Mechanism interpretation of Guhan Yangshengjing for protection against Alzheimer's disease by network pharmacology and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Guhan Yangshengjing (GHYSJ) is an effective prescription for delaying progression of Alzheimer's disease (AD) based on the ancient Chinese medical classics excavated from Mawangdui Han Tomb. Comprising a combination of eleven traditional Chinese herbs, the precise protective mechanism through which GHYSJ acts on AD progression remains unclear and has significant implications for the development of new drugs to treat AD. AIM OF THE STUDY: To investigate the mechanism of GHYSJ in the treatment of AD through network pharmacology and validate the results through in vitro experiments. MATERIALS AND METHODS: Chemical composition-target-pathway network and protein-protein interaction network were constructed by network pharmacology to predict the potential targets of GHYSJ for the treatment of AD. The interaction relationship between active ingredients and targets was verified by molecular docking and molecular force. Furthermore, the chemical constituents of GHYSJ were analyzed by LC-MS and HPLC, the effects of GHYSJ on animal tissues were analyzed by H&E staining. An Aß-induced SH-SY5Y cellular model was established to validate the core pathways and targets predicted by network pharmacology and molecular docking. RESULTS: The results of the network pharmacology analysis revealed a total of 155 bioactive compounds capable of crossing the blood-brain barrier and interacting with 677 targets, among which 293 targets specifically associated with AD, which mainly participated in and regulated the amyloid aggregation pathway and PI3K/Akt signaling pathway, thereby treating AD. In addition, molecular docking analysis revealed a robust binding affinity between the principal bioactive constituents of GHYSJ and crucial targets implicated in AD. Our findings were further substantiated by in vitro experiments, which demonstrated that Liquiritigenin and Ginsenosides Rh4, crucial constituents of GHYSJ, as well as GHYSJ pharmaceutic serum, exhibited a significant down-regulation of BACE1 expression in Aß-induced damaged SH-SY5Y cells. This study provides valuable data and theoretical underpinning for the potential therapeutic application of GHYSJ in the treatment of AD and secondary development of GHYSJ prescription. CONCLUSION: Through network pharmacology, molecular docking, LC-MS, and cellular experiments, GHYSJ was initially confirmed to delay the progression of AD by regulating the expression of BACE1 in Amyloid aggregation pathway. Our observations provided valuable data and theoretical underpinning for the potential therapeutic application of GHYSJ in the treatment of AD.

Lancao decoction alleviates cognitive dysfunction: A new therapeutic drug and its therapeutic mechanism.

BACKGROUND: Cognitive dysfunction (CD) is a neurodegenerative disease characterized primarily by the decline of learning and memory abilities. The physiological and pathological mechanisms of CD are very complex, which is mainly related to normal function of the hippocampus. Lancao decoction (LC) is a Chinese medicine formula, which has been used to treat neurodegenerative disorders. However, the potential of LC for the treatment of CD, as well as its underlying mechanisms, is unclear. PURPOSE: In the study, we aimed to reveal the functional and neuronal mechanisms of LC's treatments for CD in scopolamine-induced mice. METHODS: Gas chromatography (GC) was used to determine the stability of LC's extraction. CD model was established by the chronic induction of scopolamine (Scop, 1 mg/kg/day) for 1 week. Behavioral tests including morris water maze (MWM) and y-maze were used to evaluate learning and memory abilities of mice after LC's treatments. Immunofluorescence was used to detected the expressions of cFOS, Brdu and Ki67 after LC's treatments. Pharmacological blockade experiments explored the role of α-Amino-3­hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) in LC's treatments for CD and its relationships with regeneration, activities and differentiation of neurons. RESULTS: The results showed that LC was capable of improving spatial learning and memory and spontaneous alternating abilities in Scop-induced mice, which was similar to donepezil. LC could increase the number of cFOS positive cells, which was used as a marker of neuronal activity to upregulate by neuronal activities in hippocampus, but donepezil did not. Moreover, LC could strengthen neurogenesis and neuro-differentiation by increasing the number of Brdu and Ki67 positive cells in hippocampal dentate gyrus (DG), meanwhile, donepezil could only enhance the number of Ki67 positive cells. Transient inhibition of AMPAR by NBQX blunted the function of LC's treatment for CD and inhibited the enhanced effect of LC on Scop-induced hippocampal neuronal excitability and neurogenesis in mice. CONCLUSION: To sum up, our study demonstrated that LC had the function of treating CD by enhancing content of acetylcholine (ACh) to activate AMPAR, which further up-regulated neurogenesis and neuronal differentiation to strengthen neuroactivities in hippocampus.

Ginsenoside Rg3: A Review of its Anticancer Mechanisms and Potential Therapeutic Applications.

BACKGROUND: Traditional Chinese Medicine (TCM) has a long history of treating various diseases and is increasingly being recognized as a complementary therapy for cancer. A promising natural compound extracted from the Chinese herb ginseng is ginsenoside Rg3, which has demonstrated significant anticancer effects. It has been tested in a variety of cancers and tumors and has proven to be effective in suppressing cancer. OBJECTIVES: This work covers various aspects of the role of ginsenoside Rg3 in cancer treatment, including its biological functions, key pathways, epigenetics, and potential for combination therapies, all of which have been extensively researched and elucidated. The study aims to provide a reference for future research on ginsenoside Rg3 as an anticancer agent and a support for the potential application of ginsenoside Rg3 in cancer treatment.

Mind shift I: Fructus Aurantii - Rhizoma Chuanxiong synergistically anchors stress-induced depression-like behaviours and gastrointestinal dysmotility cluster by regulating psycho-immune-neuroendocrine network.

BACKGROUND: Researchers have not studied the integrity, orderly correlation, and dynamic openness of complex organisms and explored the laws of systems from a global perspective. In the context of reductionism, antidepressant development formerly focused on advanced technology and molecular details, clear targets and mechanisms, but the clinical results were often unsatisfactory. PURPOSE: MDD represents an aggregate of different and highly diverse disease subtypes. The co-occurrence of stress-induced nonrandom multimorbidity is widespread, whereas only a fraction of the potential clusters are well known, such as the MDD-FGID cluster. Mapping these clusters, and determining which are nonrandom, is vital for discovering new mechanisms, developing treatments, and reconfiguring services to better meet patient needs. STUDY DESIGN: Acute stress 15-minute forced swimming (AFS) or CUMS protocols can induce the nonrandom MDD-FGID cluster. Multiple biological processes of rats with depression-like behaviours and gastrointestinal dysmobility will be captured under conditions of stress, and the Fructus Aurantii-Rhizoma Chuanxiong (ZQCX) decoction will be utilized to dock the MDD-FGID cluster. METHODS/RESULTS: Here, Rhizoma Chuanxiong, one of the seven components of Chaihu-shugan-San, elicited the best antidepressant effect on CUMS rats, followed by Fructus Aurantii. ZQCX reversed AFS-induced depression-like behaviours and gastrointestinal dysmobility by regulating the glutamatergic system, AMPAR/BDNF/mTOR/synapsin I pathway, ghrelin signalling and gastrointestinal nitric oxide synthase. Based on the bioethnopharmacological analysis strategy, the determined meranzin hydrate (MH) and senkyunolide I (SI) by UPLC-PDA, simultaneously absorbed by the jejunum and hippocampus of rats, have been considered major absorbed bioactive compounds acting on behalf of ZQCX. Cotreatment with MH and SI at an equivalent dose in ZQCX synergistically replicated over 50.33 % efficacy of the parent formula in terms of antidepressant and prokinetic actions by modulating neuroinflammation and ghrelin signalling. CONCLUSION: Brain-centric mind shifts require the integration of multiple central and peripheral systems and the elucidation of the underlying neurobiological mechanisms that ultimately contribute to novel therapeutic options. Ghrelin signalling and the immune system may partially underlie multimorbidity vulnerability, and ZQCX anchors stress-induced MDD-FGID clusters by docking them. Combining the results of micro details with the laws of the macro world may be more effective in finding treatments for MDD.

P2/O3 Biphasic Cathode Material through Magnesium Substitution for Sodium-Ion Batteries.

P2-type Fe-Mn-based oxides offer excellent discharge specific capacity and are as affordable as typical layered oxide cathode materials for sodium-ion batteries (SIBs). After Cu modification, though they can improve the cycling performance and air stability, the discharge specific capacity will be reduced. Considering the complementary nature of biphasic phases in electrochemistry, hybridizing P2/O3 hybrid phases can enhance both the storage performance of the battery and specific capacity. Herein, a hybrid phase composite with high capacity and good cycle performance is deliberately designed and successfully prepared by controlling the amount of Mg doping in the layered oxide. It has been found that the introduction of Mg can activate anion redox in the oxide layer, resulting in a significant increase in the specific discharge capacity of the material. Meanwhile, the dual-phase structure can produce an interlocking effect, thus effectively alleviating structure strain. The degradation of cycling performance caused by structural damage during the high-voltage charging and discharging process is clearly mitigated. The results show that the specific discharge capacity of Na0.67Cu0.2Mg0.1Fe0.2Mn0.5O2 is as high as 212.0 mAh g-1 at 0.1C rate and 186.2 mAh g-1 at 0.2C rate. After 80 cycles, the capacity can still maintain 88.1%. Moreover, the capacity and cycle performance as well as the stability can still remain stable even in the high-voltage window. Therefore, this work offers an insightful exploration for the development of composite cathode materials for SIBs.

Molecular mechanism of Jianpiyifei II granules in the treatment of chronic obstructive pulmonary disease: Network pharmacology analysis, molecular docking, and experimental assessment.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is defined by persistent airway and lung inflammation, excessive mucus production, remodeling of the airways, and damage to the alveolar tissue. Based on clinical experience, it has been observed that Jianpiyifei II (JPYF II) granules exhibit a significant therapeutic impact on individuals suffering from stable COPD. Nevertheless, the complete understanding of JPYF II's potential mode of action against COPD remains to be further clarified. PURPOSE: To further investigate the underlying mechanism of JPYF II for treating COPD and clarify the role of the IL-17 pathway in the treatment. METHODS: A variety of databases were utilized to acquire JPYF II's bioactive components, as well as related targets of JPYF II and COPD. Cytoscape was utilized to establish multiple interaction networks for the purpose of topological analyses and core-target screening. The Metascape was utilized to identify the function of target genes and crucial signaling pathways. To evaluate the interactions between bioactive ingredients and central target proteins, molecular docking simulations were conducted. Following that, a sequence of experiments was conducted both in the laboratory and in living organisms, which included analyzing the cell counts in bronchoalveolar lavage fluid (BALF), examining lung tissue for histopathological changes, conducting immunohistochemistry, RT‒qPCR, ELISA, and Western blotting. RESULTS: In JPYF II, 88 bioactive ingredients were predicted to have a total of 342 targets. After conducting Venn analysis, it was discovered that 284 potential targets of JPYF II were linked to the provision of defensive benefits against COPD. The PPI network yielded a total of twenty-four core targets. The findings from the analysis of enrichment and gene‒pathway network suggested that JPYF II targeted Hsp90, MAPKs, ERK, AP-1, TNF-α, IL-6, COX-2, CXCL8, and MMP-9 as crucial elements for COPD treatment through the IL-17 pathway. Additionally, JPYF II might modulate MAPK signaling pathways and the downstream transcription factor AP-1 via IL-17 regulation. According to the findings from molecular docking, it was observed that the 24 core target proteins exhibited robust binding affinities towards the top 10 bioactive compounds. Furthermore, the treatment of COPD through the regulation of MAPKs in the IL-17 pathway was significantly influenced by flavonoids and sterols found in JPYF II. In vitro, these observations were further confirmed. In vivo results demonstrated that JPYF II reduced inflammatory cell infiltration in pulmonary tissues and the quantity of inflammatory cells in BALF obtained from LPS- and CS-stimulated mice. Moreover, the administration of JPYF II resulted in the inhibition of IL-17 mRNA and protein levels, phosphorylation levels of MAPK proteins, and expression of phosphorylated AP-1 proteins. It also suppressed the expression of downstream effector genes and proteins associated with the IL-17/MAPK/AP-1 signaling axis in lung tissues and BALF. CONCLUSION: This research reveals that JPYF II improves COPD by controlling the IL-17/MAPK/AP-1 signaling axis within the IL-17 pathway for the first time. These findings offer potential approaches for the creation of novel medications that specifically target IL-17 and proteins involved in the IL-17 pathway to address COPD.

The antimicrobial property of JY-1, a complex mixture of Traditional Chinese Medicine, is linked to it abilities to suppress biofilm formation and disrupt membrane permeability.

The substantial increase of infections, caused by novel, sudden, and drug-resistant pathogens, poses a significant threat to human health. While numerous studies have demonstrated the antibacterial and antiviral effects of Traditional Chinese Medicine, the potential of a complex mixture of traditional Chinese Medicine with a broad-spectrum antimicrobial property remains underexplored. This study aimed to develop a complex mixture of Traditional Chinese Medicine (TCM), JY-1, and investigate its antimicrobial properties, along with its potential mechanism of action against pathogenic microorganisms. Antimicrobial activity was assessed using a zone of inhibition assay and the drop plate method. Hyphal induction of Candida albicans was conducted using RPMI1640 medium containing 10% FBS, followed by microscopic visualization. Quantitative real-time PCR (RT-qPCR) was employed to quantify the transcript levels of hyphal-specific genes such as HWP1 and ALS3. The impact of JY-1 on biofilm formation was evaluated using both the XTT reduction assay and scanning electron microscopy (SEM). Furthermore, the cell membrane integrity was assessed by protein and nucleic acid leakage assays. Our results clearly showed that JY-1 significantly inhibits the vegetative growth of Candida spp. and Cryptococcus spp. In addition, this complex mixture is effectively against a wide range of pathogenic bacteria, including Staphylococcus aureus, Vancomycin-resistant enterococci, Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae. More interestingly, JY-1 plays a direct anti-viral role against the mammalian viral pathogen vesicular stomatitis virus (VSV). Further mechanistic studies indicate that JY-1 acts to reduce the expression of hyphal specific genes HWP1 and ALS3, resulting in the suppression of the hyphal formation of C. albicans. The antimicrobial property of JY-1 could be attributed to its ability to reduce biofilm formation and disrupt the cell membrane permeability, a process resulting in microbial cell death and the release of cellular contents. Taken together, our work identified a potent broad-spectrum antimicrobial agent, a complex mixture of TCM which might be developed as a potential antimicrobial drug.

Study on the solidification performance and mechanism of heavy metals by sludge/biomass ash ceramsites, biochar and biomass ash.

Industrial by-products are stored in large quantities in the open, leading to wasted resources and environmental pollution, and the natural environment is similarly faced with phosphate depletion and serious water and soil pollution. This study uses these by-products to produce a new sludge/biomass ash ceramsite that will be used to adsorb nitrogen and phosphorus from wastewater, and solidify heavy metals in the soil while releasing Olsen P. The sludge/biomass ash ceramsites are made using sewage sludge and biomass ash in a certain ratio calcined at high temperatures and modified for the adsorption of nitrogen and phosphorus from wastewater. Sludge/biomass ash ceramsites before and after phosphorus adsorption, biochar and biomass ash were compared to analyze their heavy metal adsorption capacity and potential as phosphate fertilizer. After phosphorus adsorption, the sludge/biomass ash ceramsites released effective phosphorus steadily and rapidly in the soil, with a greater initial release than biochar and biomass ash, and the ceramsites were in a granular form that could be easily recycled. Biochar and biomass residue, due to their surface functional groups, are better at solidifying heavy metals than sludge/biomass ash ceramsites. Biochar, biomass ash and sludge/biomass ash ceramsites significantly reduced the concentrations of Cd, Cu, Pb and Zn in the soil. Correlation analysis demonstrated that there was a synergistic relationship between the increase in soil Olsen P content and the change in pH, with the increase in soil Olsen P content and the increase in pH contributing to heavy metal solidification.

Electrochemical treatment of wastewaters containing metal-organic complexes: A one-step approach for efficient metal complex decomposition and selective metal recovery.

Metal-organic complexes, especially those of ethylenediaminetetraacetic acid (EDTA) with metals such as copper (Cu) and nickel (Ni) (denoted here as Cu-EDTA and Ni-EDTA), are common contaminants in wastewaters from chemical and plating industries. In this study, a multi-electrode (ME) system using a two-chamber reactor and two pairs of electrodes is proposed for simultaneous electrochemical oxidation of a wastewater containing both Cu-EDTA and Ni-EDTA complexes as well as separation and selective recovery of Cu and Ni onto two different cathodes via electrodeposition. Our results demonstrate that the ME system successfully achieved 90% EDTA removal, 99% solid Cu recovery at the Cu recovery cathode and 56% Ni recovery (33.3% on the Ni recovery cathode and 22.6% in the solution) after a four-hour operation. The system further achieved 85.5% Ni recovery after consecutive five cycles of operation for 20 h. While Cu removal was mainly driven by the direct reduction of EDTA-complexed Cu(II) at the cathode, oxidation of EDTA within the Ni-EDTA complex at the anode was a prerequisite for Ni removal. The oxidation of metal-bound EDTA and free EDTA was driven by •OH and direct electron transfer on the PbO2 anode surface and graphite anode, respectively. We further show that ME system performs well for all pH conditions, treatment of real wastewaters as well as wastewaters containing other metals ions (Cr and Zn) along with Cu/Ni. The separation efficiency of Cu and Ni is dependent on applied electrode potential as well as nature and concentration of binding ligand present with comparatively lower separation efficiency achieved in the presence of weaker binding capacity and/or at lower ligand concentration and lower applied electrode potential. As such, some optimization of electrode potential is required depending on the nature/concentration of ligands in the wastewaters. Overall, this study provides new insights into the design and operation of EAOP technology for effective organic abatement and metal recovery from wastewaters containing mixtures of various metal-organic complexes.

Electroacupuncture promotes the repair of the damaged spinal cord in mice by mediating neurocan-perineuronal net.

AIMS: This study aimed to investigate the effect of perineuronal net (PNN) and neurocan (NCAN) on spinal inhibitory parvalbumin interneuron (PV-IN), and the mechanism of electroacupuncture (EA) in promoting spinal cord injury (SCI) repair through neurocan in PNN. METHODS: A mouse model of SCI was established. Sham-operated mice or SCI model mice were treated with chondroitin sulfate ABC (ChABC) enzyme or control vehicle for 2 weeks (i.e., sham+veh group, sham+ChABC group, SCI+veh group, and SCI+ChABC group, respectively), and then spinal cord tissues were taken from the T10 lesion epicenter for RNA sequencing (RNA-seq). MSigDB Hallmark and C5 databases for functional analysis, analysis strategies such as differential expression gene analysis (DEG), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), and protein-protein interaction (PPI). According to the results of RNA-seq analysis, the expression of NCAN was knocked down or overexpressed by virus intervention, or/and EA intervention. Polymerase chain reaction (PCR), immunofluorescence, western blot, electrophysiological, and behavioral tests were performed. RESULTS: After the successful establishment of SCI model, the motor dysfunction of lower limbs, and the expression of PNN core glycan protein at the epicenter of SCI were reduced. RNA-seq and PCR showed that PNN core proteoglycans except NCAN showed the same expression trend in normal and injured spinal cord treated with ChABC. KEGG and GSEA showed that PNN is mainly associated with inhibitory GABA neuronal function in injured spinal cord tissue, and PPI showed that NCAN in PNN can be associated with inhibitory neuronal function through parvalbumin (PV). Calcium imaging showed that local parvalbumin interneuron (PV-IN) activity decreased after PNN destruction, whether due to ChABC treatment or surgical bruising of the spinal cord. Overexpression of neurocan in injured spinal cord can enhance local PV-IN activity. PCR and western blot suggested that overexpression or knockdown of neurocan could up-regulate or down-regulate the expression of GAD. At the same time, the activity of PV-IN in the primary motor cortex (M1) and the primary sensory cortex of lower (S1HL) extremity changed synchronously. In addition, overexpression of neurocan improved the electrical activity of the lower limb and promoted functional repair of the paralyzed hind limb. EA intervention reversed the down-regulation of neurocan, enhanced the expression of PNN in the lesioned area, M1 and S1HL. CONCLUSION: Neurocan in PNN can regulate the activity of PV-IN, and EA can promote functional recovery of mice with SCI by upregulating neurocan expression in PNN.

Efficacy and safety of Tanreqing injection for cough caused by acute trachea-bronchitis disease: A systematic review and meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Tanreqing injection (TRQI) is an intravenous herbal preparation derived from 5 types of traditional Chinese medicines including Scutellariae Radix, Lonicerae Japonicae Flos, Forsythiae Fructus, bear bile powder and goral horn, incorporating baicalin, chlorogenic acid, ursodeoxycholic acid, and goose deoxycholic acid and other compounds known for anti-inflammatory properties, is widely used in China to treat cough caused by acute trachea-bronchitis disease (ATB). AIM OF THE STUDY: To investigate the clinical efficacy and safety of Tanreqing injection (TRQI) with and without Western medicine (WM) for cough caused by acute trachea-bronchitis (ATB). MATERIALS AND METHODS: We systematically searched eight databases, including CENTRAL, Embase, PubMed, Science Direct, Wiley, China National Knowledge Infrastructure, Chinese Biomedical Literature Database and WanFang, from inception to August 2023 for randomized clinical trials (RCTs) on TRQI for cough caused by ATB. The critical outcomes of interest were time to symptom disappearance, including time for cough symptom to disappear and time to improve cough and sputum production. Important outcomes included symptom disappearance rate, adverse events (AEs) and lung function. We carried out random-effects meta-analysis using Review Manager 5.4 and assessed the certainty of evidence utilizing the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: A total of 2872 citations were identified by our search, of which 26 eligible RCTs enrolled 2731 participants. Low to moderate certainty evidence showed that when compared with WM, TRQI plus WM treatment was associated with a favorable effect on the time for cough symptom to disappear (MD -2.21 d, 95% CI -2.64 to -1.78), time to improve cough and sputum production (MD -0.68 d, 95% CI -0.83 to -0.53), symptom disappearance rate (RR 1.37, 95% CI 1.20 to 1.55), forced vital capacity, and forced expiratory volume in 1 s (MD 0.38 L, 95% CI 0.26 to 0.50; MD 2.92%, 95% CI 1.29 to 4.56, respectively). In terms of AEs, there was no association between TRQI plus WM and WM (RR 0.55, 95% CI 0.14 to 2.21; low-certainty evidence). Very low certainty evidence showed that TRQI alone was associated with reduced time to improve cough and sputum (MD -0.14 d, 95% CI -0.26 to -0.02) and increased symptom disappearance rate (RR 1.89, 95% CI 1.24 to 2.88; low certainty evidence) compared to WM. CONCLUSIONS: The overall efficacy of TRQI or WM for ATB cough is better than that of WM, and TRQI also effectively improve symptoms in patients with similar adverse events. However, due to the lack of methodological rigor of included studies, the present findings should be interpreted with caution. We advocate better high-quality and convincing clinical studies to be performed to prove the effectiveness and safety of TRQIs.

Molecular dynamics study on the interaction of phosphorus building gypsum /surfactant composites.

While surfactants are widely used in phosphogypsum, their interactions with the phosphogypsum-water interface remain unclear. This study investigates the impact of three types of surfactants, namely polycarboxylate-based surfactant (PCE-TPEG), naphthalene-based surfactant (NS), and melamine-based surfactant (MS), on the performance of phosphorus building gypsum (PBG). Additionally, a nanoscale model of the PBG-surfactant-water interface is constructed using molecular dynamics to elucidate the mechanisms underlying the interaction between different surfactants and PBG at multiple scales. The results demonstrate that all surfactants enhance the mechanical properties of PBG. PCE-TPEG exhibits the most pronounced improvement. In the model, PCE-TPEG molecules likely undergo comb-like adsorption, while NS and MS molecules tend to adsorb on both ends of the crystal plane. Changes in the potential difference between CaSO4·2H2O and H2O, as well as between CaSO4·2H2O and the surfactant, play a crucial role in adsorption. PCE-TPEG, NS, and MS molecules tend to spread horizontally in a vacuum state. With the addition of water molecules, they transition to spatial adsorption. Ca2+ easily interacts with -COO- and -SO3- groups, leading to reduced migration and flexibility of the main chain. The adsorption process of surfactants at the gypsum-water interface occurs spontaneously and Electrostatic forces are the main driving factor. This study contributes to a more comprehensive understanding on the behaviour of the phosphorus building gypsum/surfactant composites.

A spatial optimal allocation method considering multi-attribute decision making and multiple BMPs random combination in sub-watersheds.

Best management practices (BMPs) have been extensively employed in effective watershed management for non-point source pollution. The weights of objective functions and the restrictive conditions of combined BMPs are the vital requirements for BMPs allocation. Therefore, it is more beneficial to explore that a spatial optimal allocation method considering multi-attribute decision making and multiple BMPs random combination. Here is the novel framework based on Soil and Water Assessment Tool (SWAT) and the Non-dominated Sorting Genetic Algorithm II (NSGA-Ⅱ), which considers multiple objectives in deriving watershed-scale pollution control practices by considering BMPs cost and combined reduction rates of total nitrogen (TN) and total phosphorus (TP). The framework also integrates combined Entropy Weight method (EWM) and Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) to solve the weights of TN and TP, and considers the attributes of the sub-basin itself, which is more local suitability. Four categories of BMPs, tillage management, nutrient management, vegetative filter strips, and landscape management, were evaluated in the Jing River Basin (JRB) and resulted in reduction rates of 9.77%, 10.53%, 16.40%, and 14.27% averagely, respectively. BMP allocation schemes, derived from multi-objective optimization, are stratified into three financial scenarios. Low-cost scenario, costing up to 2 billion RMB, primarily targets the grain for green program in 28.81% of sub-basins. Medium-cost scenario, between 2 and 6 billion RMB, predominantly utilizes the grain for green in areas with a slope greater than 15°, accounting for 20.00% of sub-basins. High-cost scenario exceeds 6 billion RMB, mainly due to the implementation of multiple combination measures. The three configuration scenarios can provide decision-makers with a trade-off between measure costs and reduction efficiency. Overall, the innovative framework not only facilitates cost-effective implementation but provides a beneficial methodology for selecting cost-effective conservation practices in other regions.

Cellular crosstalk of macrophages and therapeutic implications in non-small cell lung cancer revealed by integrative inference of single-cell transcriptomics.

Introduction: Non-small cell lung cancer (NSCLC) exhibits heterogeneity with diverse immune cell infiltration patterns that can influence tumor cell behavior and immunotherapy. A comprehensive characterization of the tumor microenvironment can guide precision medicine. Methods: Here, we generated a single-cell atlas of 398170 cells from 52 NSCLC patients, and investigated the imprinted genes and cellular crosstalk for macrophages. Subsequently, we evaluated the effect of tumor cells on macrophages and verified the expression of marker genes using co-culture experiments, flow cytometry and RT-qPCR assays. Results: Remarkable macrophage adaptability to NSCLC environment was observed, which contributed to generating tumor-associated macrophages (TAMs). We identified 5 distinct functional TAM subtypes, of which the majority were SELENOP-positive macrophages, with high levels of SLC40A1 and CCL13. The TAMs were also involved in mediating CD8+ T cell activity and form intercellular interaction with cancer cells, as indicated by receptor-ligand binding. Indirect coculture of tumor cells SPC-A1 and THP-1 monocytes, produced M2-like TAMs that highly expressed several markers of SELENOP-positive macrophages. The abundance of this type TAMs seemed to be associated with poorer overall survival rates [hazard ratio (HR) = 1.34, 95% confidence interval (CI) = 0.98-1.83, p = 0.068] based on deconvolution of TCGA-LUAD dataset. Discussion: In summary, we provided a high-resolution molecular resource of TAMs, and displayed the acquired properties in the tumor microenvironment. Dynamic crosstalk between TAMs and tumor cells via multiple ligand-receptor pairs were revealed, emphasizing its role in sustaining the pro-tumoral microenvironment and its implications for cancer therapy.

Supplementation with high-GABA-producing Lactobacillus plantarum L5 ameliorates essential tremor triggered by decreased gut bacteria-derived GABA.

BACKGROUND: The γ-aminobutyric acid (GABA) hypothesis posits a role of GABA deficiency in the central nervous system in the pathogenesis and progression of essential tremor (ET). However, the specific causative factor for GABA deficiency is not clear. The gut microbiota in mammals has recently been considered as a significant source of GABA. Furthermore, the GABA-based signals originating from the intestine can be transmitted to the brain through the "enteric nervous system-vagus nerve-brain" axis. However, the plausible contribution of gut microbiota to ET seems inspiring but remains obscure. METHODS: Fecal samples from patients with ET and healthy controls were examined by metagenomic sequencing to compare the composition of gut microbiota and the expression of genes involved in GABA biosynthesis. The impact of gut microbiota on ET was explored through transplantation of fecal microbiota from patients with ET into the murine ET model. Lactic acid bacteria producing high amounts of GABA were identified through whole-genome sequencing and ultra-performance liquid chromatography-tandem mass spectrometry. Subsequently, mice were treated with the high-GABA-producing strain Lactobacillus plantarum L5. Tremor severity, behavioral tests, pro-inflammatory cytokines, GABA concentration, and gut microbiota composition were examined in these mice. RESULTS: The gut microbiota of patients with ET demonstrated an impaired GABA-producing capacity and a reduced fecal GABA concentration. Transplantation of the gut microbiota from patients with ET induced an extension of tremor duration and impaired mobility in the murine model of ET. L5 exhibited an augmented GABA-producing capacity, with the De Man-Rogosa-Sharpe culture broth containing 262 mg/l of GABA. In addition, administration of L5 significantly decreased the tremor severity and enhanced the movement capability and grasping ability of ET mice. In vivo mechanistic experiments indicated that L5 reshaped the gut microbial composition, supplemented the mucosa-associated microbiota with GABA-producing capacity, increased the GABA concentrations in the cerebellum, and diminished inflammation in the central nervous system. CONCLUSIONS: These findings highlight that deficiency of GABA-producing gut microbes plays an essential role in the pathogenesis of ET and that L5 is a promising candidate for treating ET.

A telomere-to-telomere reference genome provides genetic insight into the pentacyclic triterpenoid biosynthesis in Chaenomeles speciosa.

Chaenomeles speciosa (2n = 34), a medicinal and edible plant in the Rosaceae, is commonly used in traditional Chinese medicine. To date, the lack of genomic sequence and genetic studies has impeded efforts to improve its medicinal value. Herein, we report the use of an integrative approach involving PacBio HiFi (third-generation) sequencing and Hi-C scaffolding to assemble a high-quality telomere-to-telomere genome of C. speciosa. The genome comprised 650.4 Mb with a contig N50 of 35.5 Mb. Of these, 632.3 Mb were anchored to 17 pseudo-chromosomes, in which 12, 4, and 1 pseudo-chromosomes were represented by a single contig, two contigs, and four contigs, respectively. Eleven pseudo-chromosomes had telomere repeats at both ends, and four had telomere repeats at a single end. Repetitive sequences accounted for 49.5% of the genome, while a total of 45 515 protein-coding genes have been annotated. The genome size of C. speciosa was relatively similar to that of Malus domestica. Expanded or contracted gene families were identified and investigated for their association with different plant metabolisms or biological processes. In particular, functional annotation characterized gene families that were associated with the biosynthetic pathway of oleanolic and ursolic acids, two abundant pentacyclic triterpenoids in the fruits of C. speciosa. Taken together, this telomere-to-telomere and chromosome-level genome of C. speciosa not only provides a valuable resource to enhance understanding of the biosynthesis of medicinal compounds in tissues, but also promotes understanding of the evolution of the Rosaceae.

Research Note: Transcriptome analysis reveals differentially expressed genes regulated muscle development in Pekin ducks during dietary threonine deficiency.

To investigate the underlying molecular mechanism of threonine (Thr) regulation on the development of breast muscle in Pekin ducks, 240 male Pekin ducks at 1 d of age were fed a Thr deficiency diet (Thr-D), Thr sufficiency diet (Thr-S), or Thr excess diet (Thr-E) for 21 d. The results showed that Thr-D reduced body weight (BW), average weight gain (ADG), and average feed intake (ADFI), and increased the feed/gain (F/G) in Pekin ducks (P < 0.05), and Thr-E did not affect BW, ADG, ADFI, or F/G (P > 0.05), compared with Thr-S. The diameter and cross-sectional area of the breast muscle fibers in the Thr-S group were larger than those in the Thr-D group (P < 0.05). RNA sequencing revealed 1,300 differential expressed genes (DEGs) between the Thr-D and Thr-S groups, of which 625 were upregulated and 675 were downregulated by Thr-D. KEGG analysis showed that the upregulated genes were enriched in mTOR, FoxO, Wnt, fat digestion and absorption, and other signaling pathways. The downregulated genes were enriched in the MAPK signaling, glycolysis/gluconeogenesis, adipocytokine signaling, and biosynthesis of unsaturated fatty acids signaling pathways. The genes of Wnt family member 3a (Wnt3a), myogenin, myozenin 2, and insulin like growth factor 2 mRNA binding protein were upregulated, and platelet derived growth factor subunit B, PDGF receptor beta and Wnt4 were downregulated by Thr deficiency, which involving in muscle development. Our findings indicated that Thr increased breast fiber size, perhaps because Thr affected the proliferation and differentiation of satellite cells in breast muscle of ducks after hatch. Our results provide novel insights into new understanding of the molecular mechanisms underlying breast muscle development in ducks subjected to dietary Thr.

Bu-Fei Yi-Shen Granules Reduce Acute Exacerbations in Patients with GOLD 3-4 COPD: A Randomized Controlled Trial.

Purpose: Chronic obstructive pulmonary disease (COPD) is a disease characterized by frequent acute exacerbations (AEs), especially in severe and very severe cases. We aimed to evaluate the efficacy and safety of Bu-fei Yi-shen granules (BYGs) for COPD. Patients and Methods: We conducted a multicenter, randomized, double-blinded, placebo-controlled trial of 348 COPD patients with GOLD 3-4 COPD. The patients were randomly assigned into experimental or control groups in a 1:1 ratio. Patients in the experimental group were prescribed BYG, while those in the control group were administered a placebo, orally, twice daily, with 5 days on and 2 days off per week for 52 weeks. The outcomes included AEs, pulmonary function, clinical signs and symptoms, dyspnea scores (mMRC), quality of life scores, and a 6-minute walk test (6MWT). Results: A total of 280 patients completed the trial, including 135 patients in the experimental group and 145 in the control group. Compared to the control group, significant differences were observed in frequencies of AEs (mean difference: -0.35; 95% CI: -0.61, -0.10; P = 0.006) and AE-related hospitalizations (-0.18; 95% CI: -0.36, -0.01; P = 0.04), 6MWD (40.93 m; 95% CI: 32.03, 49.83; P < 0.001), mMRC (-0.57; 95% CI: -0.76, -0.37; P < 0.001), total symptoms (-2.18; 95% CI: -2.84, -1.53; P < 0.001), SF-36 (11.60; 95% CI: 8.23, 14.97; P < 0.001), and mCOPD-PRO (-0.45; 95% CI: -0.57, -0.33; P < 0.001) after treatment. However, there were no significant differences in mortality, pulmonary function, and mESQ-PRO scores (P > 0.05). No obvious adverse events were observed. Conclusion: BYG, as compared to a placebo, could significantly reduce the frequencies of AEs and AE-related hospitalizations for GOLD 3-4 COPD patients. Clinical symptoms, treatment satisfaction, quality of life, and exercise capacity improved. There was no significant improvement in mortality and pulmonary function.

Effectiveness and safety of Xingbei Zhike granules in patients with postinfectious cough: A multicenter, randomized, double-blinded, placebo-controlled trial.

BACKGROUND: Postinfectious cough (PIC) is a common symptom following a respiratory tract infection. Xingbei Zhike (XBZK) granules, a Chinese patent medicine, has been widely used for PIC in clinics. However, there is a lack of evidence on the effectiveness. PURPOSE: To investigate whether treatment with XBZK granules is effective for PIC. STUDY DESIGN: A multicenter, randomized, double-blinded, placebo-controlled trial. METHODS: Eligible participants from fourteen hospitals were randomly assigned in 3:1 ratio to receive either XBZK granules or placebo for 14 days. The primary outcome was the area under the curve (AUC) of a visual analogue scale (VAS) for cough symptoms. Secondary outcomes included cough symptom score (CSS), time and probability of recovery from cough, traditional Chinese medicine (TCM) syndrome score, relief rates of individual symptoms, Leicester Cough Questionnaire (LCQ) score, and the use of reliever drug. RESULTS: A total of 235 patients (176 in XBZK and 59 in placebo groups) were included in the analysis. The AUC for cough VAS scores was lower in the XBZK than placebo group (-8.10, 95 % CI -14.12 to -2.07, p = 0.009), indicating superiority. XBZK decreased CSS (-0.68 points, 95 % CI -1.13 to -0.22, p = 0.01), shortened time to cough recovery (-2 days, hazard ratio [HR] 1.48, 95 % CI 1.03 to 2.13, p = 0.02), enhanced the probability of cough recovery (risk ratio [RR] 1.66, 95 % CI 1.07 to 2.58, p = 0.03), lowered TCM syndrome score (-0.99 points, 95 % CI -1.58 to -0.40, p = 0.004), increased the rate of daytime (RR 1.84, 95 % CI 1.07 to 3.15, p = 0.02) and nighttime (RR 2.07, 95 % CI 1.29 to 3.35, p = 0.004) cough recovery, and reduced the viscosity of sputum (RR 2.92, 95 % CI 1.66 to 5.13, p < 0.001) compared to placebo. There were no significant differences in LCQ scores and taking reliever drugs between groups. No severe adverse events were reported in either group. CONCLUSIONS: XBZK granules are a promising therapy against PIC, effective in lowering the overall severity of cough, shortening the time to cough recovery, and reducing the viscosity of sputum.

Qualitative and quantitative analyses of chemical constituents in vitro and in vivo and systematic evaluation of the pharmacological effects of Tibetan medicine Zhixue Zhentong capsules.

Introduction: Zhixue Zhentong capsules (ZXZTCs) are a Tibetan medicine preparation solely composed of Lamiophlomis rotata (Benth.) Kudo. L. rotata is the only species of the genus Laniophlomis (family Lamiaceae) that has medicinal constituents derived from the grass or root and rhizome. L. rotata is one of the most extensively used folk medicines by Tibetan, Mongolian, Naxi, and other ethnic groups in China and has been listed as a first-class endangered Tibetan medicine. The biological effects of the plant include hemostasis, analgesia, and the removal of blood stasis and swelling. Purpose: This study aimed to profile the overall metabolites of ZXZTCs and those entering the blood. Moreover, the contents of six metabolites were measured and the hemostatic, analgesic, and anti-inflammatory effects of ZXZTCs were explored. Methods: Ultra-performance liquid chromatography-tandem quadrupole time-of-flight high-resolution mass spectrometry (UPLC-Q-TOF-MS) was employed for qualitative analysis of the metabolites of ZXZTCs and those entering the blood. Six metabolites of ZXZTCs were quantitatively determined via high-performance liquid chromatography The hemostatic, analgesic, and anti-inflammatory effects of ZXZTCs were evaluated in various animal models. Results: A total of 36 metabolites of ZXZTCs were identified, including 13 iridoid glycosides, 9 flavonoids, 9 phenylethanol glycosides, 4 phenylpropanoids, and 1 other metabolite. Overall, 11 metabolites of ZXZTCs entered the blood of normal rats. Quantitative analysis of the six main metabolites, shanzhiside methyl ester, chlorogenic acid, 8-O-acetyl shanzhiside methyl ester, forsythin B, luteoloside, and verbascoside, was extensively performed. ZXZTCs exerted hemostatic effects by reducing platelet aggregation and thrombosis and shortening bleeding time. Additionally, ZXZTCs clearly had an analgesic effect, as observed through the prolongation of the latency of writhing, reduction in writhing, and increase in the pain threshold of experimental rats. Furthermore, significant anti-inflammatory effects of ZXZTCs were observed, including a reduction in capillary permeability, the inhibition of foot swelling, and a reduction in the proliferation of granulation tissue. Conclusion: Speculative identification of the overall metabolites of ZXZTCs and those entering the blood can provide a foundation for determining its biologically active constituents. The established method is simple and reproducible and can help improve the quality control level of ZXZTCs as a medicinal product. Evaluating the hemostatic, analgesic, and anti-inflammatory activities of ZXZTCs can help reveal its mechanism.