Optical single-channel color image encryption based on chaotic fingerprint phase mask and diffractive imaging.

An optical single-channel color image encryption scheme based on chaotic fingerprint phase mask and diffractive imaging is proposed. In this proposed encryption scheme, the fingerprint used to generate the random phase masks is served as a secret key directly. Additionally, the random phase masks generated by the fingerprint, chaotic Lozi map, and secure hash algorithm (SHA-256) are used only as interim variables. With the help of the chaotic fingerprint phase masks placed at different diffraction distances, the color image that is encoded into a grayscale pattern by the phase-truncation technique is encrypted into a noise-like diffraction pattern. For decryption, the color image can be retrieved from the noise-like diffraction pattern by using an iterative phase retrieval algorithm, fingerprint, and phase keys generated from the encryption process. Since the fingerprint key shared by the sender and authorized receiver is strongly linked with the user and does not need to be transmitted over the open network, the security of this proposed encryption scheme can be greatly improved. Additionally, the parameters of the chaotic Lozi map and Fresnel diffraction distances can also provide additional security to the proposed encryption scheme. Furthermore, compared with the encryption schemes based on digital holography, the implementation of this proposed encryption scheme is relatively simple. The numerical simulations and analysis verify the feasibility, security, and robustness of this proposed encryption scheme.

Optical encoding and hiding scheme for a double image based on chaotic fingerprint phase masks and phase-shifting digital holography.

This paper proposes a novel, to the best of our knowledge, double-image hiding scheme based on the chaotic fingerprint phase masks (CFPMs) and three-step phase-shifting digital holography (PSDH). First, the two images to be hidden are encoded into a complex amplitude image, and then with the help of the CFPM located in the Fresnel transform (FrT) domain and the three-step PSDH, the complex amplitude image can be encoded into three noise-like interference holograms. Finally, the three noise-like interference holograms are hidden into the texture part of the host image by the discrete wavelet transform based fusion approach and variational image decomposition technique. This scheme can simultaneously hide two images into one host image, and the invisibility and robustness of the hiding scheme can be well balanced by embedding the secret image in the texture of the host image. Additionally, the introduction of a biometric feature increases the association of the key and the authorized user, and the parameters of the chaotic map and FrT can also provide additional security to the proposed scheme. We have verified the scheme's feasibility, security, and robustness through extensive experiments.

Copper in grape and wine industry: Source, presence, impacts on production and human health, and removal methods.

Heavy metals are of particular concern in grape and wine processing, especially copper. The sources of copper are diverse, including vineyard soil, copper-containing pesticides on the fruit surface, copper wine-making equipment, and exogenous addition in winemaking. Copper has potential risks to human nerves, metabolism, and others. It can inhibit yeast growth, delay fermentation, and also mediate oxidation reactions, which has a huge impact on the nutritional quality and sensory quality of fresh wine and aged wine. It is therefore crucial to detect, quantify, and remove copper from grapes and wine. However, the copper situations in the wine industries of various countries are complicated and diverse, and the existing forms of copper are quite different, which makes the research challenging. This review summarizes and analyzes the existence and influence of copper in the wine industry by analyzing the sources of, the current situation regarding, and the detection and removal methods for copper in wine. With the study, a better understanding of copper's impact on wine production will be gained, facilitating further control of copper in wine and helping the wine industry grow.

How to comprehensively improve juice quality: a review of the impacts of sterilization technology on the overall quality of fruit and vegetable juices in 2010-2021, an updated overview and current issues.

Fruit and vegetable juices (FVJ) are rich in nutrients, so they easily breed bacteria, which cause microbial pollution and rapid deterioration of their quality and safety. Sterilization is an important operation in FVJ processing. However, regardless of whether thermal sterilization or non-thermal sterilization is used, the effect and its impact on the overall quality of FVJ are strongly dependent on the processing parameters, microbial species, and FVJ matrix. Therefore, for different types of FVJ, an understanding of the impacts that different sterilization technologies have on the overall quality of the juice is important in designing and optimizing technical parameters to produce value-added products. This article provides an overview of the application of thermal and non-thermal technique in the field of FVJ processing over the past 10 years. The operating principle and effects of various technologies on the inactivation of microorganisms and enzymes, nutritional and functional characteristics, physicochemical properties, and sensory quality of a wide range of FVJ are comprehensively discussed. The application of different combinations of hurdle technology in the field of FVJ sterilization processing are also discussed in detail. Additionally, the advantages, limitations, and current application prospects of different sterilization technologies are summarized.

Comprehensive Analysis of Tripterine Anti-Ovarian Cancer Effects Using Weighted Gene Co-Expression Network Analysis and Molecular Docking.

BACKGROUND Ovarian cancer has the highest mortality of gynecological cancers worldwide. The aim of this study was to identify the role of tripterine against ovarian cancer. MATERIAL AND METHODS GSE18520 and GSE12470 data sets were downloaded from the GEO database. WGCNA was used to analyze gene modules and hub genes related to ovarian cancer. These hub genes were intersected with tripterine targets, and GO and KEGG enrichment analyses were performed. HPA and GEPIA determined the expression of tripterine anti-ovarian hub genes in tumor tissues. Kaplan-Meier plotter was used to explore the role of hub genes in ovarian cancer prognosis. AutoDock was used to conduct molecular docking of tripterine and hub genes to observe whether the combination was stable. RESULTS By differential analysis of gene expression and the construction of WGCNA co-expression network, 5 hub genes, ARHGAP11A, MUC1, HBB, RUNX1T1, and FUT8, were screened by module gene screening. Seven biological processes and 20 KEGG-related pathways were obtained by gene enrichment. The expression of tripterine anti-ovarian hub genes ARHGAP11A, MUC1, and FUT8 were obtained by HPA and GEPIA. Using Kaplan-Meier plotter, the survival of ovarian cancer was negatively correlated with ARHGAP11A, MUC1, and FUT8. Molecular docking showed the combination of tripterine and FUT8 was most stable, having the greatest potential role. CONCLUSIONS Tripterine may be involved in megakaryocyte development and platelet production through potential genes ARHGAP11A, MUC1, HBB, RUNX1T1, and FUT8 and may have an anti-ovarian cancer effect in immune factors signaling, transporting and exchanging oxygen pathways, and autophagy pathways, through these 5 key genes.

Asymmetric double-image encryption based on chaotic random phase encoding.

An asymmetric double-image encryption scheme based on chaotic random phase encoding (CRPE) is proposed. In this proposed encryption scheme, two grayscale images to be encrypted are first Fresnel transformed and combined into a complex image. Then, the amplitude and phase components are obtained by conducting phase-amplitude truncation on the complex image. Finally, the amplitude component is again Fresnel transformed and encrypted into a noise-like pattern by the CRPE in the Fresnel domain. Since the initial values and control parameters of the chaotic map can replace the random phase masks to serve as secret keys, the management and transmission of secret keys will become more convenient in the proposed encryption scheme. Furthermore, the Fresnel transform parameters and phase keys derived from the complex image's phase component can also act as secret keys during the decryption process. Numerical simulations have demonstrated the feasibility, security, and robustness of the proposed encryption scheme.

Early prediction of noninvasive ventilation failure after extubation: development and validation of a machine-learning model.

BACKGROUND: Noninvasive ventilation (NIV) has been widely used in critically ill patients after extubation. However, NIV failure is associated with poor outcomes. This study aimed to determine early predictors of NIV failure and to construct an accurate machine-learning model to identify patients at risks of NIV failure after extubation in intensive care units (ICUs). METHODS: Patients who underwent NIV after extubation in the eICU Collaborative Research Database (eICU-CRD) were included. NIV failure was defined as need for invasive ventilatory support (reintubation or tracheotomy) or death after NIV initiation. A total of 93 clinical and laboratory variables were assessed, and the recursive feature elimination algorithm was used to select key features. Hyperparameter optimization was conducted with an automated machine-learning toolkit called Neural Network Intelligence. A machine-learning model called Categorical Boosting (CatBoost) was developed and compared with nine other models. The model was then prospectively validated among patients enrolled in the Cardiac Surgical ICU of Zhongshan Hospital, Fudan University. RESULTS: Of 929 patients included in the eICU-CRD cohort, 248 (26.7%) had NIV failure. The time from extubation to NIV, age, Glasgow Coma Scale (GCS) score, heart rate, respiratory rate, mean blood pressure (MBP), saturation of pulse oxygen (SpO2), temperature, glucose, pH, pressure of oxygen in blood (PaO2), urine output, input volume, ventilation duration, and mean airway pressure were selected. After hyperparameter optimization, our model showed the greatest accuracy in predicting NIV failure (AUROC: 0.872 [95% CI 0.82-0.92]) among all predictive methods in an internal validation. In the prospective validation cohort, our model was also superior (AUROC: 0.846 [95% CI 0.80-0.89]). The sensitivity and specificity in the prediction group is 89% and 75%, while in the validation group they are 90% and 70%. MV duration and respiratory rate were the most important features. Additionally, we developed a web-based tool to help clinicians use our model. CONCLUSIONS: This study developed and prospectively validated the CatBoost model, which can be used to identify patients who are at risk of NIV failure. Thus, those patients might benefit from early triage and more intensive monitoring. TRIAL REGISTRATION: NCT03704324. Registered 1 September 2018, https://register. CLINICALTRIALS: gov .

Efficacy of High-Flow Nasal Cannula Oxygen Therapy in Patients with Mild Hypercapnia.

OBJECTIVES: To investigate the indications of high-flow nasal cannula (HFNC) oxygen therapy among patients with mild hypercapnia and to explore the predictors of intubation when HFNC fails. METHODS: This retrospective study was conducted based on the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Adult patients with mild hypercapnia (45 < PaCO2 ≤ 60 mmHg) received either HFNC or non-invasive ventilation (NIV) oxygen therapy. Propensity score matching (PSM) was implemented to increase between-group comparability. The Kaplan-Meier method was used to estimate overall survival and cumulative intubation rates, while 28-day mortality and 48-h and 28-day intubation rates were compared using the Chi-squared test. The predictive performances of HR/SpO2 and the ROX index (the ratio of SpO2/FiO2 to respiratory rate) at 4 h were assessed regarding HFNC failure, which was determined if intubation was given within 48 h after the initiation of oxygen therapy. The area under the receiver operating characteristic curve (AUC) for HR/SpO2 and the ROX index were calculated and compared. RESULTS: A total of 524,520 inpatient hospitalization records were screened, 106 patients in HFNC group and 106 patients in NIV group were successfully matched. No significant difference in 48-h intubation rate between the HFNC group (the treatment group) and the NIV group (the control group) (14.2% vs. 8.5%, p = 0.278); patients receiving HFNC had higher 28-day intubation rate (26.4% vs. 14.2%, p = 0.029), higher 28-day mortality (17.9% vs. 8.5%, p = 0.043), and longer ICU length of stay (4.4 vs. 3.3 days, p = 0.019), compared to those of NIV group. The AUC of HR/SpO2 at 4 h after the initiation of HFNC yielded around 0.660 for predicting 48-h intubation, greater than that of the ROX index with an AUC of 0.589 (p < 0.01). CONCLUSION: Patients with impending respiratory failure had lower intubation rate, shorter ICU length of stay, and lower mortality when treated mild hypercapnia with NIV over HFNC. As opposed to the ROX index, a modest, yet improved predictive performance is demonstrated using HR/SpO2 in predicting the failure of HFNC among these patients.

Effects of high-flow oxygen therapy on patients with hypoxemia after extubation and predictors of reintubation: a retrospective study based on the MIMIC-IV database.

BACKGROUND: To investigate the indications for high-flow nasal cannula oxygen (HFNC) therapy in patients with hypoxemia during ventilator weaning and to explore the predictors of reintubation when treatment fails. METHODS: Adult patients with hypoxemia weaning from mechanical ventilation were identified from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The patients were assigned to the treatment group or control group according to whether they were receiving HFNC or non-invasive ventilation (NIV) after extubation. The 28-day mortality and 28-day reintubation rates were compared between the two groups after Propensity score matching (PSM). The predictor for reintubation was formulated according to the risk factors with the XGBoost algorithm. The areas under the receiver operating characteristic curve (AUC) was calculated for reintubation prediction according to values at 4 h after extubation, which was compared with the ratio of SpO2/FiO2 to respiratory rate (ROX index). RESULTS: A total of 524,520 medical records were screened, and 801 patients with moderate or severe hypoxemia when undergoing mechanical ventilation weaning were included (100 < PaO2/FiO2 ≤ 300 mmHg), including 358 patients who received HFNC therapy after extubation in the treatment group. There were 315 patients with severe hypoxemia (100 < PaO2/FiO2 ≤ 200 mmHg) before extubation, and 190 patients remained in the treatment group with median oxygenation index 166[157,180] mmHg after PSM. There were no significant differences in the 28-day reintubation rate or 28-day mortality between the two groups with moderate or severe hypoxemia (all P > 0.05). Then HR/SpO2 was formulated as a predictor for 48-h reintubation according to the important features predicting weaning failure. According to values at 4 h after extubation, the AUC of HR/SpO2 was 0.657, which was larger than that of ROX index (0.583). When the HR/SpO2 reached 1.2 at 4 h after extubation, the specificity for 48-h reintubation prediction was 93%. CONCLUSIONS: The treatment effect of HFNC therapy is not inferior to that of NIV, even on patients with oxygenation index from 160 to 180 mmHg when weaning from ventilator. HR/SpO2 is more early and accurate in predicting HFNC failure than ROX index.

Effect of partial substitution of wheat flour with kiwi starch on dough rheology, microstructure, the quality attributes and shelf life of Chinese steamed bread.

Chinese steamed bread (CSB), a conventional high-GI staple food, with a short shelf life and a single flavor. In this work, 10-20 % kiwi starch (KS) was used to substitute wheat flour for the production of CSB and the effects of different substitution ratios on the quality and shelf life of mixed flour, dough, and CSB were explored. The results showed that the substitution of KS could improve the water binding capacity of mixed flour and lead to easier pasting in the system, lower the cooking power consumption, increase and improve the viscoelasticity and gas holding capacity of the dough, and make the microstructure more compact and uniform. As the substitution ratio increased, the reduction in protein content within the system further affected the formation of the gluten network, leading to a significant decrease in the CSB's specific volume and cohesiveness, whereas the chewiness and hardness were significantly improved. Meanwhile, KS substitution significantly reduced the starch hydrolysis rate and estimated glycemic index of CSB. 10 % KS substitution enriched the aroma and color of CSB, improved its internal organizational structure, and became more popular among consumers. A substitution ratio of 15-20 % was beneficial for extending the shelf life of CSB.

Manganese Dioxide Coated Piezoelectric Nanosonosensitizer for Cancer Therapy with Tumor Microenvironment Remodeling and Multienzyme-Like Catalysis.

Sonodynamic therapy (SDT) as an emerging method for cancer therapy has encountered difficulty in insufficient production of reactive oxygen species (ROS), especially in tumor microenvironment (TME) with elevated antioxidants and hypoxic conditions. In this work, the authors have fabricated heterostructured manganese dioxide (MnO2)-coated BaTiO3 nanoparticles (BTO@M NPs) as a piezoelectric sonosensitizer, which exhibits the capacity of remodeling TME and multienzyme-like catalysis for boosting SDT. Benefitting from the piezotronic effect, the formation of a p-n junction between MnO2 and piezoelectric BTO with a built-in electric field and band bending efficiently promotes the separation of charge carriers, facilitating the generation of superoxide anion (•O2 -) and hydroxyl radical (•OH) under ultrasound (US) stimulation. Moreover, BTO@M NPs can catalyze the overexpressed hydrogen peroxide (H2O2) in TME to produce oxygen for replenishing the gas source in SDT, and also deplete antioxidant glutathione (GSH), realizing TME remodeling. During this process, the reduced Mn(II) can convert H2O2 into •OH, further amplifying cellular oxidative damage. With these combination effects, the versatile BTO@M NPs exhibit prominent cytotoxicity and tumor growth inhibition against 4T1 breast cancer. This work provides a feasible strategy for constructing high-efficiency sonosensitizers for cancer SDT.

Primary biliary cirrhosis and psoriasis: a two-sample Mendelian randomization study.

Background: Primary biliary cirrhosis (PBC) and psoriasis are frequently observed to co-occur in clinical settings. However, the causal associations and underlying mechanisms between PBC and psoriasis remain poorly defined. Methods: In this study, we conducted bidirectional MR analysis to explore the causal relationship between PBC and psoriasis using four MR methods: inverse-variance weighted, MR-Egger regression, weighted median, and weighted mode. Sensitivity analyses were carried out, employing different models and testing methods for comparison to assess the influence of heterogeneity and pleiotropy on our findings and to confirm the robustness of these results. Results: A causal relationship between the risk of PBC and psoriasis was identified, as confirmed by IVW analysis (OR: 1.081, 95%CI: 1.028~1.137, P<0.05). The other three MR methods also produced similar results. However, psoriasis did not have a causal effect on PBC risk (OR: 1.022, 95%CI: 0.935~1.118, P>0.05). The intercept of MR-Egger regression was 0.0013 (P>0.05), indicating that genetic pleiotropy did not influence the results. Additionally, the leave-one-out analysis demonstrated the robustness of our MR findings. Conclusion: This study reveals a causal relationship between PBC and psoriasis, with PBC increasing the risk of psoriasis, but not the reverse. This potential causal relationship offers a new perspective on the etiology of PBC.

Numerical simulation and exergy analysis of a single-stage GM cryocooler.

Improving the efficiency of the GM cryocoolers is of great importance for energy saving and CO2 emission reduction due to the large amount of cryocoolers installed in the emerging fields of semiconductor manufacture and High Temperature Superconductors (HTS) cooling. Previous studies mainly focused on the losses analysis and optimization on the part of cold head, but the details of losses distribution in the parts of compressor and rotary valve were seldom carried out. In this paper, a numerical model of a single stage GM cryocooler including compressor, rotary valve and expander is built, and the feasibility of the model is verified by the experimental results. The losses characteristics of the whole cryocooler are studied based on the exergy analysis method with the help of the numerical model. The results indicate that the main losses are occurred in compressor and rotary valve, the value of exergy loss in compressor decrease with the cooling temperature, and accounts for more than 60% at all cooling temperature. The loss in rotary valve accounts for about 20% of the input electric power, and it does not significantly vary at different cooling temperatures. Pressure drop dominates the loss in the compressor and rotary valve. The insufficient heat exchange between the working gas and regenerative material is the main loss in regenerator, and the losses in regenerator increase significantly with the decrease of cooling temperature when the compressor and rotary valve are fixed. This study provides useful guides for the optimization of GM-type cryocoolers.

Effect of electronic health (eHealth) on quality of life in women with breast cancer: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Women with breast cancer and improved survival face some specific quality of life (QOL) issues. Electronic health (eHealth) is a useful tool aiming to enhance health services. However, evidence remains controversial about the effect of eHealth on QOL in women with breast cancer. Another unstudied factor is the effect on specific QOL functional domains. Therefore, we undertook a meta-analysis about whether eHealth could improve the overall and specific functional domains of QOL in women with breast cancer. METHODS: PubMed, Cochrane Library, EMBASE, and Web of Science were searched to identify appropriate randomized clinical trials from database inception to March 23, 2022. The standard mean difference (SMD) served as the effect size and the DerSimonian-Laird random effects model was constructed for meta-analysis. Subgroup analyses were conducted according to different participant, intervention, and assessment scale characteristics. RESULTS: We initially identified 1954 articles excluding duplicates and ultimately included 13 of them involving 1448 patients. The meta-analysis revealed that the eHealth group had significantly higher QOL (SMD 0.27, 95% confidence interval [95% CI] 0.13-0.40, p < 0.0001) than the usual care group. Additionally, although not statistically significant, eHealth tended to improve the physical (SMD 2.91, 95% CI -1.18 to 6.99, p = 0.16), cognitive (0.20 [-0.04, 0.43], p = 0.10), social (0.24 [-0.00, 0.49], p = 0.05), role (0.11 [0.10, 0.32], p = 0.32), and emotional (0.18 [0.08, 0.44], p = 0.18) domains of QOL. Overall, consistent benefits were observed in both the subgroup and pooled estimates. CONCLUSIONS: eHealth is superior to usual care in women with breast cancer for improved QOL. Implications for clinical practice should be discussed based on subgroup analysis results. Further confirmation is needed for the effect of different eHealth patterns on specific domains of QOL, which would help improve specific health issues of the target population.

Comprehensive evaluation of the effect of five sterilization methods on the quality of black carrot juice based on PCA, TOPSIS and GRA models.

The effect of thermal pasteurization (TP), high temperature long time (HTLT), ultra-high temperature instantaneous (UHT), high hydrostatic pressure (HHP) and thermosonication (TS) sterilization on the physicochemical, sensory and functional properties of black carrot juice (BCJ) were studied. And for the first time, the comprehensive quality of sterilized BCJ was quantified by mathematical modeling. UHT was the least suitable sterilization method for BCJ resulting from the most severe deterioration in functional properties. TS had adverse effects on sensory and physicochemical properties, but significantly increased the total flavonoids and anthocyanins contents (p < 0.05) and showed the strongest antioxidant activity, making it a nutritional high-value processing method. TP and HHP balanced the improvement of sensory properties and the retention of functional properties, which were the most suitable sterilization methods for BCJ. This study determined the optimal sterilization methods of BCJ, and provided a scientific solution for the screening of high quality processing methods.

Effects and impacts of technical processing units on the nutrients and functional components of fruit and vegetable juice.

Fruit and vegetable juice (FVJ) has become a favorite beverage for all age groups because of its excellent sensory and nutritional qualities. FVJ has a series of health benefits such as antioxidant, anti-obesity, anti-inflammatory, anti-microbial and anti-cancer. Except for raw materials selection, processing technology and packaging and storage also play a vital role in the nutrition and functional components of FVJ. This review systematically reviews the important research results on the relationship between FVJ processing and its nutrition and function in the past 10 years. Based on the brief elucidation of the nutrition and health benefits of FVJ and the unit operation involved in the production process, the influence of a series of key technology units, including pretreatment, clarification, homogenization, concentration, sterilization, drying, fermentation and packaging and storage, on the nutritional function of FVJ was systematically expounded. This contribution provides an update on the impacts of technical processing units on the nutrients and functional components of FVJ and new perspectives for future studies.

Optimization of strains for fermentation of kiwifruit juice and effects of mono- and mixed culture fermentation on its sensory and aroma profiles.

In this study, a quality evaluation model of fermented kiwifruit juice (KJ) based on strain growth characteristics, sensory quality and functional characteristics was established by PCA, and the effects of mono- and mixed culture fermentation on the sensory and aroma profiles of KJ were comparatively studied. Experiments determined that L. brevis (LB) was the optimal strain for monoculture fermentation, and L. plantarum (LP2):LB = 1:2 was the optimum ratio for mixed fermentation. The results showed that lactic acid bacteria (LAB) fermentation significantly reduced the pH, soluble solid content and lightness, and improved its functional characteristics and viscosity. Mixed culture fermentation was superior to monoculture fermentation in terms of colony counts, sensory quality and viscosity. In general, after LAB fermentation, the concentrations of esters, ketones, alcohols and terpenoids in KJ increased significantly, while the concentrations of aldehydes decreased significantly. The production of esters and terpenoids was more strongly promoted by monoculture fermentation, while mixed culture fermentation promoted the production of more ketones and alcohols. 2,5-octanedione and 1-octen-3-ol could be the characteristic aroma compounds of mixed fermented KJ.

In vivo adenine base editing corrects newborn murine model of Hurler syndrome.

Mucopolysaccharidosis type I (MPS I) is a severe disease caused by loss-of-function mutation variants in the α-L-iduronidase (Idua) gene. In vivo genome editing represents a promising strategy to correct Idua mutations, and has the potential to permanently restore IDUA function over the lifespan of patients. Here, we used adenine base editing to directly convert A > G (TAG>TGG) in a newborn murine model harboring the Idua-W392X mutation, which recapitulates the human condition and is analogous to the highly prevalent human W402X mutation. We engineered a split-intein dual-adeno-associated virus 9 (AAV9) adenine base editor to circumvent the package size limit of AAV vectors. Intravenous injection of the AAV9-base editor system into MPS IH newborn mice led to sustained enzyme expression sufficient for correction of metabolic disease (GAGs substrate accumulation) and prevention of neurobehavioral deficits. We observed a reversion of the W392X mutation in 22.46 ± 6.74% of hepatocytes, 11.18 ± 5.25% of heart and 0.34 ± 0.12% of brain, along with decreased GAGs storage in peripheral organs (liver, spleen, lung and kidney). Collectively, these data showed the promise of a base editing approach to precisely correct a common genetic cause of MPS I in vivo and could be broadly applicable to the treatment of a wide array of monogenic diseases.

In vivo base editing rescues photoreceptors in a mouse model of retinitis pigmentosa.

Retinitis pigmentosa (RP) is a group of retinal diseases that cause the progressive death of retinal photoreceptor cells and eventually blindness. Mutations in the ß-domain of the phosphodiesterase 6 (Pde6b) gene are the most identified causes of autosomal recessive RP. Clinically, there is no effective treatment so far that can stop the progression of RP and restore the vision. Here, we report a base editing approach in which adeno-associated virus (AAV)-mediated adenine base editor (ABE) delivering to postmitotic photoreceptors was conducted to correct the Pde6b mutation in a retinal degeneration 10 (rd10) mouse model of RP. Subretinal delivery of AAV8-ABE corrected Pde6b mutation with averaging up to 20.79% efficiency at the DNA level and 54.97% efficiency at the cDNA level without bystanders, restored PDE6B expression, preserved photoreceptors, and rescued visual function. RNA-seq revealed the preservation of genes associated with phototransduction and photoreceptor survival. Our data have demonstrated that base editing is a potential gene therapy that could provide durable protection against RP.