Effect of Copper Addition on the Formability of 304L Austenitic Stainless Steel.

To improve the antibacterial properties of 304L austenitic stainless steel, copper is often added as an antibacterial agent, but the forming performance of the resulting material is poor, impacting its actual production and use. Therefore, this study investigated the influence of copper addition on the formability of 304L austenitic stainless steel with drawing, cupping and conical cup forming tests. Mechanical properties were determined with tensile and hardness tests. The microstructure and phase transformation were further characterized by metallographic microscopy, scanning electron microscopy and x-ray diffraction analysis. It was found that the addition of copper impaired the mechanical properties of 304L austenitic stainless steel, increased the stacking fault energy of the material and inhibited the occurrence of strain-induced martensite transformation, leading to a decrease in the formability of 304L austenitic stainless steel.

A semi-packed gas chromatography column with high-density elliptic cylindrical posts.

Semi-packed columns are microfabricated gas chromatography columns which have a large surface area and high aspect ratio. In this paper, a new semi-packed column with high-density elliptic cylindrical posts (SCHECP) made by a micro-electro-mechanical system (MEMS) technique was reported. Compared to a semi-packed column with cylindrical posts (SCCP) under the same effective width, the surface area and aspect ratio of SCHECP were improved by 71.19% and 76.47%, respectively. To compare the performance of these two semi-packed columns, SCHECP and SCCP were fabricated. A 10-nm thick alumina film was deposited as the stationary phase by atomic layer deposition technique to ensure the uniformity and repeatability of the stationary-phase film. A contrast experiment was conducted, and the results showed that compared with SCCP, better separation performance was realized in SCHECP due to the increase in surface area and aspect ratio. The number of theoretical plates of nonane was increased by 541.84%, and the tailing factor was decreased by 54.31%.

Molecular mechanism of Chuanxiong Rhizoma in treating coronary artery diseases.

Objective: Most of the studies on the herb Chuanxiong Rhizoma (CR) have focused on the l-arginine-nitric oxide (NO) pathway, but the nitrate-nitrite-NO (NO3 --NO2 --NO) pathway was rarely investigated. Therefore, the aim of this study was to evaluate the effects and mechanisms of action of CR in coronary artery disease (CAD). Methods: The NO3 -, NO2 - and NO levels were examined in the NO3 --NO2 --NO pathway. High-performance ion chromatography was used to quantify NO3 - and NO2 - levels. Then, NO was quantified using a multifunctional enzyme marker with a fluorescent probe. The tension of aortic rings was measured using a multi myograph system. Results: High content of NO3 - and low content of NO2 - was found in CR, and which could potently convert NO3 - to NO2 - in the presence of endogenous reductase enzyme. Incubating human coronary artery endothelial cells (HCAECs) with CR-containing serum showed that CR significantly decreased the NO3 - content and increased the levels of NO2 - and NO in the cells under hypoxic conditions. In addition, CR significantly relaxed isolated aortic rings when the l-arginine -NO pathway was blocked. The optimal concentration of CR for relaxation was 200 mg/mL. Conclusion: CR supplements large amounts of NO in cells and vessels to achieve relaxation via the NO3 --NO2 --NO pathway, thereby making up for the deficiency caused by the lack of NO after the l-arginine-NO pathway is suppressed. This study also supports the potential use of a traditional Chinese herb for future drug development.

Near-Infrared II Phototherapy Induces Deep Tissue Immunogenic Cell Death and Potentiates Cancer Immunotherapy.

The deep and inner beds of solid tumors lack lymphocytic infiltration and are subjected to various immune escape mechanisms. Reversing immunosuppression deep within the tumor is vital in clinical cancer therapy, however it remains a huge challenge. In this work, we have demonstrated the use of a second window near-infrared (NIR(II)) photothermal treatment to trigger more homogeneous and deeper immunogenic cancer cell death in solid tumors, thereby eliciting both innate and adaptive immune responses for tumor control and metastasis prevention. Specifically, photothermal transducers with similar components, structures, and photothermal conversion efficiencies, but different absorptions in red light, NIR(I), and NIR(II) biowindows, were constructed by controlling the self-assembly of gold nanoparticles on fluidic liposomes. In vitro, photothermal treatments induced immunogenic cell death (ICD) that were accompanied by the release of damage-associated molecular patterns (DAMPs) regardless of the wavelength of incident lasers. In vivo, NIR(II) light resulted in a more homogeneous release and distribution of DAMPs in the deeper parts of the tumors. With the induction of ICD, NIR(II) photothermal therapy simultaneously triggered both innate and adaptive immune responses and enabled efficient tumor control with 5/8 of the mice remaining tumor-free in the cancer vaccination assay. Additionally, the NIR(II) photothermal treatment in combination with checkpoint blockade therapy exerted long-term tumor control over both primary and distant tumors. Finally, using systemically administered two-dimensional polypyrrole nanosheets as a NIR(II) transducer, we achieved striking therapeutic effects against whole-body tumor metastasis via a synergistic photothermal-immunological response.

BaiJiu Increases Nitric Oxide Bioactivity of Chinese Herbs Used to Treat Coronary Artery Disease Through the NO3--NO2--NO Pathway.

BaiJiu (BJ) is a type of Chinese rice wine combined with the traditional Chinese herbs GuaLou (GL) and XieBai (XB), which have been used to treat and prevent coronary artery disease for nearly 2000 years in China. However, the mechanisms behind the compatibility of the components of this compound (GLXBBJ) have not been deeply investigated. In this study, the compatibility of the GLXBBJ compounds with nitric oxide (NO) bioactivity was evaluated in herbs, cells, and isolated aortic rings. Nitrate (NO3) and nitrite (NO2) concentrations were quantified by the Griess method. Nitric oxide (NO) was quantified by a multifunctional enzyme marker using a fluorescent probe. Qualitative analysis of L-arginine-endothelial NO synthase (eNOS) was performed by Western blotting. The tension of aortic rings was measured by multimyograph system. The ability of BJ to reduce NO3 to NO2 and NO2 to NO was strongest under hypoxic conditions and was not affected by temperature. BJ-containing serum significantly decreased the NO3 content and increased the NO2 content in hypoxic cells. Combining BJ with GL, XB, or GLXB resulted in stronger vasodilation effects. These results demonstrate that BJ effectively reduces NO3/NO2, although only a small amount of NO3 is present. Once combined with GL, XB, or GLXB, which are rich in NO3/NO2, robust NO bioactivity was generated through the NO3-NO2-NO pathway. Therefore, this study supports the potential of using traditional Chinese herbs for promoting medical innovation and for future drug development.

Duration of periconceptional folic acid supplementation and risk of gestational diabetes mellitus.

BACKGROUND AND OBJECTIVES: Increased consumption of folic acid is prevalent, raising concerns about possible adverse effects. This prospective study aimed to explore the associations between the duration of folic acid supplementation and the risk of gestational diabetes mellitus (GDM) in Chinese women. METHODS AND STUDY DESIGN: A total of 326 pregnant women were prospectively included for detailed information on folic acid supplementation during pre-pregnancy and early pregnancy, lipid profiles at 16-18 weeks, and subsequent GDM diagnosis at 24-28 weeks. Associations among folic acid supplementation, lipid profiles, and risk of GDM were analyzed using linear and logistic regression models, adjusting for potential confounders. RESULTS: The incidence of GDM in participants was 10.1%. We observed a U-shape relation between duration of folic acid supplementation and risk of GDM. Women who did not take folic acid and took folic acid for >90 days had a higher incidence of GDM compared to those who took folic acid for <=60 days. Moreover, lipid profiles were positively correlated with duration of folic acid supplementation and risk of GDM. After adjusting for demographic characters, energy and nutrients intakes and lipid profiles, the adjusted OR of GDM comparing taking folic acid for >90 days with taking folic acid for <=60 days was 3.45 (95% CI: 1.01, 11.8). CONCLUSIONS: This prospective study indicate a positive association among prolonged folic acid supplementation, lipid profiles in the second trimester, and risk of GDM. Future studies are warranted to verify the causal relationship and underlying mechanisms.

A metabolomic study based on accurate mass and isotopic fine structures by dual mode combined-FT-ICR-MS to explore the effects of Rhodiola crenulata extract on Alzheimer disease in rats.

A metabolomic strategy based on accurate mass and isotopic fine structures (IFSs) by dual mode combined-Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) was established to explore the effects of Rhodiola crenulata extract (RCE) on Alzheimer disease (AD) in rats. Experimental AD model was induced in rats by bilateral hippocampal injection of Aß1-42, and Morris water maze task (MWM) was used to evaluate the effects of RCE on AD. Subsequently, the metabolomic study was performed using HPLC-FT-ICR-MS, fraction collector and direct infusion (DI)-FT-ICR-MS to screen and identify the potential biomarkers. A total of 20 metabolites contributing to AD progress were identified, and 17 metabolites of them were restored to the control-like levels after RCE treatment (daily dose: 2.24 g/kg). The metabolic pathway analysis revealed that the disturbed pathways including tryptophan metabolism, sphingolipid metabolism and glycerophospholipid metabolism in AD model rats were regulated after high dose RCE application. It is the first time that the dual mode combined-FT-ICR-MS based metabolomic strategy was applied to biochemically profile the serum metabolic pathways of AD rats affected by RCE. These outcomes provide reliable evidence to illuminate the biochemical mechanisms of AD and facilitate investigation of the therapeutic benefits of RCE in AD treatment. Notably, it indicated that the developed method based on accurate mass and IFSs has sufficient performance for identification of biomarkers in metabolomic studies.

Enzyme Degradable Hyperbranched Polyphosphoester Micellar Nanomedicines for NIR Imaging-Guided Chemo-Photothermal Therapy of Drug-Resistant Cancers.

Multidrug resistance (MDR) is the major cause for chemotherapy failure, which constitutes a formidable challenge in the field of cancer therapy. The synergistic chemo-photothermal treatment has been reported to be a potential strategy to overcome MDR. In this work, rationally designed enzyme-degradable, hyperbranched polyphosphoester nanomedicines were developed for reversing MDR via the codelivery of doxorubicin and IR-780 (hPPEDOX&IR) as combined chemo-photothermal therapy. The amphiphilic hyperbranched polyphosphoesters with phosphate bond as the branching point were synthesized via a simple but robust one-step polycondensation reaction. The self-assembled hPPEDOX&IR exhibited good serum stability, sustained release, preferable tumor accumulation, and enhanced drug influx of doxorubicin in resistant MCF-7/ADR cells. Moreover, the degradation of hPPEDOX&IR was accelerated in the presence of alkaline phosphatase, which was overexpressed in various cancers, resulting in the fast release of encapsulated doxorubicin. The enzyme-degradable polymer generated synergistic chemo-photothermal cytotoxicity against MCF-7/ADR cells and, thus, the efficient ablation of DOX-resistant tumor without regrowth. This delivery system may open a new avenue for codelivery of chemo- and photothermal therapeutics for MDR tumor therapy.

Adaptive immune cells are necessary for the enhanced therapeutic effect of sorafenib-loaded nanoparticles.

Sorafenib is a kinase inhibitor approved for the treatment of primary kidney cancer, advanced primary liver cancer, and radioactive iodine resistant advanced thyroid carcinoma. However, sorafenib usually causes serious side effects, which limit its antitumor effect. Nanoparticle based drug delivery systems have been widely used to enhance the therapeutic effects and reduce the side effects of this drug by the enhanced permeability and retention (EPR) effect. Herein, to improve the therapeutic effect of sorafenib, we developed poly(ethylene glycol)-b-poly(lactic acid-co-glycolic acid) (PEG-PLGA) based nanoparticles by a dialysis method for sorafenib encapsulation. After intravenous injection of the sorafenib loaded nanoparticles (NPsorafenib), the tumor growth of mice bearing B16-F10, MC38 and LLC tumor was significantly inhibited. Meanwhile, the dose of sorafenib was reduced to one ninth and the side effects on the hematopoietic system and immune system were abrogated. More importantly, the tumor growth inhibition effect of NPsorafenib was dramatically reduced in B16-F10 bearing Rag1-/- mice which are adaptive immune cell defective, indicating that the antitumor effects of NPsorafenib are dependent on the adaptive immune cells. These results emphasize the indispensable role of the adaptive immune system in nano-drug mediated antitumor effects and the adaptive immune system should be considered as an important factor for clinical applications.

Characterization of global metabolic profile of Rhodiola crenulata after oral administration in rat plasma, urine, bile and feces based on UHPLC-FT-ICR MS.

Rhodiola crenulata has been widely used as a health food, antifatigue and antidepressant in China and many other countries for centuries. However, to date the metabolism of it in vivo still remains unclear. In this study, UHPLC-FT-ICR MS was used to analyze the major components and their metabolites in rats after oral administration of Rhodiola crenulata for the first time. A total of 179 constituents, including 37 prototype compounds and 142 metabolites (89 phase I metabolites and 53 phase II metabolites) were tentatively identified. The metabolic pathways included hydroxylation, deglycosylation, dehydrogenation, glucuronidation and sulphate conjugation. In summary, this study showed an insight into the metabolism of Rhodiola crenulata in vivo, which may provide helpful chemical information for better understanding the multiple functions of it. And also, the developed method could be used as a reliable strategy to study the metabolic profile for other traditional chinese medicines.

Metabolic profile of Kudiezi injection in rats by UHPLC coupled with Fourier transform ion cyclotron resonance mass spectrometry.

In this study, a reliable and sensitive ultra-high performance liquid chromatography coupled with fourier transform ion cyclotron resonance mass spectrometry method was developed for the systematic study of the metabolic profile of Kudiezi injection in rat plasma, bile, urine, and feces after intravenous administration of a single dose. The chromatographic separation was performed on an Agilent Eclipse Plus C18 column (4.6 mm × 50 mm, 1.8 µm) and the identification of prototype components and metabolites was achieved on a Bruker Solarix 7.0 T ultra-high resolution spectrometer in negative ion mode. Results indicated that a total of 76 constituents including 29 prototype compounds and 47 metabolites (10 phase I metabolites and 37 phase II metabolites) were tentatively identified. And the metabolic pathways of these prototype compounds including hydroxylation, dehydrogenation, glucuronidation, and sulfate conjugation. In conclusion, the developed method with high resolution and sensitivity was effective for screening and identification of prototypes and metabolites of Kudiezi injection in vivo. Moreover, these results would provide significant information for further pharmacokinetic and pharmacological research of Kudiezi injection in vivo.

Gonadotropin-inhibitory hormone (GnIH) and its receptor in the female pig: cDNA cloning, expression in tissues and expression pattern in the reproductive axis during the estrous cycle.

Since its discovery, gonadotropin-inhibitory hormone (GnIH) has appeared to act as a key neuropeptide in the control of vertebrate reproduction. GnIH acts via the novel G protein-coupled receptor 147 (GPR147) to inhibit gonadotropin release and synthesis. To determine the physiological functions of GnIH in the pig, a study was conducted to clone and sequence the cDNA of the GnIH precursor and GPR147. Our results demonstrated that the cloned pig GnIH precursor cDNA encoded three LPXRF and that its receptor possessed typical transmembrane features. Subsequently, tissue expression studies revealed that GnIH was mainly expressed in the brain, corresponding largely with the tissue expression patterns of GPR147 in the pig. The expression patterns in the reproductive axis of the female pig across the estrous cycle were also systemically investigated. The hypothalamic levels of both GnIH and its receptor mRNA were lowest in estrus and peaked in the proestrus and diestrus phases. The highest pituitary GnIH mRNA level was detected in the metestrus, and its receptor displayed a somewhat similar pattern of expression to that of the ligand. However, the expression patterns of GnIH and GPR147 were negatively correlated in the ovary. Immunolocalization in the ovary during the estrous cycle revealed that the immunoreactivities of GnIH and GPR147 were mainly localized in the granulosa and theca cells of the antral follicles during proestrus and estrus and in the luteal cells during metestrus and diestrus. Taken together, this research provided molecular and morphological data for further study of GnIH in the pig.