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The modulation of intracellular reactive oxygen species (ROS) levels is crucial for cellular homeostasis and determination of cellular fate. A sublethal level of ROS sustains cell proliferation, differentiation and promotes tumor metastasis, while a drastic ROS burst directly induces apoptosis. Herein, surface-oxidized arsenene nanosheets (As/As x O y NSs) with type II heterojunction are fabricated with efficient ·O 2 − and 1 O 2 production and glutathione consumption through prolonging the lifetime of photo-excited electron-hole pairs. Moreover, the portion of As x O y with oxygen vacancies not only catalyzes a Fenton-like reaction, generating ·OH and O 2 from H 2 O 2 , but also inactivates main anti-oxidants to cut off the “retreat routes” of ROS. After polydopamine (PDA) and cancer cell membrane (M) coating, the engineered As/As x O y @PDA@M NSs serve as an intelligent theranostic platform with active tumor targeting and long-term blood circulation. Given its narrow-band-gap-enabled in vivo fluorescence imaging properties, As/As x O y @PDA@M NSs could be applied as an imaging-guided non-invasive and real-time nanomedicine for cancer therapy. Multifunctional materials with a number of effects are important for dealing with the complex environment in cancer therapy. Here, the authors report on surface-oxidized arsenene nanosheets coated with polydopamine and cancer cell membrane as a multi theranostic tumour targeting cancer therapy.

The treatment of diabetic ulcer (DU) remains a major clinical challenge due to the complex wound-healing milieu that features chronic wounds, impaired angiogenesis, persistent pain, bacterial infection, and exacerbated inflammation. A strategy that effectively targets all these issues has proven elusive. Herein, we use a smart black phosphorus (BP)-based gel with the characteristics of rapid formation and near-infrared light (NIR) responsiveness to address these problems. The in situ sprayed BP-based gel could act as 1) a temporary, biomimetic “skin” to temporarily shield the tissue from the external environment and accelerate chronic wound healing by promoting the proliferation of endothelial cells, vascularization, and angiogenesis and 2) a drug “reservoir” to store therapeutic BP and pain-relieving lidocaine hydrochloride (Lid). Within several minutes of NIR laser irradiation, the BP-based gel generates local heat to accelerate microcirculatory blood flow, mediate the release of loaded Lid for “on-demand” pain relief, eliminate bacteria, and reduce inflammation. Therefore, our study not only introduces a concept of in situ sprayed, NIR-responsive pain relief gel targeting the challengingwound-healing milieu in diabetes but also provides a proof-of-concept application of BP-based materials in DU treatment.

The abuse of antibiotics has led to the emergence of multidrug-resistant microbial pathogens, presenting a pressing challenge in global healthcare. Membrane-disrupting antimicrobial peptides (AMPs) combat so-called superbugs via mechanisms different than conventional antibiotics and have good application prospects in medicine, agriculture, and the food industry. However, the mechanism-of-action of AMPs has not been fully characterized at the cellular level due to a lack of high-resolution imaging technologies that can capture cellular-membrane disruption events in the hydrated state. Previously, we reported PepD2M, a de novo-designed AMP with potent and wide-spectrum bactericidal and fungicidal activity. In this study, we use cryo-electron tomography (cryo-ET) and high-speed atomic force microscopy (HS-AFM) to directly visualize the pepD2M-induced disruption of the outer and inner membranes of the Gram-negative bacterium Escherichia coli , and compared with a well-known pore-forming peptide, melittin. Our high-resolution cryo-ET images reveal how pepD2M disrupts the E. coli membrane using a carpet/detergent-like mechanism. Our studies reveal the direct membrane-disrupting consequence of AMPs on the bacterial membrane by cryo-ET, and this information provides critical insights into the mechanisms of this class of antimicrobial agents. Antimicrobial peptide mechanism of membrane disruption have not been fully characterized at the cellular level. Here, authors use cryo-electron tomography and AFM to directly visualize the disruption of the outer and inner membranes of Escherichia coli by a de novo-designed peptide.

Biotite, also called black mica (BM), is a group of sheet silicate minerals with great potential in various fields. However, synthesis of high‐quality BM nanosheets (NSs) remains a huge challenge. Here, an exfoliation approach is provided that combines calcination, n‐butyllithium exchange and intercalation, and liquid exfoliating processes for the high‐yield synthesis of ultrathin BM NSs. Due to the presence of MgO, Fe2O3, and FeO in these NSs, PEGylated BM can be engineered as an intelligent theranostic platform with the following unique features: i) Fe3+ can damage the tumor microenvironment (TME) through glutathione consumption and O2 production; ii) Generated O2 can be further catalyzed by MgO with oxygen vacancy to generate ·O2−; iii) The Fe2+‐catalyzed Fenton reaction can produce ·OH by disproportionation reactions of H2O2 in the TME; iv) Reactions in (i) and (iii) circularly regenerate Fe2+ and Fe3+ for continuous consumption of glutathione and H2O2 and constant production of ·OH and O2; v) The NSs can be triggered by a 650 nm laser to generate ·O2− from O2 as well as by an 808 nm laser to generate local hyperthermia; and vi) The fluorescent, photoacoustic, and photothermal imaging capabilities of the engineered NSs allow for multimodal imaging‐guided breast cancer treatment. 2D black mica (BM)‐based nanosheets (NSs) are fabricated through an exfoliation approach that combines grinding, calcination, n‐butyllithium exchange and intercalation, and liquid exfoliating processes. The nanoplatform based on PEGylated BM NSs exhibits multiple features, such as tumor microenvironment modulation, efficient reactive oxygen species production and photothermal conversion, high tumor site accumulation, good biocompatibility, and multimodal imaging‐guided breast cancer treatment.

Background This study examined the feasibility of transabdominal intestinal ultrasonography in evaluating acute gastrointestinal injury (AGI). Methods A total of 116 patients were included. Intestinal ultrasonography was conducted daily within 1 week after admission to the intensive care unit. Ultrasonography indicators including intestinal diameter, changes in the intestinal folds, thickness of the intestinal wall, stratification of the intestinal wall, and intestinal peristalsis (movement of the intestinal contents) were observed to determine the acute gastrointestinal injury ultrasonography (AGIUS) score. The gastrointestinal and urinary tract sonography ultrasound (GUTS) protocol score was also calculated. During the first week of the study, the gastrointestinal failure (GIF) score was determined daily. The correlations between transabdominal intestinal scores (AGIUS and GUTS) and the GIF score were analyzed to clarify the feasibility of evaluating AGI through observation of the intestine. The utility of intestinal ultrasonography indicators in predicting feeding intolerance was investigated to improve the ability of clinicians to manage AGI. Results A total of 751 ultrasonic examinations were performed with 511 images (68%) considered to be of “good quality.” AGIUS and GUTS scores differed significantly between AGI patients (GIF score 0–2) and non-AGI patients (GIF score 3–4) ( p  < 0.001). Both scores correlated positively with GIF score ( r  = 0.54, p  < 0.001; r  = 0.66, p  < 0.001). These ultrasonography indicators could predict feeding intolerance, with an area under the receiver operating characteristic curve of 0.60 (0.48–0.71; intestinal diameter), 0.76 (0.67–0.85; intestinal folds), 0.71 (0.62–0.80; wall thickness), 0.77 (0.69–0.86; wall stratification), and 0.78 (0.68–0.88; intestinal peristalsis). Compared to patients with a normal rate of peristalsis (5–10/min), patients with abnormal peristalsis rates (< 5/min or > 10/min) have increased risk for feeding intolerance (16/83 vs. 25/33, p  < 0.001). Conclusions The transabdominal intestinal ultrasonography represents an effective means for assessing gastrointestinal injury in critically ill patients. Intestinal ultrasonography indicators, especially the degree of intestinal peristalsis, may be used to predict feeding intolerance. Trial registration ClinicalTrial.gov, NCT03589248 . Registered 04 July 2018—retrospectively registered.

The use of adhesively bonded joints in place of traditional joining techniques such as bolted or rivet joints is becoming greatly popular in recent years. Interfacial stress in the adhesive is critical to the strength of adhesively bonded joints. It is necessary to predict the interfacial stresses accurately to ensure the safety of joints. In this work, an analytical model is explicitly presented to evaluate the stresses in a double lap joint. The equilibrium equations in the adhesive overlap region are derived on the basis of elasticity theory. The governing equations are presented in terms of shear and peel stresses in the adhesive. Analytical solutions are derived for the shear and peel stresses, which are considered to be the main reason for the failure of the double lap joint. To verify the analytical solutions, the finite element method is conducted using the commercial package ANSYS. Results from the analytical solution agree well with finite element results and numerical investigations available in the literature. The effect of the adhesive thickness, shear modulus, adherend Young’s modulus and bonding length on the shear and peel stresses in the adhesive of the double lap joint are studied. Numerical results demonstrate that both the maximum shear and peel stress occur at both ends of the bonding region. The maximum values of the shear and peel stresses increase as the adhesive thickness decreases and as the adhesive shear modulus increases provided that the adhesive thickness is sufficiently small. The simplicity and capability to obtain analytical expressions of the shear and peel stresses for double lap adhesive bonded joints makes the proposed analytical model applicable for the stress analysis and preliminary structural design.

Highlights2D Sn nanosheets (SnNSs) were prepared through the combination of cryogenic exfoliation and liquid-phase exfoliation.The functionalized 2D SnNSs have good stability, superior biocompatibility, high photothermal conversion efficiency, and multimode imaging capability.Stanene (Sn)-based materials have been extensively applied in industrial production and daily life, but their potential biomedical application remains largely unexplored, which is due to the absence of the appropriate and effective methods for fabricating Sn-based biomaterials. Herein, we explored a new approach combining cryogenic exfoliation and liquid-phase exfoliation to successfully manufacture two-dimensional (2D) Sn nanosheets (SnNSs). The obtained SnNSs exhibited a typical sheet-like structure with an average size of ~ 100 nm and a thickness of ~ 5.1 nm. After PEGylation, the resulting PEGylated SnNSs (SnNSs@PEG) exhibited good stability, superior biocompatibility, and excellent photothermal performance, which could serve as robust photothermal agents for multi-modal imaging (fluorescence/photoacoustic/photothermal imaging)-guided photothermal elimination of cancer. Furthermore, we also used first-principles density functional theory calculations to investigate the photothermal mechanism of SnNSs, revealing that the free electrons in upper and lower layers of SnNSs contribute to the conversion of the photo to thermal. This work not only introduces a new approach to fabricate 2D SnNSs but also establishes the SnNSs-based nanomedicines for photonic cancer theranostics. This new type of SnNSs with great potential in the field of nanomedicines may spur a wave of developing Sn-based biological materials to benefit biomedical applications.

The Leggett–Garg inequality attempts to classify experimental outcomes as arising from one of two possible classes of physical theories: those described by macrorealism (which obey our intuition about how the macroscopic classical world behaves) and those that are not (e.g., quantum theory). The development of cloud-based quantum computing devices enables us to explore the limits of macrorealism. In particular, here we take advantage of the properties of the programmable nature of the IBM quantum experience to observe the violation of the Leggett–Garg inequality (in the form of a ‘quantum witness’) as a function of the number of constituent systems (qubits), while simultaneously maximizing the ‘disconnectivity’, a potential measure of macroscopicity, between constituents. Our results show that two- and four-qubit ‘cat states’ (which have large disconnectivity) are seen to violate the inequality, and hence can be classified as non-macrorealistic. In contrast, a six-qubit cat state does not violate the ‘quantum witness’ beyond a so-called clumsy invasive-measurement bound, and thus is compatible with ‘clumsy macrorealism’. As a comparison, we also consider un-entangled product states with n = 2, 3, 4 and 6 qubits, in which the disconnectivity is low.

Use of the ResearchKit platform to track symptoms of a large cohort of asthma sufferers over time demonstrates the pros and cons of mobile health applications in large-scale observational studies. The feasibility of using mobile health applications to conduct observational clinical studies requires rigorous validation. Here, we report initial findings from the Asthma Mobile Health Study, a research study, including recruitment, consent, and enrollment, conducted entirely remotely by smartphone. We achieved secure bidirectional data flow between investigators and 7,593 participants from across the United States, including many with severe asthma. Our platform enabled prospective collection of longitudinal, multidimensional data (e.g., surveys, devices, geolocation, and air quality) in a subset of users over the 6-month study period. Consistent trending and correlation of interrelated variables support the quality of data obtained via this method. We detected increased reporting of asthma symptoms in regions affected by heat, pollen, and wildfires. Potential challenges with this technology include selection bias, low retention rates, reporting bias, and data security. These issues require attention to realize the full potential of mobile platforms in research and patient care.

Four novel, rare carbon-bridged citrinin dimers, namely dicitrinones G–J (1–4), and five known analogs (5–9) were isolated from the starfish-derived fungus Penicillium sp. GGF 16-1-2. Their structures were elucidated by extensive spectroscopic analysis and quantum chemical calculations. Compounds 1–9 exhibited strong antifungal activities against Colletotrichum gloeosporioides with LD50 values from 0.61 μg/mL to 16.14 μg/mL. Meanwhile, all compounds were evaluated for their cytotoxic activities against human pancreatic cancer BXPC-3 and PANC-1 cell lines; as a result, compound 1 showed more significant cytotoxicities than the positive control against both cell lines. In addition, based on the analyses of the protein-protein interaction (PPI) network and Western blot, 1 could induce apoptosis by activating caspase 3 proteins (CASP3).