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Abstract Background Deletion or duplication in the DMD gene is one of the most common causes of Duchenne and Becker muscular dystrophy (DMD/BMD). However, the pathogenicity of complex rearrangements involving DMD, especially segmental duplications with unknown breakpoints, is not well understood. This study aimed to evaluate the structure, pattern, and potential impact of rearrangements involving DMD duplication. Methods Two families with DMD segmental duplications exhibiting phenotypical differences were recruited. Optical genome mapping (OGM) was used to explore the cryptic pattern of the rearrangements. Breakpoints were validated using long-range polymerase chain reaction combined with next-generation sequencing and Sanger sequencing. Results A multi-copy duplication involving exons 64–79 of DMD was identified in Family A without obvious clinical symptoms. Family B exhibited typical DMD neuromuscular manifestations and presented a duplication involving exons 10–13 of DMD. The rearrangement in Family A involved complex in-cis tandem repeats shown by OGM but retained a complete copy (reading frame) of DMD inferred from breakpoint validation. A reversed insertion with a segmental repeat was identified in Family B by OGM, which was predicted to disrupt the normal structure and reading frame of DMD after confirming the breakpoints. Conclusions Validating breakpoint and rearrangement pattern is crucial for the functional annotation and pathogenic classification of genomic structural variations. OGM provides valuable insights into etiological analysis of DMD/BMD and enhances our understanding for cryptic effects of complex rearrangements.

During sudden stratospheric warming (SSW) events, significant modifications occur, not only in the neutral atmosphere, but also in the ionosphere. Specifically, sporadic E layers in the mesosphere and lower thermosphere regions significantly disrupt satellite communication. Although research has frequently focused on ionospheric alterations during SSW events, detailed studies on sporadic E layers remain limited. Examining these variations during SSW events could enhance our understanding of the interaction mechanisms between the ionosphere and the neutral atmosphere, and provide insights into the patterns of sporadic E layer alterations. This study analyzed the behavior of sporadic E layers during the 2008/2009 winter SSW period using data from three Japanese stations and satellite observations. The principal findings included the following: (1) The enhancement in the critical frequency of the sporadic E layers was most notable following the transition from easterly to westerly winds at 60° N at a 10 hPa altitude, accompanied by quasi 6-day and quasi 16-day oscillations in frequency. (2) The daily average zonal and meridional wind speeds in the MLT region also exhibited quasi 6-day and quasi 16-day oscillations, aligning with the observed periodicities in the critical frequency of the sporadic E layers. (3) Planetary waves were shown to modulate the amplitude of diurnal and semidiurnal tides, influencing the sporadic E layers. Furthermore, a wavelet analysis of foEs data with a time resolution of 0.25 h demonstrated that planetary waves also modulate the frequency of diurnal tides, thereby affecting the sporadic E layers. This research contributes to a deeper understanding of the formation mechanisms and prediction of sporadic E layer behavior.

With the development of information technology, computer technology is also gradually applied to the teaching activities of art education, and the use of multimedia technology to assist music teaching has become one of the hot research areas in universities. In order to better cultivate university students' musical exploration ability and creativity, a music note feature recognition teaching model based on Hidden Markov Model (HMM) algorithm is studied and optimized in universities by using genetic algorithm based on HMM algorithm. The music note feature recognition teaching model studied in this article combines computer multimedia technology, signal processing technology, and music theory, and uses computers to simulate the process of human cognition and analysis of music. And in this article, a music note recognition system was constructed using the features of sound level contours combined with the HMM algorithm. The data extracted during music recognition was compressed using the energy compression feature of sound level contours. At the same time, maximum likelihood estimation was used to find the optimal chord sequence, i.e., the optimal path, for the input signal. In the experimental results, the minimum value of the objective function was about 0.739 when the variance probability and crossover probability were 0.02 and 0.6, respectively. In the results, the HMM algorithm-based music note recognition model can improve the quality of music teaching and has some potential for application in the field of music teaching.

Symbiosis between soybean and rhizobia contributes to soybean yield and quality. Although secreted rhizobial type III effectors are known to regulate infection and promote nitrogen fixation, much about them remains unknown. Mutation of NopC, a type III effector from Sinorhizobium fredii HH103, reduced nodule numbers and dry weights in 310 soybean accessions, and expression of NopC in soybean hairy roots promoted symbiosis. Based on observed differences in nodule traits between Suinong 14 and Zyd 00,006 inoculated with HH103 and the NopC mutant, 11 QTL associated with rhizobia were identified in chromosome segment substitution lines (CSSLs) derived from Suinong 14 and Zyd 00006. Using chromosome fragment insertion, whole-genome sequencing of Suinong 14 and Zyd 00006, and qRT-PCR, Glyma.19G176300 (GmCRP) was identified as a candidate gene associated with NopC, and GmCRP was found to be induced by NopC to positively regulate nodulation. SNPs located in the regulatory regions of GmCRP influenced its expression response to NopC, with SNPs contributing to nodulation having been selected during domestication. Our findings reveal the function of a soybean gene encoding a rhizobial type III effector that contributes to symbiosis, and will facilitate the practical application of symbiotic nitrogen fixation in molecular breeding.

With the development of internet technology, the number of illicit websites such as gambling and pornography has dramatically increased, posing serious threats to people’s physical and mental health, as well as their financial security. Currently, the governance of such illicit websites mainly focuses on limited-scale detection through manual annotation. However, the need for effective solutions to govern illicit websites is urgent, requiring the ability to rapidly acquire large volumes of existing website data from the internet. Web mapping engines can provide massive, near real-time web data, which plays a crucial role in batch detection of illicit websites. Therefore, in this paper, we propose a method that combines web mapping engine big data to perform unsupervised multimodal clustering (MDC) for illicit website discovery. By extracting features based on contrastive learning methods from webpage screenshots and OCR text, we conduct feature similarity clustering to identify illicit websites. Finally, our unsupervised clustering model achieved an overall accuracy of 84.1% on all confidence levels, and a 92.39% accuracy at a confidence level of 0.999 or higher. By applying the MDC model to 3.7 million real web mapping data, we obtained 397,275 illicit websites primarily focused on gambling and pornography, with 14 attributes. This dataset is made publicly.

Cornelia de Lange syndrome (CdLS) is an autosomal dominant or X-linked genetic disease with significant genetic heterogeneity. Variants of the NIPBL gene are responsible for CdLS in 60% of patients. Herein, we report the case of a patient with CdLS showing distinctive facial features, microcephaly, developmental delay, and growth retardation. Whole exome sequencing was performed for the patient, and a novel de novo heterozygous synonymous variant was identified in the deep region of exon 40 in the NIPBL gene (NM_133433.4: c. 6819G > T, p. Gly2273 = ). The clinical significance of the variant was uncertain according to the ACMG/AMP guidelines; however, based on in silico analysis, it was predicted to alter mRNA splicing. To validate the prediction, a reverse transcriptase-polymerase chain reaction was conducted. The variant activated a cryptic splice donor, generating a short transcript of NIPBL. A loss of 137 bp at the 3′ end of NIPBL exon 40 was detected, which potentially altered the open reading frame by inserting multiple premature termination codons. Quantitative real-time PCR analysis showed that the ratio of the transcription level of the full-length transcript to that of the altered short transcript in the patient was 5:1, instead of 1:1. These findings may explain the relatively mild phenotype of the patient, regardless of the loss of function of the truncated protein due to a frameshift in the mRNA. To the best of our knowledge, this study is the first to report a synonymous variant in the deep exon regions of the NIPBL gene responsible for CdLS. The identified variant expands the mutational spectrum of the NIPBL gene. Furthermore, synonymous variations may be pathogenic, which should not be ignored in the clinical and genetic diagnosis of the disease.

We established an experimental apparatus by combining polarized light scattering and angle-resolved light scattering measurement technology to rapidly identify the shape of an individual aerosol particle. The experimental data of scattered light of Oleic acid, rod-shaped Silicon dioxide, and other particles with typical shape characteristics were analyzed statistically. To better study the relationship between the shape of particles and the properties of scattered light, the partial least squares discriminant analysis (PLS-DA) method was used to analyze the scattered light of aerosol samples based on the size screening of particles, and the shape recognition and classification method of the individual aerosol particle was established based on the analysis of the spectral data after nonlinear processing and grouping by particle size with the area under the receiver operating characteristic curve (AUC) as reference. The experimental results show that the proposed classification method has a good discrimination ability for spherical, rod-shaped, and other non-spherical particles, which can provide more information for atmospheric aerosol measurement, and has application value for traceability and exposure hazard assessment of aerosol particles.

Genetic populations provide the basis for genetic and genomic research, and chromosome segment substitution lines (CSSLs) are a powerful tool for the fine mapping of quantitative traits, new gene mining, and marker-assisted breeding. In this study, 213 CSSLs were obtained by self-crossing, backcrossing, and marker-assisted selection between cultivated soybean (Glycine max [L.] Merr.) variety Suinong14 (SN14) and wild soybean (Glycine soja Sieb. et Zucc.) ZYD00006. The genomes of these 213 CSSLs were resequenced and 580,524 single-nucleotide polymorphism markers were obtained, which were divided into 3,780 bin markers. The seed-pod-related traits were analyzed by quantitative trait locus (QTL) mapping using CSSLs. A total of 170 QTLs were detected, and 32 QTLs were detected stably for more than 2 years. Through epistasis analysis, 955 pairs of epistasis QTLs related to seed-pod traits were obtained. Furthermore, the hundred-seed weight QTL was finely mapped to the region of 64.4 Kb on chromosome 12, and Glyma.12G088900 was identified as a candidate gene. Taken together, a set of wild soybean CSSLs was constructed and upgraded by a resequencing technique. The seed-pod-related traits were studied by bin markers, and a candidate gene for the hundred-seed weight was finely mapped. Our results have revealed the CSSLs can be an effective tool for QTL mapping, epistatic effect analysis, and gene cloning.

Type III effectors secreted by rhizobia regulate nodulation in the host plant and are important modulators of symbiosis between rhizobia and soybean (Glycine max), although the underlying mechanisms are poorly understood. Here, we studied the type III effector NopAA in Sinorhizobium fredii HH103, confirming its secretion into the extracellular environment under the action of genistein. The enzyme activity of NopAA was investigated in vitro, using xyloglucan and β-glucan as substrates. NopAA functions were investigated by the generation of a NopAA mutant and the effects of NopAA deficiency on symbiosis were analyzed. Soybean genes associated with NopAA were identified in a recombinant inbred line (RIL) population and their functions were verified. NopAA was confirmed to be a type III effector with glycosyl hydrolase activity, and its mutant did not promote nodulation. Quantitative trait locus (QTL) analysis identified 10 QTLs with one, Glyma.19g074200 (GmARP), found to be associated with NopAA and to positively regulate the establishment of symbiosis. All these results support the hypothesis that type III effectors interact with host proteins to regulate the establishment of symbiosis and suggest the possibility of manipulating the symbiotic soybean–rhizobia interaction to promote efficient nitrogen fixation.

We demonstrate a systematic way to understand and select the accelerating voltage for maximizing cathodoluminescence (CL) by correlating the carrier diffusion length with the efficiency of ultraviolet (UV) InGaN/AlGaN multiple quantum wells (MQWs). We showed that the absorption of MQWs benefits from the absorbed energy within the diffusion length below the MQWs. With this understanding, we have achieved good agreement between the experimental data of and the Monte Carlo (CASINO) simulations on the dependence of acceleration voltage and QW number on InGaN/AlGaN MQW structures. These findings indicate that CL-based UV generation from carefully engineered III-N MQW structures with an appropriate number of QWs is highly promising. The understanding and application of this work can be extended to electron-beam pumped devices emitting in deep-UV (200–280 nm) wavelengths.

Abstract Background Nemaline myopathy 8 is a severe autosomal recessive muscle disorder characterized by fetal akinesia or hypokinesia, contractures, fractures, respiratory failure and swallowing difficulties apparent at birth. Methods An affected dizygotic twin pair from a non‐consanguineous Chinese family presented with severe asphyxia, lethargy and no response to stimuli. The dysmorphic features included prominent nasal bridge, telecanthus, excessive hip abduction, limb edema, absent palmar and sole creases, acromelia, bilateral clubfoot, appendicular hypertonia and cryptorchidism. Both infants died in the first week of life. Whole‐exome sequencing was used to identify the causative gene. Results Whole‐exome sequencing identified a recurrent missense variant c.1516A>C and a novel splice‐acceptor variant c.1153‐1G>C in KLHL40 gene in both siblings. We estimated the disease incidence in Southern Chinese population to be 2.47/100,000 based on the cumulative allele frequency of pathogenic and likely pathogenic variants in our internal database. Conclusion Our study expanded the mutation spectrum of KLHL40 and the condition could have been underdiagnosed before. We identified a recurrent missense variant c.1516A>C and provided evidence further supporting the founder effect of this variant in Southern Chinese population. Given the severity of the condition and the relative high incidence, this not‐so‐rare disorder should be included in expanded carrier screening panel for Chinese population.

PurposeROR2, a member of the ROR family, is essential for skeletal development as a receptor of Wnt5a. The present study aims to investigate the mutational spectrum of ROR2 in children with short stature and to identify the underlying molecular mechanisms.MethodsWe retrospectively analyzed clinical phenotype and whole-exome sequencing (WES) data of 426 patients with short stature through mutation screening of ROR2. We subsequently examined the changes in protein expression and subcellular location in ROR2 caused by the mutations. The mRNA expression of downstream signaling molecules of the Wnt5a–ROR2 pathway was also examined.ResultsWe identified 12 mutations in ROR2 in 21 patients, including 10 missense, one nonsense, and one frameshift. Among all missense variants, four recurrent missense variants [c.1675G > A(p.Gly559Ser), c.2212C > T(p.Arg738Cys), c.1930G > A(p.Asp644Asn), c.2117G > A(p.Arg706Gln)] were analyzed by experiments in vitro. The c.1675G > A mutation significantly altered the expression and the cellular localization of the ROR2 protein. The c.1675G > A mutation also caused a significantly decreased expression of c-Jun. In contrast, other missense variants did not confer any disruptive effect on the biological functions of ROR2.ConclusionWe expanded the mutational spectrum of ROR2 in patients with short stature. Functional experiments potentially revealed a novel molecular mechanism that the c.1675G > A mutation in ROR2 might affect the expression of downstream Wnt5a–ROR2 pathway gene by disturbing the subcellular localization and expression of the protein.

CHARGE syndrome is a life-threatening disease caused by mutations of chromodomain helicase DNA-binding protein 7 gene (CHD7). The disease is characterized by a pattern of congenital anomalies that involve multiple organs. In this study, five patients were diagnosed as CHARGE syndrome with CHD7 mutations by whole exome sequencing. Although the clinical phenotypes of probands are highly variable and typical symptoms such as coloboma and choanal atresia are not commonly manifested in this cohort, they all presented congenital heart defects. Of note, dyspnea is the most prominent symptom in all five neonatal patients, suggesting that dyspnea might be a phenotypic clue of CHARGE syndrome.

Abstract Background A very limited spectrum of ASCC1 pathogenic variants had been reported in six (mostly consanguineous) families with spinal muscular atrophy with congenital bone fractures 2 [OMIM #616867] since 2016. Methods A proband from a non‐consanguineous Chinese family presented with neonatal severe hypotonia, respiratory distress, muscle weakness, and atrophy, as well as congenital bone fractures was performed by exome sequencing. Results A compound heterozygosity of a nonsense (c.932C>G,p.Ser311Ter) and an exon 5 deletion in ASCC1 segregating with phenotypes was detected, both variants are novel and pathogenic. Since ASCC1 is a relatively new disease gene, we performed the gene curation by ClinGen SOP. The existing evidence is sufficient to support a "Definitive" level of disease‐gene relationship. Conclusion This case report expended the mutation spectrum of ASCC1 and support the notion that this novel disease also occurs in outbreed populations and this is a rare disease but may still be underdiagnosed due to its perinatal lethal outcomes.

ABSTRACT Objective Pendred syndrome (PS) is an autosomal recessive disorder characterised by sensorineural hearing loss and thyroid dyshormonogenesis. It is caused by biallelic mutations in the SLC26A4 gene encoding for pendrin. Hypothyroidism in PS can be present from birth and therefore diagnosed by neonatal screening. The aim of this study was to examine the SLC26A4 mutation spectrum and prevalence among congenital hypothyroidism (CH) patients in the Guangxi Zhuang Autonomous Region of China and to establish how frequently PS causes hearing impairment in our patients with CH. Subjects and methods Blood samples were collected from 192 CH patients in Guangxi Zhuang Autonomous Region, China, and genomic DNA was extracted from peripheral blood leukocytes. All exons of the SLC26A4 gene together with their exon-intron boundaries were screened by next-generation sequencing. Patients with SLC26A4 mutations underwent a complete audiological evaluation including otoscopic examination, audiometry and morphological evaluation of the inner ear. Results Next generation sequencing analysis of SLC26A4 in 192 CH patients revealed five different heterozygous variations in eight individuals (8/192, 4%). The prevalence of SLC26A4 mutations was 4% among studied Chinese CH. Three of the eight were diagnosed as enlargement of the vestibular aqueduct (EVA), no PS were found in our 192 CH patients. The mutations included one novel missense variant p.P469S, as well as four known missense variants, namely p.V233L, p.M147I, p.V609G and p.D661E. Of the eight patients identified with SLC26A4 variations in our study, seven patients showed normal size/location of thyroid gland, and one patients showed a decreased size one. Conclusions The prevalence of SLC26A4 pathogenic variants was 4% among studied Chinese patients with CH. Our study expanded the SLC26A4 mutation spectrum, provided the best estimation of SLC26A4 mutation rate for Chinese CH patients and indicated the rarity of PS as a cause of CH.

The InGaN multiple quantum well light-emitting diodes (LEDs) with different sizes of indium-tin-oxide (ITO) nanobowl photonic crystal (PhC) structure has been fabricated using self-assembled monolayer nanosphere lithography. The light output power (LOP) of PhC LEDs (at 350 mA) has been enhanced by 63.5% and the emission divergence exhibits a 28.8° reduction compared to conventional LEDs without PhC structure. Current-Voltage curves have shown that these PhC structures on ITO layer will not degrade the LED electrical properties. The finite-difference time-domain simulation (FDTD) has also been performed for light extraction and emission characteristics, which is consistent with the experimental results.

Multiple myeloma (MM) is a cancer of antibody-making plasma cells. It frequently harbors alterations in DNA and chromosome copy numbers, and can be divided into two major subtypes, hyperdiploid (HMM) and non-hyperdiploid multiple myeloma (NHMM). The two subtypes have different survival prognosis, possibly due to different but converging paths to oncogenesis. Existing methods for identifying the two subtypes are fluorescence in situ hybridization (FISH) and copy number microarrays, with increased cost and sample requirements. We hypothesize that chromosome alterations have their imprint in gene expression through dosage effect. Using five MM expression datasets that have HMM status measured by FISH and copy number microarrays, we have developed and validated a K-nearest-neighbor method to classify MM into HMM and NHMM based on gene expression profiles. Classification accuracy for test datasets ranges from 0.83 to 0.88. This classification will enable researchers to study differences and commonalities of the two MM subtypes in disease biology and prognosis using expression datasets without need for additional subtype measurements. Our study also supports the advantages of using cancer specific characteristics in feature design and pooling multiple rounds of classification results to improve accuracy. We provide R source code and processed datasets at www.ChengLiLab.org/software.

Sonodynamic therapy (SDT) has been recognized as a promising treatment for cancer due to its advantages of superior specificity, non-invasiveness, and deep tissue penetration. However, the antitumor effect of SDT remains restricted by the limited generation of reactive oxygen species (ROS) due to the lack of highly efficient sonosensitizers. In this work, we developed the novel sonosensitizer Pt/CeO2-xSx by constructing oxygen defects through S doping and Pt loading in situ. Large amounts of oxygen defects have been obtained by S doping, endowing Pt/CeO2-xSx with the ability to suppress electron-hole recombination, further promoting ROS production. Moreover, the introduction of Pt nanoparticles can not only produce oxygen in situ for relieving hypoxia but also form a Schottky heterojunction with CeO2-xSx for further inhibiting electron-hole recombination. In addition, Pt/CeO2-xSx could effectively deplete overexpressed glutathione (GSH) via redox reactions, amplifying oxidative stress in the tumor microenvironment (TME). Combined with the excellent POD-mimetic activity, Pt/CeO2-xSx can achieve highly efficient synergistic therapy of SDT and chemodynamic therapy (CDT). All these findings demonstrated that Pt/CeO2-xSx has great potential for cancer therapy, and this work provides a promising direction for designing and constructing efficient sonosensitizers. [ABSTRACT FROM AUTHOR]