Assessment of arterial pulsatility of cerebral perforating arteries using 7T high-resolution dual-VENC phase-contrast MRI.

PURPOSE: Directly imaging the function of cerebral perforating arteries could provide valuable insight into the pathology of cerebral small vessel diseases (cSVD). Arterial pulsatility has been identified as a useful biomarker for assessing vascular dysfunction. In this study, we investigate the feasibility and reliability of using dual velocity encoding (VENC) phase-contrast MRI (PC-MRI) to measure the pulsatility of cerebral perforating arteries at 7 T. METHODS: Twenty participants, including 12 young volunteers and 8 elder adults, underwent high-resolution 2D PC-MRI scans with VENCs of 20 cm/s and 40 cm/s at 7T. The sensitivity of perforator detection and the reliability of pulsatility measurement of cerebral perforating arteries using dual-VENC PC-MRI were evaluated by comparison with the single-VENC data. The effects of temporal resolution in the PC-MRI acquisition and aging on the pulsatility measurements were investigated. RESULTS: Compared to the single VENCs, dual-VENC PC-MRI provided improved sensitivity of perforator detection and more reliable pulsatility measurements. Temporal resolution impacted the pulsatility measurements, as decreasing temporal resolution led to an underestimation of pulsatility. Elderly adults had elevated pulsatility in cerebral perforating arteries compared to young adults, but there was no difference in the number of detected perforators between the two age groups. CONCLUSION: Dual-VENC PC-MRI is a reliable imaging method for the assessment of pulsatility of cerebral perforating arteries, which could be useful as a potential imaging biomarker of aging and cSVD.

Highly accelerated non-contrast-enhanced time-resolved 4D MRA using stack-of-stars golden-angle radial acquisition with a self-calibrated low-rank subspace reconstruction.

PURPOSE: To develop a highly accelerated non-contrast-enhanced 4D-MRA technique by combining stack-of-stars golden-angle radial acquisition with a modified self-calibrated low-rank subspace reconstruction. METHODS: A low-rank subspace reconstruction framework was introduced in radial 4D MRA (SUPER 4D MRA) by combining stack-of-stars golden-angle radial acquisition with control-label k-space subtraction-based low-rank subspace modeling. Radial 4D MRA data were acquired and reconstructed using the proposed technique on 12 healthy volunteers and 1 patient with steno-occlusive disease. The performance of SUPER 4D MRA was compared with two temporally constrained reconstruction methods (golden-angle radial sparse parallel [GRASP] and GRASP-Pro) at different acceleration rates in terms of image quality and delineation of blood dynamics. RESULTS: SUPER 4D MRA outperformed the other two reconstruction methods, offering superior image quality with a clear background and detailed delineation of cerebrovascular structures as well as great temporal fidelity in blood flow dynamics. SUPER 4D MRA maintained excellent performance even at higher acceleration rates. CONCLUSIONS: SUPER 4D MRA is a promising technique for highly accelerating 4D MRA acquisition without comprising both temporal fidelity and image quality.

Design and characterization of a self-matching photonic lantern for all few-mode fiber laser systems.

We model and demonstrate a self-matching photonic lantern (SMPL) device, which is designed to address the constraint of limited transverse modes generated by fiber lasers. The SMPL incorporates a FMF into the array at the input end of a traditional photonic lantern. The few-mode fiber at the output end is specifically configured to align with the few-mode fiber at the input, therefore named as SMPL. This paper details the design and fabrication of the SMPL device, validated by both simulation and experiment. The 980nm fundamental mode, injected via 980nm single-mode fibers, selectively excites corresponding higher-order modes at the few-mode port of the SMPL. Additionally, 1550nm fundamental and higher-order modes injected at the input end into the SMPL device demonstrates mode preservation and low-loss transmission characteristics. The SMPL is well-suited for developing a ring laser system, enabling selective excitation of 980nm pump light modes and facilitating closed-loop oscillation and transmission of 1550nm laser.

USP8 promotes the tumorigenesis of intrahepatic cholangiocarcinoma via stabilizing OGT.

Ubiquitination was considered to be a crucial factor in intrahepatic cholangiocarcinoma (iCCA) development. Herein, we identified Ubiquitin-specific peptidase 8 (USP8) as a key regulator for promoting the tumorigenesis of iCCA cell via stabilizing OGT. USP8 was overexpressed in human tumor tissues and correlated with worse survival. Moreover, the mass spectrometry and co-immunoprecipitation analysis indicated that USP8 interacted with OGT. USP8 worked as a bona fide deubiquitylase of OGT. It stabilized OGT in a deubiquitylation activity-dependent manner. Meanwhile, DUB-IN3, the USP8 inhibitor, could also restrain the malignancy of intrahepatic cholangiocarcinoma. In addition, USP8 depletion promoted the response of iCCA to pemigatinib. In conclusion, our findings pointed to a previously undocumented catalytic role for USP8 as a deubiquitinating enzyme of OGT. The USP8-OGT axis could be a potential target for iCCA therapy.

Stabilization of estrogen receptor α by USP37 contributes to the progression of breast cancer.

Breast cancer is a major cause of cancer-related morbidity and mortality in women. Estrogen receptor-positive breast cancer accounts for roughly 70%-80% of breast tumors, and estrogen receptor alpha (ERα) has been considered as a key driver in promoting breast cancer progression. In the present study, we identified USP37 as a novel modulator in modulating ERα ubiquitination and stability. The expression of USP37 was upregulated in ERα-positive breast cancer and correlated with ERα protein level. High expression of USP37 was associated with unfavorable prognosis. USP37 depletion resulted in significantly decreased ERα protein level, ERα target genes expression as well as the estrogen response element activity in breast cancer cells. Further mechanistic study revealed the interaction between USP37 and ERα: USP37 regulated ERα signaling through modulating protein stability instead of gene expression, in which it stabilized ERα protein via inhibiting the K48-specific polyubiquitination process. Additionally, USP37 depletion led to growth inhibition and cell cycle arrest of ERα-positive breast cancer cells, which could be further rescued by ERα overexpression. Overall, our study proposed a novel post-translational mechanism of ERα in promoting breast cancer progression. Targeting USP37 may be proved to be a promising strategy for patients with ERα-positive breast cancer.

The deubiquitinase EIF3H promotes hepatocellular carcinoma progression by stabilizing OGT and inhibiting ferroptosis.

Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal human malignancies, and with quite limited treatment alternatives. The proteasome is responsible for most of the protein degradation in eukaryotic cells and required for the maintenance of intracellular homeostasis. However, its potential role in HCC is largely unknown. In the current study, we identified eukaryotic translation initiation factor 3 subunit H (EIF3H), belonging to the JAB1/MPN/MOV34 (JAMM) superfamily, as a bona fide deubiquitylase of O-GlcNAc transferase (OGT) in HCC. We explored that EIF3H was positively associated with OGT in HCC and was related to the unfavorable prognosis. EIF3H could interact with, deubiquitylate, and stabilize OGT in a deubiquitylase-dependent manner. Specifically, EIF3H was associated with the GT domain of ERα via its JAB/MP domain, thus inhibiting the K48-linked ubiquitin chain on OGT. Besides, we demonstrated that the knockdown of EIF3H significantly reduced OGT protein expression, cell proliferation and invasion, and caused G1/S arrest of HCC. We also found that the deletion of EIF3H prompted ferroptosis in HCC cells. Finally, the effects of EIF3H depletion could be reversed by further OGT overexpression, implying that the OGT status is indispensable for EIF3H function in HCC carcinogenesis. In summary, our study described the oncogenic function of EIF3H and revealed an interesting post-translational mechanism between EIF3H, OGT, and ferroptosis in HCC. Targeting the EIF3H may be a promising approach in HCC. Video Abstract.

ATXN3 promotes prostate cancer progression by stabilizing YAP.

BACKGROUND: Prostate cancer (PC) is the most common neoplasm and is the second leading cause of cancer-related deaths in men worldwide. The Hippo tumor suppressor pathway is highly conserved in mammals and plays an important role in carcinogenesis. YAP is one of major key effectors of the Hippo pathway. However, the mechanism supporting abnormal YAP expression in PC remains to be characterized. METHODS: Western blot was used to measure the protein expression of ATXN3 and YAP, while the YAP target genes were measured by real-time PCR. CCK8 assay was used to detect cell viability; transwell invasion assay was used to measure the invasion ability of PC. The xeno-graft tumor model was used for in vivo study. Protein stability assay was used to detect YAP protein degradation. Immuno-precipitation assay was used to detect the interaction domain between YAP and ATXN3. The ubiquitin-based Immuno-precipitation assays were used to detect the specific ubiquitination manner happened on YAP. RESULTS: In the present study, we identified ATXN3, a DUB enzyme in the ubiquitin-specific proteases family, as a bona fide deubiquitylase of YAP in PC. ATXN3 was shown to interact with, deubiquitylate, and stabilize YAP in a deubiquitylation activity-dependent manner. Depletion of ATXN3 decreased the YAP protein level and the expression of YAP/TEAD target genes in PC, including CTGF, ANKRD1 and CYR61. Further mechanistic study revealed that the Josephin domain of ATXN3 interacted with the WW domain of YAP. ATXN3 stabilized YAP protein via inhibiting K48-specific poly-ubiquitination process on YAP protein. In addition, ATXN3 depletion significantly decreased PC cell proliferation, invasion and stem-like properties. The effects induced by ATXN3 depletion could be rescued by further YAP overexpression. CONCLUSIONS: In general, our findings establish a previously undocumented catalytic role for ATXN3 as a deubiquitinating enzyme of YAP and provides a possible target for the therapy of PC. Video Abstract.

Advanced Fiber Sensors Based on the Vernier Effect.

For decades, optical fiber interferometers have been extensively studied and applied for their inherent advantages. With the rapid development of science and technology, fiber sensors with higher detection sensitivity are needed on many occasions. As an effective way to improve measurement sensitivity, Vernier effect fiber sensors have drawn great attention during the last decade. Similar to the Vernier caliper, the optical Vernier effect uses one interferometer as a fixed part of the Vernier scale and the other as a sliding part of the Vernier scale. This paper first illustrates the principle of the optical Vernier effect, then different configurations used to produce the Vernier effect are classified and discussed. Finally, the outlook for Vernier effect fiber sensors is presented.

MINDY1 promotes bladder cancer progression by stabilizing YAP.

BACKGROUND: Bladder cancer is one of the most commonly diagnosed urological malignant tumor. The Hippo tumor suppressor pathway is highly conserved in mammals and plays an important role in carcinogenesis. YAP is one of major key effectors of the Hippo pathway. However, the mechanism supporting abnormal YAP expression in bladder cancer remains to be characterized. METHODS: Western blot was used to measure the expression of MINDY1 and YAP, while the YAP target genes were measured by real-time PCR. CCK8 assay was used to detect the cell viability. The xeno-graft tumor model was used for in vivo study. Protein stability assay was used to detect YAP protein degradation. Immuno-precipitation assay was used to detect the interaction domain between MINDY1 and YAP. The ubiquitin-based Immuno-precipitation assays were used to detect the specific ubiquitination manner happened on YAP. RESULTS: In the present study, we identified MINDY1, a DUB enzyme in the motif interacting with ubiquitin-containing novel DUB family, as a bona fide deubiquitylase of YAP in bladder cancer. MINDY1 was shown to interact with, deubiquitylate, and stabilize YAP in a deubiquitylation activity-dependent manner. MINDY1 depletion significantly decreased bladder cancer cell proliferation. The effects induced by MINDY1 depletion could be rescued by further YAP overexpression. Depletion of MINDY1 decreased the YAP protein level and the expression of YAP/TEAD target genes in bladder cancer, including CTGF, ANKRD1 and CYR61. CONCLUSION: In general, our findings establish a previously undocumented catalytic role for MINDY1 as a deubiquitinating enzyme of YAP and provides a possible target for the therapy of bladder cancer.

A prognostic eight-lncRNA expression signature in predicting recurrence of ER-positive breast cancer receiving endocrine therapy.

Long noncoding RNAs (lncRNAs) have the main role in the tumorigenesis of breast cancer. In the present study, lncRNA expression profiling was collected to identify a lncRNA expression signature from the Gene Expression Omnibus database. An eight-lncRNA signature was established to predict the survival of patients with estrogen receptor (ER)-positive breast cancer receiving endocrine therapy. Patients were separated into a low-risk group and a high-risk group based on this signature. Patients in high-risk group have worse survival compared to those in low-risk group using Kaplan-Meier curve analysis with log-rank test. Receiver operating characteristic analysis suggested good diagnostic efficiency of the eight-lncRNA signature. When adjusting the clinical features, including age, grade, lymph node status, and tumor size, this signature was independently associated with the relapse-free survival. The prognostic value of the lncRNA prognostic model was then validated in validation sets. When validated in a cohort of patients treated with neoadjuvant chemotherapy and endocrine therapy, this signature demonstrated good performance as well. Besides, we have built a nomogram that integrated the conventional clinicopathological features and the eight-lncRNA-based signature. To sum up, our results indicated that the eight-lncRNA prognostic model was a reliable tool to group patients at high and low risk of disease relapse. This signature may have possible implication in prognostic evaluations of patients with ER-positive breast cancer receiving endocrine therapy.