The path from task-specific to general purpose artificial intelligence for medical diagnostics: A bibliometric analysis.

Artificial intelligence (AI) has revolutionized many fields, and its potential in healthcare has been increasingly recognized. Based on diverse data sources such as imaging, laboratory tests, medical records, and electrophysiological data, diagnostic AI has witnessed rapid development in recent years. A comprehensive understanding of the development status, contributing factors, and their relationships in the application of AI to medical diagnostics is essential to further promote its use in clinical practice. In this study, we conducted a bibliometric analysis to explore the evolution of task-specific to general-purpose AI for medical diagnostics. We used the Web of Science database to search for relevant articles published between 2010 and 2023, and applied VOSviewer, the R package Bibliometrix, and CiteSpace to analyze collaborative networks and keywords. Our analysis revealed that the field of AI in medical diagnostics has experienced rapid growth in recent years, with a focus on tasks such as image analysis, disease prediction, and decision support. Collaborative networks were observed among researchers and institutions, indicating a trend of global cooperation in this field. Additionally, we identified several key factors contributing to the development of AI in medical diagnostics, including data quality, algorithm design, and computational power. Challenges to progress in the field include model explainability, robustness, and equality, which will require multi-stakeholder, interdisciplinary collaboration to tackle. Our study provides a holistic understanding of the path from task-specific, mono-modal AI toward general-purpose, multimodal AI for medical diagnostics. With the continuous improvement of AI technology and the accumulation of medical data, we believe that AI will play a greater role in medical diagnostics in the future.

RNA editing events and expression profiles of mitochondrial protein-coding genes in the endemic and endangered medicinal plant, Corydalis saxicola.

Corydalis saxicola, an endangered medicinal plant endemic to karst habitats, is widely used in Traditional Chinese Medicine to treat hepatitis, abdominal pain, bleeding hemorrhoids and other conditions. However, to date, the mitochondrial (mt) genome of C. saxicola has not been reported, which limits our understanding of the genetic and biological mechanisms of C. saxicola. Here, the mt genome of C. saxicola was assembled by combining the Nanopore and Illumina reads. The mt genome of C. saxicola is represented by a circular chromosome which is 587,939 bp in length, with an overall GC content of 46.50%. 40 unique protein-coding genes (PCGs), 22 tRNA genes and three rRNA genes were identified. Codon usage of the PCGs was investigated and 167 simple sequence repeats were identified. Twelve homologous fragments were identified between the mt and ct genomes of C. saxicola, accounting for 1.04% of the entire mt genome. Phylogenetic examination of the mt genomes of C. saxicola and 30 other taxa provided an understanding of their evolutionary relationships. We also predicted 779 RNA editing sites in 40 C. saxicola mt PCGs and successfully validated 506 (65%) of these using PCR amplification and Sanger sequencing. In addition, we transcriptionally profiled 24 core mt PCGs in C. saxicola roots treated with different concentrations of CaCl2, as well as in other organs. These investigations will be useful for effective utilization and molecular breeding, and will also provide a reference for further studies of the genus Corydalis.

Chronic exposure to parabens promotes non-alcoholic fatty liver disease in association with the changes of the gut microbiota and lipid metabolism.

Non-alcoholic fatty liver disease (NAFLD) has become a serious public health issue due to changing dietary patterns and composition. However, the relationship between NAFLD occurrence and food additives, such as preservatives, remains unknown. This study aimed to evaluate the toxicity of parabens, namely methylparaben (MeP) and ethylparaben (EtP), in relation to NAFLD occurrence in mice under different dietary conditions. Exposure to MeP and EtP exacerbated high-fat diet (HFD)-induced obesity, glucose intolerance, higher serum lipid concentrations, and fat accumulation by upregulating genes involved in lipid metabolism. Untargeted metabolomics revealed that arachidonic acid (AA) metabolism was the top enriched pathway upon MeP and EtP exposure in the presence of HFD. 11,12-Epoxyeicosatrienoic acid (11,12-EET) was the most abundant AA metabolite and was significantly reduced upon exposure to MeP or EtP. Moreover, an integrative analysis of differential fecal taxa at the genus level and serum AA metabolites revealed significant associations. In addition, MeP and EtP enhanced lipid accumulation in AML12 cells and HepG2 cells cultured with oleic acid. 11,12-EET supplementation could significantly alleviate lipid accumulation by suppressing the expression of lipid metabolism-related genes and proteins. The present study suggests that chronic exposure to MeP and EtP promoted NAFLD via gut microbiota-dependent AA metabolism. These results highlight the need for reducing oral exposure to synthetic preservatives to improve metabolic disturbance under HFD conditions.

Non-targeted metabolomics strategy reveals the role of Geng-Nian-Shu in regulating ferroptosis in perimenopausal syndrome.

Ovariectomy (OVX) is usually accompanied by the occurrence of metabolic syndrome. Previous studies have shown that Geng-Nian-Shu (GNS) plays an important regulatory role in perimenopausal syndrome (PMS) rats. GNS is a traditional Chinese medicine (TCM) prescription which composed of Suanzaoren Decoction and Ganmai Dazao Decoction in "Jingui Yaolue" and Siwu Decoction in "Heji Jufang". Recently, metabolomics analysis has been used to identify slight changes in the metabolic profile and to help understand disease progression and therapeutic interventions in PMS. However, the mechanism of GNS in the treatment of PMS is still unknown. We purposed to study the metabolic characteristics of PMS by serum and fecal metabolomics, and revealed the internal mechanism of GNS regulating ferroptosis against PMS. The PMS model was established by surgical removal of 4/5 ovaries of rats. HPLC-Q-TOF/MS was used to analyze the metabolomics of rat plasma and feces to explore the potential mechanism of GNS in PMS. The expression of ferroptosis-related proteins in rat ovaries was detected by tissue Prussian blue staining, Elisa kit and Western blotting. Cluster analysis of differential metabolites in plasma and feces between the control group and the model group showed that organic acids and their derivatives, lipids and lipid molecules were mainly disturbed during PMS in rats. After GNS administration, 17 differential metabolites were adjusted, involving several major pathways, such as the tricarboxylic acid (TCA) cycle, biosynthesis of amino acids and biosynthesis of unsaturated fatty acids. Further, we found that GNS affected ferroptosis in ovarian cells by regulating endogenous substances in OVX rats. Our study provides new insights into the mechanism of OVX-induced metabolic syndrome based on non-targeted metabolomics. It provides new ideas for the development and application of GNS and the diagnosis and treatment of PMS.

Pentachlorophenol exposure induced neurotoxicity by disrupting citrulline metabolism in larvae and adult zebrafish.

Pentachlorophenol (PCP) is a ubiquitous environmental toxicant with various adverse effects. Although its neurotoxicity has been reported, the underlying mechanism and subsequent detoxification remain unclear. In this study, embryos and adult zebrafish were exposed to PCP to determine its potential neurotoxic mechanism and protective indicators. The survival rate, heart rate, mobility time, active status and moving distance were significantly decreased in larvae after 30 µg/L PCP exposure. Likewise, the mobile time, latency to the first movement, velocity and moving distance of adult zebrafish were significantly reduced by PCP exposure. Untargeted metabolomics analysis of larvae revealed that arginine and proline metabolism was the primary pathway affected by PCP exposure, reflected by increased proline and decreased citrulline (CIT) contents, which were confirmed by quantitative data. PCP exposure suppressed the conversion from arginine to CIT in larvae by downregulating the expression of nos1 and nos2a. Ornithine content was increased in the brains and intestines of adult zebrafish after PCP exposure, which inhibited ornithine catabolism to CIT by downregulating otc, resulting in reduced CIT. Intriguingly, CIT supplementation significantly restored the neurobehavioral defects induced by PCP in larvae and adult zebrafish. CIT supplementation upregulated the expression of ef1α and tuba1 in larvae and inhibited the downregulation of ef1α in the brains of adult zebrafish. Taken together, these results indicated that CIT supplementation could protect against PCP-induced neurotoxicity by upregulating the expression of genes involved in neuronal development and function.

Antimicrobial Effects of Sophora flavescens Alkaloids on Metronidazole-Resistant Gardnerella vaginalis in Planktonic and Biofilm Conditions.

Bacterial vaginosis (BV) is a common infectious disease of the lower female reproductive tract, which is characterized by the augmentation of anaerobic bacteria. Gardnerella (G.) vaginalis plays a predominant role in BV recurrence relating to its higher virulence potential and biofilm formation ability. With the increased proportion of metronidazole-resistant G. vaginalis, controlling resistance to metronidazole and finding more effective drugs became a major concern. In this study, 30 clinical strains were cultured from the vaginal secretions of BV patients, followed by PCR and 16S rDNA sequencing identification. According to the CLSI guidelines for anaerobic drug sensitivity testing, 19 strains were identified as metronidazole-resistant (minimum inhibitory concentration, MIC ≥ 32 µg/mL), of which 4 clinical strains were observed to be strong biofilm producer and the final minimum biofilm inhibitory concentration (MBIC) of metronidazole was increased to 512 µg/mL. Sophora flavescens Alkaloids (SFAs), a traditional chinese medicine, could not only inhibit the growth of metronidazole-resistant G. vaginalis in planktonic (MIC: 0.3125-1.25 mg/mL), but also eliminate the biofilm formation (MBIC: 0.625-1.25 mg/mL). In the high-magnification scanning electron, it was observed that the morphology of biofilm changed from a thick to flaky shape and was nearly depleted. These results indicate that SFAs could not only inhibit the growth of metronidazole-resistant G. vaginalisin planktonic and biofilm levels, but also destroyed the biofilm morphology and microstructure, which may contribute to the prevention of BV recurrence.

Highly oxygenated germacrane-type sesquiterpenoids from the whole plant of Salvia cavaleriei H.Lév. and their biological activities.

The entire plant Salvia cavaleriei H.Lév. (Lamiaceae) is used as a traditional Chinese herbal medicine. Its leaves are edible, and the flowers can be soaked in water to make a health-care tea. In an effort to find natural bioactive chemical components, twelve undescribed germacrane-type sesquiterpenoids, salcavalins A-L, were isolated from the whole plant of S. cavaleriei and were identified as analogs. This is the first study to isolate highly oxygenated germacrane-type sesquiterpenoids from this plant. The structures of these undescribed compounds were elucidated by various spectroscopic methods, and their absolute configurations were confirmed by single-crystal X-ray diffraction analysis with Cu Kα radiation and electronic circular dichroism calculations. The biological activity of these undescribed compounds on the production of tumor necrosis factor-alpha in lipopolysaccharide induced NR8383 cells was evaluated, and salcavalins I and K showed anti-inflammatory activity to some extent. Salcavalins A-C, F and L were found to be neuroprotective with antiparkinsonic potential in a nematode (Caenorhabditis elegans) model. In addition, salcavalins F and I displayed marked phytotoxic activity against radish seeds at a low concentration of 50 ppm. Our findings provide scientific justification to show that bioactive sesquiterpenoids from the edible herb have anti-inflammatory in vitro, neuroprotective and phytotoxic activities.

Aucubin enhances the antitumor activity of cisplatin through the inhibition of PD-L1 expression in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated mortality in the world. However, the anticancer effects of aucubin against HCC have yet to be reported. Cisplatin often decreased CD8+ tumor-infiltrating lymphocytes in the tumor microenvironment through increasing programmed death-ligand 1 (PD-L1) expression, which seriously affected the prognostic effect of cisplatin in the treatment of patients with HCC. Therefore, it is necessary to identify a novel therapeutic avenue to increase the sensitivity of cisplatin against HCC. PURPOSE: This study aims to evaluate the anti-tumor effect of aucubin on HCC, and also to reveal the synergistic effects and mechanism of aucubin and cisplatin against HCC. STUDY DESIGN AND METHODS: An H22 xenograft mouse model was established for the in vivo experiments. Cancer cell proliferation was detected by MTT assay. RT-qPCR was performed to analyze CD274 mRNA expression in vitro. Western blotting was employed to determine the expression levels of the PD-L1, p-Akt, Akt, p-ß-catenin, and ß-catenin in vitro. Immunofluorescence was carried out to examine ß-catenin nuclear accumulation in HCC cells. Immunohistochemistry was used to detect tumoral PD-L1 and CD8α expression in xenograft mouse model. RESULTS: Aucubin inhibits tumor growth in a xenograft HCC mouse model, but did not affect HCC cell viability in vitro. Aucubin treatment significantly inhibited PD-L1 expression through inactivating Akt/ß-catenin signaling pathway in HCC cells. Overexpression of PD-L1 dramatically reversed aucubin-mediated tumoral CD8+ T cell infiltration and alleviated the antitumor activity of aucubin in xenograft mouse model. Moreover, Cisplatin could induce the expression of PD-L1 through the activation of the Akt/ß-catenin signaling pathway in HCC cells, which can be blocked by aucubin in vitro. In xenograft mouse model, cisplatin treatment induced PD-L1 expression and alleviated the infiltration of CD8+ T lymphocytes in the tumor microenvironment. Aucubin not only abrogated cisplatin-induced PD-L1 expression but also enhanced the antitumor efficacy of cisplatin in a mouse xenograft model of HCC. CONCLUSION: Aucubin exerts antitumor activity against HCC and also enhances the antitumor activity of cisplatin by suppressing the Akt/ß-catenin/PD-L1 axis.

Antimicrobial diterpenoids from the leaves and twigs of Croton kongensis Gagnepain.

Croton kongensis Gagnepain. belongs to the genus Croton, the Euphorbiaceae family, mainly distributed in Hainan and southern Yunnan, China. The aim of present study was to acquire secondary metabolites of the ethanol extract obtained from the leaves and twigs of C. kongensis. Three new abietane-type diterpenoids, crokongenolides A-C (1-3), together with seven known diterpenoids (4-10), were isolated from the leaves and twigs of C. kongensis. The structures of the new compounds were determined by extensive spectroscopic methods (1D and 2D NMR, IR, and HRESIMS), and their absolute configurations were confirmed by single-crystal X-ray diffraction analysis or electronic circular dichroism (ECD) calculations. The absolute configuration of 4 was determined for the first time by single-crystal X-ray diffraction analysis with Cu-Kα irradiation. Some compounds were evaluated for their antimicrobial properties by assessing their inhibitory effects on Staphylococcus aureus, Candida albicans, and Escherichia coli. Compound 10 showed significant antimicrobial activity against S. aureus with MIC value of 1.56 µg/ml.

Biochar and organic fertilizer drive the bacterial community to improve the productivity and quality of Sophora tonkinensis in cadmium-contaminated soil.

Excessive Cd accumulation in soil reduces the production of numerous plants, such as Sophora tonkinensis Gagnep., which is an important and widely cultivated medicinal plant whose roots and rhizomes are used in traditional Chinese medicine. Applying a mixture of biochar and organic fertilizers improved the overall health of the Cd-contaminated soil and increased the yield and quality of Sophora. However, the underlying mechanism between this mixed fertilization and the improvement of the yield and quality of Sophora remains uncovered. This study investigated the effect of biochar and organic fertilizer application (BO, biochar to organic fertilizer ratio of 1:2) on the growth of Sophora cultivated in Cd-contaminated soil. BO significantly reduced the total Cd content (TCd) in the Sophora rhizosphere soil and increased the soil water content, overall soil nutrient levels, and enzyme activities in the soil. Additionally, the α diversity of the soil bacterial community had been significantly improved after BO treatment. Soil pH, total Cd content, total carbon content, and dissolved organic carbon were the main reasons for the fluctuation of the bacterial dominant species. Further investigation demonstrated that the abundance of variable microorganisms, including Acidobacteria, Proteobacteria, Bacteroidetes, Firmicutes, Chloroflexi, Gemmatimonadetes, Patescibacteria, Armatimonadetes, Subgroups_ 6, Bacillus and Bacillus_ Acidiceler, was also significantly changed in Cd-contaminated soil. All these alterations could contribute to the reduction of the Cd content and, thus, the increase of the biomass and the content of the main secondary metabolites (matrine and oxymatrine) in Sophora. Our research demonstrated that the co-application of biochar and organic fertilizer has the potential to enhance soil health and increase the productivity and quality of plants by regulating the microorganisms in Cd-contaminated soil.

Information Seeking and Sensemaking in Emergency Medical Service through Simulation Video Review.

Emergency medical services (EMS) providers often face significant challenges in their work, including collecting, integrating, and making sense of a variety of information. Despite their criticality, EMS work is one of the very few medical domains with limited technical support. To design and implement effective decision support, it is essential to examine and gain a holistic understanding of the fine-grained process of sensemaking in the field. To that end, we reviewed 25 video recordings of EMS simulations to understand the nuances of EMS sensemaking work, including 1) the types of information and situation that are collected and made sense of in the field; 2) the work practices and temporal patterns of EMS sensemaking work; and 3) the challenges in EMS sensemaking and decision-making process. Based on the results, we discuss implications for technology opportunities to support rapid information acquisition and sensemaking in time-critical, high-risk medical settings such as EMS.

Kangfuxiaoyanshuan alleviates uterine inflammation and adhesion via inhibiting NF-κB p65 and TGF-ß/MMP-2 signaling pathway in pelvic inflammatory disease rats.

Background and aims: Pelvic inflammatory disease (PID) is infection-induced inflammation of the female upper reproductive tract that results in high fever, ectopic pregnancy, infertility, and varying degrees of chronic pelvic pain. Recent clinical studies have shown that Kangfuxiaoyanshuan (KFXYS), a Traditional Chinese Medicine (TCM) formulation, may short the course of the disease and reduce the occurrence of PID sequelae, but its pharmacological action and potential mechanism have not been fully elucidated. Here, we aimed to investigate the therapeutic effects and mechanism of KFXYS in rats with PID. Materials and Methods: A PID rat model was constructed through endometrial mechanical injury and pathogen infection. The rectal temperature was measured during the 14-days course of treatment, and the white blood cell (WBC) count in the blood and the levels of cytokines (IFN-γ, IL-1ß, IL-4, TNF-α) in the serum were evaluated by ELISA. Hematoxylin and eosin (HE) staining was performed to analyze pathological changes, and transmission electron microscopy (TEM) was used to observe ultrastructural changes. The p-p65/p65 protein expression was evaluated by western blotting and the levels of MMP-2 and TGF-ß in adhesion tissues were assessed by immunohistochemistry. Results: KFXYS lowered the rectal temperature and the WBC counts in the blood in the acute stage of PID and alleviated inflammatory cell infiltration of the uterus, especially when combined with levofloxacin. KFXYS significantly decreased the levels of proinflammatory cytokines (IFN-γ, IL-1ß, IL-4) and adhesion-related factors (TNF-α) and protected the ultrastructure of endometrial epithelial cells. Mechanistically, KFXYS inhibited the NF-κB activation by decreasing phosphorylation of p65, thus the alleviation of inflammation further reduced the expression of TGF-ß and MMP-2, and inhibited the occurrence of uterine adhesions. Conclusion: These results revealed that KFXYS alleviated pelvic inflammation and effectively inhibits inflammation-associated adhesion, which indicated the potential role of KFXYS for treatment of PID and the prevention of PID sequelae.

Diterpenoids with α-glucosidase inhibitory activities from the fruits of Vitex trifolia Linn.

Viticis Fructus, known as "Man-jing-zi", are the fruits of the traditional Chinese medicine Vitex trifolia Linn. and its variant Vitex trifolia Linn. var. simplicifolia. These fruits are used as folk medicines to treat various diseases. Although V. trifolia is useful for treating diabetes, the antidiabetic effect of its purified constituents is still under investigation. The phytochemical investigation on the ethanol extract of the fruits of V. trifolia yielded four new labdane diterpenoids vitetrolins A-D (1-4), together with seven (5-11) known analogs. The structures of these compounds were elucidated by spectroscopy techniques and the absolute configuration of 4 was determined by electronic circular dichroism (ECD) calculations. The isolated diterpenoids were evaluated for their α-glucosidase inhibitory activities. Compounds 5, 6, 8, and 9 exhibited moderate inhibitory activities against α-glucosidase with IC50 values ranging from 44.9 ± 6.1 to 70.5 ± 5.5 µM.

Emergent ferroelectricity in subnanometer binary oxide films on silicon.

The critical size limit of voltage-switchable electric dipoles has extensive implications for energy-efficient electronics, underlying the importance of ferroelectric order stabilized at reduced dimensionality. We report on the thickness-dependent antiferroelectric-to-ferroelectric phase transition in zirconium dioxide (ZrO2) thin films on silicon. The emergent ferroelectricity and hysteretic polarization switching in ultrathin ZrO2, conventionally a paraelectric material, notably persists down to a film thickness of 5 angstroms, the fluorite-structure unit-cell size. This approach to exploit three-dimensional centrosymmetric materials deposited down to the two-dimensional thickness limit, particularly within this model fluorite-structure system that possesses unconventional ferroelectric size effects, offers substantial promise for electronics, demonstrated by proof-of-principle atomic-scale nonvolatile ferroelectric memory on silicon. Additionally, it is also indicative of hidden electronic phenomena that are achievable across a wide class of simple binary materials.

Serum metabonomics as a diagnostic approach for cancer-related fatigue.

In the present study, differences in metabolic pathways between patients with and without cancer-related fatigue (CRF) were examined to identify metabolic serum biomarkers of CRF. In this preliminary study, metabolic profiling was applied to analyze the serum samples from 14 patients with CRF and 11 non-CRF individuals (non-fatigue cancer survivors) by ultra-performance liquid chromatography coupled with mass spectrometry. Orthogonal partial least-squares discriminant analysis was adopted to evaluate the differences between the CRF and non-CRF groups. The CRF group was characterized by increases in phosphatidylethanolamine (PE; 18:0/0:0), LysoPE (0:0/20:4 and 0:0/16:0), lysophosphatidylcholine (LysoPC; 20:4, 22:4 and 16:0) and LysoPC/PC, phosphatidylserine (21:0/0:0), glycerophosphocholine and N-docosahexaenoyl γ-aminobutyric acid. Furthermore, decreases in anandamide, uric acid, dihydrouracil, LysoPE (0:0/22:5), 2,5,7,8-tetramethyl-2(2'-carboxyethyl)-6-hydroxychroman, 19(R)-hydroxy-prostaglandin F1α, N-(3α,12α-dihydroxy-5ß-cholan-24-oyl)-glycine, ketoleucine, indoxyl sulfate, α-N-phenylacetyl-L-glutamine and 1-linoleoyl-glycerophosphocholine were detected. These data indicate a possible disturbance in the metabolism of phospholipids and adjustments in the endocannabinoid system. The metabonomic approach may be helpful to determine the pathophysiological mechanisms of CRF and the identification of potential biomarkers for the accurate diagnosis of CRF. All clinical data were obtained from the 'Research on the efficacy of traditional Chinese medicine comprehensive intervention in cancer-related fatigue' (TCM-CRF) project. Medical Ethical Approval for TCM-CRF was approved by the Chinese Ethics Committee of Registering Clinical Trials. The approval number for the TCM-CRF study was ChiECRCT-2013038, and the TCM-CRF study was completed.

Agricultural non-point sources and their effects on chlorophyll-a in a eutrophic lake over three decades (1985-2020).

Erhai Lake is the second largest freshwater lake in Yunnan Province but suffers from the deterioration of water quality and agricultural non-point source pollution (ANPSP). However, little is known about the influence of ANPSP on the water quality of Erhai Lake. The export coefficient model (ECM) was used to obtain the total nitrogen (TN) and total phosphorus (TP) loads from ANPSP in Erhai Lake Basin (ELB). The trophic status of Erhai Lake as influenced by such sources of nutrient input was also been assessed. Results indicated that the TN and TP loads in ELB increased from 1985 to 2005 due to sustainable agricultural development; thereafter, the TN and TP loads decreased from 2005 to 2020, indicating that agricultural pollution prevention improved in ELB. The northern part of ELB had higher pollution intensity than the southern part and the central part, indicating that the ecosystem in the northern part of ELB appeared to be vulnerable. Driving force analysis showed that cattle breeding was the main reason for the exported TN loads in most watersheds, and intensive agricultural planting was the major contributor to TP loads. The mean annual Chl-a concentration had a strong correlation with the TN and TP loads exported from north of ELB, and this finding suggested that ANPSP could lead to eutrophication. The results of this study demonstrate the impacts of agricultural activities on water quality at the watershed scale and provide a scientific foundation for lake management decision-making.

Two new aromatic derivatives from Codonopsis pilosula and their α-glucosidase inhibitory activities.

The ethanol extract of the roots of Codonopsis pilosula was subjected to chromatographic fractionation, which result in the isolation and characterization of two new aromatic derivatives 2,3-dihydroxypropyl 2,4-dihydroxy-3,6-dimethylbenzoate (1) and 2-oxopropyl 3-hydroxy-4-methoxybenzoate (2), along with three known compounds pilosulinene A (3), pollenfuran B (4) and (+)-pinoresinol (5). Their structures were demonstrated by HRESIMS and spectroscopic methods including NMR and IR. It is worth noting that compound 4 was isolated for the first time from the genus Codonopsis. The potential hypoglycemic properties of compounds 2-5 were evaluated by measuring their α-glucosidase inhibitory effects. As a result, compounds 2 and 3 showed weak α-glucosidase inhibitory activities with IC50 values of 154.8 ± 11.0 µM and 24.0 ± 2.2 µM, respectively.[Formula: see text].

Gene set enrichment analysis and ingenuity pathway analysis to identify biomarkers in Sheng-ji Hua-yu formula treated diabetic ulcers.

ETHNOPHARMACOLOGICAL RELEVANCE: Sheng-ji Hua-yu (SJHY) formula is a Chinese herbal prescription for diabetic ulcers (DUs) treatment, which can accelerate wound reconstruction and shorten the healing time. However, its mechanism role maintains unclear. AIM OF THE STUDY: To elucidate the molecular mechanisms of SJHY application on DUs. MATERIALS AND METHODS: To begin with, transcriptome sequencing was adopted to identified differentially expression mRNAs among normal ulcers, DUs, and DUs + SJHY treatment in vivo. Liquid chromatography-tandem mass spectrometry was applied for the quality control of SJHY formula. GO and KEGG enrichment analysis were used to identify the mechanisms underlying the therapeutic effect of SJHY formula, and then gene set enrichment analysis and ingenuity pathway analysis were conducted for functional analysis. Further, qPCR detection was performed in vivo for validation. RESULTS: SJHY administration could regulate the glucose metabolic process, AMPK and HIF-1 pathway to accelerate healing processes of DUs. Besides, CRHR1, SHH, and GAL were identified as the critical targets, and SLC6A3, GRP, FGF23, and CYP27B1 were considered as the upstream genes of SJHY treatment. Combined with animal experiments, the prediction results were validated in DUs mice model. CONCLUSIONS: This study used modular pharmacology analysis to identify the biomarkers of SJHY formula and provide the potential therapeutic targets for DUs treatment as well.

Engineering Radiosensitizer-Based Metal-Phenolic Networks Potentiate STING Pathway Activation for Advanced Radiotherapy.

Radiotherapy, a mainstay of first-line cancer treatment, suffers from its high-dose radiation-induced systemic toxicity and radioresistance caused by the immunosuppressive tumor microenvironment. The synergy between radiosensitization and immunomodulation may overcome these obstacles for advanced radiotherapy. Here, the authors propose a radiosensitization cooperated with stimulator of interferon genes (STING) pathway activation strategy by fabricating a novel lanthanide-doped radiosensitizer-based metal-phenolic network, NaGdF4 :Nd@NaLuF4 @PEG-polyphenol/Mn (DSPM). The amphiphilic PEG-polyphenol successfully coordinates with NaGdF4 :Nd@NaLuF4 (radiosensitizer) and Mn2+ via robust metal-phenolic coordination. After cell internalization, the pH-responsive disassembly of DSPM triggers the release of their payloads, wherein radiosensitizer sensitizes cancer cells to X-ray and Mn2+ promote STING pathway activation. This radiosensitizer-based DSPM remarkably benefits dendritic cell maturation, anticancer therapeutics in primary tumors, accompanied by robust systemic immune therapeutic performance against metastatic tumors. Therefore, a powerful radiosensitization with STING pathway activation mediated immunostimulation strategy is highlighted here to optimize cancer radiotherapy.

'Green' nanotherapeutics from tea leaves for orally targeted prevention and alleviation of colon diseases.

Although synthesized nanotherapeutics (NTs) are attractive for the oral treatment of colon diseases, their clinical translations are constrained by the unsatisfactory therapeutic outcomes, potential adverse effects, and high cost of mass production. Here, we report the development of tea leaf-derived natural NTs with desirable particle sizes (140.0 nm) and negative surface charge (-14.6 mV). These natural exosome-like NTs were found to contain large amounts of lipids, some functional proteins, and many bioactive small molecules. Specifically, galactose groups on the surface of NTs could mediate their specific internalization by macrophages via galactose receptor-mediated endocytosis. Moreover, these NTs were able to reduce the production of reactive oxygen species, inhibit the expression of pro-inflammatory cytokines, and increase the amount of anti-inflammatory IL-10 secreted by macrophages. Orally administered NTs could efficiently inhibit the inflammatory bowel responses, restore disrupted colonic barriers and enhance the diversity and overall abundance of gut microbiota, thereby preventing or alleviating inflammatory bowel disease and colitis-associated colon cancer. The present study brings new insights to the facile application of a versatile and robust natural nanoplatform for the prevention and treatment of colon diseases.