Cancer Burden and Attributable Risk Factors of Cancers in China: Epidemiological Insights and Comparisons With India.

BACKGROUND: Cancer is a major health concern in China. Understanding the epidemiology of cancer can guide the development of effective prevention and control strategies. This study aimed to comprehensively analyze the cancer burden, time trends, and attributable risk factors of cancers in China and compare them with those in India. METHODS: We utilized the GLOBOCAN database for 2022, Cancer Incidence in Five Continents (C15 plus) series, and Global Burden of Disease (GBD) 2021 to extract data on cancer incidence, mortality, disability-adjusted life years (DALYs), and risk factors. Time-trend analysis was performed using a join-point regression model. Correlations between cancer DALY rates and risk factors were analyzed using linear regression. RESULTS: In 2022, China experienced 4,824,703 new cancer cases and 2,574,176 cancer-related deaths. Cancers also caused approximately 71.2 million DALYs in China in 2021. Compared with India, China has higher incidence, mortality, and DALY rates for various cancers. Breast and thyroid cancers in China have shown a rapid increase in the age-standardized incidence rate (ASIR), along with a substantial burden of lung, stomach, esophageal, and colorectal cancer. However, stomach and liver cancers in China showed a downward trend in ASIR. In 2021, diet low in milk was a major risk factor among females for colorectal cancer DALYs in China (23% of age-standardized DALYs) and India (22.9%). In China, smoking has been associated with increased DALYs due to lung cancer. CONCLUSIONS: China has a heavier cancer burden than India. The heavy burden of lung, stomach, esophageal, and colorectal cancers, combined with the rising incidence of breast and thyroid cancers, pose a critical challenge to public health in China. Cancer burden may be reduced through public health initiatives that prioritize primary prevention, prompt identification, and therapeutic intervention.

Pseudomonas fluorescens Inoculation Enhances Salix matsudana Growth by Modifying Phyllosphere Microbiomes, Surpassing Nitrogen Fertilization.

The enhancement of plant growth by soil fertilization and microbial inoculation involves different mechanisms, particularly by altering the phyllosphere microbiome. This study investigated how nitrogen (N) fertilization, Pseudomonas fluorescens strain R124 inoculation and their combined effects influence the growth of different-aged Salix matsudana cuttings by modulating N dynamics within the phyllosphere microbiome. Results showed that P. fluorescens inoculation was significantly more effective than N fertilization alone, enhancing biomass, plant nutrient uptake, soil nutrient content and root development by 90.51%, 18.18%, 72.74% and 126.20%, respectively. Crucially, the inoculation notably shifted the beta-diversity of the phyllosphere microbial community, with K-strategy fungi enhancing plant N fixation and subsequent plant growth. Cuttings from middle-aged forests displayed more robust growth than those from young-aged, associated with a varied impact on phyllosphere fungi, notably increasing the relative abundance of Myriangiales in young (76.37%) and Capnodiales in middle-aged cuttings (42.37%), which improve phyllosphere stability and plant health. These findings highlight the effectiveness of microbial inoculation over N fertilization in promoting plant growth and provide valuable insights for the sustainable management of willow plantations at different stages of development.

Corrigendum: Mechanism of LncRNA Gm2044 in germ cell development.

[This corrects the article DOI: 10.3389/fcell.2024.1410914.].

Lignocellulosic biomass-derived functional nanocellulose for food-related applications: A review.

In recent years, nanocellulose (NC) has gained significant attention due to its remarkable properties, such as adjustable surface chemistry, extraordinary biological properties, low toxicity and low density. This review summarizes the preparation of NC derived from lignocellulosic biomass (LCB), including cellulose nanofibrils (CNF), cellulose nanocrystals (CNC), and lignin-containing cellulose nanofibrils (LCNF). It focuses on examining the impact of non-cellulosic components such as lignin and hemicellulose on the functionality of NC. Additionally, various surface modification strategies of NC were discussed, including esterification, etherification and silylation. The review also emphasizes the progress of NC application in areas such as Pickering emulsions, food packaging materials, food additives, and hydrogels. Finally, the prospects for producing NC from LCB and its application in food-related fields are examined. This work aims to demonstrate the effective benefits of preparing NC from lignocellulosic biomass and its potential application in the food industry.

Surface Gradient Desodiation Chemistry in Layered Oxide Cathode Materials.

Sodium-ion batteries (SIBs) as a promising technology for large-scale energy storage have received unprecedented attention. However, the cathodes in SIBs generally suffer from detrimental cathode-electrolyte interfacial side reactions and structural degradation during cycling, which leads to severe capacity fade and voltage decay. Here, we have developed an ultra-stable Na0.72Ni0.20Co0.21Mn0.55Mg0.036O2 (NCM-CS-GMg) cathode material in which a Mg-free core is encapsulated by a shell with gradient distribution of Mg using coprecipitation method with Mg-hysteretic cascade feedstock followed by calcination. From the interior to outer surface of the shell, as the content of electrochemically inactive Mg gradually increases, the Na+ deintercalation amount gradually decreases after charged. Benefiting from this surface gradient desodiation, the surface transition metal (TM) ion migration from TM layers to Na layers is effectively inhibited, thus suppressing the layered-to-rock-salt phase transition and the resultant microcracks. Besides, the less formation of high-valence TM ions on the surface contributes to a stable cathode-electrolyte interface. The as-prepared NCM-CS-GMg exhibits remarkable cycling life over 3000 cycles with a negligible voltage drop (0.127 mV per cycle). Our findings highlight an effective way to developing sustainable cathode materials without compromising on the initial specific capacity for SIBs.

Single dose of intravenous miR199a-5p delivery targeting ischemic heart for long-term repair of myocardial infarction.

Long-term treatment of myocardial infarction is challenging despite medical advances. Tissue engineering shows promise for MI repair, but implantation complexity and uncertain outcomes pose obstacles. microRNAs regulate genes involved in apoptosis, angiogenesis, and myocardial contraction, making them valuable for long-term repair. In this study, we find downregulated miR-199a-5p expression in MI. Intramyocardial injection of miR-199a-5p into the infarcted region of male rats revealed its dual protective effects on the heart. Specifically, miR-199a-5p targets AGTR1, diminishing early oxidative damage post-myocardial infarction, and MARK4, which influences long-term myocardial contractility and enhances cardiac function. To deliver miR-199a-5p efficiently and specifically to ischemic myocardial tissue, we use CSTSMLKAC peptide to construct P-MSN/miR199a-5p nanoparticles. Intravenous administration of these nanoparticles reduces myocardial injury and protects cardiac function. Our findings demonstrate the effectiveness of P-MSN/miR199a-5p nanoparticles in repairing MI through enhanced contraction and anti-apoptosis. miR199a-5p holds significant therapeutic potential for long-term repair of myocardial infarction.

Volitional modulation of neuronal activity in the external globus pallidus by engagement of the cortical-basal ganglia circuit.

Volitional modulation of neural activity is not confined to the cortex but extends to various brain regions. Yet, it remains unclear whether neurons in the basal ganglia structure, the external globus pallidus (GPe), can be volitionally controlled. Here, we employed a volitional conditioning task to compare the volitional modulation of GPe and primary motor cortex (M1) neurons as well as the underlying circuits and control mechanisms. The results revealed that the volitional modulation of GPe neuronal activity engaged both M1 and substantia nigra pars reticulata (SNr) neurons, indicating the involvement of the cortex-GPe-SNr loop. In contrast, the volitional modulation of M1 neurons primarily occurred through the engagement of M1 local circuitry. Furthermore, lesioning M1 neurons did not affect the volitional learning or volitional control signal in GPe, whereas lesioning of GPe neurons impaired the learning process for the volitional modulation of M1 neuronal activity at the intermediate stage. Additionally, lesion of GPe neurons enhanced M1 neuronal activity when performing the volitional control task without reward delivery and a random reward test. Taken together, our findings demonstrated that GPe neurons could be volitionally controlled by engagement of the cortical-basal ganglia circuit and inhibit learning process for the volitional modulation of M1 neuronal activity by regulating M1 neuronal activity. Thus, GPe neurons can be effectively harnessed for independent volitional modulation for neurorehabilitation in patients with cortical damage. KEY POINTS: The cortical-basal ganglia circuit contributes to the volitional modulation of GPe neurons. Volitional modulation of M1 neuronal activity mainly engages M1 local circuitry. Bilateral GPe lesioning impedes volitional learning at the intermediate stages. Lesioning of GPe neurons inhibits volitional learning process by regulating M1 neuronal activity.

Mechanism of LncRNA Gm2044 in germ cell development.

Germ cell development in mammals is a complex physiological process that involves the proliferation of primordial germ cells, meiosis, and the formation of male and female gametes. Long non-coding RNA (lncRNA) is a type of RNA with more than 200 nucleotides that does not code for proteins. A small number of lncRNAs have been shown to participate in spermatogenesis in the testes and in follicular development in the ovaries, but the role of the vast majority of lncRNAs and their molecular mechanisms still need further study. LncRNA Gm2044 was identified as a differentially expressed lncRNA in mouse spermatogenesis by microarray technology. In mouse testis, lncRNA Gm2044 can act as competing endogenous RNA to regulate SYCP1 expression in GC-2 cells derived from mouse spermatocyte cells, and it can also act as a host gene for miR-202 to regulate RBFOX2 protein expression. In female mouse ovaries, lncRNA Gm2044 regulates 17ß-estradiol synthesis through the miRNA-138-5p-Nr5a1 pathway or by interacting with EEF2. In addition, studies suggest that lncRNA Gm2044 is also involved in the progression of reproductive system diseases such as male nonobstructive azoospermia. Here, we summarize the roles and molecular mechanisms of lncRNA Gm2044 in male and female gametogenesis and its potential role in some infertility disorders.

Analysis of the incidence and mortality trends of esophageal cancer in cancer registry areas of China and Japan.

This study aims to analyze the prevalence trend of esophageal cancer in Japan and China to provide suggestions for the prevention and treatment of esophageal cancer. The results showed that the incidence rate for the years 2010-2018 significantly decreased with an APC of 5.66%, and the mortality rate from 2010 to 2015 had an APC of -5.87% in China. However, the incidence rate of Japanese women showed an upward trend, with an APC of 4.09% from 2010 to 2019. The mortality rate of esophageal cancer in Japan showed a downward trend, with an APC of -2.96% from 2010 to 2021. From 2010 to 2018, Chinese esophageal squamous cell carcinoma accounted for the highest proportion, accounting for 85.96%, with the largest distribution in the middle, accounting for 47.25%. Patients are mostly diagnosed at stage III, and the relative survival rate from 2012 to 2015 was 30.3%. Japan also has the highest proportion of squamous cell carcinoma, and the lesions are also mostly located in the middle segment. While Japanese esophageal cancer patients are mostly diagnosed at stage I, and the relative survival rate was 41.5% in Japan from 2009 to 2011. The results of this article indicate that the current prevalence of esophageal cancer in China and Japan is generally declining, and the quality of life of patients is gradually improving, but effective screening and prevention strategies are still needed to reduce the burden of this disease.

Molecularly Imprinted Macroporous Hydrogel Promotes Bone Regeneration via Osteogenic Induction and Osteoclastic Inhibition.

Macroporous hydrogels offer physical supportive spaces and bio-instructive environment for the seeded cells, where cell-scaffold interactions directly influence cell fates and subsequently affect tissue regeneration post-implantation. Effectively modifying bioactive motifs at the inner pore surface provides appropriate niches for cell-scaffold interactions. A molecular imprinting method and sacrificial templates are introduced to prepare inner pore surface modification in the macroporous hydrogels. In detail, acrylated bisphosphonates (Ac-BPs) chelating to templates (CaCO3 particles) are anchored on the inner pore surface of the methacrylated gelatin (GelMA)-methacrylated hyaluronic acid (HAMA)-poly (ethylene glycol) diacrylate (PEGDA) macroporous hydrogel (GHP) to form a functional hydrogel scaffold (GHP-int-BP). GHP-int-BP, but not GHP, effectively crafts artificial cell niches to substantially alter cell fates, including osteogenic induction and osteoclastic inhibition, and promote in situ bone regeneration. These findings highlight that molecular imprinting on the inner pore surface in the hydrogel efficiently creates orthogonally additive bio-instructive scaffolds for bone regeneration.

Spray-lithography of hybrid graphene-perovskite paper-based photodetectors for sustainable electronics.

Paper is an ideal substrate for the development of flexible and environmentally sustainable ubiquitous electronic systems. When combined with nanomaterial-based devices, it can be harnessed for various Internet-of-Things applications, ranging from wearable electronics to smart packaging. However, paper remains a challenging substrate for electronics due to its rough and porous nature. In addition, the absence of established fabrication methods is impeding its utilization in wearable applications. Unlike other paper-based electronics with added layers, in this study, we present a scalable spray-lithography on a commercial paper substrate. We present a non-vacuum spray-lithography of chemical vapor deposition (CVD) single-layer graphene (SLG), carbon nanotubes (CNTs) and perovskite quantum dots (QDs) on a paper substrate. This approach combines the advantages of two large-area techniques: CVD and spray-coating. The first technique allows for the growth of SLG, while the second enables the spray coating of a mask to pattern CVD SLG, electrodes (CNTs), and photoactive (QDs) layers. We harness the advantages of perovskite QDs in photodetection, leveraging their strong absorption coefficients. Integrating them with the graphene enhances the photoconductive gain mechanism, leading to high external responsivity. The presented device shows high external responsivity of ∼520 A W-1at 405 nm at <1 V bias due to the photoconductive gain mechanism. The prepared paper-based photodetectors (PDs) achieve an external responsivity of 520 A W-1under 405 nm illumination at <1 V operating voltage. To the best of our knowledge, our devices have the highest external responsivity among paper-based PDs. By fabricating arrays of PDs on a paper substrate in the air, this work highlights the potential of this scalable approach for enabling ubiquitous electronics on paper.

Turbulence-resistant free space optical communication via chaotic block-matching and 3D filtering.

In this paper, we propose a chaotic block-matching and three-dimensional (C-BM3D) filtering algorithm to remove the noise and enhance the security in the turbulent channel of free space optical (FSO) communication. We experimentally demonstrate the performance of C-BM3D by comparing it with chaotic non-local means filtering (C-NLM), chaotic Gaussian filtering and chaotic Median filtering based on Log-normal and Gamma-Gamma turbulence models. The results show that the peak signal-to-noise ratios (PSNRs) of C-BM3D in the weak turbulence under Log-normal and Gamma-Gamma models are up to 96.2956 and 93.2853, respectively. The C-BM3D also achieves superior image similarity in Log-normal turbulent channel, with its structural similarity index measures (SSIMs) nearly equal to 1. Additionally, the signal-to-noise ratio (SNR) of C-BM3D ranks the highest, and its bit error rate (BER) improves by at least 15 dB compared to that of the other three algorithms. The experimental results indicate that the C-BM3D can be a good candidate for the next generation of FSO communication in security and turbulence resistance.

Advancing PFAS Sorbent Design: Mechanisms, Challenges, and Perspectives.

Per- and polyfluoroalkyl substances (PFAS) are a group of synthetic chemicals characterized with persistence and multisurface resistance. Their accumulation in the environment and toxicity to human beings have contributed to the rapid development of regulations worldwide since 2002. The sorption strategy, taking advantage of intermolecular interactions for PFAS capture, provides a promising and efficient solution to the treatment of PFAS contaminated sources. Hydrophobic and electrostatic interactions are the two commonly found in commercially available PFAS sorbents, with the fluorous interaction being the novel mechanism applied for sorbent selectivity. The main object of this Perspective is to provide a critical review on the current design criteria of PFAS sorbents, with particular focus on their sorption and interaction mechanisms as well as limitations. An outlook on future innovative design for efficient PFAS sorbents is also provided.

Atomized inhalation of Icaritin reduces airway inflammation and remodeling in asthmatic mice.

BACKGROUND: Asthma is a disease characterized by airway hyperresponsiveness and airway inflammation. Icaritin (ICT) is a plant hormone with various pharmacological activities such as anti-inflammatory, immune regulation, and anti-tumor. This study mainly explored the effects of nebulized inhalation of ICT on airway inflammation and airway remodeling in asthmatic mice. METHOD: Different groups of ovalbumin (OVA)-induced asthma mice with acute and chronic airway inflammation received ICT. Asthmatic mice received budesonide (BDND) aerosol inhalation as a positive control, while normal control and asthma model mice received the same volume of saline. Following finishing of the study, analyses were conducted on behavioral tests, biochemical indices, and histological structures of lung tissues. RESULTS: Aerosol inhalation of ICT can notably reduce inflammatory cells infiltration around the airways and pulmonary vessels, and suppressed goblet cell hyperplasia in asthmatic mice. Long-term inhalation of ICT can decrease airway collagen deposition and airway smooth muscle hyperplasia, and alleviate airway hyperresponsiveness, mirroring the effects observed with hormone employed in clinical practice. CONCLUSION: Nebulized inhalation of ICT can effectively inhibit airway inflammation in asthmatic mice, improve airway remodeling, and reduce airway hyperresponsiveness, with effects similar to those of hormones. It may serve as a potential candidate used as a hormone replacement asthma treatment.

Association of radiotherapy for stage I-III breast cancer survivors and second primary malignant cancers: a population-based study.

PURPOSE: With life span extending, breast cancer survivors may face the possibility of developing second primary cancers (SPCs). The objective of this research is to investigate the risk factors, risk attribute to radiotherapy and the survivalship for SPCs. METHODS: A total of 445 523 breast cancer patients were enrolled from Surveillance, Epidemiology, and End Results database in 2000-2018. The risk factors for SPCs development were confirmed by competing risk model, and then were integrated to the nomogram establishment. The cumulative incidence of SPCs including SBC (second breast cancer), SGC (second gynecological cancer), and SLC (second lung cancer) were estimated. The radiotherapy-associated risk for SPCs were evaluated by Poisson regression in radiotherapy and no-radiotherapy. Propensity score matching was used to reduce possible bias for survival comparison. RESULTS: There were 57.63% patients in radiotherapy. The risk factors for developing SPCs were age, year, race, tumor size, stage, radiotherapy, grade, surgery, and histology. The cumulative incidence of SPCs was 7.75% in no-radiotherapy and 10.33% in radiotherapy. SLC, SBC, and SGC also appeared the similar results. The increased risk of developing SPCs were associated with radiotherapy in majority subgroups. The dynamic radiotherapy-associated risk for SPCs by age slightly increased risk was observed. Regardless radiotherapy or no-radiotherapy, the 10-year overall survival for SBC (radiotherapy: 59.41%; no-radiotherapy: 55.53%) and SGC (radiotherapy: 48.61%; no-radiotherapy: 35.53%) were worse than that among matched patients with only primary cancers. CONCLUSIONS: Breast cancer survivors remained a high radiotherapy-associated risk for developing SPCs. The prognosis in radiotherapy was better than in no-radiotherapy for some specific SPCs. Largely attention should be paid to these patients.

Single-cell sequencing highlights heterogeneity and malignant progression in actinic keratosis and cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the second most frequent of the keratinocyte-derived malignancies with actinic keratosis (AK) as a precancerous lesion. To comprehensively delineate the underlying mechanisms for the whole progression from normal skin to AK to invasive cSCC, we performed single-cell RNA sequencing (scRNA-seq) to acquire the transcriptomes of 138,982 cells from 13 samples of six patients including AK, squamous cell carcinoma in situ (SCCIS), cSCC, and their matched normal tissues, covering comprehensive clinical courses of cSCC. We identified diverse cell types, including important subtypes with different gene expression profiles and functions in major keratinocytes. In SCCIS, we discovered the malignant subtypes of basal cells with differential proliferative and migration potential. Differentially expressed genes (DEGs) analysis screened out multiple key driver genes including transcription factors along AK to cSCC progression. Immunohistochemistry (IHC)/immunofluorescence (IF) experiments and single-cell ATAC sequencing (scATAC-seq) data verified the expression changes of these genes. The functional experiments confirmed the important roles of these genes in regulating cell proliferation, apoptosis, migration, and invasion in cSCC tumor. Furthermore, we comprehensively described the tumor microenvironment (TME) landscape and potential keratinocyte-TME crosstalk in cSCC providing theoretical basis for immunotherapy. Together, our findings provide a valuable resource for deciphering the progression from AK to cSCC and identifying potential targets for anticancer treatment of cSCC.

High-sensitivity force sensing using a phonon laser in an active levitated optomechanical system.

Force detection with high sensitivity is of paramount importance in many fields of study, from gravitational wave detection to investigations of surface forces. Here, we propose and demonstrate a force-sensing method based on gain-enhanced nonlinearity in a nonlinear phonon laser. Experimental and simulation results show that the input force leads to the frequency shift of phonon laser, due to nonlinearity. In addition, we further investigate the influences of the pumping power, numerical aperture, and microsphere's refractive index on the performance of this force-sensing system, regarding the sensitivity and the linear response range. Our work paves a new way towards the realization of precise metrology based on the nonlinearity of phonon laser.

Ring artifacts correction for computed tomography image using unsupervised contrastive learning.

Objective.Computed tomography (CT) is a widely employed imaging technology for disease detection. However, CT images often suffer from ring artifacts, which may result from hardware defects and other factors. These artifacts compromise image quality and impede diagnosis. To address this challenge, we propose a novel method based on dual contrast learning image style transformation network model (DCLGAN) that effectively eliminates ring artifacts from CT images while preserving texture details.Approach. Our method involves simulating ring artifacts on real CT data to generate the uncorrected CT (uCT) data and transforming them into strip artifacts. Subsequently, the DCLGAN synthetic network is applied in the polar coordinate system to remove the strip artifacts and generate a synthetic CT (sCT). We compare the uCT and sCT images to obtain a residual image, which is then filtered to extract the strip artifacts. An inverse polar transformation is performed to obtain the ring artifacts, which are subtracted from the original CT image to produce a corrected image.Main results.To validate the effectiveness of our approach, we tested it using real CT data, simulated data, and cone beam computed tomography images of the patient's brain. The corrected CT images showed a reduction in mean absolute error by 12.36 Hounsfield units (HU), a decrease in root mean square error by 18.94 HU, an increase in peak signal-to-noise ratio by 3.53 decibels (dB), and an improvement in structural similarity index by 9.24%.Significance.These results demonstrate the efficacy of our method in eliminating ring artifacts and preserving image details, making it a valuable tool for CT imaging.

Characteristics of the phonon laser in the active levitated optomechanical system.

Phonon lasers, coherent oscillations of phonons, have gradually become one of the emerging frontiers in the last decades, and have promising applications in quantum sensing, information processing, and precise measurement. Recently, phonon lasers based on dissipative coupling have been realized in an active levitated optomechanical (LOM) system for the first time. Here, we further investigated the characteristics of the phonon laser in the system above regarding the oscillator amplitude and the phonon laser linewidth. We established both the experimental system and a physical model of the phonon laser. On the basis of simulations and experiments, the influences of pumping power, numerical aperture, the microsphere's diameter and refractive index on the performance of the phonon lasers are sufficiently discussed. Our work is of great significance for the high-quality phonon lasers generated by the appropriate parameters, which is the basis for the in-depth research and practical application.

An unsupervised dual contrastive learning framework for scatter correction in cone-beam CT image.

PURPOSE: Cone-beam computed tomography (CBCT) is widely utilized in modern radiotherapy; however, CBCT images exhibit increased scatter artifacts compared to planning CT (pCT), compromising image quality and limiting further applications. Scatter correction is thus crucial for improving CBCT image quality. METHODS: In this study, we proposed an unsupervised contrastive learning method for CBCT scatter correction. Initially, we transformed low-quality CBCT into high-quality synthetic pCT (spCT) and generated forward projections of CBCT and spCT. By computing the difference between these projections, we obtained a residual image containing image details and scatter artifacts. Image details primarily comprise high-frequency signals, while scatter artifacts consist mainly of low-frequency signals. We extracted the scatter projection signal by applying a low-pass filter to remove image details. The corrected CBCT (cCBCT) projection signal was obtained by subtracting the scatter artifacts projection signal from the original CBCT projection. Finally, we employed the FDK reconstruction algorithm to generate the cCBCT image. RESULTS: To evaluate cCBCT image quality, we aligned the CBCT and pCT of six patients. In comparison to CBCT, cCBCT maintains anatomical consistency and significantly enhances CT number, spatial homogeneity, and artifact suppression. The mean absolute error (MAE) of the test data decreased from 88.0623 ± 26.6700 HU to 17.5086 ± 3.1785 HU. The MAE of fat regions of interest (ROIs) declined from 370.2980 ± 64.9730 HU to 8.5149 ± 1.8265 HU, and the error between their maximum and minimum CT numbers decreased from 572.7528 HU to 132.4648 HU. The MAE of muscle ROIs reduced from 354.7689 ± 25.0139 HU to 16.4475 ± 3.6812 HU. We also compared our proposed method with several conventional unsupervised synthetic image generation techniques, demonstrating superior performance. CONCLUSIONS: Our approach effectively enhances CBCT image quality and shows promising potential for future clinical adoption.