Tribological Performance and Enhancing Mechanism of 3D Printed PEEK Coated with In Situ ZIF-8 Nanomaterial.

Polyether ether ketone (PEEK) is esteemed as a high-performance engineering polymer renowned for its exceptional mechanical properties and thermal stability. Nonetheless, the majority of polymer-based lubricating materials fail to meet the contemporary industrial demands for motion components regarding high speed, heavy loading, temperature resistance, and precise control. Utilizing 3D printing technology to design and fabricate intricately structured components, developing high-performance polymer self-lubricating materials becomes imperative to fulfill the stringent operational requirements of motion mechanisms. This study introduces a novel approach employing 3D printing technology to produce PEEK with varying filling densities and conducting in situ synthesis of zeolitic imidazolate framework (ZIF-8) nanomaterials on its surface to enhance PEEK's frictional performance. The research discusses the synthetic methodology, characterization techniques, and tribological performance evaluation of in situ synthesized ZIF-8 nanomaterials on PEEK surfaces. The findings demonstrate a significant enhancement in frictional performance of the composite material under low-load conditions, achieving a minimum wear rate of 4.68 × 10-6 mm3/N·m compared to the non-grafted PEEK material's wear rate of 1.091 × 10-5 mm3/N·m, an approximately 1.3 times improvement. Detailed characterization and analysis of the worn surface of the steel ring unveil the lubrication mechanism of the ZIF-8 nanoparticles, thereby presenting new prospects for the diversified applications of PEEK.

Rapid Access to Chiral Spiro[2.3] Lactams: Stereoselective Hydroborylation and Hydrosilylation and Remote Control of Axial Chirality by Copper-Catalyzed Desymmetrization of Spirocyclopropenes.

Chiral spirocyclopropyl ß-lactams are common motifs in bioactive compounds and pharmaceuticals. Here we disclose a diastereoselective and enantioselective hydroborylation and hydrosilylation of spirocyclopropenes, via a Cu-catalyzed desymmetrization strategy, for the rapid preparation of enantio-enriched spirocyclopropyl ß-lactams. The efficient desymmetrization strategy allows the remote control of axial chirality, offering the borylated and silylated products bearing central, spiro, and axial chirality. The combination of multichiral elements would provide a novel motif for biological evaluation in potential drug discovery.

Predictive Value of Nutritional Risk for All-Cause Death and Functional Outcomes in Chinese Elderly Patients with Acute Stroke: A 3-Year Follow-Up Study.

Purpose: To explore the predictive value of nutritional risk for all-cause death and functional outcomes among elderly acute stroke patients. Patients and Methods: A total of 479 elderly acute stroke patients were enrolled in this study. The nutritional risk of patients was screened by the GNRI and NRS-2002. The primary outcome was all-cause death, and the secondary outcome was poor prognosis defined as a modified Rankin Scale (mRS) score ≥3. Results: Based on the NRS-2002, patients with nutritional risk had a higher risk of all-cause death at 3 months (adjusted OR: 3.642, 95% CI 1.046~12.689) and at 3 years (adjusted OR: 2.266, 95% CI 1.259~4.076) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 2.748, 95% CI 1.518~4.972. Based on the GNRI, compared to those without nutritional risk, patients with mild malnutrition also had a higher risk of all-cause death at 3 months (adjusted OR: 7.186, 95% CI 1.550~33.315) and at 3 years (adjusted OR: 2.255, 95% CI 1.211~4.199) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 1.947, 95% CI 1.030~3.680), so patients with moderate and severe malnutrition had a higher risk of all-cause death at 3 months (adjusted OR: 6.535, 95% CI 1.380~30.945) and at 3 years (adjusted OR: 2.498, 95% CI 1.301~4.799) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 2.213, 95% CI 1.144~4.279). Conclusion: Nutritional risk increases the risk of poor short-term and long-term outcomes in elderly patients with acute stroke. For elderly stroke patients, we should pay attention to early nutritional risk screening, and effective intervention should be provided to improve the prognosis of such patients.

FAK inhibitor PF-562271 inhibits the migration and proliferation of high-grade serous ovarian cancer cells through FAK and FAK mediated cell cycle arrest.

Focal adhesion kinase (FAK) is a promising therapeutic target for various cancers and its inhibitor development is in full swing. PF-562271 is a classic FAK inhibitor that has shown promising preclinical data and has been found to exhibit an anti-migration effect on some cancer cells. However, its anticancer effect on high-grade serous ovarian cancer (HGSOC) has not been reported. In this study, we evaluated the anti-migration and anti-proliferation effects of PF-562271 against HGSOC SKOV3 and A2780 cells, as well as the underlying mechanism. The results demonstrated that FAK was overexpressed in clinical HGSOC tissues and was positively correlated with the pathological progression of HGSOC. Moreover, HGSOC patients with high FAK expression levels exhibited low survival rates. PF-562271 treatment significantly inhibited the cell adhesion and migration of SKOV3 and A2780 cells by inhibiting p-FAK expression and decreasing the FA surface area. Additionally, PF-562271 treatment inhibited colony formation and induced cell senescence through G1 phase cell cycle arrest mediated DNA replication inhibition. Taken together, the findings demonstrated that FAK inhibitor PF-562271 significantly inhibits HGSOC cell adhesion, migration, and proliferation process through FAK and/or FAK mediated cell cycle arrest, and suggested that PF-562271 could serve as a potential oncotherapeutic agent for HGSOC targeting treatment.

[Determination of plant growth regulators in animal-derived foods using QuEChERS-isotope-labeled internal standards with high performance liquid chromatography-tandem mass spectrometry].

As among the most widely used pesticides in agriculture, plant growth regulators (PGRs) have a positive influence on plants. However, the overuse of PGRs may induce toxicity in food and even be hazardous to human health. Numerous studies have investigated the presence and residues of PGRs on vegetables and fruits. Animal-derived foods are one of the most dominant food sources providing nutrients to fulfil the daily dietary intake, and could also be potentially contaminated by PGRs. However, there is little information on PGR residues in animal-derived foods. Standardization also lacks among the techniques for PGR determination in animal-derived foods, thereby restricting the further establishment of pesticide usage and food safety regulations. Therefore, in this study, a rapid and effective method for analyzing chlormequat chloride, thidiazuron, and paclobutrazol in animal-derived food samples was established. The method primarily involves high performance liquid chromatography-tandem mass spectrometry combined with the use of isotope-labeled internal standards. The extraction and clean-up procedures were based on the QuEChERS method. The analytes were extracted from pork, beef, chicken, pork liver, egg, and milk samples using acetonitrile, followed by 4 g anhydrous magnesium sulfate (MgSO4), and 1 g sodium chloride (NaCl). The supernatant was removed using a mixture of 50 mg N-propyl ethylenediamine (PSA), 50 mg octadecyl silane (C18), and 150 mg MgSO4, and then passed through a 0.22 µm membrane filter before determination. The Agilent ZORBAX Eclipse Plus C18 column (150 mm×3.0 mm, 1.8 µm) was used to separate the analytes under a gradient elution program, with acetonitrile and 5 mmol/L ammonium acetate solution as mobile phases. The analytes were detected by mass spectrometry using the positive and negative electrospray ionization modes under the multiple reaction monitoring mode. Matrix-matched calibration combined with internal standards was used to quantify the PGRs. The linear regression correlation coefficients (r2) for the PGRs were all greater than 0.990 in the corresponding linear concentration ranges. Chlormequat chloride, thidiazuron, and paclobutrazol showed good linearities in the range of 0.1-100 µg/L for the egg and pork liver samples and 0.1-50 µg/L for the pork, beef, and chicken samples. For the milk samples, thidiazuron and paclobutrazol showed good linearities in the range of 0.05-10 µg/L, while chlormequat chloride showed linearity in the range of 0.05-5 µg/L. The limit of detection (LOD) and limit of quantification (LOQ) for each PGR were based on the signal-to-noise (S/N) ratios. Under optimal conditions, the LODs ranged from 0.01 µg/kg to 0.1 µg/kg, where the LOD was defined as the amount of the tested compound that generated an S/N ratio higher than 3. In addition, the LOQs were in the range of 0.5-5 µg/kg, with an S/N ratio higher than 10. The precision and accuracy were evaluated by recovery experiments. At the LOQ, twice the LOQ, and 10 times the LOQ, the mean recoveries were in the range of 70.0%-117.4%, and the relative standard deviations (RSDs) ranged from 0.8% to 16.1%. The results indicated that the proposed method is accurate and reliable. This method is a modification of the QuEChERS method, and is advantageous owing to its simplicity and high sensitivity. The use of matrix-matching calibration curves and internal standards can eliminate matrix interference, thereby increasing the accuracy of the method. This method satisfies the testing requirements for chlormequat chloride, thidiazuron, and paclobutrazol residues in animal-derived foods, and is promising for the determination of other PGRs or other types of pesticides in animal-derived foods.

Combined determination of copper ions and ß-amyloid peptide by a single ratiometric electrochemical biosensor.

Copper ions (Cu2+) play a critical role in biological processes and are directly involved in ß-amyloid peptide (Aß) aggregation, which is responsible for the occurrence and development of Alzheimer's disease (AD). Therefore, combined determination of Cu2+ and Aß in one analytical system is of great significance to understand the exact nature of the AD event. This work presents a novel ratiometric electrochemical biosensor for the dual determination of Cu2+ and Aß1-42. This unique sensor is based on a 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonate) (ABTS) and poly(diallyldimethylammonium chloride) (PDDA)-bi functionalized single-walled carbon nanotubes (ABTS-PDDA/CNTs) composite. The inclusion of ABTS not only enhanced the sensitivity, but it also acted as an inner reference molecule to improve detection accuracy. The specific recognition of Cu2+ was realized by neurokinin B (NKB) coatings on the ABTS-PDDA/CNTs surface to form a [CuII(NKB)2] complex with Cu2+. The ABTS-PDDA/CNTs-NKB modified electrode also displayed an excellent electrochemical response toward the Aß1-42 monomer, when a certain amount of the Aß1-42 monomer was added to Cu2+-contained PBS buffer, which was due to the release of Cu2+ from the [CuII(NKB)2] complex through Aß binding to Cu2+. Meanwhile, our work showed that Cu2+ bound Aß1-42 was concentration-dependent. Consequently, the presented electrochemical approach was capable of quantifying two important biological species associated with AD by one single biosensor, with the detection limits of 0.04 µM for Cu2+ and 0.5 ng mL-1 for Aß1-42, respectively. Finally, the ratiometric electrode was successfully applied for monitoring Cu2+ and Aß1-42 variations in plasma and hippocampus of normal and AD rats.

[The effective parts of liangxue tongyu prescription on cooling-blood and activating-blood and analysis of chemical constituents by HPLC-MS and GC-MS].

In order to clarify material basis of effective parts of liangxue tongyu prescription, blood-heat and blood-stasis rat model induced by dry yeast was established. The changes of rectal temperature, blood viscosity and plasma viscosity were used to evaluate the cooling-blood and activating-blood effects of liangxue tongyu prescription and its parts. Compared with the model group, the extract from liangxue tongyu prescription, its volatile oil and n-butanol part could significantly reduce rectal temperature (P<0.01), and also reduce blood viscosity and plasma viscosity to various degrees (P<0.01 or P<0.05). So volatile oil and n-butanol part were primarily identified as effective parts of liangxue tongyu prescription. By using GC-MS with normalization method of area to analyze volatile oil of liangxue tongyu prescription, 70 compounds were identified, accounting for about 92.54%, mainly as ß-asarone, paeonol, α-asarone and shyobunone. 42 compounds such as peony glycosides, tannins, and iridoid glycosides were identified by HPLC-MS techniques and standard comparison. The study determined the effective parts of liangxue tongyu prescription and clarified the chemical composition providing the foundation for further studies on material basis of liangxue tongyu prescription.

Auxiliary beta subunits differentially determine pka utilization of distinct regulatory sites on Cav1.3 L type Ca2+ channels.

L-type calcium channels (Ca(v)1.1-Ca(v)1.4) link Ca(2+) influx to membrane depolarization and serve a critical role in regulating membrane excitability, muscle contraction, hormone secretion, and gene transcription. In many tissues, L-type calcium channel activity (Ca(v)1.1 and Ca(v)1.2) is enhanced by transmitters and hormones that activate the cAMP-dependent protein kinase (PKA), which is largely thought to be mediated via phosphorylation of the pore forming alpha subunit. However, the ability of PKA to regulate Ca(v)1.3 and the sites contributing to effective modulation of channel activity remains to be established. Using HEK 293 cells, we demonstrate that currents carried by the long C-terminal splice variant of Ca(v)1.3 (Ca(v)1.3L) are selectively enhanced compared to the short C-terminal splice variant (Ca(v)1.3S) when the catalytic subunit of PKA is introduced into the cell via the whole-cell recording electrode. However, the persistence of this regulation is dependent on the identity of the auxiliary beta subunit, such that PKA produces only a transient increase in the presence of beta(3) while a persistent increase is observed in the presence of the beta(2a) subunit. Site-directed mutagenesis of consensus PKA phosphorylation sites revealed that Ser1964 and Ser1743 in Ca(v)1.3L were the predominant sites controlling PKA modulation in the presence of the beta(3) and beta(2a) auxiliary subunits, respectively. Therefore, beta subunits determine the contribution of distinct sites within Ca(v)1.3 towards PKA-mediated enhancement of channel activity. These data suggest that auxiliary beta subunits govern the access of signaling enzymes to L-type calcium channels.

[Preparation and application of monoclonal antibodies to recombinant human IFN alpha].

OBJECTIVE: To prepare and apply monoclonal antibodies (McAb) against recombinant human interferon alpha (rHu IFN-alpha). METHODS: Five cell lines (2E9, 4G1, 2A7, 2C9, 4G10) secreting McAbs against rHu IFN-alpha were established by hybridoma technique. RESULTS: All the cell lines secreted monoclonal antibodies stably. Functions of secreting antibodies of the five cell lines lasted for 6 months in BALB/c mice and 8 months in cell culture. The specificity of antibody was constant. The Ig subclasses of the McAbs were IgG1. Anti-IFN McAb affinity purification column was prepared by coupling the anti IFN-alpha McAb to Sepharose 4B. The combining rate reached was higher than 95%. CONCLUSIONS: The highest purification efficiency was obtained by using 4G10 column.