A Methionine Allocation Nanoregulator for the Suppression of Cancer Stem Cells and Support to the Immune Cells by Epigenetic Regulation.

Epigenetic dysregulation is prevalent in human cancers, affecting gene expression and metabolic patterns to meet the demands of malignant evolution and abnormal epigenetic processes, and resulting in a protumor immune microenvironment. Tumors require a steady supply of methionine for maintaining epigenetic flexibility, which is the only exogenous precursor of methyl donor S-adenosylmethionine for methylation, crucial for their resistance to therapies and survival in a nutrient-deficient microenvironment. Thus, tumor cells upregulate the Lat4 transporter to compete and deprive methionine in the microenvironment, sustaining their malignant phenotypes and also impairing immune cell functions.

Convergent-beam attosecond x-ray crystallography.

Sub-ångström spatial resolution of electron density coupled with sub-femtosecond to few-femtosecond temporal resolution is required to directly observe the dynamics of the electronic structure of a molecule after photoinitiation or some other ultrafast perturbation, such as by soft X-rays. Meeting this challenge, pushing the field of quantum crystallography to attosecond timescales, would bring insights into how the electronic and nuclear degrees of freedom couple, enable the study of quantum coherences involved in molecular dynamics, and ultimately enable these dynamics to be controlled. Here, we propose to reach this realm by employing convergent-beam x-ray crystallography with high-power attosecond pulses from a hard-x-ray free-electron laser.

Metabolic Nanoregulators Induce Ferroptosis and Change Metabolite Flow to Reverse Immunosuppressive Tumor Microenvironment.

Aberrant energy and substance metabolic pathways of tumor cells critically support tumor cell proliferation by hijacking the resources from nonmalignant cells, thereby establishing a metabolite flow favorable to tumor progression. This metabolic adaptation of tumor cells further modulates the immune landscape, ultimately creating a tumor microenvironment characterized by drug resistance and immunosuppression. The synergistic regulation of energy and substance metabolic pathways might be a good antitumor therapeutic paradigm.

Fast and efficient hard X-ray projection imaging below 10 nm resolution.

High-resolution X-ray imaging of noncrystalline objects is often achieved through the approach of scanning coherent diffractive imaging known as ptychography. The imaging resolution is usually limited by the scattering properties of the sample, where weak diffraction signals at the highest scattering angles compete with parasitic scattering. Here, we demonstrate that X-ray multilayer Laue lenses with a high numerical aperture (NA) can be used to create a strong reference beam that holographically boosts weak scattering from the sample over a large range of scattering angles, enabling high-resolution imaging that is tolerant of such background.

Black phosphorus for bone regeneration: Mechanisms involved and influencing factors.

BP has shown good potential for promoting bone regeneration. However, the understanding of the mechanisms of BP-enhanced bone regeneration is still limited. This review first summarizes the recent advances in applications of BP in bone regeneration.

Intelligent micelles for on-demand drug delivery targeting extracellular matrix of pancreatic cancer.

As a key pathological feature of pancreatic ductal adenocarcinoma(PDAC), the dense extracellular matrix(ECM) limits the penetration of chemotherapy drugs and is involved in the formation of immunosuppressive microenvironment. Meanwhile, clinical practice has shown that the treatment strategy for ECM should consider its restriction of tumor cell metastasis, and the need for in-depth chemotherapy without destroying ECM is proposed. STAT3 inhibitors have been reported to regulate tumor microenvironment including interrupt the form of ECM.

X-ray focusing below 3 nm with aberration-corrected multilayer Laue lenses.

Multilayer Laue lenses are volume diffractive optical elements for hard X-rays with the potential to focus beams to sizes as small as 1 nm. This ability is limited by the precision of the manufacturing process, whereby systematic errors that arise during fabrication contribute to wavefront aberrations even after calibration of the deposition process based on wavefront metrology. Such aberrations can be compensated by using a phase plate.

EGC enhances tumor antigen presentation and CD8 T cell-mediated antitumor immunity via targeting oncoprotein SND1.

The Staphylococcal nuclease and Tudor domain containing 1 (SND1) has been identified as an oncoprotein. Our previous study demonstrated that SND1 impedes the major histocompatibility complex class I (MHC-I) assembly by hijacking the nascent heavy chain of MHC-I to endoplasmic reticulum-associated degradation. Herein, we aimed to identify inhibitors to block SND1-MHC-I binding, to facilitate the MHC-I presentation and tumor immunotherapy.

Reconciling the Cooperative-Competitive Patterns among Tumor and Immune Cells for Triple-Negative Breast Cancer Treatment Using Multimodule Nanocomplexes.

Targeting the competitive-cooperative relationships among tumor cells and various immune cells can efficiently reverse the immune-dysfunction microenvironment to boost the immunotherapies for the triple-negative breast cancer treatment. Hence, a bacterial outer membrane vesicle-based nanocomplex is designed for specifically targeting malignant cells and immune cells to reconcile the relationships based on metabolic-immune crosstalk. By uniquely utilizing the property of charge-reversal polymers to realize function separation, the nanocomplexes could synergistically regulate tumor cells and immune cells.

Novel 3D-printing bilayer GelMA-based hydrogel containing BP,-TCP and exosomes for cartilage-bone integrated repair.

The integrated repair of cartilage and bone involves the migration and differentiation of cells, which has always been a difficult problem to be solved. We utilize the natural biomaterial gelatin to construct gelatin methacryloyl (GelMA), a hydrogel scaffold with high cell affinity. GelMA is mixed with different components to print a bi-layer porous hydrogel scaffold with different modulus and composition in upper and lower layers through three-dimensional (3D) printing technology.

Gradient tumor microenvironment-promoted penetrating micelles for hypoxia relief and immunosuppression reversion in pancreatic cancer treatment.

The tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) is the main block for the penetration of chemotherapy. In the tumor microenvironment, a dense matrix composed of fibrin is formed on the exterior, while the interior is featured by high reduction, hypoxia and low pH. How to match the special microenvironment to on-demand drug release is the key to improve chemotherapeutic efficacy.

Imaging via Correlation of X-Ray Fluorescence Photons.

We demonstrate that x-ray fluorescence emission, which cannot maintain a stationary interference pattern, can be used to obtain images of structures by recording photon-photon correlations in the manner of the stellar intensity interferometry of Hanbury Brown and Twiss. This is achieved utilizing femtosecond-duration pulses of a hard x-ray free-electron laser to generate the emission in exposures comparable to the coherence time of the fluorescence. Iterative phasing of the photon correlation map generated a model-free real-space image of the structure of the emitters.

Nanomaterials with dual immunomodulatory functions for synergistic therapy of breast cancer brain metastases.

A long-standing paucity of effective therapies results in the poor outcomes of triple-negative breast cancer brain metastases. Immunotherapy has made progress in the treatment of tumors, but limited by the non-immunogenicity of tumors and strong immunosuppressive environment, patients with TNBC brain metastases have not yet benefited from immunotherapy. Dual immunoregulatory strategies with enhanced immune activation and reversal of the immunosuppressive microenvironment provide new therapeutic options for patients.

Robust ptychographic X-ray speckle tracking with multilayer Laue lenses.

In recent years, X-ray speckle tracking techniques have emerged as viable tools for wavefront metrology and sample imaging applications, and have been actively developed for use at synchrotron light sources. Speckle techniques can recover an image free of aberrations and can be used to measure wavefronts with a high angular sensitivity. Since they are compatible with low-coherence sources they can be also used with laboratory X-ray sources.

Microenvironment-tailored micelles restrain carcinoma-astrocyte crosstalk for brain metastasis.

Breast-to-brain metastatic cells can interact with the surrounding cells, including astrocytes and microglia, to generate a pro-tumorigenic niche. Breast-to-brain metastasis can be treated using a dual strategy of eliminating metastatic tumor cells and normalizing their localized microenvironment. The effective accumulation of drugs at the action site of metastasis is crucial to realizing the above strategy, especially when dealing with the blood-brain barrier (BBB)-penetrating and tumor-targeting tactics.

Smart hypoxia-responsive transformable and charge-reversible nanoparticles for the deep penetration and tumor microenvironment modulation of pancreatic cancer.

The compact extracellular matrix (ECM) of pancreatic ductal adenocarcinoma (PDAC) is the major physical barrier that hinders the delivery of anti-tumor drugs, leading to strong inherent chemotherapy resistance as well as establishing an immunosuppressive tumor microenvironment (TME). However, forcibly destroying the stroma barrier would break the balance of delicate signal transduction and dependence between tumor cells and matrix components. Uncontrollable growth and metastasis would occur, making PDAC more difficult to control.

The Ratio of NT-proBNP to CysC Predicts Heart Failure in Patients With Chronic Kidney Disease.

The N-terminal pro B type natriuretic peptide (NT-proBNP) is important for prognosis of heart failure in patients with chronic kidney disease (CKD). However, the NT-proBNP level is easily affected by renal insufficiency, which limits its clinical use. This study included 396 patients with CKD.

A Micro-Environment Regulator for Filling the Clinical Treatment Gap after a Glioblastoma Operation.

The rapid postoperative recurrence and short survival time of glioblastoma (GBM) patients necessitate immediate and effective postoperative treatment. Herein, an immediate and mild postoperative local treatment strategy is developed that regulates the postoperative microenvironment and delays GBM recurrence. Briefly, an injectable hydrogel system (imGEL) loaded with Zn(II) -AMD3100 (AMD-Zn) and CpG oligonucleotide nanoparticles (CpG NPs) is injected into the operation cavity, with long-term function to block the recruitment of microglia/ macrophages and activate cytotoxic T cells.

Macrophage-Disguised Manganese Dioxide Nanoparticles for Neuroprotection by Reducing Oxidative Stress and Modulating Inflammatory Microenvironment in Acute Ischemic Stroke.

Reperfusion injury is still a major challenge that impedes neuronal survival in ischemic stroke. However, the current clinical treatments are remained on single pathological process, which are due to lack of comprehensive neuroprotective effects. Herein, a macrophage-disguised honeycomb manganese dioxide (MnO ) nanosphere loaded with fingolimod (FTY) is developed to salvage the ischemic penumbra.

Sequentially Triggered Bacterial Outer Membrane Vesicles for Macrophage Metabolism Modulation and Tumor Metastasis Suppression.

Metabolic interactions between different cell types in the tumor microenvironment (TME) often result in reprogramming of the metabolism to be totally different from their normal physiological processes in order to support tumor growth. Many studies have attempted to inhibit tumor growth and activate tumor immunity by regulating the metabolism of tumors and other cells in TME. However, metabolic inhibitors often suffer from the heterogeneity of tumors, since the favorable metabolic regulation of malignant cells and other cells in TME is often inconsistent with each other.

Biomimetic Dendrimer-Peptide Conjugates for Early Multi-Target Therapy of Alzheimer's Disease by Inflammatory Microenvironment Modulation.

Current therapeutic strategies for Alzheimer's disease (AD) treatments mainly focus on β-amyloid (Aβ) targeting. However, such therapeutic strategies have limited clinical outcomes due to the chronic and irreversible impairment of the nervous system in the late stage of AD. Recently, inflammatory responses, manifested in oxidative stress and glial cell activation, have been reported as hallmarks in the early stages of AD.

Early-stage dynamics of chloride ion-pumping rhodopsin revealed by a femtosecond X-ray laser.

Chloride ion-pumping rhodopsin (ClR) in some marine bacteria utilizes light energy to actively transport Cl into cells. How the ClR initiates the transport is elusive. Here, we show the dynamics of ion transport observed with time-resolved serial femtosecond (fs) crystallography using the Linac Coherent Light Source.

Synchronous RNA conformational changes trigger ordered phase transitions in crystals.

Time-resolved studies of biomacromolecular crystals have been limited to systems involving only minute conformational changes within the same lattice. Ligand-induced changes greater than several angstroms, however, are likely to result in solid-solid phase transitions, which require a detailed understanding of the mechanistic interplay between conformational and lattice transitions. Here we report the synchronous behavior of the adenine riboswitch aptamer RNA in crystal during ligand-triggered isothermal phase transitions.

Ultrafast structural changes within a photosynthetic reaction centre.

Photosynthetic reaction centres harvest the energy content of sunlight by transporting electrons across an energy-transducing biological membrane. Here we use time-resolved serial femtosecond crystallography using an X-ray free-electron laser to observe light-induced structural changes in the photosynthetic reaction centre of Blastochloris viridis on a timescale of picoseconds. Structural perturbations first occur at the special pair of chlorophyll molecules of the photosynthetic reaction centre that are photo-oxidized by light.