In silico transcriptome screens identify epidermal growth factor receptor inhibitors as therapeutics for noise-induced hearing loss.

Noise-induced hearing loss (NIHL) is a common sensorineural hearing impairment that lacks U.S. Food and Drug Administration-approved drugs. To fill the gap in effective screening models, we used an in silico transcriptome-based drug screening approach, identifying 22 biological pathways and 64 potential small molecule treatments for NIHL. Two of these, afatinib and zorifertinib [epidermal growth factor receptor (EGFR) inhibitors], showed efficacy in zebrafish and mouse models. Further tests with EGFR knockout mice and EGF-morpholino zebrafish confirmed their protective role against NIHL. Molecular studies in mice highlighted EGFR's crucial involvement in NIHL and the protective effect of zorifertinib. When given orally, zorifertinib was found in the perilymph with favorable pharmacokinetics. In addition, zorifertinib combined with AZD5438 (a cyclin-dependent kinase 2 inhibitor) synergistically prevented NIHL in zebrafish. Our results underscore the potential for in silico transcriptome-based drug screening in diseases lacking efficient models and suggest EGFR inhibitors as potential treatments for NIHL, meriting clinical trials.

Utility of CT Radiomics and Delta Radiomics for Survival Evaluation in Locally Advanced Nasopharyngeal Carcinoma with Concurrent Chemoradiotherapy.

BACKGROUND: A high incidence rate of nasopharyngeal carcinoma (NPC) has been observed in Southeast Asia compared to other parts of the world. Radiomics is a computational tool to predict outcomes and may be used as a prognostic biomarker for advanced NPC treated with concurrent chemoradiotherapy. Recently, radiomic analysis of the peripheral tumor microenvironment (TME), which is the region surrounding the gross tumor volume (GTV), has shown prognostic usefulness. In this study, not only was gross tumor volume (GTVt) analyzed but also tumor peripheral regions (GTVp) were explored in terms of the TME concept. Both radiomic features and delta radiomic features were analyzed using CT images acquired in a routine radiotherapy process. METHODS: A total of 50 patients with NPC stages III, IVA, and IVB were enrolled between September 2004 and February 2014. Survival models were built using Cox regression with clinical factors (i.e., gender, age, overall stage, T stage, N stage, and treatment dose) and radiomic features. Radiomic features were extracted from GTVt and GTVp. GTVp was created surrounding GTVt for TME consideration. Furthermore, delta radiomics, which is the longitudinal change in quantitative radiomic features, was utilized for analysis. Finally, C-index values were computed using leave-one-out cross-validation (LOOCV) to evaluate the performances of all prognosis models. RESULTS: Models were built for three different clinical outcomes, including overall survival (OS), local recurrence-free survival (LRFS), and progression-free survival (PFS). The range of the C-index in clinical factor models was (0.622, 0.729). All radiomics models, including delta radiomics models, were in the range of (0.718, 0.872). Among delta radiomics models, GTVt and GTVp were in the range of (0.833, 0.872) and (0.799, 0.834), respectively. CONCLUSIONS: Radiomic analysis on the proximal region surrounding the gross tumor volume of advanced NPC patients for survival outcome evaluation was investigated, and preliminary positive results were obtained. Radiomic models and delta radiomic models demonstrated performance that was either superior to or comparable with that of conventional clinical models.

Olefin skeletal rearrangement enabling access to multiarylated N-sulfonyl amidines.

A base-promoted olefin skeletal rearrangement strategy from para-quinone methides (p-QMs) and N-fluoroarenesulfonamides is reported, enabling direct nitrogen insertion of olefins to produce a series of multiarylated (Z)-N-sulfonyl amidines with complete stereoselectivity and generally good yields. Using p-QMs without o-hydroxy substituents gave triarylated N-sulfonyl amidines, whereas tetraarylated N,N'-disulfonyl amidines were synthesized with the existence of o-hydroxy groups.

Systematic single cell RNA sequencing analysis reveals unique transcriptional regulatory networks of Atoh1-mediated hair cell conversion in adult mouse cochleae.

Regeneration of mammalian cochlear hair cells (HCs) by modulating molecular pathways or transcription factors is a promising approach to hearing restoration; however, immaturity of the regenerated HCs in vivo remains a major challenge. Here, we analyzed a single cell RNA sequencing (scRNA-seq) dataset during Atoh1-induced supporting cell (SC) to hair cell (HC) conversion in adult mouse cochleae (Yamashita et al. (2018)) using multiple high-throughput sequencing analytical tools (WGCNA, SCENIC, ARACNE, and VIPER). Instead of focusing on differentially expressed genes, we established independent expression modules and confirmed the existence of multiple conversion stages. Gene regulatory network (GRN) analysis uncovered previously unidentified key regulators, including Nhlh1, Lhx3, Barhl1 and Nfia, that guide converted HC differentiation. Comparison of the late-stage converted HCs with the scRNA-seq data from neonatal mouse cochleae (Kolla et al. (2020)) revealed that they closely resemble postnatal day 1 wild-type OHCs, in contrast to other developmental stages. Using ARACNE and VIPER, we discovered multiple key regulators likely to promote conversion to a more mature OHC-like state, including Zbtb20, Nfia, Zmiz1, Gm14418, Bhlhe40, Six2, Fosb and Klf9. Our findings provide insights into the regulation of HC regeneration in adult mammalian cochleae in vivo and demonstrate an approach for analyzing GRNs in large scRNA-seq datasets.

Discovery of Clinical Manifestations in Spontaneous Glaucoma Suspect Nonhuman Primates.

INTRODUCTION: The primary aim of this study was to assess the longitudinal changes in retinal nerve fiber layer (RNFL) thickness and relative ONH parameters using spectral-domain optical coherence tomography (SD-OCT) in the living eyes of nonhuman primates with spontaneous glaucoma. METHODS: Totally 9 macaque subjects underwent a standard fundus photo and OCT examination, including 3 adult monkeys with stable elevated intraocular pressure (IOP) as the glaucoma suspect group and 6 normal IOP monkeys as the control group. Each eye of primates with IOP measurement was repeated three times. OCT measurements recorded RNFL, Bruch's membrane opening (BMO) minimum rim width (MRW). The follow-up scan of glaucomatous subjects was undergone in 10 months. RESULTS: The mean ages of glaucoma and healthy subjects are 19.33 ± 0.33 and 20.5 ± 1.46 years. Elevated IOP was achieved in three nonhuman primate eyes with an average increase of 10 mm Hg over the study period. Elevated IOP was associated with decreased RNFL thickness in all the regions and decreased RNFL phase retardation in the superior and inferior regions. When averaged over the entire retinal area, only the whole RNFL and temporal regions showed a significant decrease. The mean IPL thicknesses are 87.17 ± 2.15 µm in glaucomatous and 93.33 ± 1.51 µm in healthy eyes (p = 0.03). Lamina cribrosa parameters are measured from the OCT images and showed significant differences between glaucoma primates and normal primates. CONCLUSIONS: Of the measured parameters, decreased RNFL and MRW were correlated with glaucomatous damage. Natural glaucoma primate can be a natural glaucoma model which is closer to glaucoma in humans.

Dbh+ catecholaminergic cardiomyocytes contribute to the structure and function of the cardiac conduction system in murine heart.

The heterogeneity of functional cardiomyocytes arises during heart development, which is essential to the complex and highly coordinated cardiac physiological function. Yet the biological and physiological identities and the origin of the specialized cardiomyocyte populations have not been fully comprehended. Here we report a previously unrecognised population of cardiomyocytes expressing Dbhgene encoding dopamine beta-hydroxylase in murine heart. We determined how these myocytes are distributed across the heart by utilising advanced single-cell and spatial transcriptomic analyses, genetic fate mapping and molecular imaging with computational reconstruction. We demonstrated that they form the key functional components of the cardiac conduction system by using optogenetic electrophysiology and conditional cardiomyocyte Dbh gene deletion models. We revealed their close relationship with sympathetic innervation during cardiac conduction system formation. Our study thus provides new insights into the development and heterogeneity of the mammalian cardiac conduction system by revealing a new cardiomyocyte population with potential catecholaminergic endocrine function.

Prognostic value of interim CT-based peritumoral and intratumoral radiomics in laryngeal and hypopharyngeal cancer patients undergoing definitive radiotherapy.

BACKGROUND AND PURPOSE: We aimed to investigate the prognostic value of peritumoral and intratumoral computed tomography (CT)-based radiomics during the course of radiotherapy (RT) in patients with laryngeal and hypopharyngeal cancer (LHC). MATERIALS AND METHODS: A total of 92 eligible patients were 1:1 randomly assigned into training and validation cohorts. Pre-RT and mid-RT radiomic features were extracted from pre-treatment and interim CT. LASSO-Cox regression was used for feature selection and model construction. Time-dependent area under the receiver operating curve (AUC) analysis was applied to evaluate the models' prognostic performances. Risk stratification ability on overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method and Cox regression. The associations between radiomics and clinical parameters as well as circulating lymphocyte counts were also evaluated. RESULTS: The mid-RT peritumoral (AUC: 0.77) and intratumoral (AUC: 0.79) radiomic models yielded better performance for predicting OS than the pre-RT intratumoral model (AUC: 0.62) in validation cohort. This was confirmed by Kaplan-Meier analysis, in which risk stratification depended on the mid-RT peritumoral (p = 0.009) and intratumoral (p = 0.003) radiomics could be improved for OS, in comparison to the pre-RT intratumoral radiomics (p = 0.199). Multivariate analysis identified mid-RT peritumoral and intratumoral radiomic models as independent prognostic factors for both OS and PFS. Mid-RT peritumoral and intratumoral radiomics were correlated with treatment-related lymphopenia. CONCLUSION: Mid-RT peritumoral and intratumoral radiomic models are promising image biomarkers that could have clinical utility for predicting OS and PFS in patients with LHC treated with RT.

Multi-Quantitative Assessment of AS-OCTA Complemented AS-OCT for Monitoring Filtering Bleb Function After Trabeculectomy.

Purpose: The purpose of this study was to explore a quantitative grading system of the filtering bleb combined anterior segment optical coherence tomography angiography (AS-OCTA) vascular features and optical coherence tomography (OCT) morphological features. Methods: One hundred three eyes of 103 patients diagnosed with primary open-angle glaucoma and undergone trabeculectomy over 6 months were divided into success and failure groups according to postoperative intraocular pressure (IOP) level. Vessel density (VD) and vessel diameter index (VDI) were examined by AS-OCTA. Bleb's morphology, including bleb height (BH), and microcyst-structure (MCS) were detected by AS-OCT. Multi-vascular model score (MVMS) was calculated by comprehensive factor analysis, and the comprehensive grading system (MVMS-MCS-BH) was analyzed by linear regression. The efficiency our method was verified by receiver operating characteristic (ROC) analysis. Results: The VD and VDI were higher in the failure group and closely related to post-trabeculectomy IOP (all P = 0.000). The MVMS was mostly consisted of VD in all regions, and VDIs of nasal, central, and temporal positions in sequence. MVMS ≥0, BH <1.33, and non-MCS were significantly associated with IOP increasing (coefficient = -3.23, -3.69, and 8.10, all P = 0.000). MVMS-BH-MCS got a higher area under curve (AUC), sensitivity, and specificity (0.92, 100%, and 80.30%) than the slit-lamp method (0.62, 72.20%, and 46.43%, respectively). Conclusions: The quantitative vascular characteristics detected by AS-OCTA were significant for the bleb monitor. The MVMS-BH-MCS grading system had achieved outstanding accuracy in reflecting the surgical results. Translational Relevance: The multi-vascular biomarker and comprehensive evaluation combined vascular and morphological parameters yield useful information on surgical outcomes, and help ophthalmologists to monitor patients effectively.

In Silico Transcriptome-based Screens Identify Epidermal Growth Factor Receptor Inhibitors as Therapeutics for Noise-induced Hearing Loss.

Noise-Induced Hearing Loss (NIHL) represents a widespread disease for which no therapeutics have been approved by the Food and Drug Administration (FDA). Addressing the conspicuous void of efficacious in vitro or animal models for high throughput pharmacological screening, we utilized an in silico transcriptome-oriented drug screening strategy, unveiling 22 biological pathways and 64 promising small molecule candidates for NIHL protection. Afatinib and zorifertinib, both inhibitors of the Epidermal Growth Factor Receptor (EGFR), were validated for their protective efficacy against NIHL in experimental zebrafish and murine models. This protective effect was further confirmed with EGFR conditional knockout mice and EGF knockdown zebrafish, both demonstrating protection against NIHL. Molecular analysis using Western blot and kinome signaling arrays on adult mouse cochlear lysates unveiled the intricate involvement of several signaling pathways, with particular emphasis on EGFR and its downstream pathways being modulated by noise exposure and Zorifertinib treatment. Administered orally, Zorifertinib was successfully detected in the perilymph fluid of the inner ear in mice with favorable pharmacokinetic attributes. Zorifertinib, in conjunction with AZD5438 - a potent inhibitor of cyclin dependent kinase 2 - produced synergistic protection against NIHL in the zebrafish model. Collectively, our findings underscore the potential application of in silico transcriptome-based drug screening for diseases bereft of efficient screening models and posit EGFR inhibitors as promising therapeutic agents warranting clinical exploration for combatting NIHL. Highlights: In silico transcriptome-based drug screens identify pathways and drugs against NIHL.EGFR signaling is activated by noise but reduced by zorifertinib in mouse cochleae.Afatinib, zorifertinib and EGFR knockout protect against NIHL in mice and zebrafish.Orally delivered zorifertinib has inner ear PK and synergizes with a CDK2 inhibitor.

Mitomycin C-loaded PTMC15-F127-PTMC15 hydrogel maintained better bleb function after filtering glaucoma surgery in monkeys with intraocular hypertension.

There is an unmet need for a safer and more effective approach for antimetabolite application to prevent bleb fibrosis after glaucoma filtering surgery. Here, we utilized our previously developed thermosensitive sustained-release agent, mitomycin C-loaded poly(trimethylene carbonate)15-F127-poly(trimethylene carbonate)15 (MMC-hydrogel), aiming to further evaluate the efficacy and safety of MMC-hydrogel in high intraocular pressure (IOP) primate eyes. Twelve primate eyes after high IOP induction were randomly divided into three groups, which respectively received phosphate-buffered saline (PBS)-hydrogel, MMC-hydrogel, and MMC treatment during trabeculectomy. IOP and bleb volume were measured using a Tonopen and anterior segment optical coherence tomography over 28 days. At the end of the experiment, all experimental primate eyes were enucleated. Histopathology and immunohistochemistry were performed to reveal myofibroblast cells and collagen deposition of filtering blebs. The MMC-hydrogel group had satisfactory IOP control (9.25 ± 4.80 mmHg) and maintained well-functioning blebs for a longer time. Fibrosis and scarring were significantly alleviated in this MMC-hydrogel group. There was no obvious toxicity to ocular surfaces or intraocular structures. Taken together, these data suggest that PTMC15-F127-PTMC15-loaded MMC-hydrogel plays a role in functional maintenance and scarring inhibition, showing high efficacy in reducing post-filtering surgery bleb fibrosis. This MMC-hydrogel may offer a new solution for filtering bleb management after glaucoma surgery.

Azofuran activation for annulative rearrangement enabled by gold(I)/Brønsted acid relay catalysis.

A novel gold(I)/Brønsted acid relay catalysis enabling azofuran activation to induce annulative rearrangement from 3-yne-1,2-diols and aryldiazonium tetrafluoroborates is reported, producing a series of furan-2-yl-substituted pyrrol-2-ones bearing a quaternary carbon center with good yields. Exchanging aryldiazonium tetrafluoroborate for azofuran led to skeletally identical but substituent-diverse furan-2-yl-containing pyrrol-2-ones with good yields, supporting the key azofuran activation and annulative rearrangement by gold/Brønsted acid relay catalysis.

Gold self-relay catalysis enabling annulative oxygenation of propargylic alcohols with O-nucleophiles.

A new gold(I) self-relay catalysis reaction enabling the annulative oxygenation of propargylic alcohols with various O-nucleophiles, such as carboxylic acids, alcohols and TBHP, is reported, producing a series of functionalized benzofurans in moderate to good yields under mild conditions. This protocol benefits from the π- and σ-Lewis acid capability of gold complexes, demonstrating high molecular convergence, broad substrate flexibility, high functional group compatibility and mild conditions.

Mediating role of physical activity in the relationship between psychological distress and intimate relationships among stroke patients.

BACKGROUND: Stroke patients often experience psychological distress, which can impact their intimate relationships with spouses, subsequently influencing their treatment and recovery. Physical activity is considered a key rehabilitation method for stroke patients. This paper aims to analyze whether psychological distress affects intimate relationship between spouses through physical activity. AIM: To explore the mediating effect of physical activity between psychological distress and intimate relationship in stroke patients. METHODS: A total of 256 stroke patients who underwent treatment at the First People's Hospital of Shangqiu between July 2021 and July 2022 were enrolled in this study. The participants completed questionnaires, including the Kessler Psychological Distress Scale (K10), the Quality of Relationship Index (QRI), International Physical Activity Questionnaire, and a general information questionnaire. Data analysis were performed using SPSS 23.0. The Harman test was employed to detect common method deviations, and Spearman correlation was used for correlation analysis. The mediating effect was assessed using Process 3.4.1, with significance testing of the regression coefficients conducted using the bias-corrected percentile Bootstrap method (5000 iterations, 95% confidence interval). Statistical significance was set at P < 0.05. RESULTS: The results showed that patients scored an average of 21.61 ± 6.44 points on the K10, 32.40 ± 6.19 points on the QRI; the median physical activity level according to the International Physical Activity Questionnaire was 1861 (566, 2846) MET·min/w. The level of physical activity (the physical activity intensity of the patients reflected by the International Physical Activity Questionnaire-Long Form scale) negatively correlated with psychological distress and intimacy (P < 0.05), and positively correlated with each other (P < 0.05), with the correlation stronger at lower physical activity levels compared to higher ones. The mediating effect of physical activity between psychological distress and intimate relationship was calculated to be 40.23%. Bootstrap analysis further validated the results. The mediating effect of psychological distress on intimate relationships through physical activity level was -0.284, with a confidence interval of -0.409 to -0.163, excluding 0, confirming a significant mediating effect of psychological distress on intimate relationships. CONCLUSION: Physical activity significantly affects relationship between psychological distress and intimate relationships among stroke patients. Addressing the role of physical activity may have implications for improving patient outcomes and rehabilitation strategies.

Quantitative analysis of choroidal vasculature in central serous chorioretinopathy using ultra-widefield swept-source optical coherence tomography angiography.

We aimed to quantitatively compare the choroid blood flow and choroid thickness at the periphery among eyes with central serous chorioretinopathy (CSC), fellow eyes and healthy eyes using ultra-widefield swept-source optical coherence tomography angiography (UWF SS-OCTA). Retrospective analysis of 49 patients with CSC (98 eyes, including unaffected fellow eyes) and 49 age and sex matched controls were included. We obtained 3-dimensional data of vertical 20 mm × horizontal 24 mm × scan depth 6 mm, comprising 9 subfields (superotemporal, upper, superonasal, temporal, central, nasal, inferotemporal, lower, inferonasal regions). CSC eyes presented with greater density of large-vessel choroidal layer in all the 9 subfields compared with controls. Compared with normal eyes, CSC eyes had greater choroidal thickness (superotemporal, upper, superonasal, temporal, central, nasal, inferotemporal, and inferonasal subfields) and choroidal volume (superotemporal, upper, superonasal, temporal, central, and nasal subfields). Compared with control eyes, the choriocapillaris density in the superotemporal, inferotemporal and inferonasal subfields was greater in patients with CSC. Our study may provide further evidence for the congestion of vortex vein in the pathogenesis of CSC. UWF SS-OCTA can be used to evaluate the abnormalities of the choroidal structures even at the periphery in eyes with CSC.

Regio- and Enantioselective Synthesis of Dihydropyrido[1,2-a]indoles via Catalytic Asymmetric Annulative Allylic Alkylation.

A palladium-catalyzed asymmetric annulative allylic alkylation reaction of 2-[(1H-indol-2-yl)methyl]malonates with (E)-but-2-ene-1,4-diyl dicarbonates is described, leading to the regio- and enantioselective synthesis of dihydropyrido[1,2-a]indoles with a chiral cyclic allyl stereocenter adjacent to the ring-junction nitrogen atom in moderate to good yields. The salient features of this protocol include mild conditions, a broad substrate scope, and good compatibility with substituents as well as high regio- and stereoselectivities, providing a catalytic asymmetric entry for fabricating chiral pyridoindole scaffolds.

Intelligent Healthcare System Using Mathematical Model and Simulated Annealing to Hide Patients Data in the Low-Frequency Amplitude of ECG Signals.

Healthcare is an important medical topic in recent years. In this study, the novelty we propose is the intelligent healthcare system using an inequality-type optimization mathematical model with signal-to-noise ratio (SNR) and wavelet-domain low-frequency amplitude adjustment techniques to hide patients' confidential data in their electrocardiogram (ECG) signals. The extraction of the hidden patient information also utilizes the low-frequency amplitude adjustment. The detailed steps of establishing the system are as follows. To integrate confidential patient data into ECG signals, we first propose a nonlinear model to optimize the quality of ECG signals with the embedded patients' confidential data including patient name, patient birthdate, date of medical treatment, and medical history. Then, we apply Simulated Annealing (SA) to solve the nonlinear model such that the ECG signals with embedded patients' confidential data have good SNR, good root mean square error (RMSE), and high similarity. In other words, the distortion of the PQRST complexes and the ECG shape caused by the embedded patients' confidential data is very small, and thus the quality of the embedded ECG signals meets the requirements of physiological diagnostics. In the terminals, one can receive the ECG signals with the embedded patients' confidential data. In addition, the embedded patients' confidential data can be received and extracted without the original ECG signals. The experimental results confirm the efficiency that our method maintains a high quality of each ECG signal with the embedded patient confidential data. Moreover, the embedded confidential data shows a good robustness against common attacks.

Azoarene activation for Schmidt-type reaction and mechanistic insights.

The Schmidt rearrangement, a reaction that enables C-C or C-H σ bond cleavage and nitrogen insertion across an aldehyde or ketone substrate, is one of the most important and widely used synthetic tools for the installation of amides and nitriles. However, such a reaction frequently requires volatile, potentially explosive, and highly toxic azide reagents as the nitrogen donor, thus limiting its application to some extent. Here, we show a Schmidt-type reaction where aryldiazonium salts act as the nitrogen precursor and in-situ-generated cyclopenta-1,4-dien-1-yl acetates serve as pronucleophiles from gold-catalyzed Nazarov cyclization of 1,3-enyne acetates. Noteworthy is that cycloketone-derived 1,3-enyne acetates enabled ring-expansion relay to access a series of 2-pyridone-containing fused heterocycles, in which nonsymmetric cycloketone-derived counterparts demonstrated high regioselectivity. Aside from investigating the scope of this Schmidt-type reaction, mechanistic details of this transformation are provided by performing systematic theoretical calculations.

The geochemical and mineralogical controls on the release characteristics of potentially toxic elements from lead/zinc (Pb/Zn) mine tailings.

Large quantities of lead/zinc (Pb/Zn) mine tailings were deposited at tailings impoundments without proper management, which have posed considerable risks to the local ecosystem and residents in mining areas worldwide. Therefore, the geochemical behaviors of potentially toxic elements (PTEs) in tailings were in-depth investigated in this study by a coupled use of batch kinetic tests, statistical analysis and mineralogical characterization. The results indicated that among these studied PTEs, Cd concentration fluctuated within a wide range of 0.83-6.91 mg/kg, and showed the highest spatial heterogeneity. The mean Cd concentrations generally increased with depth. Cd were mainly partitioned in the exchangeable and carbonate fractions. The release potential of PTEs from tailings was ranged as: Cd > Mn > Zn > Pb > As, Cd > Pb > Zn > Mn > As and Cd > Pb > Mn > Zn > As, respectively, under the assumed environmental scenarios, i.e. acid rain, vegetation restoration, human gastrointestinal digestion. The results from mineralogical characterization indicated that quartz, sericite, calcite and pyrite were typical minerals, cumulatively accounting for over 80% of the tailings. Sulfides (arsenopyrite, galena, and sphalerite), carbonates (calcite, dolomite, cerussite and kutnahorite), oxides (limonite) were identified as the most relevant PTEs-bearing phases, which significantly contributed to PTEs release from tailings. A combined result of statistical, geochemical and mineralogical approaches would be provided valuable information for the alteration characteristics and contaminant release of Pb/Zn mine tailings.

68Ga-PSMA-11 PET/CT Features Extracted from Different Radiomic Zones Predict Response to Androgen Deprivation Therapy in Patients with Advanced Prostate Cancer.

Purpose: Prediction of treatment response to androgen deprivation therapy (ADT) prior to treatment initiation remains difficult. This study was undertaken to investigate whether 68Ga-PSMA-11 PET/CT features extracted from different radiomic zones within the prostate gland might predict response to ADT in patients with advanced prostate cancer (PCa). Methods: A total of 35 patients with prostate adenocarcinoma underwent two 68Ga-PSMA-11 PET/CT scans­termed PET-1 and PET-2­before and after 3 months of ADT, respectively. The prostate was divided into three radiomic zones, with zone-1 being the metabolic tumor zone, zone-2 the proximal peripheral tumor zone, and zone-3 the extended peripheral tumor zone. Patients in the response group were those who showed a reduction ratio > 30% for PET-derived parameters measured at PET-1 and PET-2. The remaining patients were classified as non-responders. Results: Seven features (glcm_idmn, glcm_idn, glcm_imc1, ngtdm_Contrast, glrlm_rln, gldm_dn, and shape_MeshVolume) from zone-1, two features (gldm_sdlgle and shape_MinorAxisLength) from zone-2, and two features (diagnostics_Mask-interpolated_Minimum and shape_Sphericity) from zone-3 successfully distinguished responders from non-responders to ADT. One predictive feature (shape_SurfaceVolumeRatio) was consistently identified in all of the three zones. Conclusions: this study demonstrates the potential usefulness of radiomic features extracted from different prostatic zones in distinguishing responders from non-responders prior to ADT initiation.