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Progesterone functions as an endocrine-disrupting compound. Imitating endogenous hormones disrupt the animals' hormone levels. The potential hazard of progesterone in milk cannot be neglected. Thus, research has focused on establishing an efficient and convenient pretreatment and analytical approach. In this study, a metal-organic framework (MOF) material UiO-67 was prepared, which possessed a large specific surface area and excellent stability. It was employed to enrich and purify trace progesterones in a complex milk matrix as a filler to integrate the solid phase extraction column. An approach based on MOF was developed using ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). This approach could simultaneously determine seven kinds of progesterone residues in milk. The element spectra of UiO-67 were first measured and analyzed using X-ray photoelectron spectroscopy. The chemical interaction between UiO-67 and progesterone was proved by comparing the changes in binding energy and relative contents of functional groups, and the adsorption efficiency of 1 mg/L and 5 mg/L progesterones by UiO-67 was studied. The adsorption efficiencies of UiO-67 for 1 mg/L and 5 mg/L progesterones were 99.73%-99.95% and 88.87%-99.23%, respectively, according to the results. It proved the efficient adsorption of UiO-67 to progesterones and ensured that subsequent studies went smoothly. Furthermore, key parameters, such as the amount of sorbent, elution solvent type, and pH value, were examined and optimized to obtain optimal extraction recovery of the progesterones. Spiked concentrations of 50 μg/L were employed for extraction optimization. All experiments were performed three times. It also evaluated the matrix effect on mass spectrum signal of the progesterones. The optimized results showed that the seven progesterones could be satisfactorily recovered when the amount of adsorbent was 40 mg, pH value of the sample solution was 5, and elution solution was 5-mL acetone. Additionally, the matrix effect of progesterone in the milk sample was20%. The matrix effect could be neglected using the aforementioned approach to extract and purify progesterones in milk. Finally, the seven progesterones showed good linearity between 1 and 100 μg/L under the optimized conditions, with linear correlation coefficients values0.99. The limits of detection (LODs) ranged from 0.06 to 0.30 μg/L, and limits of quantification (LOQs) ranged from 0.19 to 1.0 μg/L, respectively. At various concentration levels of progesterones in milk, the recoveries were 87.10%-105.58%, with relative standard deviations of 2.66%-9.64%. Most importantly, the approach was successfully employed to determine progesterone levels in milk samples, with results in good agreement with the standard SN/T 1980-2007. The proposed approach had the advantages of high sensitivity and satisfactory accuracy compared with the reported pretreatment and detection approaches of progesterone in milk. Satisfactory experimental results can be obtained without the calibration by isotope inner standard. Meanwhile, considering the excellent performance of MOF materials in reducing matrix interference in complex samples, such the application of materials offers a new approach. It can be employed to enrich and detect hazards in a complex matrix in the future.

Background and Aims. Endotoxemia (ET) is a common critical illness in patients receiving intensive care and is associated with high mortality and prolonged hospital stay. The intestinal epithelial cell dysfunction is regarded as the “engine” of deteriorated ET. Although electroacupuncture (EA) can mitigate endotoxin-induced intestinal epithelial cell dysfunction in ET, the mechanism through which EA improves endotoxin-induced intestinal injury for preventing ET deterioration needs further investigation. Methods. An in vivo ET model was developed by injecting lipopolysaccharide (LPS) in wild-type and PINK1-knockout mice. An in vitro model was also established by incubating epithelial cells in the serum samples obtained from both groups of mice. Hemin and zinc protoporphyrin IX (ZnPP) were applied to activate or inhibit heme oxygenase 1 (HO-1) production. EA treatment was performed for 30 min consecutively for 5 days before LPS injection, and on the day of the experiment, EA was performed throughout the process. Samples were harvested at 6 h after LPS induction for analyzing tissue injury, oxidative stress, ATP production, activity of diamine oxidase (DAO), and changes in the levels of HO-1, PTEN-induced putative kinase 1 (PINK1), mitochondrial fusion and fission marker gene, caspase-1, and interleukin 1 beta (IL-1β). Results. In the wild-type models (both in vivo and vitro), EA alleviated LPS-induced intestinal injury and mitochondrial dysfunction, as indicated by decreased reactive oxygen species (ROS) production and oxygen consumption rate (OCR) and reduced levels of mitochondrial fission proteins. EA treatment also boosted histopathological morphology, ATP levels, DAO activity, and levels of mitochondrial fusion proteins in vivo and vitro. The effect of EA was enhanced by hemin but suppressed by Znpp. However, EA + AP, Znpp, or hemin had no effects on the LPS-induced, PINK1-knocked out mouse models. Conclusion. EA may improve the HO-1/PINK1 pathway-mediated mitochondrial dynamic balance to protect the intestinal barrier in patients with ET.

The improvement of lipid metabolism by capsaicin (CAP) has been extensively studied, mostly with respect to the vanilloid type 1 (TRPV1) ion channel and intestinal flora. In this study, a model was established in germ-free mice by using resiniferatoxin (RTX) to ablate TRPV1 ion channels. Bile acid composition, blood parameters, and colonic transcriptome analyses revealed that CAP could improve dyslipidemia caused by high-fat diet even in the absence of TRPV1 ion channels and intestinal flora. CAP fed to germ mice decreased the concentrations of low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), fasting blood glucose and fasting insulin, increased the concentration of high-density lipoprotein (HDL-C), and decreased the levels of plasma endotoxin and pro-inflammatory factor interleukin 6 (IL-6). Furthermore, CAP could affect both classical and alternative pathways of cholesterol conversion by changing the composition of bile acids, reducing the concentrations of glycocholic acid (GCA), ursodeoxycholic acid (UDCA) and glycochenodeoxycholic acid (GCDCA). First, changing the composition of bile acids inhibited the expression of colon Fgf15. CAP promoted the expression of Cyp7a1 (Cytochrome p450, family 7, subfamily a, and polypeptide 1) in the liver, and thus reduced TC and TG levels. In addition, it could change the composition of bile acids and increase the expression of

CRC, cancer cell; CSCs, cancer stem cells; SOCS3, suppressor of cytokine signaling 3.

Prophylactic antifungal therapy is widely adopted clinically for critical patients and effective in reducing the morbidity of invasive fungal infection and improves outcomes of those diagnosed patients; however, it is not associated with higher overall survival. As intestinal commensal fungi play a fundamental role in the host immune response in health and disease, we propose that antifungal therapy may eliminate intestinal fungi and aggravate another critical syndrome, sepsis. Here, with murine sepsis model, we found that antifungal therapy with fluconazole dismissed intestinal fungal burden and aggravated endotoxin-induced but no gram-positive bacteria-induced sepsis. Nevertheless, antifungal therapy did not exert its detrimental effect on germ-free mice. Moreover, colonizing more commensal fungi in the mouse intestine or administration of fungal cell wall component mannan protected the mice from endotoxin-induced sepsis. On the molecular level, we demonstrated that antifungal therapy aggravated endotoxin sepsis through promoting Gasdermin D cleavage in the distal small intestine. Intestinal colonization with commensal fungi inhibited Gasdermin D cleavage in response to lipopolysaccharide challenge. These findings show that intestinal fungi inhibit Gasdermin D-mediated pyroptosis and protect the mice from endotoxin-induced sepsis. This study demonstrates the protective role of intestinal fungi in the pathogenesis of endotoxin-induced sepsis in the laboratory. It will undoubtedly prompt us to study the relationship between antifungal therapy and sepsis in critical patients who are susceptible to endotoxin-induced sepsis in the future.

Summary As a typical high dimensional nonlinear dynamic problem, the difficulties of the dynamic analysis on the spatial flexible damping beam mostly result from the coupling between the spatial motion and the transverse vibration. Considering the coupling effect and the weak structure damping, the dynamic behaviors of the spatial flexible beam are investigated by a complex structure-preserving method in this paper. Based on the variational principle, the dynamic model of the spatial flexible damping beam is established which can be decoupled into two parts approximately, one controls the spatial motion and another mainly controls the transverse vibration. For the first part, the classic fourth order Runge-Kutta method can be used to discrete it expediently. For the latter part, based on the generalized multi-symplectic idea, the approximate symmetric form as well as the generalized multi-symplectic conservation law is formulated and a fifteen-point scheme equivalent to the Preissmann scheme is constructed. Numerical iterations are performed for six typical initial cases between the two parts to study the dynamic behaviors of the spatial flexible beam. In the numerical experiments, the effects of the damping factor and the initial conditions (including the initial radial velocity and the initial attitude angle) on the dynamic behaviors of the spatial flexible beam are investigated in detail. From the numerical results, it can be concluded that: the damping effect on the long-time dynamic behaviors of the spatial flexible beam could not be neglected even if it is weak; the numerical method proposed in this paper owns the tiny numerical dissipation as well as the excellent long-time numerical stability.

A catalytic system based on Na 2 WO 4 /CH 3 COOH/H 2 O 2 effectively oxidizes natural rubber (NR) to prepare telechelic epoxidised liquid natural rubber (TELNR). The Na 2 WO 4 /CH 3 COOH/H 2 O 2 catalytic system possesses a much higher epoxidation efficiency than the traditional CH 3 COOH/H 2 O 2 system: the epoxidation degree ( X epoxy ) of products increases from merely 5.6% (CH 3 COOH/H 2 O 2 ) to values as high as 52.1% (Na 2 WO 4 /CH 3 COOH/H 2 O 2 ) by reacting for 24 h at 60 °C. Moreover, this catalytic system also induces hydrolytic degradation so that the weight average molecular weight ( M w ¯ ) of NR decreases, e.g., from 14.10 × 10 5 Da (NR) to 0.57 × 10 5 Da (TELNR) after reacting for 30 h. The catalytic process probably proceeds via a mononuclear tungsten peroxo-species with coordinated peracetyl/acetyl group, as suggested by ESI-MS measurements. During oxidation, the tungstic anion [W(CH 3 COOO)(O)(O 2 ) 2 ] − not only catalyzes NR epoxidation, but also induces a further oxidation of epoxy groups to form ketones and aldehydes.

The therapeutic effect of polysaccharide of large yellow croaker swim bladder (PLYCSB) on lupus nephritis has been studied in vivo. A high concentration (50 mg/kg dose) of PLYCSB reduced the levels of serum inflammatory cytokine levels of IL-6, IL-12, TNF-α and IFN-γ compared to a low concentration (25 mg/kg dose) and control mice. SCr, BUN, TC and TG serum levels of PLYCSB treated mice were lower than those of control mice, and TP and ALB serum levels were higher than control mice. Control mice tested ds-DNA positive at the 6th week, and 50 mg/kg treated mice tested at the 10th week after the experiment began. The output of urine protein of 50 mg/kg PLYCSB treated mice was most closely comparable to the normal mice. The glomerular number of 50 mg/kg PLYCSB treated mice was more than the 25 mg/kg dose and control groups, and the 50 mg/kg dose group showed the lowest glomerular sclerosis index in lupus nephritis mice. By RT-PCR and western blot assay, PLYCSB significantly induced inflammation in kidney tissues of mice by downregulating NF-κB-p65, TGF-β1, Fas, FasL and upregulating IκB-α. These results suggest that PLYCSB showed a potential curative effect on lupus nephritis as a drug or functional food.