SDHA/B reduction promotes hepatocellular carcinoma by facilitating the deNEDDylation of cullin1 and stabilizing YAP/TAZ.

BACKGROUND AND AIMS: Succinate dehydrogenase enzyme (SDH) is frequently diminished in samples from patients with hepatocellular carcinoma (HCC), and SDH reduction is associated with elevated succinate level and poor prognosis in patients with HCC. However, the underlying mechanisms of how impaired SDH activity promotes HCC remain unclear. APPROACH AND RESULTS: In this study, we observed remarkable downregulations of SDH subunits A and B (SDHA/B) in chronic liver injury-induced murine HCC models and patient samples. Subsequent RNA sequencing, hematoxylin and eosin staining, and immunohistochemistry analyses of HCC samples revealed that Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) were significantly upregulated in HCC, with their levels inversely correlating with that of SDHA/B. YAP/TAZ stability was greatly enhanced in SDHA/B-depleted HCC cells along with accumulation of succinate. Further mechanistic analyses demonstrated that impaired activity of SDHA/B resulted in succinate accumulation, which facilitated the deNEDDylation of cullin1 and therefore disrupted the E3 ubiquitin ligase SCF ß-TrCP complex, consequently leading to YAP/TAZ stabilization and activation in HCC cells. The accelerated in vitro cell proliferation and in vivo tumor growth caused by SDHA/B reduction or succinate exposure were largely dependent on the aberrant activation of YAP/TAZ. CONCLUSIONS: Our study demonstrated that SDHA/B reduction promotes HCC proliferation by preventing the proteasomal degradation of YAP/TAZ through modulating cullin1 NEDDylation, thus binding SDH-deficient HCC cells to YAP/TAZ pathway and rendering these cells vulnerable to YAP/TAZ inhibition. Our findings warrant further investigation on the therapeutic effects of targeting YAP/TAZ in patients with HCC displaying reduced SDHA/B or elevated succinate levels.

Multi-mode resonance of bound states in the continuum in dielectric metasurfaces.

Bound states in the continuum (BIC) represent distinct non-radiative states endowed with infinite lifetime and vanishing resonance linewidth. Introducing asymmetric perturbation to the system can convert true BICs into high quality leaky modes which is useful in many photonic applications. Previously, such perturbation and resonance of interest is only limited to a single factor. However, different perturbations by unit cell gap, geometry and rotation angle result distinctive resonance modes. The combination of two perturbation factors can excite multi-mode resonance contributed from each asymmetric factor which coexist simultaneously; thus, the number of reflectance peaks can be controlled. In addition, we have carefully analyzed the electric field variations under different perturbation factors, followed by a multipolar decomposition of resonances to reveal underlying mechanisms of distinct resonance modes. Through simulations, we find that the introduction of multiple asymmetric perturbations also influences the metasurface sensitivity in refractive index sensing and compare the performance of different resonance modes. These observations provide structural design insights for achieving high quality resonance with multiple modes and ultra-sensitive sensing.

Assessment Methods and Intervention Strategies for Cleft-Related Lateral Misarticulation in Chinese-Speaking Children.

The aim of this study was to analyze the characteristics and error speech features of cleft-related lateral misarticulation and provide a basis for clinical evaluation and rational intervention. Participants who were diagnosed with lateral misarticulation after cleft palate repairment were 126 children aged 4, 6 to 16, and 11, and they had complete palatopharyngeal closure, no abnormalities in their speech organs and occlusion, and no hearing or intellectual impairments. The Chinese standard pronunciation clarity word list, the American KAY CSL4500, the Beijing Yangchen YF-16 computer speech analysis workstation, soundproof rooms, Wechsler scales of intelligence-fourth edition, and audiometers were used to evaluate the cleft-related lateral misarticulation. Statistical analysis was performed on the age, gender, error rate, corner of the mouth deviation direction, comorbidity, duration of intervention, period of treatment, and therapeutic effect of concentrated or normal intervention group in different patients. Our results showed that 2 to 3 straight stripes were visible at the onset of consonants /ti:/ /t'i:/, and 3 clear straight lines were visible in /tʂ/, indicating that the lateralized sound had 2 or 3 bursts and lasted for 1 to 2 ms. The onset age of lateralized sound was mostly below 12 years old. Chinese lateralized sound mainly occurred in vowel /i:/, and the occurrence rate of consonants with tongue surface /tɕ]/ /tɕ'/ /ɕ/ was the highest. In addition, the corner of the mouth deviation was also an indicator of lateralization sound, and other types of speech disorders mostly accompanied it. There was a significant difference in the improvement of speech clarity between the concentrated intervention group and the normal group before and after treatment. The 2 groups' average duration and course of treatment were not significantly different. Still, the period of concentrated intervention was shortened considerably, and the speech clarity of both groups of children after treatment exceeded 96%, reaching a normal level.

[A prospective cohort study of association between early childhood body mass index trajectories and the risk of overweight].

OBJECTIVE: To compare the association between body mass index (BMI) trajectories determined by different methods and the risk of overweight in early childhood in a prospective cohort study, and to identify children with higher risk of obesity during critical growth windows of early childhood. METHODS: A total of 1 330 children from Peking University Birth Cohort in Tongzhou (PKUBC-T) were included in this study. The children were followed up at birth, 1, 3, 6, 9, 12, 18, and 24 months and 3 years of age to obtain their height/length and weight data, and calculate BMI Z-score. Latent class growth mixture modeling (GMM) and longitudinal data-based k-means clustering algorithm (KML) were used to determine the grouping of early childhood BMI trajectories from birth to 24 mouths. Linear regression was used to compare the association between early childhood BMI trajectories determined by different methods and BMI Z-score at 3 years of age. The predictive performance of early childhood BMI trajectories determined by different methods in predicting the risk of overweight (BMI Z-score > 1) at 3 years was compared using the average area under the curve (AUC) of 5-fold cross-validation in Logistic regression models. RESULTS: In the study population included in this research, the three-category trajectories determined using GMM were classified as low, medium, and high, accounting for 39.7%, 54.1%, and 6.2% of the participants, respectively. The two-category trajectories determined using the KML method were classified as low and high, representing 50. 3% and 49. 7% of the participants, respectively. The three-category trajectories determined using the KML method were classified as low, medium, and high, accounting for 31.1%, 47.4%, and 21.5% of the participants, respectively. There were certain differences in the growth patterns reflected by the early childhood BMI trajectories determined using different methods. Linear regression analysis found that after adjusting for maternal ethnicity, educational level, delivery mode, parity, maternal age at delivery, gestational week at delivery, children' s gender, and breastfeeding at 1 month of age, the association between the high trajectory group in the three-category trajectories determined by the KML method (manifested by a slightly higher BMI at birth, followed by rapid growth during infancy and a stable-high BMI until 24 months) and BMI Z-scores at 3 years was the strongest. Logistic regression analysis revealed that the three-category trajectory grouping determined by the KML method had the best predictive performance for the risk of overweight at 3 years. The results were basically consistent after additional adjustment for the high bound score of the child' s diet balanced index, average daily physical activity time, and screen time. CONCLUSION: This study used different methods to identify early childhood BMI trajectories with varying characteristics, and found that the high trajectory group determined by the KML method was better able to identify children with a higher risk of overweight in early childhood. This provides scientific evidence for selecting appropriate methods to define early childhood BMI trajectories.

COVID-19 Booster Dose Vaccination Coverage and Factors Associated with Booster Vaccination among Adults, United States, March 2022.

The Centers for Disease Control and Prevention recommends a COVID-19 vaccine booster dose for all persons >18 years of age. We analyzed data from the National Immunization Survey-Adult COVID Module collected during February 27-March 26, 2022 to assess COVID-19 booster dose vaccination coverage among adults. We used multivariable logistic regression analysis to assess factors associated with vaccination. COVID-19 booster dose coverage among fully vaccinated adults increased from 25.7% in November 2021 to 63.4% in March 2022. Coverage was lower among non-Hispanic Black (52.7%), and Hispanic (55.5%) than non-Hispanic White adults (67.7%). Coverage was 67.4% among essential healthcare personnel, 62.2% among adults who had a disability, and 69.9% among adults who had medical conditions. Booster dose coverage was not optimal, and disparities by race/ethnicity and other factors are apparent in coverage uptake. Tailored strategies are needed to educate the public and reduce disparities in COVID-19 vaccination coverage.

Crosstalk between TRPV1 and immune regulation in Fuchs endothelial corneal dystrophy.

Fuchs endothelial corneal dystrophy (FECD) is the leading indication for corneal transplantation worldwide. Our aim was to investigate the role of transient receptor potential vanilloid subtype 1 (TRPV1) and the associated immune regulation contributing to this pathological condition. Significant upregulation of TRPV1 was detected in the H2O2-induced in vitro FECD model. Based on gene expression microarray dataset GSE142538 and in vitro results, a comprehensive immune landscape was studied and a negative correlation was found between TRPV1 with different immune cells, especially regulatory T cells (Tregs). Functional analyses of the 313 TRPV1-related differentially expressed genes (DEGs) revealed the involvement of TRP-regulated calcium transport, as well as inflammatory and immune pathways. Four TRPV1-related core genes (MAPK14, GNB1, GNAQ, and ARRB2) were screened, validated by microarray dataset GSE112039 and the combined validation dataset E-GEAD-399 & 564, and verified by in vitro experiments. Our study suggested a potential crosstalk between TRPV1 and immune regulation contributing to FECD pathogenesis. The identified pivotal biomarkers and immune-related pathways provide a novel framework for future mechanistic and therapeutic studies of FECD.

Racial and Ethnic Differences in COVID-19 Vaccination Coverage Among Children and Adolescents Aged 5-17 Years and Parental Intent to Vaccinate Their Children - National Immunization Survey-Child COVID Module, United States, December 2020-September 2022.

Some racial and ethnic groups are at increased risk for COVID-19 and associated hospitalization and death because of systemic and structural inequities contributing to higher prevalences of high-risk conditions and increased exposure (1). Vaccination is the most effective prevention intervention against COVID-19-related morbidity and mortality*; ensuring more equitable vaccine access is a public health priority. Differences in adult COVID-19 vaccination coverage by race and ethnicity have been previously reported (2,3), but similar information for children and adolescents is limited (4,5). CDC analyzed data from the National Immunization Survey-Child COVID Module (NIS-CCM) to describe racial and ethnic differences in vaccination status, parental intent to vaccinate their child, and behavioral and social drivers of vaccination among children and adolescents aged 5-17 years. By August 31, 2022, approximately one third (33.2%) of children aged 5-11 years, more than one half (59.0%) of children and adolescents aged 12-15 years, and more than two thirds (68.6%) of adolescents aged 16-17 years had received ≥1 COVID-19 vaccine dose. Vaccination coverage was highest among non-Hispanic Asian (Asian) children and adolescents, ranging from 63.4% among those aged 5-11 years to 91.8% among those aged 16-17 years. Coverage was next highest among Hispanic or Latino (Hispanic) children and adolescents (34.5%-77.3%). Coverage was similar for non-Hispanic Black or African American (Black), non-Hispanic White (White), and non-Hispanic other race† or multiple race (other/multiple race) children and adolescents aged 12-15 and 16-17 years. Among children aged 5-11 years, coverage among Black children was lower than that among Hispanic, Asian, and other/multiple race children. Enhanced public health efforts are needed to increase COVID-19 vaccination coverage for all children and adolescents. To address disparities in child and adolescent COVID-19 vaccination coverage, vaccination providers and trusted messengers should provide culturally relevant information and vaccine recommendations and build a higher level of trust among those groups with lower coverage.

COVID-19 Bivalent Booster Vaccination Coverage and Intent to Receive Booster Vaccination Among Adolescents and Adults - United States, November-December 2022.

COVID-19 vaccine booster doses are safe and maintain protection after receipt of a primary vaccination series and reduce the risk for serious COVID-19-related outcomes, including emergency department visits, hospitalization, and death (1,2). CDC recommended an updated (bivalent) booster for adolescents aged 12-17 years and adults aged ≥18 years on September 1, 2022 (3). The bivalent booster is formulated to protect against the Omicron BA.4 and BA.5 subvariants of SARS-CoV-2 as well as the original (ancestral) strain (3). Based on data collected during October 30-December 31, 2022, from the National Immunization Survey-Child COVID Module (NIS-CCM) (4), among all adolescents aged 12-17 years who completed a primary series, 18.5% had received a bivalent booster dose, 52.0% had not yet received a bivalent booster but had parents open to booster vaccination for their child, 15.1% had not received a bivalent booster and had parents who were unsure about getting a booster vaccination for their child, and 14.4% had parents who were reluctant to seek booster vaccination for their child. Based on data collected during October 30-December 31, 2022, from the National Immunization Survey-Adult COVID Module (NIS-ACM) (4), 27.1% of adults who had completed a COVID-19 primary series had received a bivalent booster, 39.4% had not yet received a bivalent booster but were open to receiving booster vaccination, 12.4% had not yet received a bivalent booster and were unsure about getting a booster vaccination, and 21.1% were reluctant to receive a booster. Adolescents and adults in rural areas had a much lower primary series completion rate and up-to-date vaccination coverage. Bivalent booster coverage was lower among non-Hispanic Black or African American (Black) and Hispanic or Latino (Hispanic) adolescents and adults compared with non-Hispanic White (White) adolescents and adults. Among adults who were open to receiving booster vaccination, 58.9% reported not having received a provider recommendation for booster vaccination, 16.9% had safety concerns, and 4.4% reported difficulty getting a booster vaccine. Among adolescents with parents who were open to getting a booster vaccination for their child, 32.4% had not received a provider recommendation for any COVID-19 vaccination, and 11.8% had parents who reported safety concerns. Although bivalent booster vaccination coverage among adults differed by factors such as income, health insurance status, and social vulnerability index (SVI), these factors were not associated with differences in reluctance to seek booster vaccination. Health care provider recommendations for COVID-19 vaccination; dissemination of information by trusted messengers about the continued risk for COVID-19-related illness and the benefits and safety of bivalent booster vaccination; and reducing barriers to vaccination could improve COVID-19 bivalent booster coverage among adolescents and adults.

Uncovering the role of transient receptor potential channels in pterygium: a machine learning approach.

OBJECTIVES: We aimed at identifying the role of transient receptor potential (TRP) channels in pterygium. METHODS: Based on microarray data GSE83627 and GSE2513, differentially expressed genes (DEGs) were screened and 20 hub genes were selected. After gene correlation analysis, 5 TRP-related genes were obtained and functional analyses of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed. Multifactor regulatory network including mRNA, microRNAs (miRNAs) and transcription factors (TFs) was constructed. The 5 gene TRP signature for pterygium was validated by multiple machine learning (ML) programs including support vector classifiers (SVC), random forest (RF), and k-nearest neighbors (KNN). Additionally, we outlined the immune microenvironment and analyzed the candidate drugs. Finally, in vitro experiments were performed using human conjunctival epithelial cells (CjECs) to confirm the bioinformatics results. RESULTS: Five TRP-related genes (MCOLN1, MCOLN3, TRPM3, TRPM6, and TRPM8) were validated by ML algorithms. Functional analyses revealed the participation of lysosome and TRP-regulated inflammatory pathways. A comprehensive immune infiltration landscape and TFs-miRNAs-mRNAs network was studied, which indicated several therapeutic targets (LEF1 and hsa-miR-455-3p). Through correlation analysis, MCOLN3 was proposed as the most promising immune-related biomarker. In vitro experiments further verified the reliability of our in silico results and demonstrated that the 5 TRP-related genes could influence the proliferation and proinflammatory signaling in conjunctival tissue contributing to the pathogenesis of pterygium. CONCLUSIONS: Our study suggested that TRP channels played an essential role in the pathogenesis of pterygium. The identified pivotal biomarkers (especially MCOLN3) and pathways provide novel directions for future mechanistic and therapeutic studies for pterygium.

Cluster analysis of adults unvaccinated for COVID-19 based on behavioral and social factors, National Immunization Survey-Adult COVID Module, United States.

By the end of 2021, approximately 15% of U.S. adults remained unvaccinated against COVID-19, and vaccination initiation rates had stagnated. We used unsupervised machine learning (K-means clustering) to identify clusters of unvaccinated respondents based on Behavioral and Social Drivers (BeSD) of COVID-19 vaccination and compared these clusters to vaccinated participants to better understand social/behavioral factors of non-vaccination. The National Immunization Survey Adult COVID Module collects data on U.S. adults from September 26-December 31,2021 (n = 187,756). Among all participants, 51.6% were male, with a mean age of 61 years, and the majority were non-Hispanic White (62.2%), followed by Hispanic (17.2%), Black (11.9%), and others (8.7%). K-means clustering procedure was used to classify unvaccinated participants into three clusters based on 9 survey BeSD items, including items assessing COVID-19 risk perception, social norms, vaccine confidence, and practical issues. Among unvaccinated adults (N = 23,397), 3 clusters were identified: the "Reachable" (23%), "Less reachable" (27%), and the "Least reachable" (50%). The least reachable cluster reported the lowest concern about COVID-19, mask-wearing behavior, perceived vaccine confidence, and were more likely to be male, non-Hispanic White, with no health conditions, from rural counties, have previously had COVID-19, and have not received a COVID-19 vaccine recommendation from a healthcare provider. This study identified, described, and compared the characteristics of the three unvaccinated subgroups. Public health practitioners, healthcare providers and community leaders can use these characteristics to better tailor messaging for each sub-population. Our findings may also help inform decisionmakers exploring possible policy interventions.

Serelaxin Alleviates Fibrosis in Thyroid-Associated Ophthalmopathy via the Notch Pathway.

Fibrosis is the late stage of thyroid-associated ophthalmopathy (TAO), resulting in serious complications. Effective therapeutic drugs are still lacking. We aimed to explore the mechanism of TAO fibrosis and to find a targeted drug. High-throughput RNA sequencing was performed on orbital connective tissues from twelve patients with TAO and six healthy controls. Protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and we identified the hub gene by Cytoscape software. Additionally, the RNA sequencing results were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatic prediction identified the functions of differentially expressed genes (DEGs). Further orbital connective tissue and serum samples of the TAO and control groups were collected for subsequent experiments. Histologic staining, Western blotting (WB), qRT-PCR, enzyme-linked immunosorbent assays (ELISAs), gene overexpression through lentiviral infection or silencing gene by short interfering RNA (siRNA) were performed. We found that the relaxin signaling pathway is an important regulatory pathway in TAO fibrosis pathogenesis. Serelaxin exerts antifibrotic and anti-inflammatory effects in TAO. Furthermore, the downstream Notch pathway was activated by serelaxin and was essential to the antifibrotic effect of serelaxin in TAO. The antifibrotic effect of serelaxin is dependent on RXFP1.

Sociodemographic Variation in Early Uptake of COVID-19 Vaccine and Parental Intent and Attitudes Toward Vaccination of Children Aged 6 Months-4 Years - United States, July 1-29, 2022.

COVID-19 vaccines are safe and effective for infants and young children, and on June 18, 2022, CDC recommended COVID-19 vaccination for infants and children (children) aged 6 months-4 years (1,2). As of November 9, 2022, based on administrative data reported to CDC,* 5.9% of children aged <2 years and 8.8% of children aged 2-4 years had received ≥1 dose. To better understand reasons for low coverage among children aged <5 years, CDC analyzed data from 4,496 National Immunization Survey-Child COVID Module (NIS-CCM) interviews conducted during July 1-29, 2022, to examine variation in receipt of ≥1 dose of COVID-19 vaccine and parental intent to vaccinate children aged 6 months-4 years by sociodemographic characteristics and by parental beliefs about COVID-19; type of vaccination place was also reported. Among children aged 6 months-4 years, 3.5% were vaccinated; 59.3% were unvaccinated, but the parent was open to vaccination; and 37.2% were unvaccinated, and the parent was reluctant to vaccinate their child. Openness to vaccination was higher among parents of Hispanic or Latino (Hispanic) (66.2%), non-Hispanic Black or African American (Black) (61.1%), and non-Hispanic Asian (Asian) (83.1%) children than among parents of non-Hispanic White (White) (52.9%) children and lower among parents of children in rural areas (45.8%) than among parents of children in urban areas (64.1%). Parental confidence in COVID-19 vaccine safety and receipt of a provider recommendation for COVID-19 vaccination were lower among unvaccinated than vaccinated children. COVID-19 vaccine recommendations from a health care provider, along with dissemination of information about the safety of COVID-19 vaccine by trusted persons, could increase vaccination coverage among young children.

Functional mapping of language-related areas from natural, narrative speech during awake craniotomy surgery.

Accurate localization of brain regions responsible for language and cognitive functions in epilepsy patients is important. Electrocorticography (ECoG)-based real-time functional mapping (RTFM) has been shown to be a safer alternative to electrical cortical stimulation mapping (ESM), which is currently the clinical/gold standard. Conventional methods for analyzing RTFM data mostly account for the ECoG signal in certain frequency bands, especially high gamma. Compared to ESM, they have limited accuracy when assessing channel responses. In the present study, we developed a novel RTFM method based on tensor component analysis (TCA) to address the limitations of current estimation methods. Our approach analyzes the whole frequency spectrum of the ECoG signal during natural continuous speech. We construct third-order tensors that contain multichannel time-frequency information and use TCA to extract low-dimensional temporal, spectral and spatial modes. Temporal modulation scores (correlation values) are then calculated between the time series of voice envelope features and TCA-estimated temporal courses, and significant temporal modulation determines which components' channel weightings are displayed to the neurosurgeon as a guide for follow-up ESM. In our experiments, data from thirteen patients with refractory epilepsy were recorded during preoperative evaluation for their epileptogenic zones (EZs), which were located adjacent to the eloquent cortex. Our results showed higher detection accuracy of our proposed method in a narrative speech task, suggesting that our method complements ESM and is an improvement over the prior RTFM method. To our knowledge, this is the first TCA-based method to pinpoint language-specific brain regions during continuous speech that uses whole-band ECoG.

From dendritic mesoporous silica microspheres to waxberry-like hierarchical hollow carbon spheres: rational design of carbon host for lithium sulfur batteries.

Fabricating sulfur host for the cathode with strong confinement effect and high dispersion of sulfur is vitally important to the development of high-performance lithium sulfur batteries. Benefiting from their unique and tunable structure, good conductivity and chemical inertness, hollow porous carbon materials has been considered as a promising candidate. Herein, precisely designed waxberry-like hierarchical hollow carbon spheres (h-CNS) have been synthesized as the sulfur micro-containers for lithium sulfur batteries. The prepared h-CNS/S electrode shows a good rate capability of 1311 mAh g-1at 0.1 C and 962 mAh g-1at 1 C. In addition, the h-CNS/S electrode also shows satisfactory long cycle performance with 622 mAh g-1at 0.5 C and 400 mAh g-1at 4 C over 600 cycles. The desirable performance can be attributed to the wedge-shape micro-containers which improve the high dispersion of sulfur inside the channels and inhibit the loss of intermediate polysulfide. Moreover, the unique structure can also enhance the transfer of both lithium ions and electrons which benefits to the rate capability of the lithium sulfur batteries.

Clinical application of intraoperative trial-free online-based language mapping for patients with refractory epilepsy.

OBJECTIVE: The objective of the study was to develop and clinically test a trial-free online-based language mapping method for localizing the eloquent cortex easily in epilepsy operation. METHODS: Nine patients with refractory epilepsy were included in this study according to the results of preoperative evaluation for their epileptogenic zones (EZs) located adjacent to the eloquent cortex. When patients were awakened up from general anesthesia during operation, the trial-free online-based language-mapping paradigm was performed. All positive points marked on the cortex in each test were labeled and superimposed together as the result of functional mapping for each patient. The eloquent cortex was mapped according to the results obtained both from the intraoperative trial-free task localization method and the traditional electrical cortical stimulation (ECS). RESULTS: All patients completed this paradigms twice within 10 min. Based on the results of mapping, the EZs were tried to fully resected on the premise of preserving the mapped eloquent cortex as much as possible. The postoperative follow-up showed the outcome of Engel I in six patients and Engel II in three patients, whereas only two patients had aphemia after surgery and recovered within one week and three months, respectively. SIGNIFICANCE: The intraoperative trial-free online-based language mapping method was primarily identified to be safe and effective. This novel method seems to be promising and worthy of improvement.

Assessment of nonnegative matrix factorization algorithms for electroencephalography spectral analysis.

BACKGROUND: Nonnegative matrix factorization (NMF) has been successfully used for electroencephalography (EEG) spectral analysis. Since NMF was proposed in the 1990s, many adaptive algorithms have been developed. However, the performance of their use in EEG data analysis has not been fully compared. Here, we provide a comparison of four NMF algorithms in terms of accuracy of estimation, stability (repeatability of the results) and time complexity of algorithms with simulated data. In the practical application of NMF algorithms, stability plays an important role, which was an emphasis in the comparison. A Hierarchical clustering algorithm was implemented to evaluate the stability of NMF algorithms. RESULTS: In simulation-based comprehensive analysis of fit, stability, accuracy of estimation and time complexity, hierarchical alternating least squares (HALS) low-rank NMF algorithm (lraNMF_HALS) outperformed the other three NMF algorithms. In the application of lraNMF_HALS for real resting-state EEG data analysis, stable and interpretable features were extracted. CONCLUSION: Based on the results of assessment, our recommendation is to use lraNMF_HALS, providing the most accurate and robust estimation.

Limb salvage after aneurysmal degeneration of a cryopreserved vein allograft: Searching the autologous veins of the arm is worth the effort.

CLINICAL DATA: We hereby report a case of limb salvage involving a 64-year-old man who was hospitalized with ischemic foot ulcers for two months. Endarterectomy with patching and stenting of the left iliofemoral artery failed. A composite bypass of two segments of the endarterectomized superficial femoral artery and a cryopreserved saphenous vein graft was implanted one week later. On day 4 postoperatively, an infection (Staphylococcus epidermidis and Pseudomonas aeruginosa) was treated empirically with antibiotics. Four months later, the femoro-tibial bypass thrombosed and the patency was restored by thrombolysis. The aneurysmal cryopreserved vein was excised. Iterative complications followed and final success was attained after implantation of autologous cephalic and basilic veins. Four years later, this femoro-tibial is still patent. PATHOLOGICAL ANALYSES: After a gross observation, the explant was dissected and the most significant sections were processed for histology, followed by analyses in scanning electron microscopy, light microscopy and transmission electron microscopy. RESULTS: The explanted specimen showed a smooth flow surface proximally but a severe distortion distally, with an accumulation of poorly organized mural thrombi. The wall of the arterialized vein was accompanied with an important inflammatory reaction. The degradation of the collagen structure was evidenced in TEM. The fibrils of collagen were still individualized but were fragmented and did not display parallelly. The regular banding was preserved. The presence of Pseudomonas aeruginosa was shown inside the wall of the homologous vein. COMMENTS: In case of sepsis, the most aggressive antibiotic treatments cannot fully eliminate the bacteremic colonizations within the wall of an alternative conduit. The cephalic and basilic autologous veins are proved to be preferable in absence of the autologous saphenous vein. The amputation was prevented and four years later the bypass is still patent. This is an outstanding result based upon the comorbidities of the patient. The most aggressive harvesting shall be recommended. This patient represented a considerable challenge and the clinical result is highly gratifying: the search for the autologous cephalic and basilic veins proved to be worth the effort.

PlpA, a PilZ-like protein, regulates directed motility of the bacterium Myxococcus xanthus.

The rod-shaped bacterium Myxococcus xanthus moves on surfaces along its long cell axis and reverses its moving direction regularly. Current models propose that the asymmetric localization of a Ras-like GTPase, MglA, to leading cell poles determines the moving direction of cells. However, cells are still motile in the mutants where MglA localizes symmetrically, suggesting the existence of additional regulators that control moving direction. In this study, we identified PlpA, a PilZ-like protein that regulates the direction of motility. PlpA and MglA localize into opposite asymmetric patterns. Deletion of the plpA gene abolishes the asymmetry of MglA localization, increases the frequency of cellular reversals and leads to severe defects in cell motility. By tracking the movements of single motor particles, we demonstrated that PlpA and MglA co-regulated the direction of gliding motility through direct interactions with the gliding motor. PlpA inhibits the reversal of individual gliding motors while MglA promotes motor reversal. By counteracting MglA near lagging cell poles, PlpA reinforces the polarity axis of MglA and thus stabilizes the direction of motility.

Low Molecular Seleno-Aminopolysaccharides Protect the Intestinal Mucosal Barrier of Rats under Weaning Stress.

Low molecular seleno-aminopolysaccharide (LSA) was synthesized with sodium selenite and low molecular aminopolysaccharide (LA), which is an organic selenium compound. This study is aimed to investigate the protective effect of LSA on the intestinal mucosal barrier in weaning stress rats by detecting the intestinal tissue morphology and function, mucosal thickness and permeability, the structure of MUC2, antioxidant index, the expression level of intracellular transcription factor NF-E2-related factor 2 (Nrf2), and its related factors. The results showed that LSA significantly increased the height of intestinal villi (p < 0.05) and increased the thickness of intestinal mucosa and the number of goblet cells, which indicated that LSA has a protective effect on the intestinal mucosal barrier that is damaged by weaning. Moreover, LSA significantly reduced the level of DAO, D-LA, and LPS compared with the weaning group (p < 0.05), which indicated that LSA reduced the intestinal damage and permeability of weaning rats. In addition, LSA could increase the number and length of glycans chains and the abundance of acid glycans structures in the MUC2 structure, which indicated that LSA alleviated the changes of intestinal mucus protein structure. LSA significantly increased the levels of GSH-Px, SOD, LDH, and CAT, while it decreased the level of MDA in serum and intestinal tissue, which suggested that LSA significantly enhanced the antioxidant capacity and reduced oxidative stress of weaning rats. RT-PCR results showed that LSA significantly increased the expression level of antioxidant genes (GSH-Px, SOD, Nrf2, HO-1), glycosyltransferase genes (GalNT1, GalNT3, GalNT7) and mucin gene (MUC2) in intestinal mucosa (p < 0.05). The results of western blot showed that the LSA activated the Nrf2 signaling pathway by down-regulating the expression of Keap1and up-regulating the expression of Nrf2, and protected the intestinal mucosa from oxidative stress. Overall, LSA could play a protective role in intestinal mucosal barrier of weaning rats by activating the Nrf2 pathway and alleviating the alnormal change of mucin MUC2.

MicroRNA-206 Downregulates Connexin43 in Cardiomyocytes to Induce Cardiac Arrhythmias in a Transgenic Mouse Model.

BACKGROUND: MicroRNAs (miRNAs) are critical modulators of various physiological and pathological processes, but their role in cardiac arrhythmias remains yet to be completely understood. Connexin43 (Cx43) is an important cardiac gap junction protein and a potential target of miR-206, and downregulation of Cx43 induces ventricular tachyarrhythmias. METHODS: We investigated the effects of miR-206 overexpression on the adult mouse heart and in cardiac arrhythmias. Luciferase activity assay was employed to validate Cx43 as a direct target of miR-206. Expression of Cx43 was measured in cardiac muscle cell line HL-1 securely expressing miR-206. An inducible miR-206 overexpression mouse model was established to evaluate the in vivo effect of miR-206 on Cx43 expression and cardiac rhythm. RESULTS: MiR-206 directly recognised 3'-untranslated region of Cx43 mRNA to inhibit its expression in HL-1 cells. Induction of miR-206 in the adult mouse heart suppressed Cx43 expression, particularly in the atria and ventricle. Importantly, miR-206 overexpression also induced abnormal heart-rate and PR interval, and shortened life-span in the experimental mice. CONCLUSIONS: In cardiomyocytes, miR-206 is a upstream regulator of Cx43, and its overexpression downregulates Cx43 to induce abnormal heart-rate and PR interval.