Potential antidepressant effects of Traditional Chinese botanical drug formula Chaihu-Shugan-San and its active ingredients.

Background: Depression is a severe mental disorder that poses a significant threat to both the physical and mental wellbeing of individuals. Currently, there are various methods for treating depression, including traditional Chinese herbal formulations like Chaihu-Shugan-San (CSS), which have shown effective antidepressant effects in both clinical and animal research. Objective: This review aims to provide a comprehensive synthesis of evidence related to CSS, considering both preclinical and clinical studies, to uncover its potential multi-level, multi-pathway, and multi-target mechanisms for treating depression and identify its active ingredients. Methods: A thorough search was conducted in electronic databases, including PubMed, MEDLINE, Web of Science, Google Scholar, CNKI, and Wanfang, using keywords such as "Chaihu Shugan" and "depression" to retrieve relevant literature on CSS and its active ingredients. The review process adhered to the PRISMA guidelines. Results: This review consolidates the mechanisms underlying antidepressant effects of CSS and its active ingredients. It emphasizes its involvement in the regulation of monoaminergic neurotransmitter systems, synaptic plasticity, and the hypothalamic-pituitary-adrenal axis, among other aspects. Conclusion: CSS exerts a pivotal role in treating depression through various pathways, including the monoaminergic neurotransmitter system, the hypothalamic-pituitary-adrenal axis, synaptic plasticity, inflammation, brain-derived neurotrophic factor levels, and the brain-gut axis. This review facilitates a comprehensive understanding of the current state of CSS research, fostering an in-depth exploration of the etiological mechanisms of depression and the potential discovery of novel antidepressant drugs.

A novel bHLH gene responsive to low nitrogen positively regulates the biosynthesis of medicinal tropane alkaloids in Atropa belladonna.

Medicinal tropane alkaloids (TAs), including hyoscyamine, anisodamine and scopolamine, are essential anticholinergic drugs specifically produced in several solanaceous plants. Atropa belladonna is one of the most important medicinal plants that produces TAs. Therefore, it is necessary to cultivate new A. belladonna germplasm with the high content of TAs. Here, we found that the levels of TAs were elevated under low nitrogen (LN) condition, and identified a LN-responsive bHLH transcription factor (TF) of A. belladonna (named LNIR) regulating the biosynthesis of TAs. The expression level of LNIR was highest in secondary roots where TAs are synthesized specifically, and was significantly induced by LN. Further research revealed that LNIR directly activated the transcription of hyoscyamine 6ß-hydroxylase gene (H6H) by binding to its promoter, which converts hyoscyamine into anisodamine and subsequently epoxidizes anisodamine to form scopolamine. Overexpression of LNIR upregulated the expression levels of TA biosynthesis genes and consequently led to the increased production of TAs. In summary, we functionally identified a LN-responsive bHLH gene that facilitated the development of A. belladonna with high-yield TAs under the decreased usage of nitrogen fertilizer.

Dehydrocostus lactone alleviates irinotecan-induced intestinal mucositis by blocking TLR4/MD2 complex formation.

BACKGROUND: Irinotecan (CPT-11) is used as chemotherapeutic drug for treatment of colorectal cancer. However, without satisfactory treatments, its gastrointestinal toxicities such as diarrhea and intestinal inflammation severely restrained its clinical application. Roots of Aucklandia lappa Decne. are used as traditional Chinese medicine to relieve gastrointestinal dysfunction and dehydrocostus lactone (DHL) is one of its main active components. Nevertheless, the efficacy and mechanism of DHL against intestinal mucositis remains unclear. PURPOSE: The present study aimed to investigate the protective effects of DHL on CPT-11-induced intestinal mucositis and its underlying mechanisms. METHODS: The protective effect of DHL was investigated in CPT-11-induced mice and lipopolysaccharide (LPS)+CPT-11 induced THP-1 macrophages. Body weight, diarrhea score, survival rate, colon length, and histopathological changes in mice colon and jejunum were analyzed to evaluate the protective effect of DHL in vivo. And DHL on reducing inflammatory response and regulating TLR4/NF-κB/NLRP3 pathway in vivo and in vitro were explored. Moreover, DHL on the interaction between TLR4 and MD2 was investigated. And silencing TLR4 targeted by siRNA was performed to validate the mechanisms of DHL on regulating the inflammation. RESULTS: DHL prevented CPT-11-induced intestinal damage, represented by reducing weight loss, diarrhea score, mortality rate and the shortening of the colon. Histological analysis confirmed that DHL prevented intestinal epithelial injury and improved the intestinal barrier function in CPT-11 induced mice. Besides, DHL significantly downregulated the level of inflammatory cytokines by inhibiting TLR4/NF-κB/NLRP3 signaling pathway in CPT-11-induced mice and LPS+CPT-11-induced THP-1 macrophages. In addition, DHL blocked TLR4/MD2 complex formation. Molecular docking combined with SIP and DARTS assay showed that DHL could bind to TLR4/MD2 and occludes the hydrophobic pocket of MD2. Furthermore, Silencing TLR4 abrogated the effect of DHL on LPS+CPT-11 induced inflammatory response in THP-1 macrophages. Additionally, DHL ameliorate the CPT-11-induced intestinal mucositis without affecting the anti-tumor efficacy of CPT-11 in the tumor xenograft mice. CONCLUSION: This study found that DHL exhibited the anti-inflammatory effects in CPT-11-induced intestinal mucositis by inhibiting the formation of TLR4/MD2 complex and then regulation of NF-κB/NLRP3 signaling pathway. DHL is potentially served as a novel strategy of combined medication with CPT-11.

Dracotangusions A and B, two new sesquiterpenes from Dracocephalum tanguticum Maxim. with anti-inflammatory activity.

Two new guaiane sesquiterpenoids were isolated from the dried aerial parts of Dracocephalum tanguticum Maxim., named as dracotangusions A (1) and B (2), together with four known sesquiterpenoids, which were identified as Curcumenone (3), (4Z,7Z,9Z)-11-Hydroxy-4,7,9-germacratriene-1,6-dione (4), Kobusone (5), and (1S,10S), (4S, 5S)-(+)-germacrone-1(10)-4-diepoxide (6). The structures of isolates were determined by UV, IR, HR-ESI-MS, and NMR analysis. What is noteworthy is that four known sesquiterpenoids were isolated for the first time from the genus of Dracocephalum L. All compounds inhibited the extremely significant difference (p < 0.01) in anti-inflammatory activity, suggesting that these compounds may be promising candidates as an anti-inflammatory agent.

The Effect and Mechanism of Fructus lycii on Improvement of Exercise Fatigue Using a Network Pharmacological Approach with in vitro Experimental Verification.

Objective: This study aimed to investigate the effect and underlying mechanism of Fructus lycii in improving exercise fatigue. Methods: A network pharmacological approach was used to explore potential mechanisms of action of Fructus lycii. Skeletal muscle C2C12 cells and immunofluorescence were employed to verify the effect and mechanism of the representative components in Fructus lycii predicted by network pharmacological analysis. Results: Six potential active components, namely quercetin, ß-sitosterol, stigmasterol, 7-O-methylluteolin-6-C-beta-glucoside_qt, atropine, and glycitein, were identified to have potency in improving exercise fatigue via multiple pathways, such as the PI3K-Akt, neuroactive ligand-receptor interaction, IL-17, TNF, and MAPK signaling pathways. The immunofluorescence results indicated that quercetin, a significant active component in Fructus lycii, increased the mean staining area of 2-NBDG, TMRM, and MitoTracker, and decreased the area of CellRox compared to the control. Furthermore, the protein expression levels of p-38 MAPK, p-MAPK, p-JNK, p-PI3K, and p-AKT markedly increased after quercetin treatment. Conclusion: Fructus lycii might alleviate exercise fatigue through multiple components and pathways. Among these, quercetin appears to improve exercise fatigue by enhancing energy metabolism and reducing oxidative stress. The PI3K-AKT and MAPK signaling pathways also appear to play a role in this process.

Research progress on mechanism of acupuncture in treating functional constipation. / é’ˆåˆºæ²»ç–—åŠŸèƒ½æ€§ä¾¿ç§˜çš„æœºåˆ¶ç ”ç©¶è¿›å±•.

Acupuncture treatment for functional constipation (FC) is characterized by precise efficacy, rapid onset of action in the early stages, long-term stable effects, and overall regulation. This paper reviews recent literatures on acupuncture treatment for FC, indicating that acupuncture acts from multiple perspectives and pathways, including promoting intestinal motility, regulating intestinal microbiota, modulating the brain-gut axis, alleviating intestinal inflammation, and improving rectal hyposensitivity. Future research could delve into the mechanical sensation conduction mechanisms of acupuncture in improving rectal hyposensitivity, identify key intestinal microbiota genera and metabolic characteristics regulated by acupuncture, explore the network relationships among different mechanisms, and clarify the differential mechanisms of various acupuncture treatment protocols to optimize clinical therapy and enhance the clinical efficacy of acupuncture for FC.

Does acupuncture treatment modulate inflammatory cytokines in rodent models of depression? A systematic review and meta-analysis.

Background: Despite the increasing global prevalence of depression, existing treatment methods have limitations. Acupuncture has been recognized for its potential to alleviate various diseases by regulating inflammatory cytokines. However, a comprehensive systematic analysis of the effects of acupuncture on depression through inflammatory cytokines is currently lacking. This review aims to evaluate the impact of acupuncture on inflammatory cytokines in animal models of depression. Methods: A comprehensive search was conducted in PubMed, EMBASE, MEDLINE, and the Research Information Service System to identify studies that met predefined inclusion and exclusion criteria. The quality of each included study was assessed using a 10-item checklist adapted from the Cochrane Collaboration methods and animal data review. Meta-analysis was performed using STATA 17.0 software for literature that met the inclusion criteria. Results: The meta-analysis included a total of 21 studies involving 376 rodents. The overall quality of the included reports was rated as moderate or higher. The results demonstrated that acupuncture had a significant effect on the reduction of pro-inflammatory cytokines, including: IL-1ß [SMD = 3.36, 95% CI (2.73, 4.00), I2 = 73.3%, p < 0.05], IL-6 [SMD = 3.05, 95% CI (2.45, 3.64), I2 = 68%, p < 0.05], and TNF-α [SMD = 3.30, 95% CI (2.53, 4.06), I2 = 74.5%, p < 0.05]. Conversely, acupuncture was associated with an increased expression of anti-inflammatory cytokines, notably: IL-4 [SMD = -1.64, 95% CI (-2.46, -0.82), I2 = 4.1%, p = 0.307] and IL-10 [SMD = -1.45, 95% CI (-2.24, -0.66), I2 = 0, p = 0.678]. These results suggest that acupuncture modulates cytokine levels in depressed rodents, including reducing the expression of pro-inflammatory cytokines and increasing the expression of anti-inflammatory cytokines, thereby regulating the immune-related antidepressant pathway. Conclusion: While this study is limited by the number of included studies, the results suggest that acupuncture may be a viable option for the treatment of depression, and this effect is achieved through the regulation of various inflammatory cytokines. Systematic review registration: This research endeavor was duly registered with PROSPERO (ID: CRD42023420919, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=420919).

The complete chloroplast genome sequence of Thladiantha nudiflora Hemsl. ex F.B.Forbes & Hemsl. 1887 (Cucurbitaceae).

Thladiantha nudiflora Hemsl. ex F.B.Forbes & Hemsl. 1887 (Cucurbitaceae) has been widely known as a traditional medicine plant. In this study, we sequenced, assembled, and annotated the complete chloroplast genome of T. nudiflora. The chloroplast genome of T. nudiflora is 156,824 base pair (bp) in length, containing a large single-copy region of 86,566 bp and a small single-copy region of 18,070 bp, separated by a pair of inverted repeats of 26,094 bp. The chloroplast genome contains 132 genes, including 87 protein-coding, 37 transfer RNA, and eight ribosomal RNA genes. Phylogenetic analysis of the chloroplast genome revealed that species of the genus Thladiantha were clustered together in the phylogenetic trees. This study will not only shed light on T. nudiflora's evolutionary position but also provide valuable chloroplast genomic information for future studies into the origins and diversification of the genus Thladiantha and the Cucurbitaceae family.

Plant functional traits mediate the response magnitude of plant-litter-soil microbial C: N: P stoichiometry to nitrogen addition in a desert steppe.

Global nitrogen deposition is significantly altering the carbon (C), nitrogen (N) and phosphorus (P) stoichiometry in terrestrial ecosystems, yet how N deposition simultaneously affects plant-litter-soil-soil microbial stoichiometry in arid grassland is still unclear. In a five-year experimental study conducted in a desert steppe in Northern China, we investigated the effects of N addition on the C:N:P stoichiometry of plants, litter, soil, and soil microbes. We also used structural equation modelling (SEM) exploring the direct or indirect effects of N addition, plant species diversity, functional traits and diversity, soil microbial diversity, soil pH, soil electrical conductivity (EC) and moisture on the stoichiometry in plant-soil system. The results showed that N addition increased the N, P concentrations and N:P in plants, the N concentration and N:P in litter, and the C, N concentrations, C:P and N:P in microbes. Conversely, it decreased the C:N and C:P in plants, and litter C:N. Functional traits, functional dispersion (FDis), soil pH and EC accounted for a substantial proportion of the observed variations in elemental concentrations (from 42 % to 69 %) and stoichiometry (from 9 % to 73 %) across different components. SEM results showed that N addition decreased C:N and C:P in plants and litter by increasing FDis and leaf N content, while increased plant and litter N:P by decreasing leaf C content and increasing specific leaf area, respectively. Furthermore, N addition increased microbial C:P by increasing leaf thickness. We also found the mediating effects of soil pH and EC on C:N, C:P of litter and microbial N:P. Overall, our research suggests that plant functional traits as key predictors of nutrient cycling responses in desert steppes under N addition. This study extends the application of plant functional traits, enhances our understanding of C and nutrient cycling and facilitates predicting the response of desert steppes to N deposition.

The influence mechanism of water level operation on algal blooms in canyon reservoirs and bloom prevention.

The water level operation of reservoirs affects the spatiotemporal patterns of water quality, light-heat, hydrodynamics and phytoplankton, which have implications for algal bloom prevention. However, the theoretical analysis and practical applications of related research are limited. Based on prototype observations and numerical modeling, data on algae, water level operation and environmental factors in the Zipingpu Reservoir from April and September in 2015 to 2017 and 2020 to 2022 were collected. An in-depth analysis of the causal mechanisms between algal blooms and water level operation was performed, and prevention strategies with practical application assessments were developed. Water level operation control in the reservoir from April to September can be divided into five stages (falling-rising-oscillating-falling-rising), with algal blooms occurring only in the second stage. The rising water level with inflow into the middle layers shapes a closed-loop circulation in the surface waters. This distributes the nutrients that were trapped in the surface layer during the first stage, helping algae avoid to phosphorus limitation and thrive in the closed loop circulation, leading to algal blooms (chlorophyll-a exceeding 10 mg/m3). There is a significant positive correlation (p < 0.05) between algal blooms and the rapid rise in water levels in the second stage, occurring within a span of three days. To contain the algal bloom, a water level operation limit of rising waters on the third day after a two-day consecutive rise in water level was examined. This was found to be effective after its practical application to the case reservoir in 2022, with chlorophyll-a concentrations consistently below 10 mg/m3. This study unveils the mechanisms through which water level operation affects algal blooms and presents a successful case of bloom prevention. Furthermore, it serves as a valuable reference for the management of canyon reservoirs.

Understanding apoptotic induction by Sargentodoxa cuneata-Patrinia villosa herb pair via PI3K/AKT/mTOR signalling in colorectal cancer cells using network pharmacology and cellular studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Sargentodoxa cuneata (Sargentodoxa cuneata (Oliv.) Rehder & E.H.Wilson, DXT)-Patrinia villosa(Patrinia villosa (Thunb.) Dufr, BJC) constitutes a commonly employed herb pair in Chinese medicine for colorectal cancer (CRC) treatment. Modern pharmacological investigations have revealed the anticancer activities of both Sargentodoxa cuneata and Patrinia villosa. Nevertheless, comprehensive studies are required to discern the specific antitumor active ingredients and mechanism of action when these two herbs are used in combination. AIM OF THE STUDY: Through the integration of network pharmacology, molecular docking techniques, experimental assays, and bioinformatics analysis, our study aims to forecast the active ingredients, potential targets, and molecular mechanisms underlying the therapeutic efficacy of this herb pair against CRC. MATERIALS AND METHODS: Plant names (1, Sargentodoxa cuneata (Oliv.) Rehder & E.H.Wilson; 2, Patrinia villosa (Thunb.) Dufr.) have been verified through WorldFloraOnline (www.worldFloraonline.org) and MPNs (http://mpns.kew.org). The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) were utilized for screening the active ingredients of the herb pair. The PharmMapper database was employed to predict the target proteins for each active ingredient. CRC-related targets were obtained from the Genecards database, Online Mendelian Inheritance in Man (OMIM) database, Disease Gene Network (DisGeNET) database, and Therapeutic Target Database (TTD). Common targets were identified by intersecting the target proteins of all active ingredients with CRC-related targets. Protein-protein interactions (PPI) for the common target proteins were constructed using the String database and Cytoscape 3.9.1 software. Network topology analysis facilitated the identification of core targets. These core targets were subjected to enrichment analysis of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) using the Metascape database. Molecular docking was performed using Discovery Studio 2019 to investigate the interactions between the active ingredients and core target proteins. The core targets were validated through bioinformatics analysis using GEPIA, HPA, and the cBioPortal database. Finally, a series of experiments were conducted to further validate the results in vitro. RESULT: A total of 15 active ingredients and 255 herb targets were identified, resulting in 66 common targets in conjunction with 6113 disease targets. The PPI analysis highlighted AKT1, EGFR, CASP3, SRC, and ESR1 as core targets. KEGG enrichment analysis indicated significant enrichment in the PI3K-AKT signaling pathway, a pathway associated with cancer. Molecular docking experiments confirmed favorable interactions between dihydroguaiaretic acid and the core target proteins (AKT1, EGFR, CASP3, and ESR1). Bioinformatics analysis revealed differential expression of EGFR and CASP3 in normal and CRC tissues. Cellular experiments further verified that dihydroguaiaretic acid induces apoptosis in colorectal cancer cells through the PI3K-AKT signaling pathway. CONCLUSION: Our network pharmacology study has elucidated that the Sargentodoxa cuneata-Patrinia villosa herb pair exerts the negative regulation of the PI3K/AKT/mTOR signaling pathway, ultimately leading to the induction of apoptosis in colorectal cancer cells. This research has predicted and validated the active ingredients, potential targets, and molecular mechanisms of Sargentodoxa cuneata-Patrinia villosa in the treatment of CRC, providing scientific evidence for the use of traditional Chinese medicine in managing CRC.

Intraspecific phylogeny and genomic resources development for an important medical plant Dioscorea nipponica, based on low-coverage whole genome sequencing data.

Dioscorea nipponica Makino, a perennial twining herb with medicinal importance, has a disjunctive distribution in the Sino-Japanese Floristic Region. It has a long history in traditional Chinese medicine, with demonstrated efficacy against various health conditions. However, the limited genomic data and knowledge of genetic variation have hindered its comprehensive exploration, utilization and conservation. In this study, we undertook low-coverage whole genome sequencing of diverse D. nipponica accessions to develop both plastome (including whole plastome sequences, plastome-derived SSRs and plastome-divergent hotspots) and nuclear genomic resources (including polymorphic nuclear SSRs and single-copy nuclear genes), as well as elucidate the intraspecific phylogeny of this species. Our research revealed 639 plastome-derived SSRs and highlighted six key mutational hotspots (namely CDS ycf1, IGS trnL-rpl32, IGS trnE-trnT, IGS rps16-trnQ, Intron 1 of clpP, and Intron trnG) within these accessions. Besides, three IGS regions (i.e., ndhD-cssA, trnL-rpl32, trnD-trnY), and the intron rps16 were identified as potential markers for distinguishing D. nipponica from its closely related species. In parallel, we successfully developed 988 high-quality candidate polymorphic nuclear SSRs and identified 17 single-copy nuclear genes for D. nipponica, all of which empower us to conduct in-depth investigations into phylogenetics and population genetics of this species. Although our phylogenetic analyses, based on plastome sequences and single-copy nuclear genes revealed cytonuclear discordance within D. nipponica, both findings challenged the current subspecies classification. In summary, this study developed a wealth of genomic resources for D. nipponica and enhanced our understanding of the intraspecific phylogeny of this species, offering valuable insights that can be instrumental in the conservation and strategic utilization of this economically significant plant.

Herpetrione, a New Type of PPARα Ligand as a Therapeutic Strategy Against Nonalcoholic Steatohepatitis.

Non-alcoholic fatty liver disease, especially nonalcoholic steatohepatitis (NASH), is a leading cause of cirrhosis and liver cancer worldwide; nevertheless, there are no Food and Drug Administration-approved drugs for treating NASH until now. Peroxisome proliferator-activated receptor alpha (PPARα) is an interesting therapeutic target for treating metabolic disorders in the clinic, including NASH. Herpetrione, a natural lignan compound isolated from Tibetan medicine Herpetospermum caudigerum, exerts various hepatoprotective effects, but its efficacy and molecular mechanism in treating NASH have not yet been elucidated. Here, we discovered that herpetrione lessened lipid accumulation and inflammation in hepatocytes stimulated with oleic acid and lipopolysaccharide, and effectively alleviated NASH caused by a high-fat diet or methionine-choline-deficient diet by regulating glucolipid metabolism, insulin resistance, and inflammation. Mechanistically, RNA-sequencing analyses further showed that herpetrione activated PPAR signaling, which was validated by protein expression. Furthermore, the analysis of molecular interactions illustrated that herpetrione bound directly to the PPARα protein, with binding sites extending to the Arm III domain. PPARα deficiency also abrogated the protective effects of herpetrione against NASH, suggesting that herpetrione protects against hepatic steatosis and inflammation by activation of PPARα signaling, thereby alleviating NASH. Our findings shed light on the efficacy of a natural product for treating NASH, as well as the broader prospects for NASH treatment by targeting PPARα.

StHsfB5 Promotes Heat Resistance by Directly Regulating the Expression of Hsp Genes in Potato.

With global warming, high temperatures have become a major environmental stress that inhibits plant growth and development. Plants evolve several mechanisms to cope with heat stress accordingly. One of the important mechanisms is the Hsf (heat shock factor)-Hsp (heat shock protein) signaling pathway. Therefore, the plant transcription factor Hsf family plays important roles in response to heat stress. All Hsfs can be divided into three classes (A, B, and C). Usually, class-A Hsfs are transcriptional activators, while class-B Hsfs are transcriptional repressors. In potato, our previous work identified 27 Hsfs in the genome and analyzed HsfA3 and HsfA4C functions that promote potato heat resistance. However, the function of HsfB is still elusive. In this study, the unique B5 member StHsfB5 in potato was obtained, and its characterizations and functions were comprehensively analyzed. A quantitative real-time PCR (qRT-PCR) assay showed that StHsfB5 was highly expressed in root, and its expression was induced by heat treatment and different kinds of phytohormones. The subcellular localization of StHsfB5 was in the nucleus, which is consistent with the characterization of transcription factors. The transgenic lines overexpressing StHsfB5 showed higher heat resistance compared with that of the control nontransgenic lines and inhibitory lines. Experiments on the interaction between protein and DNA indicated that the StHsfB5 protein can directly bind to the promoters of target genes small Hsps (sHsp17.6, sHsp21, and sHsp22.7) and Hsp80, and then induce the expressions of these target genes. All these results showed that StHsfB5 may be a coactivator that promotes potato heat resistance ability by directly inducing the expression of its target genes sHsp17.6, sHsp21, sHsp22.7, and Hsp80.

High-throughput screening and quantification of pesticides in Lilii Bulbus using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Lilii Bulbus is a notable flower in Chinese cuisine, and has also been used as a Chinese herbal medicine for over 2000 years. This work presents an analytical method for rapidly screening multiple pesticide residues in Lilii Bulbus using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). For sample pre-treatment, the QuEChERS method is employed, and targeted MS/MS is adopted for data acquisition. Moreover, a database containing 515 pesticides with accurate mass database and a high-resolution fragment ion spectrum library is established in this work. In addition, the qualitative and quantitative results of the screening method are validated. The results show that within the linear concentration range of 2 to 200 µg L-1, for each pesticide, 89.3% of the pesticides exhibit linear correlation coefficients R2 equal to or exceeding 0.990. The limit of quantification for all pesticides is below 50 µg kg-1. With a recovery of 70% to 120% and RSD ≤ 20% as the satisfactory standards, 387 (75.0%), 411 (79.7%) and 420 (81.4%) pesticides meet the standards at the three addition levels of 10 µg kg-1, 20 µg kg-1, and 100 µg kg-1, respectively. By utilizing the proposed method, pesticide residues in 100 samples are investigated, providing scientific data to ensure the safety of pesticide residues and demonstrating the general applicability of the method for routine monitoring of pesticide residues in Lilii Bulbus.

Elucidating the molecular mechanisms of ozone therapy for neuropathic pain management by integrated transcriptomic and metabolomic approach.

Introduction: Neuropathic pain remains a prevalent and challenging condition to treat, with current therapies often providing inadequate relief. Ozone therapy has emerged as a promising treatment option; however, its mechanisms of action in neuropathic pain remain poorly understood. Methods: In this study, we investigated the effects of ozone treatment on gene expression and metabolite levels in the brainstem and hypothalamus of a rat model, using a combined transcriptomic and metabolomic approach. Results: Our findings revealed significant alterations in key genes, including DCST1 and AIF1L, and metabolites such as Aconitic acid, L-Glutamic acid, UDP-glucose, and Tyrosine. These changes suggest a complex interplay of molecular pathways and region-specific mechanisms underlying the analgesic effects of ozone therapy. Discussion: Our study provides insights into the molecular targets of ozone treatment for neuropathic pain, laying the groundwork for future research on validating these targets and developing novel therapeutic strategies.

Right femoral vein and right dorsal artery thrombosis in childhood acute myeloid leukemia: A case report.

BACKGROUND: It is rare for newly diagnosed (de novo) or newly treated acute myeloid leukemia (AML) complicated with thrombotic complications, especially combined arterial and venous thrombosis. METHODS: We reported a 13-year-old boy diagnosed with AML and leukocytosis, who developed right femoral vein and right dorsal artery thrombosis during chemotherapy. After treatment with low molecular weight heparin, diosmin, and alprostadil, symptoms were relieved. Unfortunately, the child suffered from coagulopathy afterward, which was unexpectedly caused by vitamin K deficiency. RESULTS: After supplementation with vitamin K and prothrombin complex concentrate, coagulation function recovered. CONCLUSION: For childhood AML patients with high thrombotic risks, close monitoring during anticoagulant treatment was necessary. Concomitantly, we should be alert to past medication history and combined medication use, especially those that may lead to vitamin K deficiency, secondary bleeding, and coagulation disorders. Rational use of antibiotics, anticoagulants, and antitumor drugs must be guaranteed.

A mathematical model to simulate the release of Fe and Mn from sediments in a drinking water reservoir.

Fe and Mn release from sediments promotes the release of other chemicals and jointly affects downstream water safety, especially in drinking water reservoirs. Quantitative research on release processes and flux estimation methods for endogenous Fe and Mn in reservoirs is still limited. Static incubation experiments were designed to systematically explore the effects of water temperature (WT), dissolved oxygen (DO), pH, carbon sources, and microbial activity on Fe and Mn release. The results showed that increased WT and carbon source addition promoted the release of acid-extractable Fe and Mn from the sediments; hypoxia and acidification promoted the dissolution of reducible sediment Fe and Mn; and microorganisms participated in the cycling of Fe and Mn. Based on the experimental results, first-order kinetic equations for sediment Fe and Mn release to overlying water were proposed, and the relationships between release rate and environmental factors were mathematically represented by a surface equation (R2 = 0.88 and 0.86, respectively). A diffusion gradients in thin films (DGT) device based on the diffusion model was used in situ to obtain the diffusion fluxes of Fe (JFe = 13.93 mg m-2 d-1) and Mn (JMn = 3.48 mg m-2 d-1). When environmental factors obtained in the field were introduced into the established mathematical model, the modeled release fluxes of Fe and Mn were RFe = 20.92 mg m-2 d-1 and RMn = 13.12 mg m-2 d-1, respectively. The established model filled gaps in the diffusion model, which does not account for differences in release fluxes under changing physicochemical water conditions. This work serves as a reference for studying the release fluxes of endogenous chemicals in sediments.

Guanxinning tablets improve myocardial hypertrophy by inhibiting the activation of MEK-ERK1/2 signaling pathway.

Myocardial hypertrophy may lead to heart failure and sudden death. As traditional Chinese medicine, Guanxinning tablets (GXN) have significant pharmacological effects in the prevention and treatment of cardiovascular diseases. However, the anti-cardiac hypertrophy efficacy of GXN and its mechanism of action are still unclear. Therefore, we established a heart failure rat model and isolated primary cardiomyocytes of neonatal rat to observe the protective effect of GXN on heart failure rat model and the intervention effect on myocardial cell hypertrophy, and to explore the possible mechanism of GXN preventing and treating myocardial hypertrophy. The results of in vivo experiments showed that GXN could significantly reduce the degree of cardiac hypertrophy, reduce the size of cardiomyocytes, inhibit the degree of myocardial remodeling and fibrosis, and improve cardiac function in rats with early heart failure. The results of in vitro experiments showed that GXN was safe for primary cardiomyocytes and could improve cardiomyocyte hypertrophy and reduce the apoptosis of cardiomyocytes in pathological state, which may be related to the inhibition of the over-activation of MEK-ERK1/2 signaling pathway. In conclusion, GXN may inhibit cardiac hypertrophy and improve early heart failure by inhibiting the over-activation of MEK-ERK1/2 signaling pathway.

Differential Diagnosis of Intracranial Malignant Tumors Using MRI Based on Morphological Features and Signal Intensity Ratio of Lesions.

Objective: To investigate the clinical value of conventional MRI morphological features and signal intensity ratio in the differential diagnosis of intracranial malignant tumors (high-grade glioma (HGG), primary central nervous system Lymphoma (PCNSL) and single brain metastasis (BM). Methods: Retrospective analysis of 92 cases of HGG, 27 cases of PCNSL, and 35 cases of BM. MRI data in The General Hospital of Western Theater Command from August 2014 to December 2021, comparative analysis of morphological characteristics of tumors and lesion/normal brain parenchyma signal ratio (lesiontonormal parenchymaratio, LNR), five indexes were included T1WI signal ratio (LNRT1), T2WI signal intensity ratio (LNRT2), T2WI/T1WI signal ratio (LNRT2/T1), T1WI enhanced signal ratio (LNRT1CE) and contrast enhancement ratio (CER). The differential diagnostic performance was also assessed by subject operating characteristic (ROC) curves. Results: HGG, PCNSL, and BM were all seen more frequently in the supratentorial region, More than 50% of HGG mainly showed irregular morphology, intratumoral necrosis, cystic degeneration, peritumoral severe edema, cyclic uneven enhancement after enhancement, PCNSL significantly enhanced the main uniformity, necrosis cyst became rare, BM group showed uneven enhancement, no obvious specificity, and the differences in tumor morphology, peritumor edema, intratumor hemorrhage, necrotic cystic lesions, and enhancement patterns were statistically significant among the three (P < .05). PCNSL LNRT1 and its LNRT1CE (LNRT1: 0.558 ± 0.050, LNRT1CE: 1.637 ± 0.125) were significantly higher than those of HGG (LNRT1: 0.480 ± 0.077, LNRT1CE: 1.425 ± 0.160) and BM (LNRT1: 0.514 ± 0.120, LNRT1CE: 1.375 ± 0.122), while LNRT2 and LNRT2/T1 (LNRT2: 1.389 ± 0.086, LNRT2/T1: 2.511 ± 0.295) were significantly lower than those of HGG (LNRT2: 1.527 ± 0.191, LNRT2/T1: 3.263 ± 0.657), and BM (LNRT2: 1.504 ± 0.089, LNRT2/T1: 3.103 ± 0.830). There was no significant difference in CER among the three groups (P > .05). ROC curve analysis of LNRT1, LNRT2, LNRT1CE, and LNRT2/T1 could be used to discriminate PCNSL from HGG and BM, with LNRT1CE having the largest area under the curve of 0.873, sensitivity of 0.963 and specificity of 0.669. Conclusion: MRI lesion morphological features and signal intensity ratio are important for discriminating HGG from PCNSL and BM. As a quantitative parameter, tumor signal intensity ratio can provide an important supplement for subjective judgment, to improve the accuracy of tumor qualitative diagnosis and differential diagnosis.