Anti-MRSA mechanism of spirostane saponin in Rohdea pachynema F.T.Wang & tang.

ETHNOPHARMACOLOGY RELEVANCE: Rohdea pachynema F.T.Wang & Tang (R. pachynema), is a traditional folk medicine used for the treatment of stomach pain, stomach ulcers, bruises, and skin infections in China. Some of the diseases may relate to microbial infections in traditional applications. However few reports on its antimicrobial properties and bioactive components. AIM OF THE STUDY: To identify its bioactive constituents against methicillin-resistant Staphylococcus aureus (MRSA) in vitro and in vivo, and its mechanism. MATERIALS AND METHODS: The anti-MRSA ingredient 6α-O-[ß-D-xylopyranosyl-(1 â†’ 3)-ß-D-quinovopyranosyl]-(25S)-5α-spirostan-3ß-ol (XQS) was obtained from R. pachynema by phytochemical isolation. Subsequently, XQS underwent screening using the broth microdilution method and growth inhibition curves to assess its antibacterial activity. The mechanism of XQS was evaluated by multigeneration induction, biofilm resistance assay, scanning electron microscopy, transmission electron microscopy, and metabolomics. Additionally, a mouse skin infection model was established in vivo. RESULTS: 26 compounds were identified from the R. pachynema, in which anti-MRSA spirostane saponin (XQS) was reported for the first time with a minimum inhibitory concentration (MIC) of 8 µg/mL. XQS might bind to peptidoglycan (PGN) of the cell wall, phosphatidylglycerol (PG), and phosphatidylethanolamine (PE) of the cell membrane, then destroying the cell wall and the cell membrane, resulting in reduced membrane fluidity and membrane depolarization. Furthermore, XQS affected MRSA lipid metabolism, amino acid metabolism, and ABC transporters by metabolomics analysis, which targeted cell walls and membranes causing less susceptibility to drug resistance. Furthermore, XQS (8 mg/kg) recovered skin wounds in mice infected by MRSA effectively, superior to vancomycin (8 mg/kg). CONCLUSIONS: XQS showed anti-MRSA bioactivity in vitro and in vivo, and its mechanism association with cell walls and membranes was reported for the first, which supported the traditional uses of R. pachynema and explained its sensitivity to MRSA.

Real-world Chinese herbal medicine for Parkinson's disease: a hospital-based retrospective analysis of electronic medical records.

Background: Parkinson's disease (PD) is a progressive neurodegenerative condition. Chinese medicine therapies have demonstrated effectiveness for PD in controlled settings. However, the utilization of Chinese medicine therapies for PD in real-world clinical practice and the characteristics of patients seeking these therapies have not been thoroughly summarized. Method: The study retrospectively analyzed initial patient encounters (PEs) with a first-listed diagnosis of PD, based on electronic medical records from Guangdong Provincial Hospital of Chinese Medicine between July 2018 and July 2023. Results: A total of 3,206 PEs, each corresponding to an individual patient, were eligible for analyses. Approximately 60% of patients made initial visits to the Chinese medicine hospital after receiving a PD diagnosis, around 4.59 years after the onset of motor symptoms. Over 75% of the patients visited the Internal Medicine Outpatient Clinic at their initial visits, while a mere 13.85% visited PD Chronic Care Clinic. Rest tremor (61.98%) and bradykinesia (52.34%) are the most commonly reported motor symptoms, followed by rigidity (40.70%). The most commonly recorded non-motor symptoms included constipation (31.88%) and sleep disturbance (25.27%). Integration of Chinese medicine and conventional medicine therapies was the most common treatment method (39.15%), followed by single use of Chinese herbal medicine (27.14%). The most frequently prescribed herbs for PD included Glycyrrhiza uralensis Fisch. (gan cao), Astragalus mongholicus Bunge (huang qi), Atractylodes macrocephala Koidz. (bai zhu), Angelica sinensis (Oliv.) Diels (dang gui), Rehmannia glutinosa (Gaertn.) DC. (di huang), Paeonia lactiflora Pall. (bai shao), Bupleurum chinense DC. (chai hu), Citrus aurantium L. (zhi qiao/zhi shi/chen pi), Panax ginseng C. A. Mey. (ren shen), and Poria cocos (Schw.) Wolf (fu ling). These herbs contribute to formulation of Bu zhong yi qi tang (BZYQT). Conclusion: Patients typically initiated Chinese medical care after the establishment of PD diagnosis, ~4.59 years post-onset of motor symptoms. The prevalent utilization of CHM decoctions and patented Chinese herbal medicine products, underscores its potential in addressing both motor and non-motor symptoms. Despite available evidence, rigorous clinical trials are needed to validate and optimize the integration of CHM, particularly BZYQT, into therapeutic strategies for PD.

miR-200b-3p accelerates progression of pituitary adenomas by negatively regulating expression of RECK.

MicroRNA (miR)-200b-3p has been associated with many tumors, but its involvement in pituitary adenoma is unclear. This study investigated the molecular mechanism underlying miR-200b-3p regulation in pituitary adenomas to provide a theoretical basis for treatment. Bioinformatics was used to analyze pituitary adenoma-related genes and screen new targets related to RECK and miRNA. As well, the relationship between miR-200b-3p and RECK protein was verified using a double-luciferase reporter gene assay. The expression of miR-200b-3p in clinical samples was analyzed by in situ hybridization. Transfection of the miR-200b-3p inhibitor and small interfering-RECK (si-RECK) was verified by qPCR. GH3 cell viability and proliferation were detected using CCK8 and EdU assays. Apoptosis was detected by flow cytometry and western blotting. Wound healing and Transwell assays were used to detect cell migration and invasion. The effects of miR-200b-3p and RECK on GH3 cells were verified using salvage experiments. miR-200b-3p was highly expressed in pituitary tumor tissue. Inhibitors of miR-200b-3p inhibited cell proliferation promoted cell apoptosis, inhibited invasion and migration, and inhibited the expression of matrix metalloproteinases. Interestingly, miR-200b-3p negatively regulated RECK. The expression of RECK in pituitary adenoma tissues was lower than that in neighboring tissues. Si-RECK rescued the function of miR-200b-3p inhibitors in the above cellular behaviors, and miR-200b-3p accelerated the development of pituitary adenoma by negatively regulating RECK expression. In summary, this study investigated the molecular mechanism by which miR-200b-3p regulates the progression of pituitary adenoma through the negative regulation of RECK. The findings provide a new target for the treatment of pituitary adenoma.

Structure optimizing of flavonoids against both MRSA and VRE.

Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) cause more than 100,000 deaths each year, which need efficient and non-resistant antibacterial agents. SAR analysis of 162 flavonoids from the plant in this paper suggested that lipophilic group at C-3 was crucial, and then 63 novel flavonoid derivatives were designed and total synthesized. Among them, the most promising K15 displayed potent bactericidal activity against clinically isolated MRSA and VRE (MICs = 0.25-1.00 µg/mL) with low toxicity and high membrane selectivity. Moreover, mechanism insights revealed that K15 avoided resistance by disrupting biofilm and targeting the membrane, while vancomycin caused 256 times resistance against MRSA, and ampicillin caused 16 times resistance against VRE by the same 20 generations inducing. K15 eliminated residual bacteria in mice skin MRSA-infected model (>99 %) and abdominal VRE-infected model (>92 %), which was superior to vancomycin and ampicillin.

Thrombosis inhibited by Corydalis decumbens through regulating PI3K-Akt pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Corydalis decumbens (Thunb.) Pers. was used as stasis-eliminating medicine traditionally to treat cardiovascular disease potentially attributed to its antithrombotic effect, but lack of pharmacological research on it. AIM OF THE STUDY: To investigate the antithrombotic effect of C. decumbens and its preliminary mechanism. MATERIALS AND METHODS: A carrageenan-induced mouse thrombus model and adenosine diphosphate stimulated platelet aggregation of rabbits were used to confirm the inhibitory effect of C. decumbens extract and compounds on thrombosis in vivo. Then, H2O2-induced human umbilical vein endothelial cells (HUVECs) injury model was further adopted to verify the effects of bioactive compounds in vitro. Moreover, in silico network pharmacology analyses and molecular docking were performed to predict the underlying mechanisms, targets, and pathways, and which were further confirmed through western blotting assay. RESULTS: The administration of total extract (TE), total alkaloids (TA) and tetrahydropalmatine (TET) resulted in a significant reduction in black tail thrombus and congestion, along with a decreasing in platelet aggregation of rabbits. A superior antithrombotic effect indicated the bioactive fraction, and then the isolated bioactive compounds, TET and protopine (PRO) increased cell survival, and decreased reactive oxygen species (ROS) and lactate dehydrogenase (LDH) release in H2O2-induced HUVECs injury model. Moreover, the two alkaloids targeted 33 major proteins and influenced 153 pathways in network pharmacology prediction. Among these, HSP90AA1, COX-2, NF-κB/p65, MMP1 and HIF-1α were the key proteins and PI3K-Akt emerged as the major signaling pathway. Further western blotting results supported that five key proteins were downregulated by the two bioactive compounds in H2O2-stimulated HUVECs model. CONCLUSION: C. decumbens exerted protective effect on thrombosis through inhibiting PI3K-Akt pathway and related key proteins, which supported the traditional use and presented potential antithrombotic alkaloids for further investigation.

Exploring Abnormal Brain Functional Connectivity in Healthy Adults, Depressive Disorder, and Generalized Anxiety Disorder through EEG Signals: A Machine Learning Approach for Triple Classification.

Depressive disorder (DD) and generalized anxiety disorder (GAD), two prominent mental health conditions, are commonly diagnosed using subjective methods such as scales and interviews. Previous research indicated that machine learning (ML) can enhance our understanding of their underlying mechanisms. This study seeks to investigate the mechanisms of DD, GAD, and healthy controls (HC) while constructing a diagnostic framework for triple classifications. Specifically, the experiment involved collecting electroencephalogram (EEG) signals from 42 DD patients, 45 GAD patients, and 38 HC adults. The Phase Lag Index (PLI) was employed to quantify brain functional connectivity and analyze differences in functional connectivity among three groups. This study also explored the impact of time window feature computations on classification performance, including the XGBoost, CatBoost, LightGBM, and ensemble models. In order to enhance classification performance, a feature optimization algorithm based on Autogluon-Tabular was proposed. The results indicate that a 12 s time window provides optimal classification performance for the three groups, achieving the highest accuracy of 97.33% with the ensemble model. The analysis further reveals a significant reorganization of the brain, with the most pronounced changes observed in the frontal lobe and beta rhythm. These findings support the hypothesis of abnormal brain functional connectivity in DD and GAD, contributing valuable insights into the neural mechanisms underlying DD and GAD.

The whitening effect of cuscutin responsible for traditional use of Bergenia purpurascens.

ETHNOPHARMACOLOGICAL RELEVANCE: The roots and rhizomes of Bergenia purpurascens (Hook. f. et Thomson) Engl., was used as a sunscreen to protect against ultraviolet rays in Tibet of China historically, but its skin whitening constituents and pharmacological effects of this plant remained unknown. AIM OF THE STUDY: To investigate the anti-melanogenesis effect of B. purpurascens in vitro and in vivo, and then explore the preliminary mechanism. MATERIALS AND METHODS: An ultraviolet B (UVB)-induced skin injury model of mice was used to verify the ameliorative effect of B. purpurascens extract (BPE) on ultraviolet damage. Then, alpha-melanocyte stimulating hormone (α-MSH)-induced murine melanoma cell line (B16F10) melanin generation model was further adopted to approval the effects of BPE and its bioactive compound, cuscutin, in vitro. Moreover, α-MSH stimulated melanogenesis model in zebrafish was employed to confirm the anti-pigmentation effect of cuscutin. Then, proteins expressions associated with melanin production were observed using western blotting assay to explore preliminary mechanism. RESULTS: BPE inhibited UVB-induced mice injury and restored skin barrier function observably in vivo. BPE and cuscutin suppressed the overproduction of melanin in α-MSH induced B16F10 significantly, in which cuscutin exhibited better effect than well-known whitening agent α-arbutin at same 10 µg/mL concentration. Moreover, the pigmentation of zebrafish embryo was decreased by cuscutin. Finally, cuscutin showed significant downregulation of expressions of tyrosinase (TYR) and tyrosinase related protein-1 (TRP-1), TRP-2 and microphthalmia-associated transcription factor (MITF) in the melanogenic signaling pathway. CONCLUSION: B. purpurascens extract and its major bioactive constituent, cuscutin, showed potent anti-melanogenesis and skin-whitening effect by targeting TYR and TRP-2 proteins for the first time, which supported its traditional use.

Antimicrobial ingredients of Zanthoxylum motuoense and potential in fresh pork meat preservation.

Zanthoxylum motuoense (Tibetan prickly ash, MTHJ), different from the Chinese prickly ash species, is distributed only in the Tibet. Now the chemical characterization and antibacterial activity of MTHJ extracts were analyzed for the first time. As a result, Schinifoline (12), γ-Fagarine (8), (2E,7E,9E)-6 S-Hydroxy-N-(2-methylpropyl)-11-oxo-2, 7, 9-Dodecatrienamide (6), and Neoechinulin A (17) were found to be the major different factors by untarget LC-MS metabolomics together with quantitative analysis on target. These four compounds were also the major antibacterial constituents. Then, the antimicrobial activity of MTHJ fractions was evaluated with colony forming units (CFU), fluorescence microscopy imaging, SEM and investigating the potential food preservation. Nutritional composition, colour and sensory evaluation of extract-treated samples were evaluated along storage time. The results suggested the MTHJ may be used for meat products preservation, and the scores were significantly higher for its unique flavor, which offered a promising choice for food safety, preservation and reducing foodborne illness.

A dual mechanism with H2S inhibition and membrane damage of morusin from Morus alba Linn. against MDR-MRSA.

It's urgent to discover new antibiotics along with the increasing emergence and dissemination of multidrug resistant (MDR) bacterial pathogens. In the present investigation, morusin exhibited rapid bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) by targeting the phospholipid of bacterial inner membrane, increasing membrane rigidity and disrupting bacterial homeostasis together with the membrane permeability, which caused fundamental metabolic disorders. Furthermore, morusin can also accumulate ROS, suppress H2S production, and aggravate oxidative damage in bacteria. Importantly, morusin also inhibited the spread of wounds and reduced the bacterial burden in the mouse model of skin infection caused by MRSA. It's a chance to meet the challenge of existing antibiotic resistance and avoid the development of bacterial resistance, given the multiple targets of morusin.

Undescribed indole lactones from Alstonia scholaris protecting hepatic cell damage.

Six previously undescribed rigidly monoterpenoid indole alkaloids, alstolactines F-K (1-6), were isolated from Alstonia scholaris. Among them, a pair of cage-like epimers, 1 and 2, featuring a rare 6/5/6/6/7 ring system, represent the first example of C5→C20-olide, while compound 3 possesses unique degraded C18 and C19. The structures of the isolates were established by multiple spectroscopic analyses, quantum computational chemistry methods, and X-ray diffraction. Furthermore, the expression levels of proteins including NLRP3, TLR4, P-p65, NF-ĸB, Notch-2, IL-18, P-p38, and p38 in LPS-induced human normal hepatocyte (LO2) cells could be significantly downregulated by compounds 1-6, which showed potent anti-inflammatory bioactivity.

Structural Characterization and Anticoagulant Activities of a Keratan Sulfate-like Polysaccharide from the Sea Cucumber Holothuria fuscopunctata.

A sulfated polysaccharide (AG) was extracted and isolated from the sea cucumber H. fuscopunctata, consisting of GlcNAc, GalNAc, Gal, Fuc and lacking any uronic acid residues. Importantly, several chemical depolymerization methods were used to elucidate the structure of the AG through a bottom-up strategy. A highly sulfated galactose (oAG-1) and two disaccharides labeled with 2,5-anhydro-D-mannose (oAG-2, oAG-3) were obtained from the deaminative depolymerized product along with the structures of the disaccharide derivatives (oAG-4~oAG-6) identified from the free radical depolymerized product, suggesting that the repeating building blocks in a natural AG should comprise the disaccharide ß-D-GalS-1,4-D-GlcNAc6S. The possible disaccharide side chains (bAG-1) were obtained with mild acid hydrolysis. Thus, a natural AG may consist of a keratan sulfate-like (KS-like) glycosaminoglycan with diverse modifications, including the sulfation types of the Gal residue and the possible disaccharide branches α-D-GalNAc4S6S-1,2-α/ß-L-Fuc3S linked to the KS-like chain. Additionally, the anticoagulant activities of the AG and its depolymerized products (dAG1-9) were evaluated in vitro using normal human plasma. The AG could prolong activated partial thromboplastin time (APTT) in a dose-dependent manner, and the activity potency was positively related to the chain length. The AG and dAG1-dAG3 could prolong thrombin time (TT), while they had little effect on prothrombin time (PT). The results indicate that the AG could inhibit the intrinsic and common coagulation pathways.

Campylobacter fetus-induced primary psoas abscess in patient with gouty arthritis: A case report and literature review.

RATIONALE: Campylobacter fetus is rare pathogen with high mortality rate in immunosuppressive hosts. This study aimed to summarize clinical and pathological presentation of C fetus induced psoas abscess. PATIENT CONCERNS: A 66-year-old male patient with long medical history of poorly-controlled gouty arthritis and steroid intake complained of a severe low back pain. Physical examination showed tenderness in his psoas. DIAGNOSES: The patient underwent puncture biopsy to the lesion in the psoas under ultrasound guidance. The lesion was indicated as abscess by pathological examination, and its pathogen was indicated as C fetus by the next generation sequencing. INTERVENTIONS: Meropenem 1 g q8.h were administered intravenously for 10 days. Then the antibiotic treatment was switched to amoxicillin/clavulanate potassium 0.375g q.8.h and levofloxacin 0.5g q.d oral administration when discharge. OUTCOMES: The patient's fever and low back pain improved and infectious parameters declined. He was discharged in good general condition with advice for further monitoring and therapy. In the first month follow-up, the patient did not report recurrence or aggravation of his symptoms. LESSONS: C fetus should be noticed in immunosuppressive patient with exposure to livestock who present with rare systematic or local invasive infection. We advocated the meropenem for the first-line treatment against C fetus.

Antimelanogenic Effect of Isoquinoline Alkaloids from Plumula Nelumbinis.

Plumula Nelumbinis, the green embryo of a lotus seed, is widely consumed in China as a well-known food with medicinal effects. In this study, 14 alkaloids, including 4 new and 10 known alkaloids, were isolated from it, which were elucidated by comprehensive spectroscopic analysis, and were investigated for their antimelanogenic effects in vitro and in vivo. As a result, melanogenesis in α-MSH-stimulated B16F10 cells was reduced significantly by a new compound 4 and known compound 12 at a concentration of 0.5 µg/mL, and the tyrosinase (TYR) activities were inhibited by 78.7 and 82.0% at 4 µg/mL, prior to α-arbutin (41.3%). Additionally, compounds 4 and 12 also exhibited superior antimelanogenic effects compared to α-arbutin on a zebrafish assay model at equivalent concentrations. Mechanistically, our preliminary findings suggested that compounds 4 and 12 exerted antimelanogenesis effect probably by inhibiting key proteins involved in melanin production such as microphthalmia-associated transcription factor, TYR, TRP-1, and TRP-2. The findings highlight the potential use of Plumula Nelumbinis containing compounds 4 and 12 as functional foods for treating hyperpigmentation.

Adsorption and mechanism study for phenol removal by 10% CO2 activated bio-char after acid or alkali pretreatment.

The development of an efficient bio-char used to remove phenol from wastewater holds great importance for environmental protection. In this work, wheat straw bio-char (BC) was acid-washed by HF and activated at 900 °C with 10% CO2 to obtain bio-char (B-Ⅲ-0.1D900). Adsorption experiments revealed that B-Ⅲ-0.1D900 achieved a remarkable phenol removal efficiency of 90% within 40 min. Despite its relatively low specific surface area of 492.60 m2/g, it exhibited a high maximum adsorption capacity of 471.16 mg/g. Furthermore, B-Ⅲ-0.1D900 demonstrated a good regeneration capacity for at least three cycles (90.71%, 87.54%, 84.36%). It has been discovered that HF washing, which removes AAEM and exposes unsaturated functional groups, constitutes one of the essential prerequisites for enhancing CO2 activation efficiency at high temperatures. After 10% CO2 activation, the mesoporous structure exhibited substantial development, facilitating enhanced phenol infiltration into the pores when compared to untreated BC. The increased branching of the bio-char culminated in a more complete aromatic system, which enhances the π-π forces between the bio-char and the phenol. The presence of tertiary alcohol structure enhances the hydrogen bonding forces, thereby promoting intermolecular multilayer adsorption of phenol. With the combination of various forces, B-Ⅲ-0.1D900 has a good removal capacity for phenol. This work provides valuable insights into the adsorption of organic pollutants using activated bio-char.

New Lupanes from Alstonia scholaris Reducing Uric Acid Level.

Twelve lupanes including three new compounds named alstoscholarilups A-C (1: -3: ) were isolated from the leaves of Alstonia scholaris. Their structures were elucidated by spectroscopic analysis and ECD calculation. Structurally, compound 1: with a rare A ring-seco skeleton formed lactone and degraded C-3, while 2: with a 28-nor and 3: with a 29-nor-lupane skeleton supported the phytochemical diversity and novelty of the plant. Pharmacologically, compounds 4, 7: , and 10: reduced the serum uric acid (UA) levels of mice significantly.

Mitochondrial subtype MB-G3 contains potential novel biomarkers and therapeutic targets associated with prognosis of medulloblastoma.

BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children. There are four groups, each with different causal mutations, affected pathways and prognosis. Here, we investigated the role of mitochondria in medulloblastoma and whether there are differences between the different groups. METHODS: We compared the gene expression levels in the four different medulloblastoma groups (MB-WNT, MB-SHH, MB-G3 and MB-G4), with the focus on genes associated with mitochondria. We used several tools including Salmon, Tximeta, DESeq2, BiomaRt, STRING, Ggplot2, EnhancedVolcano, Venny 2.1 and Metscape. RESULTS: A total of 668 genes were differentially expressed and the most abundant genes were associated with cell division pathway followed by modulation of chemical synaptic transmission. We also identified several genes (ABAT, SOX9, ALDH5A, FOXM1, ABL1, NHLH1, NEUROD1 and NEUROD2) known to play vital role in medulloblastoma. Comparative expression analysis revealed OXPHOS complex-associated proteins of mitochondria. The most significantly expressed genes in the MB-SHH and MB-G4 groups were AHCYL1 and SFXN5 while PAICS was significantly upregulated in MB-WNT group. Notably, MB-G3 contained the most downregulated genes from the OXPHOS complexes, except COX6B2 which was strongly upregulated. CONCLUSIONS: We show the importance of mitochondria and compare their role in the four different medulloblastoma groups.

Depressive Disorder Recognition Based on Frontal EEG Signals and Deep Learning.

Depressive disorder (DD) has become one of the most common mental diseases, seriously endangering both the affected person's psychological and physical health. Nowadays, a DD diagnosis mainly relies on the experience of clinical psychiatrists and subjective scales, lacking objective, accurate, practical, and automatic diagnosis technologies. Recently, electroencephalogram (EEG) signals have been widely applied for DD diagnosis, but mainly with high-density EEG, which can severely limit the efficiency of the EEG data acquisition and reduce the practicability of diagnostic techniques. The current study attempts to achieve accurate and practical DD diagnoses based on combining frontal six-channel electroencephalogram (EEG) signals and deep learning models. To this end, 10 min clinical resting-state EEG signals were collected from 41 DD patients and 34 healthy controls (HCs). Two deep learning models, multi-resolution convolutional neural network (MRCNN) combined with long short-term memory (LSTM) (named MRCNN-LSTM) and MRCNN combined with residual squeeze and excitation (RSE) (named MRCNN-RSE), were proposed for DD recognition. The results of this study showed that the higher EEG frequency band obtained the better classification performance for DD diagnosis. The MRCNN-RSE model achieved the highest classification accuracy of 98.48 ± 0.22% with 8-30 Hz EEG signals. These findings indicated that the proposed analytical framework can provide an accurate and practical strategy for DD diagnosis, as well as essential theoretical and technical support for the treatment and efficacy evaluation of DD.

New and Antifungal Diterpenoids of Sunflower against Gray Mold.

Sunflower (Helianthus annuus L.) is cultivated around the world as an oil crop, and its receptacle is the byproduct and is usually deemed to be an agro-industrial waste. Then, phytochemical constituents and antifungal bioactivity of the sunflower receptacle against phytopathogenic fungi were investigated. As a result, 17 diterpenoids including 4 new compounds were isolated, and most of them showed potential antifungal activity against Botrytis cinerea, in which compounds 1, 3, 5, and 15 exhibited better inhibitory effect with the minimum inhibitory concentration values of 0.05-0.1 mg/mL. Meanwhile, four antifungal diterpenoids destructed plasma membrane integrity, suspended the biofilm formation ability, and increased the extravasation of cellular contents of B. cinerea. Moreover, the EtOAc extract of sunflower receptacle could keep 42.9% of blueberries from the invasion of B. cinerea at 1.6 mg/mL. The finding suggested that sunflower receptacle might be a biocontrol agent for preventing fruit from postharvest diseases.

Identifying NFKB1, STAT3, and CDKN1A as Baicalein's Potential Hub Targets in Parkinson's Disease-related α-synuclein-mediated Pathways by Integrated Bioinformatics Strategies.

BACKGROUND: The overexpression, accumulation, and cell-to-cell transmission of α-synuclein leads to the deterioration of Parkinson's disease (PD). Previous studies suggest that Baicalein (BAI) can bind to α-synuclein and inhibit α-synuclein aggregation and secretion. However, it is still unclear whether BAI can intervene with the pathogenic molecules in α-synuclein-mediated PD pathways beyond directly targeting α-synuclein per se. METHODS: This study aimed to systematically investigate BAI's potential targets in PD-related A53T mutant α-synuclein-mediated pathways by integrating data mining, network pharmacological analysis, and molecular docking simulation techniques. RESULTS: The results suggest that BAI may target genes that are dysregulated in synaptic transmission, vesicle trafficking, gene transcription, protein binding, extracellular matrix formation, and kinase activity in α-synucleinmediated pathways. NFKB1, STAT3, and CDKN1A are BAI's potential hub targets in these pathways. CONCLUSION: Our findings highlight BAI's potentiality to modulate α-synuclein-mediated pathways beyond directly targeting α-synuclein per se.