PresRecST: a novel herbal prescription recommendation algorithm for real-world patients with integration of syndrome differentiation and treatment planning.

OBJECTIVES: Herbal prescription recommendation (HPR) is a hot topic and challenging issue in field of clinical decision support of traditional Chinese medicine (TCM). However, almost all previous HPR methods have not adhered to the clinical principles of syndrome differentiation and treatment planning of TCM, which has resulted in suboptimal performance and difficulties in application to real-world clinical scenarios. MATERIALS AND METHODS: We emphasize the synergy among diagnosis and treatment procedure in real-world TCM clinical settings to propose the PresRecST model, which effectively combines the key components of symptom collection, syndrome differentiation, treatment method determination, and herb recommendation. This model integrates a self-curated TCM knowledge graph to learn the high-quality representations of TCM biomedical entities and performs 3 stages of clinical predictions to meet the principle of systematic sequential procedure of TCM decision making. RESULTS: To address the limitations of previous datasets, we constructed the TCM-Lung dataset, which is suitable for the simultaneous training of the syndrome differentiation, treatment method determination, and herb recommendation. Overall experimental results on 2 datasets demonstrate that the proposed PresRecST outperforms the state-of-the-art algorithm by significant improvements (eg, improvements of P@5 by 4.70%, P@10 by 5.37%, P@20 by 3.08% compared with the best baseline). DISCUSSION: The workflow of PresRecST effectively integrates the embedding vectors of the knowledge graph for progressive recommendation tasks, and it closely aligns with the actual diagnostic and treatment procedures followed by TCM doctors. A series of ablation experiments and case study show the availability and interpretability of PresRecST, indicating the proposed PresRecST can be beneficial for assisting the diagnosis and treatment in real-world TCM clinical settings. CONCLUSION: Our technology can be applied in a progressive recommendation scenario, providing recommendations for related items in a progressive manner, which can assist in providing more reliable diagnoses and herbal therapies for TCM clinical task.

Chromosome-level genome of Thymus mandschuricus reveals molecular mechanism of aroma compounds biosynthesis.

Background: Thymus mandschuricus is an aromatic and medicinal plant with notable antibacterial and antioxidant properties. However, traditional breeding methods rely on phenotypic selection due to a lack of molecular resources. A high-quality reference genome is crucial for marker-assisted breeding, genome editing, and molecular genetics. Results: We utilized PacBio and Hi-C technologies to generate a high-quality chromosome-level reference genome for T. mandschuricus, with a size of 587.05 Mb and an N50 contig size of 8.41 Mb. The assembled genome contained 29,343 predicted protein-coding genes, and evidence of two distinct whole-genome duplications in T. mandschuricus was discovered. Comparative genomic analysis revealed rapid evolution of genes involved in phenylpropanoid biosynthesis and the CYP450 gene family in T. mandschuricus. Additionally, we reconstructed the gene families of terpenoid biosynthesis structural genes, such as TPS, BAHD, and CYP, and identified regulatory networks controlling the expression of aroma-synthesis genes by integrating transcriptome data from various organs and developmental stages. We discovered that hormones and transcription factors may collaborate in controlling aroma-synthesis gene expression. Conclusion: This study provides the first high-quality genome sequence and gene annotation for T. mandschuricus, an indigenous thyme species unique to China. The genome assembly and the comprehension of the genetic basis of fragrance synthesis acquired from this research could potentially serve as targets for future breeding programs and functional studies.

Uric acid, high density lipoprotein cholesterol levels and their ratio are related to microbial enterotypes and serum metabolites in females with a blood stasis constitution.

BACKGROUND: Blood stasis constitution in traditional Chinese medicine (TCM) is believed to render individuals more susceptible to metabolic diseases. However, the biological underpinnings of this constitutional imbalance remain unclear. METHODS: This study explored the association between blood stasis constitution, serum metabolic markers including uric acid (UA), high-density lipoprotein cholesterol (HDLC), their ratio (UHR), serum metabolites, and gut microbiota. Clinical data, fecal and serum samples were acquired from 24 individuals with a blood stasis constitution and 80 individuals with a balanced constitution among healthy individuals from Guangdong. Gut microbiota composition analysis and serum metabolomics analysis were performed. RESULTS: Females with a blood stasis constitution had higher UA levels, lower HDLC levels, and higher UHR in serum, suggesting a higher risk of metabolic abnormalities. Analysis of the gut microbiome revealed two distinct enterotypes dominated by Bacteroides or Prevotella. Intriguingly, blood stasis subjects were disproportionately clustered within the Bacteroides-rich enterotype. Metabolomic analysis identified subtle differences between the groups, including lower phenylalanine and higher trimethylaminoacetone levels in the blood stasis. Several differential metabolites displayed correlations with HDLC, UA, or UHR, unveiling potential new markers of metabolic dysregulation. CONCLUSIONS: These findings elucidate the intricate interplay between host constitution, gut microbiota, and serum metabolites. The concept of blood stasis offers a unique perspective to identify subtle alterations in microbiome composition and metabolic pathways, potentially signaling underlying metabolic vulnerability, even in the presence of ostensibly healthy profiles. Continued investigation of this TCM principle may reveal critical insights into the early biological processes that foreshadow metabolic deterioration.

Multi-element Exposure and Cognitive Function in Rural Elderly Chinese.

To investigate the relationship between selenium (Se) based multi-element combined exposure and cognitive function in rural elderly individuals, a cross-sectional study was conducted. The study involved 416 older adults aged 60 and above, residing in four different areas of Enshi county, China, with varying soil Se levels. Inductively coupled plasma mass spectrometry (ICP-MS) was employed to measure the concentrations of Se, copper (Cu), iron (Fe), zinc (Zn), calcium (Ca), magnesium (Mg), cadmium (Cd), arsenic (As), and lead (Pb) in whole blood. Nine standard cognitive tests were applied to assess cognitive function. Analysis of the least absolute shrinkage and selection operator regression (LASSO), covariance (ANCOVA), and generalized linear model (GLM) were utilized to investigate the relationship between element exposure and cognitive function. The results of LASSO revealed that Se, Cu, Fe, Zn, Ca, and Pb were independently identified to be associated with cognition. Both ANCOVA and GLM demonstrated that Se and Ca were correlated with cognitive function. The multi-element model showed higher composite Z scores of 0.32 (95% CI: 0.09 to 0.55) for log-transformed Se (P = 0.007), 0.75 (95% CI: 0.01 to 1.49) for log-transformed Cu (P = 0.048), and a lower score of - 0.67 (95% CI: - 1.26 to - 0.08) for log-transformed Ca (P = 0.025). Furthermore, there was evidence that Se could counteract the negative impact of Ca on cognitive function (P for interaction = 0.031). Our findings suggested that higher levels of Se and Cu were associated with better cognitive function in the elderly and Se can counteract the cognitive damage caused by Ca.

Triptolide inhibits the proinflammatory potential of myeloid-derived suppressor cells via reducing Arginase-1 in rheumatoid arthritis.

Triptolide (TPT) is widely used in the treatment of rheumatoid arthritis (RA). However, its regulatory mechanisms are not fully understood. This study demonstrated that Myeloid-derived suppressor cells (MDSCs) were expanded in both RA patients and arthritic mice. The frequency of MDSCs was correlated with RA disease severity and T helper 17 (Th17) responses. MDSCs from RA patients promoted the polarization of Th17 cells in vitro, which could be substantially attenuated by blocking arginase-1 (Arg-1). TPT inhibited the differentiation of MDSCs, particularly the monocytic MDSCs (M-MDSCs) subsets, as well as the expression of Arg-1 in a dose dependent manner. Alongside, TPT treatment reduced the potential of MDSCs to promote the polarization of IL-17+ T cell in vitro. Consistently, TPT immunotherapy alleviated adjuvant-induced arthritis (AIA) in a mice model, and reduced the frequency of MDSCs, M-MDSCs and IL-17+ T cells simultaneously. The presented data suggest a pathogenic role of MDSCs in RA and may function as a novel and effective therapeutic target for TPT in RA.

Efficacy and safety of intraperitoneal dexamethasone on postoperative nausea and vomiting following laparoscopy: study protocol for a systematic review and meta-analysis.

INTRODUCTION: Intraperitoneal dexamethasone has been reported to be effective to reduce the incidence of postoperative nausea and vomiting (PONV). Therefore, this meta-analysis will analyse the efficacy and safety of intraperitoneal dexamethasone on PONV following laparoscopy. METHODS AND ANALYSIS: Electronic databases (eg, Cochrane Library, PubMed, Excerpta Medica Database, Web of Science, National Institute of Informatics, Oriental Medicine Advanced Searching Integrated System and China National Knowledge Infrastructure) and clinical trial registries will be systematically searched from their inception to 1 October 2022. After the study and data collection processes, we will identify randomised controlled trials that reported details of intraperitoneal dexamethasone on PONV following laparoscopy to conduct a meta-analysis. We will perform the study process and data collection separately. The collected data will be statistically analysed using Review Manager 5.4 software. The risk of bias will be assessed using the Cochrane risk-of-bias tool 2. The Grading of Recommendations Assessment, Development and Evaluation certainty assessment, and a trial sequential analysis will be conducted to ensure the accuracy of this meta-analysis. ETHICS AND DISSEMINATION: Ethical approval and patient consent are not required since this study is a systematic review and meta-analysis. The findings of this meta-analysis will be submitted to a peer-reviewed journal for publication. PROSPERO REGISTRATION NUMBER: CRD42022362924.

Characterization of changes in the intestinal microbiome following combination therapy with zinc preparation and conventional treatment for children with rotavirus enteritis.

Background: Rotavirus (RV) is one of the most common pathogens causing diarrhea in infants and young children worldwide. Routinely, antiviral therapy, intestinal mucosa protection, and fluid supplementation are used in clinic, however this is not efficacious in some severe cases. Zinc supplementation has previously been shown to improve resolution of symptoms from infectious diarrhea. Methods: In this study differences in response rate, duration of hyperthermia, vomiting, and diarrhea, and the persistence time of cough and lung rales in groups were compared. 16SrDNA gene sequencing technology was used to analyze and compare changes in the intestinal microflora of children with RV enteritis who received the conventional treatment with or without the zinc preparation. In addition, the correlations between the differential bacterial species and the related inflammatory factors were determined. Results: Conventional therapy combined with the zinc preparation significantly shortened the duration of hyperthermia, vomiting, and diarrhea compared with the conventional treatment alone. In addition, the time to symptom relief showed that the absorption time of cough and lung rales was significantly shorter in the combination treatment group than that in the conventional treatment group in the children with pneumonia. Further, compared with the conventional treatment, the combined treatment significantly increased the diversity and abundances of florae as compared with the conventional treatment. This combination therapy containing zinc preparation markedly increased the abundances of Faecalibacterium, Bacteroidales, Ruminoccoccoccus, and Lachnospiraceae at the genus level. The LEfSe analysis suggested that Clostridiumbolteae were most significantly altered after the combination therapy. In addition, a correlation analysis revealed significantly negative correlations between the inflammatory factors especially IL-6, TNF-a, CRP and some intestinal florae such as Bacteroides, Faecalibacterium, Blautia, Parabacteroides, Subdoligranulum, and Flavonifractor. Conclusion: Compared with the conventional therapy alone, the combined therapy with the zinc preparation significantly improves symptoms caused by RV. The combination therapy containing the zinc preparation significantly increases the diversity and abundances of some beneficial groups of bacteria. Further, The presence of these groups was further negatively correlated with relevant inflammatory factors. More importantly, this combination therapy containing the zinc preparation provides a reference for the clinical management of children with RV enteritis.

Indole-3-acetic acid and zinc synergistically mitigate positively charged nanoplastic-induced damage in rice.

Recent research has shown that polystyrene nanoplastics (PS-NPs) can inhibit plant growth and the development of crops, such as rice. In this study, we aimed to investigate the effects of PS-NPs of different particle sizes (80 nm, 200 nm, and 2 µm) and charges (negative, neutral, and positive) on rice growth, and to explore the underlying mechanisms and potential strategies for mitigating their impacts. Two-week-old rice plants were planted in a standard ½ Murashige-Skoog liquid medium holding 50 mg/L of different particle sizes and/or charged PS-NPs for 10 days, and the liquid medium without PS-NPs was used as control. The results showed that positively charged PS-NPs (80 nm PS-NH2) had the greatest impact on plant growth and greatly reduced the dry biomass, root length, and plant height of rice by 41.04%, 46.34%, and 37.45%, respectively. The positively charged NPs with a size of 80 nm significantly decreased the zinc (Zn) and indole-3-acetic acid (IAA, auxin) contents by 29.54% and 48.00% in roots, and 31.15% and 64.30% in leaves, respectively, and down-regulated the relative expression level of rice IAA response and biosynthesis genes. Moreover, Zn and/or IAA supplements significantly alleviated the adverse effects of 80 nm PS-NH2 on rice plant growth. Exogenous Zn and/or IAA increased seedlings' growth, decreased PS-NPs distribution, maintained redox homeostasis, and improved tetrapyrrole biosynthesis in rice treated with 80 nm PS-NH2. Our findings suggest that Zn and IAA synergistically alleviate positively charged NP-induced damage in rice.

A Near-Infrared Light-Activated Photocage Based on a Ruthenium Complex for Cancer Phototherapy.

Conventional photocages only respond to short wavelength light, which is a significant obstacle to developing efficient phototherapy in vivo. The development of photocages activated by near-infrared (NIR) light at wavelengths from 700 to 950 nm is important for in vivo studies but remains challenging. Herein, we describe the synthesis of a photocage based on a ruthenium (Ru) complex with NIR light-triggered photocleavage reaction. The commercial anticancer drug, tetrahydrocurcumin (THC), was coordinated to the RuII center to create the Ru-based photocage that is readily responsive to NIR light at 760 nm. The photocage inherited the anticancer properties of THC. As a proof-of-concept, we further engineered a self-assembled photocage-based nanoparticle system with amphiphilic block copolymers. Upon exposure to NIR light at 760 nm, the Ru complex-based photocages were released from the polymeric nanoparticles and efficiently inhibited tumor proliferation in vivo.

Efficient and simultaneous removal of aflatoxin B1, B2, G1, G2, and zearalenone from vegetable oil by use of a metal-organic framework absorbent.

Vegetable oils are usually cocontaminated with different mycotoxins, including aflatoxins and zearalenone, which cause significant food safety issues. Establishment of multitarget, high-efficiency, and low-cost adsorption methods are considered to be ideal solutions for mycotoxin removal in vegetable oils. In this study, we used metal-organic frameworks (MOFs) were used for the simultaneous removal of aflatoxins and zearalenone from vegetable oils. The results showed that MOF-235 simultaneously removed, within 30 min, more than 96.1% of aflatoxins and 83.3% of zearalenone from oils, and oils treated with MOF-235 exhibited di minimis cytotoxicity. Thus, synthesized MOF-235 exhibited sufficient efficacy to remove the targeted residues, as well as safety and reusability, which could be applied as a novel potential adsorbent in the removal of multiple mycotoxins from contaminated vegetable oils.

Add-on Chinese medicine for hospitalized chronic obstructive pulmonary disease (CHOP): A cohort study of hospital registry.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. The effect of Chinese medicine (CM) on mortality during acute exacerbation of COPD is unclear. We evaluated the real-world effectiveness of add-on personalized CM in hospitalized COPD patients with acute exacerbation. METHODS: This is a retrospective cohort study with new-user design. All electronic medical records of hospitalized adult COPD patients (n = 4781) between July 2011 and November 2019 were extracted. Personalized CM exposure was defined as receiving CM that were prescribed, and not in a fixed form and dose at baseline. A 1:1 matching control cohort was generated from the same source and matched by propensity score. Primary endpoint was mortality. Multivariable Cox regression models were used to estimate the hazard ratio (HR) adjusting the same set of covariates (most prevalent with significant inter-group difference) used in propensity score calculation. Secondary endpoints included the change in hematology and biochemistry, and the association between the use of difference CMs and treatment effect. The prescription pattern was also assessed and the putative targets of the CMs on COPD was analyzed with network pharmacology approach. RESULTS: 4325 (90.5%) patients were included in the analysis. The mean total hospital stay was 16.7 ± 11.8 days. In the matched cohort, the absolute risk reduction by add-on personalized CM was 5.2% (3.9% vs 9.1%). The adjusted HR of mortality was 0.13 (95% CI: 0.03 to 0.60, p = 0.008). The result remained robust in the sensitivity analyses. The change in hematology and biochemistry were comparable between groups. Among the top 10 most used CMs, Poria (Fu-ling), Citri Reticulatae Pericarpium (Chen-pi) and Glycyrrhizae Radix Et Rhizoma (Gan-cao) were associated with significant hazard reduction in mortality. The putative targets of the CM used in this cohort on COPD were related to Jak-STAT, Toll-like receptor, and TNF signaling pathway which shares similar mechanism with a range of immunological disorders and infectious diseases. CONCLUSION: Our results suggest that add-on personalized Chinese medicine was associated with significant mortality reduction in hospitalized COPD patients with acute exacerbation in real-world setting with minimal adverse effect on liver and renal function. Further randomized trials are warranted.

Risk factors for the postoperative bladder neck contracture in patients with small-volume prostatic hyperplasia.

OBJECTIVE: This study was to explore the risk factors for postoperative bladder neck contracture (BNC) after transurethral operation of prostate in patients with small-volume prostatic obstruction. METHODS: Clinicopathologic data at our center from February 2016 to January 2020 were retrospectively collected and analyzed. Clinicopathological characteristics between patients with and without BNC were compared. Multivariate logistic regression was used to determine the risk factors for postoperative BNC. RESULTS: There were a total of 39 patients (8.53%) with postoperative BNC. Multivariate logistic regression analysis demonstrated that preoperative bladder neck diameter (BND), intravesical prostatic protrusion (IPP), surgical methods (transurethral resection of prostate (TURP)/anatomical endoscopic enucleation of the prostate (AEEP)), and postoperative urinary tract infection (UTI) were independent risk factors for postoperative BNC in patients with small-volume prostatic obstruction (P < 0.05). The incidence of postoperative BNC in patients undergoing AEEP was significantly decreased compared with those undergoing TURP. The optimal cut-off value of preoperative IPP was 6.10 mm while the optimal cut-off value of preoperative BND was 2.52 cm. CONCLUSIONS: Larger preoperative bladder neck and higher preoperative IPP lead to decreased incidence of postoperative BNC in patients with small-volume prostatic obstruction. Active management of postoperative UTI could effectively prevent the occurrence of postoperative BNC. Compared with TURP, complete AEEP would contribute to reduce BNC in patients with small-volume prostatic obstruction.

A new benzofuran compound from the resinous exudates of Commiphora myrrha.

A new benzofuran derivative, identified as myrrhain A (1), was isolated from the resinous exudates of Commiphora myrrha, together with the four known compounds: commipharane (2), myrrhterpeniod (3), myrrhone (4), and 9-methoxymyrrhone (5). All structures were elucidated by NMR and MS analyses. DPPH assay of compounds 1-5 revealed for the first time that all of them possess moderate antioxidative activity.

Employment Intention of Chinese Medical Students During the COVID-19 Epidemic: A Cross-Sectional Survey.

Context: In the process of combating the coronavirus disease 2019 (COVID-19) epidemic, medical personnel were at the forefront of the fight. As the future medical workforce, medical students often experienced firsthand how their seniors and teachers had to commit to working hard in combating the epidemic. Many were directly involved in the front line of the fight and that experience could easily have affected their intention to seek employment in a medically related career. Objective: The study intended to evaluate the impact of the COVID-19 pandemic on Chinese medical students' employment intentions and the factors associated with them to put forward relevant suggestions to provide a basis for medical education in the future. Design: The research team conducted a cross-sectional study, using an anonymous online questionnaire. Setting: The study took place in many provinces and cities in China and was conducted in an online questionnaire. Participants: Participants were 1114 college students studying clinical medicine, college students studying nursing, and students interning during standardized resident training, medical interns. Outcome Measures: The participants completed a self-administered questionnaire, which investigated their psychological statuses related to anxiety and depression as well as COVID-19's impact on their intentions related to job searches, regarding their willingness to engage in clinical or basic research in epidemic-related specialties and epidemic-related work. Results: Compared to college students studying clinical medicine, the employment intentions of nursing students and medical interns were more vulnerable to the epidemic. Females and nursing students were more reluctant to choose clinical work, and the choice was associated with depression. Nursing college students and medical interns were significantly less willing to engage in infection medicine, respiratory medicine, and intensive care medicine (all P < .001). Medical students with a bachelor's degree and postgraduate degrees were significantly less willing to engage in infection medicine and respiratory medicine (all P < .001), but medical students from regions with stable epidemics were more willing to engage in intensive care medicine. Medical students with a bachelor's degree were significantly less likely to be involved in epidemiology-related work than undergraduate students, and students from severe epidemic regions were significantly less willing to work in isolation wards or to go to Wuhan as volunteers. Conclusions: Participants' psychological statuses related to anxiety and depression, genders, degrees, current educational statuses, and regions affected employment intentions during the epidemic.

Blood Selenium and Serum Glutathione Peroxidase Levels Were Associated with Serum ß-Amyloid in Older Adults.

BACKGROUND: Studies have established the association between blood ß-amyloid (Aß) levels and Alzheimer's disease, but population-based studies concerning the association between selenium (Se) and Aß levels in blood samples are very limited. Therefore, we explored the association in an elderly population with Se status and serum Aß measures. METHODS: A cross-sectional study on 469 elderly individuals from four rural counties with diverse soil Se levels was carried out. Fasting blood Se, serum selenoprotein P (SELENOP), and glutathione peroxidase (GPX), serum Aß42, and Aß40 were measured. Quantile regression models were used to determine the associations of blood Se, serum GPX, and SELENOP with Aß levels. RESULTS: Significant negative associations were observed between blood Se and serum Aß42 and Aß40 levels at all percentiles (P < 0.05). The associations were generally stronger at higher Aß42 and Aß40 percentiles than lower Aß42 and Aß40 percentiles. Blood Se was positively associated with serum Aß42/Aß40 ratio at 25th, 50th, and 75th percentiles. Significant positive associations were observed between serum GPX and Aß42 and Aß40 levels at all percentiles (P < 0.05). The positive associations were generally stronger at higher Aß42 and Aß40 percentiles than at lower percentiles. Serum GPX was negatively associated with Aß42/Aß40 ratio at 25th, 50th, 75th, and 95th percentiles. No associations with serum SELENOP and Aß levels were observed. CONCLUSIONS: Our results suggest that higher Se levels are associated with lower serum Aß42 and Aß40 levels and with higher Aß42/Aß40 ratio, and the results are specific for different selenoproteins.

A New 1,3-Benzodioxole Compound from Hypecoum erectum and Its Antioxidant Activity.

The purpose of this study was to identify the chemical components in aerial parts of Hypecoum erectum. A new 1,3-benzodioxole derivative, identified as Hypecoumic acid (1), was isolated, together with the three known compounds: protopine (2), coptisine (3), and cryptopine (4). Their structures were identified based on extensive spectroscopic experiments, including nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectra (HR-ESI-MS), as well as comparison with those reported in the literature. Meanwhile, the in vitro antioxidative activity of all compounds was determined using a DPPH-scavenging assay, and compound 1 (IC50 = 86.3 ± 0.2 µM) was shown to have moderate antioxidative activity.

Antidepressant-like activity, active components and related mechanism of Hemerocallis citrina Baroni extracts.

Hemerocallis citrina Baroni [Asphodelaceae], which is traditional herbal medicine, has been widely used for treating depressive disorders in Eastern-Asia countries. However, the active compounds and corresponding mechanism of anti-depression are not yet completely clarified. In this study, the anti-depressive activities of six H. citrina extracts were primarily evaluated. The results showed that the water extract of H. citrina flowers (HCW) displays significant anti-depressive activity. A total of 32 metabolites were identified from HCW by high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS) and nuclear magnetic resonance (NMR). And then, the anti-depressive activity of the high-level compound (rutin) in HCW was also estimated. The results indicated that rutin displayed significant anti-depressive activity and was one of the main active ingredients. Finally, the anti-depressive mechanisms of HCW and rutin were investigated based on the intestinal microorganisms. The results showed that HCW and rutin increase the diversity and richness of the intestinal flora and regulate the specific intestinal microorganisms such as Bacteroides and Desulfovibrio genera in depressed mice. This work marks the first comprehensive study of the active components, anti-depressive activities and corresponding mechanisms of different H. citrina extracts, which provide a potential possibility for developing new antidepressants.

Evaluation of enhancing effect of soybean oil on polymalic acid production by Aureobasidium pullulans HA-4D.

Polymalic acid (PMA) is a water-soluble polyester produced by Aureobasidium pullulans. In this study, the physiological response of A. pullulans after the addition of vegetable oils was investigated. Soybean oil (SBO) is pivotal for shortening fermentation time and achieving high PMA titer. With the addition of 1% (w/v) SBO, the titer and productivity of PMA was, respectively, increased by 34.2% and 80%. SBO acted as a chemical stimulatory agent rather than a carbon source, the enhancement on PMA production was attributed to the component of fatty acid. SBO induced the dimorphism (yeast-like cells and mycelia) of A. pullulans, in vitro enzyme activities indicated that the TCA oxidative branch for malic acid synthesis might be strengthened, which could generate more ATP for PMA synthesis, and the assay of intracellular energy supply validated this deduction. This study provided a new sight for recognizing the regulatory behavior of SBO in A. pullulans.

Gambogic acid suppresses nasopharyngeal carcinoma via rewiring molecular network of cancer malignancy and immunosurveillance.

Nasopharyngeal carcinoma (NPC) is a malignant tumor highly prevalent in Southeast Asia. The distant metastasis and disease recurrence are still unsolved clinical problems. In recent years, traditional Chinese medicine (TCM) monomers have become significantly attractive due to their advantages. Using high throughput drug sensitivity screening, we identified gambogic acid (GA) as a common TCM monomer displaying multiple anti-NPC effects. GA could effectively inhibit the proliferation of low differentiated cells and highly metastatic cells in NPC via inducing apoptosis and G2/M cell cycle arrest. In addition, GA obviously repressed the abilities of cell clone, migration, invasion, angiogenesis and represented satisfied synergistic effects combined with chemotherapy. Importantly, we found the elevated immune checkpoint CD47 stimulated after chemotherapy was dramatically impaired by GA treatment. Mechanically, the network pharmacology analyses unraveled that the oncogenic signaling pathways including STATs were rewired by GA treatment. Taken together, our study reveals a molecular basis and provides a rationale for GA application as the treatment regime in NPC therapy in future.