Berberine and chlorogenic acid-assembled nanoparticles for highly efficient inhibition of multidrug-resistant Staphylococcus aureus.

Due to the bacteria resistant to various first-line antibiotics, it is urgent to develop efficient antibiotic alternatives and formulate multidimensional strategies. Herein, supramolecular Chinese medicine nanoparticles are synthesized by self-assembly of berberine (BBR) and chlorogenic acid (CGA), which exhibit higher inhibitory effect against Staphylococcus aureus and multidrug-resistant Staphylococcus aureus (MRSA) than ampicillin, oxacillin, BBR, CGA, as well as mixture of BBR and CGA (minimum inhibitory concentration, MIC = 1.5 µM). The inhibition by BBR/CGA nanoparticles (2.5 µM) reaches 99.06 % for MRSA, which is significantly higher than ampicillin (29.03 %). The nanoparticles with 1/2 MIC can also synergistically restore the antimicrobial activity of ampicillin against MRSA. Moreover, in vivo therapeutic outcome in the murine skin wound infection model suggests that the nanoparticles are able to promote wound healing. This study provides new insights in the application of Chinese medicines self-assembly for MRSA inhibition, as well as solutions for potential persistent clinical infections and drug deficiencies.

Enhancing output current in degradable flexible piezoelectric nanogenerators through internal electrode construction.

Conventional piezoelectric nanogenerators (PNGs) face challenges in terms of degradation and reusability, which have negative environmental implications. On the other hand, biocompatible and degradable piezoelectric materials often exhibit lower piezoelectric response. In this study, potassium sodium niobate (KNN) powder and the biodegradable polymer poly(ε-caprolactone) (PCL) were used to fabricate piezoelectric composite films through solution casting. By constructing staggered electrodes, the total polarized charges quantity is increased, achieving a larger current output. The three-unit PNG (3-PNG) based on the composite film with 15 wt% KNN powder, reaches a maximum output current of 0.85 µA, which exhibits higher charging efficiency compared to 1-PNG. Moreover, the prepared 3-PNG can effectively harvest mechanical energy from human activities and maintain a stable output after 10,000 cycles of bending and releasing. The film exhibits complete degradation when exposed to acidic, neutral, and alkaline solutions. This research provides a promising option for environmentally friendly piezoelectric materials selected and output performance enhanced through optimized structural designs, making them more suitable for practical applications.

The Chinese Clinical Sleep Database: An Innovative Database System Includes Large-Scale Clinical Data of Chinese Population.

Purpose: In this study, we established the Chinese Clinical Sleep Database (CCSD), aiming to provide a safe, scalable, and user-friendly database that includes high-quality clinical data from Chinese population to facilitate sleep research. Material and Methods: We collect individual's demographic data, scales, anthropometric measurements, clinical diagnosis, and polysomnography (PSG) recordings from the routine medical process of sleep medicine centers using standardized procedures. The distributed cluster storage technology are utilized to store these data. The structured data are stored in a high-performance MySQL database, while the unstructured data are stored in an object storage service. And we have developed an online data platform to share and manage our data. Results: The data collection has been conducted in three hospitals. In the preliminary stage of data collection (from October 18, 2022 to September 4, 2023), our database included a total of 1183 patients. Among them, 56.8% were male and their ages ranged from 3 to 88 years. These patients were diagnosed with various types of sleep disorders. Conclusion: Since the CCSD's inception, it has demonstrated good stability, security, and scalability. As an public database, the CCSD also exhibits user-friendliness. The CCSD contains comprehensive clinical data, which can contribute to the advancement of the diagnosis and treatment strategies for sleep disorders, ultimately promoting sleep health.

[Mechanisms of changes of active components in Chinese medicinal materials during drying: a review].

Drying is an indispensable processing step for Chinese medicinal materials after harvesting. It often leads to significant changes in the active components of these materials, thus impacting their medicinal values. Understanding the mechanisms behind the changes during the drying process is of great importance for regulating the transformation of key active components. Therefore, this paper reviews the available studies and comprehensively expounds the mechanisms underlying the changes in active components during the drying process. The aim is to offer insights for the development of regulatory strategies and the improvement of drying techniques for Chinese medicinal materials.

Effects of ultrasonic power on drying kinetics and product quality of licorice extract during ultrasound-assisted vacuum drying.

BACKGROUND: Licorice extract is an important raw material for food additives and medicine. The quality of licorice extract is dictated by the drying process. The commonly used drying methods of licorice extract are not efficient in obtaining high-quality products so alternative techniques need to be developed and researched. In this study, ultrasound-assisted vacuum drying (UAVD) was first utilized to improve drying efficiency and produce a higher-quality product. The changes in water mobility of licorice extract during drying were characterized using low-field nuclear magnetic resonance. In addition, the effects of ultrasonic power on the drying dynamics, the contents of liquiritin and glycyrrhizic acid, the antioxidant capacity and the microstructure formation of licorice extract during the whole drying process were investigated. RESULTS: The drying times for licorice extract to reach equilibrium moisture content were reduced by 9.09-69.70% with UAVD at 40-200 W compared with that without ultrasonic treatment (0 W). Moreover, the proportions of bound water and semi-bound water in fresh concentrate were 3.75% and 96.25%. It was also found that high ultrasonic power promoted the flow of water and the formation of porous structure in licorice extract, which led to the improvement of drying efficiency. The contents of liquiritin (2.444%) and glycyrrhizic acid (6.514%) were retained to a large degree in the dried product at an ultrasonic power of 80 W. The DPPH inhibition rate of UAVD samples with different ultrasonic powers ranged from 84.07 ± 0.46% to 90.65 ± 0.22%. CONCLUSION: UAVD has the advantages of high efficiency and low energy consumption, which may be an alternative technology for vacuum drying widely used in industry. © 2024 Society of Chemical Industry.

Risk stratification of papillary thyroid cancers using multidimensional machine learning.

BACKGROUND: Papillary thyroid cancer (PTC) is one of the most common endocrine malignancies with different risk levels. However, preoperative risk assessment of PTC is still a challenge in the worldwide. Here, the authors first report a Preoperative Risk Assessment Classifier for PTC (PRAC-PTC) by multidimensional features including clinical indicators, immune indices, genetic feature, and proteomics. MATERIALS AND METHODS: The 558 patients collected from June 2013 to November 2020 were allocated to three groups: the discovery set [274 patients, 274 formalin-fixed paraffin-embedded (FFPE)], the retrospective test set (166 patients, 166 FFPE), and the prospective test set (118 patients, 118 fine-needle aspiration). Proteomic profiling was conducted by FFPE and fine-needle aspiration tissues from the patients. Preoperative clinical information and blood immunological indices were collected. The BRAFV600E mutation were detected by the amplification refractory mutation system. RESULTS: The authors developed a machine learning model of 17 variables based on the multidimensional features of 274 PTC patients from a retrospective cohort. The PRAC-PTC achieved areas under the curve (AUC) of 0.925 in the discovery set and was validated externally by blinded analyses in a retrospective cohort of 166 PTC patients (0.787 AUC) and a prospective cohort of 118 PTC patients (0.799 AUC) from two independent clinical centres. Meanwhile, the preoperative predictive risk effectiveness of clinicians was improved with the assistance of PRAC-PTC, and the accuracies reached at 84.4% (95% CI: 82.9-84.4) and 83.5% (95% CI: 82.2-84.2) in the retrospective and prospective test sets, respectively. CONCLUSION: This study demonstrated that the PRAC-PTC that integrating clinical data, gene mutation information, immune indices, high-throughput proteomics and machine learning technology in multicentre retrospective and prospective clinical cohorts can effectively stratify the preoperative risk of PTC and may decrease unnecessary surgery or overtreatment.

[Application prospect of reaction engineering approach in studying drying behavior of single droplet during spray drying of traditional Chinese medicine].

Spray drying technology is one of the most commonly used unit operations in the production of traditional Chinese medicine(TCM) preparations, offering advantages such as short drying time and uniform product quality. However, due to the properties of TCM extracts, such as high viscosity, strong hygroscopicity, and poor flowability, there is limited scope to solve the problems of wall adhesion and clumping in spray drying from the macroscopic perspective of pharmaceutical production. Therefore, it has become a trend to study and optimize the spray drying process from the microscopic point of view by investigating single droplet evaporation behavior. Based on the reaction engineering approach(REA), the single droplet drying system, as a novel method for studying droplets, collects parameter data on individual TCM droplets during the drying process and uses the REA to process the data and establish predictive models. This approach is crucial for understanding the mechanism of TCM spray drying. This paper summarized and analyzed the cha-racteristics of various single droplet systems, the application of REA in single droplet drying systems, and its significance in optimizing the process, predicting drying states, and shortening the development cycle in the field of TCM spray drying, and looked ahead to the prospects of this method, including the introduction of new parameters and imaging techniques, aiming to provide a reference for further research in the field of TCM spray drying.

Short-term outcome of total knee replacement in a patient with hemophilia: A case report and review of literature.

BACKGROUND: Hemophilia A is a rare inherited bleeding disorder caused by mutations in the factor VIII gene. This clotting factor plays an intrinsic role in the blood coagulation pathway. Patients with hemophilia may develop orthopedic manifestations such as hemarthrosis, but multiple malunion of fractures over the knee is rare and difficult to treat. CASE SUMMARY: We report a patient with hemophilia A who developed severe knee osteoarthritis along with fracture malunion and nonunion. Total knee replacement was performed using a custom-made modular hinged knee prosthesis (cemented) equipped with extended distal and proximal stems. At 3 years' follow-up, the patient exhibited excellent clinical function and remained satisfied with the surgical outcome. Surgical intervention was accompanied by rigorous coagulation factor replacement. CONCLUSION: This case highlights various unique scenarios specific to individuals with hemophilia and fracture deformity.

Cauliflower-shaped Pleurotus ostreatus cultivated in an atmosphere with high environmental carbon dioxide concentration.

Commercial aspects, physiological properties, and nutritional characteristics of Pleurotus ostreatus grown under various environmental carbon dioxide concentration ([CO2]e) conditions were assessed. As [CO2]e increased, the activity of antioxidant enzymes (catalase, peroxidase, and superoxide dismutase) in fruiting body increased, activities of succinate dehydrogenase and cytochrome c oxidase were inhibited, and malondialdehyde and adenosine triphosphate (ATP) syntheses were reduced, leading to incomplete development of pilei and stipes, or even absence of pilei. Under high [CO2]e (≥1.00%), fruiting body of P. ostreatus was morphologically altered to assume cauliflower shape. This cultivation condition resulted in high total contents of crude protein, crude fiber, and amino acids, increased levels of umami- and sweet-tasting amino acids, and reduced levels of bitter-tasting amino acids, thus enhancing the flavor of the product. In conclusion, a novel "cauliflower-shaped" mushroom (P. ostreatus) was successfully cultivated at high (≥1.00%) environmental CO2 concentration. The product has a delicious taste and high nutritional value, is relatively easy to transport and store, and has excellent potential for commercial development.

Electroencephalogram pattern association with drug-related cues in a long-duration virtual reality environment in patients with methamphetamine use disorder.

The cognitive processing of drug-related cues and the subsequent dysregulation of behaviour play a central role in the pathophysiology of substance use disorders. Prior studies are limited by small sample sizes and a lack of immersion in stimulus presentation. In the present study, we recruited patients with methamphetamine use disorder (MUD; N = 1099) from four compulsory isolated detoxification centres and healthy control participants (N = 305). With a 12-min-long virtual reality (VR) protocol stimulus, we discovered that patients showed a decrease in electroencephalogram (EEG) power across alpha to gamma bands in anterior scalp regions under methamphetamine-related VR stimuli (e.g. a glass pipe and medical tubing) compared with the control stimuli (e.g. balls and cubes). Analysis of variance (ANOVA) showed that the interaction effects of stimuli type and group were significant in five EEG bands. Using generalised linear models, we classified the stimuli type (i.e. drug-related vs. drug-unrelated cues) in MUD patients with an f1 score of 90% on an out-of-sample testing set. The decreases of EEG between drug-related cues and drug-unrelated cues in delta, theta and alpha frequency bands are more frequently seen in patients than in healthy controls, perhaps reflecting general arousal and attenuated impulsive control. Our results suggest that EEG responses elicited by long-duration methamphetamine-related VR cues showed a specific signature, which may have future clinical implications.

Nomogram model based on preoperative clinical characteristics of unilateral papillary thyroid carcinoma to predict contralateral medium-volume central lymph node metastasis.

Objectives: To explore the preoperative high-risk clinical factors for contralateral medium-volume central lymph node metastasis (conMVCLNM) in unilateral papillary thyroid carcinoma (uPTC) and the indications for dissection of contralateral central lymph nodes (conCLN). Methods: Clinical and pathological data of 204 uPTC patients who underwent thyroid surgery at the Hangzhou First People's Hospital from September 2010 to October 2022 were collected. Univariate and multivariate logistic regression analyses were conducted to determine the independent risk factors for contralateral central lymph node metastasis (conCLNM) and conMVCLNM in uPTC patients based on the preoperative clinical data. Predictive models for conCLNM and conMVCLNM were constructed using logistic regression analyses and validated using receiver operating characteristic (ROC) curves, concordance index (C-index), calibration curves, and decision curve analysis (DCA). Results: Univariate and multivariate logistic regression analyses showed that gender (P < 0.001), age (P < 0.001), tumor diameter (P < 0.001), and multifocality (P = 0.008) were independent risk factors for conCLNM in uPTC patients. Gender(P= 0.026), age (P = 0.010), platelet-to-lymphocyte ratio (PLR) (P =0.003), and tumor diameter (P = 0.036) were independent risk factors for conMVCLNM in uPTC patients. A predictive model was established to assess the risk of conCLNM and conMVCLNM, with ROC curve areas of 0.836 and 0.845, respectively. The C-index, the calibration curve, and DCA demonstrated that the model had good diagnostic value. Conclusion: Gender, age, tumor diameter, and multifocality are high-risk factors for conCLNM in uPTC patients. Gender, age, tumor diameter, and PLR are high-risk factors for conMVCLNM in uPTC patients, and preventive conCLN dissection should be performed.

CD4+ CTLs Act as a Key Effector Population for Allograft Rejection of MSCs in a Donor MHC-II Dependent Manner in Injured Liver.

Mesenchymal stromal/stem cells (MSCs) have been considered an attractive source of cytotherapy due to their promising effects on treating various diseases. Allogeneic MSCs (allo-MSCs) are extensively used in clinical trials due to their convenient preparation and credible performance. Traditionally, allo-MSCs are considered immunoprivileged with minimal immunogenicity and potent immunomodulatory capacity. However, growing evidence has suggested that allo-MSCs also induce immune response and cause rejection after transplantation, but the underlying cellular and molecular mechanisms remain to be elucidated. Here, we demonstrated that allografted MSCs upregulated MHC-II upon stimulation of IFN-γ in hepatic inflammatory environment by using mouse model of CCl4-induced liver injury. MHC-II upregulation enhanced the immunogenicity of allo-MSCs, leading to the activation of alloreactive T cells and rejection of allo-MSCs. However, MHC-II deficiency impaired the allogenic reactivity, thereby rescuing the loss of allo-MSCs. Mechanistically, CD4+ cytotoxic T lymphocytes (CTLs), rather than CD8+ CTLs, acted as the major effector for allo-MSC rejection. Under liver injury condition, the transplanted allo-MSCs upregulated CD80 and PD-L1, and CD8+ CTLs highly expressed CTLA-4 and PD-1, thereby inducing immune tolerance of CD8+ T cells to allo-MSCs. On the contrary, CD4+ CTLs minimally expressed CTLA-4 and PD-1; thus, they remain cytotoxic to allo-MSCs. Consequently, transplantation of MHC-II-deficient allo-MSCs substantially promoted their therapeutic effects in treating liver injury. This study revealed a novel mechanism of MSC allograft rejection mediated by CD4+ CTLs in injured liver, which provided new strategies for improving clinical performance of allo-MSCs in benefiting hepatic injury repair.

Corrigendum: Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participants.

[This corrects the article DOI: 10.3389/fcvm.2022.964977.].

Laminaria japonica Peptides Suppress Liver Cancer by Inducing Apoptosis: Possible Signaling Pathways and Mechanism.

The anticancer properties of Laminaria japonica peptides (LJPs) have never been studied. Here, we extracted LJPs from fresh seaweed and explored their anti-liver cancer activity (in vivo and in vitro). LJPs were isolated/purified by HPLC-ESI-MS. HepG2 cell apoptosis and cell cycle were evaluated. MTT assays were used to examine the cytotoxicity of LJPs. Caspase activation of caspases 3 and 9, cleaved caspases 3 and 9, and cleaved PARP was examined by Western blotting. The PI3K/AKT pathway and the phosphorylation states of MAPKs (p38 and JNK) were examined. We found that the LJP-1 peptide had the most antiproliferative activity in H22 cells in vitro. LJP-1 blocked H22 cells in the G0/G1 phase, accompanied by inhibition of cyclin expression. LJP-1 induced apoptosis through caspase activation and regulation of the ASK1/MAPK pathway. Concurrent in vivo studies demonstrated that LJP-1 significantly inhibited tumor growth and induced tumor cell apoptosis/necrosis. In conclusion, LJPs, particularly LJP-1, exert strong inhibitory effects on liver cancer growth in vivo and in vitro. LJP-1 induces HCC cell apoptosis through the caspase-dependent pathway and G0/G1 arrest. LJP-1 induces caspase-dependent apoptosis, in part by inhibiting PI3K, MAPK signaling pathways, and cell cycle proteins. LJP-1 has the potential to be a novel candidate for human liver cancer therapeutics.

Preliminary efficacy of a digital therapeutics smartphone application for methamphetamine use disorder: An experimental study.

Methamphetamine is the most widely used illicit drug in China. Treating methamphetamine use disorder (MUD) is challenging due to the lack of effective pharmacotherapies. This study is an experimental study to investigate the efficacy of smartphone-based digital therapeutics in treating MUD at the community level. One hundred participants were recruited and randomized into a digital therapeutics (DTx) group (n = 52) and a treatment as usual (TAU) group (n = 48). The DTx group used a smartphone application to deliver cognitive behavioral therapy, approach bias modification, cognitive training, and contingency management for 8 weeks. The TAU group received counseling from social workers and professional psychotherapists. Cue-induced craving, cognitive functions, PHQ9, and GAD7 were measured at baseline and post-intervention. Wilcoxon tests were performed with bootstrap and multiply imputation to estimate the treatment effect size. The DTx group showed a significant reduction in drug craving [Wilcoxon effect size = -0.267, 95% CI = (-0.435, -0.099), p = 0.002] and a significant improvement in cognitive function [Wilcoxon effect size = 0.220, 95% CI = (0.009, 0.432), p = 0.041]. The DTx group had overall 1, 8, and 24-week attritions of 8%, 11.5%, and 38.5%, respectively. The study shows that Digital therapeutics is feasible and potentially beneficial as a complement to community substance use treatment programs.

Predicting PTSD symptoms in firefighters using a fear-potentiated startle paradigm and machine learning.

This study develops a fear-potentiated startle paradigm (FPS) and a machine learning approach to accurately predict PTSD symptoms using electrogram data. A three-phase fear-potentiated startle paradigm was designed to assess the conditioning, generalization, and extinction of fear. Electrooculogram and electrocardiogram signals were collected during the FPS. A total of 1107 Chinese firefighters participated in the study. The Chinese version PCL-C was administered to all subjects. A cutoff of 38 or higher is used to indicate PTSD symptoms. Electrogram features were extracted and selected to build a machine learning model to classify individuals. The machine learning model was 5-fold cross validated. The importance of the selected features was calculated. Classification performance metrics were evaluated for the machine learning model. The machine learning model can identify firefighters with a PCL-C score of 38 or above with sensitivity and specificity both above 0.85 when 5-fold cross validated on a 1107-person sample. The area under the receiver operating characteristic curve of the model is 0.93. Features related to fear generalization are found to be the most important. The proposed fear-potentiated startle paradigm and machine learning approach can accurately predict PTSD symptoms in Chinese firefighters, which can improve the screening and diagnosis of PTSD.

Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participants.

Nattokinase (NK), known as a potent fibrinolytic and antithrombotic agent, has been shown to have antiatherosclerotic and lipid-lowering effects. However, data on human clinical studies are limited. In this clinical study involving 1,062 participants, our objective was to examine the efficacy of NK in atherosclerosis and hyperlipidemia and safety at the dose of 10,800 FU/day after 12 months of oral administration. Various factors, including lower doses that influence NK pharmacological actions, were also investigated. We found that NK at a dose of 10,800 FU/day effectively managed the progression of atherosclerosis and hyperlipidemia with a significant improvement in the lipid profile. A significant reduction in the thickness of the carotid artery intima-media and the size of the carotid plaque was observed. The improvement rates ranged from 66.5 to 95.4%. NK was found to be ineffective in lowering lipids and suppressing atherosclerosis progression at a dose of 3,600 FU/day. The lipid-lowering effect of NK was more prominent in subjects who smoked, drank alcohol, and subjects with higher BMI. Regular exercise further improved the effects of NK. Co-administration of vitamin K2 and aspirin with NK produced a synergetic effect. No noticeable adverse effects associated with the use of NK were recorded. In conclusion, our data demonstrate that atherosclerosis progression and hyperlipidemia can be effectively managed with NK at a dose of 10,800 FU/day. The lower dose of 3,600 FU per day is ineffective. The dose of 10,800 FU/day is safe and well tolerated. Some lifestyle factors and the coadministration of vitamin K2 and aspirin lead to improved outcomes in the use of NK. Our findings provide clinical evidence on the effective dose of NK in the management of cardiovascular disease and challenge the recommended dose of 2,000 FU per day.

Occurrences and Functions of Ly6Chi and Ly6Clo Macrophages in Health and Disease.

Macrophages originating from the yolk sac or bone marrow play essential roles in tissue homeostasis and disease. Bone marrow-derived monocytes differentiate into Ly6Chi and Ly6Clo macrophages according to the differential expression of the surface marker protein Ly6C. Ly6Chi and Ly6Clo cells possess diverse functions and transcriptional profiles and can accelerate the disease process or support tissue repair and reconstruction. In this review, we discuss the basic biology of Ly6Chi and Ly6Clo macrophages, including their origin, differentiation, and phenotypic switching, and the diverse functions of Ly6Chi and Ly6Clo macrophages in homeostasis and disease, including in injury, chronic inflammation, wound repair, autoimmune disease, and cancer. Furthermore, we clarify the differences between Ly6Chi and Ly6Clo macrophages and their connections with traditional M1 and M2 macrophages. We also summarize the limitations and perspectives for Ly6Chi and Ly6Clo macrophages. Overall, continued efforts to understand these cells may provide therapeutic approaches for disease treatment.

Application of edible coating pretreatment before drying to prevent loss of plant essential oil: A case study of Zanthoxylum schinifolium fruits.

In this study, a novel use of edible coating pretreatment before convective hot-air drying to prevent the loss of essential oil (EO) in natural aromatic plant materials was successfully conducted on Zanthoxylum schinifolium fruits. The sodium carboxymethyl cellulose (CMC) aqueous solution was used as the coating material and the effects of its different concentration of 0-2.5% (w/v) on the drying kinetics, total EO content, EO composition and micromorphology of oil chamber were studied. Results showed that increasing concentration of CMC solution significantly increased the total EO retention (p < 0.05) and restricted the change in EO composition. Moreover, the highest CMC solution concentration gave 100% total EO retention, and meanwhile increased the drying time only by 45 min. Therefore, the application of edible coating pretreatment before drying presents a promising method to achieve excellent retention of plant EO.

The platform development, adherence and efficacy to a digital Brief therapy for insomnia (dBTI) during the COVID-19 pandemic.

Brief therapy for insomnia (BTI) is a short-term cognitive behavioral therapy for insomnia. At present, there is no study combining BTI with digital technology. However, in the context of the outbreak of coronavirus disease 2019 (COVID-19), patients with acute insomnia may need an online treatment which can quickly improve insomnia symptoms. Our team built a digital BTI (dBTI) platform based on the WeChat mini program. This research provides a framework design and a course design of dBTI, and evaluates the system via recruiting participants suffering from acute insomnia in pandemic. What's more, it explores patients' adherence, the efficiency of the system and their relationship. As the result demonstrates, 68% of participants have completed more than half of the course with medium to high adherence. Gender, pre-sleep arousal scale (PSAS) somatic score and insomnia severity index (ISI) score have affected participants' adherence, and higher adherence has led to better improvement in the severity of insomnia and somatic pre-sleep arousal. It is proved that the platform we built is effective, which not only offers an entry point for the study of how to set up a dBTI platform, but also provides theoretical basis for its clinical application.