oral administration of a novel formulation of edaravone, a free radical scavenger approved for the treatment of ischaemic stroke and amyotrophic lateral sclerosis, significantly alleviated oxidative stress and cognitive impairments caused by chronic hypobaric hypoxia. Furthermore, oral edaravone treatment also mitigated neuroinflammation and restored hippocampal neural stem cell exhaustion. Additionally, periostin (Postn) is vital in the cognitive deficits caused by chronic hypobaric hypoxia and may be a molecular target of edaravone. In conclusion, our results suggest that oxidative stress plays a crucial role in the cognitive deficits caused by chronic hypobaric hypoxia and that oral edaravone is a potential medicine for protecting against cognitive deficits caused by chronic hypobaric hypoxia in high-altitude areas.

The negative effects of extracellular vesicles in the immune system.

Immunity is a critical self-defense mechanism of the human body, wherein immune cells and immune molecules play a crucial role. Extracellular vesicles (EVs), derived from immune cells or other cells, play a significant role in tumors, autoimmune diseases and other immune-related disorders by serving as carriers and facilitating intercellular communication through the transfer of cargoes. Numerous studies have revealed that EVs can exacerbate disease development by modulating immune responses. Therefore, this paper focuses on the effects of EVs on the number, activity and function of different types of immune cells and the release of immune molecules (such as cytokines, antigens, antibodies, etc) in various diseases, as well as the roles of EVs associated with different types of immune cells in various diseases. We aim to provide a comprehensive review of the negative effects that EVs play in the immune system to provide more ideas and strategies for the management of clinical immune diseases.

Single-Crystalline 3D Covalent Organic Frameworks with Exceptionally High Specific Surface Areas and Gas Storage Capacities.

Single-crystalline covalent organic frameworks (COFs) are highly desirable toward understanding their pore chemistry and functions. Herein, two 50-100 µm single-crystalline three-dimensional (3D) COFs, TAM-TFPB-COF and TAPB-TFS-COF, were prepared from the condensation of 4,4',4″,4‴-methanetetrayltetraaniline (TAM) with 3,3',5,5'-tetrakis(4-formylphenyl)bimesityl (TFPB) and 3,3',5,5'-tetrakis(4-aminophenyl)bimesityl (TAPB) with 4,4',4″,4‴-silanetetrayltetrabenzaldehyde (TFS), respectively, in 1,4-dioxane under the catalysis of acetic acid. Single-crystal 3D electron diffraction reveals the triply interpenetrated dia-b networks of TAM-TFPB-COF with atom resolution, while the isostructure of TAPB-TFS-COF was disclosed by synchrotron single-crystal X-ray diffraction and synchrotron powder X-ray diffraction with Le Bail refinements. The nitrogen sorption measurements at 77 K disclose the microporosity nature of both activated COFs with their exceptionally high Brunauer-Emmett-Teller surface areas of 3533 and 4107 m2 g-1, representing the thus far record high specific surface area among imine-bonded COFs. This enables the activated COFs to exhibit also the record high methane uptake capacities up to 28.9 wt % (570 cm3 g-1) at 25 °C and 200 bar among all COFs reported thus far. This work not only presents the structures of two single-crystalline COFs with exceptional microporosity but also provides an example of atom engineering to adjust permanent microporous structures for methane storage.

Puerarin: a hepatoprotective drug from bench to bedside.

Pueraria is a time-honored food and medicinal plant, which is widely used in China. Puerarin, the main component extracted from pueraria, has a variety of pharmacological characteristics. In recent years, puerarin has received increasing attention for its significant hepatoprotective effects, such as metabolic dysfunction-associated steatotic liver disease, alcohol-related liver disease, and hepatic carcinoma. This paper explores the pharmacological effects of puerarin on various liver diseases through multiple mechanisms, including inflammation factors, oxidative stress, lipid metabolism, apoptosis, and autophagy. Due to its restricted solubility, pharmacokinetic studies revealed that puerarin has a low bioavailability. However, combining puerarin with novel drug delivery systems can improve its bioavailability. Meanwhile, puerarin has very low toxicity and high safety, providing a solid foundation for its further. In addition, this paper discusses puerarin's clinical trials, highlighting its unique advantages. Given its excellent pharmacological effects, puerarin is expected to be a potential drug for the treatment of various liver diseases.

The value of electroencephalography features in the prognostic evaluation of large hemispheric infarction patients at different time intervals.

BACKGROUND: Large Hemispheric Infarction (LHI) is a devastating disease with high mortality. This study aimed to use electroencephalography (EEG) to evaluate the death risk of LHI patients and identify suitable evaluation time. METHODS: This study retrospectively collected clinical and EEG data from 73 LHI patients, dividing them into death and survival group at discharge. EEG data was classified as 1-5 days and 6-14 days after onset according to the time intervals of cerebral edema. Regression and receiver operator characteristic curve (ROC) analysis were applied to explore the impact of temporal changes in various EEG and clinical features on death. RESULTS: The areas under ROC curve (AUC) of death prediction for non-α frequency on non-infarct side at 6-14 days after onset was significantly higher than that at 1-5 days (p = 0.004). And there was no significant difference between the AUC of seizure activity for death prediction at 1-5 days and 6-14 days (p = 0.418). Multivariate regression analysis revealed that non-α frequency on non-infarct side and seizure activity at 6-14 days after onset were the independent risk factors for the death of LHI patients. Additionally, above two EEG features significantly improved the death predictive efficacy of clinical features in LHI patients with the integrated discrimination improvement index (IDI) of 0.174 (p = 0.015) and the net reclassification improvement (NRI) of 1.314 (p<0.001). CONCLUSIONS: Non-α frequency on non-infarct side and seizure activity were reliable indicators for death prediction. 6-14 days after onset was the better time window for death evaluation of LHI patients through EEG.

Association between Omega-3 fatty acids and autoimmune disease: Evidence from the umbrella review and Mendelian randomization analysis.

BACKGROUND: Autoimmune diseases are a group of disorders characterized by abnormal immune responses that mistakenly target and attack healthy cells, tissues, and organs, resulting in inflammation and tissue damage. Omega-3 fatty acids possess anti-inflammatory activities and may decrease abnormal immune activity. However, the role of omega-3 fatty acids in various autoimmune diseases is still unclear. This umbrella review and Mendelian randomization (MR) study aims to summarize the highest available evidence on omega-3 fatty acids and autoimmune disease. METHODS: We conducted an umbrella review by searching electronic databases to identify systematic reviews and meta-analyses. The selection criteria included systematic reviews with or without meta-analysis, which evaluated omega-3 fatty acids as the exposure and autoimmune disease as the outcome variable. Two authors independently assessed the overlapping and quality of the reviews using the AMSTAR-2 tool. We also performed MR studies to investigate the potential causal effect of fatty acids on the risk of various autoimmune diseases, utilizing data from the meta-analysis of the UKB-TOPMed and FinnGen cohorts. RESULT: The umbrella review identified 21 studies (8 systematic reviews and 13 meta-analyses) on 9 autoimmune diseases and 30 diseases in the MR study. AMSTAR 2 categorized the quality of evidence in six studies as critically low, six studies as low, eight studies as moderate, and one as high-quality evidence. The consistent result between the review and the MR study demonstrated the benefit of omega-3 fatty acids on rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Additionally, in our summary review, omega-3 fatty acids can improve disease activity and inflammation biomarkers; however, MR studies provided no consistent evidence for the causal effects of omega-3 fatty acids on psoriasis, multiple sclerosis (MS), type 1 diabetes (T1D), IgA nephropathy (IgAN), juvenile idiopathic arthritis (JIA), Crohn's disease (CD), and ulcerative colitis (UC). CONCLUSION: The current study presented solid evidence highlighting the advantageous impact of omega-3 fatty acids on SLE and RA. This was achieved through the reduction of disease risk, the decrease of disease activity, and the mitigation of inflammatory biomarkers. To stratify another autoimmune illness, it is necessary to carry out rigorous evaluations to surpass the existing findings and enhance understanding in this domain.

Thyroid autoantibodies at baseline predict longer survival in non-small cell lung cancer patients treated with anti-programmed cell death-1 blockade: a prospective study.

The presence of anti-thyroid antibodies (ATAs) is a biomarker for the development of thyroid dysfunction induced by anti-programmed cell death-1 antibodies (PD-1-Abs). While patients with thyroid dysfunction reportedly showed better overall survival (OS), it remains unknown if ATAs at baseline can predict OS. Therefore, in this study, we examined the association of ATAs at baseline with OS in non-small cell lung cancer (NSCLC) patients with different levels of programmed cell death-1 ligand 1 (PD-L1) positivity associated with PD-1-Ab treatment efficacy. A total of 81 NSCLC patients treated with PD-1-Abs were evaluated for ATAs at baseline and prospectively for OS. Among the 81 patients, 49 and 32 patients had ≥50% (group A) and <50% (group B) PD-L1 positivity, respectively. Median OS did not differ significantly between patients with (n = 13) and without (n = 36) ATAs at baseline in group A. In contrast, median OS was significantly longer in patients with (n = 10) versus without (n = 22) ATAs at baseline in group B (not reached vs 378 days, respectively; 95% CI, 182 to 574 days, p = 0.049). These findings suggest that the presence of ATAs at baseline is a biomarker to predict better treatment efficacy of PD-1-Abs in NSCLC patients with low PD-L1 positivity, while the difference in OS in those with high PD-L1 positivity may be masked by increased tumor expression of PD-L1.

Non-Cascaded and Crosstalk-Free Multi-Image Encryption Based on Optical Scanning Holography Using 2D Orthogonal Compressive Sensing.

We propose a non-cascaded and crosstalk-free multi-image encryption method based on optical scanning holography and 2D orthogonal compressive sensing. This approach enables the simultaneous recording and encryption of multiple plaintext images without mechanical scanning, while allows for independent retrieval of each image with exceptional quality and no crosstalk. Two features would bring about more substantial security and privacy. The one is that, by employing a sequence of pre-designed structural patterns as encryption keys at the pupil, multiple samplings can be achieved and ultimately the holographic cyphertext can be obtained. These patterns are generated using a measurement matrix processed with the generalized orthogonal one. As a result, one can accomplish the differentiation of images prior to the recording and thus neither need to pretreat the pending images nor to suppress the out-of-focus noise in the decrypted image. The other one is that, the non-cascaded architecture ensures that different plaintexts do not share sub-keys. Meanwhile, compared to 1D orthogonal compressive sensing, the 2D counterpart makes the proposed method to synchronously deal with multiple images of more complexity, while acquire significantly high-quality decrypted images and far greater encryption capacity. Further, the regularities of conversion between 1D and 2D orthogonal compressive sensing are identified, which may be instructive when to manufacture a practical multi-image cryptosystem or a single-pixel imaging equipment. A more general method or concept named synthesis pupil encoding is advanced. It may provide an effective way to combine multiple encryption methods together into a non-cascaded one. Our method possesses nonlinearity and it is also promising in multi-image asymmetric or public key cryptosystem as well as multi-user multiplexing.

Addition of three new species of Xylariomycetidae fungi on bamboo from Southern China.

In our ongoing research on bambusicolous Xylariomycetidae fungi, three new microfungi taxa were collected and identified as members of the genera Amphibambusa, Arecophila, and Nigropunctata. Amphibambusaaureae sp. nov., Arecophilagaofengensis sp. nov., and Nigropunctataxiaohensis sp. nov. are introduced based on morphological comparisons and phylogenetic analyses using combined ITS, LSU, tub2, and tef1α loci. Comprehensive morphological descriptions, illustrations, and a phylogenetic tree showcasing the placement of these new taxa are provided. Additionally, keys to Amphibambusa and Nigropunctata are provided.

Phylogenomic analyses of the pantropical Platycerium Desv. (Platycerioideae) reveal their complex evolution and historical biogeography.

Platycerium is a genus of pantropical epiphytic ferns consisting of ca. 18 species and are highly sought after by horticultural enthusiasts. Although the monophyly of this genus has been well supported in previous molecular studies, as an intercontinentally disjunct genus, the origin and distribution pattern of Platycerium were elusive and controversial. This is mainly due to limited taxon sampling, a plastid representing only a single coalescent history, the lack of fossil evidence, and so on. Here, by utilizing genome-skimming sequencing, transcriptome sequencing, and flow cytometry, we integrated chloroplast genomes, data of single-copy nuclear genes, ploidy levels, morphology, and geographic distribution to understand the species phylogeny and the evolutionary and biogeographic history of Platycerium. Our major results include: (1) based on both plastid and nuclear datasets, Platycerium is consistently resolved into three fully supported clades: the Afro-American (AA) clade, the Javan-Australian (JA) clade, and the Malayan-Asian (MA) clade. The AA clade and MA clade are further divided into three and two subclades, respectively; (2) a large amount of gene tree conflict, as well as cytonuclear discordance, was found and can be explained by hybridization and incomplete lineage sorting, and most of the hybridization hypotheses represented ancient hybridization events; (3) through molecular dating, the crown age of Platycerium is determined to be at approximately 32.79 Ma based on the plastid dataset or 29.08 Ma based on the nuclear dataset in the Middle Oligocene; (4) ancestral area reconstruction analysis from different datasets showed that Platycerium most likely originated from Indochina; (5) current distribution patterns are resultant from long-distance dispersals, ancient orogeny, and an ancient climate event; and (6) species diversification was driven by polyploidization, dispersal, and hybridization. This study presented here will help understand the evolution of tropical plant flora and provide a reference for the cultivation and breeding of staghorn ferns.

Sirtuin 7 ameliorates cuproptosis, myocardial remodeling and heart dysfunction in hypertension through the modulation of YAP/ATP7A signaling.

Myocardial fibrosis is a typical pathological manifestation of hypertension. However, the exact role of sirtuin 7 (SIRT7) in myocardial remodeling remains largely unclear. Here, spontaneously hypertensive rats (SHRs) and angiotensin (Ang) II-induced hypertensive mice were pretreated with recombinant adeno-associated virus (rAAV)-SIRT7, copper chelator tetrathiomolybdate (TTM) or copper ionophore elesclomol, respectively. Compared with normotensive controls, reduced SIRT7 expression and augmented cuproptosis were observed in hearts of hypertensive rats and mice with decreased FDX1 levels and increased HSP70 levels. Notably, intervention with rAAV-SIRT7 and TTM strikingly prevented DLAT oligomers aggregation, and elevated ATP7A and TOM20 expressions, contributing to the alleviation of cuproptosis, mitochondrial injury, myocardial remodeling and heart dysfunction in spontaneously hypertensive rats and Ang II-induced hypertensive mice. In cultured rat primary cardiac fibroblasts (CFs), rhSIRT7 alleviated CuCl2, Ang II or elesclomol-induced cuproptosis and fibroblast activation by blunting DLAT oligomers accumulation and downregulating α-SMA expression. Additionally, conditioned medium from rhSIRT7-pretreated CFs remarkably mitigated cellular hypertrophy and mitochondrial impairments of neonatal rat cardiomyocytes, as well as cell migration and polarization of RAW 264.7 macrophages. Importantly, verteporfin reduced CuCl2-induced cuproptosis, mitochondrial injury and fibrotic activation in CFs. Knockdown of ATP7A with si-ATP7A blocked cellular protective effects of rhSIRT7 and verteporfin in CFs. In conclusion, SIRT7 attenuates cuproptosis, myocardial fibrosis and heart dysfunction in hypertension through the modulation of YAP/ATP7A signaling. Targeting SIRT7 is of vital importance for developing therapeutic strategies in hypertension and hypertensive heart disorders.

Rapid evolution of mitochondrion-related genes in haplodiploid arthropods.

BACKGROUND: Mitochondrial genes and nuclear genes cooperate closely to maintain the functions of mitochondria, especially in the oxidative phosphorylation (OXPHOS) pathway. However, mitochondrial genes among arthropod lineages have dramatic evolutionary rate differences. Haplodiploid arthropods often show fast-evolving mitochondrial genes. One hypothesis predicts that the small effective population size of haplodiploid species could enhance the effect of genetic drift leading to higher substitution rates in mitochondrial and nuclear genes. Alternatively, positive selection or compensatory changes in nuclear OXPHOS genes could lead to the fast-evolving mitochondrial genes. However, due to the limited number of arthropod genomes, the rates of evolution for nuclear genes in haplodiploid species, besides hymenopterans, are largely unknown. To test these hypotheses, we used data from 76 arthropod genomes, including 5 independently evolved haplodiploid lineages, to estimate the evolutionary rates and patterns of gene family turnover of mitochondrial and nuclear genes. RESULTS: We show that five haplodiploid lineages tested here have fast-evolving mitochondrial genes and fast-evolving nuclear genes related to mitochondrial functions, while nuclear genes not related to mitochondrion showed no significant evolutionary rate differences. Among hymenopterans, bees and ants show faster rates of molecular evolution in mitochondrial genes and mitochondrion-related nuclear genes than sawflies and wasps. With genome data, we also find gene family expansions and contractions in mitochondrion-related genes of bees and ants. CONCLUSIONS: Our results reject the small population size hypothesis in haplodiploid species. A combination of positive selection and compensatory changes could lead to the observed patterns in haplodiploid species. The elevated evolutionary rates in OXPHOS complex 2 genes of bees and ants suggest a unique evolutionary history of social hymenopterans.

A strategy of Q-markers identification based on effect, property flavour material basis and rapid quantitative evaluation via near-infrared spectroscopy and chemometric methods for the quality control of Flos Trollii (FT).

ETHNOPHARMACOLOGICAL RELEVANCE: Flos Trollii (FT) is the dried flower of Trollius Chinensis Bunge of Ranunculaceae with the pharmacological properties of anti-inflammatory, antibacterial, antiviral, anti-oxidative. The herb FT is not only a traditional Chinese medicine (TCM) but also an extensively utilized ethnic medicine, employed by diverse ethnic groups including Mongolian, Tibetan, and Kazakh. AIM OF STUDY: FT was taken as an example to construct a strategy of quality markers (Q-markers) identification based on effect, property flavor material basis, and rapid quantitative evaluation using near-infrared (NIR) spectroscopy and chemometric methods of TCM. MATERIALS AND METHODS: Initially, the anti-inflammatory efficacy of FT from three places of origin was evaluated using the RAW264.7-cell inflammatory model, and the bitter property flavor was characterized using an electronic tongue. The high-performance liquid chromatography(HPLC) fingerprint of FT was generated, and the quality of FT from different origins was evaluated employing chemometrics. Next, potential anti-inflammatory and bitter property flavor compounds were screened utilizing a fingerprinting-effect relationship and fingerprinting-property flavor relationship model using partial least squares regression (PLSR). The Q-markers of the FT were confirmed based on the testability principle. Then, a swift, uncomplicated, and precise Q-marker content of the FT prediction model was developed by adopting NIR. RESULTS: The main common fingerprinting peaks affecting FT's efficacy and property flavor were screened. Five of these compounds, 2″-O-beta-L-galactopyranosylorientin, orientin, vitexin, veratric acid, and isoquercitrin, characterized using HPLC and ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS), could be regarded as Q-markers of FT. Q-marker content of the FT prediction model developed adopting NIR spectroscopy was rapid and effective. CONCLUSION: According to the strategy proposed in this study, a quantitative NIR spectroscopic method to identify Q-markers could be a tool to improve the QC efficiency of TCM.

68Ga-grazytracer PET for noninvasive assessment of response to immunotherapy in solid tumors and lymphomas: a phase 1/2 clinical trial.

To tackle the clinical challenge of noninvasively assessing immunotherapy efficacy in patients, here we used positron emission tomography (PET) with 68Ga-grazytracer, which targets granzyme B, a crucial effector molecule secreted by activated CD8+ T cells. In this phase 1/2 clinical trial (NCT05000372) involving a diverse cohort of 24 patients with solid tumors and lymphomas who received immunotherapies, including immune checkpoint inhibitors (either alone or with chemotherapies) and chimeric antigen receptor-T cell therapy, we examined the in vivo behaviors of 68Ga-grazytracer. Primary endpoints were safety, biodistribution, granzyme B specificity, and the predictive utility of 68Ga-grazytracer, while secondary endpoint was the relationship between 68Ga-grazytracer uptake and tumor immune phenotype. 68Ga-grazytracer exhibited a safe profile and specifically targeted granzyme B in patients. 68Ga-grazytracer PET showed superior predictive value for short-term prognosis and progression-free survival than those of conventional assessment criteria, including RECIST 1.1 and PERCIST. Moreover, the uptake of 68Ga-grazytracer in tumors was significantly higher in those with a "non-desert" immune phenotype than those with an immune "desert" phenotype, thereby meeting the primary and secondary endpoints of this trial. Collectively, we successfully visualized CD8+ T cell effector function in humans using 68Ga-grazytracer PET, offering insights for enhancing immunotherapy assessment, patient stratification and treatment planning.

Trace rare earth elements analysis in atmospheric particulates and cigar smoke by ICP-MS after pretreatment with magnetic polymers.

BACKGROUND: Some heavy metals could be ingested into human body through breathing besides diet and drinking. Atmospheric particulates and smoke are main sources of this kind for the metals' exposure to human. Compared with environmental water, the methodologies for trace metals in particulates and smoke samples with more complex matrix are much less. Magnetic functional sorbents can be designed to remove complex matrix and enrich target analytes. The combination of magnetic solid phase extraction (MSPE) with highly sensitive inductively coupled plasma mass spectrometry (ICP-MS) detection is a good alternative for the analytical purpose. (92). RESULTS: Magnetic polymers were synthesized through free radical polymerization with Fe3O4 nanoparticles as the core and 2-methyl-2-hydroxyethyl 2-acrylate-2-hydroxyethyl ester phosphate as external modifier. The sorbent showed a high phosphorus content (2.7 wt%) and good selectivity to target REEs, along with good reusability (at least 45 times) and chemical stability. With the consumption of 150 mL aqueous solution, an enrichment factor of 300 was obtained by the proposed method, leading to low detection limits (0.001-0.2 ng L-1) for 15 REEs. The application potential of the method was further evaluated by analyzing local atmospheric particulate and cigar smoke samples. Recovery of 86.3-107 % in digested total suspended particulate (TSP) was obtained for 15 REEs, demonstrating a good anti-interference ability of the method. Target REEs in TSP, PM2.5 and PM10 samples were found to be 0.01-2.81, 0.006-1.09 and 0.009-2.46 ng m-3, respectively, and none of them were detected in the collected cigar smoke. (148) SIGNIFICANCE: The method of MSPE-ICP-MS was demonstrated with good potential for trace analysis in complex sample matrix, probably due to the good selectivity of the functionalized polymers. With the design and fabrication of specific functionalized magnetic sorbents, other heavy metals can be monitored in those samples which would be intake by human breathing. It provided an efficient strategy for the evaluation of metals' health risk in particulates and smoke samples. (69).