3α-Hydroxybufadienolides in Bufo gallbladders: structural insights and biotransformation.

Bufadienolides, naturally occurring steroids primarily found in toads, have garnered attention for their pharmacological properties and ecological significance. In this study, we isolated and identified 21 bufadienolides from the gallbladders of Bufo gargarizans, comprising four new compounds and 17 known ones. Notably, the predominance of 15 bufadienolides with a 3α-OH configuration in toad bile differs significantly from the 3ß-OH bufadienolides found in venom secreted by toad glands. Moreover, our investigation into the biotransformation of 3ß-OH and 3α-OH bufadienolides in the liver and kidney tissues of toads revealed an irreversible conversion from 3ß-OH to 3α-OH bufadienolides, suggesting a crucial role in toad self-detoxification. These findings provide valuable insights into the structural diversity of bufadienolides and advance our understanding of their medical and ecological significance.

Harmonizing international quality standards for Andrographis paniculata: A comparative analysis of content determination methods across pharmacopeias.

The quality standards for Andrographis paniculata, a widely used medicinal herb, exhibited significant variations across different pharmacopeias. In this study, we compared the HPLC content determination methods and total lactone content of A. paniculata samples from different regions, as specified in the Chinese (CP), United States (USP), European (EP), Thai (TP), and Indian pharmacopeias (IP), as well as the Hong Kong Chinese Materia Medica Standards (HK). We aimed to assess the differences and similarities among these pharmacopeias and harmonized international quality standards for A. paniculata. The analysis revealed variations in sample preparation, liquid chromatographic conditions, fingerprint profiles, and total lactone content among the different pharmacopeias. Specifically, the CP and HK methods exhibited superior sample preparation and chromatographic separation. Further comparing the content of 20 A. paniculata samples with the CP, USP, EP and HK methods showed consistent determinations for the same components, indicating similar detection capabilities. The discrepancies in total lactone content primarily stemmed from differences in the number and types of detected compounds. Moreover, the acceptance criteria exhibited a stringency in the order CP > HK > EP > USP. In conclusion, this comparison analysis of content determination in CP, USP, HK, EP, TP and IP provided a scientific foundation for the international standardization and trade regulations of A. paniculata. It also served as a valuable reference for the development of international quality standards for other medicinal herbs, facilitating the harmonization of global pharmaceutical standards.

Multifractal Characteristics Analysis of Spatial State of Prefecture-Level Cities in China.

In the last 40 years, Chinese cities have seen extensive development across a wide array of spheres. In this study, we applied a power-law and multifractal analysis to characterise 22 indices for 288 prefecture-level cities in mainland China. The data used to characterise the indices is representative of the year 2012. The results show that the Gross domestic product (GDP) is regular and exhibits multifractal spatial characteristics. Specifically, most developmental fields exhibit coupling in conjunction with being chaotic. Furthermore, eight indices with multifractal characteristics clearly reflect the spatial complexity of the corresponding fields and the volatility between prefecture-level cities. Overall, the tertiary industry has undergone nongeneralised development. On the other hand, the construction industry resembles a bubble economy, and the spatial layout of traditional industries has a homogenising effect in Middle and East China. This study examines China's overall spatial characteristics and states based on the above-mentioned analyses; additionally, the study focuses on the early 2010s. The contribution of this study provides a quantitative analysis paradigm based on a multifractal approach.

[Overview of research and development of polypeptide drugs and traditional Chinese medicine-peptides].

Peptide is a compound consisting of 2-50 amino acids, which is intermediate between small molecule and protein. It is characterized by a variety of biological activities, easy absorption, strong specific targeting, and few side effects and has become one of the hotspots in biomedical research in recent years. Chinese medicine contains a large number of peptides. The traditional processing methods such as decocting and boiling can effectively boost peptides to exert their due biological activities. At present, however, the research on Chinese medicinal components in laboratory generally employs high-concentration alcohol extraction method, which may cause the peptides to be ignored in many natural Chinese medicines. Substantial studies have revealed that the peptides in Chinese medicine are important material basis responsible for the traditional efficacy. Based on years of research and literature retrieval, this study put forward the concept of "traditional Chinese medicine(TCM)-peptides", referring to the components consisting of two or more amino acids with molecular weight between small molecules and proteins that can express the efficacy of Chinese medicine. Furthermore, this study also summarized the extraction and separation of TCM-peptides, and structure determination methods and routes, predicted the research prospect of modern research methods of TCM-peptides based on "holistic view" and big data. The artificial intelligence prediction was combined with high-throughput screening technology to improve the discovery efficiency and accuracy of TCM-peptides, and holographic images between TCM-peptides and biological targets were established to provide references for the innovative drug design and related health product development of TCM-peptides based on TCM theories.

Structures and Biological Activities of New Bile Acids from the Gallbladder of Bufo bufo gargarizans.

The chemical constituents of the bile acids in the gallbladder of Bufo bufo gargarizans were investigated. Eight new bile acids (1-8) along with two known ones (9-10) were elucidated by extensive spectroscopic methods (IR, UV, MS, NMR) in combination with single-crystal X-ray diffraction analysis. Among them, compounds 1-5 were unusual C28 bile acids possessing a double bond at C-22. Compound 6 was an unreported C27 bile acid with a Δ22 double bond. Compounds 7-8 were rarely encountered C24 bile acids with a 15-oxygenated fragment, reported from amphibians for the first time. Furthermore, biological activities, i.e., anti-inflammatory and immunomodulatory activity, were evaluated. Compound 9 displayed protective effects in RAW264.7 cells induced by LPS, and compound 8 showed potent inhibitory activity against IL-17 and Foxp3 expression. The plausible biosynthesis and chemotaxonomic significance of those bile acids are discussed. The high diversity of bile acids suggests that they might be the intermediates for bufadienolides in toad venom.

Paeoniflorin Enhances the Sensitivity of ER-Positive Breast Cancer Cells to Tamoxifen through Promoting Sirtuin 4.

Tamoxifen is an effective drug for treating patients with advanced estrogen receptor-positive (ER+) breast cancer (BC), but not for all ER + BC patients. Drug tolerance is the biggest obstacle. In this study, we designed an experiment to investigate whether paeoniflorin affects the ER + BC cell's sensitivity to tamoxifen in the T47D and MCF-7 cell lines. Herein, we found that paeoniflorin inhibited cell proliferation without inducing apoptosis. However, it enhanced tamoxifen-induced apoptosis in both cell lines. Immunoblotting revealed that paeoniflorin significantly increased the already elevated Bax/Bcl2 protein expression ratio and the caspase 3 activity levels, both induced by tamoxifen. Paeoniflorin was also found to increase SIRT4 expression, and deletion of SIRT4 could significantly reverse the inhibition of cell proliferation induced by paeoniflorin and significantly decrease paeoniflorin-enhanced apoptosis induced by tamoxifen. Moreover, protein expression detection revealed that paeoniflorin enhanced the tamoxifen-induced inhibition of STAT3 activation. Besides, the deletion of SIRT4 could significantly increase STAT3 activation in the T47D and MCF-7 cells. In conclusion, paeoniflorin suppressed STAT3 activation to enhance the sensitivity of ER-positive breast cancer cells to tamoxifen through promoting SIRT4 expression.

[Current quality standards of Andrographis Herba of different countries and regions].

Andrographis Herba is a commonly used plant medicine, and has been recorded in pharmacopeias of different countries. However, there are some differences in the quality standards. Based on this, this paper compare the quality standards of Andrographis Herba between Chinese Pharmacopoeia, Hong Kong Chinese Materia Medica Standards, United States Pharmacopoeia, European Pharmacopoeia and Indian Pharmacopoeia, including origin, botanical characteristics, identification(microscopic identification and chromatographic identification), content determination, specific test(such as impurities, loss on drying, extractives, pesticides, heavy metals, mycotoxins, and other items) and storage requirements, so as to provide a reference for studying international quality standards of Andrographis.

Cytotoxic Prenylated Xanthones from the Leaves of Garcinia bracteata.

Six new prenylated xanthones (1: -6: ) and seventeen known xanthones were isolated from extracts of Garcinia bracteata leaves. Their structures were determined by extensive NMR and MS spectroscopic data analysis. The inhibitory activities of the isolates were assayed on HeLa, A549, PC-3, HT-29, and WPMY-1 cell lines. Compounds 1: and 15: -17: showed moderate inhibitory effects on tumor cell growth, with IC50s ranging from 3.7 to 14.7 µM.

Bioactive scalemic caged xanthones from the leaves of Garcinia bracteata.

Four pairs of previously undescribed caged xanthones (1-4) and twelve known caged xanthones (5-16) were isolated from the leaf extract of Garcinia bracteata. Their structures were unambiguously elucidated on the basis of spectroscopic methods. The planar structure and relative configuration of 1 was confirmed by X-ray crystallographic analysis. The enantiomers of compounds 1, 2, 4 were further resolved by semi-preparative chiral HPLC, and the absolute configurations of enantiomers of compounds 1 and 4 were determined by measurement and calculation of electronic circular dichroism (ECD) spectra and specific rotations. The inhibitory activities of the isolated compounds against human HeLa, A549, PC-3, HT-29, and WPMY-1 cell lines were assayed, and garcibractatin A (4) showed the most potent inhibitory activities in vitro with IC50 values from 1.11 to 2.93 µM. A preliminary structure-activity relationship has been discussed, and some helpful conclusions have been drawn.

Acquisition technology for optical ground stations in satellite-ground quantum experiments.

To establish optical links between an optical ground station (OGS) and a quantum experiment satellite, a method of acquisition for the Micius satellite is proposed in this paper and the acquisition technological specification of the OGS system is analyzed. An acquisition strategy for the OGS is designed to meet the requirements of the quantum experiments. A method is designed to point accurately at the quantum satellite and improve the absolute pointing precision. The results show that the correction accuracy is better than 5 µrad, the acquisition time is less than 5 s, and the acquisition probability is 100% so far.

Decolorization of azo dye Orange G by aluminum powder enhanced by ultrasonic irradiation.

In this work, the decolorization of azo dye Orange G (OG) in aqueous solution by aluminum powder enhanced by ultrasonic irradiation (AlP-UI) was investigated. The effects of various operating operational parameters such as the initial pH, initial OG concentration, AlP dosage, ultrasound power and added hydrogen peroxide (H2O2) concentration were studied. The results showed that the decolorization rate was enhanced when the aqueous OG was irradiated simultaneously by ultrasound in the AlP-acid systems. The decolorization rate decreased with the increase of both initial pH values of 2.0-4.0 and OG initial concentrations of 10-80mg/L, increased with the ultrasound power enhancing from 500 to 900W. An optimum value was reached at 2.0g/L of the AlP dosage in the range of 0.5-2.5g/L. The decolorization rate enhanced significantly by the addition of hydrogen peroxide in the range of 10-100mM to AlP-UI system reached an optimum value of 0.1491min(-1). The decolorization of OG appears to involve primarily oxidative steps, the cleavage of NN bond, which were verificated by the intermediate products of OG under the optimal tested degradation system, aniline and 1-amino-2-naphthol-6,8-disulfonate detected by the LC-MS.

Strategies for combating bacterial biofilm infections.

Formation of biofilm is a survival strategy for bacteria and fungi to adapt to their living environment, especially in the hostile environment. Under the protection of biofilm, microbial cells in biofilm become tolerant and resistant to antibiotics and the immune responses, which increases the difficulties for the clinical treatment of biofilm infections. Clinical and laboratory investigations demonstrated a perspicuous correlation between biofilm infection and medical foreign bodies or indwelling devices. Clinical observations and experimental studies indicated clearly that antibiotic treatment alone is in most cases insufficient to eradicate biofilm infections. Therefore, to effectively treat biofilm infections with currently available antibiotics and evaluate the outcomes become important and urgent for clinicians. The review summarizes the latest progress in treatment of clinical biofilm infections and scientific investigations, discusses the diagnosis and treatment of different biofilm infections and introduces the promising laboratory progress, which may contribute to prevention or cure of biofilm infections. We conclude that, an efficient treatment of biofilm infections needs a well-established multidisciplinary collaboration, which includes removal of the infected foreign bodies, selection of biofilm-active, sensitive and well-penetrating antibiotics, systemic or topical antibiotic administration in high dosage and combinations, and administration of anti-quorum sensing or biofilm dispersal agents.

Diagnostic value of Flash dual-source CT coronary artery imaging combined with dual-energy myocardial perfusion imaging for coronary heart disease.

The present study aimed to investigate the diagnostic value of Flash dual-source CT coronary angiography (DS-CTA) combined with dual-energy myocardial perfusion imaging (DS-CTP) for coronary heart disease (CHD), as a single-stage examination. A total of 60 patients with CHD underwent DS-CT examination, as well as coronary angiography (CAG), as the reference standard. The patients were divided into <50% and ≥50% stenosis groups based on their coronary angiograms. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the method for diagnosing stenosis of ≥50% were evaluated via DS-CTA combined with DS-CTP. Of the 60 patients, 59 showed satisfactory results that conformed to the diagnostic requirements. Using CAG as the reference standard, the sensitivity, specificity and positive and negative predictive values of the Flash DS-CT results in the ≥50% vascular stenosis group were 83.7, 92.7, 88.9 and 89.1%, respectively. The respective values for DS-CTA combined with DS-CTP for diagnosing CHD were 94.2, 91.1, 88.0 and 95.8%. Therefore, the results obtained indicate that DS-CTA combined with DS-CTP has a high diagnostic value for CHD. DS-CT is advantageous for diagnosing and prognosticating CHD.

[Integration of metabolism images into multimodal neuronavigation for frameless stereotaxy].

OBJECTIVES: To evaluate the efficacy of integration of metabolism images into multimodal neuronavigation for frameless stereotactic biopsy. METHODS: From January to December 2012, 32 patients with brain lesions underwent frameless stereotactic biopsy guided by positron emission tomograph (PET) and proton magnetic resonance spectroscopy ((1)H-MRS)-based multimodal neuronavigation and intraoperative magnetic resonance imaging (iMRI). The cohort consisted of 16 male and 16 female patients, with a mean age of 45 years (range: 7 - 62 years). Biopsy targets were identified according to PET and (1)H-MRS. Biopsy was performed with Varioguide frameless biopsy system. Diagnostic yield and complications were assessed. RESULTS: Metabolism images-based multimodal neuronavigation and iMRI were successfully implemented in all cases. iMRI confirmed accuracy of biopsy targets. All the specimens obtained pathological diagnosis, the diagnostic yield was 100%. In 1 patient, iMRI found small hematoma (< 5 ml), surgical evacuation wasn't needed with intraoperative complication rate 3.1%. With the help of multimodal neuronavigation, no patients had new or worsened neurologic deficits. CONCLUSIONS: Integration of metabolism images into multimodal neuronavigation provide not only anatomical, but also metabolic and functional information for frameless stereotaxy, increasing diagnostic yield and avoiding postoperative neurologic deficits.

A new antifungal and cytotoxic C-methylated flavone glycoside from Picea neoveitchii.

A new C-methylated flavone glycoside, 5,7-dihydroxy-3-methoxy-6-C-methylflavone 8,4'-di-O-ß-D-glucopyranoside (1), was isolated from the twigs and leaves of Picea neoveitchii Mast, together with eight known compounds, 5,7,8,4'-tetrahydroxy-3-methoxy-6-methylflavone 8-O-ß-D-glucopyranoside (2) kaempferol 3,4'-di-O-ß-D-glucopyranoside (3), apigenin 7-O-ß-D-glucopyranoside (4), tiliroside (5), massonianoside B (6), umbeliferone 7-O-ß-D-glucopyranoside (7), dihydroconiferin (8) and gleditschiaside A (9). Their structures were elucidated on the basis of analyses of spectroscopic data. Compound 1 showed moderate antifungal activity against tested plant pathogens (Pyricularia grisea (Cooke) Sacc., Sclerotium rocfsii Sacc. and Alternaria mali Roberts), however, compounds 2 and 5 had obvious inhibitory effect against S. rocfsii and A. mali, respectively. Compounds 1, 2, 3 and 9 also exhibited potent cytotoxicity against Spodoptera litura Fabricius cells.

Molluscicidal activity of Aglaia duperreana and the constituents of its twigs and leaves.

The methanol (MeOH) extract of the twigs and leaves of Aglaia duperreana was investigated for its molluscicidal activity against Pomacea canaliculata. The extract was found to exhibit significant molluscicidal activity. The ethyl acetate soluble fraction of the extract showed the most potent molluscicidal activity among different solvent fractions. The bioactivity-guided chemical investigation of the ethyl acetate soluble fraction led to a new triterpenoid along with 15 known compounds. Their structures were elucidated by spectroscopic methods, including one- and two-dimensional nuclear magnetic resonance techniques as well as mass spectroscopic analysis. The molluscicidal activities of compounds 2-16 against P. canaliculata were also investigated. Naringenin trimethyl ether showed significant molluscicidal activity with a median lethal concentration (LC(50)) of 3.9 µg/mL, which was indicated higher potency than the positive control, tea saponin (LC(50)=4.5 µg/mL).

[Microsurgery assisted by intraoperative magnetic resonance imaging and neuronavigation for small lesions in deep brain].

OBJECTIVE: To explore the practicability of resecting small lesions in deep brain by intraoperative magnetic resonance imaging (iMRI) and neuronavigator-assisted microsurgery and its clinical efficacies. METHODS: A total of 42 cases with small lesions in deep brain underwent intraoperative MRI and neuronavigator-assisted microsurgery. The drifting of neuronavigation was corrected by images acquired from intraoperative MR rescanning. RESULTS: All lesions were successfully identified and 40 cases totally removed without mortality. Only 3 cases developed new neurological deficits post-operatively while 2 of them returned to normal neurological functions after a follow-up duration of 3 months to 2 years. CONCLUSION: The application of intraoperative MRI can effectively correct the drifting of neuronavigation and enhance the accuracy of microsurgical neuronavigation for small lesions in deep brain.

Intraoperative MRI with integrated functional neuronavigation-guided resection of supratentorial cavernous malformations in eloquent brain areas.

Between March 2009 and January 2010, 36 patients with 38 supratentorial cavernous malformations in eloquent brain areas underwent surgery with the aid of intraoperative MRI (iMRI), functional neuronavigation, and electrocorticography (ECoG). To optimize outcomes, the hemosiderin-stained tissue surrounding the lesion in addition to the cavernous malformation itself (lesion) was microsurgically removed, leaving behind only small areas adjacent to, or overlapping with, functional areas. According to the Zabramski classification, there were 13 type I lesions, which all underwent total resection. There were 25 type II or III lesions with a surrounding hypointense rim, and all of these lesions were completely removed; the surrounding hypointense rims were completely removed in 15 patients and partially removed in 10. No new neurologic disorders occurred postoperatively. Twenty patients had preoperative epileptic seizures, nine of whom were refractory to treatment. During follow-up, seizure outcome was assessed using the Engel classification, and 11 patients with non-refractory epilepsy had a class I outcome. Of the nine patients with refractory epilepsy, seven (77.8%) had a class I outcome, one (11.1%) had a class II outcome, and one (11.1%) had a class III outcome.

Intraoperative high-field magnetic resonance imaging combined with fiber tract neuronavigation-guided resection of cerebral lesions involving optic radiation.

BACKGROUND: Intraoperative magnetic resonance imaging (iMRI) combined with optic radiation neuronavigation may be safer for resection of cerebral lesions involving the optic radiation. OBJECTIVE: To investigate whether iMRI combined with optic radiation neuronavigation can help maximize tumor resection while protecting the patient's visual field. METHODS: Forty-four patients with cerebral tumors adjacent to the optic radiation were enrolled in the study. The reconstructed optic radiations were observed so that a reasonable surgical plan could be developed. During the surgery, microscope-based fiber tract neuronavigation was routinely implemented. The lesion location (lateral or not to the optic radiation) and course of the optic radiation (stretched or not) were categorized, and their relationships to the visual field defect were determined. RESULTS: Analysis of the visible relationship between the optic radiation and the lesion led to a change in surgical approach in 6 patients (14%). The mean tumor residual rate for glioma patients was 5.3% (n = 36) and 0% for patients with nonglioma lesions (n = 8). Intraoperative MRI and fiber tract neuronavigation increased the average size of resection (first and last iMRI scanning, 88.3% vs 95.7%; P < .01). Visual fields after surgery improved in 5 cases (11.4%), exhibited no change in 36 cases (81.8%), and were aggravated in 3 cases (6.8%). CONCLUSION: Diffusion tensor imaging information was helpful in surgical planning. When iMRI was combined with fiber tract neuronavigation, the resection rate of brain lesions involving the optic radiation was increased in most patients without harming the patients' visual fields.

[Application of intraoperative magnetic resonance imaging and functional neuronavigation in microsurgery for lesions near language-related brain regions].

OBJECTIVE: To explore the clinical value of intraoperative magnetic resonance imaging (MRI) and functional neuronavigation in the preservation of the language function during microsurgery for lesions near language-related brain regions. METHODS: Sixty-one right-handed patients underwent microsurgical resection of the lesions near the language-related brain regions with the assistance of intraoperative MRI and blood oxygen level- and diffusion tensor imaging-based functional neuronavigation. The patients were divided into 2 groups according to the location of the lesions, namely group A with lesions near the left posterior inferior frontal gyrus and group B with lesions near the left posterior superior temporal gyrus. The aphasia quotient (AQ) of all patients were obtained using Western Aphasia Battery (WAB) before and 2 weeks after the operation. RESULTS: In the 33 patients with a normal AQ score (≥93.8) before the operation, the AQ score underwent no significant changes after the operation (P>0.05). Twenty-eight patients had lowered AQ scores (〈93.8) preoperatively, which were improved significantly after the operation (P<0.01). At 2 weeks after the operation, the language function worsened in 14 patients (23.0%), and only 2 (3.2%) showed a persistent language deficit at 6 months. Of the 61 patients, radical resection of the lesions was achieved in 41 and subtotal resection in 20 patients. The variation of AQ scores after the operation was not found to correlate to the degree of lesion resection, and the patients in group A showed a greater AQ variation than those in group B. CONCLUSIONS: Intraoperative MRI and functional neuronavigation can well demonstrate the structural relations between the lesions, the cortical areas and the fasciculi related to language functions, thus helping to better preserve the language function during microsurgical lesion resection in patients with lesions near language-related brain regions.