Identifying changes in dynamic plantar pressure associated with radiological knee osteoarthritis based on machine learning and wearable devices.

BACKGROUND: Knee osteoarthritis (KOA) is an irreversible degenerative disease that characterized by pain and abnormal gait. Radiography is typically used to detect KOA but has limitations. This study aimed to identify changes in plantar pressure that are associated with radiological knee osteoarthritis (ROA) and to validate them using machine learning algorithms. METHODS: This study included 92 participants with variable degrees of KOA. A modified Kellgren-Lawrence scale was used to classify participants into non-ROA and ROA groups. The total feature set included 210 dynamic plantar pressure features captured by a wearable in-shoe system as well as age, gender, height, weight, and body mass index. Filter and wrapper methods identified the optimal features, which were used to train five types of machine learning classification models for further validation: k-nearest neighbors (KNN), support vector machine (SVM), random forest (RF), AdaBoost, and eXtreme gradient boosting (XGBoost). RESULTS: Age, the standard deviation (SD) of the peak plantar pressure under the left lateral heel (f_L8PPP_std), the SD of the right second peak pressure (f_Rpeak2_std), and the SD of the variation in the anteroposterior displacement of center of pressure (COP) in the right foot (f_RYcopstd_std) were most associated with ROA. The RF model with an accuracy of 82.61% and F1 score of 0.8000 had the best generalization ability. CONCLUSION: Changes in dynamic plantar pressure are promising mechanical biomarkers that distinguish between non-ROA and ROA. Combining a wearable in-shoe system with machine learning enables dynamic monitoring of KOA, which could help guide treatment plans.

Cascaded signal amplification strategy for ultra-specific, ultra-sensitive, and visual detection of Shigella flexneri.

Pathogen infections including Shigella flexneri have posed a significant threat to human health for numerous years. Although culturing and qPCR were the gold standards for pathogen detection, time-consuming and instrument-dependent restrict their application in rapid diagnosis and economically less-developed regions. Thus, it is urgently needed to develop rapid, simple, sensitive, accurate, and low-cost detection methods for pathogen detection. In this study, an immunomagnetic beads-recombinase polymerase amplification-CRISPR/Cas12a (IMB-RPA-CRISPR/Cas12a) method was built based on a cascaded signal amplification strategy for ultra-specific, ultra-sensitive, and visual detection of S. flexneri in the laboratory. Firstly, S. flexneri was specifically captured and enriched by IMB (Shigella antibody-coated magnetic beads), and the genomic DNA was released and used as the template in the RPA reaction. Then, the RPA products were mixed with the pre-loaded CRISPR/Cas12a for fluorescence visualization. The results were observed by naked eyes under LED blue light, with a sensitivity of 5 CFU/mL in a time of 70 min. With no specialized equipment or complicated technical requirements, the IMB-RPA-CRISPR/Cas12a diagnostic method can be used for visual, rapid, and simple detection of S. flexneri and can be easily adapted to monitoring other pathogens.

Predictive value of anthropometric and biochemical indices in non-alcoholic fatty pancreas disease: a cross-sectional study.

OBJECTIVES: Triglyceride (TG), triglyceride-glucose index (TyG), body mass index (BMI), TyG-BMI and triglyceride to high-density lipoprotein ratio (TG/HDL) have been reported to be reliable predictors of non-alcoholic fatty liver disease. However, there are few studies on potential predictors of non-alcoholic fatty pancreas disease (NAFPD). Our aim was to evaluate these and other parameters for predicting NAFPD. DESIGN: Cross-sectional study design. SETTING: Physical examination centre of a tertiary hospital in China. PARTICIPANTS: This study involved 1774 subjects who underwent physical examinations from January 2016 to September 2016. PRIMARY AND SECONDARY OUTCOME MEASURES: From each subject, data were collected for 13 basic physical examination and blood biochemical parameters: age, weight, height, BMI, TyG, TyG-BMI, high-density lipoprotein (HDL), low-density lipoprotein, total cholesterol, TG, fasting plasma glucose, TG/HDL and uric acid. NAFPD was diagnosed by abdominal ultrasonography. A logistic regression model with a restricted cubic spline was used to evaluate the relationship between each parameter and NAFPD. The receiver operating characteristic (ROC) curve was used to calculate the area under the curve for each parameter. RESULTS: HDL was negatively correlated with NAFPD, height was almost uncorrelated with NAFPD and the remaining 11 parameters were positively correlated with NAFPD. ROC curve showed that weight-related parameters (weight, BMI and TyG-BMI) and TG-related parameters (TyG, TG and TG/HDL) had high predictive values for the identification of NAFPD. The combinations of multiple parameters had a better prediction effect than a single parameter. All the predictive effects did not differ by sex. CONCLUSIONS: Weight-related and TG-related parameters are good predictors of NAFPD in all populations. BMI showed the greatest predictive potential. Multiparameter combinations appear to be a good way to predict NAFPD.

Development of a selective electrochemical microsensor based on molecularly imprinted polydopamine/ZIF-67/laser-induced graphene for point-of-care determination of 3-nitrotyrosine.

3-nitrotyrosine (3-NT) is a biomarker closely associated with the early diagnosis of oxidative stress-related disorders. The development of an accurate, cost-effective, point-of-care 3-NT sensor holds significant importance for self-monitoring and clinical treatment. In this study, a selective, sensitive, and portable molecularly imprinted electrochemical sensor was developed. ZIF-67 with strong adsorption capacity was facilely modified on an electrochemically active laser-induced graphene (LIG) substrate (formed ZIF-67/LIG). Subsequently, biocompatible dopamine was chosen as the functional monomer, and interference-free ʟ-tyrosine was used as the dummy template to create molecularly imprinted polydopamine (MIPDA) on the ZIF-67/LIG, endowing the sensor with selectivity. The morphologies, electrochemical properties, and detection performance of the sensor were comprehensively investigated using scanning electron microscopy, cyclic voltammetry, electrochemical impedance spectroscopy, and differential pulse voltammetry. To achieve the best performance, several parameters were optimized, including the number of polymerization cycles (15), elution time (60 min), incubation time (7 min), and pH of the buffer solution (6). The turnaround time for this sensor is 10 min. Benefiting from the alliance of MIPDA, ZIF-67, and LIG, the sensor exhibited excellent sensitivity with a detection limit of 6.71 nM, and distinguished selectivity against 11 interfering substances. To enable convenient clinical diagnosis, a customized electrochemical microsensor with MIPDA/ZIF-67/LIG was designed, showcasing excellent reliability and convenience in detecting biological samples without pretreatment. The proposed microsensor will not only facilitate clinical diagnosis and improve patient care, but also provide inspiration for the development of other portable and accurate electrochemical biosensors.

UMP-CMP kinase 2 inhibits ZIKV replication through activation of type I IFN signaling pathway.

Cytidine/uridine monophosphate kinase 2 (UMP-CMP kinase 2, CMPK2) has been reported as an antiviral interferon-stimulated gene (ISG). We previously observed that the expression of CMPK2 was significantly upregulated after Zika Virus (ZIKV) infection in A549 cells. However, the association and the underlying mechanisms between CMPK2 induction and ZIKV replication remain to be determined. We investigated the induction of CMPK2 during ZIKV infection and the effect of CMPK2 on ZIKV replication in A549, U251, Vero, IFNAR-deficient U5A and its parental 2fTGH cells, Huh7 and its RIG-I-deficient derivatives Huh7.5.1 cells. The activation status of Jak-STAT signaling pathway was determined by detecting the phosphorylation level of STAT1, the activity of interferon stimulated response element (ISRE) and the expression of several interferon stimulated genes (ISGs). We found that ZIKV infection induced CMPK2 expression through an IFNAR and RIG-I dependent manner. Overexpression of CMPK2 inhibited while CMPK2 knockdown promoted ZIKV replication in A549 and U251 cells. Mechanically, we found that CMPK2 overexpression increased IFNß expression and activated Jak/STAT signaling pathway as shown by the increased level of p-STAT1, enhanced activity of ISRE, and the upregulated expression of downstream ISGs. These findings suggest that ZIKV infection induced CMPK2 expression, which inhibited ZIKV replication and serves as a positive feedback regulator for IFN-Jak/STAT pathway.

Proteomic characteristics of the treatment trajectory of patients with COVID-19.

The ongoing COVID-19 pandemic caused by SARS-CoV-2 has prompted global concern due to its profound impact on public health and the economy. Effective treatment of COVID-19 patients in the acute phase or of those with long COVID is a major challenge. Using data-independent acquisition (DIA) technology, we performed proteomic profiling on plasma samples from 22 COVID-19 patients and six healthy controls at Dazhou Central Hospital. Random forest and least absolute shrinkage and selection operator algorithms were used for analysis at various COVID-19 treatment stages. We identified 79 proteins that were differentially expressed between COVID-19 patients and healthy controls, mainly involving pathways associated with cell processes and binding. Across different treatment stages of COVID-19, five proteins-PI16, GPLD1, IGFBP3, KRT19, and VCAM1-were identified as potential molecular markers for dynamic disease monitoring. Furthermore, the proteins BTD, APOM, IGKV2-28, VWF, C4BPA, and C7 were identified as candidate biomarkers for distinguishing between SARS-CoV-2 positivity and negativity. Analysis of protein change profiles between the follow-up and healthy control groups highlighted cardiovascular changes as a concern for patients recovering from COVID-19. Our study revealed the infection profiles of SARS-CoV-2 at the protein expression level comparing different phases of COVID-19. DIA mass spectrometry analysis of plasma samples from COVID-19 patients undergoing treatment identified key proteins involved in signaling pathways that might be used as markers of the recovery phase. These findings provide insight for the development of therapy options and suggest potential blood biomarkers for COVID-19.

Myopia control efficacy of peripheral defocus soft contact lenses in children and adolescents: A meta-analysis.

OBJECTIVES: To evaluate the effect of peripheral defocus soft contact lenses (PDSCLs) on controlling myopia progression in children and adolescents, and to compare it with orthokeratology (Ortho-K) and single vision lenses (SVLs). METHODS: We conducted a systematic search of PubMed, the Cochrane Library, Medline, CNKI, CBM, VIP, and WanFang Data databases for randomized controlled trials (RCTs) and cohort studies that investigated the effects of PDSCLs on myopia control in children and adolescents. The published languages were limited to English and Chinese. The risk bias tool provided by the Cochrane risk-of-bias tool and Newcastle-Ottawa Scale were used to assess the risk bias of included studies of RCTs and CTs. The published biases of included studies were assessed by Egger`s test. RESULTS: We included 21 studies, comprising 13 RCTs and 8 cohort studies, with a total of 1337 participants in the PDSCLs group, 428 in the Ortho-K group, and 707 in the SVLs group. The meta-analysis indicated no significant difference between PDSCLs and Ortho-K in controlling the increase of diopter (MD = 0.01, 95% CI: -0.06, 0.09; P = 0.69) and axial length (MD = -0.01, 95% CI: -0.02, 0.00; P = 0.28). Compared with SVLs, PDSCLs had a better effect in controlling the increase of diopter (MD = 0.23, 95% CI: 0.17, 0.28; P < 0.00001) and axial length (MD = -0.11, 95% CI: -0.12, -0.09; P < 0.00001) in children and adolescents. CONCLUSIONS: Children and adolescents wearing PDSCLs can achieve better myopia control than those wearing SVLs, and their effect is comparable to that of Ortho-K.

Quantitative comparison of three thyroidectomy approaches in neck muscles, voice, and swallowing functions.

OBJECTIVE: This study compares endoscopic thyroidectomy by gasless unilateral axillary approach (ETGUA) and sternocleidomastoid leading-edge approach (SLEA) with conventional open thyroidectomy (COT) in hemithyroidectomy. The main focus is on the protection of neck muscles (sternocleidomastoid, omohyoid, sternothyroid) and the postoperative function of voice and swallowing yielded through these common approaches. METHODS: A total of 302 patients who underwent hemithyroidectomy were enrolled and divided into three groups: ETGUA (n = 101), SLEA (n = 100), and COT (n = 101). Ultrasound was used to measure the thickness of bilateral neck muscles, including the sternocleidomastoid, omohyoid, and sternothyroid. The changes in thickness on the surgical side compared to the non-surgical side. Analyzed factors included muscle thickness changes, Swallowing Impairment Score (SIS), Voice Handicap Index (VHI), Scar Cosmesis Assessment and Rating (SCAR), Neck Injury Index (NII), surgery duration, drainage volume, hospitalization, and number of lymph nodes. RESULTS: The clinical characteristics among the three groups were consistent except for differences in sex, age, and BMI. Metrics such as sternocleidomastoid muscle, NII, hypocalcemia, postoperative PTH, transient hoarseness, and number of lymph nodes showed no significant differences among the three groups. However, significant differences were found in the duration of surgery, drainage volume, hospitalization period omohyoid muscle, Sternohyoid muscle, VHI, SIS, and SCAR (all p < 0.001). CONCLUSION: In comparison to COT, ETGUA and SLEA demonstrate superiority in protecting neck muscles and preserving voice and swallowing function without compromising surgical safety or radicality.

A radiomics and genomics-derived model for predicting metastasis and prognosis in colorectal cancer.

Approximately 50% of colorectal cancer (CRC) patients would develop metastasis with poor prognosis, therefore, it is necessary to effectively predict metastasis in clinical treatment. In this study, we aimed to establish a machine-learning model for predicting metastasis in CRC patients by considering radiomics and transcriptomics simultaneously. Here, 1023 patients with CRC from three centers were collected and divided into five queues (Dazhou Central Hospital n = 517, Nanchong Central Hospital n = 120 and the Cancer Genome Atlas (TCGA) n = 386). A total of 854 radiomics features were extracted from tumor lesions on CT images, and 217 differentially expressed genes were obtained from non-metastasis and metastasis tumor tissues using RNA sequencing. Based on radiotranscriptomic (RT) analysis, a novel RT model was developed and verified through genetic algorithms (GA). Interleukin (IL)-26, a biomarker in RT model, was verified for its biological function in CRC metastasis. Furthermore, 15 radiomics variables were screened through stepwise regression, which was highly correlated with the IL26 expression level. Finally, a radiomics model (RA) was established by combining GA and stepwise regression analysis with radiomics features. The RA model exhibited favorable discriminatory ability and accuracy for metastasis prediction in two independent verification cohorts. We designed multicenter, multi-scale cohorts to construct and verify novel combined radiomics and genomics models for predicting metastasis in CRC. Overall, RT model and RA model might help clinicians in directing personalized diagnosis and therapeutic regimen selection for patients with CRC.

Nanotechnology Reprogramming Metabolism for Enhanced Tumor Immunotherapy.

Mutation burden, hypoxia, and immunoediting contribute to altered metabolic profiles in tumor cells, resulting in a tumor microenvironment (TME) characterized by accumulation of toxic metabolites and depletion of various nutrients, which significantly hinder the antitumor immunity via multiple mechanisms, hindering the efficacy of tumor immunotherapies. In-depth investigation of the mechanisms underlying these phenomena are vital for developing effective antitumor drugs and therapies, while the therapeutic effects of metabolism-targeting drugs are restricted by off-target toxicity toward effector immune cells and high dosage-mediated side effects. Nanotechnologies, which exhibit versatility and plasticity in targeted delivery and metabolism modulation, have been widely applied to boost tumor immunometabolic therapies via multiple strategies, including targeting of metabolic pathways. In this review, recent advances in understanding the roles of tumor cell metabolism in both immunoevasion and immunosuppression are reviewed, and nanotechnology-based metabolic reprogramming strategies for enhanced tumor immunotherapies are discussed.

Construction of a near infrared fluorescence system for imaging of biological tissues.

Surgical procedures often rely on unaided visual observation or endoscopic assistance, which may pose challenges in cases involving intricate anatomical relationships. Real-time imaging technologies capable of intraoperative visualization of target organs have the potential to enhance the precision of surgical procedures by facilitating accurate identification, separation, and protection of vital tissues or organs. Despite these advantages, the widespread adoption of such technologies has been hindered by factors such as the prohibitive cost of equipment. This study aims to optimize and develop a device based on Indocyanine Green (ICG) for fluorescence imaging. The objective is to monitor changes in the average fluorescence intensity of ICG in the bladder, offering valuable guidance for surgeries involving the bladder. 1. Male rabbits were administered 0.01 mg/ml ICG via the renal pelvis and ear vein to obtain fluorescence images of the ureter, bladder, and small intestine. 2. After ligating the bilateral ureters of male rabbits, a retrograde bladder perfusion of 5 ml 0.01 mg/ml ICG was conducted to capture fluorescence images of the bladder over time. The average fluorescence intensity was computed using Image Pro Plus 6.0, and the corresponding curve was generated using Prism 8.0. Using a similar methodology, the average fluorescence intensity of male rabbits without ureteral ligation was measured and plotted over time. 1. The developed device facilitated imaging of the ureter, bladder, and small intestine. 2. The bladder's average fluorescence intensity exhibited changes over time in response to urine production and ureteral ligation, contrasting with observations without ureteral ligation. We have successfully constructed and optimized a modular fluorescence imaging system for organs and tissues. This system proves effective in imaging experiments involving hollow organs in animals and offers valuable insights for relevant surgical procedures.

Predicting 3-month Functional Outcome After Endovascular Thrombectomy in Patients with Anterior Circulation Occlusion with an Arterial Transit Artifact Grading System.

PURPOSE: The objective of this study was to evaluate the relationship between arterial transit artifact (ATA), arterial spin labeling (ASL) perfusion imaging, and the outcome of patients with acute ischemic stroke (AIS) due to occlusion of large vessels in anterior circulation after endovascular thrombectomy (EVT). METHODS: Patients with anterior circulation occlusion treated with EVT between October 2017 and December 2021 were enrolled in this retrospective study, and ATA was quantified by a 4-point scale. A favorable outcome was defined by modified Rankin Scale (mRS) scores of 0-2 at 3 months. To identify independent predictors of favorable outcome, age, sex, risk factors, baseline National Institutes of Health Stroke Scale (NIHSS) score, site of occlusion, cause of stroke, and early reperfusion were evaluated with univariate and multivariate analyses. Predictive accuracy was evaluated by calculating the area under the receiver operating characteristic (ROC) curve (AUC) for the model. RESULTS: In this study 187 patients (age, 65.0 ± 12.5 years; men, 55%) were evaluated. Younger age (odds ratio, OR, 0.95; 95% confidence interval, CI, 0.92-0.98, p = 0.002), lower baseline NIHSS score (OR, 0.88; 95% CI, 0.82-0.94, p < 0.001), and lower ATA score (OR, 1.14; 95% CI, 1.06-1.22, p < 0.001) were independently associated with favorable outcomes in multivariate analysis. The ATA score has moderate to good accuracy in predicting favorable outcomes (AUC, 0.753). CONCLUSION: A high ATA score as a potential predictor, can help identify patients who may benefit from EVT.

The application value of lung ultrasound scoring in assessing disease severity: Evaluation of small-scale outbreaks of COVID-19.

PURPOSE: This study explored the use of transthoracic lung ultrasound for evaluating COVID-19 patients, compared it with computed tomography (CT), and examined its effectiveness using 8 and 12 lung regions. METHODS: A total of 100 patients with COVID-19 and 40 healthy volunteers were assessed using 12 regions (bilateral upper/lower regions of the anterior/lateral/posterior chest) and simplified 8 zones (bilateral upper/lower regions of the anterior/lateral chest) transthoracic lung ultrasound. The relationships between ultrasound, CT, and clinical indicators were analyzed to evaluate the diagnostic value of ultrasound scores in COVID-19. RESULTS: Increased disease severity correlated with increased 8- and 12-zone ultrasound and CT scores (all p < 0.05). The modified 8-zone method strongly correlated with the 12-zone method (Pearson's r = 0.908, p < 0.05). The 8- and 12-zone methods correlated with CT scoring (correlation = 0.568 and 0.635, respectively; p < 0.05). The intragroup correlation coefficients of the 8-zone, 12-zone, and CT scoring methods were highly consistent (intragroup correlation coefficient = 0.718, p < 0.01). The 8-zone ultrasound score correlated negatively with oxygen saturation (rs = 0.306, p < 0.05) and Ca (rs = 0.224, p < 0.05) and positively with IL-6 (rs = 0.0.335, p < 0.05), erythrocyte sedimentation rate (rs = 0.327, p < 0.05), alanine aminotransferase (rs = 0.230, p < 0.05), and aspartate aminotransferase (rs = 0.251, p < 0.05). The 12-zone scoring method correlated negatively with oxygen saturation (rs = 0.338, p < 0.05) and Ca (rs = 0.245, p < 0.05) and positively with IL-6 (rs = 0.354, p < 0.05) and erythrocyte sedimentation rate (rs = 0.495, p < 0.05). CONCLUSION: Lung ultrasound scores represent the clinical severity and have high clinical value for diagnosing COVID-19 pneumonia. The 8-zone scoring method can improve examination efficiency and reduce secondary injuries caused by patient movement.

Hsa_circ_0007321 regulates Zika virus replication through miR-492/NFKBID/NF-κB signaling pathway.

IMPORTANCE: Over the past decade, increasing evidence has shown that circular RNAs (circRNAs) play important regulatory roles in viral infection and host antiviral responses. However, reports on the role of circRNAs in Zika virus (ZIKV) infection are limited. In this study, we identified 45 differentially expressed circRNAs in ZIKV-infected A549 cells by RNA sequencing. We clarified that a downregulated circRNA, hsa_circ_0007321, regulates ZIKV replication through targeting of miR-492 and the downstream gene NFKBID. NFKBID is a negative regulator of nuclear factor-κB (NF-κB), and we found that inhibition of the NF-κB pathway promotes ZIKV replication. Therefore, this finding that hsa_circ_0007321 exerts its regulatory role on ZIKV replication through the miR-492/NFKBID/NF-κB signaling pathway has implications for the development of strategies to suppress ZIKV and possibly other viral infections.

Nanovaccines for Advancing Long-Lasting Immunity against Infectious Diseases.

Infectious diseases, particularly life-threatening pathogens such as small pox and influenza, have substantial implications on public health and global economies. Vaccination is a key approach to combat existing and emerging pathogens. Immunological memory is an essential characteristic used to evaluate vaccine efficacy and durability and the basis for the long-term effects of vaccines in protecting against future infections; however, optimizing the potency, improving the quality, and enhancing the durability of immune responses remains challenging and a focus for research involving investigation of nanovaccine technologies. In this review, we describe how nanovaccines can address the challenges for conventional vaccines in stimulating adaptive immune memory responses to protect against reinfection. We discuss protein and nonprotein nanoparticles as useful antigen platforms, including those with highly ordered and repetitive antigen array presentation to enhance immunogenicity through cross-linking with multiple B cell receptors, and with a focus on antigen properties. In addition, we describe how nanoadjuvants can improve immune responses by providing enhanced access to lymph nodes, lymphnode targeting, germinal center retention, and long-lasting immune response generation. Nanotechnology has the advantage to facilitate vaccine induction of long-lasting immunity against infectious diseases, now and in the future.

Graphitic Carbon Nitride/MOFs Hybrid Composite as Highly Selective and Sensitive Electrodes for Calcium Ion Detection.

The metal-organic framework (MOF) is a class of materials that exhibits a notable capacity for electron transfer. This unique framework design offers potential applications in various fields, including catalysis, gas storage, and sensing. Herein, we focused on a specific type of MOF called Ti-MOF. To enhance its properties and functionality, the composite material was prepared by incorporating graphitic carbon nitride (g-C3N4) into the Ti-MOF structure. This composite, known as g-C3N4@Ti-MOF, was selected as the active material for ion detection, specifically targeting calcium ions (Ca2+). To gain a comprehensive understanding of the structural and chemical properties of the g-C3N4@Ti-MOF composite, several analytical techniques were employed to characterize the prepared g-C3N4@Ti-MOF composite, including X-ray diffraction (XRD), SEM-EDX, and FT-IR. For comparison, different pastes were prepared by mixing Ti-MOF or g-C3N4@Ti-MOF, graphite, and o-NPOE as a plasticizer. The divalent Nernstian responses of the two best electrodes, I and II, were 28.15 ± 0.47 and 29.80 ± 0.66 mV decade-1, respectively, with concentration ranges of 1 µM-1 mM and 0.1 µM-1 mM with a content 1.0 mg Ti-MOF: 250 mg graphite: 0.1 mL o-NPOE and 0.5 mg g-C3N4@Ti-MOF: 250 mg graphite: 0.1 mL o-NPOE, respectively. The electrodes showed high sensitivity and selectivity for Ca2+ ions over different species. The suggested electrodes have been successfully employed for Ca2+ ion measurement in various real samples with excellent precision (RSD = 0.74-1.30%) and accuracy (recovery = 98.5-100.2%), and they exhibited good agreement with the HPLC.

Comprehensive multi-omics analysis reveals the core role of glycerophospholipid metabolism in rheumatoid arthritis development.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic autoimmune disease with complex causes and recurrent attacks that can easily develop into chronic arthritis and eventually lead to joint deformity. Our study aims to elucidate potential mechanism among control, new-onset RA (NORA) and chronic RA (CRA) with multi-omics analysis. METHODS: A total of 113 RA patients and 75 controls were included in our study. Plasma and stool samples were obtained for 16S rRNA sequencing, internally transcribed spacer (ITS) sequencing and metabolomics analysis. And PBMCs were obtained for RNA sequencing. We used three models, logistic regression, least absolute shrinkage and selection operator (LASSO), and random forest, respectively, to distinguish NORA from CRA, and finally we validated model performance using an external cohort of 26 subjects. RESULTS: Our results demonstrated intestinal flora disturbance in RA development, with significantly increased abundance of Escherichia-Shigella and Proteobacteria in NORA. We also found that the diversity was significantly reduced in CRA compared to NORA through fungi analysis. Moreover, we identified 29 differential metabolites between NORA and CRA. Pathway enrichment analysis revealed significant dysregulation of glycerophospholipid metabolism and phenylalanine metabolism pathways in RA patients. Next, we identified 40 differentially expressed genes between NORA and CRA, which acetylcholinesterase (ACHE) was the core gene and significantly enriched in glycerophospholipid metabolism pathway. Correlation analysis showed a strong negatively correlation between glycerophosphocholine and inflammatory characteristics. Additionally, we applied three approaches to develop disease classifier models that were based on plasma metabolites and gut microbiota, which effectively distinguished between new-onset and chronic RA patients in both discovery cohort and external validation cohort. CONCLUSIONS: These findings revealed that glycerophospholipid metabolism plays a crucial role in the development and progression of RA, providing new ideas for early clinical diagnosis and optimizing treatment strategies.

Developmental validation of a novel 8-dye fluorescent typing system with 59 Y-STRs and 3 Y-indels for forensic applications.

An 8-dye fluorescence-labeling forensic Y-chromosomal short tandem repeats (Y-STRs) kit, the 62-plex Y-STR multiplex amplification system, was developed and optimized. The system was validated by testing PCR conditions, stutter ratios (SR) and peak height ratios, sensitivity, mixture samples, precision and accuracy, species-specificity, and inhibition studies according to the Scientific Working Group on DNA Analysis Methods guidelines. PCR-based studies showed that the recommended PCR conditions were optimized for this kit. In the sensitivity study, a full profile was obtained from template DNA with a quantity of u125 pg. Consistent profiles were obtained from three different laboratories. The SRs in all loci were less than 15%, and nice balance and suitable average peak height were shown. No peaks were detected in the profiles of common animal species and microorganisms. In the male-male mixture studies, all loci were observed at a ratio of 1:8, and in the male-female mixture study, all alleles could be profiled at a ratio of 1:500 if the male DNA inputs were ≥0.5 ng/µL. An inhibitor study demonstrated that the kit had varying degrees of resistance to the presence of common inhibitors. Population study demonstrated the 62-plex Y-STR Kit improved the power of discrimination in unrelated Chinese Han males (n = 192). When haplotype diversity was 1, the probability of discrimination power of the 62-plex Y-STR Kit was 0.9948, which is suitable for forensic investigations. The results show that the developed 8-dye fluorescence labeling 62 loci system is sensitive, robust, convenient, and highly informative for forensic applications.

Novel NASICON-Type Na-V-Mn-Ni-Containing Cathodes for High-Rate and Long-Life SIBs.

Partial substitution of V by other transition metals in Na3 V2 (PO4 )3 (NVP) can improve the electrochemical performance of NVP as a cathode for sodium-ion batteries (SIBs). Herein, phosphate Na-V-Mn-Ni-containing composites based on NASICON (Natrium Super Ionic Conductor)-type structure have been fabricated by sol-gel method. The synchrotron-based X-ray study, X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) studies show that manganese/nickel combinations successfully substitute the vanadium in its site within certain limits. Among the received samples, composite based on Na3.83 V1.17 Mn0.58 Ni0.25 (PO4 )3 (VMN-0.5, 108.1 mAh g-1 at 0.2 C) shows the highest electrochemical ability. The cyclic voltammetry, galvanostatic intermittent titration technique, in situ XRD, ex situ XPS, and bond valence site energy calculations exhibit the kinetic properties and the sodium storage mechanism of VMN-0.5. Moreover, VMN-0.5 electrode also exhibits excellent electrochemical performance in quasi-solid-state sodium metal batteries with PVDF-HFP quasi-solid electrolyte membranes. The presented work analyzes the advantages of VMN-0.5 and the nature of the substituted metal in relation to the electrochemical properties of the NASICON-type structure, which will facilitate further commercialization of SIBs.

Molecular Dynamics Simulation of the Effects of Complex Surfactants on Oil-Water Interaction and Aggregation Characteristics at the Interface.

In response to the problem of complex interaction between oil and water in the oil-water interface, especially heavy oil and water, this study investigated the effects of complex surfactants on the interaction of two phases and their aggregation characteristics by molecular dynamics simulation. The results showed that increasing the content of sodium lauryl polyether carboxylate (AEC-9Na) was beneficial to the coordination between it and alkyl glycoside (APG-10), improved the interfacial activity, and enhanced the interfacial stability of the composite system, and the best effect was achieved when AEC-9Na:APG-10 = 8:2. The thickness of the oil and water film on the oil-water interface was irregular. When the concentration of AEC-9Na was lower than that of APG-10, the total thickness of the interfacial film (ttotal) first increased. When the content of AEC-9Na is higher, a large number of sodium ions were adsorbed near the -COO- group of AEC-9Na, which will polarize out of the hydration layer structure and attract water molecules from the second hydration layer on the heavy oil surface to the first hydration layer through electrostatic interaction. Then, the thickness of the interface film was compressed, and the interface film was reduced. When the ratio increased to 10:0, the oil and water phase competed to adsorb surfactant molecules, and the headgroup tended to lay on the interface. Moreover, the hydrophilicity of the surfactant layer was weakened, and the thickness of the water film decreased. The distribution of surfactant was looser than 8:2, the light components of heavy oil molecules (saturated and aromatic hydrocarbons) entered the gap between surfactants in large quantities, and the hydrophobic tail chain tended to be laid on the oil-water interface. The oleophilicity of the surfactant layer increased, and the thickness of the oil film remarkably increased, so the total thickness of the interface film increased again.