Elevated muramyl dipeptide by sialic acid-facilitated postantibiotic pathobiont expansion contributes to gut dysbiosis-induced mastitis in mice.

INTRODUCTION: In responses to antibiotics exposure, gut dysbiosis is a risk factor not only for pathogen infection but also for facilitating pathobiont expansion, resulting in increased inflammatory responses in the gut and distant organs. However, how this process is regulated has not been fully elucidated. OBJECTIVES: In this study, we investigated the role of sialic acid, a host-derived carbohydrate, in the pathogenesis of gut dysbiosis-derived inflammation in distant organs. METHODS: Ampicillin (Amp)-induced gut dysbiotic mice were treated with N-glycolylneuraminic acid (Neu5Gc) and N-acetylneuraminic acid (Neu5Ac) for three weeks to assess the role of sialic acids in mastitis. The underlying mechanism by which sialic acids regulate mastitis was explored using 16S rRNA sequencing, transcriptomics and employed multiple molecular approaches. RESULTS: Administration of Neu5Ac and Neu5Gc exacerbated gut dysbiosis-induced mastitis and systemic inflammation. The gut dysbiosis caused by Amp was also aggravated by sialic acid. Notably, increased Enterococcus expansion, which was positively correlated with inflammatory markers, was observed in both Neu5Ac- and Neu5Gc-treated gut dysbiotic mice. Treatment of mice with Enterococcus cecorum (E. cecorum) aggravated gut dysbiosis-induced mastitis. Mechanically, sialic acid-facilitated E. cecorum expansion promoted muramyl dipeptide (MDP) release, which induced inflammatory responses by activating the NOD2-RIP2-NF-κB axis. CONCLUSIONS: Collectively, our data reveal a role of sialic acid-facilitated postantibiotic pathobiont expansion in gut dysbiosis-associated inflammation, highlighting a potential strategy for disease prevention by regulating the MDP-NOD2-RIP2 axis.

A single-pixel and non-redundant branching-based algorithm for nailfold capillary skeleton line extraction.

Background: Static nailfold capillary parameters are important parameters that reflect the health of the human body. Disease onset or progression is often accompanied by changes in the physiological parameters of the nailfold. Hence, the physiological parameters of the nailfold are closely related to the study of disease, with their automated and high-precision measurements playing a crucial role in these studies. Currently, manually measured values of the nailfold's parameters are the gold standard; however, they are time consuming and labor intensive, making the development of automated measurement methods essential. Most automated measurement methods use skeleton lines; however, current skeleton-thinning algorithms have non-single pixels and redundant branches that lead to reduced measurement accuracy. This study proposes a single-pixel and non-redundant branching-based skeleton line extraction algorithm for nailfold capillaries, which is then applied to nailfold static parameter calculations to improve accuracy. Methods: The algorithm includes deletion and restoration templates combined with the depth-first search method to obtain single-pixel skeleton lines without redundant branches. These lines are applied to the static nailfold capillary parameter measurement method based on digital image processing to calculate the blood vessel diameter. Results: The results show that the proposed method can obtain the single-pixel skeleton line without the redundant branches that are required for the parameter calculations and improve the accuracy of the nailfold capillary diameter measurement. Experiments showed that the root mean square errors (RMSEs) of the labeled apical diameter, arterial limb diameter, and venous limb diameter were 0.794, 0.756, and 0.830 µm, respectively, when the calculated results were compared with those of the manual calculations. According to the accuracy formula, the accuracy of the method in this study is 90%. We calculated the P values of the algorithmic and manual measurements to P<0.001 and found that the difference in the measurements of the proposed algorithm is statistically significant. Therefore, the method in this study has high sensitivity and specificity for the measurement of normal nailfold capillaries. Conclusions: The proposed algorithm could obtain single-pixel skeleton lines without redundant branches, thereby improving the nailfold static parameter measurement accuracy.

Screening and monitoring of diabetic retinopathy in community care: the effectiveness of single-field vs multi-field fundus photography.

PURPOSE: This study aimed to evaluate the effectiveness of single-field fundus photography for diabetic retinopathy (DR) screening and monitoring versus six-field imaging in community settings. METHODS: Adults aged ≥30 years with type 2 diabetes from 15 communities in Northeast China were recruited for this prospective cohort study (n=2006 at baseline and n=1456 at follow-up). Participants underwent both single-field and six-field digital fundus photography at baseline and follow-up visits (mean duration of 21.2±3.2 months). Photographs were graded using international standards. Agreement in DR severity grading, referral recommendations, and detection of DR progression were compared between single-field and six-field fundus photography. RESULTS: Single-field grading showed substantial agreement with multi-field grading in classifying DR severity (81.9% identical at baseline, 80.6% at follow-up, Gwet's AC1 0.79 and 0.77). For referring eyes with moderate non-proliferative DR or worse, single-field grading had ∼70% sensitivity and 100% specificity compared to six-field grading. Single-field grading identified 74.9% or 79.7% of eyes progressing or regressing by six-field grading, respectively. CONCLUSIONS: Single-field fundus photography demonstrated reasonable effectiveness for DR screening and monitoring in a community setting, supporting its use for improving access to DR detection. However, reduced sensitivity compared to multi-field imaging should be acknowledged.

Analysis of different standards for life support technology in manned submersible.

Life support technology is one of the most critical technologies in manned submersibles, acting for the pilots of the submersible and thus directly affecting its underwater safety. Due to its importance, many countries and international organizations have proposed standards and specifications for life support technology. This paper presents an overview of the life support technology of manned submersibles, comparing the standards proposed for it. Furthermore, it analyzes the specific data of oxygen supply and carbon dioxide absorption, both of which are critical aspects of life support technology in each standard, and identifies the data that is widely acknowledged and recognized as the basis for establishing ISO standard 22252:2020). Finally, ISO standard data such as oxygen and carbon dioxide concentration are further confirmed by the environmental parameters of manned submersibles such as the Fendouzhe.

Caffeic acid inhibits Staphylococcus aureus-induced endometritis through regulating AMPKα/mTOR/HIF-1α signalling pathway.

Endometritis is mostly caused by childbirth or postpartum uterine infection. It is one of the important reasons leading to female infertility. Caffeic acid (CA) and its derivatives are widely found in some foods and traditional Chinese medicine, and have biological activities such as antioxidant, free radical scavenging, anti-inflammatory, and anti-infection. In this study, we aimed to explore the effect of CA on Staphylococcus aureus-induced endometritis. The contents of TNF-α and IL-1ß were detected by ELISA in S. aureus-induced endometritis model. Western blot assay was used to detect the expression of AMPKα/mTOR/HIF-1α pathway related proteins and GPX4 expression. In addition, the concentrations of MDA, GSH, and iron were tested by the assay kits. Compared with the model group, CA treatment significantly alleviated S. aureus-induced uterine injury, MPO activity, the contents of inflammatory factors TNF-α and IL-1ß, and NF-κB activation. Meanwhile, CA significantly inhibited S. aureus-induced ferroptosis, as confirmed by decreased MDA and iron concentration and up-regulated GPX4 expression and GSH level. Furthermore, CA attenuated S. aureus-induced HIF-1α and phosphorylated mTOR expression and increased phosphorylated AMPK expression. In conclusion, CA inhibits inflammation and ferroptosis by regulating AMPKα/mTOR/HIF-1α signalling pathway to alleviate S. aureus-induced endometritis in mice.

Dysregulation and impaired anti-bacterial potential of mucosal-associated invariant T cells in autoimmune liver diseases.

Autoimmune liver diseases (AILD) encompass a group of conditions in which the immune system mistakenly attacks the liver tissue. Mucosal-associated invariant T (MAIT) cells are enriched in the liver, where they play crucial roles in antibacterial defense and inflammation regulation. Compared to other autoimmune conditions affecting the synovium of the joints, MAIT cells from AILD exhibited a greater deficiency in ratio, elevated activation markers, increased apoptosis, and higher pro-inflammatory cytokines production. However, the frequency of MAIT cells in AILD was negatively correlated with anti-bacterial indexes, and their impaired responsiveness and weakened anti-bacterial potential were evidenced by reduced expansion ability, lower maximal IFN-γ production, and diminished E. coli-induced cytotoxic mediators release. Similar shifts in MAIT cell ratios and phenotypes were observed in both primary biliary cirrhosis and autoimmune hepatitis, linked to upregulation of bile acid components in the affected tissue. Specifically, ursodeoxycholic acid, a metabolic intermediate and traditional anti-primary biliary cirrhosis drug, inhibited TCR-mediated expansion and downregulated pro-inflammatory cytokines and anti-bacterial-related mediators in MAIT cells. These findings underscore the intricate interplay between hepatic pathology and MAIT cells, and highlight the importance of antibacterial monitoring during ursodeoxycholic acid treatment in AILD.

Short-term choroidal changes as early indicators for future myopic shift in primary school children: results of a 2-year cohort study.

BACKGROUND: To assess predictive value of short-term choroidal changes for future myopic shift in children. METHODS: 577 eyes of 289 primary school children were prospectively followed for 2 years. Cycloplegic refractions at baseline, 1 year and 2 years, and choroidal measurements by optical coherence tomography at baseline and 3 months, were used for analyses. Myopic shift was defined as refraction change of at least -0.50 dioptre/year, at 2 years compared with baseline. RESULTS: 228 participants (455 eyes) completed 2-year follow-up. Approximately 37.6% of 311 initially non-myopic eyes and 73.6% of 144 initially myopic eyes developed a myopic shift. Notably, at 3 months greater reductions were found in initially myopic eyes with myopic shift, than in those without myopic shift-in choroidal thickness (ChT), luminal area (LA), stromal area (SA) and total choroidal area (TCA), but no significant differences in any choroidal parameters were observed between non-myopic eyes, with and without myopic shift. Multivariable analyses showed that in myopic eyes, each percentage increase in ChT, LA, SA and TCA was associated with reduced odds of myopic shift (all p<0.001). Similar associations were observed in non-myopic eyes, with smaller effects than in myopic eyes. Adding a 3-month percentage change of each choroidal parameter to a basic model including age, gender, parental myopia and baseline refraction significantly improved the predictive performance in myopic eyes (area under the receiver operating characteristic curves increasing from 0.650 to approximately 0.800, all p<0.05), but not in non-myopic eyes. CONCLUSION: Short-term choroidal changes could act as early indicators for future myopic shift in children.

Momordica charantia L.-derived exosome-like nanovesicles stabilize p62 expression to ameliorate doxorubicin cardiotoxicity.

BACKGROUND: Doxorubicin (DOX) is a first-line chemotherapeutic drug for various malignancies that causes cardiotoxicity. Plant-derived exosome-like nanovesicles (P-ELNs) are growing as novel therapeutic agents. Here, we investigated the protective effects in DOX cardiotoxicity of ELNs from Momordica charantia L. (MC-ELNs), a medicinal plant with antioxidant activity. RESULTS: We isolated MC-ELNs using ultracentrifugation and characterized them with canonical mammalian extracellular vesicles features. In vivo studies proved that MC-ELNs ameliorated DOX cardiotoxicity with enhanced cardiac function and myocardial structure. In vitro assays revealed that MC-ELNs promoted cell survival, diminished reactive oxygen species, and protected mitochondrial integrity in DOX-treated H9c2 cells. We found that DOX treatment decreased the protein level of p62 through ubiquitin-dependent degradation pathway in H9c2 and NRVM cells. However, MC-ELNs suppressed DOX-induced p62 ubiquitination degradation, and the recovered p62 bound with Keap1 promoting Nrf2 nuclear translocation and the expressions of downstream gene HO-1. Furthermore, both the knockdown of Nrf2 and the inhibition of p62-Keap1 interaction abrogated the cardioprotective effect of MC-ELNs. CONCLUSIONS: Our findings demonstrated the therapeutic beneficials of MC-ELNs via increasing p62 protein stability, shedding light on preventive approaches for DOX cardiotoxicity.

Stitching method for panoramic nail fold images based on capillary contour enhancement.

Nail fold capillaroscopy is an important means of monitoring human health. Panoramic nail fold images improve the efficiency and accuracy of examinations. However, the acquisition of panoramic nail fold images is seldom studied and the problem manifests of few matching feature points when image stitching is used for such images. Therefore, this paper presents a method for panoramic nail fold image stitching based on vascular contour enhancement, which first solves the problem of few matching feature points by pre-processing the image with contrast-constrained adaptive histogram equalization (CLAHE), bilateral filtering (BF), and sharpening algorithms. The panoramic images of the nail fold blood vessels are then successfully stitched using the fast robust feature (SURF), fast library of approximate nearest neighbors (FLANN) and random sample agreement (RANSAC) algorithms. The experimental results show that the panoramic image stitched by this paper's algorithm has a field of view width of 7.43 mm, which improves the efficiency and accuracy of diagnosis.

[Authenticity discrimination for Galli Gigerii Endothelium Corneum based on UPLC-MS/MS and peptidomics].

Peptidomics was employed to systematically analyze the characteristic peptides in Galli Gigerii Endothelium Corneum and its adulterants and establish a method for distinguishing Galli Gigerii Endothelium Corneum from its adulterants, including the gizzard membranes from ducks, geese, and pigeons. UPLC-Q-Exactive Orbitrap-MS was combined with multivariate statistical analysis to analyze the peptides in Galli Gigerii Endothelium Corneum and its adulterants. The structures of peptides were identified by pNovo combined with manual recognition of spectra, and synthetic peptide standards were used for validation. LC-MS/MS was used to optimize the sample pre-processing conditions, including the extraction procedure, extraction time, extraction solvents, and solvent volumes, for the characteristic peptide LESY in Galli Gigerii Endothelium Corneum. Multiple reaction monitoring(MRM) in the ESI~+ mode with m/z 511.24→269.11 and 511.24→243.13 as detection ions was employed for qualitative and quantitative analyses. The established UPLC-MS/MS method demonstrated good specificity, stability, and durability. The content of LESY in 16 batches of Galli Gigerii Endothelium Corneum samples ranged from 55.03 to 113.36 µg·g~(-1). Additionally, a qualitative detection method for the common peptide RDPVLVSR in adulterants was established with m/z 471.28→785.45 and 471.28→670.41 as the detection ions. This study established a convenient, rapid, and accurate detection method for the characteristic peptides in Galli Gigerii Endothelium Corneum and its adulterants. The method possesses good specificity, stability, and durability, providing a valuable reference for the identification and quality control of Galli Gigerii Endothelium Corneum and other traditional Chinese medicines derived from animal sources.

Dysbiotic alteration in the fecal microbiota of patients with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common disease associated with high androgen and infertility. The gut microbiota plays an important role in metabolic diseases including obesity, hyperglycemia, and fatty liver. Although the gut microbiota has been associated with PCOS, little is known about the gut microbial structure and function in individuals with PCOS from Northeast China. In this study, 17 PCOS individuals and 17 age-matched healthy individuals were recruited for community structure and function analysis of the gut microbiota. The results showed that PCOS individuals have reduced diversity and richness of the gut microbiota compared with healthy individuals. Beta diversity analysis showed that the community structure of the gut microbiota of individuals with PCOS was significantly separated from healthy individuals. At the phylum level, PCOS individuals have reduced Firmicutes and Bacteroidota and increased Actinobacteriota and Proteobacteria compared with healthy individuals. At the family and genus levels, the composition of the gut microbiota between PCOS patients and healthy individuals was also significantly different. In addition, PICRUSt2 showed that individuals with PCOS have different microbial functions in the gut compared with healthy individuals. We finally confirmed that Bifidobacterium was enriched in the fecal samples of PCOS patients, while other 11 genera including Bacteroides, UCG_002, Eubacterium__coprostanoligenes_group_unclassified, Dialister, Firmicutes_unclassified, Ruminococcus, Alistipes, Christensenellaceae_R_7_group, Clostridia_UCG_014_unclassified, Roseburia, and Lachnospiraceae_unclassified were depleted compared with healthy individuals. These results indicate that individuals with PCOS have altered community structure and functions of the gut microbiota, which suggests that targeting the gut microbiota might be a potential strategy for PCOS intervention. IMPORTANCE: Gut microbiota plays a critical role in the development of PCOS. There is a complex and close interaction between PCOS and gut microbiota. The relationship between the pathogenesis and pathophysiological processes of PCOS and the structure and function of the gut microbiota needs further investigation.

Novel Lenslet-ARray-Integrated Spectacle Lenses for Myopia Control: A 1-Year Randomized, Double-Masked, Controlled Trial.

PURPOSE: To investigate the myopia control efficacy of novel Lenslet-ARray-Integrated (LARI) spectacle lenses with positive power lenslets (PLARI) and negative power lenslets (NLARI) worn for 1 year in myopic children. DESIGN: Randomized, double-masked, controlled clinical trial. PARTICIPANTS: A total of 240 children 6 to 12 years of age with spherical equivalent refraction (SER) between -4.00 and -1.00 diopters (D), astigmatism of ≤ 1.50 D, and anisometropia of ≤ 1.00 D. METHODS: Participants were assigned randomly in a 1:1:1 ratio to PLARI, NLARI, and control (single-vision [SV]) groups. Cycloplegic autorefraction and axial length were measured at baseline and 6-month intervals after lens wear. MAIN OUTCOME MEASURES: Changes in SER, axial elongation (AE), and differences between groups. RESULTS: After 1 year, SER changes and AE in the PLARI and NLARI groups were significantly less than those in the SV group (SER: -0.30 ± 0.48 D, -0.21 ± 0.35 D, and -0.66 ± 0.40 D, respectively; AE: 0.19 ± 0.20 mm, 0.17 ± 0.14 mm, 0.34 ± 0.18 mm, respectively; all P < 0.001). No significant differences were found in SER changes and AE between PLARI and NLARI groups (P = 0.54 and P = 1.00, respectively). Younger age was associated with more rapid SER increase and larger AE in the SV group (r = 0.40 [P < 0.001] and r = -0.59 [P < 0.001], respectively) and PLARI group (r = 0.46 [P < 0.001] and r = -0.52 [P < 0.001], respectively), but not in the NLARI group (r = -0.002 [P = 0.98] and r = -0.08 [P = 0.48], respectively). CONCLUSIONS: Compared with the SV group, both PLARI and NARI groups showed significantly slower myopia progression in terms of SER and AE. Faster myopia progression, in terms of both SER and AE, was associated with younger age in the SV and PLARI groups but not the NLARI group. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Machine-learning-based models assist the prediction of pulmonary embolism in autoimmune diseases: A retrospective, multicenter study.

BACKGROUND: Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD. METHODS: In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort. RESULTS: In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962-1.000 in the training cohort and 0.969-0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone. CONCLUSION: ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE. TRIAL REGISTRATION: Chictr.org.cn : ChiCTR2200059599.

Construction and analysis of competitive endogenous RNA networks and prognostic models associated with ovarian cancer based on the exoRBase database.

OBJECTIVE: To construct a competitive endogenous RNA (ceRNA) regulatory network in blood exosomes of patients with ovarian cancer (OC) using bioinformatics and explore its pathogenesis. METHODS: The exoRbase2.0 database was used to download blood exosome gene sequencing data from patients OC and normal controls and the expression profiles of exosomal mRNA, long non-coding RNA (lncRNA), and circular RNA (circRNA) were detected independently using R language for differential expression analysis. TargetScan and miRanda databases were combined for the prediction and differential expression of mRNA-binding microRNAs (miRNA). The miRcode and starBase databases were used to predict miRNAs that bind to differentially expressed lncRNAs and circRNAs repectively. The relevant mRNA, circRNA, lncRNA and their corresponding miRNA prediction data were imported into Cytoscape software for visualization of the ceRNA network. The R language and KEGG Orthology-based Annotation System (KOBAS) were used to execute and illustrate the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Hub genes were identified using The CytoHubba plugin. RESULTS: Thirty-one differentially expressed mRNAs, 17 differentially expressed lncRNAs, and 24 differentially expressed circRNAs were screened. Cytoscape software was used to construct the ceRNA network with nine mRNA nodes, two lncRNA nodes, eight circRNA nodes, and 51 miRNA nodes. Both GO and KEGG were focused on the Spliceosome pathway, indicating that spliceosomes are closely linked with the development of OC, while heterogenous nuclear ribonucleoprotein K and RNA binding motif protein X-linked genes were the top 10 score Hub genes screened by Cytoscape software, including two lncRNAs, four mRNAs, and four circRNAs. In patients with OC, the expression of eukaryotic translation initiation factor 4 gamma 2 (EIF4G2), SERPINE 1 mRNA binding protein 1 (SERBP1), ribosomal protein L15 (RPL15) and human leukocyte antigen complex P5 (HCP5) was significantly higher whereas that of testis expressed transcript, Y-linked 15 and DEAD-box helicase 3 Y-linked genes was lower compared to normal controls Immunocorrelation scores revealed that SERBP1 was significantly and negatively correlated with endothelial cells and CD4+ T cells and positively correlated with natural killer (NK) cells and macrophages, respectively; RPL15 was significantly positively correlated with macrophages and endothelial cells and negatively correlated with CD8+ T cells and uncharacterized cells, respectively. EIF4G2 was significantly and negatively correlated with endothelial cells and CD4+ T cells, and positively correlated with uncharacterized cells, respectively. Based on the survival data and the significant correlation characteristics derived from the multifactorial Cox analysis (P < 0.05), the survival prediction curves demonstrated that the prognostic factors associated with 3-year survival in patients with OC were The prognostic factors associated with survival were Macrophage, RPL15. CONCLUSION: This study successfully constructs a ceRNA regulatory network in blood exosomes of OV patients, which provides the specific targets for diagnosis and treatment of OC.

2% supramolecular salicylic acid hydrogel vs. adapaline gel in mild to moderate acne vulgaris treatment: A multicenter, randomized, evaluator-blind, parallel-controlled trial.

OBJECTIVE: Salicylic acid (SA) has been used for treatment of acne of different severity levels. However, there are few researches about the safety and efficacy for treatment of mild to moderate acne, and the improvement of the skin condition by using 2% supramolecular salicylic acid (SSA) compared to Davuwen Adapaline gel. METHODS: A multicenter, randomized, assessor-blind and parallel-controlled study was conducted. A total of 500 patients (trial group: 249, control group: 251) with mild to moderate (grade I-II) facial acne vulgaris were recruited in this study over a 16-week trial period. Patients in the trial group were treated with Broda 2% SSA hydrogel, while control group treated with Davuwen Adapaline gel once a day. The number of inflammatory papules, comedones, and pustules were counted and the rate of lesion reduction was calculated pre- and post-treatment. Then, the skin physiological indicators, including L*a*b*, TEWL, skin sebum and hydration were measured. Statistical analysis was conducted using SAS 9.4. Significance was set at p = 0.05. RESULTS: At the end of 12 weeks' therapy, the regression and markedly improvement rate of the trail group and the control group were 51.01% and 43.10% respectively, and there was no significant difference in the improvement rate between two groups (p = 0.0831). Although, there was no difference in adverse events rate between two groups, the adverse events rate of the trail group was 0.40%, a little lower than the control group (0.80%). Moreover, there was a significant difference in the numbers of pores at T1 between two groups. CONCLUSION: Both 2% SSA and Adapaline gel were equally effective in the treatment of mild to moderate acne vulgaris. 2% SSA is worth the clinical promotion and application in mild to moderate acne vulgaris.

Reconfigurable Ag/HfO2/NiO/Pt Memristors with Stable Synchronous Synaptic and Neuronal Functions for Renewable Homogeneous Neuromorphic Computing System.

Artificial synapses and bionic neurons offer great potential in highly efficient computing paradigms. However, complex requirements for specific electronic devices in neuromorphic computing have made memristors face the challenge of process simplification and universality. Herein, reconfigurable Ag/HfO2/NiO/Pt memristors are designed for feasible switching between volatile and nonvolatile modes by compliance current controlled Ag filaments, which enables stable and reconfigurable synaptic and neuronal functions. A neuromorphic computing system effectively replicates the biological synaptic weight alteration and continuously accomplishes excitation and reset of artificial neurons, which consist of bionic synapses and artificial neurons based on isotype Ag/HfO2/NiO/Pt memristors. This reconfigurable electrical performance of the Ag/HfO2/NiO/Pt memristors takes advantage of simplified hardware design and delivers integrated circuits with high density, which exhibits great potency for future neural networks.

[Clinical study of constructing nomogram model based on multi-dimensional clinical indicators to predict prognosis of knee osteoarthritis].

OBJECTIVE: To analyze the factors affecting the prognosis of patients with knee osteoarthritis, and to construct a nomogram prediction model in conjunction with multi-dimensional clinical indicators. METHODS: The clinical data of 234 patients with knee osteoarthritis who were treated in our hospital from January 2015 to June 2021 were retrospectively analyzed, including 126 males and 108 females；age more than 60 years old for 135 cases, age less than 60 years old for 99 cases. Lysholm knee function score was used to evaluate the prognosis of the patients, and the patients were divided into good prognosis group for 155 patients and poor prognosis group for 79 patients according to the prognosis. The clinical data of the subjects in the experimental cohort were analyzed by single factor and multiple factors. The patients were divided into experimental cohort and verification cohort, the results of the multiple factor analysis were visualized to obtain a nomogram prediction model, the receiver operating characteristic curve（ROC）, calibration curve and decision curve were used to evaluate the model's discrimination, accuracy and clinical benefit rate. RESULTS: The results of multivariate analysis showed that smoking, pre-treatment K-L grades of Ⅲ to Ⅳ, and high levels of interleukin 6 （IL-6） and matrix metallo proteinase-3 （MMP-3） were risk factors for the prognosis of patients with knee osteoarthritis. ROC test results showed that the area under the curve of the nomogram model in the experimental cohort and validation cohort was 0.806[95%CI（0.742, 0.866）] and 0.786[（95%CI（0.678, 0.893）], respectively. The results of the calibration curve showed that the Brier values of the experimental cohort and verification cohort were 0.151 points and 0.134 points, respectively. When the threshold probability value in the decision curve was set to 31%, the clinical benefit rates of the experimental cohort and validation cohort were 51% and 56%, respectively. CONCLUSION: The prognostic model of patients with knee osteoarthritis constructed based on multi-dimensional clinical data has both theoretical and practical significance, and can provide a reference for taking targeted measures to improve the prognosis of patients.

Efficient Spiking Neural Networks with Biologically Similar Lithium-Ion Memristor Neurons.

Benefiting from the brain-inspired event-driven feature and asynchronous sparse coding approach, spiking neural networks (SNNs) are becoming a potentially energy-efficient replacement for conventional artificial neural networks. However, neuromorphic devices used to construct SNNs persistently result in considerable energy consumption owing to the absence of sufficient biological parallels. Drawing inspiration from the transport nature of Na+ and K+ in synapses, here, a Li-based memristor (LixAlOy) was proposed to emulate the biological synapse, leveraging the similarity of Li as a homologous main group element to Na and K. The Li-based memristor exhibits ∼8 ns ultrafast operating speed, 1.91 and 0.72 linearity conductance modulation, and reproducible switching behavior, enabled by lithium vacancies forming a conductive filament mechanism. Moreover, these memristors are capable of simulating fundamental behaviors of a biological synapse, including long-term potentiation and long-term depression behaviors. Most importantly, a threshold-tunable leaky integrate-and-fire (TT-LIF) neuron is built using LixAlOy memristors, successfully integrating synaptic signals from both temporal and spatial levels and achieving an optimal threshold of SNNs. A computationally efficient TT-LIF-based SNN algorithm is also implemented for image recognition schemes, featuring a high recognition rate of 90.1% and an ultralow firing rate of 0.335%, which is 4 times lower than those of other memristor-based SNNs. Our studies reveal the ion dynamics mechanism of the LixAlOy memristor and confirm its potential in rapid switching and the construction of SNNs.

Improved nested U-structure for accurate nailfold capillary segmentation.

Changes in the structure and function of nailfold capillaries may be indicators of numerous diseases. Noninvasive diagnostic tools are commonly used for the extraction of morphological information from segmented nailfold capillaries to study physiological and pathological changes therein. However, current segmentation methods for nailfold capillaries cannot accurately separate capillaries from the background, resulting in issues such as unclear segmentation boundaries. Therefore, improving the accuracy of nailfold capillary segmentation is necessary to facilitate more efficient clinical diagnosis and research. Herein, we propose a nailfold capillary image segmentation method based on a U2-Net backbone network combined with a Transformer structure. This method integrates the U2-Net and Transformer networks to establish a decoder-encoder network, which inserts Transformer layers into the nested two-layer U-shaped architecture of the U2-Net. This structure effectively extracts multiscale features within stages and aggregates multilevel features across stages to generate high-resolution feature maps. The experimental results demonstrate an overall accuracy of 98.23 %, a Dice coefficient of 88.56 %, and an IoU of 80.41 % compared to the ground truth. Furthermore, our proposed method improves the overall accuracy by approximately 2 %, 3 %, and 5 % compared to the original U2-Net, Res-Unet, and U-Net, respectively. These results indicate that the Transformer-U2Net network performs well in nailfold capillary image segmentation and provides more detailed and accurate information on the segmented nailfold capillary structure, which may aid clinicians in the more precise diagnosis and treatment of nailfold capillary-related diseases.

Identification of genes and key pathways underlying the pathophysiological association between sarcopenia and chronic obstructive pulmonary disease.

PURPOSE: Chronic obstructive pulmonary disease (COPD) patients are likely to develop sarcopenia, while the exact mechanism underlying the association between sarcopenia and COPD is still not clear. This cohort study aims to explore the genes, signaling pathways, and transcription factors (TFs) that are related to the molecular pathogenesis of sarcopenia and COPD. METHODS: According to the strict inclusion criteria, two gene sets (GSE8479 for sarcopenia and GSE76925 for COPD) were obtained from the Gene Expression Omnibus (GEO) platform. Overlapping differentially expressed genes (DEGs) in sarcopenia and COPD were detected, and comprehensive bioinformatics analysis was conducted, including functional annotation, enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), construction of a protein-protein interaction (PPI) network, co-expression analysis, identification and validation of hub genes, and TFs prediction and verification. RESULTS: In total, 118 downregulated and 92 upregulated common DEGs were detected. Functional analysis revealed that potential pathogenesis involves oxidoreductase activity and ferroptosis. Thirty hub genes were detected, and ATP metabolic process and oxidative phosphorylation were identified to be closely related to the hub genes. Validation analysis revealed that SAA1, C3, and ACSS2 were significantly upregulated, whereas ATF4, PPARGC1A, and MCTS1 were markedly downregulated in both sarcopenia and COPD. In addition, six TFs (NFKB1, RELA, IRF7, SP1, MYC, and JUN) were identified to regulate the expression of these genes, and SAA1 was found to be coregulated by NFKB1 and RELA. CONCLUSION: This study uncovers potential common mechanisms of COPD complicated by sarcopenia. The hub gene SAA1 and the NF-κB signaling pathway could be involved, and oxidative phosphorylation and ferroptosis might be important contributors to this comorbidity.