The mitochondrial genome of Bottapotamon fukienense (Brachiura: Potamidae) is fragmented into two chromosomes.

BACKGROUND: China is the hotspot of global freshwater crab diversity, but their wild populations are facing severe pressures associated with anthropogenic factors, necessitating the need to map their taxonomic and genetic diversity and design conservation policies. RESULTS: Herein, we sequenced the mitochondrial genome of a Chinese freshwater crab species Bottapotamon fukienense, and found that it is fragmented into two chromosomes. We confirmed that fragmentation was not limited to a single specimen or population. Chromosome 1 comprised 15,111 base pairs (bp) and there were 26 genes and one pseudogene (pseudo-nad1) encoded on it. Chromosome 2 comprised 8,173 bp and there were 12 genes and two pseudogenes (pseudo-trnL2 and pseudo-rrnL) encoded on it. Combined, they comprise the largest mitogenome (23,284 bp) among the Potamidae. Bottapotamon was the only genus in the Potamidae dataset exhibiting rearrangements of protein-coding genes. Bottapotamon fukienense exhibited average rates of sequence evolution in the dataset and did not differ in selection pressures from the remaining Potamidae. CONCLUSIONS: This is the first experimentally confirmed fragmentation of a mitogenome in crustaceans. While the mitogenome of B. fukienense exhibited multiple signs of elevated mitogenomic architecture evolution rates, including the exceptionally large size, duplicated genes, pseudogenisation, rearrangements of protein-coding genes, and fragmentation, there is no evidence that this is matched by elevated sequence evolutionary rates or changes in selection pressures.

GABRG2 mutations in genetic epilepsy with febrile seizures plus: structure, roles, and molecular genetics.

Genetic epilepsy with febrile seizures plus (GEFS+) is a genetic epilepsy syndrome characterized by a marked hereditary tendency inherited as an autosomal dominant trait. Patients with GEFS+ may develop typical febrile seizures (FS), while generalized tonic-clonic seizures (GTCSs) with fever commonly occur between 3 months and 6 years of age, which is generally followed by febrile seizure plus (FS+), with or without absence seizures, focal seizures, or GTCSs. GEFS+ exhibits significant genetic heterogeneity, with polymerase chain reaction, exon sequencing, and single nucleotide polymorphism analyses all showing that the occurrence of GEFS+ is mainly related to mutations in the gamma-aminobutyric acid type A receptor gamma 2 subunit (GABRG2) gene. The most common mutations in GABRG2 are separated in large autosomal dominant families, but their pathogenesis remains unclear. The predominant types of GABRG2 mutations include missense (c.983A → T, c.245G → A, p.Met199Val), nonsense (R136*, Q390*, W429*), frameshift (c.1329delC, p.Val462fs*33, p.Pro59fs*12), point (P83S), and splice site (IVS6+2T → G) mutations. All of these mutations types can reduce the function of ion channels on the cell membrane; however, the degree and mechanism underlying these dysfunctions are different and could be linked to the main mechanism of epilepsy. The γ2 subunit plays a special role in receptor trafficking and is closely related to its structural specificity. This review focused on investigating the relationship between GEFS+ and GABRG2 mutation types in recent years, discussing novel aspects deemed to be great significance for clinically accurate diagnosis, anti-epileptic treatment strategies, and new drug development.

Salvaging the transected hypoglossal nerve using descendens hypoglossi in patients undergoing hypoglossal-facial nerve anastomosis for facial palsy: a randomized clinical trial.

OBJECTIVE: Hypoglossal-facial nerve anastomosis (HFA) is the most commonly used surgical treatment for severe facial palsy that does not respond to conservative treatments. A major complication of HFA is the loss of tongue function. The authors aimed to evaluate whether anastomosing the transected hypoglossal nerve using the ramus descendens hypoglossi could prevent tongue deviation and dysfunction in patients undergoing HFA. METHODS: In this randomized trial, adult patients with severe peripheral facial palsy (House-Brackmann grade V or VI) who did not respond to at least 6 months of conservative treatment were randomized at a 1:1 ratio to undergo either HFA alone (control group) or HFA plus anastomosis between the hypoglossal nerve and descendens hypoglossi (intervention group). The primary endpoint was tongue deviation angle at 12 months. Key secondary endpoints included tongue disability (chewing difficulty, swallowing defect, and articulation defect), tongue disability index (TDI; range 1-4, with a higher score indicating more severe disability), and facial nerve function. RESULTS: Twenty patients were enrolled (10 in each group). At 12 months, the tongue deviation angle was significantly lower in the intervention group than in the control group (7.8° ± 5.1° vs 23.6° ± 9.6°, p < 0.001). Although not statistically significant, the intervention group had lower rates of chewing difficulty (1/10 vs 3/10, p = 0.58), swallowing defect (1/10 vs 5/10, p = 0.14), and articulation defect (2/10 vs 6/10, p = 0.17). TDI was significantly lower in the intervention group (1.5 ± 0.6 vs 2.5 ± 0.3, p < 0.001). The percentage of the patients achieving House-Brackmann grade II or III was 80% in each group. CONCLUSIONS: Anastomosis of the descendens hypoglossi to the transected hypoglossal nerve attenuated tongue deviation in patients undergoing HFA for facial palsy, without compromising facial nerve function. Clinical trial registration no: ChiCTR2000034372 (Chinese Clinical Trials Registry).

Establishment and validation of a bad outcomes prediction model based on EEG and clinical parameters in prolonged disorder of consciousness.

Objective: This study aimed to explore the electroencephalogram (EEG) indicators and clinical factors that may lead to poor prognosis in patients with prolonged disorder of consciousness (pDOC), and establish and verify a clinical predictive model based on these factors. Methods: This study included 134 patients suffering from prolonged disorder of consciousness enrolled in our department of neurosurgery. We collected the data of sex, age, etiology, coma recovery scales (CRS-R) score, complications, blood routine, liver function, coagulation and other laboratory tests, resting EEG data and follow-up after discharge. These patients were divided into two groups: training set (n = 107) and verification set (n = 27). These patients were divided into a training set of 107 and a validation set of 27 for this study. Univariate and multivariate regression analysis were used to determine the factors affecting the poor prognosis of pDOC and to establish nomogram model. We use the receiver operating characteristic (ROC) and calibration curves to quantitatively test the effectiveness of the training set and the verification set. In order to further verify the clinical practical value of the model, we use decision curve analysis (DCA) to evaluate the model. Result: The results from univariate and multivariate logistic regression analyses suggested that an increased frequency of occurrence microstate A, reduced CRS-R scores at the time of admission, the presence of episodes associated with paroxysmal sympathetic hyperactivity (PSH), and decreased fibrinogen levels all function as independent prognostic factors. These factors were used to construct the nomogram. The training and verification sets had areas under the curve of 0.854 and 0.920, respectively. Calibration curves and DCA demonstrated good model performance and significant clinical benefits in both sets. Conclusion: This study is based on the use of clinically available and low-cost clinical indicators combined with EEG to construct a highly applicable and accurate model for predicting the adverse prognosis of patients with prolonged disorder of consciousness. It provides an objective and reliable tool for clinicians to evaluate the prognosis of prolonged disorder of consciousness, and helps clinicians to provide personalized clinical care and decision-making for patients with prolonged disorder of consciousness and their families.

A unified model-based framework for doublet or multiplet detection in single-cell multiomics data.

Droplet-based single-cell sequencing techniques rely on the fundamental assumption that each droplet encapsulates a single cell, enabling individual cell omics profiling. However, the inevitable issue of multiplets, where two or more cells are encapsulated within a single droplet, can lead to spurious cell type annotations and obscure true biological findings. The issue of multiplets is exacerbated in single-cell multiomics settings, where integrating cross-modality information for clustering can inadvertently promote the aggregation of multiplet clusters and increase the risk of erroneous cell type annotations. Here, we propose a compound Poisson model-based framework for multiplet detection in single-cell multiomics data. Leveraging experimental cell hashing results as the ground truth for multiplet status, we conducted trimodal DOGMA-seq experiments and generated 17 benchmarking datasets from two tissues, involving a total of 280,123 droplets. We demonstrated that the proposed method is an essential tool for integrating cross-modality multiplet signals, effectively eliminating multiplet clusters in single-cell multiomics data-a task at which the benchmarked single-omics methods proved inadequate.

Insights into the Correlation between Microbial Community Succession and Pericarp Degradation during Pepper (Piper nigrum L.) Peeling Process via Retting.

White pepper, used both as a seasoning in people's daily diets and as a medicinal herb, is typically produced by removing the pericarp of green pepper through the retting process. However, the mechanism of the retting process for peeling remains unclear. Therefore, this study aimed to investigate the changes in physicochemical factors, microbial community succession effects, and metabolites of the pepper pericarp during the pepper peeling process. The findings indicated that pre-treatment involving physical friction before the retting process effectively reduced the production time of white pepper. During the retting process, the pectinase activity increased, leading to a decrease in the pectin content in the pepper pericarp. There was a significant correlation observed between the changes in pH, pectin content, and peeling rate and the Shannon diversity index of bacteria and fungi. Prevotella, Lactococcus, and Candida were the dominant microbial genera during the retting. The functional predictions suggested that the monosaccharides degraded from the pepper pericarp could have been utilized by microbes through sugar metabolism pathways. Metabolomic analysis showed that the metabolic pathways of carbohydrates and amino acids were the main pathways altered during the pepper peeling process. The verification experiment demonstrated that the degradation of pectin into galacturonic acid by polygalacturonase was identified as the key enzyme in shortening the pepper peeling time. The structure of the pepper pericarp collapsed after losing the support of pectin, as revealed by scanning electron microscopy. These results suggest that the decomposition of the pepper pericarp was driven by key microbiota. The succession of microbial communities was influenced by the metabolites of the pepper pericarp during retting. These findings provide new insights into the retting process and serve as an important reference for the industrial production of white pepper.

Case-Case Genome-Wide Analyses Identify Subtype-Informative Variants That Confer Risk for Breast Cancer.

Breast cancer includes several subtypes with distinct characteristic biological, pathologic, and clinical features. Elucidating subtype-specific genetic etiology could provide insights into the heterogeneity of breast cancer to facilitate the development of improved prevention and treatment approaches. In this study, we conducted pairwise case-case comparisons among five breast cancer subtypes by applying a case-case genome-wide association study (CC-GWAS) approach to summary statistics data of the Breast Cancer Association Consortium. The approach identified 13 statistically significant loci and eight suggestive loci, the majority of which were identified from comparisons between triple-negative breast cancer (TNBC) and luminal A breast cancer. Associations of lead variants in 12 loci remained statistically significant after accounting for previously reported breast cancer susceptibility variants, among which, two were genome-wide significant. Fine mapping implicated putative functional/causal variants and risk genes at several loci, e.g., 3q26.31/TNFSF10, 8q22.3/NACAP1/GRHL2, and 8q23.3/LINC00536/TRPS1, for TNBC as compared with luminal cancer. Functional investigation further identified rs16867605 at 8q22.3 as a SNP that modulates the enhancer activity of GRHL2. Subtype-informative polygenic risk scores (PRS) were derived, and patients with a high subtype-informative PRS had an up to two-fold increased risk of being diagnosed with TNBC instead of luminal cancers. The CC-GWAS PRS remained statistically significant after adjusting for TNBC PRS derived from traditional case-control GWAS in The Cancer Genome Atlas and the African Ancestry Breast Cancer Genetic Consortium. The CC-GWAS PRS was also associated with overall survival and disease-specific survival among patients with breast cancer. Overall, these findings have advanced our understanding of the genetic etiology of breast cancer subtypes, particularly for TNBC. Significance: The discovery of subtype-informative genetic risk variants for breast cancer advances our understanding of the etiologic heterogeneity of breast cancer, which could accelerate the identification of targets and personalized strategies for prevention and treatment.

Self-supported porous wood carbon electrode with a MoC/carbon nanocage composite for application in a high-performance supercapacitor.

The rational design and synthesis of carbon nanocages with highly complex porous structures are continuously facing challenges in the development of high-performance supercapacitors (SCs). The electrochemical performance characteristics of electrodes rely on their compositions and fabrication methods. Here, we propose a universal and efficient approach for the in-situ synthesis of zeolitic imidazolate framework-8 (ZIF-8) on porous carbonized wood, where the selective utilization of hexacarbonyl molybdenum protects the structural integrity of the ZIF-8 precursor, preventing collapse during thermal treatment. The subsequent pyrolysis process leads to the formation of small-sized molybdenum carbide (MoC) which are embedded in carbon nanocages (CN). The composite electrode consists of MoC/CN embedded in a porous carbonized wood (PCW), and it shows area-specific capacity of 9.7F cm-2 and 9.4 F cm-2 at 5 mA cm-2 and 30 mA cm-2, respectively. Subsequently, the symmetric supercapacitor, with two MoC/CN@PCW electrodes exhibits a areal specific capacitance of 2.7 F cm-2 at 5 mA cm-2. Moreover, this supercapacitor maintains an capacitance retention rate of 98.5 % after 12,000 discharge cycles. The supercapacitor exhibits a power density of 6.5 mW cm-2, resulting in an energy density of 0.864 mWh cm-2. Therefore, the utilization of wood-based electrodes holds promise for energy storage systems.

Causal effects of gut microbiota on the risk of osteomyelitis: a Mendelian randomization study.

Background: Osteomyelitis is characterized by an inflammatory process initiated by microorganisms, leading to infection and subsequent degradation of bone tissue. Several studies have indicated a potential link between gut microbiota and the occurrence of osteomyelitis. Utilizing the benefits of Mendelian randomization, which mitigates issues of confounding and reverse causation, we employed this approach to ascertain the presence of a causal connection between gut microbiota and osteomyelitis. Additionally, we aimed to pinpoint gut microbiota that could potentially exert substantial influence. Methods: We performed a rigorous screening of single nucleotide polymorphisms in GWAS summary statistics for gut microbiota and osteomyelitis. The 2,542 instrumental variables obtained after screening were subjected to MR analyses, including inverse variance weighting, weighted median, weighted mode, MR-Egger, and Mendelian randomization pleiotropy residual sum and outlier test. We then validated the reliability of the results by performing sensitivity analyses on the MR of 196 well-defined gut microbiota. Result: We established a causal relationship between gut microbiota and osteomyelitis through MR analysis. Additionally, we identified a taxon of significant importance and six taxons with nominal significance. Specifically, the family Bacteroidales S24.7 group exhibited an association with a diminished risk of osteomyelitis development. Conversely, the class Bacilli, class Bacteroidia, order Bacteroidales, order Lactobacillales, family Streptococcaceae, and genus Coprococcus3 displayed an increased risk of developing osteomyelitis. The MR outcomes for these seven taxa remained stable throughout a series of sensitivity analyses. Conclusion: This study demonstrated a causal relationship between gut microbiota and osteomyelitis by Mendelian randomization. We hope that this study will provide a new direction for the treatment of osteomyelitis, which has a paucity of therapeutic options.

Exploring the causal association between serum metabolites and erectile dysfunction: a bidirectional Mendelian randomisation study.

Erectile dysfunction is a common sexual disorder in men. Some studies have found a strong association between some serum metabolites and erectile dysfunction. To investigate this association further, we used bidirectional Mendelian randomisation to investigate causality and possible biological mechanisms.Firstly, this study screened the statistics of genome-wide association studies of serum metabolites and erectile dysfunction to obtain instrumental variables. Inverse variance weighting was used as the primary method for causal effect analysis of instrumental variables in forward or reverse Mendelian randomisation, and the results obtained by MR-Egger regression and the weighted median method were used as references. Subsequently, the metabolites causally associated with erectile dysfunction were subjected to replication analyses and meta-analyses, and the results of the meta-analyses were analysed by pathway analyses to find influential pathways. In this process, Mendelian randomisation results need to be assessed for stability and reliability using sensitivity analysis.It was found that a total of six serum metabolites were causally associated with erectile dysfunction in a forward Mendelian randomisation study. 1,3,7-trimethyluraten (0.85 (0.73-0.99), P = 0.0368), ergothioneine (0.65 (0.45-0.94), P = 0.0226) and gamma-glutamylglutamate (0.63 (0.46-0.88), P = 0.0059) were protective against the development of erectile dysfunction, whereas 2-hydroxyhippurate (1.10 (1.02-1.19), P = 0.0152), N2,N2-dimethylguanosine (1.57 (1.02-2.40), P = 0.0395) and octanoylcarnitine (1.38 (1.06-1.82), P = 0.0183) were able to induce the development of erectile dysfunction. In addition, metabolic pathway analysis showed that 1,3,7-trimethylurate was able to influence the development of erectile dysfunction via the caffeine metabolism pathway (P = 0.0454). On the other hand, reverse Mendelian randomisation analysis showed that erectile dysfunction reduced serum homocitrulline levels (0.99 (0.97-1.00), P = 0.0360). Sensitivity analyses, including heterogeneity tests and pleiotropy tests, confirmed the reliability of the results.In conclusion, this study demonstrated a bidirectional causal relationship between serum metabolites and erectile dysfunction using bidirectional Mendelian randomisation analysis and replication meta-analysis. On this basis, this study provides a new direction of thinking and strong evidence for the therapeutic application and adjunctive diagnosis of serum metabolites in erectile dysfunction, and provides a certain reference value for subsequent related studies.

Innovative super-resolution in spatial transcriptomics: a transformer model exploiting histology images and spatial gene expression.

Spatial transcriptomics technologies have shed light on the complexities of tissue structures by accurately mapping spatial microenvironments. Nonetheless, a myriad of methods, especially those utilized in platforms like Visium, often relinquish spatial details owing to intrinsic resolution limitations. In response, we introduce TransformerST, an innovative, unsupervised model anchored in the Transformer architecture, which operates independently of references, thereby ensuring cost-efficiency by circumventing the need for single-cell RNA sequencing. TransformerST not only elevates Visium data from a multicellular level to a single-cell granularity but also showcases adaptability across diverse spatial transcriptomics platforms. By employing a vision transformer-based encoder, it discerns latent image-gene expression co-representations and is further enhanced by spatial correlations, derived from an adaptive graph Transformer module. The sophisticated cross-scale graph network, utilized in super-resolution, significantly boosts the model's accuracy, unveiling complex structure-functional relationships within histology images. Empirical evaluations validate its adeptness in revealing tissue subtleties at the single-cell scale. Crucially, TransformerST adeptly navigates through image-gene co-representation, maximizing the synergistic utility of gene expression and histology images, thereby emerging as a pioneering tool in spatial transcriptomics. It not only enhances resolution to a single-cell level but also introduces a novel approach that optimally utilizes histology images alongside gene expression, providing a refined lens for investigating spatial transcriptomics.

Analysis of clinical characteristics and histopathological transcription in 40 patients afflicted by epilepsy stemming from focal cortical dysplasia.

OBJECTIVE: This study aims to comprehensively analyze the clinical characteristics and identify the differentially expressed genes associated with drug-resistant epilepsy (DRE) in patients with focal cortical dysplasia (FCD). METHODS: A retrospective investigation was conducted from July 2019 to June 2022, involving 40 pediatric cases of DRE linked to FCD. Subsequent follow-ups were done to assess post-surgical outcomes. Transcriptomic sequencing and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to examine differential gene expression between the FCD and control groups. RESULTS: Among the 40 patients included in the study, focal to bilateral tonic-clonic seizures (13/40, 32.50%) and epileptic spasms (9/40, 22.50%) were the predominant seizure types. Magnetic resonance imaging (MRI) showed frequent involvement of the frontal (22/40, 55%) and temporal lobes (12/40, 30%). In cases with negative MRI results (13/13, 100%), positron emission tomography/computed tomography (PET-CT) scans revealed hypometabolic lesions. Fused MRI/PET-CT images demonstrated lesion reduction in 40.74% (11/27) of cases compared with PET-CT alone, while 59.26% (16/27) yielded results consistent with PET-CT findings. FCD type II was identified in 26 cases, and FCD type I in 13 cases. At the last follow-up, 38 patients were prescribed an average of 1.27 ± 1.05 anti-seizure medications (ASMs), with two patients discontinuing treatment. After a postoperative follow-up period of 23.50 months, 75% (30/40) of patients achieved Engel class I outcome. Transcriptomic sequencing and qRT-PCR analysis identified several genes primarily associated with cilia, including CFAP47, CFAP126, JHY, RSPH4A, and SPAG1. SIGNIFICANCE: This study highlights focal to bilateral tonic-clonic seizures as the most common seizure type in patients with DRE due to FCD. Surgical intervention primarily targeted lesions in the frontal and temporal lobes. Patients with FCD-related DRE showed a promising prognosis for seizure control post-surgery. The identified genes, including CFAP47, CFAP126, JHY, RSPH4A, and SPAG1, could serve as potential biomarkers for FCD. PLAIN LANGUAGE SUMMARY: This study aimed to comprehensively evaluate the clinical data of individuals affected by focal cortical dysplasia and analyze transcriptomic data from brain tissues. We found that focal to bilateral tonic-clonic seizures were the most prevalent seizure type in patients with drug-resistant epilepsy. In cases treated surgically, the frontal and temporal lobes were the primary sites of the lesions. Moreover, patients with focal cortical dysplasia-induced drug-resistant epilepsy exhibited a favorable prognosis for seizure control after surgery. CFAP47, CFAP126, JHY, RSPH4A, and SPAG1 have emerged as potential pathogenic genes for the development of focal cortical dysplasia.

Modulation of GPER1 alleviates early brain injury via inhibition of A1 reactive astrocytes activation after intracerebral hemorrhage in mice.

Background: Early brain injury (EBI) caused by inflammatory responses in acute phase of Intracerebral hemorrhage (ICH) plays a vital role in the pathological progression of ICH. Increasing evidences demonstrate A1 reactive astrocytes are associated with the severity of EBI. G-protein coupled estrogen receptor 1 (GPER1) has been proved mediating the neuroprotective effects of estrogen in central nervous system (CNS) disease. However, whether GPER1 plays a protective effect on ICH and A1 reactive astrocytes activation is not well studied. Methods: ICH model was established by infused the autologous whole blood into the right basal ganglia in wild type and GPER1 knockout mice. GPER1 specific agonist G1 and antagonist G15 were administered by intraperitoneal injection at 1 h or 0.5 h after ICH. Neurological function was detected on day 1 and day 3 by open field test and corner turn test following ICH. Besides, A1 reactive astrocytes were determined by immunofluorescence staining after ICH on day 3. To further identify the possible mechanism of GPER1 mediated neuroprotective effect, Western blot assays was performed after ICH on day 3. Results: After ICH, G1 treatment alleviated mice neurobehavior deficits on day 1 and day 3. Meanwhile, G1 treatment also significantly reduced the GFAP positive astrocytes and the C3 positive cells after ICH. Interestingly, G15 reversed the protective effect of G1 on the neurobehavior of ICH mice. Meanwhile, the expression of GFAP+C3+ A1 reactive astrocytes were also reduced by activation of GPER1. Mechanistic studies indicated TLR4 and NF-κB mediated the neuroprotective effect of GPER1. Conclusion: Generally, activation of GPER1 alleviated the EBI through inhibiting A1 reactive astrocytes activation via TLR4/NF-κB pathway after ICH in mice. Additionally, GPER1may be a promising target for ICH treatment.

Hypoxic Bone Mesenchymal Stem Cell-Derived Exosomes Direct Schwann Cells Proliferation, Migration, and Paracrine to Accelerate Facial Nerve Regeneration via circRNA_Nkd2/miR-214-3p/MED19 Axis.

Background: Facial nerves have the potential for regeneration following injury, but this process is often challenging and slow. Schwann cells (SCs) are pivotal in this process. Bone mesenchymal stem cells (BMSC)-derived exosomes promote tissue repair through paracrine action, with hypoxic preconditioning enhancing their effects. The main purpose of this study was to determine whether hypoxia-preconditioned BMSC-derived exosomes (Hypo-Exos) exhibit a greater therapeutic effect on facial nerve repair/regeneration and reveal the mechanism. Methods: CCK-8, EdU, Transwell, and ELISA assays were used to evaluate the functions of Hypo-Exos in SCs. Histological analysis and Vibrissae Movements (VMs) recovery were used to evaluate the therapeutic effects of Hypo-Exos in rat model. circRNA array was used to identify the significantly differentially expressed exosomal circRNAs between normoxia-preconditioned BMSC-derived exosomes (Nor-Exos) and Hypo-Exos. miRDB, TargetScan, double luciferase assay, qRT-PCR and WB were used to predict and identify potential exosomal cirRNA_Nkd2-complementary miRNAs and its target gene. The function of exosomal circRNA_Nkd2 in facial nerve repair/regeneration was evaluated by cell and animal experiments. Results: This study confirmed that Hypo-Exos more effectively promote SCs proliferation, migration, and paracrine function, accelerating facial nerve repair following facial nerve injury (FNI) compared with Nor-Exos. Furthermore, circRNA analysis identified significant enrichment of circRNA_Nkd2 in Hypo-Exos compared with Nor-Exos. Exosomal circRNA_Nkd2 positively regulates mediator complex subunit 19 (MED19) expression by sponging rno-miR-214-3p. Conclusion: Our results demonstrated a mechanism by which Hypo-Exos enhanced SCs proliferation, migration, and paracrine function and facial nerve repair and regeneration following FNI through the circRNA_Nkd2/miR-214-3p/Med19 axis. Hypoxic preconditioning is an effective and promising method for optimizing the therapeutic action of BMSC-derived exosomes in FNI.

Adaptation of a mutual exclusivity framework to identify driver mutations within oncogenic pathways.

Distinguishing genomic alterations in cancer-associated genes that have functional impact on tumor growth and disease progression from the ones that are passengers and confer no fitness advantage have important clinical implications. Evidence-based methods for nominating drivers are limited by existing knowledge on the oncogenic effects and therapeutic benefits of specific variants from clinical trials or experimental settings. As clinical sequencing becomes a mainstay of patient care, applying computational methods to mine the rapidly growing clinical genomic data holds promise in uncovering functional candidates beyond the existing knowledge base and expanding the patient population that could potentially benefit from genetically targeted therapies. We propose a statistical and computational method (MAGPIE) that builds on a likelihood approach leveraging the mutual exclusivity pattern within an oncogenic pathway for identifying probabilistically both the specific genes within a pathway and the individual mutations within such genes that are truly the drivers. Alterations in a cancer-associated gene are assumed to be a mixture of driver and passenger mutations with the passenger rates modeled in relationship to tumor mutational burden. We use simulations to study the operating characteristics of the method and assess false-positive and false-negative rates in driver nomination. When applied to a large study of primary melanomas, the method accurately identifies the known driver genes within the RTK-RAS pathway and nominates several rare variants as prime candidates for functional validation. A comprehensive evaluation of MAGPIE against existing tools has also been conducted leveraging the Cancer Genome Atlas data.

Causal effects of gut microbiota on the risk of erectile dysfunction: a Mendelian randomization study.

Erectile dysfunction ranks among the prevalent sexual disorders in men. Several studies have indicated a potential link between gut microbiota and erectile dysfunction. To validate this potential association, we were to screen statistical data from genome-wide association studies of gut microbiota and erectile dysfunction. p values of less than 1 × 10-5 were set as the threshold for screening instrumental variables that were strongly associated with gut microbiota. At the same time, in order to obtain more convincing findings, we further excluded instrumental variables with possible chain imbalance, instrumental variables with the presence of palindromes, instrumental variables with F-statistics less than 10, and instrumental variables associated with risk factors for erectile dysfunction. Five methods including inverse-variance weighted method, weighted median method, weighted mode, Mendelian randomization egger method and Mendelian randomization pleiotropy residual sum and outlier test were then used to analyse the 2591 instrumental variables obtained from the screening. We identified correlations between six gut microbiota and the risk of erectile dysfunction. The genus Ruminococcaceae UCG-013 exhibited an inverse association with the risk of developing erectile dysfunction (0.79 (0.65-0.97), P = 0.0214). Conversely, the genus Tyzzerella3 (1.13 (1.02-1.26), P = 0.0225), genus Erysipelotrichaceae UCG-003 (1.18 (1.01-1.38), P = 0.0412), genus LachnospiraceaeNC2004group (1.19 (1.03-1.37), P = 0.0191), genus Oscillibacter (1.23 (1.08-1.41), P = 0.0022), and family Lachnospiraceae (1.26 (1.05-1.52), P = 0.0123) demonstrated positive associations with an increased risk of erectile dysfunction. These sensitivity analyses of the gut microbiota were consistent. This study demonstrated a possible causal relationship between gut microbiota and erectile dysfunction risk through Mendelian randomization analysis, providing new potential possibilities for the prevention and treatment of erectile dysfunction.

Characteristics of metabolic inflammatory syndrome among inpatients with type 2 diabetes: A cross-sectional study in China.

BACKGROUND: As meta-inflammation is a common feature for obesity, type 2 diabetes (T2D), nonalcoholic fatty liver disease and atherosclerosis, we have proposed a new concept, metabolic inflammatory syndrome (MIS), to cluster such diseases. We aimed to characterize MIS and explore its association with coronary heart disease (CHD) among T2D inpatients in China. METHODS: A total number of 8344 T2D participants were enrolled. Each component of MIS and metabolic syndrome (MS) was analyzed. Their association with the risk of CHD was assessed using a binary logistic analysis. RESULTS: Among the T2D inpatients, the detection rate of MIS was much higher than that of MS (93.6 % vs. 53.2 %). Among all the components of MIS and MS, carotid atherosclerosis (71.9 %) was most commonly detected, which increased with aging in subgroups. Surprisingly, the most common combination of MIS was with all 4 components in T2D patients, with a constituent ratio of 30.9 %. According to the odds ratios (ORs), MIS was a better predictor of CHD than MS, especially after adjustment for age, sex, smoking, and alcohol consumption (adjusted OR for MIS: 3.083; for MS: 1.515). The presence of more components of MIS was associated with a higher detection rate of CHD (P < 0.001). Among all the components of MIS and MS, carotid atherosclerosis best predicted the risk of CHD (adjusted OR: 1.787). CONCLUSIONS: MIS is an independent risk factor for CHD, with a bigger OR value than MS. Carotid atherosclerosis, with the highest detection rate, was the best individual predictor of CHD and thus a critical component of MIS. The concept of MIS represents the understanding of metabolic diseases from the perspective of holistic integrative medicine.

Ligand-Enhanced Neodymium Doping of Perovskite Quantum Dots for Superior Exciton Confinement.

In this study, all-inorganic perovskite quantum dots (QDs) for pure blue emission are explored for full-color displays. We prepared CsPbBr3 and Cs3NdCl6 QDs via hot injection methods and mixed in various ratios at room temperature for color blending. Nd-doped CsPb(Cl/Br)3 QDs showed a blueshift in emission, and the photoluminescence quantum yields (PLQY, ΦPL) were lower in the 460-470 nm range due to surface halogen and Cs vacancies. To address this, we introduced a silane molecule, APTMS, via a ligand exchange process, effectively repairing these vacancies and enhancing Nd doping into the lattice. This modification promotes the PLQY to 94% at 466 nm. Furthermore, combining these QDs with [1]Benzothieno[3,2-b][1]benzothiophene (BTBT), a conjugated small-molecule semiconductor, in a composite film reduced PLQY loss caused by FRET in solid-state QD films. This approach achieved a wide color gamut of 124% National Television System Committee (NTSC), using a UV LED backlight and RGB perovskite QDs in a BTBT-based organic matrix as the color conversion layer. Significantly, the photostability of this composite was enhanced when used as a color conversion layer (CCL) under blue-LED excitation.

Alterations in brain network functional connectivity and topological properties in DRE patients.

Objective: The study aimed to find the difference in functional network topology on interictal electroencephalographic (EEG) between patients with drug-resistant epilepsy (DRE) and healthy people. Methods: We retrospectively analyzed the medical records as well as EEG data of ten patients with DRE and recruited five sex-age-matched healthy controls (HC group). Each participant remained awake while undergoing video-electroencephalography (vEEG) monitoring. After excluding data that contained abnormal discharges, we screened EEG segments that were free of artifacts and put them together into 20-min segments. The screened data was bandpass filtered to different frequency bands (delta, theta, alpha, beta, and gamma). The weighted phase lag index (wPLI) and the network properties were calculated to evaluate changes in the topology of the functional network. Finally, the results were statistically analyzed, and the false discovery rate (FDR) was used to correct for differences after multiple comparisons. Results: In the full frequency band (0.5-45 Hz), the functional connectivity in the DRE group during the interictal period was significantly lower than that in the HC group (p < 0.05). Compared to the HC group, in the full frequency band, the DRE group exhibited significantly decreased clustering coefficient (CC), node degree (D), and global efficiency (GE), while the characteristic path length (CPL) significantly increased (p < 0.05). In the sub-frequency bands, the functional connectivity of the DRE group was significantly lower than that of the HC group in the delta band but higher in the alpha, beta, and gamma bands (p < 0.05). The statistical results of network properties revealed that in the delta band, the DRE group had significantly decreased values for D, CC, and GE, but in the alpha, beta, and gamma bands, these values were significantly increased (p < 0.05). Additionally, the CPL of the DRE group significantly increased in the delta and theta bands but significantly decreased in the alpha, beta, and gamma bands (p < 0.05). Conclusion: The topology structure of the functional network in DRE patients was significantly changed compared with healthy people, which was reflected in different frequency bands. It provided a theoretical basis for understanding the pathological network alterations of DRE.

Mechanism of LEF1-AS1 regulating HUVEC cells by targeting miR-489-3p/S100A11 axis.

Background: The venous malformation is the most common congenital vascular malformation and exhibits the characteristics of local invasion and lifelong progressive development. Long noncoding RNA (lncRNA) regulates endothelial cells, vascular smooth muscle cells, macrophages, vascular inflammation, and metabolism and also affects the development of venous malformations. This study aimed to elucidate the role of the lncRNA LEF1-AS1 in the development of venous malformations and examine the interaction among LEF1-AS1, miR-489-3p, and S100A11 in HUVEC cells. Methods: Venous malformation tissues, corresponding normal venous tissues, and HUVEC cells were used. Agilent human lncRNA microarray gene chip was used to screen differential genes, RNA expression was detected using quantitative reverse transcription PCR, and protein expression was detected using Western blotting. The proliferation, migration, and angiogenesis of HUVEC cells were assessed using CCK8, transwell, and in vitro angiogenesis tests. Results: A total of 1,651 lncRNAs were screened using gene chip analysis, of which 1015 were upregulated and 636 were downregulated. The lncRNA LEF1-AS1 was upregulated with an obvious difference multiple, and the fold-change value was 11.03273. The results of the analysis performed using the StarBase bioinformatics prediction website showed that LEF1-AS1 and miR-489-3p possessed complementary binding sites and that miR-489-3p and S100A11 also had complementary binding sites. The findings of tissue experiments revealed that the expressions of LEF1-AS1 and S100A11 were higher in tissues with venous malformations than in normal tissues, whereas the expression of miR-489-3p was lower in venous malformations than in normal tissues. Cell culture experiments indicated that LEF1-AS1 promoted the proliferation, migration, and angiogenesis of HUVEC cells. In these cells, LEF1-AS1 targeted miR-489-3p, which in turn targeted S100A11. LEF1-AS1 acted as a competitive endogenous RNA and promoted the expression of S100A11 by competitively binding to miR-489-3p and enhancing the proliferation, migration, and angiogenesis of HUVEC cells. Thus, LEF1-AS1 participated in the occurrence and development of venous malformation. Conclusions: The expression of LEF1-AS1 was upregulated in venous malformations, and the expression of S100A11 was increased by the adsorption of miR-489-3p to venous endothelial cells, thus enhancing the proliferation, migration, and angiogenesis of HUVEC cells. In conclusion, LEF1-AS1 is involved in the occurrence and development of venous malformations by regulating the miR-489-3p/S100A11 axis, which provides valuable insights into the pathogenesis of this disease and opens new avenues for its treatment.