A model with multiple intracranial aneurysms: possible hemodynamic mechanisms of aneurysmal initiation, rupture and recurrence.

BACKGROUND: Hemodynamic factors play an important role in aneurysm initiation, growth, rupture, and recurrence, while the mechanism of the hemodynamic characteristics is still controversial. A unique model of multiple aneurysms (initiation, growth, rupture, and recurrence) is helpful to avoids the confounders and further explore the possible hemodynamic mechanisms of aneurysm in different states. METHODS: We present a model with multiple aneurysms, and including the states of initiation, growth, rupture, and recurrence, discuss the proposed mechanisms, and describe computational fluid dynamic model that was used to evaluate the likely hemodynamic effect of different states of the aneurysms. RESULTS: The hemodynamic analysis suggests that high flow impingement and high WSS distribution at normal parent artery was found before aneurysmal initiation. The WSS distribution and flow velocity were decreased in the new sac after aneurysmal growth. Low WSS was the risk hemodynamic factor for aneurysmal rupture. High flow concentration region on the neck plane after coil embolization still marked in recanalized aneurysm. CONCLUSIONS: Associations have been identified between high flow impingement and aneurysm recanalization, while low WSS is linked to the rupture of aneurysms. High flow concentration and high WSS distribution at normal artery associated with aneurysm initiation and growth, while after growth, the high-risk hemodynamics of aneurysm rupture was occurred, which is low WSS at aneurysm dome.

Result of a Pilot External Quality Assessment Scheme for Clinical Diagnosis of Inherited Metabolic Disorders in China.

BACKGROUND: We aimed to evaluate the diagnostic capabilities of Chinese laboratories for inherited metabolic disorders (IMDs) using gas chromatography-mass spectrometry (GC-MS) on urine samples. Meanwhile, based on the result of the pilot external quality assessment (EQA) scheme, we hope to establish a standardized and reliable procedure for future EQA practice. METHODS: We recruited laboratories that participated in the EQA of quantitative analysis of urinary organic acids with GC-MS before joining the surveys. In each survey, a set of five real urine samples was distributed to each participant. The participants should analyze the sample by GC-MS and report the "analytical result", "the most likely diagnosis", and "recommendation for further tests" to the NCCL before the deadline. RESULTS: A total of 21 laboratories participated in the scheme. The pass rates were 94.4% in 2020 and 89.5% in 2021. For all eight IMDs tested, the analytical proficiency rates ranged from 84.7% - 100%, and the interpretational performance rate ranged from 88.2% - 97.0%. The performance on hyperphenylalaninemia (HPA), 3-methylcrotonyl-CoA carboxylase deficiency (MCCD), and ethylmalonic encephalopathy (EE) samples were not satisfactory. CONCLUSIONS: In general, the participants of this pilot EQA scheme are equipped with the basic capability for qualitative organic acid analysis and interpretation of the results. Limited by the small size of laboratories and samples involved, this activity could not fully reflect the state of clinical practice of Chinese laboratories. NCCL will improve the EQA scheme and implement more EQA activities in the future.

[Clinical analysis and genetic diagnosis of three children with Isoleucine metabolic disorders due to variants of HSD17B10 and ACAT1 genes].

OBJECTIVE: To explore the clinical, biochemical and genetic characteristics of three children with Isoleucine metabolic disorders due to variants of HSD17B10 and ACAT1 genes. METHODS: Two children with 17ß hydroxysteroid dehydrogenase 10 (HSD17B10) deficiency and a child with ß-ketothiolase deficiency (BKD) diagnosed at Shanghai Children's Hospital between 2014 and 2021 were selected as the study subjects. Clinical data of the children were collected. The children were subjected to blood acylcarnitine, urinary organic acid and genetic testing, and candidate variants were analyzed with bioinformatic tools. RESULTS: The main symptoms of the three children had included epilepsy, developmental delay, hypotonia and acidosis. Their blood acylcarnitine methylcrotonyl carnitine (C5:1), 3-hydroxyisovalerylcarnitine (C5-OH) and 3-hydroxybutylcarnitine (C4OH) were increased to various extents, and urine organic acids including methyl crotonylglycine and 2-methyl-3-hydroxybutyric acid were significantly increased. Child 1 and child 2 were respectively found to harbor a c.347G>A (p.R116Q) variant and a c.274G>A (p.A92T) variant of the HSD17B10 gene, and child 3 was found to harbor compound heterozygous variants of the ACAT1 gene, namely c.547G>A (p.G183R) and a c.331G>C (p.A111P). Among these, the c.274G>A (p.A92T) and c.331G>C (p.A111P) variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively classified as variant of unknown significance (PP3_Strong+PM2_supporting) and likely pathogenic (PM3+PM2_Supporting+PP3_Moderate+PP4). CONCLUSION: Both the HSD17B10 deficiency and BKD can lead to Isoleucine metabolism disorders, which may be difficult to distinguish clinically. Genetic testing can further confirm the diagnosis. Discoveries of the HSD17B10: c.274G>A (p.A92T) variant and the ACAT1: c.331G>C (p.A111P) variant have enriched the mutational spectrum of the two diseases.

Comparative analysis of inherited metabolic diseases in normal newborns and high-risk children: Insights from a 10-year study in Shanghai.

BACKGROUND: Compare the differences between normal newborns and high-risk children with inherited metabolic diseases. The disease profile includes amino acidemias, fatty acid oxidation disorders, and organic acidemias. METHODS: Data was collected on newborns and children from high-risk populations in Shanghai from December 2010 to December 2020. RESULTS: 232,561 newborns were screened for disorders of organic, amino acid, and fatty acid metabolism. The initial positive rate was 0.66 % (1,526/232,561) and the positive recall rate was 77.85 %. The positive predictive value is 4.71 %. Among them, 56 cases were diagnosed as metabolic abnormalities. The total incidence rate is 1:4153. Hyperphenylalaninemia and short-chain acyl-CoA dehydrogenase are the most common diseases in newborns. In addition, in 56 children, 39 (69.42 %) were diagnosed by genetic sequencing. Some hotspot mutations in 14 IEMs have been observed, including PAH gene c.728G > A, c.611A > G, and ACADS gene c. 1031A > G, c.164C > T. A total of 49,860 symptomatic patients were screened, of which 185 were diagnosed with IEM, with a detection rate of 0.37 %. The most commonly diagnosed diseases in high-risk infants aremethylmalonic acidemia and hyperphenylalaninemia. CONCLUSION: There are more clinical cases of congenital metabolic errors diagnosed by tandem mass spectrometry than newborn screening. The spectrum of diseases, prevalence, and genetic characteristics of normal newborns and high-risk children are quite different.

Patient-derived tumor-like cell clusters for personalized chemo- and immunotherapies in non-small cell lung cancer.

Many patient-derived tumor models have emerged recently. However, their potential to guide personalized drug selection remains unclear. Here, we report patient-derived tumor-like cell clusters (PTCs) for non-small cell lung cancer (NSCLC), capable of conducting 100-5,000 drug tests within 10 days. We have established 283 PTC models with an 81% success rate. PTCs contain primary tumor epithelium self-assembled with endogenous stromal and immune cells and show a high degree of similarity to the original tumors in phenotypic and genotypic features. Utilizing standardized culture and drug-response assessment protocols, PTC drug-testing assays reveal 89% overall consistency in prospectively predicting clinical outcomes, with 98.1% accuracy distinguishing complete/partial response from progressive disease. Notably, PTCs enable accurate prediction of clinical outcomes for patients undergoing anti-PD1 therapy by combining cell viability and IFN-γ value assessments. These findings suggest that PTCs could serve as a valuable preclinical model for personalized medicine and basic research in NSCLC.

Perioperative and long-term results of ultrasonography-guided single- and multiple-tract percutaneous nephrolithotomy for staghorn calculi.

BACKGROUND: It is possible that this condition will lead to urosepsis and progressive deterioration of renal function in the absence of surgical intervention. Several recent clinical studies have shown that multi-tract percutaneous nephrolithotomy (M-PCNL) has a similar stone free rate (SFR) as standard percutaneous nephrolithotomy (S-PCNL). As a result, M-PCNL was also recommended as a treatment option for staghorn calculi. AIM: To examine the perioperative and long-term results of ultrasonography-guided single- and M-PCNL. METHODS: This was a retrospective cohort study. Between March 2021 and January 2022, the urology department of our hospital selected patients for the treatment of staghorn calculi using percutaneous nephrolithotomy. The primary outcomes were complication rate and SFR, and the characteristics of patients, operative parameters, laboratory measurements were also collected. RESULTS: In total, 345 patients were enrolled in the study (186 in the S-PCNL group and 159 in the M-PCNL group). The SFR in the M-PCNL group was significantly higher than that in the S-PCNL group (P = 0.033). Moreover, the incidence rates of hydrothorax (P = 0.03) and postoperative infection (P = 0.012) were higher in the M-PCNL group than in the S-PCNL group. Logistic regression analysis demonstrated that post-operative white blood cell count (OR = 2.57, 95%CI: 1.90-3.47, P < 0.001) and stone size (OR = 1.59, 95%CI: 1.27-2.00, P < 0.001) were associated with a higher overall complication rate in the S-PCNL group. Body mass index (OR = 1.22, 95%CI: 1.06-1.40, P = 0.004) and stone size (OR = 1.70, 95%CI: 1.35-2.15, P < 0.001) were associated with increased overall complications in the M-PCNL group. CONCLUSION: Multiple access tracts can facilitate higher SFR while slightly increasing the incidence of acceptable complications.

Two-dimensional correlation infrared spectroscopy elucidated the volatilization process of the microemulsion composed of peppermint essential oil and composite herbal extract.

Microemulsion is usually a transparent and isotropic liquid mixture composed of oil phase, water phase, surfactant and cosurfactant. The surfactant-framed nanoscale droplets in the microemulsion can penetrate into the skin surface to reduce its barrier function. This makes microemulsion an ideal preparation for the transdermal drug delivery. The permeability of microemulsion may be further enhanced when botanical essential oils that can dissolve the stratum corneum are used as the oil phase. However, the volatility of essential oils is possible to shorten the retention time of the microemulsion on the skin surface. Therefore, analytical methods are required to understand the volatilization process of the microemulsion composed of essential oils to develop the reasonable topical drug carrier system. In this research, Fourier transform infrared (FTIR) spectroscopy with an attenuated total reflection (ATR) accessory cooperated with two-dimensional correlation spectroscopy (2DCOS) to elucidate the volatilization processes of some microemulsions composed of peppermint essential oil. Principal component analysis (PCA) and moving-window two-dimensional correlation spectroscopy (MW2DCOS) revealed the multiple stages of the volatilization processes of the microemulsions. Synchronous 2D correlation infrared spectra indicated the compositional changes during each stage. It was found that the successive volatilizations of ethanol, water and menthone were the major events during the volatilization process of the microemulsion composed of peppermint essential oil. Ethanol can accelerate the volatilization of water, while the composite herbal extract seemed to not influence the volatilization of the other ingredients. After a 20-min-long volatilization process, the remaining microemulsion still contained considerable peppermint essential oil to affect the skin. The above results showed the feasibility of developing the microemulsion composed of peppermint essential oil for the transdermal drug delivery of composite herbal extract. This research also proved that the combination of ATR-FTIR spectroscopy and 2DCOS was valuable to study the volatilization process of the microemulsion.

Improving the second-tier classification of methylmalonic acidemia patients using a machine learning ensemble method.

INTRODUCTION: Methylmalonic acidemia (MMA) is a disorder of autosomal recessive inheritance, with an estimated prevalence of 1:50,000. First-tier clinical diagnostic tests often return many false positives [five false positive (FP): one true positive (TP)]. In this work, our goal was to refine a classification model that can minimize the number of false positives, currently an unmet need in the upstream diagnostics of MMA. METHODS: We developed machine learning multivariable screening models for MMA with utility as a secondary-tier tool for false positives reduction. We utilized mass spectrometry-based features consisting of 11 amino acids and 31 carnitines derived from dried blood samples of neonatal patients, followed by additional ratio feature construction. Feature selection strategies (selection by filter, recursive feature elimination, and learned vector quantization) were used to determine the input set for evaluating the performance of 14 classification models to identify a candidate model set for an ensemble model development. RESULTS: Our work identified computational models that explore metabolic analytes to reduce the number of false positives without compromising sensitivity. The best results [area under the receiver operating characteristic curve (AUROC) of 97%, sensitivity of 92%, and specificity of 95%] were obtained utilizing an ensemble of the algorithms random forest, C5.0, sparse linear discriminant analysis, and autoencoder deep neural network stacked with the algorithm stochastic gradient boosting as the supervisor. The model achieved a good performance trade-off for a screening application with 6% false-positive rate (FPR) at 95% sensitivity, 35% FPR at 99% sensitivity, and 39% FPR at 100% sensitivity. CONCLUSIONS: The classification results and approach of this research can be utilized by clinicians globally, to improve the overall discovery of MMA in pediatric patients. The improved method, when adjusted to 100% precision, can be used to further inform the diagnostic process journey of MMA and help reduce the burden for patients and their families.

The effects of methylphenidate and atomoxetine on Drosophila brain at single-cell resolution and potential drug repurposing for ADHD treatment.

The stimulant methylphenidate (MPH) and the non-stimulant atomoxetine (ATX) are frequently used for the treatment of attention-deficit/hyperactivity disorder (ADHD); however, the function of these drugs in different types of brain cells and their effects on related genes remain largely unknown. To address these questions, we built a pipeline for the simultaneous examination of the activity behavior and transcriptional responses of Drosophila melanogaster at single-cell resolution following drug treatment. We selected the Drosophila with significantly increased locomotor activities (hyperactivity-like behavior) following the administration of each drug in comparison with the control (same food as the drug-treated groups with 5% sucrose, yeast, and blue food dye solution) using EasyFlyTracker. Subsequently, single cell RNA sequencing (scRNASEQ) was used to capture the transcriptome of 82,917 cells, unsupervised clustering analysis of which yielded 28 primary cell clusters representing the major cell types in adult Drosophila brain. Indeed, both neuronal and glial cells responded to MPH and ATX. Further analysis of differentially expressed genes (DEGs) revealed distinct transcriptional changes associated with these two drugs, such as two well-studied dopamine receptor genes (Dop2R and DopEcR) were responsive to MPH but not to ATX at their optimal doses, in addition to genes involved in dopamine metabolism pathways such as Syt1, Sytalpha, Syt7, and Ih in different cell types. More importantly, MPH also suppressed the expression of genes encoding other neurotransmitter receptors and synaptic signaling molecules in many cell types, especially those for Glu and GABA, while the responsive effects of ATX were much weaker. In addition to monoaminergic neuronal transmitters, other neurotransmitters have also shown a similar pattern with respect to a stronger effect associated with MPH than with ATX. Moreover, we identified four distinct glial cell subtypes responsive to the two drugs and detected a greater number of differentially expressed genes associated with ensheathing and astrocyte-like glia. Furthermore, our study provides a rich resource of candidate target genes, supported by drug set enrichment analysis (P = 2.10E-4; hypergeometric test), for the further exploration of drug repurposing. The whole list of candidates can be found at ADHDrug ( http://adhdrug.cibr.ac.cn/ ). In conclusion, we propose a fast and cost-efficient pipeline to explore the underlying molecular mechanisms of ADHD drug treatment in Drosophila brain at single-cell resolution, which may further facilitate drug repurposing applications.

Exosomes; a Potential Source of Biomarkers, Therapy, and Cure for Type-1 Diabetes.

The scourge of type-1 diabetes (T1D) is the morbidity and mortality it and its complications cause at a younger age. This propels the constant search for better diagnostic, treatment, and management strategies, with the ultimate quest being a cure for T1D. Recently, the therapeutic potential of exosomes has generated a lot of interest. Among the characteristics of exosomes of particular interest are (a) their regenerative capacity, which depends on their "origin", and (b) their "content", which determines the cell communication and crosstalk they influence. Other functional capacities, including paracrine and endocrine homeostatic regulation, pathogenic response ability resulting in insulin secretory defects or ß-cell death under normal metabolic conditions, immunomodulation, and promotion of regeneration, have also garnered significant interest. Exosome "specificity" makes them suitable as biomarkers or predictors, and their "mobility" and "content" lend credence to drug delivery and therapeutic suitability. This review aims to highlight the functional capacities of exosomes and their established as well as novel contributions at various pathways in the onset and progression of T1D. The pathogenesis of T1D involves a complex crosstalk between insulin-secreting pancreatic ß-cells and immune cells, which is partially mediated by exosomes. We also examine the potential implications for type 2 diabetes (T2D), as the link in T2D has guided T1D exploration. The collective landscape presented is expected to help identify how a deeper understanding of exosomes (and their cargo) can provide a framework for actionable solutions to prevent, halt, or change the very course of T1D and its complications.

Enhancing supercapacitor performance using nanosheet-covered nanotube structures Co3S4/Ni0.96S@CNTs with carbon nanotubes as conductive substrates.

Transition metal sulfides have broad application prospects as supercapacitor electrode materials. However, their poor structural stability and conductivity hinder improvements in their electrochemical performance. Therefore, the introduction of highly conductive carbon nanotubes (CNTs) as sulfide growth substrates is considered to improve the microstructure and electrochemical performance of electrode materials. In this study, a highly conductive CNT solution was sprayed onto a nickel foam current collector, and Co3S4/Ni0.96S was successfully constructed on a CNT conductive substrate using a combination of hydrothermal and electrochemical deposition methods, forming a unique nanosheet-covered nanotube structure Co3S4/Ni0.96S@CNTs. The addition of an appropriate concentration of CNTs can not only serve as a substrate for the growth of Co3S4/Ni0.96S, but also effectively maintain the overall nanosheet structure. Thus, the Co3S4/Ni0.96S@CNTs (2-CSNS@CNTs) have a stable structure and a wide range of electrochemical reaction sites, ensuring excellent conductivity and cycling stability. The electrode material 2-CSNS@CNTs exhibited a specific capacity of 1427.05 C g-1 at 1 A g-1. Additionally, the asymmetric supercapacitor 2-CSNS@CNTs exhibited a high energy density of 53.76 W h kg-1 at 800 W kg-1 and a capacity retention rate of 68.5% at 10 A g-1 after 1000 cycles.

Stem Cell Therapy for Aging Related Diseases and Joint Diseases in Companion Animals.

Stem cell therapy is an attractive treatment for diseases in companion animals that cannot be treated by conventional veterinary medicine practices. The unique properties of stem cells, particularly the ability to differentiate into specific cell types, makes them a focal point in regenerative medicine treatments. Stem cell transplantation, especially using mesenchymal stem cells, has been proposed as a means to treat a wide range of injuries and ailments, resulting in tissue regeneration or repair. This review aims to summarize the veterinary use of stem cells for treating age-related and joint diseases, which are common conditions in pets. While additional research is necessary and certain limitations exist, the potential of stem cell therapy for companion animals is immense.

Surface and near-surface engineering design of transition metal catalysts for promoting water splitting.

Transition metal catalysts are widely used in the field of hydrogen production via water electrolysis. The surface state and near-surface environment of the catalysts greatly affect the efficiency of hydrogen production. Therefore, the rational design of surface engineering and near-surface engineering of transition metal catalysts can significantly improve the performance of water electrolysis. This review systematically introduces surface engineering strategies, including heteroatom doping, vacancy engineering, strain regulation, heterojunction effect, and surface reconstruction. These strategies optimize the surface electronic structure of the catalysts, expose more active sites, and promote the formation of highly active species, ultimately enhancing water electrolysis performance. Furthermore, near-surface engineering strategies, such as surface wettability, three-dimensional structure, high-curvature structure, external field assistance, and extra ion addition, are thoroughly discussed. These strategies expedite the mass transfer of reactants and gas products, improve the local chemical environment near the catalyst surface, and contribute toward achieving an industrial-level current density for overall water splitting. Finally, the key challenges faced by surface engineering and near-surface engineering of transition metal catalysts are highlighted and potential solutions are proposed. This review offers essential guidelines for the design and development of efficient transition metal catalysts for water electrolysis.

Study of the mining and aquifer interactions in complex geological conditions and its management.

The interaction of mining and the surface water or aquifer system in varying overburden strata conditions is one of the most critical aspects of sustainable mining practices, that can lead to water loss or water inrush into openings. This paper examined this phenomenon in a complex strata condition via a case study, and proposed a new mining design to minimize the impact of longwall mining on the overlaying aquifer. A range of factors have been identified contributing to the potential disturbance of the aquifer, including the extent of the water-rich area, the characteristics of overburden rock units, and the development height of the water-conducting fracture zone. In this study, the transient electromagnetic method and the high-density three-dimensional electrical method were used to identify two areas prone to water inrush danger in the working face. The vertical range of the water-rich abnormal area 1 is 45-60 m away from the roof, with an area of 3334 m2. The vertical range of the water-rich abnormal area 2 is 30-60 m away from the roof, with an area of approximately 2913 m2. The bedrock drilling method was used to determine that the thinnest part of the bedrock, with a thickness of approximately 60 m, and the thickest part, with a thickness of approximately 180 m. The maximum mining-induced height of the fracture zone was 42.64 m using empirical method, theoretical prediction based on the rock stratum group, field monitoring. In summary, the high risk area was determined, and the analysis shows that the size of the water prevention) pillar was 52.6 m, which was smaller than the safe water prevention pillar actually set in the mining range. The research conclusion provides important safety guidance significance for the mining of similar mines.

Study on the dynamic metabolic characteristic of main active ingredients in Danggui Buxue Decoction by liquid chromatography-tandem mass spectrometry based on in situ sequential metabolism strategy.

Danggui Buxue Decoction is a classic formula for replenishing qi and nourishing blood. Despite its widespread use, its dynamic metabolism involved remains unclear. Based on the sequential metabolism strategy, blood samples from different metabolic sites were obtained via in situ closed intestine ring integrated with a jugular venous continuous blood supply technique. An ultra-high-performance liquid chromatography-linear triple quadruple-Orbitrap-tandem mass spectrometry method was developed for the identification of prototypes and metabolites in rat plasma. The dynamic absorption and metabolic landscape of flavonoids, saponins, and phthalides were characterized. Flavonoids could be deglycosylated, deacetylated, demethylated, dehydroxylated, and glucuronicated in the gut and then absorbed for further metabolism. Jejunum is an important metabolic site for saponins biotransformation. Saponins that are substituted by Acetyl groups tend to lose their acetyl groups and convert to Astragaloside IV in the jejunum. Phthalides could be hydroxylated and glucuronidated in the gut and then absorbed for further metabolism. Seven components serve as crucial joints in the metabolic network and are potential candidates for the quality control of Danggui Buxue Decoction. The sequential metabolism strategy described in this study could be useful for characterizing the metabolic pathways of Chinese medicine and natural products in the digestive system.

Spatiotemporal Epidemiology of the Gonorrhea Epidemic in Relation to Neighborhood-level Structural Factors in an Eastern Province of China, 2016-2020.

Context: Gonorrhea, a highly communicable, sexually transmitted infection, remains a major public-health concern globally. In recent years, Zhejiang province, an eastern province, has had the highest incidence of gonorrhea in China. Objective: The study intended to identify the geographic distribution patterns and spaciotemporal clustering characteristics of the disease's incidence in Zhejiang between 2016 and 2020, to understand the spatial epidemiology of gonorrhea and to pinpoint the locations with relatively high risks of gonorrhea, the hotspots, which could be the key areas for disease prevention and control. Design: The research team performed a retrospective, spaciotemporal-clustering analysis of data about newly reported gonorrhea cases from January 2016 to December 2020 in Zhejiang province, using the China Information System for Disease Control and Prevention. Setting: The study took place at the Zhejiang Provincial Institute of Dermatology in Huzhou, China. Outcome Measures: The research team: (1) used the Geographic Information System software-ArcGIS 10.8 software to draw statistical maps; (2) conducted a spatial-pattern clustering analysis at the district or county level; (3) performed an autocorrelation analysis using Getis-Ord (Gi*) statistics to detect spatial patterns and the hotspots of gonorrhea incidence; and (4) used SaTScan9.7 to analyze the space-time clusters. Results: Zhejiang province reported 85 904 gonorrhea cases from 2016 to 2020, with a male to female ratio of 3.81:1. The average annual incidence rate of gonorrhea was 30.50 per 100 000 individuals in the population, ranging from 22.73 cases to 39.65 cases, and the annual incidence showed a significant downward trend over the five years (χ2 = 16.142, P < .001). The northern and central areas had a higher incidence than the southern area did. Autocorrelation analysis showed that the gonorrhea incidence had a significantly clustered distribution (Moran's I from 0.197 to 0.295, Z score from 4.749 to 6.909, P < .001). The high-high cluster areas were mainly in the urban districts of Hangzhou and some counties and districts of Jiaxing. The Gi* statistics further indicated that the hotspots of gonorrhea were mainly in Hangzhou, Jiaxing, and Huzhou. The Kuldorff's scan identified two clusters, mainly composed of 36 counties or districts in northern Zhejiang, such as Hangzhou and Jiaxing, and central Zhejiang, such as Jinhua and Shaoxing. Conclusions: The gonorrhea incidence rates in northern and central Zhejiang from 2016 to 2020 were higher than those in southern Zhejiang. An area of relatively higher risk for gonorrhea existed mainly in the urban districts of Hangzhou and some counties and districts of Jiaxing, Jinhua, and Shaoxing. In the future, the research team plans to focus on strengthening the prevention and control measures against gonorrhea in those areas.

Multivariate analysis and model building for classifying patients in the peroxisomal disorders X-linked adrenoleukodystrophy and Zellweger syndrome in Chinese pediatric patients.

BACKGROUND: The peroxisome is a ubiquitous single membrane-enclosed organelle with an important metabolic role. Peroxisomal disorders represent a class of medical conditions caused by deficiencies in peroxisome function and are segmented into enzyme-and-transporter defects (defects in single peroxisomal proteins) and peroxisome biogenesis disorders (defects in the peroxin proteins, critical for normal peroxisome assembly and biogenesis). In this study, we employed multivariate supervised and non-supervised statistical methods and utilized mass spectrometry data of neurological patients, peroxisomal disorder patients (X-linked adrenoleukodystrophy and Zellweger syndrome), and healthy controls to analyze the role of common metabolites in peroxisomal disorders, to develop and refine a classification models of X-linked adrenoleukodystrophy and Zellweger syndrome, and to explore analytes with utility in rapid screening and diagnostics. RESULTS: T-SNE, PCA, and (sparse) PLS-DA, operated on mass spectrometry data of patients and healthy controls were utilized in this study. The performance of exploratory PLS-DA models was assessed to determine a suitable number of latent components and variables to retain for sparse PLS-DA models. Reduced-features (sparse) PLS-DA models achieved excellent classification performance of X-linked adrenoleukodystrophy and Zellweger syndrome patients. CONCLUSIONS: Our study demonstrated metabolic differences between healthy controls, neurological patients, and peroxisomal disorder (X-linked adrenoleukodystrophy and Zellweger syndrome) patients, refined classification models and showed the potential utility of hexacosanoylcarnitine (C26:0-carnitine) as a screening analyte for Chinese patients in the context of a multivariate discriminant model predictive of peroxisomal disorders.

A cycle-durable hollow nanoneedle structure with a nanosheet as a conductive substrate CoS1.097/Ni9S8@RGO to enhance supercapacitor performance.

Metal sulfides are promising supercapacitor electrode materials with a large theoretical capacity and rich operability. However, its unsatisfactory cycle stability and rate performance are tough problems to be solved. Therefore, the preparation of metal sulfide-based electrode materials with a stable structure, long cycle life, and high-rate performance is an effective strategy to solve these problems. Herein, metal sulfides were first crystallized into crosslinked nanosheet and nanotube structures, which ensure abundant active sites for redox reactions. Then, the further modification of the prepared material by spraying graphene was carried out, which, as demonstrated by combining experimental data and physical characterization, leads to a more complete hollow structure, enlarged electrochemical reaction sites, and reduced electrolyte transport distance, thus improving the charge transfer kinetics. In the early stage of the charge-discharge cycle test, the electrode material undergoes a self-activation process, which transforms the electrode material from one equilibrium state to a new equilibrium state. Therefore, 2-CSNS@RGO electrode capacitance was 1650.13 C g-1 at 1 A g-1 with remarkable cycling of 3000 cycles at 10 A g-1, and it retains 186.1% capacity of the initial value. An asymmetric supercapacitor (2-CSNS@RGO//AC) was prepared by coupling 2-CSNS@RGO as the positive electrode and activated carbon (AC) as the negative electrode. 2-CSNS@RGO//AC has an energy density of 88 W h kg-1 at a power density of 0.8 kW kg-1, and the capacity retention rate is 131.6% after 30 000 cycles at 10 A g-1.

SENP1 modulates chronic intermittent hypoxia-induced inflammation of microglia and neuronal injury by inhibiting TOM1 pathway.

Chronic intermittent hypoxia (CIH) is a characteristic pathophysiological change of obstructive sleep apnea syndrome (OSAS). Inflammation of microglia induced by CIH, plays a vital role in OSAS-associated cognitive dysfunction. SUMO-specific proteases 1 (SENP1) has been implicated in tumor inflammatory microenvironment and cells migration. However, the role of SENP1 in CIH-induced neuroinflammation remains unknown. We aimed to investigate the effect of SENP1 on neuroinflammation and neuronal injury. After the preparation of SENP1 overexpression microglia and SENP1 knockout mouse, CIH microglia and mice were established using an intermittent hypoxia device. Results showed that CIH reduced the level of SENP1 and TOM1, induced the SUMOylation of TOM1, and promoted microglial migration, neuroinflammation, neuronal amyloid-beta 42 (Aß42) deposition and apoptosis in vitro and in vivo. After SENP1 overexpression in vitro, the enhanced SUMOylation of TOM1 was inhibited; the level of TOM1 and microglial migration were enhanced; neuroinflammation, neuronal Aß42 deposition and apoptosis were significantly reduced. However, the administration of siRNA-TOM1 suppressed microglial migration, neuroinflammation, neuronal Aß42 deposition and apoptosis. After SENP1 knockout in vivo, the SUMOylation enhancement of TOM1 was accelerated, microglial migration was inhibited. Neuroinflammation, neuronal Aß42 deposition and apoptosis, cognitive impairment was significantly exacerbated. Overall, the results demonstrated that SENP1 promoted microglial migration by alleviating the de-SUMOylation of TOM1, thus contributing to attenuate neuroinflammation, neuronal Aß42 deposition and neuronal apoptosis induced by CIH.