Leading and following: Noise differently affects semantic and acoustic processing during naturalistic speech comprehension.

Despite the distortion of speech signals caused by unavoidable noise in daily life, our ability to comprehend speech in noisy environments is relatively stable. However, the neural mechanisms underlying reliable speech-in-noise comprehension remain to be elucidated. The present study investigated the neural tracking of acoustic and semantic speech information during noisy naturalistic speech comprehension. Participants listened to narrative audio recordings mixed with spectrally matched stationary noise at three signal-to-ratio (SNR) levels (no noise, 3 dB, -3 dB), and 60-channel electroencephalography (EEG) signals were recorded. A temporal response function (TRF) method was employed to derive event-related-like responses to the continuous speech stream at both the acoustic and the semantic levels. Whereas the amplitude envelope of the naturalistic speech was taken as the acoustic feature, word entropy and word surprisal were extracted via the natural language processing method as two semantic features. Theta-band frontocentral TRF responses to the acoustic feature were observed at around 400 ms following speech fluctuation onset over all three SNR levels, and the response latencies were more delayed with increasing noise. Delta-band frontal TRF responses to the semantic feature of word entropy were observed at around 200 to 600 ms leading to speech fluctuation onset over all three SNR levels. The response latencies became more leading with increasing noise and decreasing speech comprehension and intelligibility. While the following responses to speech acoustics were consistent with previous studies, our study revealed the robustness of leading responses to speech semantics, which suggests a possible predictive mechanism at the semantic level for maintaining reliable speech comprehension in noisy environments.

Nanoassembly with self-regulated magnetic thermal therapy and controlled immuno-modulating agent release for improved immune response.

Cancer immunotherapy is an emerging cancer therapeutic method by activating the patient's immune system but suffers from low immunogenicity at tumor sites. Fever-like heat is known to modulate an immune-friendly tumor microenvironment. Here, temperature-responsive iron oxide nanoassemblies (IONAs) are developed by crosslinking iron oxide nanoparticles (IONPs) and loaded with JQ1 (JQ1/IONAs), an immuno-modulating agent known to down-regulate PD-L1. In the presence of an alternating magnetic field (AMF), the IONAs demonstrate a much more effective magnetic thermal effect than IONPs and are responsively disassembled to prevent overheating. Compared with IONPs + AMF (∼ 41 °C) and unresponsive nanoassemblies (uIONAs) + AMF (∼ 50 °C), the IONAs + AMF with a temperature heated around 45 °C show a much better immune response and anti-tumor effect. Further combining the mild thermal therapy with controlled release of JQ1, the JQ1/IONAs + AMF completely eradicate the primary tumors and trigger a strong immune effect to inhibit the distant tumor growth as well as prevent tumor recurrence and metastasis. Our JQ1/IONAs not only provide a magnetic thermal agent with effective heating and temperature self-regulation ability but also serve as a heat-triggered JQ1 carrier to spontaneously combine mild magnetic thermal therapy with immune checkpoint blockade therapy.

Hot-band absorption assisted single-photon frequency upconversion luminescent nanophotosensitizer for 808 nm light triggered photodynamic immunotherapy of cancer.

Frequency upconversion luminescence (FUCL) based on hot-band absorption has attracted considerable attention in bioimaging and phototherapy fields for deep-seated cancer treatment. Photoimmunotherapy, a promising therapeutic approach induced by photodynamic therapy (PDT), can selectively kill cancer cells, reverse the immunosuppressive system, boost host immune response, and elicit durable antitumor immunity. To date, few near-infrared organic photosensitizers for photodynamic immunotherapy have been reported based on hot-band absorption. Herein, we report an upconversion luminescent phthalocyanine photosensitizer PdPc(OBu)8 with anti-Stokes emission at 748 nm and highly efficient singlet oxygen generation with hot-band absorption at 808 nm. Taking advantage of nanoliposomes, FUCL phthalocyanine nano-photosensitizers (PdPc NPs) were obtained to reduce the aggregation-caused quenching and improve water solubility and biocompatibility. PdPc NPs could be effectively accumulated in tumor tissues through intravenous administration, causing FUCL-induced PDT under 808 nm irradiation. Considering its finite immune responses and tumor ablation after PDT, a combination of PdPc NP-based PDT with checkpoint inhibitors (anti-PD-L1) for near-infrared photoimmunotherapy has been used to potentiate the antitumor efficacy that could simultaneously ablate primary tumors and inhibit the progression of distant tumors. This study can promote the development of upconversion-based PDT combined with immunotherapy for tumor precision therapy.