Factors correlating the expression of PD-L1.

OBJECTIVE: PD-L1 was an important biomarker in lung adenocarcinoma. The study was to confirm the most important factor affecting the expression of PD-L1 remains undetermined. METHODS: The clinical records of 1045 lung adenocarcinoma patients were retrospectively reviewed. The High-Resolution Computed Tomography (HRCT) scanning images of all the participants were analyzed, and based on the CT characteristics, the adenocarcinomas were categorized according to CT textures. Furthermore, PD-L1 expression and Ki67 index were detected by immunohistochemistry. All patients underwent EGFR mutation detection. RESULTS: Multivariate logistic regression analysis revealed that smoking (OR: 1.73, 95% CI: 1.04-2.89, p = 0.004), EGFR wild (OR: 1.52, 95% CI: 1.11-2.07, p = 0.009), micropapillary subtypes (OR: 2.05, 95% CI: 1.46-2.89, p < 0.0001), and high expression of Ki67 (OR: 2.02, 95% CI: 1.44-2.82, p < 0.0001) were independent factors which influence PD-L1 expression. In univariate analysis, tumor size > 3 cm and CT textures of pSD showed a correlation with high expression of PD-L1. Further analysis revealed that smoking, micropapillary subtype, and EGFR wild type were also associated with high Ki67 expression. Moreover, high Ki67 expression was observed more frequently in tumors of size > 3 cm than in tumors with ≤ 3 cm size as well as in CT texture of pSD than lesions with GGO components. In addition, multivariate logistic regression analysis revealed that only lesions with micropapillary components correlated with pSD (OR: 3.96, 95% CI: 2.52-5.37, p < 0.0001). CONCLUSION: This study revealed that in lung adenocarcinoma high Ki67 expression significantly influenced PD-L1 expression, an important biomarker for immune checkpoint treatment.

Antibacterial activity of essential oils extracted from the unique Chinese spices cassia bark, bay fruits and cloves.

Spices are widely used in daily life such as diet and have certain activity. Especially in China, spices have been mainly used as condiments for thousands of years in order to improve the sensory quality of food; in addition, they and their derivatives can also be used as preservatives. In this study, three spices with unique Chinese characteristics widely used were selected: cassia bark (bark of Cinnamomum camphora Presl), bay fruits (Laurus nobilis), and cloves (Syzygiumaromaticum). The main components and antibacterial ability of these three spices were analyzed by simulated extraction method. Through headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-MS) analysis, it was determined that the main active compounds in the essential oils of cassia bark, bay fruits and cloves were cinnamaldehyde (78.11%), cinnamaldehyde (61.78%) and eugenol (75.23%), respectively. The agar plate diffusion test and the simulated food culture medium experiment confirmed that the essential oils extracted from the three flavors have antibacterial effects on Listeria monocytogenes, Listeria innocua, Listeria welshimeri, Listeria ivanovii, Listeria grayi and Vibrio parahaemolyticus. The antibacterial activity of different strains has different optimal extraction conditions. Generally speaking, cinnamon essential oil has the strongest antibacterial activity, while laurel fruit has the lowest antibacterial activity. The study proved the antibacterial activity of these three Chinese-specific spices and provided some new ideas and methods for the subsequent research and preparation of natural food additives and food antibacterial agents.

A systematic review of synthetic tyrosinase inhibitors and their structure-activity relationship.

Tyrosinase is a copper-containing oxidation enzyme, which is responsible for the production of melanin. This enzyme is widely distributed in microorganisms, animals and plants, and plays an essential role in undesirable browning of fruits and vegetables, antibiotic resistance, skin pigment formation, sclerotization of cuticle, neurodegeneration, etc. Hence, it has been recognized as a therapeutic target for the development of antibrowning agents, antibacterial agents, skin-whitening agents, insecticides, and other therapeutic agents. With great potential application in food, agricultural, cosmetic and pharmaceutical industries, a large number of synthetic tyrosinase inhibitors have been widely reported in recent years. In this review, we systematically summarized the advances of synthetic tyrosinase inhibitors in the literatures, including their inhibitory activity, cytotoxicity, structure-activity relationship (SAR), inhibition kinetics, and interaction mechanisms with the enzyme. The collected information is expected to provide a rational guidance and effective strategy to develop novel, potent and safe tyrosinase inhibitors for better practical applications in the future.

Phages and their lysins: Toolkits in the battle against foodborne pathogens in the postantibiotic era.

Worldwide, foods waste caused by putrefactive organisms and diseases caused by foodborne pathogens persist as public health problems even with a plethora of modern antimicrobials. Our over reliance on antimicrobials use in agriculture, medicine, and other fields will lead to a postantibiotic era where bacterial genotypic resistance, phenotypic adaptation, and other bacterial evolutionary strategies cause antimicrobial resistance (AMR). This AMR is evidenced by the emergence of multiple drug-resistant (MDR) bacteria and pan-resistant (PDR) bacteria, which produces cross-contamination in multiple fields and poses a more serious threat to food safety. A "red queen premise" surmises that the coevolution of phages and bacteria results in an evolutionary arms race that compels phages to adapt and survive bacterial antiphage strategies. Phages and their lysins are therefore useful toolkits in the design of novel antimicrobials in food protection and foodborne pathogens control, and the modality of using phages as a targeted vector against foodborne pathogens is gaining momentum based on many encouraging research outcomes. In this review, we discuss the rationale of using phages and their lysins as weapons against spoilage organisms and foodborne pathogens, and outline the targeted conquest or dodge mechanism of phages and the development of novel phage prospects. We also highlight the implementation of phages and their lysins to control foodborne pathogens in a farm-table-hospital domain in the postantibiotic era.

Surveillance Magnetic Resonance Imaging in Detecting the Second Breast Cancer in Women With a Personal History of Breast Cancer.

OBJECTIVE: The objective of this study was to evaluate the diagnostic performance of magnetic resonance imaging (MRI) in detecting the secondary breast cancer among women with a personal history of the lesion. MATERIALS AND METHODS: We retrospectively reviewed breast MRI examinations performed between 2007 and 2011. A total of 798 women with a history of breast cancer were included in the study. Cancer detection rate, positive predictive value (PPV), recall rate, sensitivity, and specificity were assed. Cancer detection rate was stratified by interval after surgery of the primary breast cancer. Also, we derived 1 comparison group from the women for comparing the performance of x-ray mammography, ultrasound, and MRI in detecting the second breast cancer. RESULTS: Of the 798 patients, 47 of the 49 secondary breast carcinomas were detected by MRI. The sensitivity and specificity of MRI in detecting the secondary lesions were 95.9% and 96.3%, respectively. The recall rate was 9.5%, and the PPV was 61.8%. Cancer detection rate of MRI examinations performed at more than 36 months after initial surgery was significantly higher than that at 36 months or less after initial surgery (13.7% vs 3.6, P < 0.001). In comparison group, the sensitivity and specificity of MRI, mammography, and ultrasound were 96.7% and 96.1%, 48.4% and 93.9%, and 77.4% and 96.1%, respectively. CONCLUSIONS: Surveillance MRI for women with a personal history of breast cancer has high sensitivity in finding the secondary malignancies with a reasonable recall rate and PPV.

CRISPR-Cas9 knockout of qseB induced asynchrony between motility and biofilm formation in Escherichia coli.

Generally, cell motility and biofilm formation are tightly regulated. The QseBC two-component system (TCS) serves as a bridge for bacterial signal transmission, in which the protein QseB acts as a response regulator bacterial motility, biofilm formation, and virulence. The mechanisms that govern the interaction between QseBC and their functions have been studied in general, but the regulatory role of QseB on bacterial motility and biofilm formation is unknown. In this study, the CRISPR-Cas9 system was used to construct the Escherichia coli MG1655ΔqseB strain (strain ΔqseB), and the effects of the qseB gene on changes in motility and biofilm formation in the wild type (WT) were determined. The motility assay results showed that the ΔqseB strain had higher (p < 0.05) motility than the WT strain. However, there was no difference in the formation of biofilm between the ΔqseB and WT strains. Real-time quantitative PCR illustrated that deletion of qseB in the WT strain downregulated expression of the type I pili gene fimA. Therefore, we might conclude that the ΔqseB induced the downregulation of fimA, which led to asynchrony between motility and biofilm formation in E. coli, providing new insight into the functional importance of QseB in regulating cell motility and biofilm formation.

Acidic electrolysed water delays browning by destroying conformation of polyphenoloxidase.

BACKGROUND: Browning frequently occurs at fruits, vegetables and aquatic products during storage, and it drastically reduces the consumer's acceptability, with considerable financial loss. The objective of this paper was to investigate the effects of acidic electrolysed water (AEW) technology on polyphenoloxidase (PPO), which is an essential enzyme for browning. RESULTS: AEW ice exhibited a good ability in delaying browning in shrimp. Kinetic study revealed that AEW exhibited the mixed type inhibition of PPO with a Ki value of 1.96 mmol L-1 . Moreover, both the circular dichroism spectrum and Fourier transform infrared spectroscopy analyses revealed that the α-helix in PPO decreased whereas random coil increased which indicates that PPO conformation was destroyed. CONCLUSION: Thus, this paper may provide a deeper understanding of the application of AEW technology for preventing browning in the food industry. © 2017 Society of Chemical Industry.

Reduction of infection risk mediated by co-culturing Vibrio parahaemolyticus and Listeria monocytogenes in refrigerated cooked shrimp.

BACKGROUND: Vibrio parahaemolyticus and Listeria monocytogenes are seafood pathogens of public health significance, and predictive models are effective tools for quantitative microbial risk assessment of these pathogens. However, most current predictive models are based on growth of single strains in broth cultures, and interactions of two or more bacteria in a food matrix can skew the outcomes of the predictions. Therefore, the impact of V. parahaemolyticus and L. monocytogenes when co-cultured and in monoculture on cooked shrimp in cold storage was investigated. RESULTS: The results indicated that L. monocytogenes co-cultured with V. parahaemolyticus exhibited reduced growth and longer lag phase at 4 °C and 10 °C. V. parahaemolyticus exhibited similar behavior when co-cultured with L. monocytogenes at 4 °C (death rate K =  - 0.67 log10 CFU g-1 day . The death rate K at 10 °C when V. parahaemolyticus co-cultured with L. monocytogenes was -1.62 log10 CFU g-1 day-1 . There was no significant reduction of growth in monoculture experiments. CONCLUSION: This study has revealed that interaction of V. parahaemolyticus and L. monocytogenes should be considered when quantifying risks posed by these pathogens during consumption of seafood products. © 2018 Society of Chemical Industry.

Mesoporous Tungsten Oxides with Crystalline Framework for Highly Sensitive and Selective Detection of Foodborne Pathogens.

Foodborne pathogens like Listeria monocytogenes can cause various illnesses and pose a serious threat to public health. They produce species-specific microbial volatile organic compounds, i.e., the biomarkers, making it possible to indirectly measure microbial contamination in foodstuff. Herein, highly ordered mesoporous tungsten oxides with high surface areas and tunable pores have been synthesized and used as sensing materials to achieve an exceptionally sensitive and selective detection of trace Listeria monocytogenes. The mesoporous WO3-based chemiresistive sensors exhibit a rapid response, superior sensitivity, and highly selective detection of 3-hydroxy-2-butanone. The chemical mechanism study reveals that acetic acid is the main product generated by the surface catalytic reaction of the biomarker molecule over mesoporous WO3. Furthermore, by using the mesoporous WO3-based sensors, a rapid bacteria detection was achieved, with a high sensitivity, a linear relationship in a broad range, and a high specificity for Listeria monocytogenes. Such a good gas sensing performance foresees the great potential application of mesoporous WO3-based sensors for fast and effective detection of microbial contamination for the safety of food, water safety and public health.

Regulation of retinal interneuron subtype identity by the Iroquois homeobox gene Irx6.

Interneuronal subtype diversity lies at the heart of the distinct molecular properties and synaptic connections that shape the formation of the neuronal circuits that are necessary for the complex spatial and temporal processing of sensory information. Here, we investigate the role of Irx6, a member of the Iroquois homeodomain transcription factor family, in regulating the development of retinal bipolar interneurons. Using a knock-in reporter approach, we show that, in the mouse retina, Irx6 is expressed in type 2 and 3a OFF bipolar interneurons and is required for the expression of cell type-specific markers in these cells, likely through direct transcriptional regulation. In Irx6 mutant mice, presumptive type 3a bipolar cells exhibit an expansion of their axonal projection domain to the entire OFF region of the inner plexiform layer, and adopt molecular features of both type 2 and 3a bipolar cells, highlighted by the ectopic upregulation of neurokinin 3 receptor (Nk3r) and Vsx1. These findings reveal Irx6 as a key regulator of type 3a bipolar cell identity that prevents these cells from adopting characteristic features of type 2 bipolar cells. Analysis of the Irx6;Vsx1 double null retina suggests that the terminal differentiation of type 2 bipolar cells is dependent on the combined expression of the transcription factors Irx6 and Vsx1, but also points to the existence of Irx6;Vsx1-independent mechanisms in regulating OFF bipolar subtype-specific gene expression. This work provides insight into the generation of neuronal subtypes by revealing a mechanism in which opposing, yet interdependent, transcription factors regulate subtype identity.

Quantifying viable Vibrio parahaemolyticus and Listeria monocytogenes simultaneously in raw shrimp.

A novel TaqMan-based multiplex real-time PCR method combined with propidium monoazide (PMA) treatment was firstly developed for the simultaneous quantification of viable Vibrio parahaemolyticus and Listeria monocytogenes in raw shrimp. The optimization of PMA concentration showed that 100 µM was considered optimal to effectively inhibit 10(8) CFU/mL dead cells of both bacteria. The high specificity of this method was confirmed on tests using 96 target and non-target strains. The optimized assay could detect as low as 10(1)-10(2) CFU/g of each strain on the artificially contaminated shrimp, and its amplification efficiencies were up to 100 and 106 % for V. parahaemolyticus and L. monocytogenes, respectively. Furthermore, this assay has been successfully applied to describe the behavior of these two pathogens in raw shrimps stored at 4 °C. In conclusion, this PMA TaqMan-based multiplex real-time PCR technique, where the whole procedure takes less than 5 h, provides an effective and rapid tool for monitoring contamination of viable V. parahaemolyticus and L. monocytogenes in seafood, improving seafood safety and protecting public health.

Copper-catalyzed domino addition/double cyclization: an approach to polycyclic benzimidazole derivatives.

An efficient and versatile method for the assembly of novel polycyclic benzimidazole derivatives has been developed by Cu-catalyzed domino addition/double cyclization reactions. A wide variety of polycyclic benzimidazole derivatives, which might be used as synthetic medicines and functional materials, were successfully assembled from bis-(o-haloaryl)carbodiimides. Unexpected N-methylated benzo[4,5]imidazo[1,2-a]indoles can also be selectively assembled. Multibonds and polycyclic moieties were conveniently formed in one pot during these domino processes.

Correlation of CT features of lung adenocarcinoma with sex and age.

This study aimed to retrospectively examine the computed tomography (CT) features of lung adenocarcinoma across different demographic groups. Preoperative chest CT findings from 1266 surgically resected lung adenocarcinoma cases were retrospectively analyzed. Lung adenocarcinomas were categorized based on CT characteristics into pure ground glass (pGGO), nodule-containing ground glass opacity (mGGO), and pure solid without containing ground glass opacity (pSD). These categories were correlated with sex, age, EGFR status, and five histopathological subtypes. The diameters of pGGO, mGGO, and pSD significantly increased across all patient groups (P < 0.05). Males exhibited a significantly higher proportion of pSD than females (P = 0.002). The mean diameters of pGGO and pSD were significantly larger in males than in females (P = 0.0017 and P = 0.043, respectively). The frequency of pGGO was higher in the younger age group (≤ 60 years) compared to the older group (> 60 years) for both males (P = 0.002) and females (P = 0.027). The frequency of pSD was higher in the older age group for both sexes. A linear correlation between age and diameter was observed in the entire cohort as well as in the male and female groups (P < 0.0001 for all groups). EGFR mutations were less frequent in pSD compared to pGGO (P = 0.0002) and mGGO (P < 0.0001). The frequency of lesions containing micropapillary components increased from pGGO to mGGO and pSD (P < 0.0001 for all). The frequency of lesions containing solid components also increased from pGGO to mGGO and pSD (P = 0.045, P < 0.0001, and P < 0.0001, respectively). The CT features of lung adenocarcinoma exhibit differences across genders and age groups. Male gender and older age are risk factors for lung adenocarcinoma growth.

Smartphone-assisted colorimetric biosensor for the determination of organophosphorus pesticides on the peel of fruits.

Nowadays, the widespread use of organophosphorus pesticides (OPs) in agricultural production leads to varying degrees of residues in crops, which pose a potential threat to human health. Conventional methods used in national standard for the detection of OPs in fruits and vegetables require expensive instruments or cumbersome sample pretreatment steps for the analysis. To address these challenges, in this work, we took advantage of the peroxidase-like activity of PtCu3 alloy nanocrystals (NCs) for a colorimetric and smartphone assisted sensitive detection of OPs. With the assist of a smartphone, the concentration of OPs on the peel of fruits could be obtained by comparing the B/RG value (the brightness value of blue divided by those of red and green) of a test strip with a calibration curve. This work not only provides a facile and cost-effective method to detect pesticides but also makes a positive contribution to food safety warning.

Preservation effects of photodynamic inactivation-mediated antibacterial film on storage quality of salmon fillets: Insights into protein quality.

The preservation effects of a photodynamic inactivation (PDI)-mediated polylactic acid/5-aminolevulinic acid (PLA/ALA) film on the storage quality of salmon fillets were investigated. Results showed that the PDI-mediated PLA/ALA film could continuously generate reactive oxygen species by consuming oxygen to inactivate native pathogens and spoilage bacteria on salmon fillets. Meanwhile, the film maintained the content of muscle proteins and their secondary and tertiary structures, as well as the integrity of myosin by keeping the activity of Ca2+-ATPase, all of which protected the muscle proteins from degradation. Furthermore, the film retained the activity of total superoxide dismutase (T-SOD), suppressed the accumulation of lipid peroxides (e.g., MDA), which greatly inhibited four main types of protein oxidations. As a result, the content of flavor amino acids and essential amino acids in salmon fillets was preserved. Therefore, the PDI-mediated antimicrobial packaging film greatly preserves the storage quality of aquatic products by preserving the protein quality.

Papillorenal syndrome-causing missense mutations in PAX2/Pax2 result in hypomorphic alleles in mouse and human.

Papillorenal syndrome (PRS, also known as renal-coloboma syndrome) is an autosomal dominant disease characterized by potentially-blinding congenital optic nerve excavation and congenital kidney abnormalities. Many patients with PRS have mutations in the paired box transcription factor gene, PAX2. Although most mutations in PAX2 are predicted to result in complete loss of one allele's function, three missense mutations have been reported, raising the possibility that more subtle alterations in PAX2 function may be disease-causing. To date, the molecular behaviors of these mutations have not been explored. We describe a novel mouse model of PRS due to a missense mutation in a highly-conserved threonine residue in the paired domain of Pax2 (p.T74A) that recapitulates the ocular and kidney findings of patients. This mutation is in the Pax2 paired domain at the same location as two human missense mutations. We show that all three missense mutations disrupt potentially critical hydrogen bonds in atomic models and result in reduced Pax2 transactivation, but do not affect nuclear localization, steady state mRNA levels, or the ability of Pax2 to bind its DNA consensus sequence. Moreover, these mutations show reduced steady-state levels of Pax2 protein in vitro and (for p.T74A) in vivo, likely by reducing protein stability. These results suggest that hypomorphic alleles of PAX2/Pax2 can lead to significant disease in humans and mice.

Aggregation-induced enhancement of peroxidase-mimetic activity of DNAzyme-gold nanoparticles for ultrasensitive detection of lead ions.

Lead ion (Pb2+) detection is critically important in environmental protection and health management. In this work, we developed a simple signal-enhanced colorimetric sensor for the detection of Pb2+ based on the peroxidase-mimetic property of gold nanoparticles (AuNPs). When a certain concentration of Pb2+ was added to a solution of DNAzyme-modified AuNPs, aggregation was triggered, and the result was an enhancement of the peroxidase-mimetic activity of AuNPs. Then, the chromogenic reaction of 3,3',5,5'-tetramethylbenzidine (TMB) by the catalyst of AuNPs was used for the sensitive UV-Vis and colorimetric detection of Pb2+. When a higher concentration of Pb2+ was added, the greater amount of aggregation of AuNPs resulted in the enhancement of the UV-Vis adsorption of the solution at 652 nm, with a deepening of the blue color of the solution. After optimization of the experimental conditions, a linear relationship between the absorbance of oxidized TMB at 652 nm and the logarithm of Pb2+ concentration was obtained, which had been divided into two parts (25 pM to 2.5 µM, and 2.5 µM to 250 µM). The detection limit was as low as 10 pM. The satisfactory specificity and rapid response of the sensor showed that it has promising application for the detection of Pb2+ in real samples.

Expression patterns and influence of the two-component system in Vibrio parahaemolyticus of different genotypes.

Vibrio parahaemolyticus is a foodborne pathogen that threatens global food security and human health. The two-component system (TCS) is a primary method for bacteria self-regulate and adapt to the environment. Previous studies have shown that V. parahaemolyticus has four hemolytic genotypes with diverse biological phenotypes and environmental adaptability, but the mechanism is unclear. In this study, we investigated TCS expression patterns in V. parahaemolyticus with different genotypes for the first time and explored the differences in TCS between strains. The results showed similarities in the TCS expression pattern between VPC17 (tdh+/trh-) and VPC44 (tdh-/trh-), while VPC85(tdh-/trh+) had the least similar TCS expression pattern to the other three strains. Analysis of biological information revealed that different regulations of C4 dicarboxylate transport, tetrathionate uptake, antibiotic resistance, and flagellar synthesis involved in the TCS might influence strains' growth, antibiotic resistance, biofilm, and virulence. The different TCS regulatory abilities of strains might be one of the reasons for diverse biological characteristics and different environmental adaptations. This work provides a theoretical basis and a new research direction for the strain variability of V. parahaemolyticus.

Hierarchical Flower-like WO3 Nanospheres Decorated with Bimetallic Au and Pd for Highly Sensitive and Selective Detection of 3-Hydroxy-2-butanone Biomarker.

Listeria monocytogenes, which is abundant in environment, can lead to many kinds of serious illnesses and even death. Nowadays, indirectly detecting the metabolite biomarker of L. monocytogenes, 3-hydroxy-2-butanone, has been verified to be an effective way to evaluate the contamination of L. monocytogenes. However, this detection approach is still limited by sensitivity, selectivity, and ppb-level detection limit. Herein, low-cost and highly sensitive and selective 3-hydroxy-2-butanone sensors have been proposed based on the bimetallic AuPd decorated hierarchical flower-like WO3 nanospheres. Notably, the 1.0 wt % AuPd-WO3 based sensors displayed the highest sensitivity (Ra/Rg = 84 @ 1 ppm) at 250 °C. In addition, the sensors showed outstanding selectivity, rapid response/recovery (8/4 s @ 10 ppm), and low detection limit (100 ppb). Furthermore, the evaluation of L. monocytogenes with high sensitivity and specificity has been achieved using 1.0 wt % AuPd-WO3 based sensors. Such a marvelous sensing performance benefits from the synergistic effect of bimetallic AuPd nanoparticles, which lead to thicker electron depletion layer and increased adsorbed oxygen species. Meanwhile, the unique hierarchical nanostructure of the flower-like WO3 nanospheres benefits the gas-sensing performance. The AuPd-WO3 nanosphere-based sensors exhibit a particular and highly selective method to detect 3-hydroxy-2-butanone, foreseeing a feasible route for the rapid and nondestructive evaluation of foodborne pathogens.

Identification and Characterization of Retinitis Pigmentosa in a Novel Mouse Model Caused by PDE6B-T592I.

The cGMP-phosphodiesterase 6 beta subunit (PDE6B) is an essential component in the phototransduction pathway for light responses in photoreceptor cells. PDE6B gene mutations cause the death of rod photoreceptors, named as hereditary retinitis pigmentosa (RP) in humans and retinal degeneration (RD) in rodents. Here, we report a new RD model, identified from a phenotypic screen of N-ethyl-N-nitrosourea (ENU)-induced mutant mice, which displays retinal degeneration caused by a point mutation in the Pde6b gene that results in PDE6B-T592I mutant protein. The homozygous mutant mice show an extensive loss of rod photoreceptors at the age of 3 weeks; unexpectedly, the loss of rod photoreceptors can be partly rescued by dark rearing. Thus, this RD mutant model displays a light-dependent loss of rod photoreceptors. Both western blot and immunostaining results show very low level of mutant PDE6B-T592I protein in the retina. Structure modeling suggests that the T592I mutation probably affects the function and stability of PDE6B protein by changing intramolecular interactions. We further demonstrate that the expression of wild-type PDE6B delivered by subretinally injected adeno-associated virus (rAAV) prevents photoreceptor cell death in this RD model in vivo. The PDE6B-T592I mutant is, therefore, a valuable RD model for evaluating rAAV-mediated treatment and for investigating the molecular mechanism of light-dependent rod photoreceptor cell death that is related to impaired PDE6B function.