Deciphering infected cell types, hub gene networks and cell-cell communication in infectious bronchitis virus via single-cell RNA sequencing.

Infectious bronchitis virus (IBV) is a coronavirus that infects chickens, which exhibits a broad tropism for epithelial cells, infecting the tracheal mucosal epithelium, intestinal mucosal epithelium, and renal tubular epithelial cells. Utilizing single-cell RNA sequencing (scRNA-seq), we systematically examined cells in renal, bursal, and tracheal tissues following IBV infection and identified tissue-specific molecular markers expressed in distinct cell types. We evaluated the expression of viral RNA in diverse cellular populations and subsequently ascertained that distal tubules and collecting ducts within the kidney, bursal mucosal epithelial cells, and follicle-associated epithelial cells exhibit susceptibility to IBV infection through immunofluorescence. Furthermore, our findings revealed an upregulation in the transcription of proinflammatory cytokines IL18 and IL1B in renal macrophages as well as increased expression of apoptosis-related gene STAT in distal tubules and collecting duct cells upon IBV infection leading to renal damage. Cell-to-cell communication unveiled potential interactions between diverse cell types, as well as upregulated signaling pathways and key sender-receiver cell populations after IBV infection. Integrating single-cell data from all tissues, we applied weighted gene co-expression network analysis (WGCNA) to identify gene modules that are specifically expressed in different cell populations. Based on the WGCNA results, we identified seven immune-related gene modules and determined the differential expression pattern of module genes, as well as the hub genes within these modules. Our comprehensive data provides valuable insights into the pathogenesis of IBV as well as avian antiviral immunology.

Fundus Tessellation and Parapapillary Atrophy, as Ocular Characteristics of Spontaneously High Myopia in Macaques: The Non-Human Primates Eye Study.

Purpose: This study aimed to evaluate the ocular characteristics associated with spontaneously high myopia in adult nonhuman primates (NHPs). Methods: A total of 537 eyes of 277 macaques with an average age of 18.53 ± 3.01 years (range = 5-26 years), raised in a controlled environment, were included. We measured ocular parameters, including spherical equivalent (SE), axial length (AXL), and intraocular pressure. The 45-degree fundus images centered on the macula and the disc assessed the fundus tessellation and parapapillary atrophy (PPA). Additionally, optical coherence tomography (OCT) was used to measure the thickness of the retinal nerve fiber layer (RNFL). Results: The mean SE was -1.58 ± 3.71 diopters (D). The mean AXL was 18.76 ± 0.86 mm. The prevalence rate of high myopia was 17.7%. As myopia aggravated, the AXL increased (r = -0.498, P < 0.001). Compared with non-high myopia, highly myopic eyes had a greater AXL (P < 0.001), less RNFL thickness (P = 0.004), a higher incidence of PPA (P < 0.001), and elevated grades of fundus tessellation (P < 0.001). The binary logistic regression was performed, which showed PPA (odds ratio [OR] = 4.924, 95% confidence interval [CI] = 2.375-10.207, P < 0.001) and higher grades of fundus tessellation (OR = 1.865, 95% CI = 1.474-2.361, P < 0.001) were independent risk characteristics for high myopia. Conclusions: In NHPs, a higher grade of fundus tessellation and PPA were significant biomarkers of high myopia. Translational Relevance: The study demonstrates adult NHPs raised in conditioned rooms have a similar prevalence and highly consistent fundus changes with human beings, which strengthens the foundation for utilizing macaques as an animal model in high myopic studies.

Fusion of amyloid beta with ferritin yields an isolated oligomeric beta-sheet-rich aggregate inside the ferritin cage.

Alzheimer's disease is a severe brain condition caused by the formation of amyloid plaques composed of amyloid beta (Aß) peptides. These peptides form oligomers, protofibrils, and fibrils before deposition into amyloid plaques. Among these intermediates, Aß oligomers (AßOs) were found to be the most toxic and therefore an appealing target for drug development and understanding their role in the disease. However, precise isolation and characterization of AßOs have proven challenging because AßOs tend to aggregate and form heterogeneous mixtures in solution. As a solution, we genetically fused the Aß peptide with a ferritin monomer. Such fusion allowed the encapsulation of precisely 24 Aß peptides inside the 24-mer ferritin cage. Using high-speed atomic force microscopy (HS-AFM), we disassembled ferritin and directly visualized the Aß core enclosed within the cage. The thioflavin-T assay (ThT) and attenuated total reflection infrared spectroscopy (ATR-IR) revealed the presence of a ß-sheet structure in the encapsulated oligomeric aggregate. Gallic acid, an amyloid inhibitor, can inhibit the fluorescence of ThT bound AßOs. Our approach represents a significant advancement in the isolation and characterization of ß-sheet rich AßOs and is expected to be useful for future studies of other disordered peptides such as α-synuclein and tau.

Associations of parental age at pregnancy with adolescent cognitive development and emotional and behavioural problems: a birth cohort in rural Western China.

BACKGROUND: The relationship between parental age at pregnancy and offspring development in low- and middle-income countries remains unclear. We aimed to examine the associations of parental age at pregnancy with adolescent development in rural China. METHODS: We conducted a prospective birth cohort study of offspring born to pregnant women who participated in an antenatal micronutrient supplementation trial in rural Western China. Adolescent cognitive development and emotional and behavioural problems were assessed by using the Wechsler Intelligence Scale for Children-IV and the Youth Self-Report-2001, respectively. After accounting for the possible nonlinear relationships, we examined the linear associations between parental age (in years) at pregnancy and scores of adolescent cognitive development and emotional and behavioural problems by performing generalized estimating equations. RESULTS: Among 1897 adolescents followed from birth to early adolescence, 59.5% were male with a mean age of 11.8 (standard deviation (SD): 0.8) years. The mean ages of mothers and fathers at pregnancy were 24.6 (SD: 4.4) and 27.9 (SD: 4.1) years old, respectively. All the P values of the nonlinear terms between parental age and adolescent development in all domains were greater than 0.05. Each one-year increase in maternal age at pregnancy was associated with a 0.29-point (95% confidence interval (CI) 0.06, 0.52) increase in the full-scale intelligence quotient in early adolescence. After parental age was categorized into quartiles, the total behavioural problem scores of adolescents with fathers with an age in the fourth quartile (Q4) were 6.71 (95% CI 0.86, 12.57) points higher than those of adolescents with fathers with an age in the first quartile (Q1), with a linear trend P value of 0.01. Similarly, higher scores (worse behavioural problems) were observed for internalizing behavioural problems and other emotional and behavioural symptoms related to anxiety, withdrawal, social problems, thought problems and aggressive behaviour. CONCLUSIONS: At conception, older maternal age was independently linked to better adolescent cognitive development, whereas advanced paternal age was independently associated with a greater risk of adolescent emotional and behavioral problems. These findings suggest that public health policies targeting an optimal parental age at pregnancy should be developed in the context of offspring developmental consequences.

Long-term outcomes of anti-vascular endothelial growth factor therapy with and without posterior scleral reinforcement on myopic maculopathy in myopic choroidal neovascularization eyes.

BACKGROUND: Anti-vascular endothelial growth factor (anti-VEGF) therapy is used for myopic choroidal neovascularization (mCNV). Patchy chorioretinal atrophy (pCRA) enlargement has been reported in mCNV cases associated with vision loss. Our aim was to compare the long-term effectiveness of anti-VEGF therapy alone versus anti-VEGF followed by posterior scleral reinforcement (PSR) in controlling myopic maculopathy in mCNV eyes. METHODS: We performed a retrospective review of the medical records of 95 high myopia patients (refractive error ≥ 6.00 diopters, axial length ≥ 26.0 mm) with mCNV. Patients were treated with anti-VEGF alone (group A) or anti-VEGF followed by PSR (group B). The following data were collected: refractive error, best corrected visual acuity (BCVA), ophthalmic fundus examination, ocular coherence tomography and ocular biometry at 12 and 24 months pre- and postoperatively. The primary outcomes were changes in pCRA and BCVA. RESULTS: In 26 eyes of 24 patients, the mean pCRA size significantly increased from baseline (0.88 ± 1.69 mm2) to 12 months (1.57 ± 2.32 mm2, t = 3.249, P = 0.003) and 24 months (2.17 ± 2.79 mm2, t = 3.965, P = 0.001) postoperatively. The increase in perilesional pCRA in group B (n = 12) was 98.2% and 94.2% smaller than that in group A (n = 14) at 12 and 24 months (Beta 0.57 [95% CI 0.01, 191 1.13], P = 0.048). In group B, 7 eyes (58.3%) gained more than 2 lines of BCVA compared with only 4 eyes (28.6%) in group A at 24 months. CONCLUSION: Anti-VEGF therapy followed by PSR achieved better outcomes than anti-VEGF therapy alone in controlling the development of myopic maculopathy in mCNV and may constitute a better treatment option by securing a better long-term VA outcome.

Computer-aided design to enhance the stability of aldo-keto reductase KdAKR.

The aldo-keto reductase (AKR) KdAKR from Kluyvermyces dobzhanskii can reduce t-butyl 6-chloro-(5S)-hydroxy-3-oxohexanoate ((5S)-CHOH) to t-butyl 6-chloro-(3R,5S)-dihydroxyhexanoate ((3R,5S)-CDHH), which is the key chiral intermediate of rosuvastatin. Herein, a computer-aided design that combined the use of PROSS platform and consensus design was employed to improve the stability of a previously constructed mutant KdAKRM6 . Experimental verification revealed that S196C, T232A, V264I and V45L produced improved thermostability and activity. The "best" mutant KdAKRM10 (KdAKRM6 -S196C/T232A/V264I/V45L) was constructed by combining the four beneficial mutations, which displayed enhanced thermostability. Its T50 15 and Tm values were increased by 10.2 and 10.0°C, respectively, and half-life (t1/2 ) at 40°C was increased by 17.6 h. Additionally, KdAKRM10 demonstrated improved resistance to organic solvents compared to that of KdAKRM6 . Structural analysis revealed that the increased number of hydrogen bonds and stabilized hydrophobic core contributed to the rigidity of KdAKRM10 , thus improving its stability. The results validated the feasibility of the computer-aided design strategy in improving the stability of AKRs.

Irpetones A and B, Anti-Osteoclastic Heptaketides from a Marine Mesophotic Zone Ircinia Sponge-Associated Fungus Irpex sp. NBUF088.

Chemical investigation of Irpex sp. NBUF088, associated with an Ircinia sp. sponge located at an 84 m deep mesophotic zone, led to the discovery of two new heptaketides, named irpetones A (1) and B (2). Their structures were identified by analysis of spectroscopic data and quantum-chemical calculations. Compound 1 exhibited inhibition against the receptor activator of NF-κB ligand-induced osteoclastogenesis in bone marrow monocytes with an IC50 of 6.3 ± 0.2 µM, causing no notable cytotoxicity. It was also determined that 1 inhibited the phosphorylation of ERK1/2-JNK1/2-p38 MAPKs and the nuclear translocation of NF-κB, consequently suppressing the activation of MAPK and NF-κB signaling pathways induced by the NF-κB ligand.

Machine Learning-Based Virtual Screening and Identification of the Fourth-Generation EGFR Inhibitors.

Epidermal growth factor receptor (EGFR) plays a pivotal regulatory role in treating patients with advanced nonsmall cell lung cancer (NSCLC). Following the emergence of the EGFR tertiary CIS C797S mutation, all types of inhibitors lose their inhibitory activity, necessitating the urgent development of new inhibitors. Computer systems employ machine learning methods to process substantial volumes of data and construct models that enable more accurate predictions of the outcomes of new inputs. The purpose of this article is to uncover innovative fourth-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) with the aid of machine learning techniques. The paper's data set was high-dimensional and sparse, encompassing both structured and unstructured descriptors. To address this considerable challenge, we introduced a fusion framework to select critical molecule descriptors by integrating the full quadratic effect model and the Lasso model. Based on structural descriptors obtained from the full quadratic effect model, we conceived and synthesized a variety of small-molecule inhibitors. These inhibitors demonstrated potent inhibitory effects on the two mutated kinases L858R/T790M/C797S and Del19/T790M/C797S. Moreover, we applied our model to virtual screening, successfully identifying four hit compounds. We have evaluated these hit ADME characteristics and look forward to conducting activity evaluations on them in the future to discover a new generation of EGFR-TKI.

Oncogenic KRAS effector USP13 promotes metastasis in non-small cell lung cancer through deubiquitinating ß-catenin.

KRAS mutations are frequently detected in non-small cell lung cancers (NSCLCs). Although covalent KRASG12C inhibitors have been developed to treat KRASG12C-mutant cancers, effective treatments are still lacking for other KRAS-mutant NSCLCs. Thus, identifying a KRAS effector that confers poor prognosis would provide an alternative strategy for the treatment of KRAS-driven cancers. Here, we show that KRAS drives expression of deubiquitinase USP13 through Ras-responsive element-binding protein 1 (RREB1). Elevated USP13 promotes KRAS-mutant NSCLC metastasis, which is associated with poor prognosis in NSCLC patients. Mechanistically, USP13 interacts with and removes the K63-linked polyubiquitination of ß-catenin at lysine 508, which enhances the binding between ß-catenin and transcription factor TCF4. Importantly, we identify 2-methoxyestradiol as an effective inhibitor for USP13 from a natural compound library, and it could potently suppress the metastasis of KRAS-mutant NSCLC cells in vitro and in vivo. These findings identify USP13 as a therapeutic target for metastatic NSCLC with KRAS mutations.

Effect of tixagevimab/cilgavimab for pre-exposure prophylaxis during the China Omicron outbreak.

OBJECTIVES: By the end of 2022, China had made a pivotal decision to optimize the COVID-19 policy. The dominant Omicron variant in China at that time was highly transmissible. In this study, we aimed to evaluate the real-world safety and efficacy of tixagevimab and cilgavimab against this background in China. METHODS: Participants were enrolled if they were over 12 years old and were planning to receive tixagevimab or cilgavimab. All participants received intramuscular administration of tixagevimab (150 mg) and cilgavimab (150 mg). Data were collected on demographics, underlying illness, prior infection, vaccination, adverse events, and COVID-19 outcomes (e.g., infection rate, hospitalization rate, and severe disease). RESULTS: During the study period, 168 (37.9%) of 443 who received tixagevimab/cilgavimab were diagnosed with SARS-CoV-2 infection. All infected patients had mild COVID-19. Two patients (0.5%) were hospitalized for COVID-19, but none of them were admitted to the ICU. None of the patients died during this study. 4 (0.9%) reported mild local adverse events, and no severe systemic adverse reactions were reported. CONCLUSION: Tixagevimab/cilgavimab may have protected high-risk populations against infection with the Omicron variant, hospitalization and severe disease during the China COVID-19 pandemic.

[Analysis of FDA's Review Concerns for Premarket Pathways and Predicate Product Selection of Device-led Combination Products].

By discussing the relevant requirements of the Principles of Premarket Pathways for Combination Products Guidance, this study analyzes FDA's review concerns for premarket pathways and predicate product selection of device-led combination products' five typical situations, in order to provide reference for Chinese manufacturers and investigators in device-led combination products registration.

Spatial patterns in pollution discharges from livestock and poultry farm and the linkage between manure nutrients load and the carrying capacity of croplands in China.

The rapid development of livestock and poultry farming in China has resulted in an increasing threat of water pollution. In particular, mitigating livestock-related pollutant discharges is a key issue for environmental sustainability, especially for inland surface water bodies. In order to ensure the effective control of pollution and the efficient utilization management of livestock manure, spatially explicit surveys of pollutant generation and discharge from the livestock sector must be performed. In the present study, we estimated the grid cell-level distributions in the generation and discharge of four typical pollutants (chemical oxygen demand, ammonium nitrogen, total nitrogen and total phosphorus) from the livestock sector across the country with a spatial resolution of 30 arc-seconds. The distributions were estimated using the most recent pollution source census data and multi-sourced ancillary materials by a dasymetric mapping approach. We further investigated the feasibility of the resource utilization of livestock manure by comparing manure-source nutrients with the carrying capacity of adjacent croplands. Our results show that low-intensive farming generated and discharged the majority of livestock farming pollution, with other cattle and pigs breeding identified as the two major sources of pollution from the livestock sector. Southwest, Central and East China suffered the highly densified pollutants generation and discharges. Furthermore, cropland exceeding its carrying capacity was concentrated in these regions. Our findings provide additional insights into livestock and poultry farming in the context of relocation, strengthening regulation, transforming breeding operations, and rationalizing the resource use of manure, all of which are important measures for the sustainable development of both agriculture and the environment.

Structural-guided design to improve the catalytic performance of aldo-keto reductase KdAKR.

Aldo-keto reductases (AKRs) are important biocatalysts that can be used to synthesize chiral pharmaceutical alcohols. In this study, the catalytic activity and stereoselectivity of a NADPH-dependent AKR from Kluyveromyces dobzhanskii (KdAKR) toward t-butyl 6-chloro (5S)-hydroxy-3-oxohexanoate ((5S)-CHOH) were improved by mutating its residues in the loop regions around the substrate-binding pocket. And the thermostability of KdAKR was improved by a consensus sequence method targeted on the flexible regions. The best mutant M6 (Y28A/L58I/I63L/G223P/Y296W/W297H) exhibited a 67-fold higher catalytic efficiency compared to the wild-type (WT) KdAKR, and improved R-selectivity toward (5S)-CHOH (dep value from 47.6% to >99.5%). Moreover, M6 exhibited a 6.3-fold increase in half-life (t1/2 ) at 40°C compared to WT. Under the optimal conditions, M6 completely converted 200 g/L (5S)-CHOH to diastereomeric pure t-butyl 6-chloro-(3R, 5S)-dihydroxyhexanoate ((3R, 5S)-CDHH) within 8.0 h, with a space-time yield of 300.7 g/L/day. Our results deepen the understandings of the structure-function relationship of AKRs, providing a certain guidance for the modification of other AKRs.

Implementing a digital comprehensive myopia prevention and control strategy for children and adolescents in China: a cost-effectiveness analysis.

Background: Children and adolescents' myopia is a major public problem. Although the clinical effect of various interventions has been extensively studied, there is a lack of national-level and integral assessments to simultaneously quantify the economics and effectiveness of comprehensive myopia prevention and control programs. We aimed to compare the cost-effectiveness between traditional myopia prevention and control strategy, digital comprehensive myopia prevention and control strategy and school-based myopia screening program in China. Methods: A Markov model was used to compare the cost-utility and cost-effectiveness among school-based myopia screening, traditional myopia prevention and control strategy, and digital comprehensive myopia prevention and control strategy among 6 to 18-year-old rural and urban schoolchildren. Parameters were collected from published sources. The primary outcomes were quality-adjusted life-year, disability-adjusted life-year, incremental cost-utility ratio, and incremental cost-effectiveness ratio. Extensive sensitivity analyses were performed to test the robustness and sensitivity of base-case analysis. Findings: Compared with school-based myopia screening strategy, after implementing digital comprehensive myopia prevention and control strategy, the prevalence of myopia among 18-year-old students in rural and urban areas was reduced by 3.79% and 3.48%, respectively. The incremental cost-utility ratio per quality-adjusted life-year gained with the digital myopia management plan ($11,301 for rural setting, and $10,707 for urban setting) was less than 3 times the per capita gross domestic product in rural settings ($30,501) and less than 1 time the per capita gross domestic product in urban settings ($13,856). In cost-effectiveness analysis, the incremental cost-effectiveness ratio produced by digital comprehensive myopia management strategy ($37,446 and $41,814 per disability-adjusted life-year averted in rural and urban settings) slightly exceeded the cost-effectiveness threshold. When assuming perfect compliance, full coverage of outdoor activities and spectacles satisfied the cost-effectiveness threshold, and full coverage of outdoor activities produced the lowest cost ($321 for rural settings and $808 for urban settings). Interpretations: Health economic evidence confirmed the cost-effectiveness of promoting digital comprehensive myopia prevention and control strategies for schoolchildren at the national level. Sufficient evidence provides an economic and public health reference for further action by governments, policy-makers and other myopia-endemic countries. Funding: National Natural Science Foundation of China, NSFC (82171051), Beijing Natural Science Foundation (JQ20029), Capital Health Research and Development of Special (2020-2-1081), National Natural Science Foundation of China, NSFC (82071000), National Natural Science Foundation of China, NSFC (8197030562).

Multimodal Analysis on Clinical Characteristics of the Advanced Stage in Myopic Traction Maculopathy.

INTRODUCTION: Here we investigate the clinical features of foveal detachment (FD), full-thickness macular hole (MH), and macular hole retinal detachment (MHRD) in myopic traction maculopathy (MTM). METHODS: In the retrospective observational case series, 314 eyes of 198 patients with myopic retinoschisis in Beijing Tongren Hospital were enrolled. We recorded gender, age, and axial length and evaluated fundus characteristics using optical coherence tomography. Epiretinal membranes (ERMs), vitreoretinal traction, and paravascular abnormalities (PVAs) were used to describe the vitreoretinal interface condition. Different retinoschisis layers (inner, middle, and outer retinoschisis) and the location with a range of outer retinoschisis were evaluated to reveal the retinal condition. Five patterns of the scleral shape: dome-shaped, sloped toward the optic nerve, symmetrical or asymmetrical around the fovea, and irregular were assessed to show retina-sclera condition. We regarded the FD, full-thickness MH, and MHRD as the advanced stage in MTM. Multivariate logistic regression assessed significant factors for the advanced stage with odds ratios (OR) and 95% confidence intervals (CI). RESULTS: There were 76 eyes with FD, 6 eyes with full-thickness MH, and 7 eyes with MHRD. The mean age was 52.9 ± 12.3 years. On univariate analysis, the eyes with the advanced stage were older and had higher rates of ERMs, PVAs, middle retinoschisis, outer retinoschisis, and irregular sclera shape. The number of retinoschisis layers and the grade of outer retinoschisis were higher in eyes with the advanced stage. After multivariate logistic regression, ERMs (OR 1.983; 95% CI 1.093-3.595; P = 0.024), middle retinoschisis (OR 2.967; 95% CI 1.630-5.401; P < 0.001), and higher grades of outer retinoschisis (OR 2.227; 95% CI 1.711-2.898; P < 0.001) remained associated with the advanced stage. CONCLUSION: ERMs, middle retinoschisis, and more extensive outer retinoschisis were significant characteristics of the advanced stage in MTM.

A Novel Feature Engineering Method Based on Latent Representation Learning for Radiomics: Application in NSCLC Subtype Classification.

Radiomics refers to the high-throughput extraction of quantitative features from medical images, and is widely used to construct machine learning models for the prediction of clinical outcomes, while feature engineering is the most important work in radiomics. However, current feature engineering methods fail to fully and effectively utilize the heterogeneity of features when dealing with different kinds of radiomics features. In this work, latent representation learning is first presented as a novel feature engineering approach to reconstruct a set of latent space features from original shape, intensity and texture features. This proposed method projects features into a subspace called latent space, in which the latent space features are obtained by minimizing a unique hybrid loss function including a clustering-like loss and a reconstruction loss. The former one ensures the separability among each class while the latter one narrows the gap between the original features and latent space features. Experiments were performed on a multi-center non-small cell lung cancer (NSCLC) subtype classification dataset from 8 international open databases. Results showed that compared with four traditional feature engineering methods (baseline, PCA, Lasso and L2,1-norm minimization), latent representation learning could significantly improve the classification performance of various machine learning classifiers on the independent test set (all p<0.001). Further on two additional test sets, latent representation learning also showed a significant improvement in generalization performance. Our research shows that latent representation learning is a more effective feature engineering method, which has the potential to be used as a general technology in a wide range of radiomics researches.

USP12 promotes nonsmall cell lung cancer progression through deubiquitinating and stabilizing RRM2.

RRM2 is the catalytic subunit of ribonucleotide reductase (RNR), which catalyzes de novo synthesis of deoxyribonucleotide triphosphates (dNTPs) and plays critical roles in cancer cell proliferation. RRM2 protein level is controlled by ubiquitination mediated protein degradation system; however, its deubiquitinase has not been identified yet. Here we showed that ubiquitin-specific peptidase 12 (USP12) directly interacts with and deubiquitinates RRM2 in non-small cell lung cancer (NSCLC) cells. Knockdown of USP12 causes DNA replication stress and retards tumor growth in vivo and in vitro. Meanwhile, USP12 protein levels were positively correlated to RRM2 protein levels in human NSCLC tissues. In addition, high expression of USP12 was associated with poor prognosis in NSCLC patients. Therefore, our study reveals that USP12 is a RRM2 regulator and targeting USP12 could be considered as a potential therapeutical strategy for NSCLC treatment.

Design, methodology, and preliminary results of the non-human primates eye study.

PURPOSE: To describe the normative profile of ophthalmic parameters in a healthy cynomolgus monkey colony, and to identify the characteristic of the spontaneous ocular disease non-human primates (NHP) models. METHODS: The NHP eye study was a cross-sectional on-site ocular examination with about 1,000 macaques held in Guangdong Province, southeastern China. The NHPs (Macaca fascicularis, cynomolgus) in this study included middle-aged individuals with a high prevalence of the ocular disease. The NHP eye study (NHPES) performed the information including systematic data and ocular data. Ocular examination included measurement of intraocular pressure (IOP), anterior segment- optical coherence tomography (OCT), slit-lamp examination, fundus photography, autorefraction, electroretinography, etc. Ocular diseases included measurement of refractive error, anisometropia, cataract, pterygium, etc. RESULTS: A total of 1148 subjects were included and completed the ocular examination. The average age was 16.4 ± 4.93 years. Compared to the male participants, the females in the NHPES had shorter axial length and the mean Average retinal nerve fiber layer (RNFL) thickness (except for the nasal quadrants). The mean IOP, anterior chamber depth, lens thickness, axial length, central corneal thickness, choroid thickness and other parameters were similar in each group. CONCLUSION: The NHPES is a unique and high-quality study, this is the first large macaque monkey cohort study focusing on ocular assessment along with comprehensive evaluation. Results from the NHPES will provide important information about the normal range of ophthalmic measurements in NHP.

Associations between life-course household wealth mobility and adolescent physical growth, cognitive development and emotional and behavioral problems: A birth cohort in rural western China.

Background: Parental household wealth has been shown to be associated with offspring health conditions, while inconsistent associations were reported among generally healthy population especially in low- and middle- income countries (LMICs). Whether the household wealth upward mobility in LMICs would confer benefits to child health remains unknown. Methods: We conducted a prospective birth cohort of children born to mothers who participated in a randomized trial of antenatal micronutrient supplementation in rural western China. Household wealth were repeatedly assessed at pregnancy, mid-childhood and early adolescence using principal component analysis for household assets and dwelling characteristics. We used conditional gains and group-based trajectory modeling to assess the quantitative changes between two single-time points and relative mobility of household wealth over life-course, respectively. We performed generalized linear regressions to examine the associations of household wealth mobility indicators with adolescent height- (HAZ) and body mass index-for-age and sex z score (BAZ), scores of full-scale intelligent quotient (FSIQ) and emotional and behavioral problems. Results: A total of 1,188 adolescents were followed, among them 59.9% were male with a mean (SD) age of 11.7 (0.9) years old. Per SD conditional increase of household wealth z score from pregnancy to mid-childhood was associated with 0.11 (95% CI 0.04, 0.17) SD higher HAZ and 1.41 (95% CI 0.68, 2.13) points higher FSIQ at early adolescence. Adolescents from the household wealth Upward trajectory had a 0.25 (95% CI 0.03, 0.47) SD higher HAZ and 4.98 (95% CI 2.59, 7.38) points higher FSIQ than those in the Consistently low subgroup. Conclusion: Household wealth upward mobility particularly during early life has benefits on adolescent HAZ and cognitive development, which argues for government policies to implement social welfare programs to mitigate or reduce the consequences of early-life deprivations. Given the importance of household wealth in child health, it is recommended that socioeconomic circumstances should be routinely documented in the healthcare record in LMICs.

Economic evaluation of combined population-based screening for multiple blindness-causing eye diseases in China: a cost-effectiveness analysis.

BACKGROUND: More than 90% of vision impairment is avoidable. However, in China, a routine screening programme is currently unavailable in primary health care. With the dearth of economic evidence on screening programmes for multiple blindness-causing eye diseases, delivery options, and screening frequencies, we aimed to evaluate the costs and benefits of a population-based screening programme for multiple eye diseases in China. METHODS: We developed a decision-analytic Markov model for a cohort of individuals aged 50 years and older with a total of 30 1-year cycles. We calculated the cost-effectiveness and cost-utility of screening programmes for multiple major blindness-causing eye diseases in China, including age-related macular degeneration, glaucoma, diabetic retinopathy, cataracts, and pathological myopia, from a societal perspective (including direct and indirect costs). We analysed rural and urban settings separately by different screening delivery options (non-telemedicine [ie, face-to-face] screening, artificial intelligence [AI] telemedicine screening, and non-AI telemedicine screening) and frequencies. We calculated incremental cost-utility ratios (ICURs) using quality-adjusted life-years and incremental cost-effectiveness ratios (ICERs) in terms of the cost per blindness year avoided. One-way deterministic and simulated probabilistic sensitivity analyses were used to assess the robustness of the main outcomes. FINDINGS: Compared with no screening, non-telemedicine combined screening of multiple eye diseases satisfied the criterion for a highly cost-effective health intervention, with an ICUR of US$2494 (95% CI 1130 to 2716) and an ICER of $12 487 (8773 to 18 791) in rural settings. In urban areas, the ICUR was $624 (395 to 907), and the ICER was $7251 (4238 to 13 501). Non-AI telemedicine screening could result in fewer costs and greater gains in health benefits (ICUR $2326 [1064 to 2538] and ICER $11 766 [8200 to 18 000] in rural settings; ICUR $581 [368 to 864] and ICER $6920 [3926 to 13 231] in urban settings). AI telemedicine screening dominated no screening in rural settings, and in urban settings the ICUR was $244 (-315 to 1073) and the ICER was $2567 (-4111 to 15 389). Sensitivity analyses showed all results to be robust. By further comparison, annual AI telemedicine screening was the most cost-effective strategy in both rural and urban areas. INTERPRETATION: Combined screening of multiple eye diseases is cost-effective in both rural and urban China. AI coupled with teleophthalmology presents an opportunity to promote equity in eye health. FUNDING: National Natural Science Foundation of China.