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Cuprous-based nanozymes have demonstrated great potential for cascade chemodynamic therapy (CDT) due to their higher catalytic efficiency and simple reaction conditions. Here, hollow cuprous oxide@nitrogen-doped carbon (HCONC) dual-shell structures are designed as nanozymes for CDT oncotherapy. This HCONC with a size distribution of 130 nm is synthesized by a one-step hydrothermal method using cupric nitrate and dimethyl formamide as precursors. The thin-layer carbon (1.88 nm) of HCONC enhances the water-stability and reduces the systemic toxicity of cuprous oxide nanocrystals. The dissolved Cu

The prevalence of tinnitus is positively correlated with hearing loss, although, tinnitus can also present alongside clinically normal pure-tone thresholds. As standard pure tone audiograms (PTA) only sample at octave or inter-octaves, they potentially can miss lesions between the tested frequencies. Here we investigate if tinnitus patients with normal audiograms have hearing loss missed by standard PTA testing, referred as "missed hearing loss" in the paper. Hearing thresholds in 106 tinnitus patients who have a normal PTA were tested using fine frequency resolution (1/24 octave step) audiometry, referred as precision PTA (P-PTA), at ±1/3 octave band centered at their tinnitus frequencies. Tinnitus pitch, loudness and residual inhibition were evaluated based on the result of P-PTA. DPOAEs were also tested to evaluate the function of outer hair cells (OHC). Using the P-PTA test, we found that 49% (52 out of 106) of tinnitus patients with normal audiograms showed sharply notched hearing loss and most of the notches were at their tinnitus frequencies. Using a fine frequency step (1/24 octave) to assess tinnitus pitch, the successful matching rate increased to 84%, significantly higher than the rate measured in traditional method (51%, Fisher's test, P 0.0001, n = 106). The number of patients whose tinnitus loudness was less than 5 dB SL increased from 26% to 55% after the loudness reassessment based on the tinnitus pitch match (n = 106, Chi-Square test, P 0.01). The percentage of patients who showed positive residual inhibition of tinnitus also increased from 31% to 54% (Chi-Square test, P 0.05). DPOAEs revealed significantly reduced OAE amplitude in the tinnitus patients, suggesting that OHC dysfunction may contribute to their notched hearing loss. However, in 13 out of 31 patients with notched hearing loss, their DPOAE did not show any reduction which suggests that their notched hearing loss may be induced by the dysfunction of the inner hair cells or afferent synapses (synaptopathy). Our study confirmed hidden cochlear impairments in tinnitus patients with seemingly normal audiograms. We conclude that P-PTA can help identify a mild hearing impairment that may otherwise be missed by conventional PTA and that P-PTA can also improve tinnitus evaluation accuracy.