Temporal dynamics of spatial attentional biases toward weight-related words among females with weight dissatisfaction.

Attentional bias toward weight-related stimuli plays a crucial role in the development and maintenance of body image disturbances. However, the temporal dynamics of attentional biases responsible for the previously reported behavioral effects caused by the task-irrelevant but spatial-relevant weight-related stimuli presented in the peripheral visual field among females with high weight dissatisfaction (HWD) remain unclear. The present study combined the modified dot-probe task and event-related potentials to explore the temporal dynamics of spatial attentional biases toward weight-related words among females with HWD. The results showed significantly larger N2pc amplitudes were elicited by fat-related and thin-related words than neutral words only in the HWD group. Moreover, only fat-related words elicited a significant PD for the HWD group, and the PD amplitudes were larger in the HWD group than in the control group. These findings revealed that weight-related words initially captured spatial allocation among females with HWD, and then fat-related words were actively suppressed after the initial capturing.

Targeting dysregulated lipid metabolism for the treatment of Alzheimer's disease and Parkinson's disease: Current advancements and future prospects.

Alzheimer's and Parkinson's diseases are two of the most frequent neurological diseases. The clinical features of AD are memory decline and cognitive dysfunction, while PD mainly manifests as motor dysfunction such as limb tremors, muscle rigidity abnormalities, and slow gait. Abnormalities in cholesterol, sphingolipid, and glycerophospholipid metabolism have been demonstrated to directly exacerbate the progression of AD by stimulating Aß deposition and tau protein tangles. Indirectly, abnormal lipids can increase the burden on brain vasculature, induce insulin resistance, and affect the structure of neuronal cell membranes. Abnormal lipid metabolism leads to PD through inducing accumulation of α-syn, dysfunction of mitochondria and endoplasmic reticulum, and ferroptosis. Great progress has been made in targeting lipid metabolism abnormalities for the treatment of AD and PD in recent years, like metformin, insulin, peroxisome proliferator-activated receptors (PPARs) agonists, and monoclonal antibodies targeting apolipoprotein E (ApoE). This review comprehensively summarizes the involvement of dysregulated lipid metabolism in the pathogenesis of AD and PD, the application of Lipid Monitoring, and emerging lipid regulatory drug targets. A better understanding of the lipidological bases of AD and PD may pave the way for developing effective prevention and treatment methods for neurodegenerative disorders.

Tumour organoids and assembloids: Patient-derived cancer avatars for immunotherapy.

BACKGROUND: Organoid technology is an emerging and rapidly growing field that shows promise in studying organ development and screening therapeutic regimens. Although organoids have been proposed for a decade, concerns exist, including batch-to-batch variations, lack of the native microenvironment and clinical applicability. MAIN BODY: The concept of organoids has derived patient-derived tumour organoids (PDTOs) for personalized drug screening and new drug discovery, mitigating the risks of medication misuse. The greater the similarity between the PDTOs and the primary tumours, the more influential the model will be. Recently, 'tumour assembloids' inspired by cell-coculture technology have attracted attention to complement the current PDTO technology. High-quality PDTOs must reassemble critical components, including multiple cell types, tumour matrix, paracrine factors, angiogenesis and microorganisms. This review begins with a brief overview of the history of organoids and PDTOs, followed by the current approaches for generating PDTOs and tumour assembloids. Personalized drug screening has been practised; however, it remains unclear whether PDTOs can predict immunotherapies, including immune drugs (e.g. immune checkpoint inhibitors) and immune cells (e.g. tumour-infiltrating lymphocyte, T cell receptor-engineered T cell and chimeric antigen receptor-T cell). PDTOs, as cancer avatars of the patients, can be expanded and stored to form a biobank. CONCLUSION: Fundamental research and clinical trials are ongoing, and the intention is to use these models to replace animals. Pre-clinical immunotherapy screening using PDTOs will be beneficial to cancer patients. KEY POINTS: The current PDTO models have not yet constructed key cellular and non-cellular components. PDTOs should be expandable and editable. PDTOs are promising preclinical models for immunotherapy unless mature PDTOs can be established. PDTO biobanks with consensual standards are urgently needed.

Exploring a specialized programmed-cell death patterns to predict the prognosis and sensitivity of immunotherapy in cutaneous melanoma via machine learning.

The mortality and therapeutic failure in cutaneous melanoma (CM) are mainly caused by wide metastasis and chemotherapy resistance. Meanwhile, immunotherapy is considered a crucial therapy strategy for CM patients. However, the efficiency of currently available methods and biomarkers in predicting the response of immunotherapy and prognosis of CM is limited. Programmed cell death (PCD) plays a significant role in the occurrence, development, and therapy of various malignant tumors. In this research, we integrated fourteen types of PCD, multi-omics data from TCGA-SKCM and other cohorts in GEO, and clinical CM patients to develop our analysis. Based on significant PCD patterns, two PCD-related CM clusters with different prognosis, tumor microenvironment (TME), and response to immunotherapy were identified. Subsequently, seven PCD-related features, especially CD28, CYP1B1, JAK3, LAMP3, SFN, STAT4, and TRAF1, were utilized to establish the prognostic signature, namely cell death index (CDI). CDI accurately predicted the response to immunotherapy in both CM and other cancers. A nomogram with potential superior predictive ability was constructed, and potential drugs targeting CM patients with specific CDI have also been identified. Given all the above, a novel CDI gene signature was indicated to predict the prognosis and exploit precision therapeutic strategies of CM patients, providing unique opportunities for clinical intelligence and new management methods for the therapy of CM.

Statins as a risk factor for diabetic retinopathy: a Mendelian randomization and cross-sectional observational study.

BACKGROUND: Diabetic retinopathy (DR) is the foremost cause of vision loss among the global working-age population, and statins are among the most frequently prescribed drugs for lipid management in patients with DR. The exact relationship between statins and DR has not been determined. This study sought to validate the causal association between statins usage and diabetic retinopathy. METHODS: The summary-data-based Mendelian randomization (SMR) method and inverse-variance-weighted Mendelian randomization (IVW-MR) were used to identify the causal relationship between statins and DR via the use of expression quantitative trait loci (eQTL) data for 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) (31,684 blood samples), low density lipoprotein cholesterol-related GWAS data (sample size: 440,546), and DR-related GWAS data (14,584 cases and 176,010 controls). Additionally, a cross-sectional observational study based on the data from the National Health and Nutrition Examination Survey (NHANES) was conducted to supplement the association between DR and statins (sample size: 106,911). The odds ratios (ORs) with corresponding 95% confidence intervals (CIs) was employed to evaluate the results. RESULTS: Based on the results of the MR analysis, HMGCR inhibitors were causally connected with a noticeably greater incidence of DR (IVW: OR = 0.54, 95% CI [0.42, 0.69], p = 0.000002; SMR: OR = 0.66, 95% CI [0.52, 0.84], p = 0.00073). Subgroup analysis revealed that the results were not affected by the severity of DR. The sensitivity analysis revealed the stability and reliability of the MR analysis results. The results from the cross-sectional study based on NHANES also support the association between not taking statins and a decreased risk of DR (OR = 0.54, 95% CI [0.37, 0.79], p = 0.001). CONCLUSIONS: This study revealed that a significant increase in DR risk was causally related to statins use, providing novel insights into the role of statins in DR. However, further investigations are needed to verify these findings.

Potential causal association between leisure sedentary behaviors and osteoporosis: A two-sample Mendelian randomization analysis.

Previous observational studies have observed a correlation between sedentary behavior and osteoporosis. However, conclusions from these studies have been contradictory. To explore the potential causal relationship between sedentary behavior and osteoporosis, we conducted a Mendelian randomization analysis. A two-sample Mendelian randomization was adopted to explore the causal relationship of leisure sedentary behavior with osteoporosis. We employed 5 methods to estimate the causal associations between leisure sedentary behavior and osteoporosis. Univariable Mendelian randomization results provided evidence for the causal relationship of the time spent on computer-use with the bone mineral density estimated by heel quantitative ultrasound (eBMD) (inverse variance weighted [IVW]: ß (95% confidence interval [CI]) - 0.150 (-0.270 to -0.031), P = .013; weighted median: ß (95%CI) - 0.195 (-0.336 to -0.055), P = .006). Similar associations were observed in the driving forearm bone mineral density (FABMD) (IVW: ß (95%CI) - 0.933 (-1.860 to -0.007), P = .048) and driving lumbar spine bone mineral density (IVW: ß (95%CI) - 0.649 (-1.175 to -0.124), P = .015). However, we did not find a significant causal relationship between the time spent on watching TV and bone mineral density. Research showed that there was a causal relationship between the time spent on computer use and driving time and eBMD, FABMD, and lumbar spine bone mineral density.

Heat/non-heat treatment alleviates ß-conglycinin-triggered food allergy reactions by modulating the Th1/Th2 immune balance in a BALB/c mouse model.

BACKGROUND: With the increasing popularity of plant protein-based diets, soy proteins are favored as the most important source of plant protein worldwide. However, potential food allergy risks limit their use in the food industry. This work aims to reveal the mechanism of ß-conglycinin-induced food allergy, and to explore the regulatory mechanism of heat treatment and high hydrostatic pressure (HHP) treatment in a BALB/c mouse model. RESULTS: Our results showed that oral administration of ß-conglycinin induced severe allergic symptoms in BALB/c mice, but these symptoms were effectively alleviated through heat treatment and HHP treatment. Moreover, ß-conglycinin stimulated lymphocyte proliferation and differentiation; a large number of cytokines interleukin (IL)-4, IL-5, IL-10, IL-12 and IL-13 were released and interferon γ secretion was inhibited, which disrupted the Th1/Th2 immune balance and promoted the differentiation and proliferation of naive T cells into Th2-type cells. CONCLUSION: Heat/non-heat treatment altered the conformation of soybean protein, which significantly reduced allergic reactions in mice. This regulatory mechanism may be associated with Th1/Th2 immune balance. Our results provide data support for understanding the changes in allergenicity of soybean protein within the food industry. © 2024 Society of Chemical Industry.

Quantitative profiling of human translation initiation reveals regulatory elements that potently affect endogenous and therapeutically modified mRNAs.

mRNA therapeutics offer a potentially universal strategy for the efficient development and delivery of therapeutic proteins. Current mRNA vaccines include chemically modified nucleotides to reduce cellular immunogenicity. Here, we develop an efficient, high-throughput method to measure human translation initiation on therapeutically modified as well as endogenous RNAs. Using systems-level biochemistry, we quantify ribosome recruitment to tens of thousands of human 5' untranslated regions and identify sequences that mediate 250-fold effects. We observe widespread effects of coding sequences on translation initiation and identify small regulatory elements of 3-6 nucleotides that are sufficient to potently affect translational output. Incorporation of N1-methylpseudouridine (m1Ψ) selectively enhances translation by specific 5' UTRs that we demonstrate surpass those of current mRNA vaccines. Our approach is broadly applicable to dissect mechanisms of human translation initiation and engineer more potent therapeutic mRNAs. Highlights: Measurement of >30,000 human 5' UTRs reveals a 250-fold range of translation outputSystematic mutagenesis demonstrates the causality of short (3-6nt) regulatory elementsN1-methylpseudouridine alters translation initiation in a sequence-specific mannerOptimal modified 5' UTRs outperform those in the current class of mRNA vaccines.

Biotransformation characteristics of tetracycline by strain Serratia marcescens MSM2304 and its mechanism evaluation based on products analysis and genomics.

Microbial biotransformation is a recommended and reliable method in face of formidable tetracycline (TC) with broad-spectrum antibacterial activity. Herein, comprehensive characteristics of a newfound strain and its molecular mechanism in process of TC bioremediation were involved in this study. Specifically, Serratia marcescens MSM2304 isolated from pig manure sludge grew well in presence of TC and achieved optimal removal efficiency of 61% under conditions of initial TC concentration of 10 mg/L, pH of 7.0, cell inoculation amount of 5%, and tryptone of 10 g/L as additional carbon. The pathways of biotransformation include EPS biosorption, cell surface biosorption and biodegradation, which enzymatic processes of biodegradation were occurred through TC adsorbed by biofilms was firstly broken down by extracellular enzymes and part of TC migrated towards biofilm interior and degraded by intracellular enzymes. Wherein extracellular polysaccharides in extracellular polymeric substances (EPS) from biofilm of strain MSM2304 mainly performed extracellular adsorption, and changes in position and intensity of CO, =CH and C-O-C/C-O of EPS possible further implied TC adsorption by it. Biodegradation accounting for 79.07% played a key role in TC biotransformation and could be fitted well by first-order model that manifesting rapid and thorough removal. Potential biodegradation pathway including demethylation, dihydroxylation, oxygenation, and ring opening possibly involved in TC disposal process of MSM2304, TC-degrading metabolites exhibited lower toxicity to indicator bacteria relative to parent TC. Whole genome sequencing as underlying molecular evidence revealed that TC resistance genes, dehydrogenases-encoding genes, monooxygenase-encoding genes, and methyltransferase-encoding genes of strain MSM2304 were positively related to TC biodegradation. Collectively, these results favored a theoretical evaluation for Serratia marcescens MSM2304 as a promising TC-control agent in environmental bioremediation processes.

Lei's formula attenuates osteoarthritis mediated by suppression of chondrocyte senescence via the mTOR axis: in vitro and in vivo experiments.

Lei's formula (LSF), a traditional Chinese herbal remedy, is recognized for its remarkable clinical effectiveness in treating osteoarthritis (OA). Despite its therapeutic potential, the exact molecular mechanisms underlying LSF's action in OA have remained enigmatic. Existing research has shed light on the role of the mTOR signaling pathway in promoting chondrocyte senescence, a central factor in OA-related cartilage degeneration. Consequently, targeting mTOR to mitigate chondrocyte senescence presents a promising avenue for OA treatment. The primary objective of this study is to establish LSF's chondroprotective potential and confirm its anti-osteoarthritic efficacy through mTOR inhibition. In vivo assessments using an OA mouse model reveal substantial articular cartilage degeneration. However, LSF serves as an effective guardian of articular cartilage, evidenced by reduced subchondral osteosclerosis, increased cartilage thickness, improved surface smoothness, decreased OARSI scores, elevated expression of cartilage anabolic markers (Col2 and Aggrecan), reduced expression of catabolic markers (Adamts5 and MMP13), increased expression of the chondrocyte hypertrophy marker (Col10), and decreased expression of chondrocyte senescence markers (P16 and P21). In vitro findings demonstrate that LSF shields chondrocytes from H2O2-induced apoptosis, inhibits senescence, enhances chondrocyte differentiation, promotes the synthesis of type II collagen and proteoglycans, and reduces cartilage degradation. Mechanistically, LSF suppresses chondrocyte senescence through the mTOR axis, orchestrating the equilibrium between chondrocyte anabolism and catabolism, ultimately leading to reduced apoptosis and decelerated OA cartilage degradation. LSF holds significant promise as a therapeutic approach for OA treatment, offering new insights into potential treatments for this prevalent age-related condition.

Lipidomic profiles in serum and urine in children with steroid sensitive nephrotic syndrome.

BACKGROUND: Steroid-sensitive nephrotic syndrome (SSNS) accounts for approximately 80% of cases of nephrotic syndrome. The involvement of aberrant lipid metabolism in early SSNS is poorly understood, warranting further investigation. This study aimed to explore alterations in lipid metabolism associated with SSNS pathogenesis. METHODS: A screening cohort containing serum (50 SSNS, 37 controls) and urine samples (27 SSNS, 26 controls) was analyzed by untargeted lipidomic profiling using UHPLC-QTOF-MS. Then, a validation cohort (20 SSNS, 56 controls) underwent further analysis to check the potential clinical application by ROC curve analysis. RESULTS: Lipidomic profiling of serum and urine samples revealed significant lipid alterations in SSNS patients, with the alterations in the serum samples being more significant. An elevated concentration of PE and PG and downregulated concentration of FA were observed in SSNS serum. A total of 38 dysregulated lipids and 5 lipid metabolic pathways were identified in the serum samples in SSNS patients. Validation in the second cohort confirmed differential regulation of nine kinds of lipids, including 5 up-regulated substances [SM d33:2 (m/z = 686.5361), SHexCer d34:1 (m/z = 779.521), PI 20:4_22:4 (m/z = 934.5558), Cer_NS d18:1_23:0 (m/z = 635.6216), and GM3 d36:1 (m/z = 1180.7431)], as well as 4 down-regulated substances: [CE 18:1 (m/z = 650.601), PE 38:6 (m/z = 763.5205), PC 17:0_20:4 (m/z = 795.5868) and EtherPC 16:2e_20:4 (m/z = 763.5498)]. CONCLUSIONS: Untargeted lipidomic analysis successfully identified specific lipid class changes in patients with SSNS, providing a deeper understanding of lipid alterations and underlying mechanisms associated with SSNS.

Engineered liposomes targeting hepatic stellate cells overcome pathological barriers and reverse liver fibrosis.

Dual pathological barriers, including capillarized liver sinusoidal endothelial cells (LSECs) and deposited extracellular matrix (ECM), result in insufficient drug delivery, significantly compromising the anti-fibrosis efficacy. Additionally, excessive reactive oxygen species (ROS) in the hepatic microenvironment are crucial factors contributing to the progression of liver fibrosis. Hence, hyaluronic acid (HA) modified liposomes co-delivering all-trans retinoic acid (RA) and L-arginine (L-arg) were constructed to reverse hepatic fibrosis. By exhibiting exceptional responsiveness to the fibrotic microenvironment, our cleverly constructed liposomes efficiently disrupted the hepatic sinus pathological barrier, leading to enhanced accumulation of liposomes in activated hepatic stellate cells (HSCs) and subsequent induction of HSCs quiescence. Specially, excessive ROS in liver fibrosis promotes the conversion of loaded L-arg to nitric oxide (NO). The ensuing NO serves to reestablish the fenestrae structure of capillarized LSECs, thereby augmenting the likelihood of liposomes reaching the hepatic sinus space. Furthermore, subsequent oxidation of NO by ROS into peroxynitrite activates pro-matrix metalloproteinases into matrix metalloproteinases, which further disrupts the deposited ECM barrier. Consequently, this NO-induced cascade process greatly amplifies the accumulation of liposomes within activated HSCs. More importantly, the released RA could induce quiescence of activated HSCs by significantly downregulating the expression of myosin light chain-2, thereby effectively mitigating excessive collagen synthesis and ultimately leading to the reversal of liver fibrosis. Overall, this integrated systemic strategy has taken a significant step forward in advancing the treatment of liver fibrosis.

Candida albicans Infection Disrupts the Metabolism of Vaginal Epithelial Cells and Inhibits Cellular Glycolysis.

Vulvovaginal candidiasis (VVC) is a common gynecologic disorder caused by fungal infections of the vaginal mucosa, with the most common pathogen being Candida albicans (C. albicans). Exploring metabolite changes in the disease process facilitates further discovery of targets for disease treatment. However, studies on the metabolic changes caused by C. albicans are still lacking. In this study, we used C. albicans-infected vaginal epithelial cells to construct an in vitro model of VVC, analyzed the metabolites by UHPLC-Q-Exactive MS, and screened the potential metabolites based on metabolomics. The results showed that C. albicans infection resulted in significant up-regulation of D-arabitol, palmitic acid, adenosine, etc.; significant down-regulation of lactic acid, nicotinamide (NAM), nicotinate (NA), etc.; and disruption of amino acid metabolism, and that these significantly altered metabolites might be potential therapeutic targets of VVC. Further experiments showed that C. albicans infection led to a decrease in glycolytic enzymes in damaged cells, inhibiting glycolysis and leading to significant alterations in glycolytic metabolites. The present study explored the potential metabolites of VVC induced by C. albicans infection based on metabolomics and verified the inhibitory effect of C. albicans on vaginal epithelial cell glycolysis, which is valuable for the diagnosis and treatment of VVC.

The role of NLRP3 inflammasome in aging and age-related diseases.

The gradual aging of the global population has led to a surge in age-related diseases, which seriously threaten human health. Researchers are dedicated to understanding and coping with the complexities of aging, constantly uncovering the substances and mechanism related to aging like chronic low-grade inflammation. The NOD-like receptor protein 3 (NLRP3), a key regulator of the innate immune response, recognizes molecular patterns associated with pathogens and injury, initiating an intrinsic inflammatory immune response. Dysfunctional NLRP3 is linked to the onset of related diseases, particularly in the context of aging. Therefore, a profound comprehension of the regulatory mechanisms of the NLRP3 inflammasome in aging-related diseases holds the potential to enhance treatment strategies for these conditions. In this article, we review the significance of the NLRP3 inflammasome in the initiation and progression of diverse aging-related diseases. Furthermore, we explore preventive and therapeutic strategies for aging and related diseases by manipulating the NLRP3 inflammasome, along with its upstream and downstream mechanisms.

Network pharmacology and molecular docking to elucidate the common mechanism of hydroxychloroquine treatment in lupus nephritis and IgA nephropathy.

OBJECTIVE: Hydroxychloroquine (HCQ), characterized by a broad effect on immune regulation, has been widely used in the treatment of autoimmune glomerulonephritis such as lupus nephritis (LN) and immunoglobulin A nephropathy (IgAN). The current research investigates whether HCQ plays a role in the treatment of LN and IgAN through common mechanisms since the pathogenesis of both LN and IgAN is closely related to immune complex deposition, complement activation, and ultimately inflammation. METHODS: Seventy-two common targets were obtained related to the common mechanism of HCQ treatment of LN and IgAN. Targets associated with LN and IgAN were collected based on DisGeNET, GeneCards, and OMIM databases. Possible HCQ targets were obtained from the PubChem database and PharmMapper databases. The overlapping targets of HCQ ingredients, IgAN, and LN were discovered via the Venn 2.1.0 online platform. Through the DAVID database, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted. Cytoscape (v3.9.1) was used to build a protein-protein interaction (PPI) network. Molecular docking was performed by using AutoDockTools 1.5.6 software and PyMol software to match the binding activity between HCQ and the 10 core targets. RESULTS: The results showed that core targets (including MMP 2, PPARG, IL-2, MAPK14, MMP 9, and SRC), three signaling pathways (including the PI3K-Akt, AGE-RAGE, and MAPK), and cell differentiation (including Th1, Th2, and Th17) might be related to the body's immunity and inflammation. These results suggested that HCQ might act on targets and pathways involved in inflammation and immune regulation to exert a common effect on the treatment of LN and IgAN. CONCLUSIONS: The current study provided new evidence for the protective mechanism and clinical utility of HCQ against LN and IgAN.

Characterizing immune variation and diagnostic indicators of preeclampsia by single-cell RNA sequencing and machine learning.

Preeclampsia is a multifactorial and heterogeneous complication of pregnancy. Here, we utilize single-cell RNA sequencing to dissect the involvement of circulating immune cells in preeclampsia. Our findings reveal downregulation of immune response in lymphocyte subsets in preeclampsia, such as reduction in natural killer cells and cytotoxic genes expression, and expansion of regulatory T cells. But the activation of naïve T cell and monocyte subsets, as well as increased MHC-II-mediated pathway in antigen-presenting cells were still observed in preeclampsia. Notably, we identified key monocyte subsets in preeclampsia, with significantly increased expression of angiogenesis pathways and pro-inflammatory S100 family genes in VCAN+ monocytes and IFN+ non-classical monocytes. Furthermore, four cell-type-specific machine-learning models have been developed to identify potential diagnostic indicators of preeclampsia. Collectively, our study demonstrates transcriptomic alternations of circulating immune cells and identifies immune components that could be involved in pathophysiology of preeclampsia.

Characterization the prognosis role and effects of snoRNAs in melanoma patients.

Melanoma is a melanocyte-derived malignant cancer and is known for its early metastasis and high mortality rates. It is a highly cutaneous tumour disease that could be related to the abnormal immune microenvironment, and the identification of reliable diagnostic and prognostic markers is crucial for improving patient outcomes. In the search for biomarkers, various types of RNAs have been discovered and recognized as reliable prognostic markers. Among these, small nucleolar RNAs (snoRNAs) have emerged as a promising avenue for studying early diagnosis and prognostic markers in tumours due to their widespread presence in tissues, tumour specificity and stability. In our study, we analysed snoRNAs data from melanoma samples in the TCGA-SKCM cohort and developed a prognostic model comprising 12 snoRNAs (SNORD9, SNORA31, SNORD14E, SNORA14A, SNORA5A, SNORD83A, SNORA75, AL096855, AC007684, SNORD14A, SNORA65 and AC004839). This model exhibited unique prognostic accuracy and demonstrated a significant correlation with the immune infiltration tumour microenvironment. Additionally, analysis of the GSE213145 dataset, which explored the sensitivity and resistance of immune checkpoint inhibitors, further supported the potential of snoRNAs as prognostic markers for immunotherapy. Overall, our study contributes reliable prognostic and immune-related biomarkers for melanoma patients. These findings can offer valuable insights for the future discovery of novel melanoma treatment strategies and hold promise for improving clinical outcomes in melanoma patients.

All-in-one HN@Cu-MOF nanoparticles with enhanced reactive oxygen species generation and GSH depletion for effective tumor treatment.

Non-invasive cancer therapies, especially those based on reactive oxygen species, including photodynamic therapy (PDT), have gained much interest. As emerging photodynamic nanocarriers, metal-organic frameworks (MOFs) based on porphyrin can release reactive oxygen species (ROS) to destroy cancer cells. However, due to the inefficient production of ROS by photosensitizers and the over-expression of glutathione (GSH) in the tumor microenvironment (TME), their therapeutic effect is not satisfactory. Therefore, herein, we developed a multi-functional nanoparticle, HN@Cu-MOF, to enhance the efficacy of PDT. We combined chemical dynamic therapy (CDT) and nitric oxide (NO) therapy by initiating sensitization to PDT and cell apoptosis in the treatment of tumors. The Cu2+-doped MOF reacted with GSH to form Cu+, exhibiting a strong CDT ability to generate hydroxyl radicals (˙OH). The Cu-MOF was coated with HN, which is hyaluronic acid (HA) modified by a nitric oxide donor. HN can target tumor cells over-expressing the CD44 receptor and consume GSH in the cells to release NO. Both cell experiments and in vivo experiments showed an excellent tumor inhibitory effect upon the treatment. Overall, the HN@Cu-MOF nanoparticle-integrated NO gas therapy and CDT with PDT led to a significant enhancement in GSH consumption and a remarkable elevation in ROS production.

Switchable rotation of metal nanostructures in an intensity chirality-invariant focus field.

Light-induced rotation is a fundamental motion form that is of great significance for flexible and multifunctional manipulation modes. However, current optical rotation by a single optical field is mostly unidirectional, where switchable rotation manipulation is still challenging. To address this issue, we demonstrate a switchable rotation of non-spherical nanostructures within a single optical focus field. Interestingly, the intensity of the focus field is chiral invariant. The rotation switch is a result of the energy flux reversal in front and behind the focal plane. We quantitatively analyze the optical force exerted on a metal nanorod at different planes, as well as the surrounding energy flux. Our experimental results indicate that the direct switchover of rotational motion is achievable by adjusting the relative position of the nanostructure to the focal plane. This result enriches the basic motion mode of micro-manipulation and is expected to create potential opportunities in many application fields, such as biological cytology and optical micromachining.