Programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) blocking therapy has become a major pillar of cancer immunotherapy. Compared with antibodies targeting, small-molecule checkpoint inhibitors which have favorable pharmacokinetics are urgently needed. Here we identified berberine (BBR), a proven anti-inflammation drug, as a negative regulator of PD-L1 from a set of traditional Chinese medicine (TCM) chemical monomers. BBR enhanced the sensitivity of tumour cells to co-cultured T-cells by decreasing the level of PD-L1 in cancer cells. In addition, BBR exerted its antitumor effect in Lewis tumor xenograft mice through enhancing tumor-infiltrating T-cell immunity and attenuating the activation of immunosuppressive myeloid-derived suppressor cells (MDSCs) and regulatory T-cells (Tregs). BBR triggered PD-L1 degradation through ubiquitin (Ub)/proteasome-dependent pathway. Remarkably, BBR selectively bound to the glutamic acid 76 of constitutive photomorphogenic-9 signalosome 5 (CSN5) and inhibited PD-1/PD-L1 axis through its deubiquitination activity, resulting in ubiquitination and degradation of PD-L1. Our data reveals a previously unrecognized antitumor mechanism of BBR, suggesting BBR is small-molecule immune checkpoint inhibitor for cancer treatment.

The high redox level of tumor microenvironment inhibits the oxidation treatment and the immune response. Here, we innovatively develop maleimide liposome (ML) adjuvants to promote immunogenic cell death (ICD) induction and dendritic cells (DCs) maturation by glutathione (GSH) depletion for augmenting the photothermal immunotherapy of breast cancer. The ML effectively depletes the intracellular GSH and up-regulates reactive oxygen species (ROS) in both tumor cells and DCs. In tumor cells, the ROS boosted the ABTS·+ production to activate photothermal-induced ICD. In DCs, it relieved the immunosuppression, promoting DC maturation (57%) and antigen presenting. As a result of the ML assistant, the therapeutic systems improved the infiltration of CD8+ T cells to 53% in tumor tissues, eliciting strong abscopal effect and antimetastasis effect. The MLs were believed to be a superior candidate of adjuvants for enhancing immune response and cancer therapeutic efficacy.

With the innovation of microelectronics technology, the heat dissipation problem inside the device will face a severe test. In this work, cellulose aerogel (CA) with highly enhanced thermal conductivity (TC) in vertical planes was successfully obtained by constructing a vertically aligned silicon carbide nanowires (SiC NWs)/boron nitride (BN) network via the ice template-assisted strategy. The unique network structure of SiC NWs connected to BN ensures that the TC of the composite in the vertical direction reaches 2.21 W m−1 K−1 at a low hybrid filler loading of 16.69 wt%, which was increased by 890% compared to pure epoxy (EP). In addition, relying on unique porous network structure of CA, EP-based composite also showed higher TC than other comparative samples in the horizontal direction. Meanwhile, the composite exhibits good electrically insulating with a volume electrical resistivity about 2.35 × 1011 Ω cm and displays excellent electromagnetic wave absorption performance with a minimum reflection loss of − 21.5 dB and a wide effective absorption bandwidth (< − 10 dB) from 8.8 to 11.6 GHz. Therefore, this work provides a new strategy for manufacturing polymer-based composites with excellent multifunctional performances in microelectronic packaging applications.

Insomnia is a common sleep disorder which is prevalent in women and the elderly. Current insomnia drugs mainly target the γ-aminobutyric acid (GABA) receptor, melatonin receptor, histamine receptor, orexin, and serotonin receptor. GABAA receptor modulators are ordinarily used to manage insomnia, but they are known to affect sleep maintenance, including residual effects, tolerance, and dependence. In an effort to discover new drugs that relieve insomnia symptoms while avoiding side effects, numerous studies focusing on the neurotransmitter GABA and herbal medicines have been conducted. Traditional herbal medicines, such as Piper methysticum and the seed of Zizyphus jujuba Mill var. spinosa, have been widely reported to improve sleep and other mental disorders. These herbal medicines have been applied for many years in folk medicine, and extracts of these medicines have been used to study their pharmacological actions and mechanisms. Although effective and relatively safe, natural plant products have some side effects, such as hepatotoxicity and skin reactions effects of Piper methysticum. In addition, there are insufficient evidences to certify the safety of most traditional herbal medicine. In this review, we provide an overview of the current state of knowledge regarding a variety of natural plant products that are commonly used to treat insomnia to facilitate future studies.

No abstract

Stretchability and multifunctional heating abilities are highly desired for wearable electromagnetic interference (EMI) shielding fabrics to tackle the growing electromagnetic pollution for special crowd, such as pregnant women. Herein, we fabricated stretchable MXene-coated thermoplastic polyurethane (TPU) fabrics by simple uniaxial prestretching and spraying methods. The obtained unique wrinkled structure endowed the film with effective strain-invariant electrical conductivity and EMI shielding properties. Specifically, the prepared stretchable film with an extremely low MXene loading (0.417 mg cm–2) exhibited a stable EMI shielding effectiveness of approximately 30 dB under 50% tensile strain and durability during stretching and bending cycles. More importantly, owing to the high electrical conductivity and localized surface plasmon resonance (LSPR) effect of the MXene layer, the stretchable fabrics exhibited excellent Joule heating (up to 104 °C at a voltage of 5 V) and superior photothermal conversion abilities. Moreover, the unique wrinkled MXene-coating layer not only endows the fabrics with stretchable heat abilities but also enhances the photothermal conversion performance by increasing the light absorption area and travel path. We believe that this study offers a novel strategy for the versatile design of stretchable and multifunctional wearable shielding fabrics.

The Square Kilometre Array (SKA) project is an international effort to build the world’s largest radio telescope, with a one-square-kilometre collecting area. In addition to its ambitious scientific objectives, such as probing cosmic dawn and the cradle of life, the SKA demands several revolutionary technological breakthroughs, such as ultra-high precision synchronisation of the frequency references for thousands of antennas. In this report, with the purpose of application to the SKA, we demonstrate a frequency reference dissemination and synchronisation scheme in which the phase-noise compensation function is applied at the client site. Hence, one central hub can be linked to a large number of client sites, thus forming a star-shaped topology. As a performance test, a 100-MHz reference frequency signal from a hydrogen maser (H-maser) clock is disseminated and recovered at two remote sites. The phase-noise characteristics of the recovered reference frequency signal coincide with those of the H-maser source and satisfy the SKA requirements.

Glutathione (GSH) is abundant in “cold” tumors and adversely affects ferroptosis therapy and immune response. In their Research Article (e202202843), Minjie Sun and co‐workers developed cinnamaldehyde‐dimer‐based vesicles (CDC dimersomes) capable of depleting intracellular GSH via Michael addition to potentiate the ferroptosis and immunotherapy of breast cancer by turning the “cold” tumor into a “hot” tumor. CDC is the first drug‐dimer‐based vesicle applied for immune activation, inspiring the future design of functional vesicles.