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With the success of immune checkpoint inhibitors (ICIs), significant progress has been made in the field of cancer immunotherapy. Despite the long-lasting outcomes in responders, the majority of patients with cancer still do not benefit from this revolutionary therapy. Increasing evidence suggests that one of the major barriers limiting the efficacy of immunotherapy seems to coalesce with the hypoxic tumor microenvironment (TME), which is an intrinsic property of all solid tumors. In addition to its impact on shaping tumor invasion and metastasis, the hypoxic TME plays an essential role in inducing immune suppression and resistance though fostering diverse changes in stromal cell biology. Therefore, targeting hypoxia may provide a means to enhance the efficacy of immunotherapy. In this review, the potential impact of hypoxia within the TME, in terms of key immune cell populations, and the contribution to immune suppression are discussed. In addition, we outline how hypoxia can be manipulated to tailor the immune response and provide a promising combinational therapeutic strategy to improve immunotherapy.

The ubiquity of short videos has demonstrated vast potential for health communication. An expansion of research has examined the persuasive effect of health communication in short videos, yet a synthesis of the research is lacking. This paper aims to provide an overview of the literature by examining the persuasive effect of health communication in short videos, offering guidance for researchers and practitioners. In particular, it seeks to address 4 key research questions: What are the characteristics of short videos, samples, and research designs in short video-based health communication literature? What theories underpin the short video-based health communication literature? What are the persuasive effects of health communication in short videos? and What directions should future research in this area take? Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, an electronic search of 10 databases up to March 10, 2023, generated 4118 results. After the full-text screening, 18 articles met the eligibility criteria. The current research lacks a uniform definition of short videos, demonstrates sample biases in location and education, and adopts limited methodologies. Most studies in this synthesis are theoretically grounded or use theoretical concepts, which are predominantly well examined in persuasion research. Moreover, relevant topics and suitable themes are effective in persuasive health communication outcomes, whereas the impact of diverse narrative techniques remains ambiguous. We recommend that future research extends the definition of short videos beyond time constraints and explores non-Western and less-educated populations. In addition, researchers should consider diverse methods to provide a more comprehensive examination and investigate the impact of audience targeting and narrative techniques in short video health communication. Finally, investigating how the unique aspects of short videos interact with or challenge traditional persuasion theories is essential.

Plants benefit extensively from endophytic bacteria, which live in host plant tissues exerting no harmful effects. Bacterial endophytes promote the growth of host plants and enhance their resistance toward various pathogens and environmental stresses. They can also regulate the synthesis of secondary metabolites with significant medicinal properties and produce various biological effects. This review summarizes recent studies on the relationships between bacterial endophytes and medicinal plants. Endophytic bacteria have numerous applications in agriculture, medicine, and other industries: improving plant growth, promoting resistance toward both biotic and abiotic stresses, and producing metabolites with medicinal potential. Their distribution and population structure are affected by their host plant’s genetic characteristics and health and by the ecology of the surrounding environment. Understanding bacterial endophytes can help us use them more effectively and apply them to medicinal plants to improve yield and quality.

It is extremely difficult to accurately predict the rock damage evolution during the underground space development or the deep excavation activity. In this paper, based on the statistical damage mechanics, a plastic strain-induced damage model of porous rock was established to describe the damage evolution and the constitutive behavior of porous rock under different stress paths. In the proposed model, the modified porosity was introduced which considered the effect of the generalized plastic shear strain. Besides, the proposed damage evolution function was also controlled by the generalized plastic shear strain. To validate the proposed damage model, the sandstone is selected as the experimental specimen due to it is a typical porous rock, and a series of conventional tri-axial compressive experiments (CTC) and confining pressure unloading experiments under constant deviatoric stress (UCP-CDS) were carried out. Furthermore, the confining pressure unloading experimental data under increscent deviatoric stress (UCP-IDS) was referenced to further validate the applicability of the proposed model. The results showed that the deviatoric strain-damage curves were an “S” shape, moreover, the relationship between the damage variable with the unloading ratio was exponential function. The proposed damage model could better reflect the void volume change and the radial dilation during the unloading process. Moreover, the model could successfully capture the damage evolution law and the mechanical behavior of sandstone by matching a set of tri-axial compressive experiments under different stress paths. Finally, it is found that the strength, strain-hardening and strain-softening characteristics were controlled by the Weibull distributed parameters m0 and F0.HighlightsThe modified porosity was introduced which considered the effect of the generalized plastic shear strain.The relationship between the damage variable with the unloading ratio was exponential function.The proposed model could reflect the void volume and the radial dilation.The proposed model could reflect the stress-strain behavior under different stress paths.

In the human body, 50–70 billion cells die every day, resulting in the generation of a large number of apoptotic bodies. However, the detailed biological role of apoptotic bodies in regulating tissue homeostasis remains unclear. In this study, we used Fas-deficient MRL/ lpr and Caspase 3 −/− mice to show that reduction of apoptotic body formation significantly impaired the self-renewal and osteo-/adipo-genic differentiation of bone marrow mesenchymal stem cells (MSCs). Systemic infusion of exogenous apoptotic bodies rescued the MSC impairment and also ameliorated the osteopenia phenotype in MRL/ lpr , Caspase 3 −/− and ovariectomized (OVX) mice. Mechanistically, we showed that MSCs were able to engulf apoptotic bodies via integrin αvβ3 and reuse apoptotic body-derived ubiquitin ligase RNF146 and miR-328-3p to inhibit Axin1 and thereby activate the Wnt/β-catenin pathway. Moreover, we used a parabiosis mouse model to reveal that apoptotic bodies participated in the circulation to regulate distant MSCs. This study identifies a previously unknown role of apoptotic bodies in maintaining MSC and bone homeostasis in both physiological and pathological contexts and implies the potential use of apoptotic bodies to treat osteoporosis.

Background Apoptotic vesicles are extracellular vesicles generated by apoptotic cells that were previously regarded as containing waste or harmful substances but are now thought to play an important role in signal transduction and homeostasis regulation. Methods In the present review, we reviewed many articles published over the past decades on the subtypes and formation of apoptotic vesicles and the existing applications of these vesicles. Results Apoptotic bodies were once regarded as vesicles released by apoptotic cells, however, apoptotic vesicles are now regarded to include apoptotic bodies, apoptotic microvesicles and apoptotic exosomes, which exhibit variation in terms of biogenesis, sizes and properties. Applications of apoptotic vesicles were first reported long ago, but such reports have been rarer than those of other extracellular vesicles. At present, apoptotic vesicles have been utilized mainly in four aspects, including in direct therapeutic applications, in their engineering as carriers, in their construction as vaccines and in their utilization in diagnosis. Conclusion Building on a deeper understanding of their composition and characteristics, some studies have utilized apoptotic vesicles to treat diseases in more novel ways. However, their limitations for clinical translation, such as heterogeneity, have also emerged. In general, apoptotic vesicles have great application potential, but there are still many barriers to overcome in their investigation. DRFuKD8DSSWF6QPQHjkUrj Video Abstract

Mesenchymal stem cell transplantation (MSCT) promotes cutaneous wound healing. Numerous studies have shown that the therapeutic effects of MSCT appear to be mediated by paracrine signaling. However, the cell-cell interaction during MSCT between MSCs and macrophages in the region of cutaneous wound healing is still unknown. In this study, early depletion of macrophages delayed the wound repair with MSC injection, which suggested that MSC-mediated wound healing required macrophages. Moreover, we demonstrated that systemically infused bone marrow MSCs (BMMSCs) and jaw bone marrow MSCs (JMMSCs) could translocate to the wound site, promote macrophages toward M2 polarization, and enhance wound healing. In vitro coculture of MSCs with macrophages enhanced their M2 polarization. Mechanistically, we found that exosomes derived from MSCs induced macrophage polarization and depletion of exosomes of MSCs reduced the M2 phenotype of macrophages. Infusing MSCs without exosomes led to lower number of M2 macrophages at the wound site along with delayed wound repair. We further showed that the miR-223, derived from exosomes of MSCs, regulated macrophage polarization by targeting pknox1. These findings provided the evidence that MSCT elicits M2 polarization of macrophages and may accelerate wound healing by transferring exosome-derived microRNA.

Phosphoglycerate dehydrogenase (PHGDH) catalyzes the committed step in de novo serine biosynthesis. Paradoxically, PHGDH and serine synthesis are required in the presence of abundant environmental serine even when serine uptake exceeds the requirements for nucleotide synthesis. Here, we establish a mechanism for how PHGDH maintains nucleotide metabolism. We show that inhibition of PHGDH induces alterations in nucleotide metabolism independent of serine utilization. These changes are not attributable to defects in serine-derived nucleotide synthesis and redox maintenance, another key aspect of serine metabolism, but result from disruption of mass balance within central carbon metabolism. Mechanistically, this leads to simultaneous alterations in both the pentose phosphate pathway and the tri-carboxylic acid cycle, as we demonstrate based on a quantitative model. These findings define a mechanism whereby disruption of one metabolic pathway induces toxicity by simultaneously affecting the activity of multiple related pathways. Serine synthesis from glucose is required even when serine is available from the environment. Here, the authors explain this paradox by showing that the enzyme PHGDH enables nucleotide synthesis by coordinating anabolic fluxes related to central carbon metabolism, independent of its role in serine production.

Thermal-resistance temperature sensors generally employ temperature-sensitive materials as active layers, which are always deposited on a flexible substrate to improve flexibility. Such a temperature sensor is usually integrated in wearable devices with other sensors, such as pressure sensors and stretchable sensors. In prior works, the temperature and pressure sensors are usually located in different layers in a multifunction sensor, which results in a complicated fabrication process, as well as a large thickness of devices. Meanwhile, many temperature sensors are based on large areas of non-transparent materials, leading to difficulties in integrating display applications. In this paper, we demonstrate a flexible temperature sensor based on polyaniline/graphene (GPANI)–polyvinyl butyral (PVB) thin film and indium tin oxides (ITO)- polyethylene terephthalate (PET) substrates. The GPANI particles embedded in PVB film not only contribute to temperature detection, but also response to external pressures, due to weak deformations. In addition, the thin composite film (2.7 μm) highly improved the transparency. By optimizing the device structure, the sensor integrates temperature and pressure detection into one single layer, which shows a wide temperature range of 25–80 °C, a pressure range of 0–30 kPa, and a high transparency (>80%). The temperature sensor offers great potential for applications in emerging wearable devices and electronic skins.

Background As the major interface between the body and the external environment, the skin is liable to various injuries. Skin injuries often lead to severe disability, and the exploration of promising therapeutic strategies is of great importance. Exogenous mesenchymal stem cell (MSC)-based therapy is a potential strategy due to the apparent therapeutic effects, while the underlying mechanism is still elusive. Interestingly, we observed the extensive apoptosis of exogenous bone marrow mesenchymal stem cells (BMMSCs) in a short time after transplantation in mouse skin wound healing models. Considering the roles of extracellular vesicles (EVs) in intercellular communication, we hypothesized that the numerous apoptotic bodies (ABs) released during apoptosis may partially contribute to the therapeutic effects. Methods ABs derived from MSCs were extracted, characterized, and applied in mouse skin wound healing models, and the therapeutic effects were evaluated. Then, the target cells of ABs were explored, and the effects of ABs on macrophages were investigated in vitro. Results We found ABs derived from MSCs promoted cutaneous wound healing via triggering the polarization of macrophages towards M2 phenotype. In addition, the functional converted macrophages further enhanced the migration and proliferation abilities of fibroblasts, which together facilitated the wound healing process. Conclusions Collectively, our study demonstrated that transplanted MSCs promoted cutaneous wound healing partially through releasing apoptotic bodies which could convert the macrophages towards an anti-inflammatory phenotype that plays a crucial role in the tissue repair process.