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Rhein is a key ingredient in many herbal remedies and is widely used. However, herbs containing rhein are frequently associated with poisoning incidents, especially in elderly subjects. Acute and subchronic toxicity of rhein in Kunming mice (KM) was investigated in this experiment. Acute toxicity tests showed a 40% lethality at a given rhein dose of 4000 mg/kg, and the LD50 of rhein was calculated by the bliss method to be greater than 2185.6 mg/kg. In subchronic toxicity, d-gal-induced aged and immature animals were randomized into three groups that were exposed to rhein of 0, 175, and 375 mg/kg/d for 75 days, respectively. No mortality was observed in immature mice group, whereas 55.5% (5/9) subjects in aged mice groups died in the high dosage group. AST, ALT, IL-6, TNF-α levels and typical histopathological changes indicate that rhein causes liver injury. In addition, our investigation explored possible hepatotoxic mechanisms of rhein and experimental results showed increased ROS production, NRF-2 and MDA levels and decreased SOD levels, demonstrating that rhein causes oxidative stress. MMP and mitochondrial swelling levels were able to assess the impact of rhein on mitochondrial function. Furthermore, the effect of rhein on apoptosis can be detected by flow cytometry. Our studies suggested that rhein induces oxidative stress leading to mitochondria dysfunction and apoptotic activation. Multidrug resistance protein (MRP) is an efflux transporter protein and is capable of transporting cellular oxidative stress-related substances. To further clarify the role of MRP in rhein induced oxidative stress, we examined MRP expression in the liver. However, the expression of MRP has no statistical significance. [ABSTRACT FROM AUTHOR]

In this paper, the boundary-based finite element method (BFEM) is developed for the bending-extension coupling analysis of shear deformable laminated composite curved beams with non-uniform thickness. The curved beams are discretized into a series of uniform straight segments. Based upon the first order shear deformation theory and the reciprocal theorem of Betti and Rayleigh, the boundary integral equations (BIEs) associated with each beam segment are derived and expressed in explicit form. The fundamental solutions required in the BIEs are obtained explicitly from the associated Green's function. Since no singular integrals, numerical integrations and function interpolations are involved in the BIEs, our proposed BFEM provides an exact solution for a straight beam with uniform thickness, and only one single element with two end nodes is required for our analysis. Even only an approximate solution is provided for a curved beam with non-uniform thickness, BFEM converges faster than the conventional finite element method, and the results are in well agreement with those obtained by the commercial finite element software. Through the illustrated numerical examples, its generality is shown by: (1) stacking sequence of laminates: symmetric or unsymmetric; (2) beam geometries: straight, stepped, or curvilinear with uniform or non-uniform thickness; (3) loading types: axial force, transverse force and/or bending moment; distributed or concentrated; and (4) supporting conditions: clamped, simply supported, or free; with or without internal supports. • Incorporate with bending-extensional coupling and transverse shear deformations. • Develop BFEM for composite laminated curved beams with non-uniform thickness. • Solve all involved integrals and construct element stiffness matrices explicitly. • Derive explicit-form analytical solutions for straight uniform laminated beams. • Provide more efficient and accurate results than conventional finite element method. [ABSTRACT FROM AUTHOR]

Consider the coupling of stretching-bending deformation induced by the arbitrarily laminated composites, and the transverse shear deformation caused by the thick beams. A mathematical model based upon Timoshenko beam theory is established for the general laminated composite beams, and a proper replacement of stiffness is suggested for narrow or wide beam. By using the state-space approach, a general solution is expressed in terms of matrix exponential, which is applicable for any possible loading and boundary conditions. Expand the matrix exponential through Taylor series, an explicit analytical solution is obtained for the arbitrarily laminated composite beams under general loading conditions. With the obtained general solutions, several analytical solutions are derived explicitly such as the Green's functions for an infinite laminated composite thick beam, and the solutions for some typical beam problems. For example, a cantilever beam, a simply supported beam, or a fixed-end beam, subjected to uniformly distributed load, concentrated force/moment, or sinusoidal load, etc. To cover more complicated beam structures, we develop the boundary element method by using the obtained Green's functions. Three numerical examples are implemented to investigate the influences of stacking sequences and beam geometry, and to validate the applicability of boundary element method. [Display omitted] • Derive analytical solutions for arbitrarily laminated composite thick beams. • Incorporate with coupled stretching-bending and transverse shear deformations. • Provide explicit-form solutions for various loading and supported conditions. • Derive Green's function to develop BEM for curved beams with non-uniform thickness. • Discuss the effects of lamination, thickness, width, and non-uniformity. [ABSTRACT FROM AUTHOR]

Variations in the level of quality and extractive nitrogenous components were investigated in the fresh muscle and commercial dried products of rabbitfish Siganus fuscescens collected from Penghu, Taiwan. The respective freshness quality for fresh muscle is as follows: trimethylamine oxide (TMAO), 29.50 mg N/100 g; trimethylamine (TMA), 2.30 mg N/100 g; NH3, 6.61 mg/100 g; total volatile basic nitrogen (TVBN), 13.32 mg/100 g; aerobic plate count, 1.53 log CFU/g; and K-value, 28.80%. The respective freshness quality for dried products is as follows: TMAO, 43.44 mg N/100 g; TMA, 25.56 mg N/100 g wet wt.; NH3, 52.00 mg/100 g wet wt.; TVBN, 149.98 mg/100 g; aerobic plate count, 4.16 log CFU/g; and K-value, 89.73%. The major fatty acids in the fresh muscle and dried products are C16:0, C18:1 n-9, C18:0, C16:1 C22:6 n-3, and C22:5 n-3. The major nucleotide compound is inosine 5ʹ-monophosphate (IMP) in the fresh muscle (68%) and hypoxanthine (Hx) in the dried products (79%). The level of total free amino acids in the dried products shows significant variation depending on the processing method of the plants. [ABSTRACT FROM AUTHOR]

Three new cage-like monoterpenoid indole alkaloids, scholarisines T–V ( 1 – 3 ), together with three known analogues 4 – 6 were isolated from the leaves of Alstonia scholaris . Among them, 2 represents a unique degraded derivative, whereas 3 shares a rare 5,16- seco lactone scaffold. The structures were mainly established by extensive spectroscopic data analyses, and their plausible biosynthesis pathway from picrinine were proposed. Compared with positive control cefotaxime, alkaloid 2 showed remarkable antibacterial activity against Bacillus subtilis with an MIC value of 3.12 μg/mL, whereas 1 – 3 exhibited significant antibacterial effects on Escherichia coli with an MIC value of 0.78 μg/mL. [ABSTRACT FROM AUTHOR]

Risk factors were examined for subgroups of breast cancer characterized by estrogen receptor (ER) and progesterone receptor (PR) status. Data from the Carolina Breast Cancer Study, a population-based, North Carolina case-control study of 862 breast cancer cases aged 20–74 years diagnosed during 1993–1996 and 790 controls frequency matched on race and age, were obtained by personal interview. ER and PR status was retrieved from medical records (80%) or was determined in the authors' laboratory (11%) but was missing for 9% of cases. The receptor status distribution was as follows: 53% ER+PR+, 11% ER+PR−, 8% ER−PR+, and 28% ER−PR−. Several hormone-related factors were associated with stronger increased risks for ER+PR+ than for ER−PR− breast cancer: the elevated odds ratios were strongest for ER+PR+ breast cancer among postmenopausal women who had an early age at menarche (odds ratio (OR) = 1.6, 95% confidence interval (CI): 1.0, 2.4), nulliparity/late age at first full-term pregnancy (OR = 1.7, 95% CI: 0.9, 3.2 and OR = 1.6, 95% CI: 1.0, 2.7, respectively), or a high body mass index (OR = 1.6, 95% CI: 0.9, 3.0) and among pre-/perimenopausal women who had a high waist-hip ratio (OR = 1.9, 95% CI: 1.2, 3.1). In contrast, family history of breast or ovarian cancer and medical radiation exposure to the chest produced higher odds ratios for ER−PR− than for ER+PR+ breast cancer, especially among pre-/perimenopausal women. Am J Epidemiol 2000;151:703–14. [ABSTRACT FROM PUBLISHER]

Background Bacillus cereus is a ubiquitous gram-positive rod-shaped bacterium that can cause sepsis and neuroinvasive disease in patients with acute leukemia or neutropenia. Methods A single-center retrospective review was conducted to evaluate patients with acute leukemia, positive blood or cerebrospinal fluid test results for B cereus , and abnormal neuroradiographic findings between January 2018 and October 2022. Infection control practices were observed, environmental samples obtained, a dietary case-control study completed, and whole genome sequencing performed on environmental and clinical Bacillus isolates. Results Five patients with B cereus neuroinvasive disease were identified. All patients had acute myeloid leukemia (AML), were receiving induction chemotherapy, and were neutropenic. Neurologic involvement included subarachnoid or intraparenchymal hemorrhage or brain abscess. All patients were treated with ciprofloxacin and survived with limited or no neurologic sequelae. B cereus was identified in 7 of 61 environmental samples and 1 of 19 dietary protein samples—these were unrelated to clinical isolates via sequencing. No point source was identified. Ciprofloxacin was added to the empiric antimicrobial regimen for patients with AML and prolonged or recurrent neutropenic fevers; no new cases were identified in the ensuing year. Conclusions B cereus is ubiquitous in the hospital environment, at times leading to clusters with unrelated isolates. Fastidious infection control practices addressing a range of possible exposures are warranted, but their efficacy is unknown and they may not be sufficient to prevent all infections. Thus, including B cereus coverage in empiric regimens for patients with AML and persistent neutropenic fever may limit the morbidity of this pathogen. [ABSTRACT FROM AUTHOR]

Background: Some researchers have reported that Toxoplasma gondii can cause serious reproductive impairment in male animals. Specifically, T. gondii destroy the quality of sperm in the epididymis, which affects their sexual ability. However, among such studies, none have investigated the male reproductive transcriptome. Therefore, to investigate the relationship between T. gondii and sperm maturation, we infected mice with T. gondii prugniaud (PRU) strain and performed transcriptome sequencing of the epididymis. Results: Compared with the control group, 431 upregulated and 229 downregulated differentially expressed genes (DEGs) were found (P-value < 0.05, false discovery rate (FDR) < 0.05 and |log2 (fold change)| ≥ 1). According to results of a bioinformatics analysis, Gene Ontology (GO) function is divided into three categories: cellular component, molecular function and biological process. Upon performing GO analysis, we found that some DEGs correlated with an integral part of membrane, protein complex, cell surface, ATP binding, immune system process, signal transduction and metabolic process which are responsible for the epididymal injury. DEGs were mapped to 101 unique KEGG pathways. Pathways such as cytokine-cytokine receptor interaction, glycolysis/gluconeogenesis and apoptosis are closely related to sperm quality. Moreover, Tnfsf10 and spata18 can damage the mitochondria in sperm, which decreases sperm motility and morphology. Conclusions: We sequenced the reproductive system of male mice chronically infected with T. gondii, which provides a new direction for research into male sterility caused by Toxoplasma infection. This work provides valuable information and a comprehensive database for future studies of the interaction between T. gondii infection and the male reproductive system. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Leaf of Alstonia scholaris (L.) R. Br. (Apocynaceae), a wide used ethic-medicine in many Asia and Africa counties, has also been recorded as the common traditional Chinese medicine for treatment of illnesses in respiratory system by Dai people. Aim of the study To provide experimental data of clinical adaption of total indole alkaloids (TA) from leaf of A. scholaris for treating post-infectious cough in phase II clinical trial. Materials and methods To model post-infectious cough, all animals except control group were instilled intra-tracheal with lipopolysaccharide (LPS) (80 μg/50 µL/mouse), followed by subsequent exposure to cigarette smoke (CS) for 30 min per day for a total of 30 days. Mice were orally given TA at dose of 10, 25, 50 mg/kg, and four main alkaloids (Sch: scholaricine, Epi: 19-epischolaricine, Val: vallesamine, Pic: picrinine) once daily. Cellular infiltration was assessed in the broncho-alveolar lavage fluid (BALF). Expression of interleukin-6 (IL-6) and C-reactive protein (CRP) in the serum was determined, the superoxide dismutase (SOD) activity as well as malondialdehyde (MDA) content in the serum and homogenate were examined. Finally, histopathological examination in the lungs was assessed by H. E. staining. Results After administration of TA and four major alkaloids respectively, the symptoms of cough in mice were obviously attenuated. Total white blood cells (WBC) and neutrophils (NEU) amounts in BALF were reduced obviously and the pathological damage of lung was also attenuated. There was also significant reduction in IL-6, CRP, MDA and a marked improvement in SOD. Conclusions The efficacy of indole alkaloids against post-infectious cough (PIC) was shown in the down-regulation of inflammatory cells, cytokines, and the balance of antioxidants. What's more, the pharmacological effects of TA were better than single indole alkaloid, which might be related to the synergic effect of four major alkaloids. [ABSTRACT FROM AUTHOR]

Gelselegandines A-C ( 1 – 3 ), three unprecedented gelsedines incorporating additional C 9 aromatic unit as side chain, were isolated from Gelsemium elegans . Their structures were elucidated by means of spectroscopic techniques and electronic circular dichroism (ECD) calculation. Additionally, gelselegandines A–C showed moderate antimicrobial activities against four bacterial strains and two fungi. [ABSTRACT FROM AUTHOR]

Unlike reported bisindoles linked by single bond directly, alstoniasidines A ( 1 ) and B ( 2 ), from Alstonia scholaris featuring unprecedented skeleton with two indole moieties bridged by a sugar, represented a novel bisindole type having strictosamide-glucopyranose-picraline scaffold. Both compounds exhibited selective cytotoxicity against human glioma stem cells (GSCs) and induced caspase-3 dependent extrinsic apoptosis by increasing the expression of interleukin 1 (IL-1), tumor necrosis factor (TNF-α), and the cleaved caspase-3, while damaged the unlimited proliferation and self-renewal capacity of GSCs. This finding might provide new type of leads for the selective killing of human glioma stem cells. [ABSTRACT FROM AUTHOR]