Danggui Sini decoction alleviates oxaliplatin-induced peripheral neuropathy by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

BACKGROUND: Danggui Sini decoction (DSD), a traditional Chinese medicine formula, has the function of nourishing blood, warming meridians, and unblocking collaterals. Our clinical and animal studies had shown that DSD can effectively protect against oxaliplatin (OXA)-induced peripheral neuropathy (OIPN), but the detailed mechanisms remain uncertain. Multiple studies have confirmed that gut microbiota plays a crucial role in the development of OIPN. In this study, the potential mechanism of protective effect of DSD against OIPN by regulating gut microbiota was investigated. METHODS: The neuroprotective effects of DSD against OIPN were examined on a rat model of OIPN by determining mechanical allodynia, biological features of dorsal root ganglia (DRG) as well as proinflammatory indicators. Gut microbiota dysbiosis was characterized using 16S rDNA gene sequencing and metabolism disorders were evaluated using untargeted and targeted metabolomics. Moreover the gut microbiota mediated mechanisms were validated by antibiotic intervention and fecal microbiota transplantation. RESULTS: DSD treatment significantly alleviated OIPN symptoms by relieving mechanical allodynia, preserving DRG integrity and reducing proinflammatory indicators lipopolysaccharide (LPS), IL-6 and TNF-α. Besides, DSD restored OXA induced intestinal barrier disruption, gut microbiota dysbiosis as well as systemic metabolic disorders. Correlation analysis revealed that DSD increased bacterial genera such as Faecalibaculum, Allobaculum, Dubosiella and Rhodospirillales_unclassified were closely associated with neuroinflammation related metabolites, including positively with short-chain fatty acids (SCFAs) and sphingomyelin (d18:1/16:0), and negatively with pi-methylimidazoleacetic acid, L-glutamine and homovanillic acid. Meanwhile, antibiotic intervention apparently relieved OIPN symptoms. Furthermore, fecal microbiota transplantation further confirmed the mediated effects of gut microbiota. CONCLUSION: DSD alleviates OIPN by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

Metals/bisulfite system involved generation of 24-sulfonic-25-ene ginsenoside Rg1, a potential quality control marker for sulfur-fumigated ginseng.

Ginseng is a most popular health-promoting food with ginsenosides as its main bioactive ingredients. Illegal sulfur-fumigation causes ginsenosides convert to toxic sulfur-containing derivatives, and reduced the efficacy/safety of ginseng. 24-sulfo-25-ene ginsenoside Rg1 (25-ene SRg1), one of the sulfur-containing derivatives, is a potential quality control marker of fumigated ginseng, but with low accessibility owing to its unknown generation mechanism. In this study, metals/bisulfite system involved generation mechanism was investigated and verified. The generation of 25-ene SRg1 in sulfur-fumigated ginseng is that SO2, formed during sulfur-fumigation, reacted with water and ionized into HSO3-. On the one hand, under the metals/bisulfite system, HSO3- generates HSO5- and free radicals which converted ginsenoside Rg1 to 24,25-epoxide Rg1; on the other hand, as a nucleophilic group, HSO3- reacted with 24,25-epoxide Rg1 and further dehydrated to 25-ene SRg1. This study provided a technical support for the promotion of 25-ene SRg1 as the characteristic quality control marker of sulfur-fumigated ginseng.

Artificial intelligence significantly facilitates development in the mental health of college students: a bibliometric analysis.

Objective: College students are currently grappling with severe mental health challenges, and research on artificial intelligence (AI) related to college students mental health, as a crucial catalyst for promoting psychological well-being, is rapidly advancing. Employing bibliometric methods, this study aim to analyze and discuss the research on AI in college student mental health. Methods: Publications pertaining to AI and college student mental health were retrieved from the Web of Science core database. The distribution of publications were analyzed to gage the predominant productivity. Data on countries, authors, journal, and keywords were analyzed using VOSViewer, exploring collaboration patterns, disciplinary composition, research hotspots and trends. Results: Spanning 2003 to 2023, the study encompassed 1722 publications, revealing notable insights: (1) a gradual rise in annual publications, reaching its zenith in 2022; (2) Journal of Affective Disorders and Psychiatry Research emerged were the most productive and influential sources in this field, with significant contributions from China, the United States, and their affiliated higher education institutions; (3) the primary mental health issues were depression and anxiety, with machine learning and AI having the widest range of applications; (4) an imperative for enhanced international and interdisciplinary collaboration; (5) research hotspots exploring factors influencing college student mental health and AI applications. Conclusion: This study provides a succinct yet comprehensive overview of this field, facilitating a nuanced understanding of prospective applications of AI in college student mental health. Professionals can leverage this research to discern the advantages, risks, and potential impacts of AI in this critical field.

Effects of antibiotics on secondary metabolism and oxidative stress in oilseed rape seeds.

Cruciferae brassica oilseed rape is the third largest oilseed crop in the world and the first in China, as well as a fertilizer-dependent crop. With the increased application of organic fertilizers from livestock manure in agricultural production in recent years, the resulting antibiotic pollution and its ecological health effects have attracted widespread attention. In this study, typical tetracycline and sulfonamide antibiotics tetracycline (TC) and sulfamethoxazole (SMZ) were used to investigate the effects of antibiotics on rapeseed quality and oxidative stress at the level of secondary metabolism on the basis of examining the effects of the two drugs on the growth of soil-cultivated rapeseed seedlings. The results showed that both plant height and biomass of rapeseed seedlings were significantly suppressed and ROS were significantly induced in rapeseed by exposure to high concentrations (2.5 mg/kg) of TC and SMZ. Carotenoids, tocopherols, and SOD enzymes were involved in the oxidative stress response to scavenge free radicals in rapeseed, but phenolic acids and flavonoids contents were decreased, which reduced the quality of the seeds to some extent.

Cytosolic pH is a direct nexus in linking environmental cues with insulin processing and secretion in pancreatic ß cells.

Pancreatic ß cells actively respond to glucose fluctuations through regulating insulin processing and secretion. However, how this process is elaborately tuned in circumstance of variable microenvironments as well as ß cell-intrinsic states and whether its dysfunction links to metabolic diseases remain largely elusive. Here, we show that the cytosolic pH (pHc) in ß cells is increased upon glucose challenge, which can be sensed by Smad5 via its nucleocytoplasmic shuttling. Lesion of Smad5 in ß cells results in hyperglycemia and glucose intolerance due to insulin processing and secretion deficiency. The role of Smad5 in regulating insulin processing and secretion attributes to its non-canonical function by regulating V-ATPase activity for granule acidification. Genetic mutation of Smad5 or administration of alkaline water to mirror cytosolic alkalization ameliorated glucose intolerance in high-fat diet (HFD)-treated mice. Collectively, our findings suggest that pHc is a direct nexus in linking environmental cues with insulin processing and secretion in ß cells.

Layered assembly of PEGylated graphene oxide and Mg-Al layered double hydroxide nanosheets with superior adsorption capacity and selective isolation of hemoglobin.

This study developed a novel organic-inorganic hybrid composite, shortly as GO-PEG-LDHs, by self-assembly of exfoliated Mg-Al layer double hydroxide (LDHs) on the polyethylene glycol (PEG) grafted graphene oxide (GO) to achieve the selective adsorption of hemoglobin (Hb). The prepared GO-PEG-LDHs has a hierarchical structure with a homogeneous loading of exfoliated LDHs nano-sheets on its surface. The adsorption test reveals that GO-PEG-LDHs exhibits an adsorption efficiency of 95.03% for Hb and 3.45% for bovine serum albumin (BSA). The adsorption of Hb follows the Langmuir model, with an ultrahigh adsorption capacity of 55248.6 mg/g, which is higher than any previously reported materials. Meanwhile, the adsorbed Hb can be efficiently recovered through elution with a 50 mM Tris-HCl buffer, with an elution efficiency of 80.77%. Circular dichroism (CD) spectra indicate no conformational change for Hb during the process of adsorption/desorption. Furthermore, the composite demonstrates the ability to selectively isolate Hb in the presence of interfering protein BSA, indicating its potential for practical applications.

The deubiquitinase Otud7b suppresses cone photoreceptor degeneration in mouse models of retinal degenerative diseases.

Primary and secondary cone photoreceptor death in retinal degenerative diseases, including age-related macular degeneration (AMD) and retinitis pigmentosa (RP), leads to severe visual impairment and blindness. Although the cone photoreceptor protection in retinal degenerative diseases is crucial for maintaining vision, the underlying molecular mechanisms are unclear. Here, we found that the deubiquitinase Otud7b/Cezanne is predominantly expressed in photoreceptor cells in the retina. We analyzed Otud7b-/- mice, which were subjected to light-induced damage, a dry AMD model, or were mated with an RP mouse model, and observed increased cone photoreceptor degeneration. Using RNA-sequencing and bioinformatics analysis followed by a luciferase reporter assay, we found that Otud7b downregulates NF-κB activity. Furthermore, inhibition of NF-κB attenuated cone photoreceptor degeneration in the light-exposed Otud7b-/- retina and stress-induced neuronal cell death resulting from Otud7b deficiency. Together, our findings suggest that Otud7b protects cone photoreceptors in retinal degenerative diseases by modulating NF-κB activity.

Sex differences in functional connectivity and the predictive role of the connectome-based predictive model in Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive decline. Sex differences in the progression of AD exist, but the neural mechanisms are not well understood. The purpose of the current study was to explore sex differences in brain functional connectivity (FC) at different stages of AD and their predictive ability on Montreal Cognitive Assessment (MoCA) scores using connectome-based predictive modeling (CPM). Resting-state functional magnetic resonance imaging was collected from 81 AD patients (44 females), 78 amnestic mild cognitive impairment patients (44 females), and 92 healthy controls (50 females). The FC analysis was conducted and the interaction effect between sex and group was investigated using two-factor variance analysis. The CPM was used to predict MoCA scores. There were sex-by-group interaction effects on FC between the left dorsolateral superior frontal gyrus and left middle temporal gyrus, left precuneus and right calcarine fissure surrounding cortex, left precuneus and left middle occipital gyrus, left middle temporal gyrus and left precentral gyrus, and between the left middle temporal gyrus and right cuneus. In the CPM, the positive network predictive model significantly predicted MoCA scores in both males and females. There were significant sex-by-group interaction effects on FC between the left precuneus and left middle occipital gyrus, and between the left middle temporal gyrus and right cuneus could predict MoCA scores in female patients. Our results suggest that there are sex differences in FC at different stages of AD. The sex-specific FC can further predict MoCA scores at individual level.

Age- and Sex-Specific MR-Feature Tracking Reference Values of Right Atrial Deformation in Healthy Adults.

BACKGROUND: Although right atrial (RA) myocardial deformation has important implications for patient diagnosis, prognosis, and risk stratification, its implementation in clinical practice has been hampered by limited normal reference values, especially in Asian populations. PURPOSE: To establish age- and sex-specific reference values for RA strain, strain rate (SR), and displacement based on a large sample of healthy Chinese adults using MR-feature tracking (MR-FT). STUDY TYPE: Retrospective. POPULATION: 524 healthy Chinese adults (287 male; mean age 43.7 ± 11.9 years). FIELD STRENGTH/SEQUENCE: 1.5T/balanced steady-state free precession. ASSESSMENT: RA deformation parameters, including reservoir, conduit, and booster strain (εs, εe, and εa), peak positive, early negative, and late negative SR (SRs, SRe, and SRa), and total, passive, and active displacement (Ds, De, and Da), were assessed using MR-FT. STATISTICAL TESTS: Student's t-test, one-way ANOVA, coefficients of determination (r2 ), intraclass correlation coefficients (ICC), and Bland-Altman plots. A P value <0.05 was considered significant. RESULTS: Women demonstrated significantly greater magnitudes of RA deformation parameters than men: εs (57.4% ± 15.1% vs. 44.3% ± 12.6%), εe (37.5% ± 13.4% vs. 27.4% ± 10.9%), εa (19.9% ± 5.7% vs. 16.9% ± 5.0%), SRs (2.62 ± 0.88 sec-1 vs. 2.00 ± 0.63 sec-1 ), SRe (-2.98 ± 1.26 sec-1 vs. -2.16 ± 0.92 sec-1 ), SRa (-2.28 ± 0.75 sec-1 vs. -1.84 ± 0.62 sec-1 ), Ds (-7.80 ± 1.90 mm vs. -7.46 ± 1.70 mm), and De (-4.84 ± 1.31 mm vs. -4.49 ± 1.21 mm). For both sexes, aging was significantly associated with decreased RA reservoir and conduit function (εs, SRs, Ds, εe, SRe, and De), and with increased εa and Da. RA deformation measurements had good to excellent intraobserver and interobserver reproducibility, with ICCs ranging from to 0.790 to 0.972. DATA CONCLUSION: This study provides age- and sex-specific reference values of RA strain, SR, and displacement based on a large cohort of healthy Chinese adults using MR-FT. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

A smartwatch sphygmomanometer-based model for predicting short-term new-onset hypertension in individuals with high-normal blood pressure: a cohort study.

OBJECTIVES: The objective was to utilize a smartwatch sphygmomanometer to predict new-onset hypertension within a short-term follow-up among individuals with high-normal blood pressure (HNBP). METHODS: This study consisted of 3180 participants in the training set and 1000 participants in the validation set. Participants underwent both ambulatory blood pressure monitoring (ABPM) and home blood pressure monitoring (HBPM) using a smartwatch sphygmomanometer. Multivariable Cox regressions were used to analyze cumulative events. A nomogram was constructed to predict new-onset hypertension. Discrimination and calibration were assessed using the C-index and calibration curve, respectively. RESULTS: Among the 3180 individuals with HNBP in the training set, 693 (21.8%) developed new-onset hypertension within a 6-month period. The nomogram for predicting new-onset hypertension had a C-index of 0.854 (95% CI, 0.843-0.867). The calibration curve demonstrated good agreement between the nomogram's predicted probabilities and actual observations for short-term new-onset hypertension. In the validate dataset, during the 6-month follow-up, the nomogram had a good C-index of 0.917 (95% CI, 0.904-0.930) and a good calibration curve. As the score increased, the risk of new-onset hypertension significantly increased, with an HR of 8.415 (95% CI: 5.153-13.744, p = .000) for the middle-score vs. low-score groups and 86.824 (95% CI: 55.071-136.885, p = .000) for the high-score vs. low-score group. CONCLUSIONS: This study provides evidence for the use of smartwatch sphygmomanometer to monitor blood pressure in individuals at high risk of developing new-onset hypertension in the near future. TRIAL REGISTRATION: ChiCTR2200057354.

Analytical characterization of full, intermediate, and empty AAV capsids.

Manufacturing of recombinant adeno-associated virus (AAV) vectors produces three types of capsids: full, intermediate, and empty. While there are different opinions about the impact of intermediate and empty capsids on safety and efficacy of AAV products, they are generally considered impurities because they are not the intended fully intact vector product. The presence of these impurities could impact product efficacy due to potential competition with fully packaged AAVs for cellular transduction, as well as have potential implications to patient safety due to increased capsid load during dosing. To determine the impact of intermediate capsids on potency, an AAV preparation was separated into fractions enriched for full, intermediate, or empty capsids. Using a matrix of in vitro (infectivity, gene expression, biological activity) and in vivo potency assays to determine potency as a function of capsid content, our results indicate that while intermediate capsids contribute to the vector genome titer of the product and are equally as infectious as full capsids, they do not contribute to the potency of the AAV product. This study confirms the criticality of reducing and controlling the level of intermediate capsids to ensure a more efficacious AAV product.

Rationality of the ethanol precipitation process in modern preparation production of Zishui-Qinggan decoction evaluated by integrating UPLC-QTOF-MS/MS-based chemical profiling/serum pharmacochemistry and network pharmacology.

INTRODUCTION: Zishui-Qinggan decoction (ZQD) is a classical traditional Chinese medicine formula (TCMF) for alleviating menopausal symptoms (MPS) induced by endocrine therapy in breast cancer patients. In the production of TCMF modern preparations, ethanol precipitation (EP) is a commonly but not fully verified refining process. OBJECTIVES: Chemical profiling/serum pharmacochemistry and network pharmacology approaches were integrated for exploring the rationality of the EP process in the production of ZQD modern preparations. MATERIAL AND METHODS: Ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS) was applied to identify the chemical profiles and absorbed components of ZQD. Network pharmacology was used to identify targets and pathways related to MPS-relieving efficacy. RESULTS: The chemicals of ZQDs without/with EP process (referred to as ZQD-W and ZQD-W-P, respectively) were qualitatively similar with 89 and 87 components identified, respectively, but their relative contents were different; 51 components were detectable in the serum of rats orally administered with ZQD-W, whereas only 19 were detected in that administered with ZQD-W-P. Key targets, such as AKT1, and pathways, such as the PI3K-Akt signalling pathway, affected by ZQD-W and ZQD-W-P were similar, while the neuroactive ligand-receptor interaction pathway among others and the MAPK signalling pathway among others were specific pathways affected by ZQD-W and ZQD-W-P, respectively. The specifically absorbed components of ZQD-W could combine its specific key targets. CONCLUSION: The EP process quantitatively altered the chemical profiles of ZQD, subsequently affected the absorbed components of ZQD, and then affected the key targets and pathways of ZQD for relieving MPS. The EP process might result in variation of the MPS-relieving efficacy of ZQD, which deserves further in vivo verification.

Effects of a periodic intermittent theta burst stimulation in Alzheimer's disease.

Background: Previous studies have demonstrated that excitatory repetitive transcranial magnetic stimulation (rTMS) can improve the cognitive function of patients with Alzheimer's disease (AD). Intermittent theta burst stimulation (iTBS) is a novel excitatory rTMS protocol for brain activity stimulation with the ability to induce long-term potentiation-like plasticity and represents a promising treatment for AD. However, the long-term effects of iTBS on cognitive decline and brain structure in patients with AD are unknown. Aims: We aimed to explore whether repeating accelerated iTBS every three months could slow down the cognitive decline in patients with AD. Methods: In this randomised, assessor-blinded, controlled trial, iTBS was administered to the left dorsolateral prefrontal cortex (DLPFC) of 42 patients with AD for 14 days every 13 weeks. Measurements included the Montreal Cognitive Assessment (MoCA), a comprehensive neuropsychological battery, and the grey matter volume (GMV) of the hippocampus. Patients were evaluated at baseline and after follow-up. The longitudinal pipeline of the Computational Anatomy Toolbox for SPM was used to detect significant treatment-related changes over time. Results: The iTBS group maintained MoCA scores relative to the control group (t=3.26, p=0.013) and reduced hippocampal atrophy, which was significantly correlated with global degeneration scale changes. The baseline Mini-Mental State Examination (MMSE) score, apolipoprotein E genotype and Clinical Dementia Rating were indicative of MoCA scores at follow-up. Moreover, the GMV of the left (t=0.08, p=0.996) and right (t=0.19, p=0.977) hippocampus were maintained in the active group but significantly declined in the control group (left: t=4.13, p<0.001; right: t=5.31, p<0.001). GMV change in the left (r=0.35, p=0.023) and right (r=0.36, p=0.021) hippocampus across the intervention positively correlated with MoCA changes; left hippocampal GMV change was negatively correlated with global degeneration scale (r=-0.32, p=0.041) changes. Conclusions: DLPFC-iTBS may be a feasible and easy-to-implement non-pharmacological intervention to slow down the progressive decline of overall cognition and quality of life in patients with AD, providing a new AD treatment option. Trial registration number: NCT04754152.

Prevalence and serotype distribution of nasopharyngeal carriage of Streptococcus pneumoniae among healthy children under 5 years of age in Hainan Province, China.

BACKGROUND: The thirteen-valent pneumococcal conjugate vaccine (PCV13) is not included in the national immunization program and is administered voluntarily with informed consent in China. In preparation for assessing the impact of pilot introduction in Hainan Province, we conducted a carriage study among children under 5 years of age from four locations in Hainan Province, China. METHODS: From March to June 2022, nasopharyngeal (NP) swabs, collected from healthy children aged younger than 59 months who lived in the 4 different locations (Haikou, Wanning, Baisha and Qiongzhong) in Hainan Province, were tested for pneumococcus using conventional culture. Pneumococcal isolates were serotyped using the Quellung reaction. Risk factors associated with pneumococcal colonization were assessed using univariate analysis and multivariable logistic regression adjusting for age, daycare attendance and other factors. RESULTS: Pneumococcus was isolated in 710 (30.4%) of the 2333 children enrolled. Of 737 pneumococci, 29 serotypes were identified; 60.9% were PCV13 serotypes; the most common vaccine serotypes were 6B (20.4%), 19F (13.0%), 6A (11.9%) and 23F (6.1%); and the most common nonvaccine serotypes were 23A (12.9%), 34 (6.1%) and nontypeable (NT) pneumococci (5.6%). Children vaccinated with PCV13 had lower carriage (17.7% vs 32.5%; P = 0.0001) and fewer PCV13 serotypes (41.9% vs 62.7%; P = 0.0017) compared to unimmunized children. After adjustment, NP carriage was higher among children attending daycare (aOR = 2.3, 95% CI: 1.7-3.2), living in rural areas (aOR = 1.4, 95% CI: 1.1-1.8), living with siblings (aOR = 1.3, 95% CI: 1.0-1.6) and whose mothers had completed senior high/technical secondary school (aOR = 1.5, 95% CI: 1.1-2.0). In contrast, completion of 3-4 doses of PCV13 were associated with a lower carriage rate (aOR = 0.6, 95% CI: 0.4-0.9). CONCLUSIONS: We established the baseline of pneumococcal carriage, serotype distribution and PCV13 immunization rates among healthy children under 5 years of age in Hainan Province, prior to the introduction of PCV13 into the national immunization program. The high proportion of PCV13 serotypes suggests that PCV13 introduction will likely have a substantial impact on pneumococcal carriage in Hainan Province.

Lyophilization enhances the stability of Panax notoginseng total saponins-loaded transfersomes without adverse effects on ex vivo/in vivo skin permeation.

Transfersomes (TFSs) have been extensively investigated to enhance transdermal drug delivery. As a colloidal dispersion system, TFSs are prone to problems such as particle aggregation and sedimentation, oxidation and decomposition of phospholipids. To enhance the stability of panax notoginseng saponins (PNS)-loaded transfersomes (PNS-TFSs) without adverse influences on their skin permeation, we prepared lyophilized PNS-loaded transfersomes (PNS-FD-TFSs), clarified their physicochemical characteristics and investigated their in vitro drug release, ex vivo skin permeation/deposition and in vivo pharmacokinetics. In this study, a simple, fast and controllable process was developed for preparing lyophilized PNS-TFSs. In the optimized PNS-FD-TFS formulation, sucrose and trehalose were added to the PNS-TFS dispersion with a mass ratio of trehalose, sucrose, and phospholipid of 3:2:1, and the mixture was frozen at -80 °C for 12 h followed by lyophilization at -45 °C and 5 Pa for 24 h. The optimized formulation of PNS-FD-TFSs was screened based on the appearance and reconstitution time of the lyophilized products, vesicle size, and PDI of the freshly reconstituted dispersions. It maintained stable physicochemical properties for at least 6 months at 4 °C. The vesicle size of PNS-FD-TFSs was below 100 nm and homogenous with a polydispersity index of 0.2 after reconstitution. The average encapsulation efficiencies of the five index saponins notoginsenoside R1 (NGR1), ginsenoside Rg1 (GRg1), ginsenoside Re (GRe), ginsenoside Rb1 (GRb1) and ginsenoside Rd (GRd) in PNS-FD-TFSs were 68.41 ± 5.77%, 68.95 ± 6.08%, 65.46 ± 10.95%, 91.50 ± 5.62% and 95.78 ± 1.70%, respectively. The reconstituted dispersions of PNS-FD-TFSs were similar to PNS-TFSs in in vitro release, ex vivo skin permeation, and deposition. The pharmacokinetic studies showed that, compared with the PNS liposomes (PNS-LPS), the PNS-FD-TFS-loaded drug could permeate through the skin and enter the blood rapidly. It can be concluded that the lyophilization process can effectively improve the stability of PNS-TFSs without compromising their transdermal absorption properties.

Construction of a cleavable linker chemistry-based HBEXO-Chip to isolate circulating exosomes for breast cancer diagnosis.

Breast cancer is presently the most common form of malignant tumour globally, and its precise diagnosis is vital for enhancing patient survival rates and their quality of life. Exosomes, which are small extracellular vesicles containing proteins and nucleic acid molecules, have emerged as ideal cancer markers for liquid biopsy-based diagnostics. Nevertheless, the current methods for isolating exosomes present challenges for clinical implementation. Although immunoaffinity-based microfluidics hold potential for exosome-based cancer diagnostics, existing microfluidic chips struggle to capture and release intact, high-purity, and highly specific exosomes effectively. To surmount these obstacles, we developed the HBEXO-Chip, an innovative immunoaffinity microfluidic device that employs cleavable linker chemistry technology. This chip enables rapid isolation and detection of breast cancer-derived exosomes in peripheral blood. The fishbone-like microfluidic chip design of the HBEXO-Chip heightens the binding likelihood between specific exosomes and antibodies, significantly augmenting capture efficiency. Furthermore, the gentle reaction conditions of the cleavable linker chemistry retain the exosomes' membrane structure's integrity during the release process, which is advantageous for downstream experimental analysis. Our study demonstrated the effectiveness of the HBEXO-Chip in distinguishing breast cancer patients, patients with benign breast tumours, and healthy controls. By quantitatively analysing Epcam+ exosomes in clinical plasma samples, this technology platform provides a quick, user-friendly, highly sensitive, and specific assay for detecting tumour exosomes in peripheral blood, making it a valuable liquid biopsy tool for clinicians to diagnose breast cancer.

Baseline Pneumococcal IgG Levels and Response to 23-Valent Pneumococcal Polysaccharide Vaccine among Adults from Beijing, China.

PURPOSE: To investigate the baseline levels of serotype-specific IgG antibodies to Streptococcus pneumoniae (S. pneumoniae) and assess their impact on the assessment of vaccine immunogenicity. METHODS: We used a subset of serum samples from a randomized controlled trial. The blood of 584 healthy participants was collected on day 0 before and day 28 after the 23-valent pneumococcal polysaccharide vaccine (PPSV23) vaccination. Serotype-specific IgG against PPSV23-covered serotypes were measured by the World Health Organization (WHO) reference enzyme-linked immunosorbent assay (ELISA). Vaccine immunogenicity was compared using conversion rates (proportion of participants with IgG levels following immunization that are 2-fold greater than the baseline) and geometric mean fold rises (GMFRs) between the two groups, which were grouped according to pre-vaccination (baseline) IgG antibody levels. RESULTS: Our data showed that over half of individuals have baseline IgG levels for 15 out of 23 serotypes above 1.3 µg/mL, and geometric mean concentrations (GMCs) were generally higher in the elderly group and the female group; significant differences were found in 15 serotypes for vaccine immunogenicity based on the seroconversion rate or GMFRs between individuals with baseline IgG ≥ 1.3 µg/mL and individuals with baseline IgG < 1.3 µg/mL. The seroconversion rate decreased with the increase of baseline IgG levels according to a linear regression model. CONCLUSIONS: The assessment of vaccine immunogenicity could be impacted by the fact that many adults had high baseline antibody levels. This study is registered in the Chinese Clinical Trial Registry, number NCT05298800.

Healthy Adult Left and Right Ventricular Torsion and Torsion Rates With MR-Feature Tracking.

BACKGROUND: The clinical value of myocardial torsion quantification in prognostic assessment and risk stratification of various cardiovascular diseases is gradually being recognized. However, normal values of left and right ventricular (LV and RV) torsion and torsion rates (TRs) have not been fully determined, and their correlation with age and gender has not been well studied. PURPOSE: To establish normal ranges of biventricular torsion, peak systolic and diastolic TRs using magnetic resonance feature tracking (MR-FT) technique based on a large sample of healthy adults, and further investigate their relationship with age and gender. STUDY TYPE: Retrospective. POPULATION: 566 Healthy adults (312 males, aged 43 ± 10 years; 254 females, aged 43 ± 11 years). FIELD STRENGTH/SEQUENCE: 1.5T/gradient echo. ASSESSMENT: Biventricular torsion, peak systolic, and diastolic TRs. STATISTICAL TESTS: Shapiro-Wilk test, Student's t-test, Mann-Whitney-U test, linear regression, intraclass correlation coefficient, Bland-Altman analysis. Differences were regarded as statistically significant at P < 0.05. RESULTS: Women demonstrated greater magnitudes of left ventricle (LV) torsion (1.23 ± 0.44 vs. 1.00 ± 0.42°/cm), peak systolic TR (9.69 ± 3.70 vs. 8.27 ± 3.73°/cm*sec), peak diastolic TR (-7.78 ± 2.82 vs. -6.06 ± 2.44°/cm*sec), and RV torsion (2.20 ± 1.23 vs. 1.65 ± 1.11°/cm*sec), peak systolic TR (16.07 ± 8.18 vs. 12.62 ± 7.08°/cm*sec), peak diastolic TR (-15.39 ± 6.53 vs. -11.70 ± 6.03°/cm*sec). For both genders, the magnitudes of LV and RV torsion, peak systolic, and diastolic TRs increased linearly with age. All the measurements of biventricular torsion, peak systolic and diastolic TRs achieved good to excellent intraobserver and interobserver reproducibility, with all intraclass correlation coefficients >0.70. DATA CONCLUSION: The present study systematically provided age- and sex-stratified reference values for LV and RV torsion and TRs using MR-FT technique. Women and aging are associated with greater magnitudes of biventricular torsion, peak systolic, and diastolic TRs. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Deep Learning-based Prediction of Percutaneous Recanalization in Chronic Total Occlusion Using Coronary CT Angiography.

Background CT is helpful in guiding the revascularization of chronic total occlusion (CTO), but manual prediction scores of percutaneous coronary intervention (PCI) success have challenges. Deep learning (DL) is expected to predict success of PCI for CTO lesions more efficiently. Purpose To develop a DL model to predict guidewire crossing and PCI outcomes for CTO using coronary CT angiography (CCTA) and evaluate its performance compared with manual prediction scores. MATERIALS AND METHODS: Participants with CTO lesions were prospectively identified from one tertiary hospital between January 2018 and December 2021 as the training set to develop the DL prediction model for PCI of CTO, with fivefold cross validation. The algorithm was tested using an external test set prospectively enrolled from three tertiary hospitals between January 2021 and June 2022 with the same eligibility criteria. All participants underwent preprocedural CCTA within 1 month before PCI. The end points were guidewire crossing within 30 minutes and PCI success of CTO.Results A total of 534 participants (mean age, 57.7 years ± 10.8 [SD]; 417 [78.1%] men) with 565 CTO lesions were included. In the external test set (186 participants with 189 CTOs), the DL model saved 85.0% of the reconstruction and analysis time of manual scores (mean, 73.7 seconds vs 418.2-466.9 seconds) and had higher accuracy than manual scores in predicting guidewire crossing within 30 minutes (DL, 91.0%; CT Registry of Chronic Total Occlusion Revascularization, 61.9%; Korean Multicenter CTO CT Registry [KCCT], 68.3%; CCTA-derived Multicenter CTO Registry of Japan (J-CTO), 68.8%; P < .05) and PCI success (DL, 93.7%; KCCT, 74.6%; J-CTO, 75.1%; P < .05). For DL, the area under the receiver operating characteristic curve was 0.97 (95% CI: 0.89, 0.99) for the training test set and 0.96 (95% CI: 0.90, 0.98) for the external test set. Conclusion The DL prediction model accurately predicted the percutaneous recanalization outcomes of CTO lesions and increased the efficiency of noninvasively grading the difficulty of PCI. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Pundziute-do Prado in this issue.

Corrosion Degree Evaluation of Polymer Anti-Corrosive Oil Well Cement under an Acidic Geological Environment Using an Artificial Neural Network.

Oil well cement is prone to corrosion and damage in carbon dioxide (CO2) acidic gas wells. In order to improve the anti-corrosion ability of oil well cement, polymer resin was used as the anti-corrosion material. The effect of polymer resin on the mechanical and corrosion properties of oil well cement was studied. The corrosion law of polymer anti-corrosion cement in an acidic gas environment was studied. The long-term corrosion degree of polymer anti-corrosion cement was evaluated using an improved neural network model. The cluster particle algorithm (PSO) was used to improve the accuracy of the neural network model. The results indicate that in acidic gas environments, the compressive strength of polymer anti-corrosion cement was reduced under the effect of CO2, and the corrosion depth was increased. The R2 of the prediction model PSO-BPNN3 is 0.9970, and the test error is 0.0136. When corroded for 365 days at 50 °C and 25 MPa pressure of CO2, the corrosion degree of the polymer anti-corrosion cement was 43.6%. The corrosion depth of uncorroded cement stone is 76.69%, which is relatively reduced by 33.09%. The corrosion resistance of cement can be effectively improved by using polymer resin. Using the PSO-BP neural network to evaluate the long-term corrosion changes of polymer anti-corrosion cement under complex acidic gas conditions guides the evaluation of its corrosion resistance.