Exploring the effective components of honey-processed licorice (Glycyrrhiza uralensis Fisch.) in attenuating Doxorubicin-induced myocardial cytotoxicity by combining network pharmacology and in vitro experiments.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice is widely used clinically as one of the most famous traditional Chinese herbs. Its herb roasted with honey is called honey-processed licorice (HPL). Modern studies have shown that HPL has a stronger cardioprotective ability compared to raw licorice (RL), however the material basis and mechanism of action of the potential cardioprotection have not been fully elucidated. AIM OF THE STUDY: To screen and validate the material basis of cardioprotection exerted by HPL and to preliminarily predict the potential mechanism of action. MATERIALS AND METHODS: UPLC-QTOF-MS/MS was used to analyze HPL samples with different processing levels, and differential compounds were screened out through principal component analysis. Network pharmacology and molecular docking were applied to explore the association between differential compounds and doxorubicin cardiomyopathy and their mechanisms of action were predicted. An in vitro model was established to verify the cardioprotective effects of differential compounds. RESULTS: Six differential compounds were screened as key components of HPL for potential cardioprotection. Based on network pharmacology, 113 potential important targets for the treatment of Dox-induced cardiotoxicity were screened. KEGG enrichment analysis predicted that the PI3K-Akt pathway was closely related to the mechanism of action of active ingredients. Molecular docking results showed that the six differential compounds all had good binding activity with Nrf2 protein. In addition, in vitro experiments had shown that five of the active ingredients (liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, and licochalcone A) can significantly increase Dox-induced H9c2 cell viability, SOD activity, and mitochondrial membrane potential, significantly reduces MDA levels and inhibits ROS generation. CONCLUSION: Liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin and licochalcone A are key components of HPL with potential cardioprotective capabilities. Five active ingredients can alleviate Dox-induced cardiotoxicity by inhibiting oxidative stress and mitochondrial damage.

[Application status and challenges of molecular docking in development of traditional Chinese medicine].

Traditional Chinese medicine is precious treasure of ancient Chinese science and a key to unlocking the treasure trove of Chinese civilization. To elucidate the efficacy and mechanism of traditional Chinese medicines, scientists have been engaged in the research on the molecular basis and regulatory targets. Molecular docking is a computer-aided drug design method capable of visualizing the interaction between components and target proteins. With the progress in the modernization of traditional Chinese medicine and the advancement of algorithms and computing power, molecular docking has become an essential approach in the development of new traditional Chinese medicines. This article summarizes the recent research progress in molecular docking in the development of traditional Chinese medicine, aiming to provide valuable references for further screening of active components and offering insights for improving the development of new traditional Chinese medicines.

Therapeutic effects of Huayu Jiedu formula on endometriosis via downregulating GATA 6 expression.

Background: Endometriosis (EMs) is a common chronic inflammatory disease which is characterized by multiple clinical symptoms and high recurrence rate due to the absence of effective therapies. Huayu Jiedu Formula (HYJDF), is a traditional Chinese medicine prescription with five major herbs. It has been used as traditional medicine to treat EMs for more than twenty years and exerted a good therapeutic effect. However, the underlying mechanism is unclear. Here we aim to observe the effects of HYJDF on EMs and investigate the therapeutic mechanism. Methods: The extract components of HYJDF were identified and quantified by an UHPLC-QE-MS method. Network pharmacology was used to obtain the core targets of HYJDF for the treatment of EMs and the specific biologic processes involved. A total of 68 EMs cases were randomly divided into control (gestrinone) and observation (HYJDF) groups. The overall effectiveness, pain scores, cyst-size changes, serum CA125 levels, quality-of-life scores, safety, and adverse events were evaluated before and after treatment. For the mechanism research, DNA methylation-chip analysis was performed to determine the differential genes. EMs mice models and human ectopic stromal cells (ESCs) were treated with HYJDF and its pharmaceutical serum, respectively. The ectopic foci was measured via H&E staining while the expressions of the target genes were verified by real-time PCR and Western blot analysis. The inflammatory cytokine levels in the peritoneal fluid of mice were detected by ELISA. The proliferative potential of cells was analyzed by MTS whereas the apoptosis and cell cycle were determined through flow analysis. Results: The total number of components detected in positive and negative ion modes was 839 and 597, respectively. Network pharmacology suggested that HYJDF treated EMs through DNA methylation. We found that HYJDF and gestrinone exerted good therapeutic effect with no obvious difference, but the HYJDF treatment group had fewer side effects. GATA 6, which was hypomethylated and abundant in endometriotic cells, potently induced inflammatory response. This finding indicated the important role of GATA 6 in EMs development. Moreover, HYJDF ameliorated inflammatory response (i.e., reduced the levels of IL-1ß and PGE2 in peritoneal fluid), suppressed ESCs proliferation, and increased cell apoptosis by down-regulating GATA 6 expression. Conclusion: We demonstrated that HYJDF has anti-inflammation activity and increased cell apoptosis through the reduction of GATA 6 expression in ectopic tissues, which showed good therapeutic effect without any obvious side effects. These findings suggest that HYJDF may be a new and efficient traditional Chinese medicine for the treatment of EMs.

Selenium Concentration Is Positively Associated with Triglyceride-Glucose Index and Triglyceride Glucose-Body Mass Index in Adults: Data from NHANES 2011-2018.

Compiling evidence supports that selenium plays a vital role in glucose metabolism. Triglyceride-glucose index (TyG) and triglyceride-glucose-body mass index (TyG-BMI) are commonly used in epidemiologic studies to evaluate insulin resistance and cardiovascular disease (CVD) risks. This study is aimed to investigate the association between whole blood selenium concentration and TyG and TyG-BMI. A total of 6290 participants (age ≥ 20 years) from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 were included. Multiple linear regression models were used to examine the association between blood selenium quartiles and TyG and TyG-BMI. Subgroup analysis stratified by diabetes status was also performed. The adjusted model showed a positive association between TyG and blood selenium concentration (ß [95%CI] = 0.099 [0.063, 0.134], p < 0.001) and TyG-BMI (ß [95%CI] = 3.185 [2.102, 4.268], p < 0.001). The association persisted after stratification by diabetes status (p < 0.001). Participants were stratified into four quartiles based on selenium concentration (Q1: 1.08-2.24 µmol/L, Q2: 2.25-2.42 µmol/L, Q3: 2.43-2.62 µmol/L, Q4: 2.63-8.08). Compared with the Q1 group, TyG in the Q3 and Q4 groups was significantly higher (ß = 0.075 [95%CI 0.039 to 0.112] and ß = 0.140 [95%CI 0.103 to 0.176], respectively). Additionally, TyG-BMI in the Q2, Q3, and Q4 groups was higher than that in the Q1 group (ß = 1.189 [95%CI 0.065 to 2.314], ß = 2.325 [95%CI 1.204 to 3.446], and ß = 4.322 [95%CI 3.210 to 5.435], respectively). Blood level of selenium was positively associated with TyG and TyG-BMI, indicating that excessive blood selenium may be associated with impaired insulin sensitivity and increased risk of cardiovascular disease.

Network pharmacology combined with metabolomics to explore the mechanism for Lonicerae Japonicae flos against respiratory syncytial virus.

BACKGROUND: Respiratory Syncytial Virus (RSV) stands out as a primary contributor to lower respiratory tract infections and hospitalizations, particularly in infants. Lonicerae japonicae flos (LJF), a traditional Chinese medicine renowned for its efficacy against various viral infections, including RSV, has been widely employed. Despite its common use, the precise therapeutic mechanism of LJF against RSV remains elusive. This study aimed to investigate the underlying mechanism of LJF against RSV through network pharmacology and metabolomics. METHODS: In this study, based on network pharmacology, potential targets related to LJF and RSV were obtained from PubChem and Swiss Target Prediction. The core targets and pathways were established and verified by enrichment analysis and molecular docking. The anti-RSV efficacy of LJF was determined by in vitro experiments. Additionally, metabolomics analysis was integrated, allowing for the identification of differential metabolites and their correlation with targets following LJF treatment in the context of RSV infection. RESULTS: A total of 23 active ingredients and 780 targets were obtained, of which 102 targets were associated with LJF anti-RSV. The construction of the corresponding Protein-Protein Interaction (PPI) network unveiled potential core targets, including STAT3, TNF, and AKT1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that LJF's anti-RSV effects primarily involve key pathways such as the PI3K-Akt signaling pathway, EGFR tyrosine kinase inhibitor resistance, and FoxO signaling pathway. Molecular docking showed that ZINC03978781, 4,5'-Retro-.beta.,.beta.-Carotene -3,3'-dione, 4',5'-didehydro and 7-epi-Vogeloside had better binding ability. The cellular assay showed that the therapeutic index of LJF against RSV was 4.79. Furthermore, 18 metabolites were screened as potential biomarkers of LJF against RSV, and these metabolites were mainly involved in the pathways of purine metabolism, linoleic acid metabolism, alpha-linolenic acid metabolism, and other related pathways. CONCLUSIONS: The intergration of network pharmacology and metabolomics can clarify the active targets and related pathways of LJF against RSV, which could provide a valuable reference for further research and clinical application of LJF.

Functional divergence of CYP76AKs shapes the chemodiversity of abietane-type diterpenoids in genus Salvia.

The genus Salvia L. (Lamiaceae) comprises myriad distinct medicinal herbs, with terpenoids as one of their major active chemical groups. Abietane-type diterpenoids (ATDs), such as tanshinones and carnosic acids, are specific to Salvia and exhibit taxonomic chemical diversity among lineages. To elucidate how ATD chemical diversity evolved, we carried out large-scale metabolic and phylogenetic analyses of 71 Salvia species, combined with enzyme function, ancestral sequence and chemical trait reconstruction, and comparative genomics experiments. This integrated approach showed that the lineage-wide ATD diversities in Salvia were induced by differences in the oxidation of the terpenoid skeleton at C-20, which was caused by the functional divergence of the cytochrome P450 subfamily CYP76AK. These findings present a unique pattern of chemical diversity in plants that was shaped by the loss of enzyme activity and associated catalytic pathways.

Long-Term Outcomes After Stenting in Extracranial vs. Intracranial Stenosis.

Objective: The purpose of this pilot study is to explore the difference in safety and effectiveness after stenting in patients with extracranial or intracranial vertebral artery stenosis. Methods: The study involved 26 patients treated with stents for ≥70% stenosis between January 1, 2017, and September 8, 2020. The patients were divided into intracranial and extracranial groups based on the location of the target vessel stenosis. The incidence of stroke or death within 30 days, long-term recurrence of ischemic symptoms, and restenosis during follow-up were monitored. Results: Within 30 days, no stroke or death was observed in the 26 patients, During the follow-up period, the risk of recurrence of posterior circulation stroke or transient ischemic attack was 23.1% (6/26). Vascular-related complications were 5.6% vs. 12.5% (P = .529) in the intracranial vs. extracranial stenosis group. After 1 year, stroke or transient ischemic attack of posterior circulation was observed in 12.5% (1/8) vs. 16.7% (3/18) in the intracranial and extracranial stenosis group, respectively. The restenosis rate in the intracranial stenosis group was higher than the extracranial stenosis group (37.5% vs. 28.6%, P > .05). This trend was also found in the asymptomatic restenosis rate (25% vs. 7.1%, P = .527). Conclusions: The study results showed that there was no significant difference in the safety and effectiveness after stenting in extracranial and intracranial vertebral artery stenosis, but intracranial vertebral artery stenosis has a low rate of symptomatic restenosis. Symptomatic restenosis may be an important problem that limits the efficacy of extracranial vertebral artery stenting.

Intravascular Intervention Combined with Standard Drug Therapy in Patients with Severe Intracranial Atherosclerotic Stenosis and Plaque Enhancement.

Objective: The purpose of this retrospective cohort study was to evaluate clinical outcomes in high-risk patients with symptomatic intracranial atherosclerotic stenosis (sICAS) resulting from plaque enhancement who underwent balloon dilation or stent implantation. Plaque features were identified based on high-resolution magnetic resonance vessel wall imaging (HRMR-VWI). Methods: A total of 37 patients with sICAS (degree of stenosis ≥70%) were enrolled between January 2018 and March 2022 at a single center. All patients underwent HRMR-VWI and received standard drug treatment after hospital admission. The patients were divided into 2 groups based on whether they underwent interventional treatment (n = 18) or non-interventional treatment (n = 19). The grade of enhancement and enhancement rate (ER) of culprit plaque were evaluated using 3D-HRMR-VWI. The risk of symptom recurrence was compared between the 2 groups during follow-up. Results: There was no statistical difference between the intervention and non-intervention groups in the rate and type of enhancement. Median clinical follow-up time was 17.8 (10.0 to 26.0) months and median follow-up time was 3.6 (3.1 to 6.2) months. In the intervention group, 2 patients had stent restenosis, but no stroke or transient ischemia attacks (TIAs) occurred. In contrast, 1 patient in the non-intervention group had an ischemic stroke and 4 patients had TIAs. The incidence of the primary outcome was lower in the intervention group than in the non-intervention group (0 vs 26.3%; P = .046). Conclusions: High-resolution magnetic resonance intracranial vessel wall imaging (HR MR-IVWI) can be used to identify vulnerable plaque features. It is safe and effective in high-risk patients with sICAS with responsible plaque enhancement to undergo intravascular intervention combined with standard drug therapy. Further studies are needed to analyze the link between plaque enhancement and symptom recurrence in the medication group at baseline.

Neuroprotective effects of PRG on Aß25-35-induced cytotoxicity through activation of the ERK1/2 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Phylloporia ribis (Schumach:Fr.)Ryvarden is a genus of needle Phellinus medicinal fungi, parasitic on the living rhizomes of hawthorn and pear trees. As a traditional Chinese medicine, Phylloporia ribis was used in folklore for long-term illness, weakness and memory loss in old age. Previous studies have shown that polysaccharides from Phylloporia ribis (PRG) significantly promoted synaptic growth in PC12 cells in a dose-dependent manner, exhibiting "NGF"-like neurotrophic activity. Aß25-35 damage to PC12 cells produced neurotoxicity and decreased cell survival, and PRG reduced the apoptosis rate, suggesting that PRG has neuroprotective effects. The studies confirmed that PRG had the potential to be a neuroprotective agent, but its neuroprotective mechanism remained unclear. AIM OF THE STUDY: We aimed to elucidate the neuroprotective effects of PRG in an Aß25-35-induced Alzheimer's disease (AD) model. MATERIALS AND METHODS: Highly-differentiated PC12 cells were treated with Aß25-35 (AD model) and PRG, and were assessed for cellular apoptosis, inflammatory factors, oxidative stress, and kinase phosphorylation. RESULTS: The results showed that the PRG groups effectively inhibited the neurotoxicity, mainly manifested by inhibiting mitochondrial oxidative stress, attenuating neuroinflammatory responses, and improving mitochondrial energy metabolism, eventually resulting in higher cell survival. The expression of p-ERK, p-CREB and BDNF proteins was increased in the PRG groups compared to the model group, which confirmed that PRG reversed the inhibition of the ERK pathway. CONCLUSION: We provide evidence for neuroprotection conferred by PRG and its mechanism by inhibiting ERK1/2 hyper-phosphorylation, prevention of mitochondrial stress, and subsequent prevention of apoptosis. The study highlights PRG as a promising candidate with neuroprotective effects, the potential of which can be harnessed for identifying novel therapeutic targets.

Preparation and antibacterial mechanism of cinnamaldehyde/tea polyphenol/polylactic acid coaxial nanofiber films with zinc oxide sol to Shewanella putrefaciens.

In this study, the coaxial nanofiber films were prepared by coaxial electrospinning technique with cinnamaldehyde (CMA) and tea polyphenol (TP) as core material and polylactic acid (PLA) as shell material, and to obtain food packaging materials with great physicochemical and antibacterial properties, zinc oxide (ZnO) sol were added into PLA, and ZnO/CMA/TP-PLA coaxial nanofiber films were prepared. Meanwhile, the microstructure and physicochemical properties were determined, and the antibacterial properties and mechanism were investigated with Shewanella putrefaciens (S. putrefaciens) as target. The results show that the ZnO sol makes the physicochemical properties and antibacterial properties of the coaxial nanofiber films improve. Among them, the 1.0 % ZnO/CMA/TP-PLA coaxial nanofibers have smooth and continuous uniform surfaces, and their encapsulation effect on CMA/TP and antibacterial properties are the optimal. The synergistic action of CMA/TP and ZnO sol cause severe depression and folding of the cell membrane of S. putrefaciens, makes cell membrane permeability increase and of intracellular materials spillage, interference the bacteriophage protein expression, and makes macromolecular protein degraded. In this study, the introduction of oxide sols into polymeric shell materials by in-situ synthesis technique can provide theoretical support and methodological guidance for the application of electrospinning technology in the field of food packaging.

Multi-factor correlation analysis of the effect of root-promoting practices on tobacco rhizosphere microecology in growth stages.

Some agronomic practices not only promote the development of crop roots and increase overall plant performance but also affect colonisation by rhizosphere microorganisms. However, the composition and temporal dynamics of the tobacco rhizosphere microbiota under different root-promoting practices are poorly understood. Here, we characterised the tobacco rhizosphere microbiota at the knee-high, vigorous growing, and maturity stages under the application of potassium fulvic acid (PFA), γ-Polyglutamic acid (PGA), soymilk root irrigation (SRI), and conventional fertilization (CK) and its correlation with root characteristics and soil nutrients. The results showed that three root-promoting practices notably improved the dry and fresh root weights. Total nitrogen and phosphorus, available phosphorus and potassium, and organic matter contents in the rhizosphere markedly increased at the vigorous growing stage. The rhizosphere microbiota was changed through root-promoting practices. However, with tobacco growth, the change of rhizosphere microbiota showed a pattern of slow first and then fast and the microbiota of different treatments gradually approached. SRI reduced plant-pathogenic fungi but increased chemoheterotrophic and phototrophic bacteria, and arbuscular mycorrhizal fungi. PFA and PGA markedly increased arbuscular mycorrhizal and ectomycorrhizal fungi at the knee-high stage, which benefitted tobacco nutrient absorption. The correlation between rhizosphere microorganisms and environmental factors varied at different growth stages. Notably, the rhizosphere microbiota was more sensitive to environmental factors at the vigorous growing stage, and the interactions were more complex than in other stages. Furthermore, a variance partitioning analysis showed that the influence of root-soil interaction on the rhizosphere microbiota increased with tobacco growth. Overall, all three root-promoting practices could improve root characteristics, rhizosphere nutrient, and rhizosphere microbiota to varying degrees and increase the tobacco biomass, among which PGA had the most obvious effect and most suitable for tobacco cultivation. Our findings revealed the role of root-promoting practices in shaping the rhizosphere microbiota during plant growth and elucidated the assembly patterns and environmental drivers of crop rhizosphere microbiota driven by the application of root-promoting practices in agricultural production.

Hydroxysafflor yellow A regulates lymphangiogenesis and inflammation via the inhibition of PI3K on regulating AKT/mTOR and NF-κB pathway in macrophages to reduce atherosclerosis in ApoE-/- mice.

BACKGROUND: Macrophage-mediated inflammatory infiltration and pathological lymphangiogenesis around atherosclerotic plaques are newly highlighted treatment targets of atherosclerosis. Although the effect of Hydroxysafflor yellow A(HSYA) on atherosclerosis was clear, few studies focus on the regulation of HSYA on such mechanisms. PURPOSE: This study aimed to uncover the key site of HSYA on improving atherosclerosis by regulating macrophage-induced inflammation and lymphangiogenesis. STUDY DESIGN: This study was designed to explore the new mechanism of HSYA on alleviating atherosclerosis in vitro and in vivo. METHODS: We determined the expression of vascular endothelial growth factor C(VEGF-C) in Raw264.7 cells and high-fat diet fed ApoE knockout (ApoE-/-) mice. Raw264.7 cells were treated with HSYA under the stimulation of LPS and ox-LDL. HFD induced ApoE-/- mice were given different concentrations of HSYA-saline solution by tail vein injection and ATV-saline suspension by gavage. C57/B6j mice fed with chow diet were used for the control group. H&E, oil red O and immunofluorescence staining analysis were used for visualizing the pathological changes. The biological impact of HSYA was evaluated by body weight, lipid metabolism, inflammation levels, and corresponding function indexes of kidney and liver. RT-qPCR and western blot methods were conducted to determine the expression of the inflammation and lymphangiogenesis factors. Molecular docking and microscale thermophoresis analysis were used to verify the combination of HSYA and PI3K. RESULTS: In vivo, HSYA reduced the plaque formation, hepatic steatosis and inflammation-related lymphangiogenesis (IAL). It also changed the serum levels of inflammation (VEGF-C, TNF-α, IL-6, VCAM1, MCP1), lipid indexes (LDL, CHOL, TRIG) and relevant lymphangiogenesis (VEGF-C and LYVE-1) and inflammation (VCAM-1 and IL-6) signals in the aorta. In vitro, HSYA regulated Akt/mTOR and NF-κB activation by the inhibition of PI3K in macrophages. CONCLUSION: HSYA affects inflammation and inflammation-associated lymphangiogenesis via suppressing PI3K to affect AKT/mTOR and NF-B pathway activation in macrophages, showing a comprehensive protective effect on atherosclerosis.

Synergistic analysis of performance, functional genes, and microbial community assembly in SNDPR process under Zn(II) stress.

One of the most prevalent heavy metals found in rural sewage is Zn(II), while its effect on simultaneous nitrification, denitrification and phosphorus removal (SNDPR) remains unclear. In this work, the responses of SNDPR performance to long-term Zn(II) stress were investigated in a cross-flow honeycomb bionic carrier biofilm system. The results indicated that Zn(II) stress at 1 and 5 mg L-1 could increase nitrogen removal. Maximum ammonia nitrogen, total nitrogen, and phosphorus removal efficiencies of up to 88.54%, 83.19%, and 83.65% were obtained at Zn(II) concentration of 5 mg L-1. The functional genes, such as archaeal amoA, bacterial amoA, NarG, NirS, NapA, and NirK, also reached the highest value at 5 mg L-1 Zn(II), with the absolute abundances of 7.73 × 105, 1.57 × 106, 6.68 × 108, 1.05 × 109, 1.79 × 108, and 2.09 × 108 copies·g-1 dry weight, respectively. The neutral community model demonstrated that deterministic selection was responsible for the system's microbial community assembly. Additionally, response regimes with extracellular polymeric substances and cooperation among microorganisms facilitated the stability of the reactor effluent. Overall, the findings of this paper contribute to improving the efficiency of wastewater treatment.

Hydrogel-Integrated Multimodal Response as a Wearable and Implantable Bidirectional Interface for Biosensor and Therapeutic Electrostimulation.

A hydrogel that fuses long-term biologic integration, multimodal responsiveness, and therapeutic functions has received increasing interest as a wearable and implantable sensor but still faces great challenges as an all-in-one sensor by itself. Multiple bonding with stimuli response in a biocompatible hydrogel lights up the field of soft hydrogel interfaces suitable for both wearable and implantable applications. Given that, we proposed a strategy of combining chemical cross-linking and stimuli-responsive physical interactions to construct a biocompatible multifunctional hydrogel. In this hydrogel system, ureidopyrimidinone/tyramine (Upy/Tyr) difunctionalization of gelatin provides abundant dynamic physical interactions and stable covalent cross-linking; meanwhile, Tyr-doped poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) acts as a conductive filler to establish electrical percolation networks through enzymatic chemical cross-linking. Thus, the hydrogel is characterized with improved conductivity, conformal biointegration features (i.e., high stretchability, rapid self-healing, and excellent tissue adhesion), and multistimuli-responsive conductivity (i.e., temperature and urea). On the basis of these excellent performances, the prepared multifunctional hydrogel enables multimodal wearable sensing integration that can simultaneously track both physicochemical and electrophysiological attributes (i.e., motion, temperature, and urea), providing a more comprehensive monitoring of human health than current wearable monitors. In addition, the electroactive hydrogel here can serve as a bidirectional neural interface for both neural recording and therapeutic electrostimulation, bringing more opportunities for nonsurgical diagnosis and treatment of diseases.

One-Pot Synthesis of Bi2 S3 /TiO2 /rGO Heterostructure with Red Light-Driven Photovoltaic Effect for Remote Electrotherapy-Assisted Wound Repair.

The past decades have witnessed the rational design of novel functional nanomaterials and the potential to revolutionize many applications. With the increasing focus on electronic biological processes, novel photovoltaic nanomaterials are highly expectable for empowering new therapeutic strategies such as establishing a link between endogenous electric field (EEF) and electrotherapy. Compared to traditional invasive stimulation, the light-initiating strategy has the advantages of non-invasion, non-power supply, and precise controllability. Whereas, common photoactivated materials require short-wavelength light excitation accompanied by poor tissue penetration and biohazard. Herein, by the construction of p-n heterostructured Bi2 S3 /TiO2 /rGO (BTG) nanoparticles, broadener light absorption and higher light conversion than regular UV excitation are realized. Simultaneously, the photoelectric performance of BTG heterostructure, as well as the synergistic effect of Bi2 S3 morphology, are revealed. Besides, the rationally designed biomimetic hydrogel matrix consisting of collagen and hyaluronic acid provides appropriate bioactivity, interface adhesion, mechanical matching, and electron transfer. Therefore, the photovoltaic BTG-loaded matrix provides a platform of light-driven electrical stimulation, coupling the EEF to modulate the electrophysiological and regeneration microenvironment. The implementation of photoelectric stimulation holds broad prospects for non-drug therapy and electrical-related biological process modulation including osseointegration, nerve regeneration, electronic skin, and wound healing.

Simultaneous nitrification, denitrification and phosphorus removal: What have we done so far and how do we need to do in the future?

Nitrogen and phosphorus contamination in wastewater is a serious environmental concern and poses a global threat to sustainable development. In this paper, a comprehensive review of the studies on simultaneous nitrogen and phosphorus removal (SNPR) during 1986-2022 (538 publications) was conducted using bibliometrics, which showed that simultaneous nitrification, denitrification, and phosphorus removal (SNDPR) is the most promising process. To better understand SNDPR, the dissolved oxygen, carbon to nitrogen ratio, carbon source type, sludge retention time, Cu2+ and Fe3+, pH, salinity, electron acceptor type of denitrifying phosphorus-accumulating organisms (DPAOs), temperature, and other influencing factors were analyzed. Currently, SNDPR has been successfully implemented in activated sludge systems, aerobic granular sludge systems, biofilm systems, and constructed wetlands; sequential batch mode of operation is a common means to achieve this process. SNDPR exhibits a significant potential for phosphorus recovery. Future research needs to focus on: (1) balancing the competitiveness between denitrifying glycogen-accumulating organisms (DGAOs) and DPAOs, and countermeasures to deal with the effects of adverse conditions on SNDPR performance; (2) achieving SNDPR in continuous flow operation; and (3) maximizing the recovery of P during SNDPR to achieve resource sustainability. Overall, this study provides systematic and valuable information for deeper insights into SNDPR, which can help in further research.

An updated review of functional properties, debittering methods, and applications of soybean functional peptides.

Soybean functional peptides (SFPs) are obtained via the hydrolysis of soybean protein into polypeptides, oligopeptides, and a small amount of amino acids. They have nutritional value and a variety of functional properties, including regulating blood lipids, lowering blood pressure, anti-diabetes, anti-oxidant, preventing COVID-19, etc. SFPs have potential application prospects in food processing, functional food development, clinical medicine, infant milk powder, special medical formulations, among others. However, bitter peptides containing relatively more hydrophobic amino acids can be formed during the production of SFPs, seriously restricting the application of SFPs. High-quality confirmatory human trials are needed to determine effective doses, potential risks, and mechanisms of action, especially as dietary supplements and special medical formulations. Therefore, the physiological activities and potential risks of soybean polypeptides are summarized, and the existing debitterness technologies and their applicability are reviewed. The technical challenges and research areas to be addressed in optimizing debittering process parameters and improving the applicability of SFPs are discussed, including integrating various technologies to obtain higher quality functional peptides, which will facilitate further exploration of physiological mechanism, metabolic pathway, tolerance, bioavailability, and potential hazards of SFPs. This review can help promote the value of SFPs and the development of the soybean industry.

A Network Pharmacology Study on the Similarities and Differences in the Mechanisms of Zuo Gui Wan/You Gui Wan for the Treatment of Premature Ovarian Failure.

BACKGROUND: Premature ovarian failure is a heterogeneous disease that severely affects the quality of life of women in their reproductive years. The ancient classical Chinese medicine compounds Zuo Gui Wan and You Gui Wan have great potential to treat premature ovarian failure, but the similarities and differences in their pharmacological mechanisms for treating POF are not yet clear. METHODS: In this study, the public database was used to screen the active ingredients and potential targets of Zuo Gui Wan and You Gui Wan. The similarities and differences in the potential targets of both pills for the treatment of POF were analysed using the POF-related genes obtained from OMIM and GeneCards. The protein-protein interaction network was established and collated to form a drug-active ingredient-target gene network using STRING. Finally, the drug-target-pathway network was constructed by enrichment analysis to find the differences in target enrichment on the same pathway. RESULTS: Pharmacological analysis of the network showed that Zuo Gui Wan contains 72 active ingredients, while You Gui Wan has 112. A total of 62 common compositions, such as quercetin and kaempferol, were identified. Amongst them were 10 unique compounds, such as hydroxyproline and cholesterol, in Zuo Gui Wan and 50 exclusive compounds, such as Karanjin and betacarotene, in You Gui Wan. In addition, 14 overlapping targets, including MAPK1, CXCL8, TNF, IL6, and EGFR, were determined amongst the first 20 targets in the treatment of POF by both pills, demonstrating that the core mechanism of POF treatment is similar between the two. Pathway enrichment analysis showed 87 identical and significant pathways between Zuo Gui Wan and You Gui Wan, including IL-17, TNF, PI3K-Akt, oestrogen, VEGF, and other pathways. Zuo Gui Wan has 12 special pathways, such as natural killer cell-mediated cytotoxicity and intestinal immune network for IgA production. You Gui Wan has nine unique pathways, such as insulin secretion and glucagon signalling pathway. CONCLUSION: Zuo Gui Wan and You Gui Wan could treat POF by inhibiting oxidative stress and inflammation, regulating hormone levels, improving ovarian function, and promoting follicular development. Zuo Gui Wan is inclined to immune regulation, while You Gui Wan prefers insulin regulation. Therefore, similarities and differences clearly exist in the specific mechanisms of Zuo Gui Wan and You Gui Wan in the treatment of POF.

Carvacrol Treatment Reduces Decay and Maintains the Postharvest Quality of Red Grape Fruits (Vitis vinifera L.) Inoculated with Alternaria alternata.

In this study, we isolated and identified pathogenic fungi from the naturally occurring fruits of red grapes, studied their biological characteristics, screened fifteen essential oil components to find the best natural antibacterial agent with the strongest inhibitory effect, and then compared the incidence of postharvest diseases and storage potential of red grapes treated with two concentrations (0.5 EC50/EC50) of essential oil components (inoculated with pathogenic fungi) during storage for 12 d at room temperature. In our research, Alternaria alternata was the primary pathogenic fungus of red grapes. Specifically, red grapes became infected which caused diseases, regardless of whether they were inoculated with Alternaria alternata in an injured or uninjured state. Our findings demonstrated that the following conditions were ideal for Alternaria alternata mycelial development and spore germination: BSA medium, D-maltose, ammonium nitrate, 28 °C, pH 6, and exposure to light. For the best Alternaria alternata spore production, OA medium, mannitol, urea, 34 °C, pH 9, and dark conditions were advised. Furthermore, with an EC50 value of 36.71 µg/mL, carvacrol demonstrated the highest inhibitory impact on Alternaria alternata among the 15 components of essential oils. In the meantime, treatment with EC50 concentration of carvacrol was found to be more effective than 0.5 EC50 concentration for controlling Alternaria alternata-induced decay disease of red grapes. The fruits exhibited remarkable improvements in the activity of defense-related enzymes, preservation of the greatest hardness and total soluble solids content, reduction in membrane lipid peroxidation in the peel, and preservation of the structural integrity of peel cells. Consequently, carvacrol was able to prevent the Alternaria alternata infestation disease that affects red grapes, and its EC50 concentration produced the greatest outcomes.

"Jing-Ning Granules" Can Alleviate Attention Deficit Hyperactivity Disorder in Rats by Modulating Dopaminergic D2/D1-Like Receptor-Mediated Signaling Pathways.

Background: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by attention deficit, hyperactivity, and impulsivity. Jing-Ning Granules (JNG) is a traditional Chinese medicine (TCM) that can alleviate ADHD. Although JNG is commonly used for the effective treatment of ADHD and has obtained the national invention patent, the exact mechanism of action remains unclear. Objective: In this study, we examined the effect and mechanism of JNG in spontaneously hypertensive rats (SHRs). We hypothesized that JNG affects dopaminergic D2/D1-like receptors and related pathways. Materials and Methods: Six rat groups were used in the experiment: Wistar-Kyoto rats (WKY, control group) and five SHR groups, including a model group; atomoxetine (ATX, positive control) group; and low, medium, and high-dose JNG groups. The corresponding treatments were daily administered to each group for 6 weeks. A behavioral test, including a step-down test and open field test (OFT), was carried out at the end of treatment. After the behavioral test, all animals were sacrificed, and the brain tissue was collected and analyzed ex vivo; histopathological analysis was performed to assess the pathological changes of the hippocampus; expression of D1-like and D2-like receptors, sensor protein calmodulin (CaM), protein kinase A (PKA), and calcium/calmodulin-dependent serine/threonine protein kinase (CaMKII) in the striatum and hippocampus was measured by western blot and real-time quantitative PCR (RT-PCR); cyclic adenosine monophosphate (cAMP) levels in the striatum were analyzed using an enzyme-linked immunosorbent assay (ELISA), while the level of Ca2+ in the striatum was analyzed by a calcium kit. Results: Our results showed that ATX or JNG could ameliorate the hyperactive/impulsive behavior and cognitive function of ADHD by promoting neuroprotection. Mechanistically, ATX or JNG could prompt the expressions of Dl-like and D2-like receptors and improve the mRNA and protein levels of cAMP/PKA and Ca2+/CAM/CAMKII signaling pathways. Conclusion: These results indicate that JNG can produce therapeutic effects by regulating the balance of D2/D1-like receptor-mediated cAMP/PKA and Ca2+/CaM/CaMKII signaling pathways.