OTUD1 enhances gastric cancer aggressiveness by deubiquitinating EBV-encoded protein BALF1 to stabilize the apoptosis inhibitor Bcl-2.

The Epstein-Barr virus (EBV) is implicated in several cancers, including EBV-associated gastric cancer (EBVaGC). This study focuses on EBV-encoded BALF1 (BamH1 A fragment leftward reading frame 1), a key apoptosis regulator in EBV-related cancers, whose specific impact on EBVaGC was previously unknown. Our findings indicate that BALF1 overexpression in gastric cancer cells significantly enhances their proliferation, migration, and resistance to chemotherapy-induced apoptosis, confirming BALF1's oncogenic potential. A novel discovery is that BALF1 undergoes degradation via the ubiquitin-proteasome pathway. Through analysis of 69 deubiquitinating enzymes (DUBs), ovarian tumor protease (OTU) domain-containing protein 1 (OTUD1) emerged as a vital regulator for maintaining BALF1 protein stability. Furthermore, BALF1 was found to play a role in regulating the stability of the B-cell lymphoma-2 (Bcl-2) protein, increasing its levels through deubiquitination. This mechanism reveals BALF1's multifaceted oncogenic role in gastric cancer, as it contributes both directly and indirectly to cancer progression, particularly by stabilizing Bcl-2, known for its anti-apoptotic characteristics. These insights significantly deepen our understanding of EBV's involvement in the pathogenesis of gastric cancer. The elucidation of OTUD1's role in BALF1 regulation and its influence on Bcl-2 stabilization provide new avenues for therapeutic intervention in EBVaGC, bridging the gap between viral oncogenesis and cellular protein regulation and offering a more holistic view of gastric cancer development under the influence of EBV.

Validation of photoacoustic/ultrasound dual imaging in evaluating blood oxygen saturation.

Photoacoustic imaging (PAI) was performed to evaluate oxygen saturation (sO2) of blood-mimicking phantoms, femoral arteries in beagles, and radial arteries in humans at various sO2 plateaus. The accuracy (root mean square error, RMSE) of PAI sO2 compared with reference sO2 was calculated. In blood-mimicking phantoms, PAI achieved an accuracy of 1.49% and a mean absolute error (MAE) of 1.09% within 25 mm depth, and good linearity (R = 0.968; p < 0.001) was obtained between PAI sO2 and reference sO2. In canine femoral arteries, PAI achieved an accuracy of 2.16% and an MAE of 1.58% within 8 mm depth (R = 0.965; p < 0.001). In human radial arteries, PAI achieved an accuracy of 3.97% and an MAE of 3.28% in depth from 4 to 14 mm (R = 0.892; p < 0.001). For PAI sO2 evaluation at different depths in healthy volunteers, the RMSE accuracy of PAI sO2 increased from 2.66% to 24.96% with depth increasing from 4 to 14 mm. Through the multiscale method, we confirmed the feasibility of the hand-held photoacoustic/ultrasound (PA/US) in evaluating sO2. These results demonstrate the potential clinical value of PAI in evaluating blood sO2. Consequently, protocols for verifying the feasibility of medical devices based on PAI may be established.

In vivo Nakagami-m parametric imaging of microbubble-enhanced ultrasound regulated by RF and VF processing techniques.

PURPOSE: Application of the Nakagami statistical model and associated m parameter has the potential to suppress artifacts from adjustable system parameters and operator selections typical in echo amplitude-coded microbubble-enhanced ultrasound (MEUS). However, the feasibility of applying m estimation and determination of the associated Nakagami distribution features for in vivo MEUS remain to be investigated. Sensitivity and discriminability of m-coded MEUS are often limited since raw envelopes are regulated by complex radiofrequency (RF) and video-frequency (VF) processing. This study aims to develop an improved imaging approach for the m parameter estimation which can overcome the above limitations in in vivo condition. METHOD: The regulation effects of RF processing of pulse-inversion (PI) harmonic detection techniques and VF processing of logarithmic compression in Nakagami distributions were investigated in MEUS. A window-modulated compounding moment estimator was developed to estimate the MEUS m values. The sensitivity and discriminability of m-coded MEUS were quantified with contrast-to-tissue ratio (CTR), contrast-to-noise ratio (CNR), and axial and lateral resolutions, which were validated through in vivo perfusion experiments on rabbit kidneys. RESULTS: Regulated by RF and VF processing, the distributions of MEUS obeyed the Nakagami statistical model. The Nakagami-fitted correlation coefficient was 0.996 ± 0.003 (P < 0.05 in the t test and P < 0.001 in the Kolmogorov-Smirnov test). Among each of the m-coded MEUS methods, the logarithmic m-coded PI-MEUS scheme effectively characterized the peripheral rim perfusion features and details within the renal cortex. The CTR and CNR in this region reached 7.9 ± 1.5 dB and 34.4 ± 1.7 dB, respectively, which were higher than those of standard amplitude-coded MEUS; and the axial and lateral resolutions were 1.02 ± 0.02 and 0.91 ± 0.02 mm, respectively, which were slightly longer than those of amplitude-coded MEUS. CONCLUSIONS: The Nakagami statistical model could characterize MEUS even when the envelope distributions were regulated by RF and VF processing. The logarithmic m-coded PI-MEUS scheme significantly improved the sensitivity, discriminability, and robustness of m estimation in MEUS. The scheme provides an option to remove artifacts in echo amplitude-coded MEUS and to distinctly characterize the inherent microvasculature enhanced by microbubbles, with potential to improve and expand the role of MEUS in diagnostic ultrasound.

Numerical and experimental investigation of impacts of nonlinear scattering encapsulated microbubbles on Nakagami distribution.

PURPOSE: The Nakagami statistical model and Nakagami shape parameter m have been widely used in linear tissue characterization and preliminarily characterized the envelope distributions of nonlinear encapsulated microbubbles (EMBs). However, the Nakagami distribution of nonlinear scattering EMBs lacked a systematical investigation. Thus, this study aimed to investigate the Nakagami distribution of EMBs and illustrate the impact of EMBs' nonlinearity on the Nakagami model. METHOD: A group of simulated EMB phantoms and in vitro EMB dilutions with an increasing concentration distribution under various EMB nonlinearities, as regulated by acoustic parameters, were characterized by using the window-modulated compounding Greenwood-Durand estimator. RESULTS: Raw envelope histograms of simulated and in vitro EMBs were well matched with the Nakagami distribution with a high correlation coefficient of 0.965 ± 0.021 (P < 0.005). The mean values and gradients of m parameters of simulated and in vitro EMBs were smaller than those of linear scatterers due to the stronger nonlinearity. These m values exhibited a quasi-linear improvement with the increase in second harmonic nonlinear-to-linear component ratio regulated by pulse lengths and excitation frequencies at low- and high-concentration conditions. CONCLUSIONS: The Nakagami distribution was suitable for the EMBs characterization but the corresponding m parameter was affected by the EMBs' nonlinearity. These validations provided support and nonlinear impact assessment for the EMBs' characterization using the Nakagami statistical model in the future.

Influence of guided waves in bone on pulse-inversion contrast-enhanced ultrasound.

PURPOSE: Guided waves generated from bone cortex inevitably act on microbubbles flowing through skeletal muscle capillaries in contrast-enhanced ultrasound (CEUS) and might influence the image quality. However, the action mechanism underlying the guided waves influence is still unknown, especially under contrast pulse-inversion transmission mode. This study aimed to clarify the influence of guided waves on pulse-inversion CEUS, which was investigated via in vitro infusion experiments. METHOD: Tibia guided waves were detected at pulse-inversion transmission and then characterized by using a short-time Fourier transform energy distribution. Using results at normal incidence as a baseline, the influence of guided wave dispersion on the contrast and resolution of pulse-inversion CEUS was investigated at an oblique incidence through continuous microbubbles infusion experiments in a vessel-tibia flow phantom. RESULTS: Frequency-dispersive property of tibia guided waves was observed at phases 0° and 180°, which improved the contrast of CEUS and reduced its resolution. Pulse-inversion CEUS balanced the contrast enhancement and resolution degeneration induced by guided waves. By contrast, contrast-to-tissue ratio of pulse-inversion CEUS increased by up to 109.1 ± 13.2% (P < 0.05) due to guided waves and its resolution was up to 0.9 ± 0.1 times that of baseline. CONCLUSIONS: Alterations of contrast and resolution in pulse-inversion CEUS induced by guided waves might provide an additional assessment for the capillary perfusion in the skeletal muscle near the bone cortex.