Novel variants and genotype-phenotype correlation in a multicentre cohort of GNE myopathy in China.

BACKGROUND: GlcNAc2-epimerase (GNE) myopathy is a rare autosomal recessive disorder caused by pathogenic variants in the GNE gene, which is essential for the sialic acid biosynthesis pathway. OBJECTIVE: This multi-centre study aimed to delineate the clinical phenotype and GNE variant spectrum in Chinese patients, enhancing our understanding of the genetic diversity and clinical manifestation across different populations. METHODS: We retrospectively analysed GNE variants from 113 patients, integrating these data with external GNE variants from online databases for a global perspective, examining their consequences, distribution, ethnicity and severity. RESULTS: This study revealed 97 distinct GNE variants, including 35 (36.08%) novel variants. Two more patients with deep intronic variant c.862+870C>T were identified, while whole genome sequencing (WGS) uncovered another two novel intronic variants: c.52-8924G>T and c.1505-12G>A. Nanopore long reads sequencing (LRS) and further PCR analysis verified a 639 bp insertion at chr9:36249241. Missense variants predominantly located in the epimerase/kinase domain coding region, indicating the impairment of catalytic function as a key pathogenic consequence. Comparative studies with Japanese, Korean and Jewish, our cohorts showed later onset ages by 2 years. The high allele frequency of the non-catalytic GNE variant, c.620A>T, might underlie the milder phenotype of Chinese patients. CONCLUSIONS: Comprehensive techniques such as WGS and Nanopore LRS warrants the identifying of GNE variants. Patients with the non-catalytic GNE variant, c.620A>T, had a milder disease progression and later wheelchair use.

Transcription factor SlSTOP1 regulates Small Auxin-Up RNA Genes for tomato root elongation under aluminum stress.

Aluminum (Al) stress, a prevalent constraint in acidic soils, inhibits plant growth by inhibiting root elongation through restricted cell expansion. The molecular mechanisms of Al-induced root inhibition, however, are not fully understood. This study aimed to elucidate the role of Small Auxin-up RNAs (SlSAURs), which function downstream of the key Al stress-responsive transcription factor SENSITIVE TO PROTON RHIZOTOXICITY 1 (SlSTOP1) and its enhancer STOP1-INTERACTING ZINC-FINGER PROTEIN 1 (SlSZP1), in modulating root elongation under Al stress in tomato (Solanum lycopersicum). Our findings demonstrated that tomato lines with knocked out SlSAURs exhibited shorter root lengths when subjected to Al stress. Further investigation into the underlying mechanisms revealed that SlSAURs interact with Type 2C Protein Phosphatases (SlPP2Cs), specifically D-clade Type 2C Protein Phosphatases (SlPP2C.Ds). This interaction was pivotal as it suppresses the phosphatase activity, leading to the degradation of SlPP2C.D's inhibitory effect on plasma membrane H+-ATPase. Consequently, this promoted cell expansion and root elongation under Al stress. These findings increase our understanding of the molecular mechanisms by which Al ions modulate root elongation. The discovery of the SlSAUR-SlPP2C.D interaction and its impact on H+-ATPase activity also provides a perspective on the adaptive strategies employed by plants to cope with Al toxicity, which may lead to the development of tomato cultivars with enhanced Al stress tolerance, thereby improving crop productivity in acidic soils.

High-risk screening for late-onset Pompe disease in China: An expanded multicenter study.

Late-onset Pompe disease (LOPD) is caused by a genetic deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to progressive limb-girdle weakness and respiratory impairment. The insidious onset of non-specific early symptoms often prohibits timely diagnosis. This study aimed to validate the high-risk screening criteria for LOPD in the Chinese population. A total of 726 patients were included, including 96 patients under 14 years of age. Dried blood spots (DBS) and tandem mass spectrometry (MS/MS) were employed to evaluate serum GAA activity. Forty-four patients exhibited a decreased GAA activity, 16 (2.2%) of which were confirmed as LOPD by genetic testing. Three previously unreported GAA mutations were also identified. The median diagnostic delay was shortened to 3 years, which excelled the previous retrospective studies. At diagnosis, most patients exhibited impaired respiratory function and/or limb-girdle weakness. Elevated serum creatine kinase (CK) levels were more frequently observed in patients who manifested before age 16. Overall, high-risk screening is a feasible and efficient method to identify LOPD patients at an early stage. Patients over 1 year of age with either weakness in axial and/or proximal limb muscles, or unexplained respiratory distress shall be subject to GAA enzymatic test, while CK levels above 2 times the upper normal limit shall be an additional criterion for patients under 16. This modified high-risk screening criteria for LOPD requires further validation in larger Chinese cohorts.

Pathology and physiology of acid-sensitive ion channels in the bladder.

Acid-sensitive ion channels (ASICs) are sodium-permeable channels activated by extracellular acidification. They can be activated and trigger the inward flow of Na+ when the extracellular environment is acidic, leading to membrane depolarization and thus inducing action potentials in neurons. There are four ASIC genes in mammals (ASIC1-4). ASIC is widely expressed in humans. It is closely associated with pain, neurological disorders, multiple sclerosis, epilepsy, migraines, and many other disorders. Bladder pain syndrome/interstitial cystitis (BPS/IC) is a specific syndrome characterized by bladder pain. Recent studies have shown that ASICs are closely associated with the development of BPS/IC. A study revealed that ASIC levels are significantly elevated in a BPS/IC model. Additionally, researchers have reported differential changes in ASICs in the bladders of patients with neurogenic lower urinary tract dysfunction (NLUTD) caused by spinal cord injury (SCI). In this review, we summarize the structure and physiological functions of ASICs and focus on the mechanisms by which ASICs mediate bladder disease.

Exosomes That Have Different Cellular Origins Followed by the Impact They Have on Prostate Tumor Development in the Tumor Microenvironment.

BACKGROUND: Prostate cancer (PCa) is the most common urinary tumor with the highest incidence rate and the second among the leading causes of death worldwide for adult males. In the worldwide cancer incidence rate, PCa is on the increase. The cancerous cells in the prostate and cells in the microenvironment surrounding the tumor communicate through signal transduction, which is crucial for the development and spread of PCa. RECENT FINDINGS: Exosomes are nanoscale vesicles released into body fluids by various cells that can aid intercellular communication by releasing nucleic acids and proteins. Exosomes published by different types of cells in the tumor microenvironment can have varying impacts on the proliferation and growth of tumor cells via various signaling pathways, modes of action, and secreted cytokines. CONCLUSION: The main purpose of this review is to describe the effects of different cell-derived exosomes in the tumor microenvironment of PCa on the progression of tumor cells, as well as to summarize and discuss the prospects for the application of exosomes in the treatment and diagnosis of PCa.

Human induced pluripotent stem cell line (FDHSi005-A) derived from a patient with a deep intronic variant in the GNE gene.

GlcNAc2-epimerase myopathy is a rare autosomal recessive myopathy characterized by distal involvement in the lower extremities. Our study reprogrammed human-induced pluripotent stem cells from peripheral blood mononuclear cells of a patient with GNE gene deep intronic variant c.862 + 870C>T and c.478C>T compound heterozygous mutations that co-segregated with the disease. The generated iPSCs express pluripotent cell markers with no mycoplasma contamination. Additionally, these iPSCs demonstrated pluripotency, the capacity to differentiate into the three germ layers, and maintained normal karyotypes. Importantly, we identified that these iPSCs possess the same specific mutations as the patient, making them a robust model for studying GNE myopathy and developing potential therapeutic interventions.

Multimodal deep learning using on-chip diffractive optics with in situ training capability.

Multimodal deep learning plays a pivotal role in supporting the processing and learning of diverse data types within the realm of artificial intelligence generated content (AIGC). However, most photonic neuromorphic processors for deep learning can only handle a single data modality (either vision or audio) due to the lack of abundant parameter training in optical domain. Here, we propose and demonstrate a trainable diffractive optical neural network (TDONN) chip based on on-chip diffractive optics with massive tunable elements to address these constraints. The TDONN chip includes one input layer, five hidden layers, and one output layer, and only one forward propagation is required to obtain the inference results without frequent optical-electrical conversion. The customized stochastic gradient descent algorithm and the drop-out mechanism are developed for photonic neurons to realize in situ training and fast convergence in the optical domain. The TDONN chip achieves a potential throughput of 217.6 tera-operations per second (TOPS) with high computing density (447.7 TOPS/mm2), high system-level energy efficiency (7.28 TOPS/W), and low optical latency (30.2 ps). The TDONN chip has successfully implemented four-class classification in different modalities (vision, audio, and touch) and achieve 85.7% accuracy on multimodal test sets. Our work opens up a new avenue for multimodal deep learning with integrated photonic processors, providing a potential solution for low-power AI large models using photonic technology.

SlWRKY37 targets SlLEA2 and SlABI5-like7 to regulate seed germination vigor in tomato.

Seed germination is a critical phase for the life cycle and propagation of higher plants. This study explores the role of SlWRKY37, a WRKY transcription factor in tomato, in modulating seed germination. We discovered that SlWRKY37 expression is markedly downregulated during tomato seed germination. Through CRISPR/Cas9-mediated editing, we demonstrate that SlWRKY37 knockout enhances germination, while its overexpression results in a delay compared to the wild type. Transcriptome analysis revealed 679 up-regulated and 627 down-regulated genes in Slwrky37-CRISPR deletion mutants relative to the wild type. Gene ontology (GO) enrichment analysis indicated these differentially expressed genes are linked to seed dormancy, abscisic acid homeostasis, and protein phosphorylation pathways. Bioinformatics and biochemical assays identified SlABI5-like7 and SlLEA2 as key transcriptional targets of SlWRKY37, integral to tomato seed dormancy regulation. Additionally, SlWRKY37 was found to be post-translationally phosphorylated at Ser65, a modification crucial for its transcriptional activation. Our findings elucidate the regulatory role of SlWRKY37 in seed dormancy, suggesting its potential as a target for gene editing to reduce seed dormancy in tomato breeding programs.

Branch Chain Amino Acid Metabolism Promotes Brain Metastasis of NSCLC through EMT Occurrence by Regulating ALKBH5 activity.

Metabolic reprogramming is one of the essential features of tumors that may dramatically contribute to cancer metastasis. Employing liquid chromatography-tandem mass spectrometry-based metabolomics, we analyzed the metabolic profile from 12 pairwise serum samples of NSCLC brain metastasis patients before and after CyberKnife Stereotactic Radiotherapy. We evaluated the histopathological architecture of 144 surgically resected NSCLC brain metastases. Differential metabolites were screened and conducted for functional clustering and annotation. Metabolomic profiling identified a pathway that was enriched in the metabolism of branched-chain amino acids (BCAAs). Pathologically, adenocarcinoma with a solid growth pattern has a higher propensity for brain metastasis. Patients with high BCAT1 protein levels in lung adenocarcinoma tissues were associated with a poor prognosis. We found that brain NSCLC cells had elevated catabolism of BCAAs, which led to a depletion of α-KG. This depletion, in turn, reduced the expression and activity of the m6A demethylase ALKBH5. Thus, ALKBH5 inhibition participated in maintaining the m6A methylation of mesenchymal genes and promoted the occurrence of epithelial-mesenchymal transition (EMT) in NSCLC cells and the proliferation of NSCLC cells in the brain. BCAA catabolism plays an essential role in the metastasis of NSCLC cells.

Single-beam three-axis SERF atomic magnetometer based on coordinate system rotation.

We propose what we believe to be a new single-beam three-axis spin exchange relaxation free (SERF) vector atomic magnetometer scheme based on coordinate system deflection. A theoretical model for the system response under arbitrary angle deflection was established for the first time, and the system response at different angles was simulated and analyzed. The simulation results show that the system response increases in the direction of the non-sensitive axis and decreases in the direction of the sensitive axis as the deflection angle increases, and the two responses tend to be the same when the angle is deflected to 45-degrees. Experimental measurements were carried out at a deflection angle of 45-degrees and the results showed that the sensitivity of the magnetometer was 55fT/Hz1/2 in the x1-axis, 38fT/Hz1/2 in the y1-axis and 60fT/Hz1/2 in the z1-axis. This single-beam magnetometer can be used to construct a miniaturized and low-cost weak magnetic sensor, which is expected to be used for vector measurement of biomagnetism.

A study on the potential of digital economy in reducing agricultural carbon emissions.

Agriculture is a significant source of carbon emissions, which have a substantial environmental impact. The digital economy plays a vital role in mitigating these emissions through innovative digital solutions. As a leading agricultural nation, China faces substantial pressure to reduce its agricultural carbon emissions(ACE). This paper aims to thoroughly examine the relationship between the growth of the rural digital economy and ACE. To achieve this, we utilize an extensive panel dataset covering China's provinces from 2011 to 2020, analyzing the dynamic and spatial effects of digital economy development on ACE. The key findings of this research are as follows: (1) The rapid expansion of the digital economy significantly reduces ACE. (2) The impact of digital economic development on lowering ACE varies spatially, with a clear progression from eastern to western regions. (3) The digital economy helps reduce ACE through three specific channels: fostering technological innovation, enhancing scale efficiency management, and providing agricultural financial incentives. Based on these findings, this study proposes policy recommendations to improve digital infrastructure, promote balanced regional development in the digital economy, and optimize the management of agricultural science and technology. These policy insights aim to transform agriculture and achieve the goal of reducing ACE, thereby contributing to broader environmental sustainability.

Effects of system parameters on a single-beam synthetic gradiometer with a dual-cell structure.

We report a single-beam synthetic gradiometer operated in the spin-exchange-relaxation free (SERF) regime, using the structure of two separate atomic vapor cells spaced 2 cm apart. To improve the capability of the gradiometer in suppressing the common-mode magnetic field noise, we are aiming at investigating the effects of the system parameters on the gradiometer common-mode rejection ratio (CMRR). The mathematical expression for the relationship between the gradiometer CMRR and the two variables including the linewidth ratio and the pumping factor ratio is constructed for the first time, to our knowledge. This means that the CMRR can be optimized by controlling the linewidth and the pumping factor, which is easy to implement in the operation process. As a result, a CMRR of 246 is achieved and a gradiometer sensitivity of 4.5 fT/cm/Hz1/2 is also measured. This method provides a theoretical and experimental basis for the automated operation of gradiometers, and the gradiometer system performance can be tuned to a desired state by simply controlling the linewidth and the incident light intensity.

CsHSFA1d Promotes Drought Stress Tolerance by Increasing the Content of Raffinose Family Oligosaccharides and Scavenging Accumulated Reactive Oxygen Species in Cucumber.

Drought is the most severe form of stress experienced by plants worldwide. Cucumber is a vegetable crop that requires a large amount of water throughout the growth period. In our previous study, we identified that overexpression of CsHSFA1d could improve cold tolerance and the content of endogenous jasmonic acid in cucumber seedlings. To explore the functional diversities of CsHSFA1d, we treat the transgenic plants under drought conditions. In this study, we found that the heat shock transcription factor HSFA1d (CsHSFA1d) could improve drought stress tolerance in cucumber. CsHSFA1d overexpression increased the expression levels of galactinol synthase (CsGolS3) and raffinose synthase (CsRS) genes, encoding the key enzymes for raffinose family oligosaccharide (RFO) biosynthesis. Furthermore, the lines overexpressing CsHSFA1d showed higher enzymatic activity of GolS and raffinose synthase to increase the content of RFO. Moreover, the CsHSFA1d-overexpression lines showed lower reactive oxygen species (ROS) accumulation and higher ROS-scavenging enzyme activity after drought treatment. The expressions of antioxidant genes CsPOD2, CsAPX1 and CsSOD1 were also upregulated in CsHSFA1d-overexpression lines. The expression levels of stress-responsive genes such as CsRD29A, CsLEA3 and CsP5CS1 were increased in CsHSFA1d-overexpression lines after drought treatment. We conclude that CsHSFA1d directly targets and regulates the expression of CsGolS3 and CsRS to promote the enzymatic activity and accumulation of RFO to increase the tolerance to drought stress. CsHSFA1d also improves ROS-scavenging enzyme activity and gene expression indirectly to reduce drought-induced ROS overaccumulation. This study therefore offers a new gene target to improve drought stress tolerance in cucumber and revealed the underlying mechanism by which CsHSFA1d functions in the drought stress by increasing the content of RFOs and scavenging the excessive accumulation of ROS.

Quantum-Geometry-Induced Anomalous Hall Effect in Nonunitary Superconductors and Application to Sr_{2}RuO_{4}.

The polar Kerr effect and the closely related anomalous charge Hall effect are among the most distinguishing signatures of the superconducting state in Sr_{2}RuO_{4}, as well as in several other compounds. These effects are often thought to be derived from chiral superconducting pairing, and different mechanisms have been invoked for the explanation. However, the intrinsic mechanisms proposed previously often involve unrealistically strong interband Cooper pairing. We show in this Letter that, even without interband pairing, nonunitary superconducting states can support the intrinsic anomalous charge Hall effect, thanks to the quantum geometric properties of the Bloch electrons. The key here is to have a normal-state spin Hall effect, for which a nonzero spin-orbit coupling is essential. A finite charge Hall effect then naturally arises at the onset of a spin-polarized nonunitary superconducting pairing. It depends on both the spin polarization and the normal-state electron Berry curvature, the latter of which is the imaginary part of the quantum geometric tensor of the Bloch states. Applying our results to the weakly paired Sr_{2}RuO_{4} we conclude that, if the reported Kerr effect is of intrinsic origin, the superconducting state is most likely nonunitary and has odd parity. Our theory may be generalized to other superconductors that exhibit the polar Kerr effect.

Pseudoexon activation by deep intronic variation in GNE myopathy with thrombocytopenia.

INTRODUCTION/AIMS: GNE myopathy is a rare autosomal recessive disorder caused by pathogenic variants in the GNE gene, which is essential for the sialic acid biosynthesis pathway. Although over 300 GNE variants have been reported, some patients remain undiagnosed with monoallelic pathogenic variants. This study aims to analyze the entire GNE genomic region to identify novel pathogenic variants. METHODS: Patients with clinically compatible GNE myopathy and monoallelic pathogenic variants in the GNE gene were enrolled. The other GNE pathogenic variant was verified using comprehensive methods including exon 2 quantitative polymerase chain reaction and nanopore long-read single-molecule sequencing (LRS). RESULTS: A deep intronic GNE variant, c.862+870C>T, was identified in nine patients from eight unrelated families. This variant generates a cryptic splice site, resulting in the activation of a novel pseudoexon between exons 5 and 6. It results in the insertion of an extra 146 nucleotides into the messengerRNA (mRNA), which is predicted to result in a truncated humanGNE1(hGNE1) protein. Peanut agglutinin（PNA） lectin staining of muscle tissues showed reduced sialylation of mucin O-glycans on sarcolemmal glycoproteins. Notably, a third of patients with the c.862+870C>T variant exhibited thrombocytopenia. A common core haplotype harboring the deep intronic GNE variant was found in all these patients. DISCUSSION: The transcript with pseudoexon activation potentially affects sialic acid biosynthesis via nonsense-mediated mRNA decay, or resulting in a truncated hGNE1 protein, which interferes with normal enzyme function. LRS is expected to be more frequently incorporated in genetic analysis given its efficacy in detecting hard-to-find pathogenic variants.

Enterovirus 71 Activates Plasmacytoid Dendritic Cell-Dependent PSGL-1 Binding Independent of Productive Infection.

Enterovirus 71 (EV71) is a significant causative agent of hand, foot, and mouth disease, with potential serious neurologic complications or fatal outcomes. The lack of effective treatments for EV71 infection is attributed to its elusive pathogenicity. Our study reveals that human plasmacytoid dendritic cells (pDCs), the main type I IFN-producing cells, selectively express scavenger receptor class B, member 2 (SCARB2) and P-selectin glycoprotein ligand 1 (PSGL-1), crucial cellular receptors for EV71. Some strains of EV71 can replicate within pDCs and stimulate IFN-α production. The activation of pDCs by EV71 is hindered by Abs to PSGL-1 and soluble PSGL-1, whereas Abs to SCARB2 and soluble SCARB2 have a less pronounced effect. Our data suggest that only strains binding to PSGL-1, more commonly found in severe cases, can replicate in pDCs and induce IFN-α secretion, highlighting the importance of PSGL-1 in these processes. Furthermore, IFN-α secretion by pDCs can be triggered by EV71 or UV-inactivated EV71 virions, indicating that productive infection is not necessary for pDC activation. These findings provide new insights into the interaction between EV71 and pDCs, suggesting that pDC activation could potentially mitigate the severity of EV71-related diseases.

SlMYC2 promotes SlLBD40-mediated cell expansion in tomato fruit development.

As a plant-specific transcription factor, lateral organ boundaries domain (LBD) protein was reported to regulate plant growth and stress response, but the functional research of subfamily II genes is limited. SlMYC2, a master regulator of Jasmonic acid response, has been found to exhibit high expression levels in fruit and has been implicated in the regulation of fruit ripening and resistance to Botrytis. However, its role in fruit expansion remains unknown. In this study, we present evidence that a subfamily II member of LBD, namely SlLBD40, collaborates with SlMYC2 in the regulation of fruit expansion. Overexpression of SlLBD40 significantly promoted fruit growth by promoting mesocarp cell expansion, while knockout of SlLBD40 showed the opposite result. Similarly, SlMYC2 knockout resulted in a significant decrease in cell expansion within the fruit. Genetic analysis indicated that SlLBD40-mediated cell expansion depends on the expression of SlMYC2. SlLBD40 bound to the promoter of SlEXPA5, an expansin gene, but did not activate its expression directly. While, the co-expression of SlMYC2 and SlLBD40 significantly stimulated the activation of SlEXPA5, leading to an increase in fruit size. SlLBD40 interacted with SlMYC2 and enhanced the stability and abundance of SlMYC2. Furthermore, SlMYC2 directly targeted and activated the expression of SlLBD40, which is essential for SlLBD40-mediated fruit expansion. In summary, our research elucidates the role of the interaction between SlLBD40 and SlMYC2 in promoting cell expansion in tomato fruits, thus providing novel insights into the molecular genetics underlying fruit growth.

Melatonin serves as a novel treatment in bladder fibrosis through TGF-ß1/Smad and EMT.

BACKGROUND: Melatonin (MEL) is an indole amine molecule primarily produced in the pineal gland. Melatonin has been shown in numerous studies to have antifibrotic effects on the kidney, liver, and other organs. However, it is still unclear how melatonin works in bladder fibrosis. We explored how melatonin affects animals with bladder fibrosis and the underlying mechanisms. MATERIALS AND METHODS: MEL was used to treat human bladder smooth muscle cells (HBdSMCs) after they were stimulated with transforming growth factor-ß1 (TGF-ß1) in vitro. Proteomic analysis and bioinformatic analysis of the altered expression of these proteins were subsequently performed on HBdSMCs from the different processing methods. To construct an in vivo bladder fibrosis model, we injected protamine sulfate (PS) and lipopolysaccharide (LPS) twice a week into the rat bladder for six weeks. After two weeks of PS/LPS treatment, the mice in the treatment group were treated with MEL (20 mg/kg/d) for 4 weeks. Finally, we detected the expression of fibrosis markers from different perspectives. The TGF-ß1/Smad pathway and epithelial-mesenchymal transition (EMT) in cell and bladder tissues were also identified. Further proteomic analysis was also performed. RESULTS: In vitro, we found that TGF-ß1 treatment enhanced the expression of the fibrosis markers collagen III and α-SMA in HBdSMCs. E-cadherin expression decreased while the TGF-ß1/Smad pathway was activated. Vimentin and N-cadherin expression was also elevated at the same time. Similar findings were observed in the LPS group. After MEL treatment, the expression of collagen III and α-SMA decreased, the expression of E-cadherin increased, and the expression of vimentin and N-cadherin also decreased. According to our quantitative proteomics analysis, CCN1 and SQLE may be important proteins involved in the development of bladder fibrosis. MEL decreased the expression of these genes, leading to the relief of bladder fibrosis. Bioinformatics analysis revealed that the extracellular space structure related to metabolic pathways, actin filament binding, and stress fibers can serve as a pivotal focus in the management of fibrosis. CONCLUSION: Melatonin attenuates bladder fibrosis by blocking the TGF-ß1/Smad pathway and EMT. CCN1 appears to be a possible therapeutic target for bladder fibrosis.

Diagnostic delay in late-onset Pompe disease among Chinese patients: A retrospective study.

Surveys and retrospective studies have revealed considerable delays in diagnosing late-onset Pompe disease (LOPD) in China, where the contributing factors remain poorly represented. Our study analyzed the diagnostic journey of 34 LOPD patients seen at our neuromuscular clinic from 2005 to 2022. We defined diagnostic delay as the time from the onset of the first relevant symptoms and laboratory findings suggestive of LOPD to the eventual diagnosis, and we constructed a correlation matrix to assess relationships among these variables. The cohort consisted of 34 patients with an equal male-to-female ratio, and the mean age at diagnosis was 27.68 ± 10.03 years. We found the median diagnostic delay to be 5 years, with a range of 0.3 to 20 years, with 97.1% having been misdiagnosed previously, most commonly with "Type II Respiratory insufficiency" (36.7%). Notably, patients at earlier onset (mean age, 18.19 years vs. 31 years; p < 0.005) tended to have higher creatine kinase (CK) levels. Furthermore, 92.6% reported difficulty in sitting up from a supine position since childhood. Our research emphasizes the role of early indicators like dyspnea and difficulty performing sit-ups in adolescents for timely LOPD diagnosis and treatment initiation. The importance of early high-risk screening using dried blood spot testing cannot be overstated.

Skin-Integrated Electrodes Based on Room-Temperature Curable, Highly Conductive Silver/Polydimethylsiloxane Composites.

The quality of electrophysiological (EP) signals heavily relies on the electrode's contact with the skin. However, motion or exposure to water can easily destabilize this connection. In contrast to traditional methods of attaching electrodes to the skin surface, this study introduces a skin-integration strategy inspired by the skin's intergrown structure. A highly conductive and room-temperature curable composite composed of silver microflakes and polydimethylsiloxane (Ag/PDMS) is applied to the skin. Before curing, the PDMS oil partially diffuse into the stratum corneum (SC) layer of the skin. Upon curing, the composite solidifies into an electrode that seamlessly integrated with the skin, resembling a natural extension. This skin-integration strategy offers several advantages. It minimizes motion artifacts resulting from relative electrode-skin displacement, significantly reduces interface impedance (67% of commercial Ag/AgCl gel electrodes at 100 Hz) and withstands water flushes due to its hydrophobic nature. These advantages pave the way for promising advancements in EP signal recording, particularly during motion and underwater conditions.