Accumulating evidence shows that cellular and acellular components in tumor microenvironment (TME) can reprogram tumor initiation, growth, invasion, metastasis, and response to therapies. Cancer ...research and treatment have switched from a cancer-centric model to a TME-centric one, considering the increasing significance of TME in cancer biology. Nonetheless, the clinical efficacy of therapeutic strategies targeting TME, especially the specific cells or pathways of TME, remains unsatisfactory. Classifying the chemopathological characteristics of TME and crosstalk among one another can greatly benefit further studies exploring effective treating methods. Herein, we present an updated image of TME with emphasis on hypoxic niche, immune microenvironment, metabolism microenvironment, acidic niche, innervated niche, and mechanical microenvironment. We then summarize conventional drugs including aspirin, celecoxib, β-adrenergic antagonist, metformin, and statin in new antitumor application. These drugs are considered as viable candidates for combination therapy due to their antitumor activity and extensive use in clinical practice. We also provide our outlook on directions and potential applications of TME theory. This review depicts a comprehensive and vivid landscape of TME from biology to treatment.
Ink‐based processes, which enable scalable fabrication of flexible devices based on nanomaterials, are one of the practical approaches for the production of wearable electronics. However, carbon ...nanotubes (CNTs), which possess great potential for flexible electronics, are facing challenges for use in inks due to their low dispersity in most solvents and suspicious cytotoxicity. Here, a stable and biocompatible CNT ink, which is stabilized by sustainable silk sericin and free from any artificial chemicals, is reported. The ink shows stability up to months, which can be attributed to the formation of sericin–CNT (SSCNT) hybrid through non‐covalent interactions. It is demonstrated that the SSCNT ink can be used for fabricating versatile circuits on textile, paper, and plastic films through various techniques. As proofs of concept, electrocardiogram electrodes, breath sensors, and electrochemical sensors for monitoring human health and activity are fabricated, demonstrating the great potential of the SSCNT ink for smart wearables.
A highly stable and biocompatible conductive ink is developed based on carbon nanotubes and natural silk sericin. Owing to its high electrical conductivity, high colloidal stability, and good biocompatibility, this ink holds great potential in flexible and wearable electronics.
Live‐imaging of signaling molecules released from living cells is a fundamental challenge in life sciences. Herein, we synthesized liquid crystal elastomer microspheres functionalized with ...horse‐radish peroxidase (LCEM‐HRP), which can be immobilized directly on the cell membrane to monitor real‐time release of H2O2 at the single‐cell level. LCEM‐HRP could report H2O2 through a concentric‐to‐radial (C‐R) transfiguration, which is due to the deprotonation of LCEM‐HRP and the break of inter or intra‐chain hydrogen bonding in LCEM‐HRP caused by HRP‐catalyzed reduction of H2O2. The level of transfiguration of LCEM‐HRP revealed the different amounts of H2O2 released from cells. The estimated detection sensitivity was ≈2.2×10−7 μm for 10 min of detection time. The cell lines and cell–cell heterogeneity was explored from different configurations. LCEM‐HRP presents a new approach for in situ real‐time imaging of H2O2 release from living cells and can be the basis for seeking more advanced chemical probes for imaging of various signaling molecules in the cellular microenvironment.
Liquid‐crystal elastomer microspheres functionalized with horse‐radish peroxidase (LCEM‐HRP) were directly immobilized on the cell membrane for real‐time imaging of H2O2 released from single living cells. Each LCEM‐HRP could report H2O2 through a concentric‐to‐radial transfiguration. The level of the transfiguration of LCEM‐HRP revealed different amounts of released H2O2 and mapped the cell lines and cell–cell heterogeneity.
Adhesion of single cells is the foundation of manifold cellular behaviors and life processes. However, investigating the function of a specific cell is still challenging due to deficiency of adhesion ...or interference from surrounding cells. Herein, an open microfluidic system is reported for culturing adherent single cells, implemented by a micrometer‐scale droplet matrix on an inkjet‐printed polylysine template. The target cells are isolated from any cell from other droplets, and their adhesion strength is determined to be comparable to conventional petri dishes via an in‐situ investigation with a microfluidic extractor. On this proposed platform, isolated single cells are observed to display an entirely distinct spreading behavior featuring total absence of elongation, indicating drastic cell behavior change from their “singleness.” This system has high versatility and compatibility for various assaying methods, assuring a promising potential in detailed single cell behavior and cell heterogeneity studies.
Single cells are cultured on inkjet‐printed microculture dishes that support adhesion and spreading and assist restoration of their function. The openness of the system allows in situ analysis. Isolated single cells exhibit distinctness in morphology from previous studies where intercellular communication remains present, enticing future interest in isolated single cell behavior.
A microfluidic assembly method based on a microfluidic chip and capillary device was developed to create multicompartmental particles. The microfluidic chip design endows the particles with regulable ...internal structure. By adjusting the microstructure of the chip, the diameter of the capillary, the gap length between the two microfluidic components, and the flow rates, the size of the particles and the number or the ratio of different regions within the particle could be widely varied. As a proof of concept, we have produced some complicated particles that even contain 20 compartments. Furthermore, the potential applications of the anisotropic particles are explored by encapsulating magnetic beads, fluorescent nanoparticles, and the cells into different compartments of the microparticles. We believe that this method will open new avenues for the design and application of multicompartmental particles.
A microfluidic device, consisting of a microfluidic chip and capillary, was developed to produce multicompartmental particles. By adjusting various parameters of the device, the size of the particles and the number of different compartments within the particle could be varied. These were used to encapsulate magnetic beads, fluorescent nanoparticles, and cells.
Cellular membranes are composed of a variety of lipids in different amounts and proportions, and alterations of them are usually closely related to various diseases. To reveal the intercellular ...heterogeneity of the lipid variation, an integrated microfluidic system is designed, which consists of droplet‐based inkjet printing, dielectrophoretic electrodes, and de‐emulsification interface to achieve on‐line single‐cell encapsulation, manipulation, and mass spectrometry (MS) detection. This integrated system effectively improves the single‐cell encapsulation rate, and meanwhile reduces the matrix interference and continuous oil phase interference to the MS detection. Using this system, the heterogeneities between the normal and cancer cells are compared, and the heterogeneity of the same cells before and after the drug treatment changed obviously, indicating that this system can be used as a promising tool for studying the link between the alterations of lipid homeostasis and various diseases.
A single cell analysis system is fabricated by combining inkjet printing, dielectrophoresis channel, asymmetrically bifurcate structure, and de‐emulsification interface coupled to nano‐electron spray ionization (ESI)‐mass spectrometry (MS) to achieve on‐line lipid profiling with a throughput of 10 droplets per minute. This integrated system effectively improves the single‐cell encapsulation rate, and meanwhile reduces the matrix interference and continuous oil phase interference to the MS detection.
In this work, a class of bubble‐containing multicompartmental particles with self‐orienting capability is developed, where a single bubble is enclosed at the top of the super‐segmented architecture. ...Such bubbles, driven by potential energy minimization, cause the particles to have a bubble‐upward preferred orientation in liquid, enabling efficient decoding of their high‐density signals in an interference‐resistant manner. The particle preparation involves bubble encapsulation via the impact of a multicompartmental droplet on the liquid surface and overall stabilization via rational crosslinking. The conditions for obtaining these particles are systematically investigated. Methodological compatibility with materials is demonstrated by different hydrogel particles. Finally, by encapsulating cargoes of interest, these particles have found broad applications in actuators, multiplexed detection, barcodes, and multicellular systems.
A novel class of bubble‐containing multicompartmental particles is reported. The bubbles cause the particles to have a preferred bubble‐upward orientation driven by potential energy minimization. By loading cargoes of interest, these particles can be used as actuators, multiplexed detectors, anti‐counterfeiting barcodes, and multicellular systems.
Reactive oxygen species (ROS) generation is of intense interest because of its crucial role in many fields. Here we demonstrate that MoS2-QDs exhibit a promising capability for the generation of ...reactive oxygen species, which leads to enhanced chemiluminescence. We discovered that the unique performance is due to hydroxyl radical activation increasing the active catalytic sites on molybdenum sulphide quantum dots (MoS2-QDs). The reactive oxygen species, such as hydroxyl radicals (·OH), superoxide radicals (·O2−) and singlet oxygen (1O2) have been efficiently generated from H2O2 solution in alkaline conditions. In particular, the maximum ·OH yield was enhanced significantly (9.18 times) compared to the Fe(ii)/H2O2 Fenton system under neutral conditions. These findings not only enrich our understanding of the fascinating performance of MoS2 QDs, but also provide a new pathway for ROS generation in all kinds of pH environment.
Wuhan was the first epicentre of COVID-19 in the world, accounting for 80% of cases in China during the first wave. We aimed to assess household transmissibility of severe acute respiratory syndrome ...coronavirus 2 (SARS-CoV-2) and risk factors associated with infectivity and susceptibility to infection in Wuhan.
This retrospective cohort study included the households of all laboratory-confirmed or clinically confirmed COVID-19 cases and laboratory-confirmed asymptomatic SARS-CoV-2 infections identified by the Wuhan Center for Disease Control and Prevention between Dec 2, 2019, and April 18, 2020. We defined households as groups of family members and close relatives who did not necessarily live at the same address and considered households that shared common contacts as epidemiologically linked. We used a statistical transmission model to estimate household secondary attack rates and to quantify risk factors associated with infectivity and susceptibility to infection, accounting for individual-level exposure history. We assessed how intervention policies affected the household reproductive number, defined as the mean number of household contacts a case can infect.
27 101 households with 29 578 primary cases and 57 581 household contacts were identified. The secondary attack rate estimated with the transmission model was 15·6% (95% CI 15·2–16·0), assuming a mean incubation period of 5 days and a maximum infectious period of 22 days. Individuals aged 60 years or older were at a higher risk of infection with SARS-CoV-2 than all other age groups. Infants aged 0–1 years were significantly more likely to be infected than children aged 2–5 years (odds ratio OR 2·20, 95% CI 1·40–3·44) and children aged 6–12 years (1·53, 1·01–2·34). Given the same exposure time, children and adolescents younger than 20 years of age were more likely to infect others than were adults aged 60 years or older (1·58, 1·28–1·95). Asymptomatic individuals were much less likely to infect others than were symptomatic cases (0·21, 0·14–0·31). Symptomatic cases were more likely to infect others before symptom onset than after (1·42, 1·30–1·55). After mass isolation of cases, quarantine of household contacts, and restriction of movement policies were implemented, household reproductive numbers declined by 52% among primary cases (from 0·25 95% CI 0·24–0·26 to 0·12 0·10–0·13) and by 63% among secondary cases (from 0·17 0·16–0·18 to 0·063 0·057–0·070).
Within households, children and adolescents were less susceptible to SARS-CoV-2 infection but were more infectious than older individuals. Presymptomatic cases were more infectious and individuals with asymptomatic infection less infectious than symptomatic cases. These findings have implications for devising interventions for blocking household transmission of SARS-CoV-2, such as timely vaccination of eligible children once resources become available.
National Natural Science Foundation of China, Fundamental Research Funds for the Central Universities, US National Institutes of Health, and US National Science Foundation.
In this work, chemiluminescent (CL) property of the carbon dots in the presence of peroxynitrous acid was studied. Peroxynitrous acid is formed by online mixing of nitrite and acidified hydrogen ...peroxide. The CL intensity was increased linearly with nitrite concentration in the range from 1.0 × 10(-7) M to 1.0 × 10(-5) M, and the detection limit was 5.3 × 10(-8) M (signal-to-noise ratio of S/N = 3). This method has been successfully applied to the determination of nitrites in pond water, river water, and pure milk, with recoveries in the range of 98%-108%. The CL mechanism of the peroxynitrous acid-carbon dots system was investigated using the CL, ultraviolet-visible light (UV-vis), and electron paramagnetic resonance (EPR) spectra. The electron-transfer annihilation of hole-injected and electron-injected carbon dots could mainly account for the CL emission, which sheds new light on the optical properties of the carbon dots.
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