Taking Photoacoustic Force into Account in Liquid-Phase Peak Force Infrared Microscopy.

The microscopic structure of the material's solid-liquid interface significantly influences its physicochemical properties. Peak force infrared microscopy (PFIR) is a powerful technique for analyzing these interfaces at the nanoscale, revealing crucial structure-activity relationships. PFIR is recognized for its explicit photothermal signal generation mechanism but tends to overlook other photoinduced forces, which can disturb the obtained infrared spectra, thereby reducing spectral signal-to-noise ratio (SNR) and sensitivity. We have developed a multiphysics-coupled theoretical model to assess the magnitudes of various photoinduced forces in PFIR experiments and have found that the magnitude of the photoacoustic force is comparable to that of the photothermal expansion force in a liquid environment. Our calculations show that through simple modulation of the pulse waveform it is possible to effectively suppress the photoacoustic interference, thereby improving the SNR and sensitivity of PFIR. This work aims to alert researchers to the potential for strong photoacoustic interference in liquid-phase PFIR measurements and enhance the performance of PFIR by clarifying the photoinduced forces entangled in the signals.

ThermomiR-377-3p-induced suppression of Cirbp expression is required for effective elimination of cancer cells and cancer stem-like cells by hyperthermia.

BACKGROUND: In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying hyperthermia resistance are still poorly understood. In this study, we investigated the roles of cold­inducible RNA binding protein (Cirbp) in regulating hyperthermia resistance and underlying mechanisms in nasopharyngeal carcinoma (NPC). METHODS: CCK-8 assay, colony formation assay, tumor sphere formation assay, qRT-PCR, Western blot were employed to examine the effects of hyperthermia (HT), HT + oridonin(Ori) or HT + radiotherapy (RT) on the proliferation and stemness of NPC cells. RNA sequencing was applied to gain differentially expressed genes upon hyperthermia. Gain-of-function and loss-of-function experiments were used to evaluate the effects of RNAi-mediated Cirbp silencing or Cirbp overexpression on the sensitivity or resistance of NPC cells and cancer stem-like cells to hyperthermia by CCK-8 assay, colony formation assay, tumorsphere formation assay and apoptosis assay, and in subcutaneous xenograft animal model. miRNA transient transfection and luciferase reporter assay were used to demonstrate that Cirbp is a direct target of miR-377-3p. The phosphorylation levels of key members in ATM-Chk2 and ATR-Chk1 pathways were detected by Western blot. RESULTS: Our results firstly revealed that hyperthermia significantly attenuated the stemness of NPC cells, while combination treatment of hyperthermia and oridonin dramatically increased the killing effect on NPC cells and cancer stem cell (CSC)­like population. Moreover, hyperthermia substantially improved the sensitivity of radiation­resistant NPC cells and CSC­like cells to radiotherapy. Hyperthermia noticeably suppressed Cirbp expression in NPC cells and xenograft tumor tissues. Furthermore, Cirbp inhibition remarkably boosted anti­tumor­killing activity of hyperthermia against NPC cells and CSC­like cells, whereas ectopic expression of Cirbp compromised tumor­killing effect of hyperthermia on these cells, indicating that Cirbp overexpression induces hyperthermia resistance. ThermomiR-377-3p improved the sensitivity of NPC cells and CSC­like cells to hyperthermia in vitro by directly suppressing Cirbp expression. More importantly, our results displayed the significantly boosted sensitization of tumor xenografts to hyperthermia by Cirbp silencing in vivo, but ectopic expression of Cirbp almost completely counteracted hyperthermia-mediated tumor cell-killing effect against tumor xenografts in vivo. Mechanistically, Cirbp silencing-induced inhibition of DNA damage repair by inactivating ATM-Chk2 and ATR-Chk1 pathways, decrease in stemness and increase in cell death contributed to hyperthermic sensitization; conversely, Cirbp overexpression-induced promotion of DNA damage repair, increase in stemness and decrease in cell apoptosis contributed to hyperthermia resistance. CONCLUSION: Taken together, these findings reveal a previously unrecognized role for Cirbp in positively regulating hyperthermia resistance and suggest that thermomiR-377-3p and its target gene Cirbp represent promising targets for therapeutic hyperthermia.

Inhibitory effect of baicalein on mice tremor induced by oxotremorine and mechanisms / 中国药理学与毒理学杂志

OBJECTIVE To investigate the anti- tremor effect and mechanism of baicalein on oxotremorine- induced muscle tremor in mice. METHODS The acute model of muscular tremor was induced by intraperitoneal injection of oxotremorine, and the latency, duration and frequency of muscle tremor in mice were measured immediately; the saliva of mice was measured to reflect the correlation between tremor and peripheral nerve function; the aim of this study was to determine the content of MDA and the activity of GSH-PX, and to investigate the anti-oxidation of mice with tremor model. The activity of acetylcholinesterase (AchE) and acetylcholine transferase (ChAT) can indirectly reflect the level of acetylcholine in the brain. The level of monoamine neurotransmitters in brain tissue was determined by high performance liquid chromatography (HPLC-ECD). RESULTS The animals in the model group appeared obvious tremoring, salivating and erecting and other symptoms. Compared to the model group, there was no obvious inhibitory effect on the administration of each dose. After 7, 14, 21 and 28 d of continuous administration, the latency, duration and tremor frequency of tremor mice were significantly shortened, the levels of acetylcholine were significantly decreased, the changes of DOPAC and DA neurotransmitters in the brain of model group were recovered, regulate the dynamic balance of acetylcholine and dopamine in the brain. CONCLUSION Long- term administration can improve the tremor behavior of mice, the mechanismmay be related to the regulation of neurotransmittersin brain.