Impact of changes in collagen construction and molecular state on integrin - binding properties.

The interaction between the integrin and collagen is important in cell adhesion and signaling. Collagen, as the main component of extracellular matrix, is a base material for tissue engineering constructs. In tissue engineering, the collagen structure and molecule state may be altered to varying degrees in the process of processing and utilizing, thereby affecting its biological properties. In this work, the impact of changes in collagen structure and molecular state on the binding properties of collagen to integrin α2ß1 and integrin specific cell adhesion were explored. The results showed that the molecular structure of collagen is destroyed under the influence of heating, freeze-grinding and irradiation, the triple helix integrity is reduced and molecular breaking degree is increased. The binding ability of collagen to integrin α2ß1 is increased with the increase of triple helix integrity and decays exponentially with the increase of molecular breaking degree. The collagen molecular state can also influences the binding ability of collagen to cellular receptor. The collagen fibrils binding to integrin α2ß1 and HT1080 cells is stronger than to collagen monomolecule. Meanwhile, the hybrid fibril exhibits a different cellular receptor binding performance from corresponding single species collagen fibril. These findings provide ideas for the design and development of new collagen-based biomaterials and tissue engineering research.

Establishment of a model to predict mortality after decompression craniotomy for traumatic brain injury.

BACKGROUND: The mortality rate of patients with traumatic brain injury (TBI) is still high even while undergoing decompressive craniectomy (DC), and the expensive treatment costs bring huge economic burden to the families of patients. OBJECTIVE: The aim of this study was to identify preoperative indicators that influence patient outcomes and to develop a risk model for predicting patient mortality by a retrospective analysis of TBI patients undergoing DC. METHODS: A total of 288 TBI patients treated with DC, admitted to the First Affiliated Hospital of Shantou University Medical School from August 2015 to April 2021, were used for univariate and multivariate logistic regression analysis to determine the risk factors for death after DC in TBI patients. We also built a risk model for the identified risk factors and conducted internal verification and model evaluation. RESULTS: Univariate and multivariate logistic regression analysis identified four risk factors: Glasgow Coma Scale, age, activated partial thrombin time, and mean CT value of the superior sagittal sinus. These risk factors can be obtained before DC. In addition, we also developed a 3-month mortality risk model and conducted a bootstrap 1000 resampling internal validation, with C-indices of 0.852 and 0.845, respectively. CONCLUSIONS: We developed a risk model that has clinical significance for the early identification of patients who will still die after DC. Interestingly, we also identified a new early risk factor for TBI patients after DC, that is, preoperative mean CT value of the superior sagittal sinus (p < .05).

Structural basis for phage-mediated activation and repression of bacterial DSR2 anti-phage defense system.

Silent information regulator 2 (Sir2) proteins typically catalyze NAD+-dependent protein deacetylation. The recently identified bacterial Sir2 domain-containing protein, defense-associated sirtuin 2 (DSR2), recognizes the phage tail tube and depletes NAD+ to abort phage propagation, which is counteracted by the phage-encoded DSR anti-defense 1 (DSAD1), but their molecular mechanisms remain unclear. Here, we determine cryo-EM structures of inactive DSR2 in its apo form, DSR2-DSAD1 and DSR2-DSAD1-NAD+, as well as active DSR2-tube and DSR2-tube-NAD+ complexes. DSR2 forms a tetramer with its C-terminal sensor domains (CTDs) in two distinct conformations: CTDclosed or CTDopen. Monomeric, rather than oligomeric, tail tube proteins preferentially bind to CTDclosed and activate Sir2 for NAD+ hydrolysis. DSAD1 binding to CTDopen allosterically inhibits tube binding and tube-mediated DSR2 activation. Our findings provide mechanistic insight into DSR2 assembly, tube-mediated DSR2 activation, and DSAD1-mediated inhibition and NAD+ substrate catalysis in bacterial DSR2 anti-phage defense systems.

Bioavailability and mechanisms of dietary polyphenols affected by non-thermal processing technology in fruits and vegetables.

Plant polyphenols play an essential role in human health. The bioactivity of polyphenols depends not only on their content but also on their bioavailability in food. The processing techniques, especially non-thermal processing, improve the retention and bioavailability of polyphenolic substances. However, there are limited studies summarizing the relationship between non-thermal processing, the bioavailability of polyphenols, and potential mechanisms. This review aims to summarize the effects of non-thermal processing techniques on the content and bioavailability of polyphenols in fruits and vegetables. Importantly, the disruption of cell walls and membranes, the inhibition of enzyme activities, free radical reactions, plant stress responses, and interactions of polyphenols with the food matrix caused by non-thermal processing are described. This study aims to enhance understanding of the significance of non-thermal processing technology in preserving the nutritional properties of dietary polyphenols in plant-based foods. It also offers theoretical support for the contribution of non-thermal processing technology in improving food nutrition.

[Research progress of haematopoietic stem cells to generate immune cells and its application].

Hematopoietic stem cells (HSCs) posses the potential for highly self-renewal, proliferation and multi-lineage differentiation. HSC transplantation has long been the primary method for treating hematologic disorders and autoimmune diseases, and the ability to rebuild the immune system after transplantation is a key indicator of success. To enhance the reconstruction ability of the immune system after transplantation, current research focuses on genetic engineering and the use of HSCs modified by clustered regularly interspaced short palindromic repeats (CRISPR) gene editing technology as a source of transplant cells. This article summaries the biological characteristics, regulatory mechanism, ability to differentiate into immune cells, as well as the application and advance in the treatment of blood disorders, immune deficiencies, cancers and other related diseases, aiming to provide references for the research on relevant diseases.

Mechanisms of chondrocyte regulated cell death in osteoarthritis: Focus on ROS-triggered ferroptosis, parthanatos, and oxeiptosis.

Osteoarthritis (OA) is a common chronic inflammatory degenerative disease. Since chondrocytes are the only type of cells in cartilage, their survival is critical for maintaining cartilage morphology. This review offers a comprehensive analysis of how reactive oxygen species (ROS), including superoxide anions, hydrogen peroxide, hydroxyl radicals, nitric oxide, and their derivatives, affect cartilage homeostasis and trigger several novel modes of regulated cell death, including ferroptosis, parthanatos, and oxeiptosis, which may play roles in chondrocyte death and OA development. Moreover, we discuss potential therapeutic strategies to alleviate OA by scavenging ROS and provide new insight into the research and treatment of the role of regulated cell death in OA.

A versatile engineered extracellular vesicle platform simultaneously targeting and eliminating senescent stromal cells and tumor cells to promote tumor regression.

Chemotherapy is an important therapeutic approach for malignant tumors for it triggers apoptosis of cancer cells. However, chemotherapy also induces senescence of stromal cells in the tumor microenvironment to promote tumor progression. Strategies aimed at killing tumor cells while simultaneously eliminating senescent stromal cells represent an effective approach to cancer treatment. Here, we developed an engineered Src-siRNA delivery system based on small extracellular vesicles (sEVs) to simultaneously eliminate senescent stromal cells and tumor cells for cancer therapy. The DSPE-PEG-modified urokinase plasminogen activator (uPA) peptide was anchored to the membranes of induced mesenchymal stem cell-derived sEVs (uPA-sEVs), and Src siRNA was loaded into the uPA-sEVs by electroporation (uPA-sEVs-siSrc). The engineered uPA-sEVs-siSrc retained the basic sEVs properties and protected against siSrc degradation. uPA peptide modification enhanced the sEVs with the ability to simultaneously target doxorubicin-induced senescent stromal cells and tumor cells. Src silencing by uPA-sEVs-siSrc induced apoptosis of both senescent stromal cells and tumor cells. The uPA-sEVs-siSrc displayed preferential tumor accumulation and effectively inhibited tumor growth in a tumor xenograft model. Furthermore, uPA-sEVs-siSrc in combination with doxorubicin significantly reduced the senescence burden and enhanced the therapeutic efficacy of chemotherapy. Taken together, uPA-sEVs-siSrc may serve as a promising therapy to kill two birds with one stone, not only killing tumor cells to achieve remarkable antitumor effect, but also eliminating senescent cells to enhance the efficacy of chemotherapeutic agent in tumor regression.

Nanomedicine targeted anti-inflammatory therapy to deal with the 'crux' of rheumatoid arthritis.

Rheumatoid arthritis is a chronic and complex autoimmune disease that is marked by an inflammatory response, synovial hyperplasia, vascularisation, fascial formation, cartilage and bone destruction, which can lead to joint deformity and even loss of function, ultimately affecting a person's health and quality of life. Although the pathogenesis of RA is unclear, growing evidence suggests that inflammation-associated cells infiltrate joints, causing tissue damage, inflammation and pain. This disruption in the balance between host tolerance and immune homeostasis the progression of RA. Existing drug therapy and surgical treatments for RA are unable to completely cure the disease or reverse its accelerated progression. Therefore, the design and development of an appropriate and effective drug delivery system will substantially improve the therapeutic effect. In this review, by describing the inflammatory microenvironment of rheumatoid arthritis and the associated inflammatory cells, the progress of targeting strategies and applications of nanotechnology in the disease is summarised, which will be helpful in providing new ideas for the subsequent treatment of rheumatoid arthritis.

Effect of estradiol after bacterial infection on the Wnt/ß-catenin pathway in bovine endometrium epithelial cells and organoids.

Endometritis is a disease caused by a postpartum bacterial infection with a poor prognosis that primarily affects dairy cows. Three-dimensional organoids have been used as a model for endometritis, because they exhibit a structure comparable to that of the endometrium, demonstrating both expansibility and hormone responsiveness. These characteristics render them an ideal platform for in vitro investigations of endometrial diseases. Estradiol (E2) is an endogenous steroid hormone with demonstrated anti-inflammatory properties, and the objective of this study was to determine the mechanism by which E2 modulates the inflammatory response and the Wnt signal transduction pathway in bovine endometrial epithelial cells and organoids following E. coli infection. We present the techniques for isolating and culturing primary bovine endometrial epithelial cells (BEECs), and producing endometrial organoids. For the experiments, the endometrial epithelial cells and organoids were infected with E. coli for 1 h, followed by incubation with E2 for 12 h. The mRNA and protein expressions of the inflammation-related genes, IL-1ß, IL-6, TLR4, and NF-κB, as well as the Wnt pathway-related genes, Wnt4, ß-catenin, c-Myc, and CyclinD1, were assessed using real-time quantitative-PCR and western blotting, respectively. The CCK8 viable cell counting assay was utilized to determine the optimal concentration of the Wnt inhibitor, IWR-1. The mRNA and protein expression of Wnt pathway-related genes was assessed following IWR-1 treatment, while the expression levels of proliferation-associated genes (Ki67, PCNA) and barrier repair genes (occludin, claudin, and Zo-1) in BEECs and organoids were evaluated after E2 treatment. The results of this study show that mRNA expression of the inflammatory genes, IL-1ß, TLR4, and NF-κB (P < 0.05) decreased in BEECs following E2 treatment compared to the E. coli group. The protein expression of the IL-1ß, IL-6, TLR4 and NF-κB genes was also inhibited (P < 0.05). Similar results were observed in tests on the organoids. Our findings demonstrate that E2 significantly upregulates the expression of Wnt-related genes, including ß-catenin and c-Myc, while concurrently downregulating the expression of GSK3ß (P < 0.05). Next, we treated E. coli-infected BEECs and organoids with the Wnt inhibitor, IWR-1. Compared with E. coli and E. coli + E2, the expression of mRNA and protein from Wnt 4, ß-catenin, and CyclinD1 in E. coli + E2 and E. coli + IWR-1 was down-regulated (P < 0.05). The expression of the proliferation genes, Ki67, PCNA, and the tight junction genes, occludin, claudin1, and Zo-1, in organoids was significantly higher than that in BEECs (P < 0.05). In summary, we found strong potential for E2 mitigation of the E. coli-induced inflammatory response in BEECs and organoids, through activation of the Wnt pathway. In addition, the proliferation and repair capacity of organoids was much higher than that of BEECs.

Nano-medicine therapy reprogramming metabolic network of tumour microenvironment: new opportunity for cancer therapies.

Metabolic heterogeneity is one of the characteristics of tumour cells. In order to adapt to the tumour microenvironment of hypoxia, acidity and nutritional deficiency, tumour cells have undergone extensive metabolic reprogramming. Metabolites involved in tumour cell metabolism are also very different from normal cells, such as a large number of lactate and adenosine. Metabolites play an important role in regulating the whole tumour microenvironment. Taking metabolites as the target, it aims to change the metabolic pattern of tumour cells again, destroy the energy balance it maintains, activate the immune system, and finally kill tumour cells. In this paper, the regulatory effects of metabolites such as lactate, glutamine, arginine, tryptophan, fatty acids and adenosine were reviewed, and the related targeting strategies of nano-medicines were summarised, and the future therapeutic strategies of nano-drugs were discussed. The abnormality of tumour metabolites caused by tumour metabolic remodelling not only changes the energy and material supply of tumour, but also participates in the regulation of tumour-related signal pathways, which plays an important role in the survival, proliferation, invasion and metastasis of tumour cells. Regulating the availability of local metabolites is a new aspect that affects tumour progress. (The graphical abstract is by Figdraw).

Metabolic heterogeneity is one of the important characteristics of tumour cells, and the metabolites of tumour cells are very different from those of normal cells.Lactate, fatty acids, glutamine, arginine, tryptophan and adenosine are all important metabolites in tumour metabolism.Nano-medicines are used to regulate tumour metabolites, affecting the energy and material supply of tumour cells, thus achieving therapeutic effects.

Retinitis after haematopoietic stem cell transplantation with multiple intraocular viral infections (cytomegalovirus, Epstein‒Barr virus and herpes simplex virus)- a case report.

BACKGROUND: To report a case of retinitis with multiple intraocular viral infections after second haematopoietic stem cell transplantation. CASE PRESENTATION: A 39-year-old female patient developed retinitis after a second haematopoietic stem cell transplant. Right eye was tested for three viral infections- cytomegalovirus, Epstein‒Barr virus and herpes simplex virus, while left was infected with cytomegalovirus. The patient was subsequently treated with vitreous cavity ganciclovir injections, and 1 week later both eyes tested negative for aqueous humour viruses. DISCUSSION AND CONCLUSION: CMV, EBV and HSV belong to the herpes virus family. They are all commonly observed in the body and represent opportunity infectious viruses. The retinitis they cause have different characteristics. But simultaneous infection of the eye by multiple viruses is quite rare. In this case, three viruses were detected in the patient's eye, but whether the retina was caused by all three viruses at the same time could not be determined. A satisfactory outcome was achieved after treatment with vitreous cavity ganciclovir injection.

Correction: Critical role of hydrogen bonding between microcrystalline cellulose and g-C3N4 enables highly efficient photocatalysis.

Correction for 'Critical role of hydrogen bonding between microcrystalline cellulose and g-C3N4 enables highly efficient photocatalysis' by Zhaoqiang Wang et al., Chem. Commun., 2024, 60, 204-207, https://doi.org/10.1039/D3CC04800D.

Truncated FRMD7 proteins in congenital Nystagmus: novel frameshift mutations and proteasomal pathway implications.

Idiopathic congenital nystagmus (ICN) manifests as involuntary and periodic eye movements. To identify the genetic defect associated with X-linked ICN, Whole Exome Sequencing (WES) was conducted in two affected families. We identified two frameshift mutations in FRMD7, c.1492dupT/p.(Y498Lfs*15) and c.1616delG/p.(R539Kfs*2). Plasmids harboring the mutated genes and qPCR analysis revealed mRNA stability, evading degradation via the NMD pathway, and corroborated truncated protein production via Western-blot analysis. Notably, both truncated proteins were degraded through the proteasomal (ubiquitination) pathway, suggesting potential therapeutic avenues targeting this pathway for similar mutations. Moreover, we conducted a comprehensive analysis, summarizing 140 mutations within the FRMD7 gene. Our findings highlight the FERM and FA structural domains as mutation-prone regions. Interestingly, exons 9 and 12 are the most mutated regions, but 90% (28/31) mutations in exon 9 are missense while 84% (21/25) mutations in exon 12 are frameshift. A predominant occurrence of shift code mutations was observed in exons 11 and 12, possibly associated with the localization of premature termination codons (PTCs), leading to the generation of deleterious truncated proteins. Additionally, our conjecture suggests that the loss of FRMD7 protein function might not solely drive pathology; rather, the emergence of aberrant protein function could be pivotal in nystagmus etiology. We propose a dependence of FRMD7 protein normal function primarily on its anterior domain. Future investigations are warranted to validate this hypothesis.

Ultrahigh pressure field: A friendly pathway for regulating the cellular adhesion and migration capacity of collagen.

Customized control of the biological response between the material matrix and cells is a crucial aspect in the development of the next generation of collagen materials. This study aims to investigate the effects of ultrahigh pressure treatment on the interaction between collagen and cells by subjecting bovine tendon collagen to different intensities of ultrahigh pressure field. The results indicate that ultrahigh pressure treatment alters the spatial folding of collagen, causing distortion of its triple helical conformation and exposing more free amino groups and hydrophobic regions. As a result, collagen's cell adhesion capability and ability to promote cell migration are significantly enhanced. Optimal cell adhesion and migration capabilities are observed in collagen samples treated at 500 MPa for 15 min. However, further increasing the intensity of the ultrahigh pressure treatment leads to severe damage to the triple-helical structure of collagen, along with re-aggregation of free amino groups and hydrophobic moieties, thereby reducing collagen's cell adhesion capability and ability to promote cell migration. Therefore, ultrahigh pressure treatment offers a promising method to effectively regulate collagen-cell adhesion and promote cell migration without the need for external components. This provides a potential means for the customized enhancement of collagen-based material interfaces.

Target ssDNA activates the NADase activity of prokaryotic SPARTA immune system.

Argonaute proteins (Agos), which use small RNAs or DNAs as guides to recognize complementary nucleic acid targets, mediate RNA silencing in eukaryotes. In prokaryotes, Agos are involved in immunity: the short prokaryotic Ago/TIR-APAZ (SPARTA) immune system triggers cell death by degrading NAD+ in response to invading plasmids, but its molecular mechanisms remain unknown. Here we used cryo-electron microscopy to determine the structures of inactive monomeric and active tetrameric Crenotalea thermophila SPARTA complexes, revealing mechanisms underlying SPARTA assembly, RNA-guided recognition of target single-stranded DNA (ssDNA) and subsequent SPARTA tetramerization, as well as tetramerization-dependent NADase activation. The small RNA guides Ago to recognize its ssDNA target, inducing SPARTA tetramerization via both Ago- and TIR-mediated interactions and resulting in a two-stranded, parallel, head-to-tail TIR rearrangement primed for NAD+ hydrolysis. Our findings thus identify the molecular basis for target ssDNA-mediated SPARTA activation, which will facilitate the development of SPARTA-based biotechnological tools.

Nanotip-Induced Electric Field for Hydrogen Catalysis.

Local electric field induced by the lightning-rod effect attracts great attention for regulating the local microenvironment and electronic properties of active sites. Nevertheless, local electric-field-assisted applications are mainly limited to metals with strong surface plasmonic resonance properties (e.g., Au, Ag, and Cu). Herein, we fabricate RuCu snow-like nanosheets (SNSs) with high-curvature nanotips for enhancing the hydrogen oxidation reaction (HOR) and hydrogen evolution reaction (HER). Theoretical simulations show that RuCu SNSs can induce a strong local electric field around the sharp nanotips, which favors the accumulation of OH- for HOR and H+ for HER. Cu incorporation can modulate the binding strength of OH* and H*, leading to significantly enhanced HOR and HER performance. Impressively, the mass activity of RuCu SNSs for alkaline HOR is 31.3 times higher than that of RuCu nanocrystals without sharp tips. Besides, the required overpotential for reaching 10 mA cm-2 during HER over RuCu SNSs is 14.0 mV.

Critical role of hydrogen bonding between microcrystalline cellulose and g-C3N4 enables highly efficient photocatalysis.

Developing a highly efficient photocatalyst for energy and environmental applications is urgently required. Herein, graphitic carbon nitride (CN) coupled with microcrystalline cellulose (MCC) (denoted as MCC-X/CN) shows excellent photocatalytic performance for tetracycline (TC) degradation and H2 evolution. And the optimized MCC-0.05/CN shows an improved TC degradation rate (Kapp = 0.019 min-1) and H2 evolution rate (642.71 µmol g-1 h-1), which are 1.9 and 22 times higher than those of pure CN, respectively. This improvement primarily results from hydrogen bonding (H-bonding) between CN and MCC, which enables excellent charge separation and migration, leading to the outstanding photoelectrochemical properties of MCC-0.05/CN.

High-security three-dimensional optical transmission mechanism utilizing time-frequency-space interleaving disruption.

In this paper, we propose a high-security three-dimensional optical transmission system utilizing time-frequency-space interleaving chaos, which simultaneously enhances the reliability and security of the system. The four-wing 3D chaos model encrypts the time-frequency space interleaved modulation domain of a orthogonal time-frequency space (OTFS) modulation signal and the modulated phase information simultaneously, improving the system's security. We also experimentally validate the proposed high-security 3D-OTFS method, utilizing the hexadecimal modulation technique. The modulated OTFS signal achieves a transmission rate of 34.1 Gb/s over a 2-km seven-core fiber link, with the OTFS signal exhibiting a maximum of 1.31 dB receiver sensitivity gain compared to orthogonal frequency division multiplexing (OFDM) signals under the forward error correction threshold of the bit error rate. The achieved keyspace is equal to 5 × 1048. The findings demonstrate that the proposed high-security three-dimensional optical transmission mechanism, based on time-frequency-space interleaved disruption, exhibits excellent anti-interference ability and confidentiality performance. Consequently, it holds promising prospects for future applications in optical communications.

Tumor Microenvironment Sequential Drug/Gene Delivery Nanosystem for Realizing Multistage Boosting of Cancer-Immunity Cycle on Cancer Immunotherapy.

The antitumor immune response of cancer immunotherapy is a cascade of cancer-immunity cycles (CIC). The immunosuppression of the tumor microenvironment and low immunogenicity of tumor cells, insufficient T lymphocyte activation, trafficking, and infiltration caused the failure to initiate and run the continuous multistage CIC, leading to unsatisfactory cancer immunotherapy outcomes. A doxorubicin/interleukin-12 plasmid DNA/celecoxib (DOX/pIL-12/CXB) combination strategy was designed by targeting the cascade CIC. Then, an intratumoral CXB-detachable nanosystem, or DOX/PAC/pIL-12 micelleplexes, was developed for sequential drug/gene delivery to facilitate the multistage boosting of CIC on synergistic cancer immunotherapy. The DOX/PAC/pIL-12 micelleplexes could program intratumorally sequential release of CXB to remodulate the tumor microenvironment immunosuppression by suppressing the cyclooxygenase-2/prostaglandin E2 (COX-2/PGE2) pathway. The smaller sizes and surface charge-switched micelleplexes facilitated the codelivery and corelease of DOX and pIL-12 inside 4T1 tumor cells. These micelleplexes exerted a synergistic antitumor immune response using CIC cascade activation and amplification, providing therapeutic antitumor and antimetastasis efficacy. The drug/gene sequential delivery nanosystem provides a complete CIC-boosted combinatory strategy for developing immunotherapy against cancer.

Recent advancements in nanomedicine based lipid metabolism for tumour immunotherapy.

Therapy on lipid metabolism is emerging as a groundbreaking cancer treatment, offering the unprecedented opportunity to effectively treat and in several cases. Tumorigenesis is inextricably linked to lipid metabolism. In this regard, the features of lipid metabolism include lipid synthesis, decomposition, metabolism and lipid storage and mobilisation from intracellular lipid droplets. Most importantly, the regulation of lipid metabolism is central to the appropriate immune response of tumour cells, and ultimately to exert the immune efforts to realise the perspective of many anti-tumour effects. Different cancers and immune cells have different dependence on lipid metabolism, playing a pivotal role in differentiation and function of immune cells. However, what lies before the immunotherapy targeting lipid metabolism is side effects of systemic toxicity and defects of individual drugs, which strongly highlights that nanodelivery strategy is a magnet for it to enhance drug efficiency, reduce drug toxicity and improve application deficiencies. This review will first focus on emerging research progress of lipid metabolic reprogramming mechanism, and then explore the complex role of lipid metabolism in the tumour cells including the effect on immune cells and their nano-preparations of monotherapy and multiple therapies used in combination, in a shift away from conventional cancer research.HighlightsThe regulation of lipid metabolism is central to the appropriate immune response of tumour cells, and ultimately to exert the immune efforts to realise the perspective of many anti-tumour effects.Preparations of focusing lipid metabolism have side effects of systemic toxicity and defects of individual drugs. It strongly highlights that nanodelivery strategy is a magnet for it to enhance drug efficiency, reduce drug toxicity and improve application deficiencies.This review will first focus on emerging research progress of lipid metabolic reprogramming mechanism, and then explore the complex role of lipid metabolism in the tumour cells including the effect on immune cells as well as their nano-preparations of monotherapy and multiple therapies used in combination, in a shift away from conventional cancer research.