The potential role of CMC1 as an immunometabolic checkpoint in T cell immunity.

T cell immunity is critical for human defensive immune response. Exploring the key molecules during the process provides new targets for T cell-based immunotherapies. CMC1 is a mitochondrial electron transport chain (ETC) complex IV chaperon protein. By establishing in-vitro cell culture system and Cmc1 gene knock out mice, we evaluated the role of CMC1 in T cell activation and differentiation. The B16-OVA tumor model was used to test the possibility of targeting CMC1 for improving T cell anti-tumor immunity. We identified CMC1 as a positive regulator in CD8+T cells activation and terminal differentiation. Meanwhile, we found that CMC1 increasingly expressed in exhausted T (Tex) cells. Genetic lost of Cmc1 inhibits the development of CD8+T cell exhaustion in mice. Instead, deletion of Cmc1 in T cells prompts cells to differentiate into metabolically and functionally quiescent cells with increased memory-like features and tolerance to cell death upon repetitive or prolonged T cell receptor (TCR) stimulation. Further, the in-vitro mechanistic study revealed that environmental lactate enhances CMC1 expression by inducing USP7, mediated stabilization and de-ubiquitination of CMC1 protein, in which a mechanism we propose here that the lactate-enriched tumor microenvironment (TME) drives CD8+TILs dysfunction through CMC1 regulatory effects on T cells. Taken together, our study unraveled the novel role of CMC1 as a T cell regulator and its possibility to be utilized for anti-tumor immunotherapy.

Graphene-integrated mesh electronics with converged multifunctionality for tracking multimodal excitation-contraction dynamics in cardiac microtissues.

Cardiac microtissues provide a promising platform for disease modeling and developmental studies, which require the close monitoring of the multimodal excitation-contraction dynamics. However, no existing assessing tool can track these multimodal dynamics across the live tissue. We develop a tissue-like mesh bioelectronic system to track these multimodal dynamics. The mesh system has tissue-level softness and cell-level dimensions to enable stable embedment in the tissue. It is integrated with an array of graphene sensors, which uniquely converges both bioelectrical and biomechanical sensing functionalities in one device. The system achieves stable tracking of the excitation-contraction dynamics across the tissue and throughout the developmental process, offering comprehensive assessments for tissue maturation, drug effects, and disease modeling. It holds the promise to provide more accurate quantification of the functional, developmental, and pathophysiological states in cardiac tissues, creating an instrumental tool for improving tissue engineering and studies.

Patterning ganglionic eminences in developing human brain organoids using a morphogen-gradient-inducing device.

In early neurodevelopment, the central nervous system is established through the coordination of various neural organizers directing tissue patterning and cell differentiation. Better recapitulation of morphogen gradient production and signaling will be crucial for establishing improved developmental models of the brain in vitro. Here, we developed a method by assembling polydimethylsiloxane devices capable of generating a sustained chemical gradient to produce patterned brain organoids, which we termed morphogen-gradient-induced brain organoids (MIBOs). At 3.5 weeks, MIBOs replicated dorsal-ventral patterning observed in the ganglionic eminences (GE). Analysis of mature MIBOs through single-cell RNA sequencing revealed distinct dorsal GE-derived CALB2+ interneurons, medium spiny neurons, and medial GE-derived cell types. Finally, we demonstrate long-term culturing capabilities with MIBOs maintaining stable neural activity in cultures grown up to 5.5 months. MIBOs demonstrate a versatile approach for generating spatially patterned brain organoids for embryonic development and disease modeling.

Broccoli Improves Lipid Metabolism and Intestinal Flora in Mice with Type 2 Diabetes Induced by HFD and STZ Diet.

Globally, type 2 diabetes (T2DM) is on the rise. Maintaining a healthy diet is crucial for both treating and preventing T2DM.As a common vegetable in daily diet, broccoli has antioxidant, anti-inflammatory and anticarcoma physiological activities. We developed a mouse model of type 2 diabetes and carried out a systematic investigation to clarify the function of broccoli in reducing T2DM symptoms and controlling intestinal flora. The findings demonstrated that broccoli could successfully lower fasting blood glucose (FBG), lessen insulin resistance, regulate lipid metabolism, lower the levels of TC, TG, LDL-C, and MDA, stop the expression of IL-1ß and IL-6, and decrease the harm that diabetes causes to the pancreas, liver, fat, and other organs and tissues. Furthermore, broccoli altered the intestinal flora's makeup in mice with T2DM. At the genus level, the relative abundance of Allobaculum decreased, and that of Odoribacter and Oscillospira increased; At the family level, the relative abundances of Odoribacteraceae, Rikenellaceae and S24-7 decreased, while the relative abundances of Erysipelotrichaceae and Rikenellaceae increased.

Directional Cell Migration Guided by a Strain Gradient.

Strain gradients widely exist in development and physiological activities. The directional movement of cells is essential for proper cell localization, and directional cell migration in responses to gradients of chemicals, rigidity, density, and topography of extracellular matrices have been well-established. However; it is unclear whether strain gradients imposed on cells are sufficient to drive directional cell migration. In this work, a programmable uniaxial cell stretch device is developed that creates controllable strain gradients without changing substrate stiffness or ligand distributions. It is demonstrated that over 60% of the single rat embryonic fibroblasts migrate toward the lower strain side in static and the 0.1 Hz cyclic stretch conditions at ≈4% per mm strain gradients. It is confirmed that such responses are distinct from durotaxis or haptotaxis. Focal adhesion analysis confirms higher rates of contact area and protrusion formation on the lower strain side of the cell. A 2D extended motor-clutch model is developed to demonstrate that the strain-introduced traction force determines integrin fibronectin pairs' catch-release dynamics, which drives such directional migration. Together, these results establish strain gradient as a novel cue to regulate directional cell migration and may provide new insights in development and tissue repairs.

Superoxide Anion-Mediated Afterglow Mechanism-Based Water-Soluble Zwitterion Dye Achieving Renal-Failure Mice Detection.

Afterglow materials-based biological imaging has promising application prospects, due to negligible background. However, currently available afterglow materials mainly include inorganic materials as well as some organic nanoparticles, which are difficult to translate to the clinic, resulting from non-negligible metabolic toxicity and even leakage risk of inorganic heavy metals. Although building small organic molecules could solve such obstacles, organic small molecules with afterglow ability are extremely scarce, especially with a sufficient renal metabolic capacity. To address these issues, herein, we designed water-soluble zwitterion Cy5-NF with renal metabolic capacity and afterglow luminescence, which relied on an intramolecular cascade reaction between superoxide anion (O2•-, instead of 1O2) and Cy5-NF to release afterglow luminescence. Of note, compared with different reference contrast agents, zwitterion Cy5-NF not only had excellent afterglow properties but also had a rapid renal metabolism rate (half-life period, t1/2, around 10 min) and good biocompatibility. Unlike prior afterglow nanosystems possessing a large size, for the first time, zwitterion Cy5-NF has achieved the construction of water-soluble renal metabolic afterglow contrast agents, which showed higher sensitivity and signal-to-background ratio in afterglow imaging than fluorescence imaging for the kidney. Moreover, zwitterion Cy5-NF had a longer kidney retention time in renal-failure mice (t1/2 more than 15 min). More importantly, zwitterion Cy5-NF can be metabolized very quickly even in severe renal-failure mice (t1/2 around 25-30 min), which greatly improved biosecurity. Therefore, we are optimistic that the O2•--mediated afterglow mechanism-based water-soluble zwitterion Cy5-NF is very promising for clinical application, especially rapid detection of kidney failure.

Imaging and detecting intercellular tensile forces in spheroids and embryoid bodies using lipid-modified DNA probes.

Cells continuously experience and respond to different physical forces that are used to regulate their physiology and functions. Our ability to measure these mechanical cues is essential for understanding the bases of various mechanosensing and mechanotransduction processes. While multiple strategies have been developed to study mechanical forces within two-dimensional (2D) cell culture monolayers, the force measurement at cell-cell junctions in real three-dimensional (3D) cell models is still pretty rare. Considering that in real biological systems, cells are exposed to forces from 3D directions, measuring these molecular forces in their native environment is thus highly critical for the better understanding of different development and disease processes. We have recently developed a type of DNA-based molecular probe for measuring intercellular tensile forces in 2D cell models. Herein, we will report the further development and first-time usage of these molecular tension probes to visualize and detect mechanical forces within 3D spheroids and embryoid bodies (EBs). These probes can spontaneously anchor onto live cell membranes via the attached lipid moieties. By varying the concentrations of these DNA probes and their incubation time, we have first characterized the kinetics and efficiency of probe penetration and loading onto tumor spheroids and stem cell EBs of different sizes. After optimization, we have further imaged and measured E-cadherin-mediated forces in these 3D spheroids and EBs for the first time. Our results indicated that these DNA-based molecular tension probes can be used to study the spatiotemporal distributions of target mechanotransduction processes. These powerful imaging tools may be potentially applied to fill the gap between ongoing research of biomechanics in 2D systems and that in real 3D cell complexes.

Study on the hypolipidemic activity of rapeseed protein-derived peptides.

Hyperlipidaemia, a common chronic disease, is the cause of cardiovascular diseases such as myocardial infarction and atherosclerosis. Generally, drugs for lowering blood lipids have disadvantages such as short or poor efficacy, high toxicity, and side effects. Rapeseed active peptides are excellent substitutes for lipid-lowering drugs because of their high biological safety, strong penetration, and easy absorption by the human body. This study separated and purified the rapeseed peptides using gel chromatography and mass spectrometry. Rapeseed peptides amino acid sequences were determined to obtain Glu-Phe-Leu-Glu-Leu-Leu (EFLELL) peptides with good hypolipidaemic activity and IC50 values of 0.1973 ± 0.05 mM (sodium taurocholate), 0.375 ± 0.03 mM (sodium cholate), and 0.203 ± 0.06 mM (sodium glycine cholate). The EFLELL hypolipidaemic activity was evaluated, and its mechanism of action was investigated using cell lines. Rapeseed peptide treatment significantly decreased the total cholesterol (T-CHO), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels, and the protein and gene expression levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) and low-density lipoprotein cholesterol (LDLR) suggested the mechanism. Molecular docking revealed that the binding energy between rapeseed peptide and LDLR-PCSK9 molecules was -6.3 kcal/mol and -8.1 kcal/mol. In conclusion, the rapeseed peptide EFLELL exerts a favourable hypolipidaemic effect by modulating the LDLR-PCSK9 signalling pathway.

Co-encapsulation of rutinoside and ß-carotene in liposomes modified by rhamnolipid: Antioxidant activity, antibacterial activity, storage stability, and in vitro gastrointestinal digestion.

The surfactant rhamnolipid (RL) was used to modify the liposomes. ß-carotene (ßC) and rutinoside (Rts) were utilized to generate co-encapsulated liposomes through an ethanol injection method that used both hydrophilic and hydrophobic cavities to fabricate a novel cholesterol-free composite delivery system. The RL complex-liposomes loaded with ßC and Rts (RL-ßC-Rts) showed higher loading efficiency and good physicochemical properties (size = 167.48 nm, zeta-potential = -5.71 mV, and polydispersity index = 0.23). Compared with other samples, the RL-ßC-Rts showed better antioxidant activities and antibacterial ability. Moreover, dependable stability was uncovered in RL-ßC-Rts with still 85.2% of ßC storage from nanoliposome after 30 days at 4°C. Furthermore, in simulated gastrointestinal digestion, ßC exhibited good release kinetic properties. The present study demonstrated that liposomes constructed from RLs offer a promising avenue for the design of multicomponent nutrient delivery systems using both hydrophilic.

Space-Confined Metal Ion Strategy for Carbon Materials Derived from Cobalt Benzimidazole Frameworks with High Desalination Performance in Simulated Seawater.

Various metal ions with different valence states (Mg2+ , Al3+ , Ca2+ , Ti4+ , Mn2+ , Fe3+ , Ni2+ , Zn2+ , Pb2+ , Ba2+ , Ce4+ ) are successfully confined in quasi-microcube shaped cobalt benzimidazole frameworks using a space-confined synthesis strategy. More importantly, a series of derived carbon materials that confine metal ions are obtained by high-temperature pyrolysis. Interestingly, the derived carbon materials exhibited electric double-layer and pseudocapacitance properties because of the presence of metal ions with various valence states. Moreover, the presence of additional metal ions within carbon materials may create new phases, which can accelerate Na+ insertion/extraction and thus increase electrochemical adsorption. Density functional theory results showed that carbon materials in which Ti ions are confined exhibit enhanced insertion/extraction of Na+ resulting from the presence of the characteristic anatase crystalline phases of TiO2 . The Ti-containing materials have an impressive desalination capacity (62.8 mg g-1 ) in capacitive deionization (CDI) applications with high cycling stability. This work provides a facile synthetic strategy for the confinement of metal ions in metal-organic frameworks and thus supports the further development of derived carbon materials for seawater desalination by CDI.

Design of Uniform Hollow Carbon Nanoarchitectures: Different Capacitive Deionization between the Hollow Shell Thickness and Cavity Size.

Carbon-based materials with high capacitance ability and fast electrosorption rate are ideal electrode materials in capacitive deionization (CDI). However, traditional carbon materials have structural limitations in electrochemical and desalination performance due to the low capacitance and poor transmission channel of the prepared electrodes. Therefore, reasonable design of electrode material structure is of great importance for achieving excellent CDI properties. Here, uniform hollow carbon materials with different morphologies (hollow carbon nanospheres, hollow carbon nanorods, hollow carbon nano-pseudoboxes, hollow carbon nano-ellipsoids, hollow carbon nano-capsules, and hollow carbon nano-peanuts) are reasonably designed through multi-step template method and calcination of polymer precursors. Hollow carbon nanospheres and hollow carbon nano-pseudoboxes exhibit better capacitance and higher salt adsorption capacity (SAC) due to their stable carbonaceous structure during calcination. Moreover, the effects of the thickness of the shell and the size of the cavity on the CDI performance are also studied. HCNSs-0.8 with thicker shell (≈20 nm) and larger cavity (≈320 nm) shows the best SAC value of 23.01 mg g-1 due to its large specific surface area (1083.20 m2  g-1 ) and rich pore size distribution. These uniform hollow carbon nanoarchitectures with functional properties have potential applications in electrochemistry related fields.

A deficient MIF-CD74 signaling pathway may play an important role in immunotherapy-induced hyper-progressive disease.

BACKGROUND: With the advent of immune checkpoint inhibitors (ICIs) therapies, a major breakthrough has been made in cancer treatment. However, instead of good results, some patients experienced a deterioration of their disease. This unexpected result is termed as hyper-progressive disease (HPD). The biology of HPD is currently not fully understood. METHODS: Isolation of CD3+ cells from peripheral blood mononuclear cells (PBMC) in healthy control, tumor patients receiving immunotherapy with or without immunotherapy-induced HPD, then conducted single-cell RNA sequencing (scRNA-seq). RESULTS: By analyzing scRNA-seq data, we identified 15 cell clusters. We observed developed-exhausted CD4+ T cells and regulatory T cells (Tregs) increasingly enriched in HPD group. Meanwhile, some effector T cells were decreased in HPD. The imbalance potentially contributes to the occurrence of HPD and poor clinical prognosis. In addition, we analyzed ligand-receptor interactions between subsets. The ligand-receptor interaction "CD74-MIF" was absent in HPD. However, in vitro experiment, we found that CD74 regulated effector function of effector CD8+ T cells. Overall, the article provides a primary study of immune profile in HPD.

An Electrochemical Sensor for Sunset Yellow Detection Based on Cu@Cu2O-BNPC Formed by Modified Porous Carbon.

Control and detection of sunset yellow (SY) are an utmost demanding issue due to its high risk of detrimental effects on living systems caused by excessive ingestion. In this study, we reported the synthesis of Cu@Cu2O nanoparticle-decorated B and N codoped porous carbon (BNPC) and its use in developing a novel electrochemical sensor for SY. The Cu@Cu2O-BNPC catalyst was fabricated through single-step polymerization, followed by carbonization. Scanning electron microscopy, transmission electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy characterization results showed that Cu@Cu2O anchored on the porous BNPC successfully. Compared with the BNPC-modified electrode, it was found that the Cu@Cu2O-BNPC-modified electrode showed superior electrocatalytic activity in both electrochemical impedance spectroscopy and cyclic voltammetry tests. The as-prepared Cu@Cu2O-BNPC catalyst directly acted as a sensor for amperometric detection of SY without further assembling, which exhibited an ultrahigh sensitivity of 0.09 µA nM-1 cm-2, a low limit of detection (2.4 nM), and a wide linear detection ranging from 10 nM to 8 µM. To further validate its possible application, the proposed method was successfully used for the determination of SY in Fanta drinks with satisfactory results.

Emission of volatile sulphur compounds during swine manure composting: Source identification, odour mitigation and assessment.

This study aimed to identify the sources of volatile sulphur compounds (VSCs) and evaluate their mitigation by ferric oxide (Fe2O3) during swine manure composting. Four chemicals, including l-cysteine, l-methionine, sodium sulphite, and sodium sulphate, were further added to simulate organic and inorganic sulphur-containing substances in swine manure to track VSC sources during composting. Results show that sulphur simulants induced the emission of six common VSCs, including methyl sulphide (Me2S), dimethyl sulphide (Me2SS), carbonyl sulphide (COS), carbon disulphide (CS2), methyl mercaptan (MeSH), and ethyl mercaptan (EtSH), during swine manure composting. Of them, COS, CS2, MeSH and Me2SS were predominantly contributed by the biodegradation of methionine and cysteine, while Me2S and EtSH were dominated by the reduction of sulphite and sulphate. Further Fe2O3 addition at 1.5 % of total wet weight of composting materials immobilized elemental sulphur and inhibited sulphate reduction to reduce the emission of VSCs by 46.7-80.9 %. Furthermore, odour assessment indicated that adding Fe2O3 into composting piles significantly reduced the odour intensity level to below 4, the odour value of VSCs by 47.1-81.3 %, and thus the non-carcinogenic risk by 68.4 %.

HCl-activated porous nitrogen-doped carbon nanopolyhedras with abundant hierarchical pores for ultrafast desalination.

Exploring an emerging carbon-based material with optimized structure and controlled porosity is of significance for further heightening the capacitive deionization (CDI) performance and solving the problem of emergency fresh water supply. Herein, a porous nitrogen-doped carbon nanopolyhedra with hierarchical pores prepared via using zeolite-type metal-organic framework (ZIF-8) as precursor is reported and used for CDI. In order to prepare the nanomaterials with abundant hierarchical pore structure, the synthetic route of carbonization followed by HCl-activation is adopted. The resulting nitrogen-doped carbon materials exhibit a bimodal porosity containing micro- and meso-pores, high specific surface area, and numerous exposed adsorption active sites. The excellent performance in structure ensures the ultrahigh desalination capacity of 37.52 mg g-1 and excellent recyclability (retained 90% over 30 cycles) of the as-prepared carbon electrode material. Notably, the above electrode demonstrates ultrafast desalination rate of 16.01 mg g-1 min-1, which is 2-8 times faster than the conventional carbon materials. This present work may provide a new insight for developing efficient MOF-derived CDI electrode materials and realizing rapid water resource supply in emergencies such as outdoor survival or unexpected natural disasters.

Bioinspired two-in-one nanotransistor sensor for the simultaneous measurements of electrical and mechanical cellular responses.

The excitation-contraction dynamics in cardiac tissue are the most important physiological parameters for assessing developmental state. We demonstrate integrated nanoelectronic sensors capable of simultaneously probing electrical and mechanical cellular responses. The sensor is configured from a three-dimensional nanotransistor with its conduction channel protruding out of the plane. The structure promotes not only a tight seal with the cell for detecting action potential via field effect but also a close mechanical coupling for detecting cellular force via piezoresistive effect. Arrays of nanotransistors are integrated to realize label-free, submillisecond, and scalable interrogation of correlated cell dynamics, showing advantages in tracking and differentiating cell states in drug studies. The sensor can further decode vector information in cellular motion beyond typical scalar information acquired at the tissue level, hence offering an improved tool for cell mechanics studies. The sensor enables not only improved bioelectronic detections but also reduced invasiveness through the two-in-one converging integration.

Hollow mesoporous carbon nanospheres space-confining ultrathin nanosheets superstructures for efficient capacitive deionization.

In this work, we propose a novel strategy to fabricate nickel silicate nanoflakes inside hollow mesoporous carbon spheres (Ni3Si2O5(OH)4/C). Hollow mesoporous carbon spheres (HMCSs) can well regulate and limit the growth of Ni3Si2O5(OH)4 nanosheets, which obviously enhance the structural stability and conductivity of the composites. The core-shell Ni3Si2O5(OH)4/C superstructure has been proven to possess an extremely excellent electrosorption capacity of 28.7 mg g-1 at 1.2 V under a NaCl concentration of 584 mg L-1 for capacitive deionization (CDI). This outstanding property can be attributed to the core-shell superstructure with ultrathin Ni3Si2O5(OH)4 nanosheets as the stable core and mesoporous carbon as the conductive shell. This work will provide a direction for the application of core-shell superstructure carbon-based nanomaterials as high-performance electrode materials for CDI.

In Situ Growth of Three-Dimensional MXene/Metal-Organic Framework Composites for High-Performance Supercapacitors.

In this study, we propose a versatile method for synthesizing uniform three-dimensional (3D) metal carbides, nitrides, and carbonitrides (MXenes)/metal-organic frameworks (MOFs) composites (Ti3 C2 TX /Cu-BTC, Ti3 C2 TX /Fe,Co-PBA, Ti3 C2 TX /ZIF-8, and Ti3 C2 TX /ZIF-67) that combine the advantages of MOFs and MXenes to enhance stability and improve conductivity. Subsequently, 3D hollow Ti3 C2 TX /ZIF-67/CoV2 O6 composites with excellent electron- and ion-transport properties derived from Ti3 C2 TX /ZIF-67 were synthesized. The specific capacitance of the Ti3 C2 TX /ZIF-67/CoV2 O6 electrode was 285.5 F g-1 , which is much higher than that of the ZIF-67 and Ti3 C2 TX /ZIF-67 electrode. This study opens a new avenue for the design and synthesis of MXene/MOF composites and complex hollow structures with tailorable structures and compositions for various applications.

Humification and maturation of kitchen waste during indoor composting by individual households.

This study evaluated the humification and maturation of kitchen waste during indoor composting by individual households. In total, 50 households were randomly selected to participate in this study using kitchen waste of their own for indoor composting using a standard 20 L sealed composter. Garden waste was also collected from their local communities and used as the bulking agent. Both effective microorganisms and lime were inoculated at 1% (wet weight) of raw composting materials to facilitate the composting initiation. Results from this study demonstrate for the first time that ordinary residents could correctly follow the instruction to operate indoor composting at household level to manage urban kitchen waste at source. Overall, 30 households provided valid and complete data to show an increase (to ~50 °C) and then decrease in temperature in response to the decline of biodegradable organic substances during indoor composting. The compost physiochemical characteristics varied significantly toward maturation with an increase in seed germination index to above 50% for most households. Furthermore, organic humification occurred continuously during indoor composting as indicated by the enhanced content of humic substances, degree of polymerization, and spectroscopic characteristics.

Applications of Metal-Organic Frameworks in Water Treatment: A Review.

The ever-expanding scale of industry and agriculture has led to the gradual increase of pollutants (e.g., heavy metal ions, synthetic dyes, and antibiotics) in water resources, and the ecology and wastewater are grave problems that need to be solved urgently and has attracted widespread attention from the research community and industry in recent years. Metal-organic frameworks (MOFs) are a type of organic-inorganic hybrid material with a distinctive 3D network crystal structure. Lately, MOFs have made striking progress in the fields of adsorption, catalytic degradation, and biomedicine on account of their large specific surface and well-developed pore structure. This review summarizes the latest research achievements in the preparation of pristine MOFs, MOF composites, and MOF derivatives for various applications including the removal of heavy metal ions, organic dyes, and other harmful substances in sewage. Furthermore, the working mechanisms of utilizing adsorption, photocatalytic degradation, and membrane separation technologies are also briefly described for specific pollutants removal from sewage. It is expected that this review will provide inspiration and references for the synthesis of pristine MOFs as well as their composites and derivatives with excellent water treatment performance.