Utilizing a Dual Human Transporter MDCKII-MDR1-BCRP Cell Line to Assess Efflux at the Blood Brain Barrier.

To facilitate the design of drugs readily able to cross the blood brain barrier (BBB), a Madin-Darby canine kidney (MDCK) cell line was established that over expresses both P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP), the main human efflux transporters of the BBB. Proteomics analyses indicate BCRP is expressed at a higher level than Pgp in this cell line. This cell line shows good activity for both transporters [BCRP substrate dantrolene efflux ratio (ER) 16.3 ± 0.9, Pgp substrate quinidine ER 27.5 ± 1.2], and use of selective transporter inhibitors enables an assessment of the relative contributions to overall ERs. The MDCKII-MDR1-BCRP ER negatively correlates with rat unbound brain/unbound plasma ratio, Kpuu Highly brain penetrant compounds with rat Kpuu ≥ 0.3 show ERs ≤ 2 in the MDCKII-MDR1-BCRP assay while compounds predominantly excluded from the brain, Kpuu ≤ 0.05, demonstrate ERs ≥ 20. A subset of compounds with MDCKII-MDR1-BCRP ER < 2 and rat Kpuu < 0.3 were shown to be substrates of rat Pgp using a rat transfected cell line, MDCKII-rMdr1a. These compounds also showed ERs > 2 in the human National Institutes of Health (NIH) MDCKI-MDR1 (high Pgp expression) cell line, which suggests that they are weak human Pgp substrates. Characterization of 37 drugs targeting the central nervous system in the MDCKII-MDR1-BCRP efflux assay show 36 have ERs < 2. In drug discovery, use of the MDCKII-MDR1-BCRP in parallel with the NIH MDCKI-MDR1 cell line is useful for identification of compounds with high brain penetration. SIGNIFICANCE STATEMENT: A single cell line that includes both the major human efflux transporters of the blood brain barrier (MDCKII-MDR1-BCRP) has been established facilitating the rapid identification of efflux substrates and enabling the design of brain penetrant molecules. Efflux ratios using this cell line demonstrate a clear relationship with brain penetration as defined by rat brain Kpuu.

Multiple omics integration analysis reveals the regulatory effect of chitosan oligosaccharide on testicular development.

Infertility is a global health problem affecting millions of people of reproductive age worldwide, with approximately half caused by males. Chitosan oligosaccharide (COS) has strong antioxidant capacity, but its impact on the male reproductive system has not been effectively evaluated. To address this, we integrated RNA-seq, serum metabolomics and intestinal 16 S rDNA analysis to conduct a comprehensive investigation on the male reproductive system. The results showed that COS has potential targets for the treatment of oligospermia, which can promote the expression of meiotic proteins DDX4, DAZL and SYCP1, benefit germ cell proliferation and testicular development, enhance antioxidant capacity, and increase the expression of testicular steroid proteins STAR and CYP11A1. At the same time, COS can activate PI3K-Akt signaling pathway in testis and TM3 cells. Microbiome and metabolomics analysis suggested that COS alters gut microbial community composition and cooperates with serum metabolites to regulate spermatogenesis. Therefore, COS promotes male reproduction by regulating intestinal microorganisms and serum metabolism, activating PI3K-Akt signaling pathway, improving testicular antioxidant capacity and steroid regulation.

Phenylboronic acid-functionalized cross-linked chitosan magnetic adsorbents for the magnetic solid-phase extraction of benzoylurea pesticides.

In this study, a 4-formylphenylboronic acid-modified cross-linked chitosan magnetic nanoparticle (FPBA@CCHS@Fe3 O4 ) was fabricated. The synthesized material was utilized as the magnetic solid-phase extraction adsorbent for the enrichment of six benzoylurea pesticides. In addition to B-N coordination, FPBA@CCHS@Fe3 O4 interacts with benzoylureas through hydrogen bonds and π-π stacking interaction on account of rich active groups (amino and hydroxyl) and aromatic rings in structure. Compared to traditional extraction methods, less adsorbent (20 mg) and reduced extraction time (3 min) were achieved. The adsorbent also exhibited good reusability (no less than 10 times). Coupled with a high-performance liquid chromatography-diode array detector, satisfactory recoveries (89.1-103.9%) and an acceptable limit of detection (0.2-0.7 µg/L) were obtained. Under optimized conditions, the established method was successfully applied to the tea infusion samples from six major tea categories with acceptable recoveries ranging from 76.8 to 110%, indicating its application potential for the quantitative detection of pesticides in complex matrices.

Binding versus Conventional Pancreaticojejunostomy in Preventing Postoperative Pancreatic Fistula: A Systematic Review and Meta-Analysis.

BACKGROUND: The aim of this study was to compare the safety and efficacy of a new technology, binding pancreaticojejunostomy (BPJ), with conventional pancreaticojejunostomy (CPJ) after pancreaticoduodenectomy in preventing postoperative pancreatic fistula (POPF). METHODS: Randomized controlled trials and observational studies were retrieved from literature searches. Pooled OR with 95% CI for dichotomous variables and weighted mean difference with 95% CI for continuous variables were calculated. Fixed-effect and random-effect models as well as subgroup analysis were used for sensitivity analysis. RESULTS: No statistically significant differences were found in the incidence of POPF, delayed gastric emptying, postpancreatectomy hemorrhage, reoperation, morbidity, mortality, operation time, intraoperative blood loss, blood transfusion, and hospital stay between 2 groups. However, the total costs of hospitalization and ordinary stay were higher in BPJ group (€10,513 ± €6,536 vs. €8,238 ± €4,687, p = 0.002; €7,946 ± €5,023 vs. €5,700 ± €2,902, p = 0.015, respectively). CONCLUSIONS: Our study showed BPJ was as safe as CPJ. However, no significant superiority was found in BPJ group regarding the incidence of POPF. The total costs of hospital stay were higher for patients undergoing BPJ. Surgeons can prefer to perform the digestive tract reconstruction of their choice.

Are capecitabine and the active metabolite 5-Fu CNS penetrable to treat breast cancer brain metastasis?

Brain metastasis (BM) is increasingly diagnosed in Her2 positive breast cancer (BC) patients. Lack of effective treatment to breast cancer brain metastases (BCBMs) is probably due to inability of the current therapeutic agents to cross the blood-brain barrier. The central nervous system (CNS) response rate in BCBM patients was reported to improve from 2.6%-6% (lapatinib) to 20%-65% (lapatinib in combination with capecitabine). Lapatinib is a poor brain penetrant. In this study, we evaluated the CNS penetration of capecitabine and hoped to interpret the mechanism of the improved CNS response from the pharmacokinetic (PK) perspective. Capecitabine does not have antiproliferative activity and 5-fluorouracil (5-FU) is the active metabolite. Capecitabine was orally administered to mouse returning an unbound brain-to-blood ratio (Kp,uu,brain) at 0.13 and cerebrospinal fluid (CSF)-to-unbound blood ratio (Kp,uu,CSF) at 0.29 for 5-FU. Neither free brain nor CSF concentration of 5-FU can achieve antiproliferative concentration for 50% of maximal inhibition of cell proliferation of 4.57 µM. BCBM mice were treated with capecitabine monotherapy or in combination with lapatinib. The Kp,uu,brain value of 5-FU increased to 0.17 in the brain tumor in the presence of lapatinib, which is still far below unity. The calculated free concentration of 5-FU and lapatinib in the brain tumor did not reach the antiproliferative potency and neither treatment showed antitumor activity in the BCBM mice. The CNS penetration of 5-FU in human was predicted based on the penetration in preclinical brain tumor, CSF, and human PK and the predicted free CNS concentration was below the antiproliferative potency. These results suggest that CNS penetration of 5-FU and lapatinib are not desirable and development of a true CNS penetrable therapeutic agent will further improve the response rate for BCBM.

[Prevalence status for smokers of undergraduates in Huaihua and the influential factors].

OBJECTIVE: To investigate the prevalence status and the influential factors for smokers of undergraduates in Huaihua. METHODS: The undergraduates from different grades and different professions in Huaihua were selected randomly and investigated using a self-developed questionnaire. The influential factors for smokers of students were analyzed using a Chi-square test and a logistic regression. RESULTS: A total of 1 050 undergraduates were surveyed in our study. Among them, 973 were valid. The rate for students with a habit of smoking was 21.17%. 53.7% of smokers began to smoke at the stage of primary and high schools. The main reason for smoking was due to curious (47.1%) or depressive (45.2%). The male students were more likely to smoke than female students (OR=6.730). The attitudes of parents on smoking, such as no intervention, were important risk factors that affect the children's behavior on smoking (OR=1.866). CONCLUSION: The periods in primary and high school are the most possible time for student to begin smoking. The curiosity and depression are the most risk factors, and the gender and family education are also the important factors that affect the behavior of undergraduates on smoking.

Rapid visual dual-mode detection of Zr(IV) based on L-histidine functionalized gold nanoparticles.

Heavy metal pollution has always been a great threat to human health and safety. Compared with other heavy metals, although zirconium ion (Zr(IV)) is equally harmful, due to the lack of research on Zr(IV) in the biological systems and environment, its detection does not seem to have received the attention it deserves. Herein, a rapid visual dual-mode detection (colorimetric and chrominance method) of Zr(IV) based on L-histidine functionalized gold nanoparticles (HIS-AuNPs) has been reported. AuNPs and HIS-AuNPs before and after adding Zr(IV) were characterized by UV-Vis, TEM, DLS, Zeta potential, EDS and FT-IR, etc. These results showed that L-histidine was successfully modified on the surface of AuNPs by forming a stable Au-N bond, and its modification had little effect on the dispersion degree of AuNPs. After the addition of Zr(IV), interaction of this metal ion with the imidazolyl group on L-histidine can obviously cause the aggregation of HIS-AuNPs within 12 min, and the dispersion state and particle size of HIS-AuNPs can be significantly changed. These two detection modes were established by means of absorbance and color change of solution, and being used in addition and recovery experiments of Zr(IV) in natural water. Under the optimal conditions, these two modes exhibited good linearity within 15-70 and 20-100 µmol L-1, and limit of detection of 2.62 and 6.25 µmol L-1. The proposed method was highly sensitive and selective, which provided a new convenient way to realize the detection of Zr(IV).

Optimized Ginkgo leaf biochar: An efficient adsorbent for 2,4-D herbicide removal from wastewater.

This research exploited biochar, sourced from Ginkgo leaves (GLs), to facilitate the adsorption of 2,4-dichlorophenoxyacetic acid (2,4-D) in aqueous environments. The results reveal that GL biochar, activated with ZnCl2 at a temperature of 500°C (500-ZGBC), demonstrated the greatest specific surface area (SBET) of 536.0 m2 g-1 for 2,4-D adsorption. The biochar's properties, including specific surface area, morphology, structure, thermal stability, and functional groups, were analyzed. Additionally, studies of kinetic and isotherm profiles were conducted, yielding the highest recorded adsorption capacity of 281.8 mg g-1. Pore filling, hydrogen bonding, π-π interactions, surface complexation with Zn groups, and electrostatic interactions contribute significantly to the adsorption performance of 500-ZGBC for 2,4-D. Optimal adsorption was determined to occur at pH 2.117, with a dose of 0.4230 g L-1 of 500-ZGBC, and an initial concentration of 2,4-D at 294.7 mg L-1, as evidenced by the application of the response surface method (RSM). PRACTITIONER POINTS: Premium pharmaceutical-grade biochar, derived from Ginkgo leaves, boasting a SBET of 536.0 m2 g-1 was produced. An absorption capacity reaching 281.8 mg g-1 was observed in Ginkgo leaf biochar for 2,4-dichlorophenoxyacetic acid (2,4-D) adsorption. The adsorption procedure was refined through the employment of response surface methodology.

A multi-omics approach reveals that lotus root polysaccharide iron ameliorates iron deficiency-induced testicular damage by activating PPARγ to promote steroid hormone synthesis.

Iron deficiency is a common nutritional issue that seriously affects male reproductive health. Lotus root polysaccharide iron (LRPF), a novel nutritional supplement, may ameliorate the damage caused by iron deficiency, however, the mechanism is unclear. In this study, we comprehensively determined the benefits of LRPF on reproduction in iron-deficient mice by integrating transcriptomics, microbiomics and serum metabolomics. Microbiomics showed that LRPF could restore changes to the intestinal microbiota caused by iron deficiency. Metabolomics results showed that LRPF stabilised steroid hormone and fatty acid metabolism in iron-deficient mice, reduced the content of ethyl chrysanthemumate (EC) and ameliorated the reproductive impairment. The transcriptomic analysis showed that LRPF regulated steroid hormone synthesis and the peroxisome proliferator-activated receptor (PPAR) signalling pathway in iron-deficient mice. In vitro experiments showed that LRPF could promote steroid hormone synthesis in Leydig cells by activating PPARγ. In conclusion, this study highlights the advantage of LRPF to improve testicular development.

A comprehensive review on potential role of selenium, selenoproteins and selenium nanoparticles in male fertility.

Selenium (Se), a component of selenoproteins and selenocompounds in the human body, is crucial for the development of male reproductive organs, DNA synthesis, thyroid hormone, metabolism, and defence against infections and oxidative damage. In the testis, it must exceed a desirable level since either a shortage or an overabundance causes aberrant growth. The antioxidant properties of selenium are essential for preserving human reproductive health. Selenoproteins, which have important structural and enzymatic properties, control the biological activities of Se primarily. These proteins specifically have a role in metabolism and a variety of cellular processes, such as the control of selenium transport, thyroid hormone metabolism, immunity, and redox balance. Selenium nanoparticles (SeNPs) are less hazardous than selenium-based inorganic and organic materials. Upon being functionalized with active targeting ligands, they are both biocompatible and capable of efficiently delivering combinations of payloads to particular cells. In this review, we discuss briefly the chemistry, structure and functions of selenium and milestones of selenium and selenoproteins. Next we discuss the various factors influences male infertility, biological functions of selenium and selenoproteins, and role of selenium and selenoproteins in spermatogenesis and male fertility. Furthermore, we discuss the molecular mechanism of selenium transport and protective effects of selenium on oxidative stress, apoptosis and inflammation. We also highlight critical contribution of selenium nanoparticles on male fertility and spermatogenesis. Finally ends with conclusion and future perspectives.

Bacillus licheniformis ameliorates Aflatoxin B1-induced testicular damage by improving the gut-metabolism-testis axis.

Global aflatoxin B1 (AFB1) contamination is inevitable, and it can significantly damage testicular development. However, the current mechanism is confusing. Here, by integrating the transcriptome, microbiome, and serum metabolome, we comprehensively explain the impact of AFB1 on testis from the gut-metabolism-testis axis. Transcriptome analysis suggested that AFB1 exposure directly causes abnormalities in testicular inflammation-related signalling, such as tumor necrosis factor (TNF) pathway, and proliferation-related signalling pathways, such as phosphatidylinositide 3-kinases-protein kinase B (PI3K-AKT) pathway, which was verified by immunofluorescence. On the other hand, we found that upregulated inflammatory factors in the intestine after AFB1 exposure were associated with intestinal microbial dysbiosis, especially the enrichment of Bacilli, and enrichment analysis showed that this may be related to NLR family pyrin domain containing 3 (NLRP3)-mediated NOD-like receptor signalling. Also, AFB1 exposure caused blood metabolic disturbances, manifested as decreased hormone levels and increased oxidative stress. Significantly, B. licheniformis has remarkable AFB1 degradation efficiency (> 90%). B. licheniformis treatment is effective in attenuating gut-testis axis damage caused by AFB1 exposure through the above-mentioned signalling pathways. In conclusion, our findings indicate that AFB1 exposure disrupts testicular development through the gut-metabolism-testis axis, and B. licheniformis can effectively degrade AFB1.

Quantification of Hypsarrhythmia in Infantile Spasmatic EEG: A Large Cohort Study.

Infantile spasms (IS) is a neurological disorder causing mental and/or developmental retardation in many infants. Hypsarrhythmia is a typical symptom in the electroencephalography (EEG) signals with IS. Long-term EEG/video monitoring is most frequently employed in clinical practice for IS diagnosis, from which manual screening of hypsarrhythmia is time consuming and lack of sufficient reliability. This study aims to identify potential biomarkers for automatic IS diagnosis by quantitative analysis of the EEG signals. A large cohort of 101 IS patients and 155 healthy controls (HC) were involved. Typical hypsarrhythmia and non-hypsarrhythmia EEG signals were annotated, and normal EEG were randomly picked from the HC. Root mean square (RMS), teager energy (TE), mean frequency, sample entropy (SamEn), multi-channel SamEn, multi-scale SamEn, and nonlinear correlation coefficient were computed in each sub-band of the three EEG signals, and then compared using either a one-way ANOVA or a Kruskal-Wallis test (based on their distribution) and the receiver operating characteristic (ROC) curves. The effects of infant age on these features were also investigated. For most of the employed features, significant ( ) differences were observed between hypsarrhythmia EEG and non-hypsarrhythmia EEG or HC, which seem to increase with increased infant age. RMS and TE produce the best classification in the delta and theta bands, while entropy features yields the best performance in the gamma band. Our study suggests RMS and TE (delta and theta bands) and entropy features (gamma band) to be promising biomarkers for automatic detection of hypsarrhythmia in long-term EEG monitoring. The findings of our study indicate the feasibility of automated IS diagnosis using artificial intelligence.

Identification of Novel, Selective Ataxia-Telangiectasia Mutated Kinase Inhibitors with the Ability to Penetrate the Blood-Brain Barrier: The Discovery of AZD1390.

The inhibition of ataxia-telangiectasia mutated (ATM) has been shown to chemo- and radio-sensitize human glioma cells in vitro and therefore might provide an exciting new paradigm in the treatment of glioblastoma multiforme (GBM). The effective treatment of GBM will likely require a compound with the potential to efficiently cross the blood-brain barrier (BBB). Starting from clinical candidate AZD0156, 4, we investigated the imidazoquinolin-2-one scaffold with the goal of improving likely CNS exposure in humans. Strategies aimed at reducing hydrogen bonding, basicity, and flexibility of the molecule were explored alongside modulating lipophilicity. These studies identified compound 24 (AZD1390) as an exceptionally potent and selective inhibitor of ATM with a good preclinical pharmacokinetic profile. 24 showed an absence of human transporter efflux in MDCKII-MDR1-BCRP studies (efflux ratio <2), significant BBB penetrance in nonhuman primate PET studies (Kp,uu 0.33) and was deemed suitable for development as a clinical candidate to explore the radiosensitizing effects of ATM in intracranial malignancies.

The role of aquaporin 1 activated by cGMP in myocardial edema caused by cardiopulmonary bypass in sheep.

BACKGROUND/AIMS: Most cardiac procedures involve the use of cardiopulmonary bypass (CPB), which pumps oxygenated blood to the body while the heart and lungs are isolated. CPB can cause profound alterations V in the homeostasis of physiological fluids, which often results in myocardial edema. In our study, we used sheep CPB model of in vivo and in vitro to assess the relationship between cGMP and AQP1 during CPB. METHODS: ODQ, a specific inhibitor of soluble guanylate cyclase (sGC), was used to treat the CPB animals or cardiomyocytes. Left ventricular function of each group was determined by pressure-volume system. Water content of myocardial tissue was assessed by dry-wet weight, and cardiomyocytes water permeability was also calculated. The concentration of cGMP was determined by Radioimmunoassay (RIA). mRNA and protein expression of AQP1 were detected by real-time PCR and western blot, respectively. RESULTS: The relative expression level of AQP1 mRNA and protein at each time point (0, 6, 12, 24 or 48 h) after CPB was significantly increased (1.18-fold at 12 h, 1.77-fold at 24 h and 2.18-fold at 48h) compared with each sham group, the protein expression of AQP1 also showed a rising trend after CPB. The degree of myocardial edema (75.1% at 12 h, 79.3% at 24 h and 81.0% at 48h) increased following the CPB surgery. The mRNA expression level of AQP1 was significantly decreased by 39.7% (p<0.01) upon treatment with ODQ compared with the CPB-only group, and inhibition of cGMP pathway also can significantly decrease the degree of myocardial edema (84.7% in control group, while 75.2% in ODQ group) and improve cardiac function in sheep after CPB. Results of in vitro experiments showed the same changing trends as in vivo. CONCLUSION: cGMP pathway controls water channels and then affects water intake during CPB through an AQP1-mediated pathway.

The involvement of AQP1 in heart oedema induced by global myocardial ischemia.

Aquaporin-1 (AQP1) is a member of aquaporin family that was previously proven to be involved in myocardial dysfunction; however, the role of AQP1 in myocardial stunning is less clear. To determine the change of AQP1 expression level in the heart and its effect on oedema after global myocardial ischemia, 40 adult goats underwent cardiopulmonary bypass (CPB) with an aortic cross-clamp time of 2 h and total bypass time of 6, 12, 24, 48 and 72 h followed by subsequent reperfusion. AQP1 function of eight goats was inhibited by HgCl(2) during the 24 h on CPB. All groups were compared with eight sham bypass control goats. Myocardial water content was measured, and the APQ1 mRNA and protein levels were detected by RT-PCR and immunoblotting, respectively. The results showed that the degree of myocardial oedema increased significantly at 6, 12, 24 and 48 h of reperfusion after CPB as compared with the control and recovered at 72 h of subsequent reperfusion. Expression levels of AQP1 mRNA and protein began to increase at 12 h and peaked at 24 h of CPB following reperfusion. Furthermore, myocardial oedema was reduced in the HgCl(2) group compared with the time-matched CPB and control groups. These data suggested that AQP1 expression increases in CPB and AQP1 plays an important role in myocardial oedema during CPB.

Construction of multiple modes using gold nanoparticles as probes for the rapid detection of fenpyroximate.

Herein, three patterns for the detection of fenpyroximate based on the response signal of gold nanoparticles are described. The strong interaction between the guanidine group of arginine-modified gold nanoparticles and the ester group of fenpyroximate led to the aggregation of the nanoparticles and to a variation of ultraviolet-visible light spectrum and color of the solution. Sensors were constructed based on the correlation of the concentration of fenpyroximate with the absorbance ratio (A650/A525) and the R value was obtained by extracting the color of the test solution by using a smartphone to take a photo of the solution, which was then analyzed by colorimeter software. The absorbance ratio increased linearly in the range of 0.225-0.375 mg L-1 and the limit of detection was 0.215 mg L-1, while the R value declined linearly in the range of 0.20-0.40 mg L-1 and the limit of detection was 0.21 mg L-1. Further, the gold nanoparticles could cause a fluorescence quenching of fluorescent dyes, such as rhodamine B, and it was found that the fluorescence could be quenched and then restored after aggregation; therefore, a fluorescence method based on fluorescence "off-on" was constructed, and the fluorescence quenching was found to increase linearly in the range of 0.0-1.0 mg L-1 and the limit of detection was 0.013 mg L-1. These three patterns indicated highly selective and sensitive response signals for fenpyroximate, and all were applied to the detection of fenpyroximate in apple juice, pear juice, and environmental water samples, with the results showing that the three methods could be mutually verified, with the recoveries ranging from 94.15% to 110.65%.

Myxofibrosarcoma involving brachial plexus diagnoses by contrast-enhanced ultrasound: A case report.

RATIONALE: Myxofibrosarcoma most commonly arises as a slowly enlarging, painless mass. We describe an unusual case of low-grade myxofibrosarcoma in the axillary fossa, which infiltrated the brachial plexus, axillary artery, and axillary vein, causing severe pain. The low incidence and complex anatomical structure make imaging examination and surgery face great challenges. To the best of our knowledge, such presentation of a low-grade myxofibrosarcoma that showed an extreme infiltrative growth pattern and presented severe pain has not been reported before. PATIENT CONCERNS: We reported a case of low-grade myxofibrosarcoma developed around the axillary neurovascular bundle, with multiple peripheral metastases in an 87-year-old male. Physical examination revealed a mass on the right axillary fossa measuring 5 × 4 cm. The patient underwent computed tomography but no definite diagnosis was obtained. Because he had claustrophobia and could not perform MRI examination. Thus, he underwent conventional ultrasound and contrast-enhanced ultrasound. Ultrasonic examination not only accurately determines the invasion scope of the tumor, but also clearly shows that the nerve has suffered from the invasion of the exogenous tumor and multiple metastatic foci around it. The contrast enhancement mode of the tumor showed centripetal high-enhancement, uneven internal enhancement, visible enhanced bridge, and non-enhancing central area. DIAGNOSES: Combined with the results of conventional ultrasound and contrast-enhanced ultrasound, we highly suspected it to be soft tissue sarcoma, giving strong clinical assistance. INTERVENTIONS: Given the risk of sarcoma implantation along the needle track and the underestimation of tumor malignancy, an excisional biopsy was considered the most practical choice to avoid unnecessary pain and potential implantation. OUTCOMES: The patient underwent surgery and a histopathological examination of the lesion confirmed it as low-grade myxofibrosarcoma. LESSONS SUBSECTIONS: This report describes a rare case of myxofibrosarcoma of the axillary fossa. High-resolution ultrasound is increasingly used for the initial assessment of soft-tissue masses. However, there are few reports about the ultrasound and contrast-enhanced ultrasound examinations of myxofibrosarcoma. Accurate preoperative diagnosis and proper treatment strategies are critical in managing patients with myxofibrosarcoma. Our case may provide diagnosis experiences and will help better understand and treat this disease.

Exploring pharmaphylogeny from multiple perspectives: a case study on Lithospermeae.

Lithospermeae Dumort., a tribe under the subfamily Boraginoidae, is a perennial herb containing approximately 470 species under 26 genera, primarily distributed in temperate and tropical regions. To gain a deeper understanding of the medicinal plants of Lithospermeae and better protect and develop plant medicinal resources, the phytochemistry, pharmacology, and traditional use of Lithospermeae with medicinal value were analyzed. Phylogenetic analysis was carried out based on the internal transcribed spacer sequence. Through spatial analysis and the species distribution model, the spatial distribution pattern of Lithospermeae medicinal plants was analyzed. Meanwhile, the relevant targets and pathways involved in the pharmacological effects of commonly used medicinal plants were predicted using network pharmacology to further explore the genetic origin of Lithospermeae and enrich the pharmaphylogeny of medicinal plants. In this study, the chemical composition, traditional efficacy, and modern pharmacological activity of Lithospermeae were collected for the first time and analyzed in combination with the geographical distribution model, molecular phylogeny, and network pharmacology. Based on our findings, the pharmaphylogeny of Lithospermeae was preliminarily discussed, providing the scientific basis for basic research regarding Lithospermeae. Concurrently, this study explored the relationship between the development of the regional medicinal plant industry and the protection of biodiversity. Furthermore, our findings provide direction and theoretical guidance for the study of the phylogenetic relationships in medicinal plants and the development of Lithospermeae medicinal plant resources.

Three new compounds with their anti-glioma effects from the roots of Arnebia guttata Bunge.

Three new compounds, arneatas A-C (1-3), together with three known compounds (4-6) were isolated from the roots of Arnebia guttata Bunge. The structures were established on the basis of extensive spectroscopic data including NMR and HRESIMS. All the new compounds (1-3) were tested for their cytotoxic activity against two glioma cell lines (U118-MG and U373-MG) in vitro after treatment for 48 h. Compound 1 exhibited moderate cytotoxic activity against U118-MG and U373-MG glioma cell lines, with IC50 values of 10.4 and 17.5 µM, respectively.

Exploring the optical properties and molecular characteristics of dissolved organic matter in a large river-connected lake (Poyang Lake, China) using optical spectroscopy and FT-ICR MS analysis.

River-connected lakes are complicated and dynamic ecosystems due to their distinctive hydrological pattern, which could significantly impact the generation, degradation, and transformation processes of dissolved organic matter (DOM) and further regulate DOM chemistry in lakes. However, the molecular compositions and characteristics of DOM in river-connected lakes are still poorly understood. Thus, here the spatial variations of optical properties and molecular characteristics of DOM in a large river-connected lake (Poyang Lake) were explored via spectroscopic techniques and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). The results showed high degree of spatial heterogeneity of DOM chemistry (variations in DOC concentrations, optical parameters, and molecular compounds) in Poyang Lake, and the diversity at the molecular level was primarily caused by the heteroatom compounds (N- and S- containing). Compared with classic lakes and rivers, DOM compositions of the river-connected lake had distinctive characteristics (differences in the AImod and DBE values, and CHOS proportions). And the composition characteristics of DOM between the southern and northern parts of Poyang Lake were different (such as the lability and molecular compounds), suggesting the changes of hydrologic conditions may affect the DOM chemistry. In addition, various sources of DOM (autochthonous, allochthonous, and anthropogenic inputs) were identified agreeably based on optical properties and molecular compounds. Overall, this study first characterizes the DOM chemistry and reveals its spatial variations in Poyang Lake at the molecular level, which could improve our understanding of DOM in large river-connected lake systems. Further studies are encouraged to investigate the seasonal variations of DOM chemistry under different hydrologic conditions in Poyang Lake to enrich the knowledge of carbon cycling in river-connected lake systems.