Design, Synthesis, and Biological Evaluation of New Improved Ferrostatin-1 Derived Ferroptosis Inhibitors.

Ferrostatin-1 (Fer-1), a first potent ferroptosis inhibitor, faces limitations in clinical use due to its low potency and metabolic instability. This study introduces a series of novel Ferrostatin-1 analogs designed to enhance plasm stability. Our design strategy focused on the modification of the 3-NH2 of Fer-1 with benzenesulfonyl groups, resulting in analogs 9-25. Biological evaluation revealed that compound 18, with an EC50 value of 0.57 µM, outperformed Fer-1 in inhibiting ferroptosis. It reduced intracellular ferrous ion accumulation, lipid peroxidation, and restored glutathione (GSH) and glutathione peroxidase 4 (GPX4) levels effectively. Moreover, compound 18 exhibited favorable solubility and remarkable metabolic stability in rat plasma. These results position compound 18 as a promising candidate for developing therapeutics against ferroptosis-related diseases.

Responses of suspended sludge and biofilm in a SNAD system under C/N elevation: Microbial activity, nitrogen conversion flux and molecular ecological network.

The simultaneous partial nitrification, anammox and denitrification (SNAD) process had received widespread attention as an advanced wastewater treatment process. In this study, the SNAD mainstream nitrogen removal process with the incorporation of polyurethane sponge packing under different C/N conditions was investigated. Results showed that the highest nitrogen removal efficiency of the system was achieved at the C/N of 2.0, while the high C/N (3.5) significantly deteriorate the nitrogen removal efficiency. Meanwhile, high C/N (3.5) significantly inhibited the activity and abundance of anammox bacteria (mainly Candidatus_Kuenenia), resulting in the decreased contribution of anammox (from 63.14 % to 48.09 %). The significant divergence of microbial interactions in the suspended sludge and biofilm was observed with increasing C/N. Compared with suspended sludge, biofilm facilitated higher abundance and activity of anammox bacteria, and the molecular ecological network of biofilm displayed better stability and more efficient mass transfer efficiency between microorganisms. The C/N of 3.5 simplified the subnetworks of Chloroflexi and Proteobacteria but increased the positive interactions between Planctomycetota and other microbes. Anammox bacteria were found as keystone species only in biofilm system. This study provided a theoretical basis and technical guidance for the application of SNAD process in municipal wastewater treatment.

Treatment of intracranial aneurysms using the Tubridge flow diverter.

OBJECTIVE: The Tubridge flow diverter (TFD) was recently developed to treat intracranial aneurysm (IA). In this study, we aimed to assess the safety and efficacy of this novel device. METHODS: A retrospective cohort of consecutive patients with IA was recruited between June 2017 and February 2022. The studied outcomes were perioperative complications, clinical quality of life, and angiographic IA occlusion. Multivariate logistic regression was performed to explore the potential predictors of perioperative stroke events and IA occlusion. A comprehensive literature review was conducted across five databases for evidence synthesis. RESULTS: Among the patients with IA in our cohort, 144 underwent successful TFD implantation. Postoperative stroke was observed in 11 (7.6%) patients, and 130 (90.3%) patients were discharged with modified Rankin scales (mRS) of ≤2. In the last clinical follow-up (mean, 16.9 months), 96.6% of the patients reported a satisfactory quality of life (mRS ≤2). IA occlusion was observed in 84.6% of the patients at the last angiographic follow-up (mean, 10.4 months). Aneurysmal subarachnoid hemorrhage [odds ratio (OR), 6.98; 95% confidence interval (CI), 1.11-43.91] and giant IA (OR, 5.63; 95% CI, 1.15-27.48) were associated with perioperative stroke events. The evidence synthesis found high rates of satisfactory quality of life (rate, 98.8%; 95% CI, 97.1-99.9%) and IA obliteration (rate, 78.5%; 95% CI, 74.0-82.7%) after TFD treatment. The pooled complication rate was 13.6% (95% CI, 10.9-16.5%). CONCLUSIONS: This study identified a high rate of IA occlusion in patients who received TFD treatment. These patients also reported a satisfactory quality of life. Further studies in larger prospective cohorts with longer follow-up periods are warranted to verify our findings. Key message What is already known on this topic  Flow diverter (FD) devices are an optimal tool to modify hemodynamics and treat intracranial aneurysms (IAs). However, the safety and efficacy of a novel self-expanding FD, namely the Tubridge flow diverter (TFD), remain to be fully established owing to the short-term follow-up periods and limited sample size of existing studies. What this study adds  In our cohort of patients who received TFD treatment, 96.6% of patients reported satisfactory quality of life at the last clinical follow-up (mean, 16.9 months); and 84.6% of IAs were successfully occluded at the last angiographic follow-up (mean, 10.4 months). Our comprehensive review and evidence synthesis of existing studies on TFD found high rates of satisfactory quality of life (98.8%; 97.1-99.9%) and IA obliteration (78.5%; 74.0-82.7%). How this study might affect research, practice or policy  TFD demonstrated satisfactory performance in the treatment of IAs in our cohort. Studies with larger prospective cohorts and longer follow-up periods are warranted to further investigate this promising novel approach.

Advantages and disadvantages of various hydrogel scaffold types: A research to improve the clinical conversion rate of loaded MSCs-Exos hydrogel scaffolds.

Mesenchymal stem cell-derived exosomes(MSCs-Exos) offer promising therapeutic potential for a wide range of tissues and organs such as bone/cartilage, nerves, skin, fat, and endocrine organs. In comparison to the application of mesenchymal stem cells (MSCs), MSCs-Exos address critical challenges related to rejection reactions and ethical concerns, positioning themselves as a promising cell-free therapy. As exosomes are extracellular vesicles, their effective delivery necessitates the use of carriers. Consequently, the selection of hydrogel materials as scaffolds for exosome delivery has become a focal point of contemporary research. The diversity of hydrogel scaffolds, which can take various forms such as injectable types, dressings, microneedles, and capsules, leads to differing choices among researchers for treating diseases within the same domain. This variability in hydrogel materials poses challenges for the translation of findings into clinical practice. The review highlights the potential of hydrogel-loaded exosomes in different fields and introduces the advantages and disadvantages of different forms of hydrogel applications. It aims to provide a multifunctional and highly recognized hydrogel scaffold option for tissue regeneration at specific sites, improve clinical translation efficiency, and benefit the majority of patients.

Exploring the Effects and Potential Mechanisms of Hesperidin for the Treatment of CPT-11-Induced Diarrhea: Network Pharmacology, Molecular Docking, and Experimental Validation.

Chemotherapy-induced diarrhea (CID) is a potentially serious side effect that often occurs during anticancer therapy and is caused by the toxic effects of chemotherapeutic drugs on the gastrointestinal tract, resulting in increased frequency of bowel movements and fluid contents. Among these agents, irinotecan (CPT-11) is most commonly associated with CID. Hesperidin (HPD), a flavonoid glycoside found predominantly in citrus fruits, has anti-oxidation properties and anti-inflammation properties that may benefit CID management. Nevertheless, its potential mechanism is still uncertain. In this study, we firstly evaluated the pharmacodynamics of HPD for the treatment of CID in a mouse model, then used network pharmacology and molecular docking methods to excavate the mechanism of HPD in relieving CID, and finally further proved the predicted mechanism through molecular biology experiments. The results demonstrate that HPD significantly alleviated diarrhea, weight loss, colonic pathological damage, oxidative stress, and inflammation in CID mice. In addition, 74 potential targets for HPD intervention in CID were verified by network pharmacology, with the top 10 key targets being AKT1, CASP3, ALB, EGFR, HSP90AA1, MMP9, ESR1, ANXA5, PPARG, and IGF1. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the PI3K-Akt pathway, FoxO pathway, MAPK pathway, TNF pathway, and Ras pathway were most relevant to the HPD potential treatment of CID genes. The molecular docking results showed that HPD had good binding to seven apoptosis-related targets, including AKT1, ANXA5, CASP3, HSP90AA1, IGF1, MMP9, and PPARG. Moreover, we verified apoptosis by TdT-mediated dUTP nick-end labeling (TUNEL) staining and immunohistochemistry, and the hypothesis about the proteins above was further verified by Western blotting in vivo experiments. Overall, this study elucidates the potential and underlying mechanisms of HPD in alleviating CID.

A comprehensive review of quantum machine learning: from NISQ to fault tolerance.

Quantum machine learning, which involves running machine learning algorithms on quantum devices, has garnered significant attention in both academic and business circles. In this paper, we offer a comprehensive and unbiased review of the various concepts that have emerged in the field of quantum machine learning. This includes techniques used in Noisy Intermediate-Scale Quantum (NISQ) technologies and approaches for algorithms compatible with fault-tolerant quantum computing hardware. Our review covers fundamental concepts, algorithms, and the statistical learning theory pertinent to quantum machine learning.

Selection of indigenous Saccharomyces cerevisiae strains with good oenological and aroma characteristics for winemaking in Ningxia China.

Ningxia is one of the well-known wine producing regions in China. However, the oenological and aroma characteristics of indigenous yeasts remains hidden. The fermentative and oenological properties including stress resistance, hydrogen sulfide, foam production levels; killer phenotype, and flocculation of 89 Ningxia indigenous Saccharomyces cerevisiae isolates and ten commercial yeasts were evaluated. The fermentative and oenological properties of the tested strains varied significantly. They could resist 500 g/L glucose, 300 mg/L SO2, 14% (v/v) ethanol and pH 2.8, and produce more esters. They also produce low levels of ethanol and could conduct fermentations vigorously and at a high rate. Cabernet Sauvignon wines made with NXU 21-24 showed the high intensity of tropical fruit, dry fruit, temperate fruit, and spicy flavor. The floral flavor in NXU 21-102 fermented wine is very intense. The indigenous S. cerevisiae strains of NXU 21-102 and NXU 21-24 exhibited potential use as starter cultures in wine production.

Female hormonal and reproductive factors and the risk of subarachnoid hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH), primarily caused by rupture of intracranial aneurysm, has a high incidence rate in women. We aimed to evaluate the association between female hormonal and reproductive factors and SAH. METHODS: A prospective cohort of 226,469 participants from the UK Biobank was followed for a median period of 14.75 years. Cox proportional hazards models and restricted cubic splines were used to explore the associations between 13 major factors and SAH, including menarche age, menopausal status, age at menopause, reproductive lifespan, pregnancy history, age at first and last live births, number of live births, adverse fertility outcomes, history of oral contraception or hormone-replacement therapy (HRT) use, and surgical history of hysterectomy or bilateral oophorectomy. RESULTS: SAH occurred in 769 of participants during the follow-up period. Both women with a younger age at menarche (< 12 years) and post-menopausal women had a higher SAH risk (hazard ratio (HR), 1.28; 95% confidence interval (CI), 1.06-1.54) and (HR, 1.48; 95% CI, 1.10-1.99), respectively. A higher risk of SAH was identified in those with an earlier age at menopause (< 40 years: HR, 2.09; 95% CI, 1.43-3.06; 40-44 years: HR, 1.68; 95% CI, 1.23-2.29). A shorter reproductive lifespan (< 30 years) was associated with increased SAH risk (HR, 1.64; 95% CI, 1.28-2.11), while a longer reproductive lifespan (> 42 years) showed a protective effect (HR, 0.65; 95% CI, 0.55-0.77). Younger age at first live birth (< 24 years) was associated with SAH (HR, 1.39; 95% CI, 1.13-1.72). Hysterectomy (HR, 2.55; 95% CI, 2.12-3.05) or bilateral oophorectomy (HR, 1.51; 95% CI, 1.14-2.01) also predisposed women to SAH. Age at last live birth, number of live births, pregnancy history, adverse fertility outcomes, and HRT or oral contraceptive use were not associated with SAH. CONCLUSIONS: Female hormonal and reproductive factors are important for evaluating SAH risk in women. In particular, earlier menopause is associated with an increased risk of SAH. DATA ACCESS STATEMENT: The data utilized in this study were sourced from a third party and are not publicly accessible. The UK Biobank data that support the findings of this research are available from the UK Biobank (www.ukbiobank.ac.uk), subject to review and approval by the UK Biobank.

Mussel-Bioinspired Lignin Adhesive for Wearable Bioelectrodes.

As a natural "binder," lignin fixes cellulose in plants to foster growth and longevity. However, isolated lignin has a poor binding ability, which limits its biomedical applications. In this study, inspired by mussel adhesive proteins, acidic/basic amino acids (AAs) are introduced in alkali lignin (AL) to form ionic-π/spatial correlation interactions, followed by demethylation to create catechol residues for enhanced adhesion activity. Atomic force microscopy reveals that catechol residues are the primary adhesion structures, with basic AAs exhibiting superior synergistic effects compared to acidic AAs. Demethylated lysine-grafted AL exhibits the strongest adhesion force toward skin tissue. Molecular dynamic simulation and density functional theory calculations indicate that adhesion against skin tissue mainly results from hydrogen bonds and cation-π interactions, with the adhesion mechanism being based on the Gibbs free energy of the Schiff base reaction. In summary, a biomimetic electrode based on lignin inspired by mussel adhesive proteins is prepared; the presented method offers a straightforward strategy for the development of biomimetic adhesives. Furthermore, this mussel-inspired adhesive can be used as a wearable bioelectrode in biomedical applications.

Research Progress of Natural Rubber Wet Mixing Technology.

The performance of natural rubber (NR), a naturally occurring and sustainable material, can be greatly enhanced by adding different fillers to the NR matrix. The homogeneous dispersion of fillers in the NR matrix is a key factor in their ability to reinforce. As a novel method, wet mixing technology may effectively provide good filler dispersion in the NR matrix while overcoming the drawbacks of conventional dry mixing. This study examines the literature on wet mixing fillers, such as graphene, carbon nanotubes, silica, carbon black, and others, to prepare natural rubber composites. It also focuses on the wet preparation techniques and key characteristics of these fillers. Furthermore, the mechanism of filler reinforcement is also examined. To give guidance for the future development of wet mixing technology, this study also highlights the shortcomings of the current system and the urgent need to address them.

Pharmacokinetics, safety, and efficacy of Fuqi Guben Gao in the treatment of kidney-yang deficiency syndrome: a randomized, double-blind phase I trial.

Introduction: Fuqi Guben Gao (FQGBG) is a botanical drug formulation composed of FuZi (FZ; Aconitum carmichaelii Debeaux [Ranunculaceae; Aconiti radix cocta]), Wolfberry (Lycium barbarum L. [Solanaceae; Lycii fructus]), and Cinnamon (Neolitsea cassia (L.) Kosterm. [Lauraceae; Cinnamomi cortex]). It has been used to clinically treat nocturia caused by kidney-yang deficiency syndrome (KYDS) for over 30 years and warms kidney yang. However, the pharmacological mechanism and the safety of FQGBG in humans require further exploration and evaluation. Methods: We investigated the efficacy of FQGBG in reducing urination and improving immune organ damage in two kinds of KYDS model rats (hydrocortisone-induced model and natural aging model), and evaluated the safety of different oral FQGBG doses through pharmacokinetic (PK) parameters, metabonomics, and occurrence of adverse reactions in healthy Chinese participants in a randomized, double-blind, placebo-controlled, single ascending dose clinical trial. Forty-two participants were allocated to six cohorts with FQGBG doses of 12.5, 25, 50, 75, 100, and 125 g. The PKs of FQGBG in plasma were determined using a fully validated LC-MS/MS method. Results: FQGBG significantly and rapidly improved the symptoms of increased urination in both two KYDS model rats and significantly resisted the adrenal atrophy in hydrocortisone-induced KYDS model rats. No apparent increase in adverse events was observed with dose escalation. Major adverse drug reactions included toothache, thirst, heat sensation, gum pain, diarrhea, abdominal distension, T-wave changes, and elevated creatinine levels. The PK results showed a higher exposure level of benzoylhypaconine (BHA) than benzoylmesaconine (BMA) and a shorter half-life of BMA than BHA. Toxic diester alkaloids, aconitine, mesaconitine, and hypaconitine were below the lower quantitative limit. Drug-induced metabolite markers primarily included lysophosphatidylcholines, fatty acids, phenylalanine, and arginine metabolites; no safety-related metabolite changes were observed. Conclusion: Under the investigated dosing regimen, FQGBG was safe. The efficacy mechanism of FQGBG in treating nocturia caused by KYDS may be related to the improvement of the hypothalamus-pituitary-adrenal axis function and increased energy metabolism. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=26934, identifier ChiCTR1800015840.

Chemical modification, structure elucidation and antifungal mechanism studies of a peptide extracted from garlic (Allium sativum L.).

BACKGROUND: Garlic is a promising source of antimicrobial peptide separation, and chemical modification is an effective method for activity improvement. The present study aimed to improve the antifungal activity of a peptide extracted from garlic. Chemical modifications were conducted, and the structure-activity relationship and antifungal mechanism were investigated. RESULTS: The results indicated that the cationic charge induced by Lys residue at the N-terminal was important for the antimicrobial activity, and the modified sequence exhibited significant antifungal activity with low mammalian toxicity and a low tendency of drug resistance (p < 0.05). The structure-activity relationship analysis revealed that the modified active peptide had a predominant α-helical structure and an inner cyclic correlation. Transcriptomic analysis showed that peptide KMLKKLFR (Lys-Met-Leu-Lys-Lyse-Leu-Phe-Arg) affected the rRNA processing and carbon metabolism process of Candida albicans. In addition, the membrane potential study indicated a non-membrane destruction mechanism, and molecular docking analysis and a DNA interaction assay suggested promising inner targets. CONCLUSION: The results of the present study indicate that chemical modification by amino acid substitution was effective for antimicrobial activity improvement. The present study would benefit future antimicrobial peptide development and suggests that garlic is a great source of antibacterial peptides and peptide template separations for coping with antibiotic resistance. © 2024 Society of Chemical Industry.

Lightweight strip steel defect detection algorithm based on improved YOLOv7.

The precise identification of surface imperfections in steel strips is crucial for ensuring steel product quality. To address the challenges posed by the substantial model size and computational complexity in current algorithms for detecting surface defects in steel strips, this paper introduces SS-YOLO (YOLOv7 for Steel Strip), an enhanced lightweight YOLOv7 model. This method replaces the CBS module in the backbone network with a lightweight MobileNetv3 network, reducing the model size and accelerating the inference time. The D-SimSPPF module, which integrates depth separable convolution and a parameter-free attention mechanism, was specifically designed to replace the original SPPCSPC module within the YOLOv7 network, expanding the receptive field and reducing the number of network parameters. The parameter-free attention mechanism SimAM is incorporated into both the neck network and the prediction output section, enhancing the ability of the model to extract essential features of strip surface defects and improving detection accuracy. The experimental results on the NEU-DET dataset show that SS-YOLO achieves a 97% mAP50 accuracy, which is a 4.5% improvement over that of YOLOv7. Additionally, there was a 79.3% reduction in FLOPs(G) and a 20.7% decrease in params. Thus, SS-YOLO demonstrates an effective balance between detection accuracy and speed while maintaining a lightweight profile.

Sorbremnoids A and B: NLRP3 Inflammasome Inhibitors Discovered from Spatially Restricted Crosstalk of Biosynthetic Pathways.

Crosstalk-oriented chemical evolution of natural products (NPs) is an efficacious strategy for generating novel skeletons through coupling reactions between NP fragments. In this study, two NOD-like receptor protein 3 (NLRP3) inflammasome inhibitors, sorbremnoids A and B (1 and 2), with unprecedented chemical architectures were identified from a fungus Penicillium citrinum. Compounds 1 and 2 exemplify rare instances of hybrid NPs formed via a major facilitator superfamily (MFS)-like enzyme by coupling reactive intermediates from two separate biosynthetic gene clusters (BGCs), pcisor and pci56. Both sorbremnoids A and B are NLRP3 inflammasome inhibitors. Sorbremnoid A demonstrated strong inhibition of IL-1ß by directly binding to the NLRP3 protein, inhibiting the assembly and activation of the NLRP3 inflammasome in vitro, with potential application in diabetic refractory wound healing through the suppression of excessive inflammatory responses. This research will inspire the development of anti-NLRP3 inflammasome agents as lead treatments and enhance knowledge pertaining to NPs derived from biosynthetic crosstalk.

A systematic review and meta-analysis of Danshen combined with mesalazine for the treatment of ulcerative colitis.

Purpose: Current pharmacological treatments for Ulcerative Colitis (UC) have limitations. Therefore, it is important to elucidate any available alternative or complementary treatment, and Chinese herbal medicine shows the potential for such treatment. As a traditional Chinese herbal medicine, Danshen-related preparations have been reported to be beneficial for UC by improving coagulation function and inhibiting inflammatory responses. In spite of this, the credibility and safety of this practice are incomplete. Therefore, in order to investigate whether Danshen preparation (DSP) is effective and safe in the treatment of UC, we conducted a systematic review and meta-analysis. Methods: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Database and CQVIP Database were searched for this review.The main observation indexes were the effect of DSP combined with mesalazine or DSP on the effective rate, platelet count (PLT), mean platelet volume (MPV) and C-reactive protein (CRP) of UC. The Cochrane risk of bias tool was used to assess the risk of bias. The selected studies were evaluated for quality and data processing using RevMan5.4 and Stata17.0 software. Results: A total of 37 studies were included. Among them, 26 clinical trials with 2426 patients were included and 11 animal experimental studies involving 208 animals were included. Meta-analysis results showed that compared with mesalazine alone, combined use of DSP can clearly improve the clinical effective rate (RR 0.86%, 95% CI:0.83-0.88, p < 0.00001) of UC. Furthermore it improved blood coagulation function by decreasing serum PLT and increasing MPV levels, and controlled inflammatory responses by reducing serum CRP, TNF-α, IL-6, and IL-8 levels in patients. Conclusion: Combining DSP with mesalazine for UC can enhance clinical efficacy. However, caution should be exercised in interpreting the results of this review due to its flaws, such as allocation concealment and uncertainty resulting from the blinding of the study. Systematic Review Registration: http://www.crd.york.ac.uk/PROSPERO/myprospero.php, identifier PROSPERO: CRD42022293287.

Three-dimensional spatio-angular fluorescence microscopy with a polarized dual-view inverted selective-plane illumination microscope (pol-diSPIM).

Polarized fluorescence microscopy is a valuable tool for measuring molecular orientations, but techniques for recovering three-dimensional orientations and positions of fluorescent ensembles are limited. We report a polarized dual-view light-sheet system for determining the three-dimensional orientations and diffraction-limited positions of ensembles of fluorescent dipoles that label biological structures, and we share a set of visualization, histogram, and profiling tools for interpreting these positions and orientations. We model our samples, their excitation, and their detection using coarse-grained representations we call orientation distribution functions (ODFs). We apply ODFs to create physics-informed models of image formation with spatio-angular point-spread and transfer functions. We use theory and experiment to conclude that light-sheet tilting is a necessary part of our design for recovering all three-dimensional orientations. We use our system to extend known two-dimensional results to three dimensions in FM1-43-labelled giant unilamellar vesicles, fast-scarlet-labelled cellulose in xylem cells, and phalloidin-labelled actin in U2OS cells. Additionally, we observe phalloidin-labelled actin in mouse fibroblasts grown on grids of labelled nanowires and identify correlations between local actin alignment and global cell-scale orientation, indicating cellular coordination across length scales.

Plant-derived inducers in tumor differentiation therapy:A systematic review.

BACKGROUND: Differentiation therapy, a highly regarded treatment method in tumor research, aims to induce tumor cells to differentiate back to normal cells, deviating from the malignant pathway and returning to a benign state. Its development relies on the continuous discovery of efficient and low-toxic differentiation inducers, including plant-derived active components that offer significant biological utilization and therapeutic potential. For this reason, the exploration of plant-derived inducers, particularly in their application in differentiation therapy, holds great promise in advancing cancer treatment strategies toward more effective and safer alternatives. PURPOSE: This paper aims to provide a valuable reference for researchers seeking to identify natural, efficient, and low-toxic differentiation inducers from plants and highlights a promising research direction for the application of differentiation therapy in malignant tumor treatment. METHODS: For the collection of pertinent information, an extensive search was conducted across diverse literature and electronic databases, including PubMed, ScienceDirect, Wiley, ACS, CNKI, Springer, Taylor & Francis, Web of Science, Google Scholar, and Baidu Scholar. This comprehensive approach aimed to retrieve and include all relevant literature from 1985 to 2023. Primary keywords such as "Natural medicinal plant," "Differentiation therapy," and "Differentiation inducer" were utilized, supplemented by secondary search terms including "Cancer," "Tumor," "Herbal medicine," "Induced differentiation," and "Cancer treatment." RESULTS: This study systematically evaluated the application of plant-derived inducers in tumor-induced differentiation therapy. Through extensive literature review, specific plant components with confirmed differentiation-inducing properties were identified. Furthermore, potential molecular mechanisms underlying this process were outlined, shedding light on the future development of differentiation therapy in cancer treatment. CONCLUSION: Plant-derived active components exhibit substantial biological utility and therapeutic potential. Delving deeper into the research on these components as differentiation inducers holds promise for the selection of novel cancer drugs and the unveiling of novel pathways for cancer treatment. These results emphasize the importance of continued exploration and in-depth research into natural, efficient, and low-toxic differentiation inducers from plants, which could significantly advance cancer treatment strategies. Moreover, the highlighted research direction underscores the relevance of differentiation therapy in the context of malignant tumor treatment, indicating its potential as a safer and more effective alternative in cancer therapy.

Updated Progress on Polysaccharides with Anti-Diabetic Effects through the Regulation of Gut Microbiota: Sources, Mechanisms, and Structure-Activity Relationships.

Diabetes mellitus (DM) is a common chronic metabolic disease worldwide. The disturbance of the gut microbiota has a complex influence on the development of DM. Polysaccharides are one type of the most important natural components with anti-diabetic effects. Gut microbiota can participate in the fermentation of polysaccharides, and through this, polysaccharides regulate the gut microbiota and improve DM. This review begins by a summary of the sources, anti-diabetic effects and the gut microbiota regulation functions of natural polysaccharides. Then, the mechanisms of polysaccharides in regulating the gut microbiota to exert anti-diabetic effects and the structure-activity relationship are summarized. It is found that polysaccharides from plants, fungi, and marine organisms show great hypoglycemic activities and the gut microbiota regulation functions. The mechanisms mainly include repairing the gut burrier, reshaping gut microbiota composition, changing the metabolites, regulating anti-inflammatory activity and immune function, and regulating the signal pathways. Structural characteristics of polysaccharides, such as monosaccharide composition, molecular weight, and type of glycosidic linkage, show great influence on the anti-diabetic activity of polysaccharides. This review provides a reference for the exploration and development of the anti-diabetic effects of polysaccharides.

Multiple serum anti-glutamate receptor antibody levels in clozapine-treated/naïve patients with treatment-resistant schizophrenia.

BACKGROUND: Glutamatergic function abnormalities have been implicated in the etiology of treatment-resistant schizophrenia (TRS), and the efficacy of clozapine may be attributed to its impact on the glutamate system. Recently, evidence has emerged suggesting the involvement of immune processes and increased prevalence of antineuronal antibodies in TRS. This current study aimed to investigate the levels of multiple anti-glutamate receptor antibodies in TRS and explore the effects of clozapine on these antibody levels. METHODS: Enzyme linked immunosorbent assay (ELISA) was used to measure and compare the levels of anti-glutamate receptor antibodies (NMDAR, AMPAR, mGlur3, mGluR5) in clozapine-treated TRS patients (TRS-C, n = 37), clozapine-naïve TRS patients (TRS-NC, n = 39), and non-TRS patients (nTRS, n = 35). Clinical symptom severity was assessed using the Positive and Negative Symptom Scale (PANSS), while cognitive function was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). RESULT: The levels of all four glutamate receptor antibodies in TRS-NC were significantly higher than those in nTRS (p < 0.001) and in TRS-C (p < 0.001), and the antibody levels in TRS-C were comparable to those in nTRS. However, no significant associations were observed between antibody levels and symptom severity or cognitive function across all three groups after FDR correction. CONCLUSION: Our findings suggest that TRS may related to increased anti-glutamate receptor antibody levels and provide further evidence that glutamatergic dysfunction and immune processes may contribute to the pathogenesis of TRS. The impact of clozapine on anti-glutamate receptor antibody levels may be a pharmacological mechanism underlying its therapeutic effects.