Simulation study on functional group-modified Ni-MOF-74 for CH4 /N2 adsorption separation.

This study employs grand canonical Monte Carlo (GCMC) simulations to investigate the impact of functional group modifications (CH3 , OH, NH2 , and OLi) on the adsorption performance of CH4 /N2 on Ni-MOF-74. The results revealed that functional group modifications significantly increased the adsorption capacity of Ni-MOF-74 for both CH4 and N2 . The packed methyl groups in CH3 -Ni-MOF-74 create an environment conducive to CH4 , leading to the highest CH4 adsorption capacity. The electrostatic potential distribution indicates that the strong electron-donating effect introduced by the alkali metal Li results in the highest electrostatic potential gradient in Li-O-Ni-MOF-74, leading to the strongest adsorption of N2 , this is unfavorable for CH4 /N2 separation. At 1500 kPa the selectivity order of adsorbents for mixed gases was as follows: CH3 -Ni-MOF-74 > NH2 -Ni-MOF-74 > OH-Ni-MOF-74 > Ni-MOF-74 > Li-O-Ni-MOF-74. This study highlights that CH3 -Ni-MOF-74 possesses optimal CH4 selectivity and adsorption performance. Given the current lack of research on functionalized MOF-74 for the separation of CH4 and N2 , the findings of this study will serve as a theoretical guide and provide references for the applications of CH4 adsorption and CH4 /N2 separation.

A de novo PKD1 mutation in a Chinese family with autosomal dominant polycystic kidney disease.

BACKGROUND: PKD1, which has a relatively high mutation rate, is highly polymorphic, and the role of PKD1 is incompletely defined. In the current study, in order to determine the molecular etiology of a family with autosomal dominant polycystic kidney disease, the pathogenicity of an frameshift mutation in the PKD1 gene, c.9484delC, was evaluated. METHODS: The family clinical data were collected. Whole exome sequencing analysis determined the level of this mutation in the proband's PKD1, and Sanger sequencing and bioinformatics analysis were performed. SIFT, Polyphen2, and MutationTaster were used to evaluate the conservation of the gene and pathogenicity of the identified mutations. SWISS-MODEL was used to predict and map the protein structure of PKD1 and mutant neonate proteins. RESULTS: A novel c.9484delC (p.Arg3162Alafs*154) mutation of the PKD1 gene was identified by whole exome sequencing in the proband, which was confirmed by Sanger sequencing in his sister (II7). The same mutation was not detected in the healthy pedigree members. Random screening of 100 normal and end-stage renal disease patients did not identify the c.9484delC mutation. Bioinformatics analysis suggested that the mutation caused the 3162 nd amino acid substitution of arginine by alanine and a shift in the termination codon. As a result, the protein sequence was shortened from 4302 amino acids to 3314 amino acids, the protein structure was greatly changed, and the PLAT/LH2 domain was destroyed. Clustal analysis indicated that the altered amino acids were highly conserved in mammals. CONCLUSION: A novel mutation in the PKD1 gene has been identified in an affected Chinese family. The mutation is probably responsible for a range of clinical manifestations for which reliable prenatal diagnosis and genetic counseling may be provided.

Oil addition increases the heat resistance of Clostridium sporogenes spores in braised sauce beef: Perspectives from spore surface characteristics and microstructure.

During thermal processing of braised sauce beef, the lipid content of circularly used sauce increased accordingly because of lipid migration from beef to sauce, which may impact the bacterial heat resistance in the products. This study aims to characterize the heat resistance of Clostridium sporogenes spores in braised sauce beef, and investigate the effects of oil on the spore surface characteristics and microstructure. The results indicated that the heat resistance of C. sporogenes spores in beef was significantly higher than that in sauce. Oil addition remarkably enhanced the spore heat resistance in sauce, with D95°C value three times more than that without oil added, and even higher than that in beef. The results of spore surface characteristics indicated that oil addition led to an increase of hydrophobicity and a decrease of zeta potential, which ultimately increased spore heat resistance. Microstructure analysis indicated that exosporium maintenance and cortex expansion induced by oil addition might contribute to the increase of spore heat resistance. This study has sufficiently verified the importance of oil content on the heat resistance of C. sporogenes spores, which should be taken into consideration when developing thermal processes for controlling the spores in food matrices.

Representation of event and object concepts in ventral anterior temporal lobe and angular gyrus.

Semantic knowledge includes understanding of objects and their features and also understanding of the characteristics of events. The hub-and-spoke theory holds that these conceptual representations rely on multiple information sources that are integrated in a central hub in the ventral anterior temporal lobes. The dual-hub theory expands this framework with the claim that the ventral anterior temporal lobe hub is specialized for object representation, while a second hub in angular gyrus is specialized for event representation. To test these ideas, we used representational similarity analysis, univariate and psychophysiological interaction analyses of fMRI data collected while participants processed object and event concepts (e.g. "an apple," "a wedding") presented as images and written words. Representational similarity analysis showed that angular gyrus encoded event concept similarity more than object similarity, although the left angular gyrus also encoded object similarity. Bilateral ventral anterior temporal lobes encoded both object and event concept structure, and left ventral anterior temporal lobe exhibited stronger coding for events. Psychophysiological interaction analysis revealed greater connectivity between left ventral anterior temporal lobe and right pMTG, and between right angular gyrus and bilateral ITG and middle occipital gyrus, for event concepts compared to object concepts. These findings support the specialization of angular gyrus for event semantics, though with some involvement in object coding, but do not support ventral anterior temporal lobe specialization for object concepts.

Association between body mass index and respiratory symptoms in US adults: a national cross-sectional study.

The correlation between body mass index (BMI) and the development of cough, shortness of breath, and dyspnea is unclear. Therefore, this study aimed to investigate the association between these parameters. Data from individuals who participated in the National Health and Nutrition Examination Survey between 2003 and 2012 were analyzed. Weighted logistic regression analysis and smoothed curve fitting were used to examine the correlation between BMI and respiratory symptoms. In addition, the relationship between BMI, chronic obstructive pulmonary disease (COPD), and bronchial asthma was examined. Stratified analysis was used to discover inflection points and specific groups. Weighted logistic regression and smoothed curve fitting revealed a U-shaped relationship between BMI and respiratory symptoms. The U-shaped relationship in BMI was also observed in patients with bronchial asthma and COPD. Stratified analysis showed that the correlation between BMI and wheezing and dyspnea was influenced by race. In addition, non-Hispanic black individuals had a higher risk of developing cough than individuals of the other three races [OR 1.040 (1.021, 1.060), p < 0.0001], and they also exhibited an inverted U-shaped relationship between BMI and bronchial asthma. However, the association of BMI with cough, wheezing, dyspnea, COPD, and asthma was not affected by sex. High or low BMI was associated with cough, shortness of breath, and dyspnea, and has been linked to bronchial asthma and COPD. These findings provide new insights into the management of respiratory symptoms and respiratory diseases.

Separation of anti-TMV active components and modes of action of Omphalia lapidescens.

BACKGROUND: Omphalia lapidescens is a saprophytic and parasitic fungus belonging to the Polypora genus of Tricholomataceae. It has repellent, insecticidal, anti-inflammatory and immunomodulatory effects. RESULT: This study found that the extract of O. lapidescens had significant anti-TMV activity, and the main active component was homopolysaccharide LW-1 by Bioassay-guided fractionation. LW-1 is a glucan with ß-(1,3) glucoside bond as the main chain and ß-(1,6) glucoside bond as the branch chain, with molecular weight in the range of 172,916-338,827 Da. The protective and inactive efficacies of LW-1(100 mg/L) against TMV were 78.10% and 48.20%, but had no direct effect on the morphology of TMV particles. The results of mechanism of action showed that LW-1 induced the increase of the activity of defense enzymes such as POD, SOD and PAL in Nicotiana glutinosa. The overexpression of resistance genes such as NPR1, PR1 and PR5, and the increase of SA content. Further transcriptome sequencing showed that LW-1 activated MAPK signaling pathway, plant-pathogen interaction pathway and glucosinolide metabolic pathway in Arabidopsis thaliana. Besides, LW-1 induced crops resistance against plant pathogenic fungi. CONCLUSION: Taken together, the anti-TMV mechanism of LW-1 was to activate MAPK signaling pathway, inducing overexpression of resistance genes, activating plant immune system, and improving the synthesis and accumulation of plant defencins such as glucosinolide. LW-1-induced plant disease resistance has the advantages of broad spectrum and long duration, which has the potential to be developed as a new antiviral agent or plant immune resistance inducer.

Life-cycle risk assessment of graphene-enabled textiles in fire protection gear.

A nanomaterial life-cycle risk assessment (Nano LCRA) of a graphene-enabled textile used in the construction of heat and fire-resistant personal protective equipment (PPE) was conducted to develop, analyze, and prioritize potential occupational, health and environmental risks. The analysis identifies potential receptors and exposure pathways at each product life-cycle stage and makes a qualitative evaluation of the potential significance of each scenario. A literature review, quality evaluation, and database were developed as part of the LCRA to identify potential hazards associated with graphene-based materials (GBMs) throughout the product life-cycle. Generally, risks identified from graphene-enabled textiles were low. Of the developed exposure scenarios, occupational inhalation exposures during raw material and product manufacturing ranked highest. The analysis identifies the key potential human and environmental hazards and exposures of the products across the product life-cycle of graphene enabled textiles. Priority research gaps to reduce uncertainty include evaluating long-term, low dose graphene exposures typical of the workplace, as well as the potential release and hazard characterization of graphene-acrylic nanocomposites.

Relationship between depression severity and respiratory symptoms in US adults: A national cross-sectional study.

OBJECTIVE: The relationship between depression severity and cough, wheeze and exertional dyspnoea is unclear. The aim of this study was to explore this relationship. METHODS: We used weighted logistic regression analysis and fitted curves to explore the relationship between depression severity and respiratory symptoms. In addition, we examined the relationship between depression and COPD and asthma. Stratified analyses were used to analyse specific populations. RESULTS: We weighted 10,142 subjects to reflect the entire US population. Using the population without depression as a reference, the risk of cough and asthma in the severely depressed population was 3.32 times (OR 3.324, 95% CI 1.567-7.050) and 2.84 times (OR 2.842, 95% CI 1.521-5.311) higher than that in the population without depressive symptoms, and the risk of asthma and COPD was 2.4 times and 2.6 times (OR 2.410, 95% CI 1.371-4.236; OR 2.566, 95% CI 1.236-4.921). In subgroup analyses, the correlation between depression scores and prevalence of cough and wheeze was corrected for gender level. In addition, smoking status and marital status were interaction factors between depression score and prevalence of cough. The prevalence of exertional dyspnoea by depression score was influenced by CVD. CONCLUSIONS: Depression severity was associated with respiratory symptoms, asthma, and COPD. Gender corrected the correlation between depression and cough and asthma, and depressive state was an independent risk factor for asthma and COPD. This finding provides new ideas for the management of respiratory symptoms and diseases.

Generational Differences in Food Consumption among Chinese Adults of Different Ages.

Limited knowledge currently exists regarding the dynamics of generational shifts in food consumption among adult residents in China. This study aimed to investigate the generational differences in dietary status among different generations of Chinese adult residents aged 20 years and older. Survey participants from four waves (1991, 2000, 2009, and 2018) of the China Health and Nutrition Survey (CHNS) cohort were included in the study (N = 40,704), providing three-day 24 h dietary data. Participants were categorized into six age groups (20-29, 30-39, 40-49, 50-59, 60-69, and ≥70 years old), each corresponding to specific generations (Gen 10, 20, 30, 40, 50, 60, 70, 80, and 90) based on their age at the time of the survey. This study examined generational differences in the intake of cereals, animal-based foods, vegetables, fruits, dairy, energy, and the contribution of macronutrients to energy using chi-square tests and Kruskal-Wallis tests. All analyses were stratified by gender. Our findings revealed that younger generations exhibited lower daily intake of cereals, vegetables, energy, and contribution of carbohydrates to energy, compared to their older counterparts, regardless of gender. Conversely, regardless of male or female, younger generations showed higher daily consumption of animal-based foods, average fruit and dairy intake, fruit and dairy consumption rates, as well as contributions of protein and fat to energy, compared to older generations. The magnitude of generational differences in food consumption varied by age and gender. In addition, cereal and vegetable intake, energy intake, and contribution of carbohydrates to energy declined with age across all generations, while average dairy intake, fruit and dairy consumption rates, and the contribution of fat to energy tended to increase, regardless of gender. In conclusion, generational differences in food consumption were evident among different generations of Chinese adult residents, characterized by an increase in animal-based food intake and the contribution of fat to energy among generations. Attention should be directed towards addressing the eating behavior of younger generations.

A diagnostic biomarker of acid glycoprotein 1 for distinguishing malignant from benign pulmonary lesions.

BACKGROUND: The acid glycoprotein 1 (AGP1) is downregulated in lung cancer. However, the performance of AGP1 in distinguishing benign from malignant lung lesions is still unknown. METHODS: The expression of AGP1 in benign diseases and lung cancer samples was detected by Western blot. The receiver operating characteristic curves, bivariate correlation, and multivariate analysis was analyzed by SPSS software. RESULTS: AGP1 expression levels were significantly downregulated in lung cancer and correlated with carcinoembryonic antigen (CEA), CA199, and CA724 tumor biomarkers. The diagnostic performance of AGP1 for distinguishing malignant from benign pulmonary lesions was better than the other four clinical biomarkers including CEA, squamous cell carcinoma-associated antigen, neuron-specific enolase, and cytokeratin 19 fragment 21-1, with an area under the curve value of 0.713 at 88.8% sensitivity. Furthermore, the multivariate analysis indicated that the variates of thrombin time and potassium significantly affected the AGP1 levels in lung cancer. CONCLUSIONS: Our study indicates that AGP1 expression is decreased in lung cancer compared to benign samples, which helps distinguish benign and malignant pulmonary lesions.

Optical properties of the dual circularly polarized lights reflected from ITO films under electric and thermal fields.

Indium tin oxide (ITO) is widely used in optoelectronic devices due to its excellent optical and electrical properties. The real-time characterization of the ITO surface under electric and thermal fields plays an important role in determining its performance. The Goos-Hänchen (GH) and Imbert-Fedorov (IF) shifts and polarization properties of the dual circularly polarized lights reflected from ITO films can be used to describe its features. The dual circularly polarized lights, right circularly polarized (RCP, S 3≈+1) and left circularly polarized (LCP, S 3≈-1) lights, are obtained by rotating the linear polarizer and quarter-wave plate. The polarization properties and the lateral shifts of the RCP and LCP lights were studied by a polarimeter and a slim beam profiler. The results show that the polarization properties of the dual circularly polarized lights are mainly affected by temperature. The degree of the polarization properties of the RCP and LCP lights changed from 97.85% to 97.40%, and from 98.40 % to 83.50%, respectively. The reflectivity of the RCP and LCP lights changed from 42.19% to 40.37%, and from 43.80% to 0.80%, respectively. The GH and IF shifts of the RCP light are 156.50 µm and186.00 µm, respectively. The GH and IF shifts of the LCP light are 233.00 µm and 257.00 µm, respectively. The ITO film has more effect on the LCP light than that of the RCP light due to its strong ITO film (400) plane.

Exploring factors that influence the behavioural intention of medical students to use 3D gastroscopic model to learn how to operate gastroscope using UTAUT Model.

BACKGROUND: The application of virtual reality (VR) in gastroscopic operation teaching can be safe and effective, but the advantages can be realized only when students accept and use it. This study aims to identify the factors influencing Chinese clinical medical postgraduates on their intention to use the 3D gastroscopic model constructed based on VR technology using Unified Theory of Acceptance and Use of Technology (UTAUT) model. Students' demographic factors are also taken into consideration. METHODS: All methods were carried out in accordance with relevant guidelines. Data were collected from clinical medical postgraduates students in China using stratified sampling. A total of 292 questionnaires including valid responses were used in this study. Data were processed using Amos 24.0 and SPSS 26.0 software and the statistical analysis technique was based on structural equation modeling (SEM). RESULTS: The results showed that different from the mediator of home location and year of clinical learning, mediator of gender, university kind and graduate degree did not affect the behavioral intention. In addition, performance expectancy, facilitating condition, and social influence directly and indirectly have effect on behavioral intention. Also, the significance between social influence and performance expectancy, social influence and effort expectancy were verified. CONCLUSIONS: This study manifested that the proposed framework based on the UTAUT had explanatory power to identify the factors influencing the students' behavioral intention to use the 3D gastroscopic model constructed based on VR technology. Whereas, an important variable of effort expectancy in the frame of the SEM were not certified, thereby indicating that particular attention should be paid to this variable by universities and teachers before applying 3D gastroscopic model constructed based on VR technology in teaching. Added preparatory work is required such as explaining the basic knowledge of the operating steps of VR model and make students adequately understand its accessibility, which can probably improve the intentions of them to use it. The positive effects of social influence on performance expectancy and effort expectancy we proposed was also verified in this study, which provided a direction for future research.

Overexpression of SERPINA3 suppresses tumor progression by modulating SPOP/NF­κB in lung cancer.

The pathogenesis mechanism of lung cancer is very complex, with high incidence and mortality. Serpin family A member 3 (SERPINA3) expression levels were reduced in the sera of patients with lung cancer and may be a candidate diagnostic and prognostic survival biomarker in lung cancer, as previously reported. However, the detailed biological functions of SERPINA3 in the pathogenesis of lung cancer remain unknown. In the present study, it was aimed to explore the effects of SERPINA3 on the occurrence of lung cancer. SERPINA3 expression was assessed using bioinformatics database analysis and experimental detection. Then, the biological effects of SERPINA3 were investigated in a cell culture system and a xenograft model of human lung cancer. The potential regulatory mechanism of SERPINA3 in lung cancer was explored by data­independent acquisition mass spectrometry (DIA­MS) detection and further validated by western blotting (WB). The results indicated that SERPINA3 expression levels were significantly downregulated in lung cancer tissues and cell lines. At the cellular level, it was revealed that overexpressed SERPINA3 inhibited cell growth, proliferation, migration and invasion and promoted the apoptosis of lung cancer cells. Moreover, overexpressed SERPINA3 enhanced the sensitivity of lung cancer cells to osimertinib. In vivo, a xenograft model of human lung cancer was established with BALB/c nude mice. After the injection of A549 cells, the tumor growth of the tumor­bearing mice in the SERPINA3­overexpressing group increased more slowly, and the tumor volume was smaller than that in the empty­vector group. Mechanistically, a total of 65 differentially expressed proteins were identified. It was found that the speckle­type POZ protein (SPOP) was significantly upregulated in SERPINA3­overexpressing H157 cells using DIA­MS detection and analysis. WB validation showed that SPOP expression increased, and NF­kappaB (NF­κB) p65 was inhibited in cell lines and tumor tissues of mice when SERPINA3 was overexpressed. The present findings suggest that SERPINA3 is involved in the development of lung cancer and has an antineoplastic role in lung cancer.

Taxonomic and thematic relations rely on different types of semantic features: Evidence from an fMRI meta-analysis and a semantic priming study.

Taxonomic and thematic relations are major components of semantic representation but their neurocognitive underpinnings are still debated. We hypothesised that taxonomic relations preferentially activate parts of anterior temporal lobe (ATL) because they rely more on colour and shape features, while thematic relations preferentially activate temporoparietal cortex (TPC) because they rely more on action and location knowledge. We first conducted activation likelihood estimation (ALE) meta-analysis to assess evidence for neural specialisation in the existing fMRI literature (Study 1), then used a primed semantic judgement task to examine if the two relations are primed by different feature types (Study 2). We find that taxonomic relations show minimal feature-based specialisation but preferentially activate the lingual gyrus. Thematic relations are more dependent on action and location features and preferentially engage TPC. The meta-analysis also showed that lateral ATL is preferentially engaged by Thematic relations, which may reflect their greater reliance on verbal associations.

Preparation and usage of nanomaterials in biomedicine.

Nanotechnology is one of the most promising and decisive technologies in the world. Nanomaterials, as the primary research aspect of nanotechnology, are quite different from macroscopic materials because of their unique optical, electrical, magnetic, thermal properties, and more robust mechanical properties, which make them play an essential role in the field of materials science, biomedical field, aerospace field, and environmental energy. Different preparation methods for nanomaterials have various physical and chemical properties and are widely used in different areas. In this review, we focused on the preparation methods, including chemical, physical, and biological methods due to the properties of nanomaterials. We mainly clarified the characteristics, advantages, and disadvantages of different preparation methods. Then, we focused on the applications of nanomaterials in biomedicine, including biological detection, tumor diagnosis, and disease treatment, which provide a development trend and promising prospects for nanomaterials.

Persistent HPV infection after conization of cervical intraepithelial neoplasia-- a systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate several factors of persistent human papillomavirus (HPV) infection following conization in patients with cervical intraepithelial neoplasia (CIN). METHODS: PubMed, EMBASE and the Cochrane Library were searched from January 1, 1998 to September 10, 2021. Random-effects models for meta-analyses were used and pooled relative risks with 95% confidence intervals were reported. Literature screening, data extraction, and assessment of the risk of bias in the included studies were conducted independently by two researchers. Data analysis was performed with Stata software, version 12.0. RESULTS: A total of 28 studies were included in this study. Meta-analysis revealed that surgical margin and residual disease were positively correlated with persistent HPV infection after conization. Compared with patients infected with other types of HPV, CIN patients with HPV 16 had a higher persistent infection rate (OR = 1.967, 95% CI (1.232-3.140), P < 0.05). CONCLUSIONS: CIN patients who are postmenopausal, have positive surgical margins and residual lesions, and are positive for HPV 16 are prone to persistent HPV infection after conization.

A multidimensional learning curve analysis of totally laparoscopic ileostomy reversal using a single surgeon' s experience.

Purpose: Recently, totally laparoscopic ileostomy reversal (TLAP) has received increasing attention and exhibited promising short-term outcomes. The aim of this study was to detail the learning process of the TLAP technique. Methods: Based on our initial experience with TLAP from 2018, a total of 65 TLAP cases were enrolled. Demographics and perioperative parameters were assessed using cumulative sum (CUSUM), moving average, and risk-adjusted CUSUM (RA-CUSUM) analyses. Results: The overall mean operative time (OT) was 94 min and the median postoperative hospitalization period was 4 days, and there was an estimated 10.77% incidence rate of perioperative complications. Three unique phases of the learning curve were derived from CUSUM analysis, and the mean OT of phase I (1-24 cases) was 108.5 min, that of phase II (25-39 cases) was 92 min, and that of phase III (40-65 cases) was 80 min, respectively. There was no significant difference in perioperative complications between these 3 phases. Similarly, moving average analysis indicated that the operation time was reduced significantly after the 20th case and reached a steady state after the 36th case. Furthermore, complication-based CUSUM and RA-CUSUM analyses indicated an acceptable range of complication rates during the whole learning period. Conclusion: Our data demonstrated 3 distinct phases of the learning curve of TLAP. For an experienced surgeon, surgical competence in TLAP can be grasped at around 25 cases with satisfactory short-term outcomes.

Relationship between pyroptosis-mediated inflammation and the pathogenesis of prostate disease.

The largest solid organ of the male genitalia, the prostate gland, is comprised of a variety of cells such as prostate epithelial cells, smooth muscle cells, fibroblasts, and endothelial cells. Prostate diseases, especially prostate cancer and prostatitis, are often accompanied by acute/chronic inflammatory responses or even cell death. Pyroptosis, a cell death distinct from necrosis and apoptosis, which mediate inflammation may be closely associated with the development of prostate disease. Pyroptosis is characterized by inflammasome activation via pattern recognition receptors (PRR) upon recognition of external stimuli, which is manifested downstream by translocation of gasdermin (GSDM) protein to the membrane to form pores and release of inflammatory factors interleukin (IL)-1ß and IL-18, a process that is Caspase-dependent. Over the past number of years, many studies have investigated the role of inflammation in prostate disease and have suggested that pyroptosis may be an important driver. Understanding the precise mechanism is of major consequence for the development of targeted therapeutic strategies. This review summarizes the molecular mechanisms, regulation, and cellular effects of pyroptosis briefly and then discuss the current pyroptosis studies in prostate disease research and the inspiration for us.

Ryanodine receptor 2 (RYR2) dysfunction activates the unfolded protein response and perturbs cardiomyocyte maturation.

AIMS: Calcium-handling capacity is a major gauge of cardiomyocyte maturity. Ryanodine receptor 2 (RYR2) is the pre-dominant calcium channel that releases calcium from the sarcoplasmic reticulum/endoplasmic reticulum (SR/ER) to activate cardiomyocyte contraction. Although RYR2 was previously implied as a key regulator of cardiomyocyte maturation, the mechanisms remain unclear. The aim of this study is to solve this problem. METHODS AND RESULTS: We performed Cas9/AAV9-mediated somatic mutagenesis to knockout RYR2 specifically in cardiomyocytes in mice. We conducted a genetic mosaic analysis to dissect the cell-autonomous function of RYR2 during cardiomyocyte maturation. We found that RYR2 depletion triggered ultrastructural and transcriptomic defects relevant to cardiomyocyte maturation. These phenotypes were associated with the drastic activation of ER stress pathways. The ER stress alleviator tauroursodeoxycholic acid partially rescued the defects in RYR2-depleted cardiomyocytes. Overexpression of ATF4, a key ER stress transcription factor, recapitulated defects in RYR2-depleted cells. Integrative analysis of RNA-Seq and bioChIP-Seq data revealed that protein biosynthesis-related genes are the major direct downstream targets of ATF4. CONCLUSION: RYR2-regulated ER homeostasis is essential for cardiomyocyte maturation. Severe ER stress perturbs cardiomyocyte maturation primarily through ATF4 activation. The major downstream effector genes of ATF4 are related to protein biosynthesis.