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Over the past decade, a marked escalation in the prevalence of hepatic pathologies has been observed, adversely impacting the quality of life for many. The predominant therapeutic strategy for liver diseases has been pharmacological intervention; however, its efficacy is often constrained. Currently, liposomes are tiny structures that can deliver drugs directly to targeted areas, enhancing their effectiveness. Specifically, cell membrane-associated liposomes have gained significant attention. Despite this, there is still much to learn about the binding mechanism of this type of liposome. Thus, this review comprehensively summarizes relevant information on cell membrane-associated liposomes, including their clinical applications and future development directions. First, we will briefly introduce the composition and types of cell membrane-associated liposomes. We will provide an overview of their structure and discuss the various types of liposomes associated with cell membranes. Second, we will thoroughly discuss various strategies of drug delivery using these liposomes. Lastly, we will discuss the application and clinical challenges associated with using cell membrane-associated liposomes in treating liver diseases. We will explore their potential benefits while also addressing the obstacles that need to be overcome. Furthermore, we will provide prospects for future development in this field. In summary, this review underscores the promise of cell membrane-associated liposomes in enhancing liver disease treatment and highlights the need for further research to optimize their utilization. In summary, this review underscores the promise of cell membrane-associated liposomes in enhancing liver disease treatment and highlights the need for further research to optimize their utilization.

Cell encapsulated in biomaterials for organ repair or disease treatment is indeed an emerging field. Currently, microfluidics is being utilized to precisely control the quantity, size, and scaffold structure of encapsulated cells. Specifically, microfluidics offers the ability to design biomimetic morphologies that enhance the activity and function of encapsulated cells, thereby improving the effectiveness of disease treatment. In this review, we report the latest advancements in microfluidic-based biomimetic cell encapsulation. To begin with, we provide a brief overview of various naturally derived biomimetic structures that promote cellular functionality, such as those inspired by cells, plants, animals, and natural responses. Moving forward, we discuss recent cell encapsulation methods based on microtechnology and provide detailed descriptions of the relevant processes. Finally, we address the challenges and future directions of biomimetic cell encapsulation in disease treatment and clinical applications.

Liver diseases have consistently posed substantial challenges to global health. It is crucial to find innovative methods to effectively prevent and treat these diseases. In recent times, there has been an increasing interest in the use of mRNA formulations that accumulate in liver tissue for the treatment of hepatic diseases. In this review, we start by providing a detailed introduction to the mRNA technology. Afterward, we highlight types of liver diseases, discussing their causes, risks, and common therapeutic strategies. Additionally, we summarize the latest advancements in mRNA technology for the treatment of liver diseases. This includes systems based on hepatocyte growth factor, hepatitis B virus antibody, left–right determination factor 1, human hepatocyte nuclear factor α, interleukin-12, methylmalonyl-coenzyme A mutase, etc. Lastly, we provide an outlook on the potential of mRNA technology for the treatment of liver diseases, while also highlighting the various technical challenges that need to be addressed. Despite these difficulties, mRNA-based therapeutic strategies may change traditional treatment methods, bringing hope to patients with liver diseases.

Natural polymers are complex organic molecules that occur in the natural environment and have not been subjected to artificial synthesis. They are frequently encountered in various creatures, including mammals, plants, and microbes. The aforementioned polymers are commonly derived from renewable sources, possess a notable level of compatibility with living organisms, and have a limited adverse effect on the environment. As a result, they hold considerable significance in the development of sustainable and environmentally friendly goods. In recent times, there has been notable advancement in the investigation of the potential uses of natural polymers in the field of biomedicine, specifically in relation to natural biomaterials that exhibit antibacterial and antioxidant characteristics. This review provides a comprehensive overview of prevalent natural polymers utilized in the biomedical domain throughout the preceding two decades. In this paper, we present a comprehensive examination of the components and typical methods for the preparation of biomaterials based on natural polymers. Furthermore, we summarize the application of natural polymer materials in each stage of skin wound repair. Finally, we present key findings and insights into the limitations of current natural polymers and elucidate the prospects for their future development in this field.

ABSTRACTIntroductionSelf-triggered micro-/milli-devices (STMDs), which are artificial devices capable of responding to the surrounding environment and transferring external energy into kinetic energy, thus realizing autonomous movement, have come to the forefront as a powerful tool in cargo delivery via gastrointestinal tract. Urgent needs have been raised to overview the development of this area.Areas coveredWe summarize the advancement of designing STMDs for delivery via gastrointestinal tract. We first give a brief overview on the opportunities and challenges of delivery via gastrointestinal tract involving gastric barriers and intestinal barriers. Then, emphasis is laid on the design and applications of STMDs for delivery via gastrointestinal tract. We focus on their morphological characteristics and function design, expounding their working mechanisms in the complex gastrointestinal tract.Expert opinionAlthough with much progress in STMDs, there is still a huge gap between laboratory researches and clinical applications due to some limitations including latent digestive burden, sophisticated fabrication, unstable delivery, and so on. We give a discussion on the potential, challenges, and prospects of developing STMDs for delivery via gastrointestinal tract.

Acute liver failure (ALF) is a life-threatening disease that occurs secondary to drug toxicity, infection or a devastating immune response. Orthotopic liver transplantation is an effective treatment but limited by the shortage of donor organs, the requirement for life-long immune suppression and surgical challenges. Stem cell transplantation is a promising alternative therapy for fulminant liver failure owing to the immunomodulatory abilities of stem cells. Here, we report that when transplanted into the liver, human endoderm stem cells (hEnSCs) that are germ layer-specific and nontumorigenic cells derived from pluripotent stem cells are able to effectively ameliorate hepatic injury in multiple rodent and swine drug-induced ALF models. We demonstrate that hEnSCs tune the local immune microenvironment by skewing macrophages/Kupffer cells towards an anti-inflammatory state and by reducing the infiltrating monocytes/macrophages and inflammatory T helper cells. Single-cell transcriptomic analyses of infiltrating and resident monocytes/macrophages isolated from animal livers revealed dramatic changes, including changes in gene expression that correlated with the change of activation states, and dynamic population heterogeneity among these cells after hEnSC transplantation. We further demonstrate that hEnSCs modulate the activation state of macrophages/Kupffer cells via cystatin SN (CST1)-mediated inhibition of interferon signaling and therefore highlight CST1 as a candidate therapeutic agent for diseases that involve over-activation of interferons. We propose that hEnSC transplantation represents a novel and powerful cell therapeutic treatment for ALF.

As one of the important aviation equipment components, rolling bearings will bring hidden dangers to the safety of aviation equipment once they fail. In aviation equipment, the sensor is far away from the bearing, and the collected signal of the rolling bearing is relatively weak. In this paper, the deconvolution algorithm is used to compensate the transfer function, and the optimal resonance demodulation algorithm based on the improved multi-resolution singular value decomposition (MRSVD) is constructed to determine the resonance frequency band, and then the bearing fault state is determined by the normalized squared envelope spectrum. The analysis results of the rolling bearing seed fault experiment show that this algorithm can adaptively extract the periodic fault pulse components under strong noise; compared with the normal spectral analysis and fast spectral kurtosis methods, this algorithm can completely extract the bearing fault characteristic frequency components, and effectively improve the bearing fault diagnosis accuracy.

Forward Freight Agreements (FFAs) are consequential derivatives for risk hedging in the shipping market. This paper presents the first empirical study of convenience yield in the shipping market with a sample of C3 (Tubarao to Qingdao) and C5 (Western Australia to Qingdao) FFAs from 2013 to 2023. First, single-factor and two-factor models are constructed to analyze the random behavior of freight rates in the shipping market, and the existence of convenience yield is empirically tested. The results provide evidence of the existence of convenience yield in the shipping market, with its stochastic variation being a critical factor in shaping the term structure characteristics of FFAs. Second, an ARMAX model is developed for the freight rate index, and the predictive role of the estimated convenience yield and its difference in spot freight rates is analyzed by operating the two-factor model. The findings reveal a significant predictive effect of convenience yield and its difference on spot freight rates. Last but not least, this study emphasizes the importance of convenience yield as a crucial parameter in the shipping market, particularly regarding the transportation of bulk commodities. Changes in the supply and demand of bulk commodities directly impact the fluctuations in shipping market capacity and convenience yield. This study delivers a new explanatory perspective for price formation in the shipping market and is highly valuable for risk management in this sector.

AbstractMost hospitals have financial assistance programs for low-income patients. We use administrative data from Kaiser Permanente to study the effects of financial assistance on health care utilization. Using a regression discontinuity design based on an income threshold for program eligibility, we find that financial assistance increases the likelihood of inpatient, ambulatory, and emergency department encounters by 3.6 pp (59 percent), 13.4 pp (20 percent), and 6.7 pp (53 percent), respectively, though effects dissipate three quarters after program receipt. Financial assistance also increases the detection and management of treatment-sensitive conditions (e.g., drugs treating diabetes), suggesting that financial assistance may increase receipt of high-value care. (JEL G51, I11, I12, I13, I32)

Microphysiological systems (MPSs), also known as organ chips, are micro‐units that integrate cells with diverse physical and biochemical environmental cues. In the field of liver MPSs, cellular components have advanced from simple planar cell cultures to more sophisticated 3D formations such as spheroids and organoids. Additionally, progress in microfluidic devices, bioprinting, engineering of matrix materials, and interdisciplinary technologies have significant promise for producing MPSs with biomimetic structures and functions. This review provides a comprehensive summary of biomimetic liver MPSs including their clinical applications and future developmental potential. First, the key components of liver MPSs, including the principal cell types and engineered structures utilized for cell cultivation, are briefly introduced. Subsequently, the biomedical applications of liver MPSs, including the creation of disease models, drug absorption, distribution, metabolism, excretion, and toxicity, are discussed. Finally, the challenges encountered by MPSs are summarized, and future research directions for their development are proposed. This review elucidates the primary cellular composition and biomimetic engineering structures of liver microphysiological systems (MPSs), and explores the biomedical applications of liver MPSs. It also encapsulates the challenges faced by MPSs and proffers prospective directions for future development.

Targeted analysis of data-independent acquisition (DIA) data needs a spectral library, which is generated by data-dependent acquisition (DDA) experiments or directly from DIA data. A comparison of the DDA library and DIA library in analyzing DIA data has been reported. However, the effects of different spectral libraries on the analysis of diaPASEF data have not been investigated. Here, we generate different spectral libraries with varying proteome coverage to analyze parallel accumulation–serial fragmentation (diaPASEF) data. Besides, we also employ the library-free strategy. The library, constructed by extensive fractionation DDA experiments, produces the highest numbers of precursors and proteins but with a high percentage of missing values. The library-free strategy identifies 10–20% fewer proteins than the library-based method but with a high degree of data completeness. A further study shows that the library-free strategy, although it identifies fewer proteins than the library-based method, leads to similar biological conclusions as the library-based method.

The volcano-shaped activity curve has long been used to reveal the activity trends among different catalysts and is a fundamental tool for catalyst screening. Although generally the peak height of the curve is considered as the highest possible activity, the understanding for its origin and inherent constraints is still a comparatively open issue. Herein, on the basis of microkinetic analysis and first-principles calculations, we quantitatively demonstrate that the peak height is strongly affected by the structural features of catalyst surfaces and could be largely improved by reducing the intercept of the Brønsted–Evans–Polanyi (BEP) relation. Focusing on various transition metal oxides (TMOs), we explore the BEP relations for the dissociation of small molecules, and the intercepts are shown to be smaller than those of flat metals. This reduction in intercept originates from the distinct local structure of oxide surfaces, which contributes to the weak binding ability and more final-state-like transition state. Taking NO oxidation as an example, we illustrate that the activity curve of rutile-type oxides is obviously higher than metals at typical medium–high temperatures, suggesting that rutile-type oxides possess inherently superior activity. Furthermore, general application of TMOs in breaking through the activity limit of metals for molecule dissociation is discussed.

Meyer wavelet filters are the key building blocks of empirical wavelet transform. In mechanical fault diagnosis, however, the boundaries of Meyer wavelet filters are usually defined empirically. In order to solve the problems, this paper proposes a new index called harmonic infinite-taxicab norm to guide grasshopper optimization algorithm to primarily optimize a band-pass filter and thus, concurrently and secondarily optimize a low-pass filter and a high-pass filter of Meyer wavelet. The proposed index is inspired by spectral Lp/Lq norm and it is closely related to fault characteristic frequency of rotating machinery. In addition, only three Meyer wavelet filters are demanded in each iteration of optimization. The effectiveness of the proposed method is validated by comparing with fast kurtogram method on analyzing faulty bearing data and gearbox data.

With currently available molecular imaging techniques, hepatocellular carcinoma (HCC), a liver cancer with high mortality rates and poor treatment responses, is mostly diagnosed at its late stage. This is largely due to the lack of highly sensitive contrast agents with high liver specificity. Herein, we report a novel bimodal contrast agent molecule CNCI-1 for the effective detection of HCC at its early stage both in vitro and in vivo. The agent has high liver specificity with effective X-ray computed tomography (CT)/near-infrared (NIR) imaging functions. It has been successfully applied to in vivo NIR imaging with high sensitivity and high selectivity to the HCC region of the HepG2 tumor-xenografted mice model and LM3 orthotopic hepatoma mice model. Moreover, the agent was found to be noninvasive and hepatocarcinoma cells preferential. Furthermore, it also enhanced the tumor imaging by revealing the blood vessels nearby for the CT image acquisition in the VX2 orthotopic hepatoma rabbit model. Our design strategy provides a new avenue to develop the medical relevant bimodal contrast agents for diagnosis of HCC at its early stage.

Wound healing remains a critical challenge in regenerative engineering. Great efforts are devoted to develop functional patches for wound healing. Herein, a novel sprayable black phosphorus (BP)‐based multifunctional hydrogel with on‐demand removability is presented as a joints’ skin wound dressing. The hydrogel is facilely prepared by mixing dopamine‐modified oxidized hyaluronic acid, cyanoacetategroup‐functionalized dextran containing black phosphorus, and the catalyst histidine. The catechol‐containing dopamine can not only enhance tissue adhesiveness, but also endow the hydrogel with antioxidant capacity. In addition, benefiting from the photothermal conversion ability of the BP and thermally reversible performance of the formed C═C double bonds between aldehyde groups and cyanoacetate groups, the resulting hydrogel displays excellent antibacterial performance and on‐demand dissolving ability under NIR irradiation. Moreover, by loading vascular endothelial growth factor into the hydrogel, the promoted migration and angiogenesis effects of endothelial cells can also be achieved. Based on these features, it is demonstrated that such sprayable BP hydrogels can effectively facilitate joint wounds healing by accelerating angiogenesis, alleviating inflammation, and improving wound microenvironment. Thus, it is believed that this NIR‐responsive removable BP hydrogel dressing will put forward an innovative concept in designing wound dressings. A novel sprayable black phosphorus (BP)‐based multifunctional hydrogel wound dressing is prepared here. The obtained hydrogel displays tissue adhesiveness, antioxidant, antibacterial, and promotes angiogenesis, and NIR‐responsive on‐demand dissolution behaviors, which can be used as promising wound dressings.

Anthrax is a severe infectious illness triggered by the bacterium Bacillus anthracis. This bacterium is naturally found in soil and mainly impacts domestic and wild animals. Human anthrax infection occurs primarily through close occupational contact with infected livestock. Anthrax has been reported each year in China for decades since it became a reportable disease. However, concerns about anthrax are growing in recent years. In this paper, we reviewed the literature on Anthrax and Bacillus anthracis. We delineated the epidemiological traits of human anthrax in China as well as the potential risk factors for outbreaks. Additionally, we offer recommendations for prevention and control. We emphasize that effective management of anthrax in humans largely depends on the successful control of the disease in animals. It is also suggested that anthrax is unlikely to completely disappear or escalate into a large-scale epidemic in China in the near future. Human cases of anthrax are expected to remain at a low prevalence, which alleviates the need for excessive panic. Instead, proactive measures should be implemented to enhance the prevention and control of anthrax, ultimately leading to further improvements in public health.

Hydrogels are considered as a promising medical patch for wound healing. Researches in this aspect are focused on improving their compositions and permeability to enhance the effectiveness of wound healing. Here, novel prolamins‐assembled porous hydrogel microfibers with the desired merits for treating diabetes wounds are presented. Such microfibers are continuously generated by one‐step microfluidic spinning technology with acetic acid solution of prolamins as the continuous phase and deionized water as the dispersed phase. By adjusting the prolamin concentration and flow rates of microfluidics, the porous structure and morphology as well as diameters of microfibers can be well tailored. Owing to their porosity, the resultant microfibers can be employed as flexible delivery systems for wound healing actives, such as bacitracin and vascular endothelial growth factor (VEGF). It is demonstrated that the resultant hydrogel microfibers are with good cell‐affinity and effective drug release efficiency, and their woven patches display superior in vivo capability in treating diabetes wounds. Thus, it is believed that the proposed prolamins‐assembled porous hydrogel microfibers will show important values in clinic wound treatments. Novel prolamins‐assembled porous hydrogel microfibers generated from microfluidic spinning technology for wound healing are presented. The resultant microfibers possess porous structure and could be served as the drug‐loaded carrier. The drug‐loaded microfibers show good cell‐affinity and effective drug release efficiency, which have potential values in wound disease treatment.

Investigation of patient-derived primary tissues is of great importance in the biomedical field, but recent tissue slicing and cultivation techniques still have difficulties in satisfying clinical requirements. Here, we propose a controllable histotomy strategy that utilizes hierarchical magnetic microneedle array robots to tailor primary tissues and establish the desired high-throughput tissue-on-a-chip. This histotomy was performed using a three-dimensional printed, mortise-tenon-structured slicing device coupled with a magnetic-particle-loaded and pagoda-shaped microneedle array scaffold. Due to the multilayered structure of these microneedles, tissue specimens can be fixed onto the microneedle scaffold via mechanical interlocking, thereby effectively avoiding tissue slipping during the slicing process. Owing to the encapsulation of magnetic microneedle fragments, these tissue pieces can act as magnetically responsive biohybrid microrobots and can be easily manipulated by magnetic fields, facilitating their separation, transportation, and dynamic culture. Using this strategy, we demonstrated that primary pancreatic cancer tissues can be tailored into tiny pieces and cultured in multilayered microfluidic chips for efficient high-throughput drug screening, indicating the promising future of this technique’s application in clinical settings.

Hydrogel microcarrier-based drug delivery systems are of great value in the combination therapy of tumors. Current research directions concentrate on the development of more economic, convenient, and effective combined therapeutic platforms. Herein, we developed novel adhesive composite microparticles (MPPMD) with combined chemo- and photothermal therapy ability viamicrofluidic electrospray technology for local hepatocellular carcinoma treatment. These composite microparticles consisted of doxorubicin (DOX)-loaded and polydopamine-wrapped mesoporous silicon and alginate. Benefiting from such a strategy of hierarchical structure drug loading, DOX could be gradually released from the system, effectively avoiding the direct toxicity of chemotherapeutics to the body. Additionally, the designed microparticles could not only effectively treat tumors by releasing the chemotherapy drug DOX but also show excellent photothermal properties under the irradiation of near-infrared light, achieving combined chemo- and photothermal treatment effects. Based on these advantages, the MPPMDcould remarkably eliminate tumor cells in vitroand enormously restrict tumor development in vivo. These results illustrate that such composite microparticles are ideal combination treatment platforms, possessing promising expectations for cancer therapy.

We aimed to develop an efficient detection platform that can identify a larger number of suspicious samples in a single test, saving time, manpower, and material costs, and providing vital support to the public health system in coping with the current challenging and dynamic bioterrorism threat landscape, particularly in regions of turmoil and conflict. We have successfully developed a high-throughput, multitarget fluorescent array detection platform by effectively combining integrating multiprobe amplification (MPA) with melting curve analysis. Specifically, we have established reliable laboratory testing methods for eight highly pathogenic bacteria, including Bacillus anthracis, Yersinia pestis, Brucellaspp., Burkholderia pseudomallei, Francisella tularensis, Vibrio cholerae, Salmonella typhi, and Staphylococcus aureus. Our method achieves sensitive and specific simultaneous detection of eight target bacteria in one well by optimizing the reaction conditions of MPA. In the assessment of 192 simulated environmental samples, both positive and negative coincidence rates were 100.00%. Among 48 simulated clinical samples, the positive coincidence rate reached 97.73%, while maintaining a perfect negative coincidence rate of 100.00%. Moreover, the detection platform holds immense potential for attaining a more comprehensive bioterrorism screening, and its high cost-effectiveness enables the provision of diverse and adaptable diagnostic methods for public health quarantine in underdeveloped countries and regions.

Stimuli-responsive gene delivery nanocarriers (GDNCs) possess huge potential in the gene therapy field owing to their effective protection, prolonged blood circulation, selective and targeted delivery, and controlled release of nucleic acid drugs.Recent advances in stimuli-responsive GDNCs for cancer therapy are classified, summarized, and exhibited by representative examples.The potential challenges and prospects of stimuli-responsive GDNCs toward clinical translation are outlined and the future research directions are outlooked.

Studying the self-assembly behavior of DNA origami allows a better understanding of molecular assembly characteristics at the nanoscale. Presently, the mechanisms governing growth and dynamics of DNA origami assembly are still not very clear and there is a lack of direct visualization of the growth processes on the long single-strand scaffold. Here, we investigate the kinetics, especially the real-time seeding growth process of six special designs of 2D DNA origami at room temperature (RT) without the assistance of denaturing chemicals. The prealignment of single-strand long scaffold and logical seeding growth behaviors are revealed during the growth process at RT. Furthermore, we studied the thermal stability of the DNA nanostructures under limited structural defects. Revealed characteristics of seeding growth can be used to build large and complex DNA nanodevices capable of performing logical operations with nanometer precision.

ABSTRACTEpsilon-toxin (ETX) is produced by types B and D strains of Clostridium perfringens, which cause fatal enterotoxaemia in sheep, goats and cattle. Previous studies showed that only a restricted number of cell lines are sensitive to ETX and ETX-induced hemolysis has not previously been reported. In this study, the hemolytic ability of ETX was examined using erythrocytes from 10 species including murine, rabbit, sheep, monkey and human. We found that ETX caused hemolysis in human erythrocytes (HC50 = 0.2 μM) but not erythrocytes from the other test species. Moreover, the mechanism of ETX-induced hemolysis was further explored. Recent studies showed that some bacterial toxins induce hemolysis through purinergic receptor (P2) activation. Hence, the function of purinergic receptors in ETX-induced hemolysis was tested, and we found that the non-selective P2 receptor antagonists PPADS inhibited ETX-induced lysis of human erythrocytes in a concentration-dependent manner, indicating that ETX-induced hemolysis requires activation of purinergic receptors. P2 receptors comprise seven P2X (P2X1–7) and eight P2Y (P2Y1, P2Y2, P2Y4, P2Y6, and P2Y11–P2Y14) receptor subtypes. The pattern of responsiveness to more selective P2-antagonists implies that both P2Y13 and P2X7 receptors are involved in ETX-induced hemolysis in human species. Furthermore, we demonstrated that extracellular ATP is likely not involved in ETX-induced hemolysis and the activation of P2 receptors. These findings clarified the mechanism of ETX-induced hemolysis and provided new insight into the activities and ETX mode of action.

ABSTRACTCronobacter sakazakii505108 was isolated from a sputum specimen of a neonate with severe pneumonia. C. sakazakii505108 co-harbors 3 resistance plasmids of the IncHI2, IncX3, and IncFIB incomparability groups, respectively. These 3 plasmids have acquired several accessory modules, which carry an extremely large number of resistance genes, especially including those involved in resistance to carbapenems, aminoglycoside, tetracyclines, and phenicols and sulphonamide/trimethoprim. These plasmid-borne antibiotic resistance genes were associated with insertion sequences, integrons, and transposons, indicating that the assembly and mobilization of the corresponding accessory modules with complex chimera structures are facilitated by transposition and/or homologous recombination. This is the first report of fully sequence plasmids in clinical Cronobacter, which provides a deeper insight into plasmid-mediated multi-drug resistance in Cronobacterfrom hospital settings.

Aim:This study aims to evaluate the genetic and population structure of Vibrio parahaemolyticusin the major coastal regions of China. Materials & methods:Multilocus sequence typing was performed. Results:Insertion of large sequence into recAhappened in nearly 30 strains, which were untypeable by multilocus sequence typing. A collection of 307 V. parahaemolyticusisolates were typed into 160 sequence types, including 117 novel ones. eBURST analysis revealed five clonal complexes, 11 doublets, and 108 singletons. The 160 sequence types formed two main lineages in the phylogenetic analysis. Conclusion:V. parahaemolyticusalong the Chinese coastal regions exhibits high levels of genetic diversity and has undergone significant purifying selection and frequent recombination. A deeper understanding of V. parahaemolyticusgenetic diversity could be obtained at the level of genome sequences.

Indium oxide (In2O3) has demonstrated to be an effective non-noble metal catalyst for methanol steam reforming reaction (MSR). However, the reaction mechanism of MSR and crucial structure-activity relations determining the catalytic performance of In2O3are still not fully understood yet. Using density functional theory (DFT) calculation, we systematically investigate the MSR process over a high-index In2O3(211) and a favoured catalytic cycle of MSR is determined. The results show that In2O3(211) possesses excellent dehydrogenation and oxidizing ability, on which CH3OH can readily adsorb on the In4csite and be easily activated by the reactive lattice oxygens, resulting in a total oxidation into CO2rather than CO, while the H2formation through surface H–H coupling limits the overall MSR activity because of the strong H adsorption on the two-coordinated lattice O (O2c). Our analyses show that the relatively inert three-coordinated lattice O (O3c) could play an important catalytic role. To uncover the influence of the local coordination of surface In atoms and lattice O on the catalytic activity, we evaluate the activity trend of several types of In2O3surfaces including (211), (111), and (100) by examining the rate-limiting, which reveals the following activity order: (211)>(111)>(100). These findings provide an in-depth understanding on the MSR reaction mechanism over In2O3catalysts and some basic structure-activity relations at the atomic scale, could facilitate the rational design of In2O3-based catalysts for MSR by controlling the local coordination environment of surface active sites.

MYCproto-oncogene dysregulation alters metabolism, translation, and other functions in ways that support tumor induction and maintenance. Although Myc+/−mice are healthier and longer-lived than control mice, the long-term ramifications of more complete Mycloss remain unknown. We now describe the chronic consequences of body-wide Mycinactivation initiated postnatally. “MycKO” mice acquire numerous features of premature aging, including altered body composition and habitus, metabolic dysfunction, hepatic steatosis, and dysregulation of gene sets involved in functions that normally deteriorate with aging. Yet, MycKO mice have extended lifespans that correlate with a 3- to 4-fold lower lifetime cancer incidence. Aging tissues from normal mice and humans also downregulate Myc and gradually alter many of the same Myc target gene sets seen in MycKO mice. Normal aging and its associated cancer predisposition are thus highly linked via Myc.

This study presents a comprehensive cellular atlas describing the ongoing pulmonary immune responses in the early stages of diffuse alveolar damage. This work indicates a vital role of the hyper‐inflammatory fibroblast subset around the bronchus, in mediating neutrophil infiltration through secreting soluble signaling mediators, thus boosting neutrophilic airway inflammation.

Diffuse alveolar damage (DAD) triggers neutrophilic inflammation in damaged tissues of the lung, but little is known about the distinct roles of tissue structural cells in modulating the recruitment of neutrophils to damaged areas. Here, by combining single‐cell and spatial transcriptomics, and using quantitative assays, we systematically analyze inflammatory cell states in a mouse model of DAD‐induced neutrophilic inflammation after aerosolized intratracheal inoculation with ricin toxin. We show that homeostatic resident fibroblasts switch to a hyper‐inflammatory state, and the subsequent occurrence of a CXCL1‐CXCR2 chemokine axis between activated fibroblasts (AFib) as the signal sender and neutrophils as the signal receiver triggers further neutrophil recruitment. We also identify an anatomically localized inflamed niche (characterized by a close‐knit spatial intercellular contact between recruited neutrophils and AFib) in peribronchial regions that facilitate the pulmonary inflammation outbreak. Our findings identify an intricate interplay between hyper‐inflammatory fibroblasts and neutrophils and provide an overarching profile of dynamically changing inflammatory microenvironments during DAD progression. Diffuse alveolar damage (DAD) triggers intense neutrophilic airway inflammation. This work demonstrates that proinflammatory activated fibroblasts (AFib) are induced in a mouse model of DAD. Neutrophil infiltration into the airway crucially depends on their cross‐talk with AFib via the soluble CXCL1‐CXCR2 chemokine axis.

Aim:This study aimed to characterize plasmid-mediated antimicrobial resistance in clinical Klebsiella pneumoniae1220 carrying blaCTX-M-14and qnrB4. Materials & methods:Plasmid p1220-CTXM was transformed from the 1220 isolate into Escherichia colithrough conjugal transfer and then fully sequenced. Antimicrobial susceptibility was determined by VITEK. Results:p1220-CTXM was an IncFIIKplasmid genetically closely related to pKP048 and carried resistance markers including blaCTX-M-14, blaDHA-1, qnrB4, sul1and qacEΔ1, all of which were harbored in a 35.7-kb multidrug-resistant region. blaCTX-M-14was located in a truncated ISEcp1-blaCTX-M-14-orf477transposition unit, and qnrB4and blaDHA-1were in a truncated qnrB4-blaDHA-1region. Conclusion:This study provided the insight into the co-occurrence of blaCTX-M-14and qnrB4and the evolution of pKP048-related IncFIIKplasmids.

ABSTRACTEpsilon toxin (ETX), a potent toxin, is produced by types B and D strains of Clostridium perfringens, which could cause severe diseases in humans and domestic animals. Mutant rETXF199Ewas previously demonstrated to be a good vaccine candidate. However, the mechanism concerned remains unknown. To clarify how F199E substitution reduced ETX toxicity, we performed a series of experiments. The results showed that the cell-binding and pore-forming ability of rETXF199Ewas almost abolished. We speculated that F199E substitution reduced toxicity by depriving the receptor binding capability of ETX, which contributed to the hypothesis that domain I of ETX is responsible for cell binding. In addition, our data suggested that ETX could cause Ca2+release from intracellular Ca2+stores, which may underlie an alternate pathway leading to cell death. Furthermore, ETX induced crenation of the MDCK cells was observed, with sags and crests first appearing on the surface of condensed MDCK cells, according to scanning electron microscopy. The data also demonstrated the safety and potentiality of rETXF199Eas a vaccine candidate for humans. In summary, findings of this work potentially contribute to a better understanding of the pathogenic mechanism of ETX and the development of vaccine against diseases caused by ETX, using mutant proteins.

To date, development of organic sensitizers has been predominately focused on light harvesting, highest occupied molecular orbital and lowest unoccupied molecular orbital energy levels, and the electron transferring process. In contrast, their adsorption mode as well as the dynamic loading behavior onto nanoporous TiO2is rarely considered. Herein, we have employed the time-of-flight secondary ion mass spectrometry (TOF-SIMS) to gain insight into the competitive dye adsorption mode and kinetics in the cosensitized porphyrin system. Using novel porphyrin dye FW-1and D–A−π–A featured dye WS-5, the different bond-breaking mode in TOF-SIMS and dynamic dye-loading amount during the coadsorption process are well-compared with two different anchoring groups, such as benzoic acid and cyanoacrylic acid. With the bombardment mode in TOF-SIMS spectra, we have speculated that the cyano group grafts onto nanoporous TiO2as tridentate binding for the common anchoring unit of cyanoacrylic acid and confirmed it through extensive first-principles density functional theory calculation by anchoring either the carboxyl or cyano group, which shows that the cyano group can efficiently participate in the adsorption of the WS-5molecule onto the TiO2nanocrystal. The grafting reinforcement interaction between the cyano group and TiO2in WS-5can well-explain the rapid adsorption characteristics. A strong coordinate bond between the lone pair of electrons on the nitrogen or oxygen atom and the Lewis acid sites of TiO2can increase electron injection efficiencies with respect to those from the bond between the benzoic acid group and the Brønsted acid sites of the TiO2surface. Upon optimization of the coadsorption process with dye WS-5, the photoelectric conversion efficiency based on porphyrin dye FW-1is increased from 6.14 to 9.72%. The study on the adsorption dynamics of organic sensitizers with TOF-SIMS analysis might provide a new venue for improvement of cosensitized solar cells.

Salmonellacan cause global foodborne illnesses in humans and many animals. The current diagnostic gold standard used for detecting Salmonellainfection is microbiological culture followed by serological confirmation tests. However, these methods are complicated and time-consuming. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis offers some advantages in rapid identification, for example, simple and fast sample preparation, fast and automated measurement, and robust and reliable identification up to genus and species levels, possibly even to the strain level. In this study, we established a reference database for species identification using whole-cell MALDI-TOF MS; the database consisted of 12 obtained main spectra of the Salmonellaculture collection strains belonged to seven serotypes. Eighty-two clinical isolates of Salmonellawere identified using established database, and partial 16S rDNA gene sequencing and serological method were used as comparison. We found that MALDI-TOF mass spectrometry provided high accuracy in identification of Salmonellaat species level but was limited to type or subtype Salmonellaserovars. We also tried to find serovar-specific biomarkers and failed. Our study demonstrated that (a) MALDI-TOF MS was suitable for identification of Salmonellaat species level with high accuracy and (b) that MALDI-TOF MS method presented in this study was not useful for serovar assignment of Salmonellacurrently, because of its low matching with serological method and (c) MALDI-TOF MS method presented in this study was not suitable to subtype S. typhimuriumbecause of its low discriminatory ability.

•The immunochromatographic assay was established in combination with TRFIA technology.•TRFIA technology effectively improves the sensitivity of the detection for TDH.•This method can effectively detect TDH in seafood samples.