Amelioration of melittin on adjuvant-induced rheumatoid arthritis: Integrated transcriptome and metabolome.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease lacking a definitive cure. Although conventional treatments such as dexamethasone and methotrexate are prevalent, their usage is constrained by potential adverse effects. Melittin (MLT) has emerged as a promising natural anti-rheumatic drug; however, studies focusing on the role of MLT in modulating the expression and metabolism of RA-related genes are scarce. METHOD: Arthritis was induced in rats using Complete Freund's Adjuvant (CFA), followed by MLT injections for treatment. Post-treatment, the inflammatory status of each group was assessed, and the mechanistic underpinnings of MLT's ameliorative effects on RA were elucidated through transcriptomic and metabolomic analyses. Additionally, this study conducted qRT-PCR validation of key therapeutic genes and characterized the molecular docking interactions of MLT with key receptor proteins (TNF-α and IL-1ß) using the AutoDock Vina software. RESULT: MLT significantly diminished redness and swelling in affected joints, ameliorated inflammatory cell infiltration, and mitigated joint damage. Integration of transcriptomic and metabolomic data revealed that MLT predominantly regulated the transcription levels of pathways and genes related to cytokines and immune responses, and the metabolic biomarkers of Sphingomyelin, fatty acid, and flavonoid. qRT-PCR confirmed MLT's downregulation of inflammation-related genes such as Il6, Jak2, Stat3, and Ptx3. Molecular docking simulations demonstrated the stable binding of MLT to TNF-α and IL-1ß. CONCLUSION: MLT demonstrated significant efficacy in alleviating RA. This study provides a comprehensive summary of MLT's impact on gene expression and metabolic processes associated with RA.

Impact of Brood Cell Cocoons on Metal Accumulation and CYP450 Detoxification Gene Expression in Apis cerana cerana.

Honey bees play a critical role as pollinators. However, their reproduction success and survival face severe threats due to the deterioration of their living environment. Notably, environmental conditions during their preimaginal stage inside brood cells can influence their immune capabilities and overall health after emergence. During the in-cell developmental stage, workers are in close contact with cocoons, which can become a source of stress due to accumulated metals. To investigate this potential threat, experiments were conducted to examine the impact of cocoons in brood cells used to rear different generations on the metal content and detoxification gene expression levels in Apis cerana cerana. Our findings indicated significant differences in the layers, weight, base thickness, and metal contents like Cr, Cd, Pb, Mn, Ni, and As of cocoons in multi-generation brood cells compared to single-generation brood cells. These increases led to significant elevations in metal levels and upregulations of the four CYP450 detoxification genes in both six-day-old larvae and newly emerged workers. In conclusion, this study highlights the negative impact of cocoons in multi-generation brood cells on bee health and provides evidence supporting the development of rational apiculture management strategies for ecosystem stability.

Analysis of comb-gnawing behavior in Apis cerana cerana (Hymenoptera: Apidae).

Apis cerana cerana exhibits a prominent biological trait known as comb gnawing. In this study, gnawed combs from colonies during different seasons were collected, investigating the comb age and locations of gnawing. Patterns of comb gnawing were recorded, and the effects of 2 factors, namely, comb type and season, on the mass of wax residues and the gnawed surface area were measured. The results revealed that A. c. cerana predominantly gnaws combs that have been used for over 6 months, with gnawing concentrated in the brood-rearing area. In the first 3 seasons, significantly higher masses of wax residues and larger gnawed surface areas were found in greater wax moth larvae (GWML)-infested combs compared to newly built and old combs. Also, there were significantly higher masses and areas gnawed by A. c. cerana in old combs compared to newly built combs in all 4 seasons. Compared to other seasons, it exhibited significantly higher masses and areas resulting from comb-gnawing in newly built or old combs in winter. However, there were no significant differences in the masses of wax residues and surface areas gnawed in GWML-infested combs across the first 3 seasons. In conclusion, this study documented the impact of comb type and season on the comb-gnawing behavior of A. c. cerana, contributing to beekeeping management practices and the current understanding of bee biology.

Melittin promotes dexamethasone in the treatment of adjuvant rheumatoid arthritis in rats.

Background: Rheumatoid arthritis (RA) is an erosive-destructive inflammation of the joints, and the chronic, long-term stiffness and deformation induced by RA are some of the symptoms of arthritis that are difficult to treat. Dexamethasone (DEX) and melittin (MLT) are two interesting anti-inflammatory substances, both of which possess anti-inflammatory effects exerted through the suppression of the immune system. The purpose of this study was to explore the role of MLT in the treatment of RA by DEX as well as to clarify the influence of MLT on the efficacy and side effects of DEX. Method: The rats were injected with Complete Freund's Adjuvant (CFA) to induce arthritis, followed by treatment with different doses of DEX and/or MLT. The relevant indexes of paw inflammation were determined, and the appetite, growth status, arthritis status, cytokine levels, and organ coefficient of the rats were evaluated. In addition, the paraffin sections of the joint tissues were prepared to analyze the pathological changes. Result: DEX exhibited side effects, notably hindering feed intake and growth, and inducing immune organ lesions in the rats. MLT significantly reduced the side effects of DEX and promoted its efficacy. DEX in combination with MLT demonstrated a synergistic efficacy in RA treatment, showing advantages in detumescence reduction, pro-inflammatory cytokine inhibition, and joint internal pathological improvement. Conclusion: Thus, MLT promoted the efficacy of DEX in adjuvant RA treatment in rats, offering an approach to reduce the use dosage and side effects of DEX.

Exploring potential network pharmacology-and molecular docking-based mechanism of melittin in treating rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a type of difficult-to-cure arthralgia with a worldwide prevalence. It severely affects people's living standards. For a long time, bee venom has been used to treat RA and has shown good results. Melittin is the main active component of bee venom used for RA treatment, but the molecular mechanism of melittin in RA treatments remains unclear. METHODS: Potential melittin and RA targets were obtained from relevant databases, and common targets of melittin and RA were screened. The STRING database was used to build the PPI network and screen the core targets after visualization. The core targets were enriched by Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway. Finally, the binding of melittin to target proteins was evaluated through simulated molecular docking, which verified the reliability of the prediction results of network pharmacology. RESULTS: In total, 138 melittin targets and 5795 RA targets were obtained from relevant databases, and 90 common targets were obtained through intersection. Eighteen core targets, such as STAT3, AKT1, tumor necrosis factor, and JUN, were screened out. Enrichment analysis results suggested that melittin plays an anti-RA role mainly through tumor necrosis factor, interleukin-17, toll-like receptors, and advanced glycation end products-RAGE signaling pathways, and pathogenic bacterial infection. Molecular docking results suggested that melittin has good docking activity with core target proteins. CONCLUSION: RA treatment with melittin is the result of a multi-target and multi-pathway interaction. This study offers a theoretical basis and scientific evidence for further exploring melittin in RA therapy.

A pH­responsive hyaluronic acid nano­vehicle co­encapsulating doxorubicin and all­trans retinoic acid for the inhibition of hepatic stellate cell­induced tumor growth and metastasis.

All­trans retinoic acid (ATRA) has been implicated in the differentiation of hepatic stellate cells (HSCs). In the present study, the liver­targeting hyaluronic acid micelles (ADHG) were prepared for co­delivery of ATRA and doxorubicin (DOX) to block the HSC­hepatoma interrelation. To simulate the tumor microenvironment, an in vitro dual­cell model and an in vivo co­implantation mouse model were established for anticancer studies. The experimental methods involved the MTT assay, wound­healing assay, cellular uptake, flow cytometry and and in vivo antitumor study. The results revealed that the HSCs in the research models notably promoted tumor proliferation and migration. Furthermore, ADHG were readily internalized by cancer cells and HSCs simultaneously, and widely distributed in cancer regions. The in vivo antitumor studies demonstrated that ADHG could notably decrease HSC activation and extracellular matrix deposition, as well as constrain tumor growth and metastasis. Therefore, ATRA could facilitate DOX­induced anti­proliferation and anti­metastasis effects, and ADHG are a promising nano­sized formulation for the combination therapy of hepatocellular carcinoma.

Diagnosis of covert coarctation of the aorta in adolescents.

Objectives: By reviewing the diagnostic process for adolescents with coarctation of the aorta (CoA) in our institution, we analyzed the reasons for delayed diagnosis of CoA. We also proposed a diagnostic protocol to improve the detection rate of CoA. Methods: In this retrospective study, we included 48 patients aged 12-18 years who were diagnosed with CoA in our hospital from January 2000 to November 2022. Clinical data from involved cases in local hospitals and our institution were collected. Results: All patients had blood pressure (BP) measurements in upper and lower extremities in our institution. They all had hypertension, 29 (60.4%) of whom had known histories of the same. BP in the upper limbs of 47 (97.9%) patients was ≥20 mmHg higher than that in the lower limbs, and BP in the upper limb of 1 (2.1%) patient was greater than 0 and less than 20 mmHg than that in the lower limb. Echocardiography (ECHO) was performed in all patients, computed tomography (CT) or magnetic resonance imaging (MRI) was performed in 44 patients (91.7%). There were 38 (79.2%) patients who visited local hospitals. Among them, a total of 20 (52.6%) patients had their right upper extremity BP measured, 18 (47.4%) only had their left upper extremity BP measured, and 16 (42.1%) had their lower extremity BP measured. ECHO was performed in 27 (56.2%) patients and CT/MRI was performed in 18 (37.5%) patients. The detection rate for CT/MRI was 100%, and those of ECHO were 72.9% and 18.5% at our institution and a local hospital, respectively. Forty-eight (100%) and 23 (60.5%) patients were detected in our institution and local hospitals (P < 0.0001). Conclusion: We recommend measuring BP in the bilateral upper extremities. Measurement of BP in the lower extremities is recommended if hypertension is diagnosed. MRI/CT is recommended when BP in the upper extremity is greater than that in the lower extremity.

Comb Cell Structure and Morphological Characteristics of the Chinese Honey Bee, Apis cerana cerana (Hymenoptera: Apidae), Under Successive Generations.

This study investigated the changes in comb cell structure and external morphological characteristics of the Chinese honey bee under ten successive generations to determine the optimal time to replace the old combs. Accordingly, ten Chinese honey bee experimental colonies were established, and natural combs were constructed for continuous rearing of workers for 1-10 generations. The brood comb thickness, brood cell structure, birth weight, and morphological characteristics of workers were determined. Pearson correlation analyses between brood comb structure and morphological characteristics of workers were carried out. The results revealed that under ten successive generations, the color of the brood comb deepens from white or light yellow to brown and finally to black. Also, concerning the brood cell shape, the cell base changes from the three-rhomboid structure to the hemisphere, and the cell body changes from the hexagonal prism structure to the cylinder. The brood cell depth increases with an increase in brood comb thickness. The cell volume reduces with the hexagonal cell's decreasing inner circumference side length, and diameter. A smaller cell volume leads to a decrease in the birth weight and body size of the worker, in addition, the Chinese honey bee has gnawed off the comb cells that have been cultivated for eight generations. This study suggests that the combs of Chinese honey bees should be replaced after eight generations to improve colony strength and production performance.

Atrial septal defect with a rare occupying lesion in heart.

BACKGROUND: Cardiac epicardium hemangiomas are exceedingly rare; however, they can cause significant hemodynamic impairment and large pericardial effusions. On rare occasion, cardiac tumors coexist with malformations of the heart. CASE PRESENTATION: We present the case of a 10-month-old female infant with a rare cardiac surface hemangioma coexisting with malformations of the heart. It revealed an atrial septal defect (ASD) coexisting with an abnormal occupying lesion with high echogenicity. It was 35*12*9 mm in size and was found in the anterior atrioventricular junction to the posterior atrioventricular junction at the bottom of the ventricular septum by transthoracic echocardiography. We performed surgical treatment of the atrial septal defect and performed biopsy with the occupying lesion. The histopathological examination reported a benign tumor as hemangioma. As far as we know, this is the first case in which cardiac surface hemangioma was found to coexist with an atrial septal defect. CONCLUSIONS: Cardiac epicardium hemangiomas is a rare solid tumor of the heart. If the mass is impossible to resect and does not cause hemodynamic impairment, only mass biopsy is possible.

Deletion of 11q24.2-qter in a male child with cleft lip and palate: an atypical feature of Jacobsen syndrome.

Jacobsen syndrome (JS) is caused by the terminal deletion at the long arm of chromosome 11. It is characterized by growth retardation, intellectual disability, facial dysmorphism, and other congenital abnormalities. The subband 11q24.1 has been confirmed to be the critical region for the typical features of JS. The patient in the current study is a 2-year-old male child with prominent craniofacial abnormalities and congenital heart disease. High-resolution single-nucleotide polymorphism arrays revealed breakage in chromosome 11q beginning at 11q24.2, with complete deletion of the distal portion. We collected all available reports describing patients with breakages at 11q24.1 or 11q24.2, and compared it with the typical features of JS. We found that the phenotype of cleft lip and palate (CLP) was present in both groups of patients with no overlap region in the deletion region (between 11q21-q23 and 11q24.2-qter), which indicated that other genes may be related to CLP in JS.

Cell orientation characteristics of the natural combs of honey bee colonies.

The cell orientation characteristics of the natural combs of honey bees have received much research attention. Although natural combs have been shown to be composed of cells with three orientations-vertical, intermediate (oblique), and horizontal-the proportion of comb cells in these three orientations varies. Knowledge of the comb-building preferences of honey bees is essential for the installation of wax comb foundations, and clarification of the cell orientation characteristics of natural honey bee combs is important for beekeeping. The purpose of this study was to determine the cell orientation characteristics of natural combs of Eastern honey bees (Apis cerana cerana) and Western honey bees (Apis mellifera ligustica). Newly built combs were used to measure the orientation of hexagonal cells and calculate the proportion of cells in different orientations relative to the total number of cells. The number of eggs laid by queens in the cells of different orientations was also determined. The orientation of cells in the natural combs of Eastern and Western honey bees was determined based on the value of the minimum included angle between the pair of parallel cell walls and a vertical line connecting the top and bottom bars of the movable frame in the geometric plane of the comb: 0°≤θ≤10°, 10°<θ≤20°, and 20°<θ≤30° for vertical, intermediate, and horizontal orientations, respectively. Natural combs were composed of cells with at least one orientation (vertical or horizontal), two orientations (vertical + intermediate (oblique) or vertical + horizontal), or three orientations (vertical + intermediate + horizontal), and the proportions of combs with the three aforementioned configurations differed. Both Eastern honey bees and Western honey bees preferred building combs with cells in a vertical orientation. Queens showed no clear preference for laying eggs in cells of specific orientations. The results of this study provide new insight that could aid the production and cutting of wax comb foundations of Eastern and Western honey bees. Our study highlights the importance of installing wax comb foundations compatible with the comb-building preferences of bees.

Flavonoid glycosides from the nectar of Camellia reticulata Lindl.

The nectar of Camellia reticulata Lindl. contains sugar, amino acids and other nutritional components, suggesting that it could be developed for food and food additives. To understand the effects of the nectar on human health, we investigated its chemical constituents. Two new flavonoid glycosides, cameretiins A and B (1 and 2), and two known flavonoid glycosides, kaempferol 3-O-(2''-O-E-p-coumaroyl)-ß-D-glucopyranoside (3) and tiliroside (4) were obtained from the nectar of Camellia reticulata Lindl. Their structures were determined based on analysis of their spectroscopic data and by comparison with 1D NMR spectroscopic data of known compounds reported in the literature. Compounds (1-4) were first isolated from the nectar of Camellia reticulata Lindl.

Effect of rTMS intervention on upper limb motor function after stroke: A study based on fNIRS.

Background: Stroke is a disease with a high fatality rate worldwide and a major cause of long-term disability. In the rehabilitation of limb motor function after stroke, the rehabilitation of upper limb function takes a long time and the recovery progress is slow, which seriously affects the patients' self-care ability in daily life. Repeated transcranial magnetic stimulation (rTMS) has been increasingly used to improve limb dysfunction in patients with stroke. However, a standardized reference for selecting a magnetic stimulation regimen is not available. Whether to increase the inhibition of the contralateral hemispheric motor cortex remains controversial. This study has evaluated the effects of different rTMS stimulation programs on upper limb function and corresponding brain functional network characteristics of patients with stroke and sought a new objective standard based on changes in brain network parameters to guide accurate rTMS stimulation programs. Method: Thirty-six patients with stroke were selected and divided into control group and treatment group by number table method, with 18 patients in each group, and 3 patients in the control group were turned out and lost due to changes in disease condition. The treatment group was divided into two groups. TMS1 group was given 1 Hz magnetic stimulation in the M1 region of the contralesional hemisphere +10 Hz magnetic stimulation in the M1 region of the affected hemisphere, and the TMS2 group was given 10 Hz magnetic stimulation in the M1 region of the affected hemisphere. The control group was given false stimulation. The treatment course was once a day for 5 days a week for 4 weeks. The Fugl-Meyer Assessment for upper extremity (FMA-UE) sand near-infrared brain function were collected before treatment, 2 weeks after treatment, and 4 weeks after treatment, and the brain function network was constructed. Changes in brain oxygenated hemoglobin concentration and brain network parameters were analyzed with the recovery of motor function (i.e., increased FMA score). Meanwhile, according to the average increment of brain network parameters, the rTMS stimulation group was divided into two groups with good efficacy and poor efficacy. Network parameters of the two groups before and after rTMS treatment were analyzed statistically. Results: (1) Before treatment, there was no statistical difference in Fugl-Meyer score between the control group and the magnetic stimulation group (p = 0.178).Compared with before treatment, Fugl-Meyer scores of 2 and 4 weeks after treatment were significantly increased in both groups (p <0.001), and FMA scores of 4 weeks after treatment were significantly improved compared with 2 weeks after treatment (p < 0.001). FMA scores increased faster in the magnetic stimulation group at 2 and 4 weeks compared with the control group at the same time point (p <0.001).TMS1 and TMS2 were compared at the same time point, FMA score in TMS2 group increased more significantly after 4 weeks of treatment (p = 0.010). (2) Before treatment, HbO2 content in healthy sensory motor cortex (SMC) area of magnetic stimulation group and control group was higher than that in other region of interest (ROI) area, but there was no significant difference in ROI between the two groups. After 4 weeks of treatment, the HbO2 content in the healthy SMC area was significantly decreased (p < 0.001), while the HbO2 content in the affected SMC area was significantly increased, and the change was more significant in the magnetic stimulation group (p < 0.001). (3) In-depth study found that with the recovery of motor function (FMA upper limb score increase ≥4 points) after magnetic stimulation intervention, brain network parameters were significantly improved. The mean increment of network parameters in TMS1 group and TMS2 group was significantly different (χ 2 = 5.844, p = 0.016). TMS2 group was more advantageous than TMS1 group in improving the mean increment of brain network parameters. Conclusion: (1) The rTMS treatment is beneficial to the recovery of upper limb motor function in stroke patients, and can significantly improve the intensity of brain network connection and reduce the island area. The island area refers to an isolated activated brain area that cannot transmit excitation to other related brain areas. (2) When the node degree of M1_Healthy region less than 0.52, it is suggested to perform promotion therapy only in the affected hemisphere. While the node degree greater than 0.52, and much larger than that in the M1_affected region. it is suggested that both inhibition in the contralesional hemisphere and high-frequency excitatory magnetic stimulation in the affected hemisphere can be performed. (3) In different brain functional network connection states, corresponding adjustment should be made to the treatment plan of rTMS to achieve optimal therapeutic effect and precise rehabilitation treatment.

A comparison study of superovulation strategies for C57BL/6J and B6D2F1 mice in CRISPR-Cas9 mediated genome editing.

Reproductive techniques such as superovulation and in vitro fertilisation (IVF) have been widely used in generating genetically modified animals. The current gold standard for superovulation in mice is using coherent treatments of equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG). An alternative method using inhibin antiserum (IAS) instead of eCG has been recently reported. Here, we evaluate different superovulation strategies in C57BL/6J and B6D2F1 mice. Firstly, we found that using 5-week-old C57BL/6J and 4-week-old B6D2F1 donors could achieve better superovulation outcomes. Then, we compared eCG-hCG, IAS-hCG and eCG-IAS-hCG with different dosages in both mouse strains. Significantly increased numbers of oocytes were obtained by using IAS-hCG and eCG-IAS-hCG methods. However, low fertilisation rates (36.3-38.8%) were observed when natural mating was applied. We then confirmed that IVF could dramatically ameliorate the fertilisation rates up to 89.1%. Finally, we performed CRISPR-Cas9 mediated genome editing targeting Scn11a and Kcnh1 loci, and successfully obtained mutant pups using eCG-hCG and IAS-hCG induced zygotes, which were fertilised by either natural mating or IVF. Our results showed that IAS is a promising superovulation reagent, and the efficiency of genome editing is unlikely to be affected by using IAS-induced zygotes.

Case Report: Transcatheter Closure of Ruptured Sinus of Valsalva With Ventricular Septal Defect Occluder in a 3-Year-Old Child After Repair of Ventricular Septal Defect.

Sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly that can undergo spontaneous rupture into other cardiac chambers or the pericardial space. A ruptured SVA has a very poor prognosis with high morbidity and mortality. These aneurysms often present as a rupture from the right coronary sinus into the right ventricle. Transcatheter closure has become an effective alternative to surgical treatment. However, it has been rarely reported in patients after ventricular defect repair in the past. We here describe a 3-year-and-3-month-old boy who was found to have a ruptured sinus of Valsalva. He underwent surgical closure of a ventricular septal defect at the age of 2 months, which occurred in the non-coronary sinus (NCS) and ruptured into the right atrium. We successfully occluded the ruptured sinus of Valsalva with a ventricular septal occluder.

Evaluating and Comparing the Natural Cell Structure and Dimensions of Honey Bee Comb Cells of Chinese Bee, Apis cerana cerana (Hymenoptera: Apidae) and Italian Bee, Apis mellifera ligustica (Hymenoptera: Apidae).

The hexagonal structure of the honey bee comb cell has been the source of many studies attempting to understand its structure and function. In the storage area of the comb, only honey is stored and no brood is reared. We predicted that honey bees may construct different hexagonal cells for brood rearing and honey storage. We used quantitative analyses to evaluate the structure and function of the natural comb cell in the Chinese bee, Apis cerana cerana and the Italian bee, A. mellifera ligustica. We made cell molds using a crystal glue solution and measured the structure and inclination of cells. We found that the comb cells of A. c. cerana had both upward-sloping and downward-sloping cells; while the A. m. ligustica cells all tilted upwards. Interestingly, the cells did not conform to the regular hexagonal prism structure and showed irregular diameter sizes. In both species, comb cells also were differentiated into worker, drone and honey cells, differing in their diameter and depth. This study revealed unique differences in the structure and function of comb cells and showed that honey bees design their cells with precise engineering to increase storage capacity, and to create adequate growing room for their brood.

Results of two different echocardiography-guided approaches to closure of perimembranous ventricular septal defects.

OBJECTIVES: The feasibility of mini-invasive closure of perimembranous ventricular septal defects has been proven, but can cause surgical incision or sternum injury. A relevant but, to date, unanswered question is whether there exists a treatment without surgical trauma, radiation exposure and arterial complications. METHODS: From May 2017 to January 2020, a total of 449 patients with perimembranous ventricular septal defect [mean age 5.0 ± 6.1 years (range 0.8-52.0 years)] were involved in this study and underwent 2 different echocardiography-guided operative procedures [percutaneous device closure (group A) or percardiac device closure (group B)] based on the patients' or their parents' choice. The clinical data were collected and a retrospective analysis was performed. RESULTS: Fifty-five (96.5%) cases were successfully occluded in group A, and 2 (3.5%) patients were converted to percardiac device closure; 379 (96.7%) patients in group B underwent percardiac device closure, and 13 patients (3.3%) were turned to open-heart surgery after occlusion procedure failure. There were statistically significant differences (P < 0.05) between the 2 groups in operation time, postoperative hospitalization time and blood transfusion requirement. No acute complications or severe adverse events (death, valve injury, complete atrioventricular block and embolism) occurred either in the early period or during the follow-up. CONCLUSIONS: Percutaneous device closure can achieve the same validity and safety as percardiac device closure for treating perimembranous ventricular septal defects with a more rapid recovery and less trauma.

Identification of KIAA0196 as a novel susceptibility gene for myofibril structural disorganization in cardiac development.

BACKGROUND: Congenital heart disease is one of the most common cardiac malformation-related diseases worldwide. Some causative genes have been identified but can explain only a small proportion of all cases; therefore, the discovery of novel susceptibility genes and/or modifier genes for abnormal cardiac development remains a major challenge. METHODS: We used a single nucleotide polymorphism (SNP) array, and next-generation sequencing (NGS) was conducted to screen and quickly identify candidate genes. KIAA0196 knockout zebrafish and mice were generated by CRISPR/Cas9 to detect whether or how KIAA0196 deficiency would influence cardiac development. RESULTS: Homozygous, but not heterozygous, zebrafish and mice showed early embryonic lethality. At the embryonic stage, microscopic examination and dissection revealed pericardial edema and ventricle enlargement in homozygous zebrafish and obviously delayed cardiac development in heterozygous mice, while echocardiography and tissue staining showed that significantly decreased cardiac function, ventricle enlargement, myofibril loss, and significantly reduced trabecular muscle density were observed in adult heterozygous zebrafish and mice. Most importantly, immunostaining and electron microscopy showed that there was a significant increase in sarcomere structural disorganization and myofibril structural integrity loss in KIAA0196 mutants. Furthermore, substantial downregulation in other sarcomeric genes and proteins was detected and verified in a mouse model via transcriptome and proteomics analyses; these changes especially affected the myosin heavy or light chain (MYH or MYL) family genes. CONCLUSION: We identified KIAA0196 for the first time as a susceptibility gene for abnormal cardiac development. KIAA0196 deficiency may cause abnormal heart development by influencing the structural integrity of myofibrils.