Identification of Methamphetamine Abusers Can Be Supported by EEG-Based Wavelet Transform and BiLSTM Networks.

Methamphetamine (MA) is a neurological drug, which is harmful to the overall brain cognitive function when abused. Based on this property of MA, people can be divided into those with MA abuse and healthy people. However, few studies to date have investigated automatic detection of MA abusers based on the neural activity. For this reason, the purpose of this research was to investigate the difference in the neural activity between MA abusers and healthy persons and accordingly discriminate MA abusers. First, we performed event-related potential (ERP) analysis to determine the time range of P300. Then, the wavelet coefficients of the P300 component were extracted as the main features, along with the time and frequency domain features within the selected P300 range to classify. To optimize the feature set, F_score was used to remove features below the average score. Finally, a Bidirectional Long Short-term Memory (BiLSTM) network was performed for classification. The experimental result showed that the detection accuracy of BiLSTM could reach 83.85%. In conclusion, the P300 component of EEG signals of MA abusers is different from that in normal persons. Based on this difference, this study proposes a novel way for the prevention and diagnosis of MA abuse.

Uncovering the mechanism of Clostridium butyricum CBX 2021 to improve pig health based on in vivo and in vitro studies.

Introduction: As a symbiotic probiotic for the host, Clostridium butyricum (CB) has the potential to strengthen the body's immune system and improve intestinal health. However, the probiotic mechanism of CB is not completely understood. The Clostridium butyricum CBX 2021 strain isolated by our team from a health pig independently exhibits strong butyric acid production ability and stress resistance. Therefore, this study comprehensively investigated the efficacy of CBX 2021 in pigs and its mechanism of improving pig health. Methods: In this study, we systematically revealed the probiotic effect and potential mechanism of the strain by using various methods such as microbiome, metabolites and transcriptome through animal experiments in vivo and cell experiments in vitro. Results: Our in vivo study showed that CBX 2021 improved growth indicators such as daily weight gain in weaned piglets and also reduced diarrhea rates. Meanwhile, CBX 2021 significantly increased immunoglobulin levels in piglets, reduced contents of inflammatory factors and improved the intestinal barrier. Subsequently, 16S rRNA sequencing showed that CBX 2021 treatment implanted more butyric acid-producing bacteria (such as Faecalibacterium) in piglets and reduced the number of potentially pathogenic bacteria (like Rikenellaceae RC9_gut_group). With significant changes in the microbial community, CBX 2021 improved tryptophan metabolism and several alkaloids synthesis in piglets. Further in vitro experiments showed that CBX 2021 adhesion directly promoted the proliferation of a porcine intestinal epithelial cell line (IPEC-J2). Moreover, transcriptome analysis revealed that bacterial adhesion increased the expression of intracellular G protein-coupled receptors, inhibited the Notch signaling pathway, and led to a decrease in intracellular pro-inflammatory molecules. Discussion: These results suggest that CBX 2021 may accelerate piglet growth by optimizing the intestinal microbiota, improving metabolic function and enhancing intestinal health.

Prognostic and clinicopathological significance of systemic immune-inflammation index in upper tract urothelial carcinoma: a meta-analysis of 3911 patients.

Background: Systemic immune-inflammation index (SII), a novel prognostic indicator, is being more commonly utilized in different types of cancer. This research project involved combining information from previously published studies to examine how pre-treatment SII can predict outcomes in individuals with upper tract urothelial carcinoma (UTUC). Further examination of the correlation between SII and clinical and pathological features in UTUC. Methods: We thoroughly chose pertinent articles from various databases including PubMed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI), WanFang database, and Chinese Scientific Journal Database (VIP) until March 10, 2022.The data collected was analyzed using Stata 17.0 software (Stat Corp, College Station, TX). Subsequently, the impact of SII on the survival outcomes of UTUC patients was evaluated by combining HRs with 95% confidence intervals. Results: Six included studies were finally confirmed, including 3911 UTUC patients in seven cohorts. The results showed that high SII before treatment predicted poor overall survival (HR =1.87, 95%CI 1.20-2.92, p=0.005), cancer specific survival (HR=2.70, 95%CI 1.47-4.96, P=0.001), and recurrence-free survival (HR =1.52, 95%CI 1.12-2.07, P=0.007). And the elevated SII may be related to LVI (present vs. absent) (OR=0.83, 95% CI=0.71-0.97, p=0.018), pT stage (pT ≥3 vs. < 3) (OR=1.82, 95% CI=1.21-2.72, p=0.004), and pN stage (N+ vs. N0) (OR=3.27, 95% CI=1.60-6.71, p=0.001). Conclusion: A comprehensive analysis of all included articles in this study showed that higher pretreatment SII was related to poorer survival outcomes and adverse pathological features independently. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022316333.

Hsa_Circ_002144 Promotes Glycolysis and Immune Escape of Breast Cancer Through miR-326/PKM Axis.

Background: Breast cancer is a leading cause of cancer-related deaths in women worldwide, posing a significant threat to female health. Therefore, it is crucial to search for new therapeutic targets and prognostic biomarkers for breast cancer patients. Method: Bioinformatics analysis, quantitative real-time PCR (qRT-PCR), and fluorescence in situ hybridization (FISH) were employed to investigate the expression of hsa_circ_002144 in breast cancer. Transwell assay, Western blotting, and cell viability assay were utilized to assess the impact of hsa_circ_002144 on the proliferation, migration, and invasion of breast cancer cells. Additionally, a mouse model was established to validate its functionality. Flow cytometry, WB analysis, enzyme-linked immunosorbent assay (ELISA), qRT-PCR, exosomes isolation, and co-culture system were employed to elucidate the molecular mechanism underlying macrophage polarization. Result: we have discovered for the first time that hsa_circ_002144 is highly expressed in breast cancer. It affected tumor growth and metastasis and could influence macrophage polarization through the glycolytic pathway. Conclusion: This finding provides a new direction for breast cancer treatment and prognosis assessment.

H19 lncRNA triggers ferroptosis, exacerbating ox-LDL-induced artery endothelial cell damage in vitro.

BACKGROUND: The precise association between lncRNA H19 and ferroptosis in the context of atherosclerosis remains uncertain. OBJECTIVE: This study is to clarify the underlying process and propose novel approaches for the advancement of therapeutic interventions targeting atherosclerosis. METHODS: Assessment of ferroptosis, which entails the evaluation of cell viability using CCK-8 and the quantification of intracellular MDA, GSH, and ferrous ions. Simultaneously, the protein expression levels of assessed by western blot analysis, while the expression level of lncRNA H19 was also determined. Furthermore, HAECs that were cultured with ox-LDL were subjected to Fer-1 interference. HAECs were exposed to ox-LDL and then transfected with H19 shRNA and H19 overexpression vector pcDNA3.1. The level of ferroptosis in the cells was then measured. Then, HAECs were subjected to incubation with ox-LDL, followed by transfection with H19 shRNA and treated with Erastin to assess the levels of ferroptosis, cell viability, and inflammatory factor production. and the ability for blood vessel development. RESULTS: The survival rate of HAECs in the ox-LDL group was much lower. Ox-LDL resulted in an upregulation of ACSL4 expression in HAECs, while the expression of SLC7A11 and GPX4 decreased. CONCLUSIONS: lncRNA H19 enhances ferroptosis and exacerbates arterial endothelial cell damage induced by LDL.

Dynamic changes of gut microbiota in mouse models of metabolic dysfunction-associated steatohepatitis and its transition to hepatocellular carcinoma.

Dysbiosis of gut microbiota may account for pathobiology in simple fatty liver (SFL), metabolic dysfunction-associated steatohepatitis (MASH), fibrotic progression, and transformation to MASH-associated hepatocellular carcinoma (MASH-HCC). The aim of the present study is to investigate gut dysbiosis in this progression. Fecal microbial rRNA-16S sequencing, absolute quantification, histopathologic, and biochemical tests were performed in mice fed high fat/calorie diet plus high fructose and glucose in drinking water (HFCD-HF/G) or control diet (CD) for 2, 16 weeks, or 14 months. Histopathologic examination verified an early stage of SFL, MASH, fibrotic, or MASH-HCC progression with disturbance of lipid metabolism, liver injury, and impaired gut mucosal barrier as indicated by loss of occludin in ileum mucosa. Gut dysbiosis occurred as early as 2 weeks with reduced α diversity, expansion of Kineothrix, Lactococcus, Akkermansia; and shrinkage in Bifidobacterium, Lactobacillus, etc., at a genus level. Dysbiosis was found as early as MAHS initiation, and was much more profound through the MASH-fibrotic and oncogenic progression. Moreover, the expansion of specific species, such as Lactobacillus johnsonii and Kineothrix alysoides, was confirmed by an optimized method for absolute quantification. Dynamic alterations of gut microbiota were characterized in three stages of early SFL, MASH, and its HCC transformation. The findings suggest that the extent of dysbiosis was accompanied with MASH progression and its transformation to HCC, and the shrinking or emerging of specific microbial species may account at least in part for pathologic, metabolic, and immunologic alterations in fibrogenic progression and malignant transition in the liver.

Optimal dosage ranges of various exercise types for enhancing timed up and go performance in Parkinson's disease patients: a systematic review and Bayesian network meta-analysis.

Objective: To examine the dose-response relationship between specific types of exercise for alleviating Timed up and Go (TUG) in Parkinson's disease PD. Design: Systematic review and Bayesian network meta-analysis. Data sources: PubMed, Medline, Embase, PsycINFO, Cochrane Library, and Web of Science were searched from inception until February 5th, 2024. Study analysis: Data analysis was conducted using R software with the MBNMA package. Effect sizes of outcome indicators were expressed as mean deviation (MD) and 95% confidence intervals (95% CrI). The risk of bias in the network was evaluated independently by two reviewers using ROB2. Results: A total of 73 studies involving 3,354 PD patients. The text discusses dose-response relationships in improving TUG performance among PD patients across various exercise types. Notably, Aquatic (AQE), Mix Exercise (Mul_C), Sensory Exercise (SE), and Resistance Training (RT) demonstrate effective dose ranges, with AQE optimal at 1500 METs-min/week (MD: -8.359, 95% CI: -1.398 to -2.648), Mul_C at 1000 METs-min/week (MD: -4.551, 95% CI: -8.083 to -0.946), SE at 1200 METs-min/week (MD: -5.145, 95% CI: -9.643 to -0.472), and RT at 610 METs-min/week (MD: -2.187, 95% CI: -3.161 to -1.278), respectively. However, no effective doses are found for Aerobic Exercise (AE), Balance Gait Training (BGT), Dance, and Treadmill Training (TT). Mind-body exercise (MBE) shows promise with an effective range of 130 to 750 METs-min/week and an optimal dose of 750 METs-min/week (MD: -2.822, 95% CI: -4.604 to -0.996). According to the GRADE system, the included studies' overall quality of the evidence was identified moderate level. Conclusion: This study identifies specific exercise modalities and dosages that significantly enhance TUG performance in PD patients. AQE emerges as the most effective modality, with an optimal dosage of 1,500 METs-min/week. MBE shows significant benefits at lower dosages, catering to patients with varying exercise capacities. RT exhibits a nuanced "U-shaped" dose-response relationship, suggesting an optimal range balancing efficacy and the risk of overtraining. These findings advocate for tailored exercise programs in PD management, emphasizing personalized prescriptions to maximize outcomes.Systematic Review Registration: International Prospective Register of Systematic Reviews (PROSPERO) (CRD42024506968).

Exploring the potential of the TCR repertoire as a tumor biomarker (Review).

T cells play an important role in adaptive immunity. Mature T cells specifically recognize antigens on major histocompatibility complex molecules through T-cell receptors (TCRs). As the TCR repertoire is highly diverse, its analysis is vital in the assessment of T cells. Advances in sequencing technology have provided convenient methods for further investigation of the TCR repertoire. In the present review, the TCR structure and the mechanisms by which TCRs function in tumor recognition are described. In addition, the potential value of the TCR repertoire in tumor diagnosis is reviewed. Furthermore, the role of the TCR repertoire in tumor immunotherapy is introduced, and the relationships between the TCR repertoire and the effects of different tumor immunotherapies are discussed. Based on the reviewed literature, it may be concluded that the TCR repertoire has the potential to serve as a biomarker for tumor prognosis. However, a wider range of cancer types and more diverse subjects require evaluation in future research to establish the TCR repertoire as a biomarker of tumor immunity.

Interannual fluctuations in precipitation shape the trajectory of ecosystem respiration along a grazing exclusion chronosequence in a typical steppe in Inner Mongolia.

Grazing exclusion (GE), as an effective strategy for revitalizing degraded grasslands, possesses the potential to increase ecosystem respiration (Re) and significantly influence the capacity of grassland soils to sequester carbon. However, our current grasp of Re dynamics in response to varying durations of GE, particularly in the context of precipitation fluctuations, remains incomplete. To fill this knowledge gap, we conducted a monitoring of Re over a 40-year GE chronosequence within Inner Mongolia temperate typical steppe across two distinct hydrologically years. Overall, Re exhibited a gradual saturation curve and an increasing trend with the duration of GE in the wet year of 2021 and the normal precipitation year of 2022, respectively. The variance primarily stemmed from relatively higher microbial biomass carbon observed in the short-term GE during 2022 in contrast to 2021. Moreover, the impacts of GE on the sensitivities of Re to moisture and temperature were intricately tied to precipitation patterns. increasing significantly with prolonged GE duration in 2022 but not in 2021. Our study highlights the intricate interplay between GE duration, precipitation variability, and Re dynamics. This deeper understanding enhances our ability to predict and manage carbon cycling within typical steppe in Inner Mongolia, offering invaluable insights for effective restoration strategies and climate change mitigation.

Conditioned culture medium of bone marrow mesenchymal stem cells promotes phenotypic transformation of microglia by regulating mitochondrial autophagy.

Objective: To study the mechanism by which conditioned medium of bone marrow mesenchymal stem cells (BMSCs-CM) facilitates the transition of pro-inflammatory polarized microglia to an anti-inflammatory phenotype. Methods: BV2 cells, a mouse microglia cell line, were transformed into a pro-inflammatory phenotype using lipopolysaccharide. The expression of phenotypic genes in BV2 cells was detected using real-time quantitative PCR (RT-qPCR). Enzyme-linked immunosorbent assay was used to measure inflammatory cytokine levels in BV2 cells co-cultured with BMSCs-CM. The expressions of mitophagy-associated proteins were determined using western blot. The mitochondrial membrane potential and ATP levels in BV2 cells were measured using JC-1 staining and an ATP assay kit, respectively. Additionally, we examined the proliferation, apoptosis, and migration of C8-D1A cells, a mouse astrocyte cell line, co-cultured with BV2 cells. Results: After co- culture with BMSCs -CM, the mRNA expression of tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase significantly decreased in pro-inflammatory BV2 cells, whereas the expression of CD206 and arginase-1 significantly increased. Moreover, TNF-α and interleukin-6 levels significantly decreased, whereas transforming growth factor-ß and interleukin-10 levels significantly increased. Furthermore, co-culture with BMSCs-CM increased mitophagy-associated protein expression, ATP levels, mitochondrial and lysosomal co-localization in these cells and decreased reactive oxygen species levels. Importantly, BMSCs-CM reversed the decrease in the proliferation and migration of C8-D1A cells co-cultured with pro-inflammatory BV2 cells and inhibited the apoptosis of C8-D1A cells. Conclusion: BMSCs-CM may promote the transition of polarized microglia from a pro-inflammatory to an anti-inflammatory phenotype by regulating mitophagy and influences the functional state of astrocytes.

Development and validation of an interpretable machine learning model for predicting post-stroke epilepsy.

BACKGROUND: Epilepsy is a serious complication after an ischemic stroke. Although two studies have developed prediction model for post-stroke epilepsy (PSE), their accuracy remains insufficient, and their applicability to different populations is uncertain. With the rapid advancement of computer technology, machine learning (ML) offers new opportunities for creating more accurate prediction models. However, the potential of ML in predicting PSE is still not well understood. The purpose of this study was to develop prediction models for PSE among ischemic stroke patients. METHODS: Patients with ischemic stroke from two stroke centers were included in this retrospective cohort study. At the baseline level, 33 input variables were considered candidate features. The 2-year PSE prediction models in the derivation cohort were built using six ML algorithms. The predictive performance of these machine learning models required further appraisal and comparison with the reference model using the conventional triage classification information. The Shapley additive explanation (SHAP), based on fair profit allocation among many stakeholders according to their contributions, is used to interpret the predicted outcomes of the naive Bayes (NB) model. RESULTS: A total of 1977 patients were included to build the predictive model for PSE. The Boruta method identified NIHSS score, hospital length of stay, D-dimer level, and cortical involvement as the optimal features, with the receiver operating characteristic curves ranging from 0.709 to 0.849. An additional 870 patients were used to validate the ML and reference models. The NB model achieved the best performance among the PSE prediction models with an area under the receiver operating curve of 0.757. At the 20 % absolute risk threshold, the NB model also provided a sensitivity of 0.739 and a specificity of 0.720. The reference model had poor sensitivities of only 0.15 despite achieving a helpful AUC of 0.732. Furthermore, the SHAP method analysis demonstrated that a higher NIHSS score, longer hospital length of stay, higher D-dimer level, and cortical involvement were positive predictors of epilepsy after ischemic stroke. CONCLUSIONS: Our study confirmed the feasibility of applying the ML method to use easy-to-obtain variables for accurate prediction of PSE and provided improved strategies and effective resource allocation for high-risk patients. In addition, the SHAP method could improve model transparency and make it easier for clinicians to grasp the prediction model's reliability.

Systematic Mendelian Randomization Exploring Druggable Genes for Hemorrhagic Strokes.

Patients with hemorrhagic stroke have high rates of morbidity and mortality, and drugs for prevention are very limited. Mendelian randomization (MR) analysis can increase the success rate of drug development by providing genetic evidence. Previous MR analyses only analyzed the role of individual drug target genes in hemorrhagic stroke; therefore, we used MR analysis to systematically explore the druggable genes for hemorrhagic stroke. We sequentially performed summary-data-based MR analysis and two-sample MR analysis to assess the associations of all genes within the database with intracranial aneurysm, intracerebral hemorrhage, and their subtypes. Validated genes were further analyzed by colocalization. Only genes that were positive in all three analyses and were druggable were considered desirable genes. We also explored the mediators of genes affecting hemorrhagic stroke incidence. Finally, the associations of druggable genes with other cardiovascular diseases were analyzed to assess potential side effects. We identified 56 genes that significantly affected hemorrhagic stroke incidence. Moreover, TNFSF12, SLC22A4, SPARC, KL, RELT, and ADORA3 were found to be druggable. The inhibition of TNFSF12, SLC22A4, and SPARC can reduce the risk of intracranial aneurysm, subarachnoid hemorrhage, and intracerebral hemorrhage. Gene-induced hypertension may be a potential mechanism by which these genes cause hemorrhagic stroke. We also found that blocking these genes may cause side effects, such as ischemic stroke and its subtypes. Our study revealed that six druggable genes were associated with hemorrhagic stroke, and the inhibition of TNFSF12, SLC22A4, and SPARC had preventive effects against hemorrhagic strokes.

The antagonistic role of an E3 ligase pair in regulating plant NLR-mediated autoimmunity and fungal pathogen resistance.

Plant immune homeostasis is achieved through a balanced immune activation and suppression, enabling effective defense while averting autoimmunity. In Arabidopsis, disrupting a mitogen-activated protein (MAP) kinase cascade triggers nucleotide-binding leucine-rich-repeat (NLR) SUPPRESSOR OF mkk1/2 2 (SUMM2)-mediated autoimmunity. Through an RNAi screen, we identify PUB5, a putative plant U-box E3 ligase, as a critical regulator of SUMM2-mediated autoimmunity. In contrast to typical E3 ligases, PUB5 stabilizes CRCK3, a calmodulin-binding receptor-like cytoplasmic kinase involved in SUMM2 activation. A closely related E3 ligase, PUB44, functions oppositely with PUB5 to degrade CRCK3 through monoubiquitylation and internalization. Furthermore, CRCK3, highly expressed in roots and conserved across plant species, confers resistance to Fusarium oxysporum, a devastating soil-borne fungal pathogen, in both Arabidopsis and cotton. These findings demonstrate the antagonistic role of an E3 ligase pair in fine-tuning kinase proteostasis for the regulation of NLR-mediated autoimmunity and highlight the function of autoimmune activators in governing plant root immunity against fungal pathogens.

The role of radiotherapy in patients with refractory Hodgkin's lymphoma after treatment with brentuximab vedotin and/or immune checkpoint inhibitors.

Background: Approximately 10%-30% of patients with Hodgkin's lymphoma (HL) experience relapse or refractory (R/R) disease after first-line standard therapy. Brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs) have important roles in the salvage treatment of R/R HL. However, subsequent treatment for HL refractory to BV and/or ICI treatment is challenging. Methods: We retrospectively analyzed patients in two institutions who had R/R HL, experienced BV or ICI treatment failure, and received radiotherapy (RT) thereafter. The overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were analyzed. Results: Overall, 19 patients were enrolled. First-line systemic therapy comprised doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD, 84.2%); AVD plus ICIs (10.5%); and bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP, 5.3%). After first-line therapy, 15 (78.9%) and four patients (21.1%) had refractory disease and relapsed, respectively. After R/R HL diagnosis, six (31.6%), two (10.5%), and 11 (57.9%) patients received BV and ICIs concurrently, BV monotherapy, and ICI monotherapy, respectively. All patients received intensity-modulated RT (n = 12, 63.2%) or volumetric modulated arc therapy (VMAT; n = 7, 36.8%). The ORR as well as the complete response (CR) rate was 100%; the median DOR to RT was 17.2 months (range, 7.9-46.7 months). Two patients showed progression outside the radiation field; one patient had extensive in-field, out-of-field, nodal, and extranodal relapse. With a median follow-up time of 16.2 months (range, 9.2-23.2 months), the 1-year PFS and OS were 84.4% and 100%, respectively. PFS was associated with extranodal involvement (P = 0.019) and gross tumor volume (P = 0.044). All patients tolerated RT well without adverse events of grade ≥ 3. Conclusion: RT is effective and safe for treating HL refractory to BV or ICIs and has the potential to be part of a comprehensive strategy for HL.

Large Language Model-Augmented Auto-Delineation of Treatment Target Volume in Radiation Therapy.

Radiation therapy (RT) is one of the most effective treatments for cancer, and its success relies on the accurate delineation of targets. However, target delineation is a comprehensive medical decision that currently relies purely on manual processes by human experts. Manual delineation is time-consuming, laborious, and subject to interobserver variations. Although the advancements in artificial intelligence (AI) techniques have significantly enhanced the auto-contouring of normal tissues, accurate delineation of RT target volumes remains a challenge. In this study, we propose a visual language model-based RT target volume auto-delineation network termed Radformer. The Radformer utilizes a hierarichal vision transformer as the backbone and incorporates large language models to extract text-rich features from clinical data. We introduce a visual language attention module (VLAM) for integrating visual and linguistic features for language-aware visual encoding (LAVE). The Radformer has been evaluated on a dataset comprising 2985 patients with head-and-neck cancer who underwent RT. Metrics, including the Dice similarity coefficient (DSC), intersection over union (IOU), and 95th percentile Hausdorff distance (HD95), were used to evaluate the performance of the model quantitatively. Our results demonstrate that the Radformer has superior segmentation performance compared to other state-of-the-art models, validating its potential for adoption in RT practice.

[Effect of different initial processing treatments on commercial characters and chemical components of Fritillaria taipaiensis].

To investigate the effects of different initial processing methods on the quality of Fritillaria taipaiensis, this study explored the effects of anti-browning treatment, drying methods, and drying temperatures on the commercial characters, chromaticity values, and alkaloid and nucleoside components of Fritillariae Taipaiensis Bulbus. The results were comprehensively evaluated through correlation analysis(CA), principal component analysis(PCA), and hierarchical clustering analysis(HCA). Compared with those of the direct drying group(WD60), the chromaticity values(ΔE*) of the groups with scraped outer skin( FHB1) and mixed lime powder treatments(FHB2) were significantly reduced, indicating the inhibition of the browning process. The total alkaloid content of the group with mixed raw soil treatment(FHB3) and the FHB2 group showed no significant change, whereas that of the group with 5%Na Cl O solution rinse treatment(FHB4) was the lowest. Compared with air-blast dried(WD50) samples, the ΔE* values of freezedried(FS6) and vacuum-dried(FS5) samples were significantly decreased, with an increase in total alkaloid contents. Conversely,the ΔE* values of shade-dried(FS1) and sun-dried(FS2) samples were significantly increased, with severe browning and low total alkaloid contents. The total alkaloid contents of heat-pump-dried(FS4) samples showed no significant change, and their ΔE* value was significantly decreased, with a light degree of browning and favorable commercial characters. The total alkaloid content of air-blast dried samples initially increased and then decreased within the range of 40-80 ℃, and the highest content was recorded at 70 ℃. The ΔE* values of high-temperature air-blast dried samples(70-80 ℃) were smaller with a light degree of browning, whereas their texture was compact and lacked powder. CA revealed a significant relationship between the uracil content and chromaticity value of the samples(P< 0. 05). The clustering relationships among samples subjected to different treatments were visualized via PCA and HCA. The results showed that FHB2 and air-blast drying(50-60 ℃) were more suitable for large-scale production, and heat pump drying could be a promising direction for future development. This study provides a scientific basis for optimizing the initial processing methods of Fritillaria taipaiensis.

Optimal dose and type of non-pharmacological treatments to improve cognitive function in people with Alzheimer's disease: a systematic review and network meta-analysis.

OBJECTIVES: To evaluate and rank the effectiveness of specific non-pharmacological treatments (NPTs) in improving the global cognitive function in individuals with Alzheimer's disease (AD) and to examine the dose-response relationship. METHOD: We conducted a systematic search in PubMed, MEDLINE, Embase, PsycINFO, CENTRAL, WOS, and CNKI from their inception to 15 February 2023. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for outcomes using random effects models. RESULTS: We included 68 studies involving 5053 participants in this meta-analysis. The treatments with the highest cumulative probabilities for improving global cognitive function were transcranial direct current stimulation (tDCS), followed by physical exercise (PE), and repetitive transcranial magnetic stimulation (rTMS). Additionally, cognitive stimulation (CS), cognitive training CT), multidisciplinary program (MD), and reminiscence treatment (RT) also significantly improve the global cognitive function of people with AD. A non-linear dose-response association was observed for tDCS, PE, rTMS, CS, and CT with global cognitive improvement. Notably, no minimal threshold was identified for the beneficial effects of PE on cognition. The estimated minimal doses for clinically relevant changes in cognition were 33 min per week for tDCS, 330 MET-min per week for PE, and 8000 pulses per week for rTMS. CONCLUSION: tDCS, PE, and rTMS are the better effective NPTs for enhancing global cognitive function in individuals with AD. Properly dosing these treatments can yield significant clinical benefits. Our findings support the clinical utility of low-dose exercise in improving cognition in people with AD.

Biodegradation of humic acids by Streptomyces rochei to promote the growth and yield of corn.

Humic acids (HAs) are organic macromolecules that play an important role in improving soil properties, plant growth and agronomic parameters. However, the feature of relatively complex aromatic structure makes it difficult to be degraded, which restricts the promotion to the crop growth. Thus, exploring microorganisms capable of degrading HAs may be a potential solution. Here, a HAs-degrading strain, Streptomyces rochei L1, and its potential for biodegradation was studied by genomics, transcriptomics, and targeted metabolomics analytical approaches. The results showed that the high molecular weight HAs were cleaved to low molecular aliphatic and aromatic compounds and their derivatives. This cleavage may be associated with the laccase (KatE). In addition, the polysaccharide deacetylase (PdgA) catalyzes the removal of acetyl groups from specific sites on the HAs molecule, resulting in structural changes. The field experiment showed that the degraded HAs significantly promote the growth of corn seedlings and increase the corn yield by 3.6 %. The HAs-degrading products, including aromatic and low molecular weight aliphatic substances as well as secondary metabolites from S. rochei L1, might be the key components responsible for the corn promotion. Our findings will advance the application of HAs as soil nutrients for the green and sustainable agriculture.

Reactive astrogliosis induced by TNF-α is associated with upregulated AEG-1 together with activated NF-κB pathway in vitro.

Astrocyte-elevated gene-1 (AEG-1/MTDH/LYRIC) has garnered signficant attention in cancer research, yet, its role in inflammation-associated astrogliosis remains underexplored. This study aims to elucidate the effects of AEG-1 on reactive astrogliosis, including proliferation, migration, and glutamate uptake in primary astrocytes derived from rats. We first confirmed the effect of AEG-1 on these parameters. Subsequently, we investigated whether AEG-1 plays a role in the process of pro-inflammation factors such as tumor necrosis factor-alpha (TNF-α) induced astrogliosis. Our findings revealed that AEG-1-lentivirus infection led to hypertrophic cell bodies and enhanced expression of astrogliosis markers, including glial fibrillary acidic protein (GFAP) and vimentin. Additionally, AEG-1 was found to upregulate the mRNA and protein expression levels of EAAT2, a major glutamate transporter in the brain predominantly expressed by astrocytes and responsible for 90% of glutamate clearance. Furthermore, TNF-α was shown to promote astrogliosis, as well as astrocyte proliferation and migration, by upregulating AEG-1 expression through the NF-κB pathway. Collectively, these results suggest a potential role for AEG-1 in inflammation-related astrogliosis.

Influences of bisphenol A on hydrogen production from food waste by thermophilic dark fermentation.

The extensive use of plastic products in food packaging and daily life makes them inevitably enter the treatment process of food waste (FW). Plasticizer as a new pollutant is threatening the dark fermentation of FW. Our study showed that bisphenol A (BPA) at > 250 mg/L had a significant inhibition on hydrogen production from FW by thermophilic dark fermentation. The endogenous ATP content and lactate dehydrogenase (LDH) release showed that high level of BPA not only inhibited the growth of hydrogen-producing consortium, but also led to cell death. In addition, BPA mainly affects the hydrogen-producing consortium by reducing cell membrane fluidity, damaging cell membrane integrity and reducing cell membrane potential, resulting in cell death. This study provides some new insights into the mechanism of the effect of BPA on hydrogen production from FW by thermophilic dark fermentation, and lays the foundation on the utilization of FW.