Polydopamine Enhanced Interactions of Graphene Nanosheets to Fabricate Graphene/Polydopamine Aerogels with Effectively Clear Organic Pollutants.

Graphene/polydopamine aerogels (GPDXAG, where X represents the weight ratio of DA·HCl to GO) were prepared by the chemical reduction of graphene oxide (GO) using dopamine (DA) and l-ascorbic acid as reducing agents. During the gelation process, DA was polymerized to form polydopamine (PDA). The introduction of PDA in the gelation of aerogels led to a deeper reduction of GO and stronger interactions between graphene nanosheets forced by covalent cross-linking and noncovalent bonding including π-π stacking and hydrogen bonding. The weight ratio of DA·HCl to GO influencing the formation and morphology of GPDXAG was explored. With the increasing content of DA in gelation, the reduction of GO and the cross-linking degree of graphene nanosheets were enhanced, and the resulting GPDXAG had a more regular pore distribution. Additionally, introducing PDA into GPDXAG improved its hydrophobicity because of the adhesion of PDA to a network of aerogels. GPDXAG exhibited a higher removal efficiency for organic pollutants than the controlled graphene aerogels (GAG). Specifically, the adsorption capacity of GPDXAG for organic solvents was superior to that of GAG, and organic solvent was completely separated from the oil/water mixture by GPDXAG. The equilibrium adsorption capacity of GPDXAG for malachite green (MG) was measured to be 768.50 mg/g, which was higher than that for methyl orange (MO). In MG/MO mixed solutions, aerogels had obvious adsorption selectivity for the cationic dye. The adsorption mechanism of aerogels for MG was also discussed by simulating adsorption kinetic models and adsorption isothermal models.

Estimating the Amount of the Wild Artemisia annua in China Based on the MaxEnt Model and Spatio-Temporal Kriging Interpolation.

In order to determine the distribution area and amount of Artemisia annua Linn. (A. annua) in China, this study estimated the current amount of A. annua specimens based on the field survey sample data obtained from the Fourth National Census of Chinese Medicinal Resources. The amount was calculated using the maximum entropy model (MaxEnt model) and spatio-temporal kriging interpolation. The influencing factors affecting spatial variations in the amount were studied using geographic probes. The results indicated that the amount of A. annua in China was about 700 billion in 2019. A. annua was mainly distributed in the circular coastal belt of Shandong Peninsula, central Hebei, Tianjin, western Liaoning, and along the Yangtze River and in the middle and lower reaches of Jiangsu, Anhui, and the northern Chongqing provinces. The main factors affecting the amount are the precipitation in the wettest and the warmest seasons, the average annual precipitation, and the average temperature in the coldest and the driest seasons. The results show that the amount of A. annua is strongly influenced by precipitation and temperature.

Mechanism of Smilax china L. in the treatment of intrauterine adhesions based on network pharmacology, molecular docking and experimental validation.

BACKGROUND: Smilax china L. (SCL) is a traditional herbal medicine for the potential treatment of intrauterine adhesion (IUA). However, the mechanisms of action have not yet been determined. In this study, we explored the effects and mechanisms of SCL in IUA by network pharmacology, molecular docking and molecular biology experiments. METHODS: Active ingredients and targets of SCL were acquired from TCMSP and SwissTargetPrediction. IUA-related targets were collected from the GeneCards, DisGeNET, OMIM and TTD databases. A protein‒protein interaction (PPI) network was constructed by Cytoscape 3.9.1 and analysed with CytoHubba and CytoNCA to identify the core targets. The DAVID tool was used for GO and KEGG enrichment analyses. Furthermore, molecular docking was employed to assess the interaction between the compounds and key targets. Finally, the mechanisms and targets of SCL in IUA were verified by cellular experiments and western blot. RESULTS: A total of 196 targets of SCL were identified, among which 93 were related to IUA. Topological and KEGG analyses results identified 15 core targets that were involved in multiple pathways, such as inflammation, apoptosis, and PI3K/AKT signalling pathways. Molecular docking results showed that the active compounds had good binding to the core targets. In vitro experiments showed that astilbin (AST), a major component of SCL, significantly reduced TGF-ß-induced overexpression of fibronectin (FN), activation of the PI3K/AKT signalling pathway and the expression of downstream factors (NF-κB and BCL2) in human endometrial stromal cells, suggesting that AST ameliorates IUA by mediating the PI3K/AKT/NF-κB and BCL2 proteins. CONCLUSIONS: AST, a major component of SCL, may be a potential therapeutic agent for IUA. Moreover, its mechanism is strongly associated with regulation of the PI3K/AKT signalling pathway and the downstream NF-κB and BCL2 proteins. This study will provide new strategies that utilize AST for the treatment of IUA.

Rational control of the typical surface defects of hybrid perovskite using tetrahexylammonium iodide.

There are numerous defects existing on the surface and grain boundary of perovskite, which adversely affect the performance and stability of perovskite solar cell devices. Systematic first-principles calculations show that the I vacancy (VI), Pb vacancy (VPb), Pb-I antisite (PbI), and I-Pb antisite (IPb) defects can significantly affect the electronic properties of the surface of formamidinium lead triiodide (FAPbI3); in particular the VPb, PbI and IPb surface defects can introduce defect energy levels in the band gap. Tetrahexylammonium iodide (THAI) that is strongly adsorbed on the (1 0 0) surface of FAPbI3 by forming Pb-I coordination bonds and I⋯H hydrogen bonds could eliminate or reduce the defect states near the band edge or in the band gap by transferring electrons between THAI and the surface of FAPbI3. In particular, the defect states introduced by VPb could be completely eliminated after the adsorption of THAI. This study shows an in-depth understanding of the influence of defects on the electronic properties of the surface of FAPbI3, as well as the passivation mechanism of organic salts on the surface defects of perovskite.

Analysis of the Risk Factors for Plastic Bronchitis in Children with Severe Adenovirus Pneumonia: A Retrospective Study.

Purpose: Plastic bronchitis (PB), a rare complication of respiratory infection characterized by the formation of casts in the tracheobronchial tree, can lead to airway obstruction and severe condition. Adenovirus is one of the common pathogens of PB caused by infection. This study aimed to evaluate the clinical features and risk factors for PB in children with severe adenovirus pneumonia. Methods: A retrospective study of children with severe adenovirus pneumonia with bronchoscopy results at Guangzhou Women and Children's Hospital between January 2018 and January 2020 was performed. Based on bronchoscopy, we divided children with severe adenovirus pneumonia into two groups: PB and non-PB. Binary logistic regression analysis was used to identify independent risk factors for PB in patients with severe adenovirus pneumonia after univariate analysis. Results: Our study examined 156 patients with severe adenovirus pneumonia with bronchoscopy results in hospital. Among them, 18 developed PB and 138 did not. On multivariate analysis, the independent risk factors of PB in children with severe adenovirus pneumonia were history of allergies (OR 10.147, 95% CI 1.727-59.612; P=0.010), diminished breath sounds (OR 12.856, 95% CI 3.259-50.713; P=0.001), and increased proportion of neutrophils (>70%; OR 8.074, 95% CI 1.991-32.735; P=0.003). Conclusion: Children with severe adenovirus pneumonia with a history of allergies, diminished breath sounds, and increased the proportion of neutrophils >70% may show higher risk of PB.

Fully connected-convolutional (FC-CNN) neural network based on hyperspectral images for rapid identification of P. ginseng growth years.

P. ginseng is a precious traditional Chinese functional food, which is used for both medicinal and food purposes, and has various effects such as immunomodulation, anti-tumor and anti-oxidation. The growth year of P. ginseng has an important impact on its medicinal and economic values. Fast and nondestructive identification of the growth year of P. ginseng is crucial for its quality evaluation. In this paper, we propose a FC-CNN network that incorporates spectral and spatial features of hyperspectral images to characterize P. ginseng from different growth years. The importance ranking of the spectra was obtained using the random forest method for optimal band selection. Based on the hyperspectral reflectance data of P. ginseng after radiometric calibration and the images of the best five VNIR bands and five SWIR bands selected, the year-by-year identification of P. ginseng age and its identification experiments for food and medicinal purposes were conducted, and the FC-CNN network and its FCNN and CNN branch networks were tested and compared in terms of their effectiveness in the identification of P. ginseng growth years. It has been experimentally verified that the best year-by-year recognition was achieved by utilizing images from five visible and near-infrared important bands and all spectral curves, and the recognition accuracy of food and medicinal use reached 100%. The FC-CNN network is significantly better than its branching model in the effect of edible and medicinal identification. The results show that for P. ginseng growth year identification, VNIR images have much more useful information than SWIR images. Meanwhile, the FC-CNN network utilizing the spectral and spatial features of hyperspectral images is an effective method for the identification of P. ginseng growth year.

The super-pangenome of Populus unveils genomic facets for its adaptation and diversification in widespread forest trees.

Understanding the underlying mechanisms and links between genome evolution and adaptive innovations stands as a key goal in evolutionary studies. Poplars, among the world's most widely distributed and cultivated trees, exhibit extensive phenotypic diversity and environmental adaptability. In this study, we present a genus-level super-pangenome comprising 19 Populus genomes, revealing the likely pivotal role of private genes in facilitating local environmental and climate adaptation. Through the integration of pangenomes with transcriptomes, methylomes, and chromatin accessibility mapping, we unveil that the evolutionary trajectories of pangenes and duplicated genes are closely linked to local genomic landscapes of regulatory and epigenetic architectures, notably CG methylation in gene-body regions. Further comparative genomic analyses have enabled the identification of 142 202 structural variants across species that intersect with a significant number of genes and contribute substantially to both phenotypic and adaptive divergence. We have experimentally validated a ∼180-bp presence/absence variant affecting the expression of the CUC2 gene, crucial for leaf serration formation. Finally, we developed a user-friendly web-based tool encompassing the multi-omics resources associated with the Populus super-pangenome (http://www.populus-superpangenome.com). Together, the present pioneering super-pangenome resource in forest trees not only aids in the advancement of breeding efforts of this globally important tree genus but also offers valuable insights into potential avenues for comprehending tree biology.

Passive trapping of biomolecules in hotspots with all-dielectric terahertz metamaterials.

Electromagnetic metamaterials feature the capability of squeezing photons into hotspot regions of high intensity near-field enhancement for strong light-matter interaction, underpinning the next generation of emerging biosensors. However, randomly dispersed biomolecules around the hotspots lead to weak interactions. Here, we demonstrate an all-silicon dielectric terahertz metamaterial sensor design capable of passively trapping biomoleculars into the resonant cavities confined with powerful electric field. Specifically, multiple controllable high-quality factor resonances driven by bound states in the continuum (BIC) are realized by employing longitudinal symmetry breaking. The dielectric metamaterial sensor with nearly 15.2 experimental figure-of-merit enabling qualitative and quantitative identification of different amino acids by delivering biomolecules to the hotspots for strong light-matter interactions. It is envisioned that the presented strategy will enlighten high-performance meta-sensors design from microwaves to visible frequencies, and serve as a potential platform for microfluidic sensing, biomolecular capture, and sorting devices.

Exenatide and Metformin Improve Serum Indices and Intestinal Flora in patients with Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease.

The aim of the study was to investigate th e in flue nce of Exenatide comb ined with Met formin on fasti ng blood glucose, postpr andial glucose, triglycerides, total cholesterol, alanine aminotransferase, aspartate aminotransferase, and inte s tinal flora in typ e 2 diab etes mellitus cases with non-alcoholic fatty liver disease. A total of 128 type 2 diabetes mellitus patients with non-alcoholic fatty liver disease, diagnosed from Januar y 2019 to January 2022, were included and randomly assigned to either G roup A (n=64) or Gro up B (n =64). Group A received Metformin, while Group B received Exenatide injection and Metfor min. After 24 weeks of treat ment, blood glucose indices (fasting blood glucose and postprandial glucose), blood lipid indices (triglycerides and total cholesterol), liver func tion indices (alanine aminotransferase and aspar tate aminotransferase) were all lower in Group B than in Group A (p<0.001 for all). Counts o f Escherichia coli and Enterococcus faecalis were lower in Group B than in Group A (both p<0.05), counts of Bifidobacteria and Lactobacillus were highe r i n Group B than in Grou p A (both p<0.05). Combin ation of Exenati de and Metformi n may have synergistic effects in improving metabo lic an d hepatic pa rameters, a s well as re gulat ing intestinal flora, which cou ld provide a pro misin g therapeutic option for the management of these patients.

Circular RNA CircACAP2 regulates temporomandibular joint osteoarthritis via miR-21-5p/PLAG1 axis.

OBJECTIVES: The pathogenesis of temporomandibular joint osteoarthritis (TMJOA) remains not fully understood. Our previous studies demonstrated that miR-21-5p may participate in the TMJOA development and the interaction between circRNA-ACAP2 (CircACAP2) and miR-21-5p. Our present study aimed to explore the biological functions and regulatory mechanisms of CircACAP2 in TMJOA. MATERIALS AND METHODS: The differential expression pattern of CircACAP2 in OA and normal tissues or cells was detected. CircACAP2 biological functions experiments were performed in chondrocytes by overexpression and interference techniques. The interaction of CircACAP2 with miR-21-5p and downstream target mRNA, polymorphic adenoma gene 1 (PLAG1), was predicted by bioinformatic databases and then demonstrated by dual-luciferase reporter assay. The biological role of CircACAP2 in TMJOA was investigated and validated in a mouse model. RESULTS: The expression level of CircACAP2 was markedly reduced in OA cartilage and directly related to chondrocyte proliferation and apoptosis as well as ECM metabolism in the cartilage. CircACAP2 functioned in chondrocytes via targeting miR-21-5p and PLAG1. Overexpressing of CircACAP2 alleviated TMJOA in mouse models. CONCLUSIONS: The present study unveiled that CircACAP2/miR-21-5p/PLAG1 axis may play an important regulatory role in TMJOA progression, which may highlight a potentially effective intervention and therapeutic strategy for the treatment of TMJOA.

Floral Volatile Organic Compounds Change the Composition and Function of the Endophytic Fungal Community in the Flowers of Osmanthus fragrans.

Endophytic fungi in flowers influence plant health and reproduction. However, whether floral volatile organic compounds (VOCs) affect the composition and function of the endophytic fungal community remains unclear. Here, gas chromatography-mass spectrometry (GC-MS) and high-throughput sequencing were used to explore the relationship between floral VOCs and the endophytic fungal community during different flower development stages in Osmanthus fragrans 'Rixiang Gui'. The results showed that the composition of the endophytic fungal community and floral VOCs shifted along with flowering development. The highest and lowest α diversity of the endophytic fungal community occurred in the flower fading stage and full blooming stage, respectively. The dominant fungi, including Dothideomycetes (class), Pleosporales (order), and Neocladophialophora, Alternaria, and Setophoma (genera), were enriched in the flower fading stage and decreased in the full blooming stage, demonstrating the enrichment of the Pathotroph, Saprotroph, and Pathotroph-Saprotroph functions in the flower fading stage and their depletion in the full blooming stage. However, the total VOC and terpene contents were highest in the full blooming stage and lowest in the flower fading stage, which was opposite to the α diversity of the endophytic fungal community and the dominant fungi during flowering development. Linalool, dihydro-ß-ionone, and trans-linalool oxide(furan) were key factors affecting the endophytic fungal community composition. Furthermore, dihydro-ß-ionone played an extremely important role in inhibiting endophytic fungi in the full blooming stage. Based on the above results, it is believed that VOCs, especially terpenes, changed the endophytic fungal community composition in the flowers of O. fragrans 'Rixiang Gui'. These findings improve the understanding of the interaction between endophytic fungi and VOCs in flowers and provide new insight into the mechanism of flower development.

Long-term response of the microbial community to the degradation of DOC released from Undaria pinnatifida.

With the aim to study the mechanism underlying the macroalgal carbon sequestration driven by microbes, we investigated the microbial community using metagenomics methods and its long-term degradation of dissolved organic carbon (DOC) derived from Undaria pinnatifida. It was observed that after removing U. pinnatifida, the concentration of the DOC decreased significantly (p < 0.05) within 4 days. Over a period of 120 days of degradation, the concentration of remaining DOC (26%) remained stable. The succession of microbial community corresponded to the three stages of DOC concentration variation. Moreover, the structure of microbes community and its metabolic function exhibited evident patterns of succession. The concentration of DOC was correlated negatively with the abundances of Planctomycetaceae (p < 0.01), and was correlated positively with the abundances of Roseobacteraceae and Rhodobacteraceae (p < 0.01). In addition, the metabolic pathways related to "Glycolysis/Gluconeogenesis", "Alanine, aspartate, and glutamate metabolism", "Citrate cycle (TCA cycle)" and "Tryptophan metabolism" was significantly correlated with the variations in DOC concentration (p < 0.05). These findings indicate that the variation in the DOC concentration was closely linked to the succession of Planctomycetaceae, Roseobacteraceae, Rhodobacteraceae, and the degradation of DOC derived from U. pinnatifida appeared to be influenced by metabolic functions.

All-potassium channel CRISPR screening reveals a lysine-specific pathway of insulin secretion.

OBJECTIVE: Genome-scale CRISPR-Cas9 knockout coupled with single-cell RNA sequencing (scRNA-seq) has been used to identify function-related genes. However, this method may knock out too many genes, leading to low efficiency in finding genes of interest. Insulin secretion is controlled by several electrophysiological events, including fluxes of KATP depolarization and K+ repolarization. It is well known that glucose stimulates insulin secretion from pancreatic ß-cells, mainly via the KATP depolarization channel, but whether other nutrients directly regulate the repolarization K+ channel to promote insulin secretion is unknown. METHODS: We used a system involving CRISPR-Cas9-mediated knockout of all 83 K+ channels and scRNA-seq in a pancreatic ß cell line to identify genes associated with insulin secretion. RESULTS: The expression levels of insulin genes were significantly increased after all-K+ channel knockout. Furthermore, Kcnb1 and Kcnh6 were the two most important repolarization K+ channels for the increase in high-glucose-dependent insulin secretion that occurred upon application of specific inhibitors of the channels. Kcnh6 currents, but not Kcnb1 currents, were reduced by one of the amino acids, lysine, in both transfected cells, primary cells and mice with ß-cell-specific deletion of Kcnh6. CONCLUSIONS: Our function-related CRISPR screen with scRNA-seq identifies Kcnh6 as a lysine-specific channel.

Metabolites from Lysobacter gummosus YMF3.00690 Against Meloidogyne javanica.

The strains in Lysobacter spp. have the potential to control plant-parasitic nematodes. In our experiment, L. gummosus YMF3.00690 showed antagonistic effects against plant root-knot nematode. Nine metabolites were isolated and identified from cultures of L. gummosus YMF3.00690, of which compound 1 was identified as a new metabolite tetrahydro-4,4,6-trimethyl-6-[(tetrahydro-6,6-dimethyl-2-oxo-4(1H)-pyrimidinylidene) methyl]-2(1H)-pyrimidinone. The activity assay showed that two compounds, 5-(hydroxymethyl)-1H-pyrrole-2-carbaldehyde (2) and 1H-pyrrole-2-carboxylic acid (3), had nematicidal activities against Meloidogyne javanica with mortalities of 69.93 and 90.54% at 400 ppm for 96 h, respectively. These two compounds were further tested for the inhibition activity of eggs hatching, and compound 3 showed a significant inhibition rate of 63.36% at 50 ppm for 48 h. In the chemotactic activity assay, three compounds (1 to 3) were found to have concentration-dependent chemotactic activity, of which compound 1 showed attractive activity. This experiment explored the active metabolites of L. gummosus YMF3.00690 against M. javanica and laid the foundation for biopesticide development.

B-Site Co-Doping Coupled with Additive Passivation Pushes the Efficiency of Pb-Sn Mixed Inorganic Perovskite Solar Cells to Over 17.

Pb-Sn mixed inorganic perovskite solar cells (PSCs) have garnered increasing interest as a viable solution to mitigate the thermal instability and lead toxicity of hybrid lead-based PSCs. However, the relatively poor structural stability and low device efficiency hinder its further development. Herein, high-performance manganese (Mn)-doped Pb-Sn-Mn-based inorganic perovskite solar cells (PSCs) are successfully developed by introducing Benzhydroxamic Acid (BHA) as multifunctional additive. The incorporation of smaller divalent Mn cations contributes to a contraction of the perovskite crystal, leading to an improvement in structural stability. The BHA additive containing a reductive hydroxamic acid group (O═C-NHOH) not only mitigates the notorious oxidation of Sn2+ but also interacts with metal ions at the B-site and passivates related defects. This results in films with high crystallinity and low defect density. Moreover, the BHA molecules tend to introduce a near-vertical dipole moment that parallels the built-in electric field, thus facilitating charge carrier extraction. Consequently, the resulting device delivers a champion PCE as high as 17.12%, which represents the highest reported efficiency for Pb-Sn-based inorganic PSCs thus far. Furthermore, the BHA molecule provides an in situ encapsulation of the perovskite grain boundary, resulting in significant enhancement of device air stability.

De novo transcriptional analysis of the response to starvation stress in the white ridgetail prawn, Exopalaemon carinicauda.

To study the mechanism of the biomolecular response in Exopalaemon carinicauda to starvation stress, we subjected muscle tissue RNA samples from four stress points, including 0 d(control group), 10 d, 20 d, and 30 d, to starvation stress on white ridgetail prawn with a body weight of 1.41 + 0.42 g, aquaculture water temperature of 23-25 °C, salinity of 26, dissolved oxygen ≥5 mg/L, and pH 8-8.5, Then performed de novo transcriptome assembly and gene expression analysis using BGISEQ-500 with a tag-based digital gene expression (DGE) system. By de novo assembling at the four times, we obtained 28,167, 21,115, 24,497, and 27,080 reads, respectively. The results showed that the stress at 10 d led to no significant difference in the expressed genes, while the stress at 20 d and 30 d showed a significant increase (or decrease) in the expression of 97 (276) and 143 (410) genes, respectively, which were involved in 8 different metabolic pathways. In addition, we detected 2647 unigene transcription factors. Eleven upregulated and sixteen downregulated genes from the different starvation stress groups were choose to verify the reliability of the transcriptome data, and the results showed that the expression trends of these genes were consistent with the results shown by the transcriptome. The analysis of the experimental data and our discussion of the response mechanism of white ridgetail prawn under starvation stress provides a foundation for further screening of the key genes of starvation stress and may help to elucidate their functions.

An ultra-broadband frequency-agile terahertz perfect absorber with perturbed MoS2 plasmon modes.

Multidomain dynamic manipulations for terahertz (THz) absorbers usually necessitate the orchestrated actions of several active elements, inevitably complicating the structural design and elongating the modulation time. Herein, we utilize the coupling between the total reflection prism and electrically-driven MoS2 to activate a tight field confinement in a deep-subwavelength interlayer, ultimately achieving frequency-agile absorption adjustments only with a gate voltage. Theoretical and simulation analysis results indicate that the redistributed electric field and susceptible dielectric response are attributed to the limited spatial near-field perturbation of surface plasmon resonances. We also demonstrate that perturbed MoS2 plasmon modes promote the formation of dual-phase singularities, significantly suppressing the attenuation of the absorption amplitude as large-scale frequency shifts, thereby extending the relative tuning range (WRTR) to 175.4%. These findings offer an efficient approach for expanding the horizon of THz absorption applications that require ultra-broadband and swift-response capabilities.

[Medicinal plant resources in Inner Mongolia autonomous region of China and Mongolia: a comparative study].

Inner Mongolia autonomous region of China and Mongolia are the primary regions where Chinese and Mongolian medicine and its medicinal plant resources are distributed. In this study, 133 families, 586 genera, and 1 497 species of medicinal plants in Inner Mongolia as well as 62 families, 261 genera, and 467 species of medicinal plants in Mongolia were collected through field investigation, specimen collection and identification, and literature research. And the species, geographic distribution, and influencing factors of the above medicinal plants were analyzed. The results revealed that there were more plant species utilized for medicinal reasons in Inner Mongolia than in Mongolia. Hotspots emerged in Hulunbuir, Chifeng, and Tongliao of Inner Mongolia, while there were several hotspots in Eastern province, Sukhbaatar province, Gobi Altai province, Bayankhongor province, Middle Gobi province, Kobdo province, South Gobi province, and Central province of Mongolia. The interplay of elevation and climate made a non-significant overall contribution to the diversity of plant types in Inner Mongolia and Mongolia. The contribution of each factor increased significantly when the vegetation types of Inner Mongolia and Mongolia were broadly divided into forest, grassland and desert. Thus, the distribution of medicinal plant resources and vegetation cover were jointly influenced by a variety of natural factors such as topography, climate and interactions between species, and these factors contributed to and constrained each other. This study provided reference for sustainable development and rational exploitation of medicinal plant resources in future.

Screening and verifying the mutations in the LDLR and APOB genes in a Chinese family with familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder. The primary objective of this study was to identify the major pathogenic mutations in a Chinese family with FH. METHODS: Whole-genome sequencing (WGS) was used to identify variants of FH-related genes, including low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9). Bioinformatics software was used to predict signal peptides, transmembrane structures, and spatial construction information of the mutated sequences. Western blotting was performed on the mutant protein to determine the presence of the major structural domains of the LDLR. The PCSK9 and APOB genes were screened and analyzed. Moreover, the proband and his brother were treated with a PCSK9 inhibitor for 1 year, and the effect of the treatment on lipid levels was assessed. RESULTS: WGS revealed two potentially pathogenic mutations in the LDLR gene. One was a novel mutation, c.497delinsGGATCCCCCAGCTGCATCCCCCAG (p. Ala166fs), and the other was a known pathogenic mutation, c.2054C>T (p. Pro685Leu). Bioinformatics prediction and in vitro experiments revealed that the novel mutation could not be expressed on the cell membrane. Numerous gene variants were identified in the APOB gene that may have a significant impact on the family members with FH. Thus, it is suggested that the severe manifestation of FH in the proband primarily resulted from the cumulative genetic effects of variants in both LDLR and APOB. However, a subsequent study indicated that treatment with a PCSK9 inhibitor (Evolocumab) did not significantly reduce the blood lipid levels in the proband or his brother. CONCLUSIONS: The cumulative effect of LDLR and APOB variants was the primary cause of elevated blood lipid levels in this family. However, PCSK9 inhibitor therapy did not appear to be beneficial for the proband. This study emphasizes the importance of genetic testing in determining the most suitable treatment options for patients with FH.