Synergistic SDT/cuproptosis therapy for liver hepatocellular carcinoma: enhanced antitumor efficacy and specific mechanisms.

The efficacy of sonodynamic therapy (SDT), an emerging approach for tumor treatment, is hindered by the high levels of the antioxidant glutathione (GSH) in the tumor microenvironment (TME). In this study, we constructed nanobubbles loaded with the sonosensitizer HMME and the tumor-targeting peptide RGD (HMME-RGD@CF NBs) for synergistic SDT/cuproptosis therapy of liver hepatocellular carcinoma (LIHC) in combination with Elesclomol-Cu as cuproptosis inducers. Endogenous GSH is consumed by Cu to modulate the complex TME, thereby amplifying oxidative stress and further improving SDT performance.

Mechanism exploration of synergistic photo-immunotherapy strategy based on a novel exosome-like nanosystem for remodeling the immune microenvironment of HCC.

The immunosuppressive tumor microenvironment (TME) has become a major challenge in cancer immunotherapy, with abundant tumor-associated macrophages (TAMs) playing a key role in promoting tumor immune escape by displaying an immunosuppressive (M2) phenotype. Recently, it was reported that M1 macrophage-derived nanovesicles (M1NVs) can reprogram TAMs to an anti-tumor M1 phenotype, thereby significantly alleviating the immunosuppressive TME and enhancing the anti-tumor efficacy of immunotherapy. Herein, we developed M1NVs loaded with mesoporous dopamine (MPDA) and indocyanine green (ICG), which facilitated the recruitment of M2 TAMs through synergistic photothermal and photodynamic therapy.

The choroid plexus synergizes with immune cells during neuroinflammation.

The choroid plexus (ChP) is a vital brain barrier and source of cerebrospinal fluid (CSF). Here, we use longitudinal two-photon imaging in awake mice and single-cell transcriptomics to elucidate the mechanisms of ChP regulation of brain inflammation. We used intracerebroventricular injections of lipopolysaccharides (LPS) to model meningitis in mice and observed that neutrophils and monocytes accumulated in the ChP stroma and surged across the epithelial barrier into the CSF.

Sensory neurons: An integrated component of innate immunity.

The sensory nervous system possesses the ability to integrate exogenous threats and endogenous signals to mediate downstream effector functions. Sensory neurons have been shown to activate or suppress host defense and immunity against pathogens, depending on the tissue and disease state. Through this lens, pro- and anti-inflammatory neuroimmune effector functions can be interpreted as evolutionary adaptations by host or pathogen.

Basophils are important for development of allergic skin inflammation.

Background: Atopic dermatitis skin lesions exhibit increased infiltration by basophils. Basophils produce IL-4, which plays an important role in the pathogenesis of atopic dermatitis.

Objective: We sought to determine the role of basophils in a mouse model of antigen-driven allergic skin inflammation.

S. aureus drives itch and scratch-induced skin damage through a V8 protease-PAR1 axis.

Itch is an unpleasant sensation that evokes a desire to scratch. The skin barrier is constantly exposed to microbes and their products. However, the role of microbes in itch generation is unknown.

Uniformity improvement of a mini-LED backlight by a quantum-dot color conversion film with nonuniform thickness.

Mini-LED backlights energized by quantum-dot color conversion (QDCC) hold great potential for technological breakthroughs of liquid crystal displays. However, luminance uniformity issues should still be urgently solved owing to the large interval of direct-lit mini-LEDs, especially when covering with a QDCC film (QDCCF) with uniform thickness. Herein, we propose a uniformity improvement approach of mini-LED backlights by employing a QDCCF with nonuniform thickness based on the Lambertian distribution of mini-LEDs, which is demonstrated by screen-printing preparation and ray-tracing simulation.

A collaboration between immune cells and the choroid plexus epithelium in brain inflammation.

The choroid plexus (ChP) is a vital brain barrier and source of cerebrospinal fluid (CSF). Here, we use chronic two-photon imaging in awake mice and single-cell transcriptomics to demonstrate that in addition to these roles, the ChP is a complex immune organ that regulates brain inflammation. In a mouse meningitis model, neutrophils and monocytes accumulated in ChP stroma and surged across the epithelial barrier into the CSF.

On-person adaptive evolution of Staphylococcus aureus during treatment for atopic dermatitis.

The opportunistic pathogen Staphylococcus aureus frequently colonizes the inflamed skin of people with atopic dermatitis (AD) and worsens disease severity by promoting skin damage. Here, we show, by longitudinally tracking 23 children treated for AD, that S. aureus adapts via de novo mutations during colonization.

Estimation of effects of extreme temperature on the risk of hospitalisation in Taiwan.

Background: Extreme temperatures are triggering and exacerbating hospital admissions and health burdens; however, it is still understudied. Therefore, we evaluated the effects of the average temperature on overall hospitalisation and the average length of hospital stay.

Methods: Daily area-specific age-sex stratified hospitalisation records from 2006 to 2020 were collected from the National Health Research Institutes of Taiwan.

Bacteria hijack a meningeal neuroimmune axis to facilitate brain invasion.

The meninges are densely innervated by nociceptive sensory neurons that mediate pain and headache. Bacterial meningitis causes life-threatening infections of the meninges and central nervous system, affecting more than 2.5 million people a year.

Quantifying the effects of anomalies of temperature, precipitation, and surface water storage on diarrhea risk in Taiwan.

Objectives: Diarrheal disease continues to be a significant cause of morbidity and mortality. We investigated how anomalies in monthly average temperature, precipitation, and surface water storage (SWS) impacted bacterial, and viral diarrhea morbidity in Taiwan between 2004 and 2015.

Methods: A multivariate analysis using negative binomial generalized estimating equations was employed to quantify age-specific and cause-specific cases of diarrhea associated with anomalies in temperature, precipitation, and SWS.

Immunity to the microbiota promotes sensory neuron regeneration.

Tissue immunity and responses to injury depend on the coordinated action and communication among physiological systems. Here, we show that, upon injury, adaptive responses to the microbiota directly promote sensory neuron regeneration. At homeostasis, tissue-resident commensal-specific T cells colocalize with sensory nerve fibers within the dermis, express a transcriptional program associated with neuronal interaction and repair, and promote axon growth and local nerve regeneration following injury.

A broad-spectrum antibacterial and tough hydrogel dressing accelerates healing of infected wound in vivo.

Infection can disturb the wound healing process and lead to poor skin regeneration, chronic wound, septicemia and even death. To combat the multi-drug resistance bacteria or fungi, it is urgent and necessary to develop advanced antimicrobial wound dressings. In this study, a composite hydrogel dressing composed of polyvinyl alcohol (PVA), agarose, glycerol and antibacterial hyperbranched polylysine (HBPL) was prepared by a freeze-thawing method.

The impact of temperature and precipitation on all-infectious-, bacterial-, and viral-diarrheal disease in Taiwan.

Background: The ongoing climate change will elevate the incidence of diarrheal in 2030-2050 in Asia, including Taiwan. This study investigated associations between meteorological factors (temperature, precipitation) and burden of age-cause-specific diarrheal diseases in six regions of Taiwan using 13 years of (2004-2016) population-based data.

Methods: Weekly cause-specific diarrheal and meteorological data were obtained from 2004 to 2016.

Nociceptor neurons direct goblet cells via a CGRP-RAMP1 axis to drive mucus production and gut barrier protection.

Neuroepithelial crosstalk is critical for gut physiology. However, the mechanisms by which sensory neurons communicate with epithelial cells to mediate gut barrier protection at homeostasis and during inflammation are not well understood. Here, we find that Nav1.

Promoting the healing of infected diabetic wound by an anti-bacterial and nano-enzyme-containing hydrogel with inflammation-suppressing, ROS-scavenging, oxygen and nitric oxide-generating properties.

The diabetic wound is easily to develop into a chronic wound because of the extremely serious and complex inflammatory microenvironment including biofilm formation, over-expressed reactive oxygen species (ROS), hypoxia and insufficiency of nitric oxide (NO) synthesis. In this work, a multifunctional hydrogel was designed and prepared by crosslinking hydrophilic poly(PEGMA-co-GMA-co-AAm) (PPGA) polymers with hyperbranched poly-L-lysine (HBPL)-modified manganese dioxide (MnO) nanozymes. Pravastatin sodium, which is supposed to participate in the synthesis of NO, was further loaded to obtain the HMP hydrogel.

A tough synthetic hydrogel with excellent post-loading of drugs for promoting the healing of infected wounds in vivo.

Bacterial infection is a major obstacle to the wound healing process. The hydrogel dressings with a simpler structure and good antibacterial and wound healing performance are appealing for clinical application. Herein, a robust hydrogel was synthesized from acrylamide (AM), acrylic acid (AA) and N,N'-methylene diacrylamide (MBA) via a redox initiating polymerization.

A neuropeptide regulates immunity across species.

Communication between the nervous system and immune system is important for regulating immunity in health and disease. Yu et al. (2022) show that neuropeptide Y and its homolog NPF serve as a "language" to facilitate crosstalk between these two systems across species, enabling neurons to downregulate harmful immune responses.

Cordycepin augments the chemosensitivity of osteosarcoma to cisplatin by activating AMPK and suppressing the AKT signaling pathway.

Background: Osteosarcoma is the most common primary bone tumor in children and adolescents. However, some patients with osteosarcoma develop resistance to chemotherapy, leading to a poor clinical prognosis. Hence, effective therapeutic agents that can improve the response to chemotherapy drugs to improve the prognosis of patients with osteosarcoma are urgently needed.