Feasibility and reproducibility of cardiovascular magnetic resonance-feature tracking for quantitative right atrial function in dilated cardiomyopathy patients.

Background: The importance of right heart assessment in dilated cardiomyopathy (DCM) is increasingly recognized. The development of cardiovascular magnetic resonance-feature tracking (CMR-FT) has provided a novel approach to quantify myocardial deformation and evaluate cardiac function. In this study, we aimed to evaluate the feasibility and reproducibility of CMR-FT for the quantitative derivation of right atrial (RA) strain and strain rate (SR) in patients with DCM. Methods: A total of 68 DCM patients (84% male; aged 50.6±13.2 years) and 58 healthy controls (81% male; aged 48.4±11.2 years) were retrospectively enrolled from September 2018 to August 2022 at the First Affiliated Hospital of Zhejiang Chinese Medical University and Shenzhen Clinical Medical College of Guangzhou University of Chinese Medicine. RA reservoir, conduit, and booster strain (εs, εe, and εa) and peak positive, peak early negative, and peak late negative SR (SRs, SRe, and SRa) were measured using CMR-FT and compared between 2 groups using Student's t-test. Intra- and inter-observer reproducibility was evaluated using intraclass correlation coefficients (ICC) and Bland-Altman plots. Results: Compared to healthy controls, DCM patients showed significantly lower RA strain (εs: 19.7%±9.0% vs. 44.4%±9.7%; εe: 7.9%±5.3% vs. 25.8%±8.6%; εa: 11.8%±6.2% vs. 18.6%±5.1%, all P<0.001) and SR (SRs: 1.17±0.48 vs. 1.92±0.62 s-1; SRe: -0.85±0.56 vs. -1.94±0.63 s-1; SRa: -1.39±0.71 vs. -2.01±0.65 s-1, all P<0.001). There was no significant difference in RA maximum volume index between the 2 groups. Simple linear regression analysis demonstrated a significant correlation between N-terminal B-type natriuretic peptide (NT-proBNP), RA emptying fraction passive (RAEF passive), and RA εe [(NT-proBNP and εe): r=-0.48, P<0.001, 95% confidence interval (CI): -0.64 to -0.26; and (RAEF passive and εe): r=0.41, P=0.001, 95% CI: 0.22 to 0.56, respectively] in DCM patients. Intra- and inter-observer reproducibility was excellent (all ICCs >0.85) for RA deformation measurements. Conclusions: CMR-FT is a promising, noninvasive approach for the quantitative assessment of RA phasic function in patients with DCM. DCM patients exhibit impaired RA reservoir, conduit, and booster pump function prior to visible RA enlargement.

Abnormal EEG microstates in Alzheimer's disease: predictors of ß-amyloid deposition degree and disease classification.

Electroencephalography (EEG) microstates are used to study cognitive processes and brain disease-related changes. However, dysfunctional patterns of microstate dynamics in Alzheimer's disease (AD) remain uncertain. To investigate microstate changes in AD using EEG and assess their association with cognitive function and pathological changes in cerebrospinal fluid (CSF). We enrolled 56 patients with AD and 38 age- and sex-matched healthy controls (HC). All participants underwent various neuropsychological assessments and resting-state EEG recordings. Patients with AD also underwent CSF examinations to assess biomarkers related to the disease. Stepwise regression was used to analyze the relationship between changes in microstate patterns and CSF biomarkers. Receiver operating characteristics analysis was used to assess the potential of these microstate patterns as diagnostic predictors for AD. Compared with HC, patients with AD exhibited longer durations of microstates C and D, along with a decreased occurrence of microstate B. These microstate pattern changes were associated with Stroop Color Word Test and Activities of Daily Living scale scores (all P < 0.05). Mean duration, occurrences of microstate B, and mean occurrence were correlated with CSF Aß 1-42 levels, while duration of microstate C was correlated with CSF Aß 1-40 levels in AD (all P < 0.05). EEG microstates are used to predict AD classification with moderate accuracy. Changes in EEG microstate patterns in patients with AD correlate with cognition and disease severity, relate to Aß deposition, and may be useful predictors for disease classification.

Integrating UPLC-QTOF-MS/MS and UPLC-DAD to evaluate the influence of sulfur-fumigated Paeoniae Radix Alba on the overall quality of three Si-Wu-Tang formulations.

INTRODUCTION: Sulfur-fumigation of Paeoniae Radix Alba (PRA) could induce the chemical transformation of its bioactive component paeoniflorin into a sulfur-containing derivative paeoniflorin sulfite, and thus alter the quality, bioactivities, pharmacokinetics, and toxicities of PRA. However, how sulfur-fumigated PRA (S-PRA) affects the quality of PRA-containing complex preparations has not been intensively evaluated. OBJECTIVES: We intend to evaluate the influence of S-PRA on the overall quality of three kinds of Si-Wu-Tang (SWT) formulations, i.e., decoction (SWT-D), granule (SWT-G), and mixture (SWT-M). MATERIAL AND METHODS: An UPLC-DAD multi-components quantification method was used to compare the transfer rates of paeoniflorin sulfite and other 10 bioactive components between S-PRA-containing and NS-PRA-containing SWT formulations. An UPLC-QTOF-MS/MS-based target metabolomics approach was applied to explore the differential sulfur-containing derivatives in S-PRA-containing SWT formulations. RESULTS: The transfer rates of paeoniflorin sulfite in three S-PRA-containing SWT formulations were all higher than 100%. Moreover, S-PRA also increased the transfer rate of 5-hydroxymethylfurfural, 1,2,3,4,6-O-pentagalloylglucose, whereas decreased that of paeoniflorin, albiflorin, and ferulic acid in three SWT formulations. Six pinane monoterpene glucoside sulfites originally identified in S-PRA, were also detectable in three S-PRA-containing SWT formulations. In addition, seven phenolic acid sulfites including (3Z)-6-sulfite-ligustilide, (3E)-6-sulfite-ligustilide, 6,8-disulfite-ligustilide, ferulic acid sulfite, neochlorogenic acid sulfite, chlorogenic acid sulfite, and angelicide sulfite (or isomer) were newly identified in these three S-PRA-containing formulations. CONCLUSION: S-PRA could differentially affect the transfer rate of paeoniflorin sulfite and other bioactive components during the preparation of three SWT formulations and subsequently the overall quality thereof.

The contributions of vaccination and natural infection to the production of neutralizing antibodies against the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) prototype strain and variants.

OBJECTIVES: To evaluate the neutralizing antibody (NAbs) levels against the SARS-CoV-2 Omicron variants BF.7, BQ.1, BQ.1.1, XBB.1, and XBB.1.5 after vaccination and natural infection. METHODS: The NAbs against the different viral strains of 490 SARS-CoV-2 infected and 187 uninfected individuals in Beijing COVID-19 outbreak during December 2022 to January 2023 were analyzed. RESULTS: In uninfected individuals, limited levels of NAbs were produced against both the prototype and variant strains after two doses vaccine, but significantly increased after three or four doses vaccine. The infected individuals had high NAbs levels against the BF.7, BQ.1, and BQ.1.1 variants and moderate NAbs levels against the XBB.1 and XBB.1.5 variants. The highest NAbs levels were observed after two inoculation doses. The third and fourth doses vaccine did not result in a significant increase the NAbs levels. After the last dose of vaccination, the NAbs levels peaked at 12 months for the prototype and BF.7 and between 6 to 12 months for the BQ.1, BQ.1.1, XBB.1, and XBB.1.5 variants. CONCLUSION: The immune response decreases as the virus mutates. If booster vaccination is considered necessary, it is suggested for at least 6 months after infection.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Environmental enrichment improves behaviors rather than the growth and physiology of rock bream Oplegnathus fasciatus.

Environmental enrichment has the potential to improve the welfare and post-release survival of hatchery fish stocked for conservation purposes. However, the effectiveness of environmental enrichment is partly dependent on the fish species, life stage, and specific enrichment structure used. To enhance the effectiveness of environmental enrichment, it is crucial to focus on characteristic differences in enrichment structures, such as type and level. This study investigated how differences in enrichment type and level affected physiological and behavioral aspects of the welfare of pre-release juvenile rock bream Oplegnathus fasciatus by evaluating growth performance, basal and stressed cortisol levels, antioxidant enzyme activities, and exploratory behaviors regarding anxiety and flexibility. Fish were reared for 4 weeks in different enrichment treatments: barren, low-level cover structure, high-level cover structure, low-level interference structure (LI), and high-level interference structure (HI). The results revealed that fish reared with the LI treatment showed less anxiety and greater flexibility with respect to exploratory behaviors, without oxidative damage being detected. Despite exhibiting less anxiety as well, fish reared in the HI treatment had oxidative damage, indicated by lower superoxide dismutase activity, compared to those in the barren treatment. In addition, none of these enrichment structures enhanced growth performance or mitigate chronic and acute stress responses. Overall, the low-level interference structure may be more favorable in promoting the behavioral welfare of the fish. Application of this type and level of enrichment may increase the survival of the hatchery fish after release, which is critical to stocking success.

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.