Dynamic surface reconstruction of individual gold nanoclusters by using a co-reactant enables color-tunable electrochemiluminescence.

Here we report for the first time the phenomenon of continuously color-tunable electrochemiluminescence (ECL) from individual gold nanoclusters (Au NCs) confined in a porous hydrogel matrix by adjusting the concentration of the co-reactant. Specifically, the hydrogel-confined Au NCs exhibit strong dual-color ECL in an aqueous solution with triethylamine (TEA) as a co-reactant, with a record-breaking quantum yield of 95%. Unlike previously reported Au NCs, the ECL origin of the hydrogel-confined Au NCs is related to both the Au(0) kernel and the Au(i)-S surface. Surprisingly, the surface-related ECL of Au NCs exhibits a wide color-tunable range of 625-829 nm, but the core-related ECL remains constant at 489 nm. Theoretical and experimental studies demonstrate that the color-tunable ECL is caused by the dynamic surface reconstruction of Au NCs and TEA radicals. This work opens up new avenues for dynamically manipulating the ECL spectra of core-shell emitters in biosensing and imaging research.

The Role of Protein Degradation in Estimation Postmortem Interval and Confirmation of Cause of Death in Forensic Pathology: A Literature Review.

It is well known that proteins are important bio-macromolecules in human organisms, and numerous proteins are widely used in the clinical practice, whereas their application in forensic science is currently limited. This limitation is mainly attributed to the postmortem degradation of targeted proteins, which can significantly impact final conclusions. In the last decade, numerous methods have been established to detect the protein from a forensic perspective, and some of the postmortem proteins have been applied in forensic practice. To better understand the emerging issues and challenges in postmortem proteins, we have reviewed the current application of protein technologies at postmortem in forensic practice. Meanwhile, we discuss the application of proteins in identifying the cause of death, and postmortem interval (PMI). Finally, we highlight the interpretability and limitations of postmortem protein challenges. We believe that utilizing the multi-omics method can enhance the comprehensiveness of applying proteins in forensic practice.

Lactobacillus acidophilus Expressing Murine Rotavirus VP8 and Mucosal Adjuvants Induce Virus-Specific Immune Responses.

Rotavirus diarrhea-associated illness remains a major cause of global death in children under five, attributable in part to discrepancies in vaccine performance between high- and low-middle-income countries. Next-generation probiotic vaccines could help bridge this efficacy gap. We developed a novel recombinant Lactobacillus acidophilus (rLA) vaccine expressing rotavirus antigens of the VP8* domain from the rotavirus EDIM VP4 capsid protein along with the adjuvants FimH and FliC. The upp-based counterselective gene-replacement system was used to chromosomally integrate FimH, VP8Pep (10 amino acid epitope), and VP8-1 (206 amino acid protein) into the L. acidophilus genome, with FliC expressed from a plasmid. VP8 antigen and adjuvant expression were confirmed by flow cytometry and Western blot. Rotavirus naïve adult BALB/cJ mice were orally immunized followed by murine rotavirus strain ECWT viral challenge. Antirotavirus serum IgG and antigen-specific antibody-secreting cell responses were detected in rLA-vaccinated mice. A day after the oral rotavirus challenge, fecal antigen shedding was significantly decreased in the rLA group. These results indicate that novel rLA constructs expressing VP8 can be successfully constructed and used to generate modest homotypic protection from rotavirus challenge in an adult murine model, indicating the potential for a probiotic next-generation vaccine construct against human rotavirus.

Exploration of 2D and 3D-QSAR analysis and docking studies for novel dihydropteridone derivatives as promising therapeutic agents targeting glioblastoma.

Background: Dihydropteridone derivatives represent a novel class of PLK1 inhibitors, exhibiting promising anticancer activity and potential as chemotherapeutic drugs for glioblastoma. Objective: The aim of this study is to develop 2D and 3D-QSAR models to validate the anticancer activity of dihydropteridone derivatives and identify optimal structural characteristics for the design of new therapeutic agents. Methods: The Heuristic method (HM) was employed to construct a 2D-linear QSAR model, while the gene expression programming (GEP) algorithm was utilized to develop a 2D-nonlinear QSAR model. Additionally, the CoMSIA approach was introduced to investigate the impact of drug structure on activity. A total of 200 novel anti-glioma dihydropteridone compounds were designed, and their activity levels were predicted using chemical descriptors and molecular field maps. The compounds with the highest activity were subjected to molecular docking to confirm their binding affinity. Results: Within the analytical purview, the coefficient of determination (R2) for the HM linear model is elucidated at 0.6682, accompanied by an R2 cv of 0.5669 and a residual sum of squares (S2) of 0.0199. The GEP nonlinear model delineates coefficients of determination for the training and validation sets at 0.79 and 0.76, respectively. Empirical modeling outcomes underscore the preeminence of the 3D-QSAR model, succeeded by the GEP nonlinear model, whilst the HM linear model manifested suboptimal efficacy. The 3D paradigm evinced an exemplary fit, characterized by formidable Q2 (0.628) and R2 (0.928) values, complemented by an impressive F-value (12.194) and a minimized standard error of estimate (SEE) at 0.160. The most significant molecular descriptor in the 2D model, which included six descriptors, was identified as "Min exchange energy for a C-N bond" (MECN). By combining the MECN descriptor with the hydrophobic field, suggestions for the creation of novel medications were generated. This led to the identification of compound 21E.153, a novel dihydropteridone derivative, which exhibited outstanding antitumor properties and docking capabilities. Conclusion: The development of 2D and 3D-QSAR models, along with the innovative integration of contour maps and molecular descriptors, offer novel concepts and techniques for the design of glioblastoma chemotherapeutic agents.

Guillain Barré syndrome after combined diphtheria, tetanus, and acellular pertussis (DTaP) vaccine: A rare pediatric case report and review of literature.

A 20-month-old girl was diagnosed with Guillain - Barré syndrome (GBS) based on progressive muscle weakness, areflexia, and albuminocytologic dissociation of the cerebrospinal fluid. Despite timely and systematic treatment, she eventually became paralyzed. There is a temporal correlation between the girl's GBS and the DTaP vaccination, but the exact causal relationship between the two is still debatable. Furthermore, we summarized clinical features of other 45 published GBS cases after DTP vaccines (or vaccine substances containing tetanus) through a systematic review. The mean onset age, sex distribution, onset time after vaccination, detection of antiganglioside antibodies, and other basic clinical features of GBS after DTP vaccination (or vaccine substances containing tetanus) were analyzed. The temporal pattern of GBS after vaccination was similar to that of GBS after infection. Herein, we report this rare case of presumptive pediatric GBS after DTaP vaccination and review similar cases to draw the attention of medical personnel to similar events after vaccination. An association between DTP vaccines and GBS has been proposed, and the causal relationship between these two incidents are worthy further exploration. Moreover, surveillance and vigilance for GBS after vaccination are highly recommended.

Genome-Wide Comparative Analysis of Lactiplantibacillus pentosus Isolates Autochthonous to Cucumber Fermentation Reveals Subclades of Divergent Ancestry.

Lactiplantibacillus pentosus, commonly isolated from commercial cucumber fermentation, is a promising candidate for starter culture formulation due to its ability to achieve complete sugar utilization to an end pH of 3.3. In this study, we conducted a comparative genomic analysis encompassing 24 L. pentosus and 3 Lactiplantibacillus plantarum isolates autochthonous to commercial cucumber fermentation and 47 lactobacillales reference genomes to determine species specificity and provide insights into niche adaptation. Results showed that metrics such as average nucleotide identity score, emulated Rep-PCR-(GTG)5, computed multi-locus sequence typing (MLST), and multiple open reading frame (ORF)-based phylogenetic trees can robustly and consistently distinguish the two closely related species. Phylogenetic trees based on the alignment of 587 common ORFs separated the L. pentosus autochthonous cucumber isolates from olive fermentation isolates into clade A and B, respectively. The L. pentosus autochthonous clade partitions into subclades A.I, A.II, and A.III, suggesting substantial intraspecies diversity in the cucumber fermentation habitat. The hypervariable sequences within CRISPR arrays revealed recent evolutionary history, which aligns with the L. pentosus subclades identified in the phylogenetic trees constructed. While L. plantarum autochthonous to cucumber fermentation only encode for Type II-A CRISPR arrays, autochthonous L. pentosus clade B codes for Type I-E and L. pentosus clade A hosts both types of arrays. L. pentosus 7.8.2, for which phylogeny could not be defined using the varied methods employed, was found to uniquely encode for four distinct Type I-E CRISPR arrays and a Type II-A array. Prophage sequences in varied isolates evidence the presence of adaptive immunity in the candidate starter cultures isolated from vegetable fermentation as observed in dairy counterparts. This study provides insight into the genomic features of industrial Lactiplantibacillus species, the level of species differentiation in a vegetable fermentation habitat, and diversity profile of relevance in the selection of functional starter cultures.

A harmful MYH11 variant detected in a family with thoracic aortic dissection and patent ductus arteriosus.

Thoracic aortic dissection (TAD) is an important cause of sudden cardiac death and is characterized by high morbidity, mortality, and a poor prognosis. Patent ductus arteriosus (PDA) is a common congenital heart disease. The pathogenesis of both TAD and PDA has been reported to be related to genetic factors. The MYH11 gene, which encodes myosin heavy chain 11, has been reported in individuals with both TAD and PDA. Herein, we first detected a harmful MYH11 missense variant (c. T3728C, p. L1243P) in a TAD and PDA family. This missense variant co-segregated with the TAD/PDA phenotype in this family of four individuals, providing evidence of its harmfulness. Histopathological examinations revealed the presence of fragmented, broken, and lessened elastic fibers and the deposition of proteoglycans in the median of aortic dissection. Moreover, the immunofluorescence results showed that the labeled MYH11 protein in the tissue of the aortic dissection was weaker than that in the normal aorta. We present this familial case to stress the necessity of postmortem genetic testing in such cases among forensic practices. Identifying those culprit gene variants can direct effective genetic counseling and personalized health management in family members (especially first-degree relatives) with high-risk genotypes.

Fatal hyperthermia among children in school buses: Analysis of 47 cases in China.

The school bus is an important mode of transportation for school-age children, and safety-related issues are always the focus of public concern. Fatal hyperthermia occurring in school buses is an uncommon type of school bus-related injury. An internet search using Chinese internet search engines based on various combinations of keywords including 'vehicles', 'school bus', 'children or babies', 'hyperthermia or heat stroke' and 'death' was performed. Forty-seven cases of fatal hyperthermia in children which occurred in school buses were retrieved in the study. High ambient temperature, younger age and poor management were identified as risk factors. There is a lack of consensus regarding the legal nature and liability for fatal hyperthermia occurring in school buses. Pre-employment education should be focused on awareness of the dangers of leaving children alone in a school bus. Most importantly, the relevant legislation and regulations on school buses should be implemented. An internal alarm-raising system is recommended to avoid this kind of tragedy.

Identification and Quantification of 5-Methylcytosine and 5-Hydroxymethylcytosine on Random DNA Sequences by a Nanoconfined Electrochemiluminescence Platform.

5-Methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are two of the most abundant epigenetic marks in mammalian genomes, and it has been proven that these dual epigenetic marks give a more accurate prediction of recurrence and survival in cancer than the individual mark. However, due to the similar structure and low expression of 5mC and 5hmC, it is challenging to distinguish and quantify the two methylation modifications. Herein, we employed the ten-eleven translocation family dioxygenases (TET) to convert 5mC to 5hmC via a specific labeling process, which realized the identification of the two marks based on a nanoconfined electrochemiluminescence (ECL) platform combined with the amplification strategy of a recombinase polymerase amplification (RPA)-assisted CRISPR/Cas13a system. Benefiting from the TET-mediated conversion strategy, a highly consistent labeling pathway was developed for identifying dual epigenetic marks on random sequence, which reduced the system error effectively. The ECL platform was established via preparing a carbonized polymer dot embedded SiO2 nanonetwork (CPDs@SiO2), which exhibited higher ECL efficiencies and more stable ECL performance compared to those of the scattered emitters due to the nanoconfinement-enhanced ECL effect. The proposed bioanalysis strategy could be employed for the identification and quantification of 5mC and 5hmC in the range from 100 aM to 100 pM, respectively, which provides a promising tool for early diagnosis of diseases associated with abnormal methylation.

AgInZnS quantum dots as anodic emitters with strong and stable electrochemiluminescence for biosensing application.

Quantum dots (QDs) have become promising electrochemiluminescence (ECL) emitters with high quantum yield and size-tunable luminescence. However, most QDs generate strong ECL emission at the cathode, developing anodic ECL-emitting QDs with excellent performance is challenging. In this work, low-toxic quaternary AgInZnS QDs synthesized by a one-step aqueous phase method were used as novel anodic ECL emitters. AgInZnS QDs exhibited strong and stable ECL emission and a low excitation potential, which could avoid the side reaction of oxygen evolution. Furthermore, AgInZnS QDs displayed high ECL efficiency (ΦECL) of 5.84, taking the ΦECL of Ru(bpy)32+/tripropylamine (TPrA) ECL system as 1. Compared to AgInS2 QDs without Zn doping and traditional anode luminescent CdTe QDs, the ECL intensity of AgInZnS QDs was 1.62 times and 3.64 times higher than that of AgInS2 QDs and CdTe QDs, respectively. As a proof-of-concept, we further designed an "on-off-on" ECL biosensor for detecting microRNA-141 based on a dual isothermal enzyme-free strand displacement reaction (SDR), which not only to achieve the cyclic amplification of the target and ECL signal, but also to construct a switch of the biosensor. The ECL biosensor had a wide linear range from 100 aM to 10 nM with a low detection limit of 33.3 aM. Together, the constructed ECL sensing platform is a promising tool for rapid and accurate diagnosis of clinical diseases.

Bile salt hydrolases shape the bile acid landscape and restrict Clostridioides difficile growth in the murine gut.

Bile acids (BAs) mediate the crosstalk between human and microbial cells and influence diseases including Clostridioides difficile infection (CDI). While bile salt hydrolases (BSHs) shape the BA pool by deconjugating conjugated BAs, the basis for their substrate selectivity and impact on C. difficile remain elusive. Here we survey the diversity of BSHs in the gut commensals Lactobacillaceae, which are commonly used as probiotics, and other members of the human gut microbiome. We structurally pinpoint a loop that predicts BSH preferences for either glycine or taurine substrates. BSHs with varying specificities were shown to restrict C. difficile spore germination and growth in vitro and colonization in pre-clinical in vivo models of CDI. Furthermore, BSHs reshape the pool of microbial conjugated bile acids (MCBAs) in the murine gut, and these MCBAs can further restrict C. difficile virulence in vitro. The recognition of conjugated BAs by BSHs defines the resulting BA pool, including the expansive MCBAs. This work provides insights into the structural basis of BSH mechanisms that shape the BA landscape and promote colonization resistance against C. difficile.

Two new compounds from edible mushroom Sarcomyxa edulis.

Chemical investigation of the edible mushroom Sarcomyxa edulis led to the isolation of one new highly degraded sterol (1), and one new ß-carboline alkaloid (2), along with nine known compounds (3-11) for the first time from this mushroom. The structures of new compounds were elucidated using HR-ESI-MS data and NMR spectroscopy. In addition, anti-inflammatory activity of new compounds was evaluated against lipopolysaccharide-induced NO production in RAW 264.7 macrophages. Compound 2 exhibited a good anti-inflammatory activity with IC50 value of 9.88 ± 0.48 µM, and compound 1 exhibited a weak inhibitory effect with IC50 value of 71.36 ± 5.11 µM.

Application of P/VB staining to identify antemortem injury in a decomposed cadaver.

It is challenging in forensic pathology to determine whether an injury is formed antemortem or postmortem in putrefied tissues. Hematoxylin-eosin (HE) staining fails to work in highly decomposed corpses. Ponceau/Victoria blue B (P/VB) staining is usually used to show collagen fibers and muscles. Here, we used P/VB to show antemortem laceration injury on the scalp in a severely decomposed cadaver 1.5 years after death. This method is a simple and alternative method for the diagnosis of antemortem injury.

The Structural Characterization and Immunomodulatory Activity of Polysaccharides from Pleurotus abieticola Fruiting Bodies.

Polysaccharides obtained from mushrooms have been reported to possess immunomodulatory properties. In this study, a water-soluble polysaccharide was purified from the fruiting bodies of Pleurotus abieticola, entitled PAPS1. After its composition and structural analysis, the immunomodulatory activity was investigated in immunosuppressed mice induced by cyclophosphamide (CTX) at a dosage of 70 mg/kg by intraperitoneal injection for 7 days. After 28 days of intragastric administration, PAPS1 alleviated cyclophosphamide (CTX)-induced histopathological damage and increased the expressions of splenic CD4, CD8, CD56 and IgM in the serums of immunosuppressed mice. PAPS1 suppressed the oxidative stress indicated by preventing the increases in ROS and MDA levels. According to the intestinal microflora analysis, PAPS1 regulated 11 bacteria at the gene level, including Helicobacter and Paraprevotella, which are related to immunity and oxidative capacity. Compared with CTX-treated mice, significant increases in immune-related cytokines, such as interleukin (IL)-2, IL-6 and IL-12 in the serums of mice treated with PAPS1, were observed. Finally, PAPS1 can strongly increase the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream proteins. In conclusion, PAPS1-boosted immunity may be related to its suppression on oxidative stress via enhancing the activity of Nrf2 signaling. Thus, PAPS1 can be investigated as a candidate for immunomodulatory therapy.

Wireframe Orbit-Accelerated Bipedal DNA Walker for Electrochemiluminescence Detection of Methyltransferase Activity.

In spite of the DNA walkers executing the signal accumulation task in the process of moving along the predetermined paths, the enhancement of walking dynamics and walking path controllability are still challenging due to the unprogrammed arrangements of DNA orbits. Taking these dilemmas into account, a bipedal DNA walker was designed skillfully by the virtue of wireframe orbits assembled by DNA cubes in order, which improved the efficiency and the continuity of walking. It could be attributed to the fact that both the contact chance and the dynamic interaction between walking strands and designated orbits were beneficial to minimize the possibility of derailment and improve the accumulation of signal. In addition, the hollow titanium dioxide nanospheres coated with rubrene (Rub@TiO2 NSs) were prepared by the etching of inner silicon dioxide nanoparticles (SiO2 NPs) to regulate the distribution pattern of rubrene (Rub) molecules and expose more electrochemically active sites for high-efficient electrochemiluminescence (ECL). Benefiting by the pore confinement-enhanced ECL, the electron and mass transfer was significantly accelerated because of the hollow structure of Rub@TiO2 NSs. Subsequently, endogenous dissolved oxygen as the coreactant and palladium nanoparticles (Pd NPs) as the coreaction accelerator were employed to constitute a ternary ECL system with explosive signal response. Combining with this ECL platform, the bipedal walker activated by the target can autonomously and directionally move on the DNA wireframe orbits to release the quenching probes continuously. In this way, the biosensor displayed a low detection limit (2.30 × 10-8 U·mL-1) and a wide linear range (1.0 × 10-7 to 1.0 × 10-1 U·mL-1) for the sensitive detection of Dam methyltransferase (Dam MTase) activity. Therefore, a novel strategy for the accurate quantification of epigenetic targets was developed by virtue of improving the walking dynamics of DNA walker and amplifying the ECL of Rub molecules.

Genomic and epigenetic landscapes drive CRISPR-based genome editing in Bifidobacterium.

Bifidobacterium is a commensal bacterial genus ubiquitous in the human gastrointestinal tract, which is associated with a range of health benefits. The advent of CRISPR-based genome editing technologies provides opportunities to investigate the genetics of important bacteria and transcend the lack of genetic tools in bifidobacteria to study the basis for their health-promoting attributes. Here, we repurpose the endogenous type I-G CRISPR-Cas system and adopt an exogenous CRISPR base editor for genome engineering in B. animalis subsp. lactis, demonstrating that both genomic and epigenetic contexts drive editing outcomes across strains. We reprogrammed the endogenous type I-G system to screen for naturally occurring large deletions up to 27 kb and to generate a 500-bp deletion in tetW to abolish tetracycline resistance. A CRISPR-cytosine base editor was optimized to install C•G-to-T•A amber mutations to resensitize multiple B. lactis strains to tetracycline. Remarkably, we uncovered epigenetic patterns that are distributed unevenly among B. lactis strains, despite their genomic homogeneity, that may contribute to editing efficiency variability. Insights were also expanded to Bifidobacterium longum subsp. infantis to emphasize the broad relevance of these findings. This study highlights the need to develop individualized CRISPR-based genome engineering approaches for distinct bacterial strains and opens avenues for engineering of next generation probiotics.

Morpho-Molecular Evidence Reveals Four Novel Species of Gymnopus (Agaricales, Omphalotaceae) from China.

Nine collections of gymnopoid fungi were studied based on morpho-molecular characteristics. The macromorphology was made according to the photograph of fresh basidiomata and field notes, while the micromorphology was examined via an optical microscope. Simultaneously, the phylogenetic analyses were performed by maximum likelihood and Bayesian inference methods based on a combined dataset of nrITS1-nr5.8S-nrITS2-nrLSU sequences. Integrated analysis of these results was therefore, G. efibulatus belonging to sect. Androsacei, G. iodes and G. sinopolyphyllus belonging to sect. Impudicae and G. strigosipes belonging to sect. Levipedes are proposed as new to science. The detailed descriptions, colour photos of basidiomata and line-drawings of microscopic structures are provided. The comparisons with closely related species and a key to known species of Gymnopus s. str. reported with morpho-molecular evidence in China is also given.

A bibliometric analysis of the cause of sudden unexplained death in forensic medicine: Research trends, hot spots and prospects.

To better understand the cause of sudden unexplained death, our group evaluated the scientific results of related studies in a global context. A systematic search of the Web of Science, PubMed and MEDLINE databases identified 2001 studies related to this field published from 1997 to 2020. The studies were analyzed using bibliometric methods, and statistical maps were drawn to explore research trends and research frontiers. Sudden cardiac death and sudden unexpected epilepsy death were the two major causes of sudden unexplained deaths. With the rapid development of high-throughput sequencing technology and bioinformatics in the past 10 years, molecular autopsy has become an effective research method as well as a research hotspot for exploring the cause of sudden unexplained deaths. However, molecular autopsy is underutilized in the investigation of sudden unexpected death in epilepsy. Developing standardized guidelines for diagnostic strategies for the deceased and their families, expanding the screening of mutation spectrum of related diseases, studying the association between variants and diseases in complex genetic diseases, and improving variants interpretation guidelines and disease sequencing databases are future research directions.

Rare Variants and Polymorphisms of FBN1 Gene May Increase the Risk of Non-Syndromic Aortic Dissection.

Aortic dissection (AD) is a cardiovascular disease characterized by high mortality and poor prognosis. Although FBN1 is associated with syndromic AD, its association with non-syndromic AD remains unclear. In this study, DNA samples from 90 Chinese individuals with non-syndromic AD (60 Stanford A, 30 Stanford B types) were analyzed to determine the relationship between diverse genotypes of the FBN1 gene and non-syndromic AD. Eleven pathogenic/likely pathogenic variants (1 novel) were identified in 12.2% of patients with non-syndromic AD. Patients with positive variants suffered from AD at a younger age than those in the negative variant group. Among the six positive missense mutations associated with cysteine residue hosts, four (66.7%) were Stanford A AD, whereas two (33.3%) were Stanford B AD. Three (100%) positive splicing/truncation variant hosts were Stanford A AD. The splicing/truncation variants and missense variants involving cysteine residues in the FBN1 gene increased the risk of Stanford A AD. Ten common SNPs that increased susceptibility to AD were identified. In particular, five SNPs were detected significantly in Stanford A AD, whereas another four SNPs were significantly detected in Stanford B AD. These significant variants can function as biomarkers for the identification of patients at risk for AD. Our findings have the potential to broaden the database of positive mutations and common SNPs of FBN1 in non-syndromic AD among the Chinese population.

Postmortem detection of COL gene family variants in two aortic dissection cases.

Aortic dissection (AD) usually remains undiagnosed, but its manifestation is abrupt and is associated with high morbidity and poor prognosis, leading to sudden cardiac death. Variants in COL family genes are associated with AD. In case 1, a 32-year-old Chinese man was admitted to the hospital with complaints of abdominal pain and died on the next day. In case 2, a 36-year-old Chinese woman was admitted to the hospital because of waist pain and died the next afternoon. According to autopsy findings, the cause of death in both cases was an acute cardiac tamponade, which was attributed to AD rupture. Whole-exome sequencing was performed on the blood collected from the hearts of the two deceased patients. Positive variants in COL family genes were found in both cases, without positive variants in other AD-associated genes. In case 1, a novel, likely pathogenic, missense variant was identified in COL6A1. In case 2, we identified one novel, likely pathogenic, frameshift deletion in COL23A1 and one novel, likely pathogenic, missense mutation in COL1A2. Based on these two cases, physicians should consider the role and significance of COL family gene mutations in AD in young patients. Furthermore, molecular anatomy is clearly necessary and significant in cases of sudden cardiac death attributed to AD, particularly in younger individuals.