γδT Cells Induce the Inflammatory Response of Human Fibroblast-Like Synoviocytes Directly or by Stimulating B Cells to Activate IL-17/STAT3 Signaling Pathway.

INTRODUCTION: Rheumatoid arthritis (RA) combined with hashimoto thyroiditis (HT) is an important cause of various fatal comorbidities of RA. There is no precise conclusion about the cause of this disease. METHODS: Peripheral blood and synovial tissue were collected from healthy participants, patients with RA, and patients with both RA and HT. Immunofluorescence staining and Pearson correlation analysis were used to detect the levels of γδTCR and the correlation between IL-17 and p-STAT3, respectively. ELISA, chemiluminescence assays, qRT-PCR and Western blot were performed to detect the levels of IgG, IgM, IFN-γ, IL-1ß, TNF-α, Tg-Ab, Tpo-Ab, IL-17, IL-2, p-SATA3, and STAT3, respectively. RESULTS: There was increased proportion of γδT cells, IL-17, and p-STAT3 levels in RA and HT patients. IL-17 was positively correlated with p-STAT3. γδT cells significantly promoted the expression of IgG, Tg-Ab, Tpo-Ab, and IL-17. When γδT and human fibroblast-like synoviocytes (FLSs) were co-cultured, the levels of IL-2, IFN-γ, IL-1ß, TNF-α, and IL-17 were increased, and the IL-17/STAT3 signaling pathway was activated. When IL-17-silenced γδT cells and STAT3-silenced FLSs were co-cultured, the levels of IL-1ß and TNF-α in FLSs were significantly decreased. Furthermore, when STAT3-silenced FLSs were added to the co-culture medium of B cells and γδT cells, the levels of IL-1ß and TNF-α were also decreased significantly. CONCLUSION: γδT cells induced RA directly or by stimulating B cells to activate STAT3 through IL-17.

Development of fermented Atemoya (Annona cherimola × Annona squamosa)-Amazake increased intestinal next-generation probiotics.

Akkermansia muciniphila and Faecalibacterium prausnitzii are next-generation probiotics, which has been reported to protect disease and effectively utilize various carbohydrates (starch and pectin) as nutrients for growth. Atemoya exhibiting fruity flavor, which is suitable for enhancing aroma and attenuating unpleasant taste caused by the koji metabolites. Results indicated that malic acid was increased (from 42.4 to 70.1 mg/100 g) in fermented Atemoya-Amazake. In addition, fermented Atemoya-Amazake elevated growthes in A. muciniphila and F. prausnitzii. Similarly, the populations of Parabacteroides (5.7 fold) and Akkermansia (1.66 fold) were elevated by fermented Atemoya-Amazake treatment in an in vitro simulated gastrointestinal system compared to the control group. Results revealed that fermented Atemoya-Amazake modulated the intestinal microbiota through increasing the production of short-chain fatty acids (exhibiting anti-pathogenic activity) for 2.1, 2.5, 2.6, and 2.1 folds in acetic acid, propionic acid, isobutyric acid, and butyric acid, respectively; suggesting this fermented Atemoya-Amazake could be applied in intestinal protection.

Association between thyroid function and nonalcoholic fatty liver disease: a dose-response meta-analysis.

Background: Thyroid hormones (THs) have been found that it is closely associated with the onset and progression of non-alcoholic fatty liver disease (NAFLD). However, the current study could not verify the intrinsic relationship between thyroid hormones and NAFLD, which requires further research. Methods: The searches of studies reported both TH level in serum and NAFLD were performed in PubMed, Web of Science, Cochrane Library, and Embase databases. We combined an overall meta-analysis with a dose-response meta-analysis to assess the correlation and dose-response relationship between thyroid function levels and the risk of NAFLD. Results: Overall, 10 studies were included with a total of 38,425 individuals. We found that the non-linear dose-response model showed that for every 1 ng/dL increase in FT4, the risk of NAFLD was reduced by 10.56% (p=0.003). The odds ratios (ORs) for NAFLD with high free triiodothyronine (FT3) exposure compared to those with low FT3 were 1.580 (95% CI 1.370 to 1.830, I2 = 0.0%, p<0.001) in the overall meta-analysis. The continuous variable meta-analysis indicated that individuals with high levels of TSH (SMD=1.32, 95% CI 0.660 to 1.970, p<0.001) had significantly higher levels of liver fibrosis than those with low levels. Conclusions: Our findings only validate that there is a correlation between the occurrence of NAFLD and abnormal levels of THs, and it is expected that more observational studies will still be conducted in the future to further demonstrate the relationship between thyroid hormones and NAFLD. Trial registration: Registered number in PROSPERO: CRD42023405052.

Structural analysis of Salvia miltiorrhiza polysaccharide and its regulatory functions on T cells subsets in tumor-bearing mice combined with thymopentin.

Salvia miltiorrhiza ethanol-extracted polysaccharide (SMEP) and thymopentin (TP5) have been proved with strong immunomodulatory activity, and T cells subsets play pivotal roles in the inhibition of solid tumors growth. In the present study, the structure of SMEP was further identified via methylation and nuclear magnetic resonance spectra, and the immunomodulatory activity in combination with TP5 was investigated via evaluating T cell subsets spatial distributions in tumor-bearing mice, finally the cellular status of solid tumor cells was analyzed. The results revealed that SMEP was a neutral heteropolysaccharide using (1 â†’ 4)-α-D-Glcp and (2 â†’ 1)-ß-D-Fruf as the main chain, along with branched chains of (1 â†’ 6)-α-D-Galp. The SMEP+TP5 treatments could effectively promote the differentiation and improve the specific recognition capacity of CD4+ T cells in tumor-bearing mice, thereby activate tumor-infiltrating CD8+ T cells to exert cytotoxic effects, finally promoting the tumor cells apoptosis via blocking cell cycle at G0/G1 phase, which might be relevant with suppression of Wnt/ß-catenin signaling pathway. These findings highlighted the potential of SMEP as an immunoadjuvant for patients bearing immune-deficiency related diseases, and provided data support for the functional researches of T cell subsets in tumor immunity.

Biochemical insights into proline metabolism and its contribution to the endurant cell wall structure under metal stress.

The cell wall serves as the primary barrier against the entry of heavy metal ions into cells. However, excessive accumulation of heavy metals within plants can lead to alterations in the spatial structure and physical properties of the cell wall, thereby affecting the capacity of plants to capture heavy metals. Proline (Pro) is involved in the synthesis of the cell wall, modulating the stability and integrity of its structure. Extensins, core proteins that maintain the cell wall structure, are proline/hydroxyproline-rich glycoproteins that contain the characteristic sequence Ser-[Pro]3-5. They act as intermediates in the regulation of biological processes such as cell wall synthesis, assembly, and signal transduction, typically forming a network structure of cell wall proteins through cross-linking with pectin. This network is essential for the self-assembly expansion of the plant cell wall and plays an indispensable role in cell wall stress signal transduction through its interaction with intracellular signalling molecules. However, the mechanisms by which Pro affects the synthesis of cell wall structural proteins, cell wall assembly, and the sensing of cell wall stress under heavy metal stress remain unclear. This review, from the perspectives of biochemistry and molecular biology, comprehensively elaborates on the impact of Pro and Pro-rich proteins on the structure and function of the cell wall. These findings emphasize the mechanism by which Pro enhances the ability of the cell wall to capture heavy metals, providing new research ideas for the use of genetic engineering to manipulate cell wall synthesis and repair, thereby reducing the phytotoxicity of heavy metals.

Prevalence and molecular detection of Babesia microti in rodents in Southeastern Shanxi, China.

Babesia is a tick-transmitted parasite that infects wild and domestic animals, causes babesiosis in humans, and is an increasing public health concern. Here, we investigated the prevalence and molecular characteristics of Babesia infections in the rodents in Southeastern Shanxi, China. Small rodents were captured, and the liver and spleen tissues were used for Babesia detection using traditional PCR and sequencing of the partial 18S rRNA gene. The analysis revealed that 27 of 252 small rodents were positive for Babesia, with an infection rate of 10.71%. The infection rates in different sexes and rodent tissues were not statistically different, but those in different rodent species, habitats, and sampling sites were statistically different. The highest risk of Babesia infection was observed in Niviventer confucianus captured from the forests in Huguan County. Forty-three sequences from 27 small rodents positive for Babesia infection were identified as Babesia microti, including 42 sequences from 26 N. confucianus, and one sequence from Apodemus agrarius. Phylogenetic analysis showed that all sequences were clustered together and had the closest genetic relationship with Babesia microti strains isolated from Rattus losea and N. confucianus in China, and belonged to the Kobe-type, which is pathogenic to humans. Compared to other Kobe-type strains based on the nearly complete 18S rRNA gene, the sequences obtained in this study showed the difference by 1-3 bp. Overall, a high prevalence of Babesia microti infection was observed in small rodents in Southeastern Shanxi, China, which could benefit us to take the implementation of relevant prevention and control measures in this area.

Effects of compatibility of Clostridium butyricum and Bacillus subtilis on growth performance, lipid metabolism, antioxidant status and cecal microflora of broilers during the starter phase.

Objective: This study aimed to determine the effects of compatibility of Clostridium butyricum and Bacillus subtilis on growth performance, lipid metabolism, antioxidant status and cecal microflora of broilers during the starter phase. Methods: A total of 600 1-day-old Ross 308 broilers were randomly divided into two groups with six replicates in each group. Chickens in the control group were fed a basal diet, while chickens in the experimental group were fed a diet supplemented with 2 × 108 CFU/kg of C. butyricum and 1 × 109 CFU/kg of B. subtilis. The experimental period was 21 days. Results: Addition of C. butyricum and B. subtilis significantly increased (p<0.05) the body weight and liver NADP-malic enzyme (NADP-ME) activity of broilers, enhanced (p<0.05) the average daily gain and average daily feed intake of broilers. However, the addition of C. butyricum and B. subtilis did not significantly affect the concentrations of triglyceride and total cholesterol in the serum, the activities of fatty acid synthase and acetyl-CoA carboxylase in the liver, the total antioxidant capacity, glutathione peroxidase activity and malondialdehyde content in the serum and liver. Besides, microbial analysis revealed that supplementation of C. butyricum and B. subtilis increased (p<0.05) the abundance of Firmicutes such as CHKCI001 and Faecalibacterium, decreased (p<0.05) the abundance of Bacteroidota such as Bacteroides and Alistipes. Spearman correlation analysis confirmed that the above cecal microbiota were closely related to the growth performance of broilers (p<0.05). In addition, simultaneous supplementation of C. butyricum and B. subtilis significant affected (p<0.05) 33 different functional pathways such as lipid metabolism and carbohydrate metabolism. This explains the phenomenon of increased growth performance and liver NADP-ME activity in the probiotics group. Conclusion: The compatibility of C. butyricum and B. subtilis could improve the growth of broilers during the starter phase by changing the cecal microflora.

Investigation of the Microbial Diversity in the Oryza sativa Cultivation Environment and Artificial Transplantation of Microorganisms to Improve Sustainable Mycobiota.

Rice straw is not easy to decompose, it takes a long time to compost, and the anaerobic bacteria involved in the decomposition process produce a large amount of carbon dioxide (CO2), indicating that applications for rice straw need to be developed. Recycling rice straw in agricultural crops is an opportunity to increase the sustainability of grain production. Several studies have shown that the probiotic population gradually decreases in the soil, leading to an increased risk of plant diseases and decreased biomass yield. Because the microorganisms in the soil are related to the growth of plants, when the soil microbial community is imbalanced it seriously affects plant growth. We investigated the feasibility of using composted rice stalks to artificially cultivate microorganisms obtained from the Oryza sativa-planted environment for analyzing the mycobiota and evaluating applications for sustainable agriculture. Microbes obtained from the water-submerged part (group-A) and soil part (group-B) of O. sativa were cultured in an artificial medium, and the microbial diversity was analyzed with internal transcribed spacer sequencing. Paddy field soil was mixed with fermented paddy straw compost, and the microbes obtained from the soil used for O. sativa planting were designated as group-C. The paddy fields transplanted with artificially cultured microbes from group-A were designated as group-D and those from group-B were designated as group-E. We found that fungi and yeasts can be cultured in groups-A and -B. These microbes altered the soil mycobiota in the paddy fields after transplantation in groups-D and -E compared to groups-A and -B. Development in O. sativa post treatment with microbial transplantation was observed in the groups-D and -E compared to group-C. These results showed that artificially cultured microorganisms could be efficiently transplanted into the soil and improve the mycobiota. Phytohormones were involved in improving O. sativa growth and rice yield via the submerged part-derived microbial medium (group-D) or the soil part-derived microbial medium (group-E) treatments. Collectively, these fungi and yeasts may be applied in microbial transplantation via rice straw fermentation to repair soil mycobiota imbalances, facilitating plant growth and sustainable agriculture. These fungi and yeasts may be applied in microbial transplantation to repair soil mycobiota imbalances and sustainable agriculture.

Super-enhancer-driven IRF2BP2 enhances ALK activity and promotes neuroblastoma cell proliferation.

BACKGROUND: Super-enhancers (SEs) typically govern the expression of critical oncogenes and play a fundamental role in the initiation and progression of cancer. Focusing on genes that are abnormally regulated by SE in cancer may be a new strategy for understanding pathogenesis. In the context of this investigation, we have identified a previously unreported SE-driven gene IRF2BP2 in neuroblastoma (NB). METHODS: The expression and prognostic value of IRF2BP2 were detected in public databases and clinical samples. The effect of IRF2BP2 on NB cell growth and apoptosis was evaluated through in vivo and in vitro functional loss experiments. The molecular mechanism of IRF2BP2 was investigated by the study of chromatin regulatory regions and transcriptome sequencing. RESULTS: The sustained high expression of IRF2BP2 results from the activation of a novel SE established by NB master transcription factors MYCN, MEIS2 and HAND2, and they form a new complex that regulates the gene network associated with the proliferation of NB cell populations. We also observed a significant enrichment of the AP-1 family at the binding sites of IRF2BP2. Remarkably, within NB cells, AP-1 plays a pivotal role in shaping the chromatin accessibility landscape, thereby exposing the binding site for IRF2BP2. This orchestrated action enables AP-1 and IRF2BP2 to collaboratively stimulate the expression of the NB susceptibility gene ALK, thereby upholding the highly proliferative phenotype characteristic of NB. CONCLUSION: Our findings indicate that SE-driven IRF2BP2 can bind to AP-1 to maintain the survival of tumor cells via regulating chromatin accessibility of NB susceptibility gene ALK.

The performance of large language model powered chatbots compared to oncology physicians on colorectal cancer queries.

BACKGROUND: Large language model (LLM)-powered chatbots have become increasingly prevalent in healthcare, while their capacity in oncology remains largely unknown. To evaluate the performance of LLM-powered chatbots compared to oncology physicians in addressing to colorectal cancer queries. METHODS: This study was conducted between August 13, 2023, and January 5, 2024. A total of 150 questions were designed, and each question was submitted three times to eight chatbots: ChatGPT-3.5, ChatGPT-4, ChatGPT-4 Turbo, Doctor GPT, Llama-2-70B, Mixtral-8x7B, Bard, and Claude 2.1. No feedback was provided to these chatbots. The questions were also answered by nine oncology physicians, including three residents, three fellows, and three attendings. Each answer was scored based on its consistency with guidelines, with a score of 1 for consistent answers and 0 for inconsistent answers. The total score for each question was based on the number of corrected answers, ranging from 0 to 3. The accuracy and scores of the chatbots were compared to those of the physicians. RESULTS: Claude 2.1 demonstrated the highest accuracy, with an average accuracy of 82.67%, followed by Doctor GPT at 80.45%, ChatGPT-4 Turbo at 78.44%, ChatGPT-4 at 78%, Mixtral-8x7B at 73.33%, Bard at 70%, ChatGPT-3.5 at 64.89%, and Llama-2-70B at 61.78%. Claude 2.1 outperformed residents, fellows, and attendings. Doctor GPT outperformed residents and fellows. Additionally, Mixtral-8x7B outperformed residents. In terms of scores, Claude 2.1 outperformed residents and fellows. Doctor GPT, ChatGPT-4 Turbo and ChatGPT-4 outperformed residents. CONCLUSIONS: This study shows that LLM-powered chatbots can provide more accurate medical information compared to oncology physicians.

Fabrication of fully bio-based malleable thermoset derived from cellulose, furfural and plant oil for advanced capacitive sensor.

Fabrication of sustainable bio-based malleable thermosets (BMTs) with excellent mechanical properties and reprocessing ability for applications in electronic devices has attracted more and more attention but remains significant challenges. Herein, the BMTs with excellent mechanical robustness and reprocessing ability were fabricated via integrating with radical polymerization and Schiff-base chemistry, and employed as the flexible substrate to prepare the capacitive sensor. To prepare the BMTs, an elastic bio-copolymer derived from plant oil and 5-hydroxymethylfurfural was first synthesized, and then used to fabricate the dynamic crosslinked BMTs through Schiff-base chemistry with the amino-modified cellulose and polyether amine. The synergistic effect of rigid cellulose backbone and the construction of dynamic covalent crosslinking network not only achieved high tensile strength (8.61 MPa) and toughness (3.77 MJ/m3) but also endowed the BMTs with excellent reprocessing ability with high mechanical toughness recovery efficiency of 104.8 %. More importantly, the BMTs were used as substrates to fabricate the capacitive sensor through the CO2-laser irradiation technique. The resultant capacitive sensor displayed excellent and sensitive humidity sensing performance, which allowed it to be successfully applied in human health monitoring. This work paved a promising way for the preparation of mechanical robustness malleable bio-thermosets for electronic devices.

Identifying High-Quality Non-Instrumental Dysphagia Screening Tools for Detection of Adult Dysphagia Case in Acute-Care Settings: A Systematic Review.

INTRODUCTION: As patients nowadays tend to have multiple diseases and complex medical histories, our aim was to identify high-quality, non-instrumental dysphagia screening tools used for the detection of adult dysphagia cases in all disease categories in acute-care settings. METHOD: A literature search was conducted in five databases from each database's earliest inception to 31 July 2021 and guided by five keywords: 'dysphagia', 'deglutition', 'screening', 'test' and 'measure'. Without limiting the search in any specific disease category, reviewers assessed original studies and identified tools if they had been validated against instrumental evaluations and if they had been designed as a pass-fail procedure to screen whether dysphagia is absent or present. We further excluded any tool if it was (1) for pediatric focus, or (2) a patient self-report questionnaire. All final tool candidates underwent a methodological quality appraisal using the Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). RESULT: Out of 195 studies with 165 tools identified, 20 tool candidates underwent QUADAS-2 review. We found six high-quality, non-instrumental screening tools for detecting adult dysphagia cases in acute-care settings, including the Yale Swallow Protocol, Gugging Swallowing Screen, Toronto Bedside Swallowing Screening Test (both English and Portuguese versions), Sapienza Global Bedside Evaluation of Swallowing and Two-Step Thickened Water Test. These high-quality tools were developed primarily for patients with stroke. Only Yale Swallow Protocol was originally tested for heterogeneous populations with stroke, multiple sclerosis, traumatic brain injury, oesophageal surgery, neurosurgery and head-and-neck cancer. CONCLUSIONS: The results highlight the gap in the unavailability of high-quality dysphagia screening tool in several emerged high-risk populations including elderly inpatients, or patients following endotracheal extubation. Further research is needed to determine whether these six tools can be effectively applied across different high-risk populations in acute-care settings to screen for cases finding.

Functional near-infrared spectroscopy-based neurofeedback training regulates time-on-task effects and enhances sustained cognitive performance.

Time-on-task effect is a common consequence of long-term cognitive demand work, which reflects reduced behavioral performance and increases the risk of accidents. Neurofeedback is a neuromodulation method that can guide individuals to regulate their brain activity and manifest as changes in related symptoms and cognitive behaviors. This study aimed to examine the effects of functional near-infrared spectroscopy-based neurofeedback training on time-on-task effects and sustained cognitive performance. A randomized, single-blind, sham-controlled study was performed: 17 participants received feedback signals of their own dorsolateral prefrontal cortex activity (neurofeedback group), and 16 participants received feedback signals of dorsolateral prefrontal cortex activity from the neurofeedback group (sham-neurofeedback group). All participants received 5 neurofeedback training sessions and completed 2 sustained cognitive tasks, including a 2-back task and a psychomotor vigilance task, to evaluate behavioral performance changes following neurofeedback training. Results showed that neurofeedback relative to the sham-neurofeedback group exhibited increased dorsolateral prefrontal cortex activation, increased accuracy in the 2-back task, and decreased mean response time in the psychomotor vigilance task after neurofeedback training. In addition, the neurofeedback group showed slower decline performance during the sustained 2-back task after neurofeedback training compared with sham-neurofeedback group. These findings demonstrate that neurofeedback training could regulate time-on-task effects on difficult task and enhance performance on sustained cognitive tasks by increasing dorsolateral prefrontal cortex activity.

Screening of active components of Ganoderma lucidum and decipher its molecular mechanism to improve learning and memory disorders.

Learning and memory impairment (LMI), a common degenerative central nervous system disease. Recently, more and more studies have shown that Ganoderma lucidum (GL) can improve the symptoms of LMI. The active ingredients in GL and their corresponding targets were screened through TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) and BATMAN-TCM (Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine) databases, and the potential LMI targets were searched for through GeneCard (GeneCards Human Gene Database) and DrugBank. Then, we construct a "main active ingredient-target" network and a protein-protein interaction (PPI) network diagram.The GO (Gene Ontology) functional enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway annotation analysis were performed on the common targets through DAVID (Database for Annotation Visualization and Integrated Discovery) to clarify the potential molecular mechanism of action of active ingredients in GL. The TNF protein was verified by western blot;Twenty one active ingredients in GL and 142 corresponding targets  were screened out, including 59 targets shared with LMI. The 448 biological processes shown by the GO functional annotation results and 55 signal pathways shown by KEGG enrichment analysis were related to the improvement of LMI by GL, among which the correlation of Alzheimer disease pathway is the highest, and TNF was the most important protein; TNF can improve LMI.GL can improve LMI mainly by 10 active ingredients in it, and they may play a role by regulating Alzheimer disease pathway and TNF protein.

MiR-34a promotes mitochondrial pathway of apoptosis in human salivary gland epithelial cells by activating NF-κB signaling.

To investigate the potential molecular mechanism of miR-34a in Sjögren's syndrome (SS). Transmission electron microscopy was used to observe the salivary gland tissues of mild and severe SS patients. SS mouse model was constructed and injected with miR-34a antagonist. HSGE cells were transfected with miR-34a mimic. Starbase predicted miR-34a binding sites and validated them with dual-luciferase reporter assays. Immunohistochemistry, HE staining, CCK-8, TUNEL assay, flow cytometry, immunofluorescence and Western Blot were used to investigate the effects of miR-34a on NF-κB signaling and mitochondrial pathway of apoptosis in HSGE cells. Severe SS patients showed obvious mitochondrial damage and apoptosis in salivary glands. MiR-34a was overexpressed and NF-κB signaling is activated in salivary glands of severe SS patients. Inhibition of miR-34a alleviated salivary gland injury in SS mice, as well as inhibited the activation of NF-κB signaling and mitochondrial pathway of apoptosis. In conclusion, miR-34a promoted NF-κB signaling by targeting IκBα, thereby causing mitochondrial pathway apoptosis and aggravating SS-induced salivary gland damage.

Nickel-catalysed highly regioselective synthesis of ß-acyl naphthalenes under reductive conditions.

Over the past decade, significant progress has been made in the direct C-H acylation of naphthalenes, occurring at the α or ß-positions to yield valuable ketones through Friedel-Crafts acylation or transition-metal-catalysed carbonylative coupling reactions. Nevertheless, highly regioselective acylation of naphthalenes remains a formidable challenge. Herein, we developed a nickel-catalysed reductive ring-opening reaction of 7-oxabenzonorbornadienes with acyl chlorides as the electrophilic coupling partner, providing a new method for the exclusive preparation of ß-acyl naphthalenes.

Tumor Microenvironment Specific Regulation Ca-Fe-Nanospheres for Ferroptosis-Promoted Domino Synergistic Therapy and Tumor Immune Response.

Reactive oxygen species (ROS)-mediated emerging treatments exhibit unique advantages in cancer therapy in recent years. While the efficacy of ROS-involved tumor therapy is greatly restricted by complex tumor microenvironment (TME). Herein, a dual-metal CaO2@CDs-Fe (CCF) nanosphere, with TME response and regulation capabilities, are proposed to improve ROS lethal power by a multiple cascade synergistic therapeutic strategy with domino effect. In response to weak acidic TME, CCF will decompose, accompanied with intracellular Ca2+ upregulated and abundant H2O2 and O2 produced to reverse antitherapeutic TME. Then the exposed CF cores can act as both Fenton agent and sonosensitizer to generate excessive ROS in the regulated TME for enhanced synergistic CDT/SDT. In combination with calcium overloading, the augmented ROS induced oxidative stress will cause more severe mitochondrial damage and cellular apoptosis. Furthermore, CCF can also reduce GPX4 expression and enlarge the lipid peroxidation, causing ferroptosis and apoptosis in parallel. These signals of damage will finally initiate damage-associated molecular patterns to activate immune response and to realize excellent antitumor effect. This outstanding domino ROS/calcium loading synergistic effect endows CCF with excellent anticancer effect to efficiently eliminate tumor by apoptosis/ferroptosis/ICD both in vitro and in vivo.

Rejuvenation of peripheral immune cells attenuates Alzheimer's disease-like pathologies and behavioral deficits in a mouse model.

Immunosenescence contributes to systematic aging and plays a role in the pathogenesis of Alzheimer's disease (AD). Therefore, the objective of this study was to investigate the potential of immune rejuvenation as a therapeutic strategy for AD. To achieve this, the immune systems of aged APP/PS1 mice were rejuvenated through young bone marrow transplantation (BMT). Single-cell RNA sequencing revealed that young BMT restored the expression of aging- and AD-related genes in multiple cell types within blood immune cells. The level of circulating senescence-associated secretory phenotype proteins was decreased following young BMT. Notably, young BMT resulted in a significant reduction in cerebral Aß plaque burden, neuronal degeneration, neuroinflammation, and improvement of behavioral deficits in aged APP/PS1 mice. The ameliorated cerebral amyloidosis was associated with an enhanced Aß clearance of peripheral monocytes. In conclusion, our study provides evidence that immune system rejuvenation represents a promising therapeutic approach for AD.