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The properties of nanopipettes largely rely on the materials introduced onto their inner walls, which allow for a vast extension of their sensing capabilities. The challenge of simultaneously enhancing the sensitivity and selectivity of nanopipettes for pH sensing remains, hindering their practical applications. Herein, we report insulin-modified nanopipettes with excellent pH response performances, which were prepared by introducing insulin onto their inner walls via a two-step reaction involving silanization and amidation. The pH response intensity based on ion current rectification was significantly enhanced by approximately 4.29 times when utilizing insulin-modified nanopipettes compared with bare ones, demonstrating a linear response within the pH range of 2.50 to 7.80. In addition, insulin-modified nanopipettes featured good reversibility and selectivity. The modification processes were monitored using the I-V curves, and the relevant mechanisms were discussed. The effects of solution pH and insulin concentration on the modification results were investigated to achieve optimal insulin introduction. This study showed that the pH response behavior of nanopipettes can be greatly improved by introducing versatile molecules onto the inner walls, thereby contributing to the development and utilization of pH-responsive nanopipettes. [ABSTRACT FROM AUTHOR]

Amorphous alloy is a new kind of metastable metallic materials, which exhibits many excellent mechanical, physical and chemical properties due to its disordered structure. Since its birth in the 1960s, amorphous alloy has been attracting much attention from the materials field and the industry. Among the developed alloy systems, Fe-based amorphous alloys have the characteristics of high strength, high hardness, relatively low production cost,strong corrosion resistance and excellent soft magnetic properties, hence have a broad application prospect in the field of structural materials and functional materials. However, the relatively weak glass-forming ability and room temperature brittleness seriously restrict the wide application of Fe-based amorphous alloys. Based on this, the two aspects of the Fe-base amorphous alloy was reviewed in the present article, which covers the glass forming rule (including components types, preparation technology, raw material purity, composition design,etc.) and room-temperature mechanical properties (involving strength,toughness, composition and structure design,etc.). The research status, influencing factors and improved methods of glass-forming ability and room temperature mechanical properties of Fe-based amorphous alloys were emphatically analyzed,especially the latest research results of our group in the field of Fe-base amorphous alloy in nearly a decade were covered.In addition, the current difficulties in research and the future development of Fe-based amorphous alloys were also prospected.

E-Zhu (Curcuma zedoaria) is known as a classical traditional Chinese medicine and widely used in the treatment of cancers, cardiovascular disease, inflammation, and other diseases. Its main components include curcumol and curcumin, which have anti-inflammatory and antifibrosis effects. Here we established an in vitro inflammatory injury model by stimulating RAW246.7 cells with cigarette smoke extract (CSE) and detected the intervention effects of curcumin and curcumol on CSE-treated Raw246.7 macrophage cells to explore whether the two compounds inhibited the expression of inflammatory cytokines by inhibiting the NF-κB signaling pathway. We detected the antifibrosis effects of curcumin and curcumol via TGF-β1/Smads signaling pathways. The model of macrophage damage group was established by CSE stimulation. Curcumol and curcumin were administered to Raw246.7 macrophage cells. The efficacy of curcumol and curcumin was evaluated by comparing the activation of proinflammatory factors, profibrotic factors, and NF-κB and TGF-β1/Smads signaling pathway. In addition, CSE-treated group was employed to detect whether the efficacy of curcumol and curcumin was dependent on the NF-κB signaling via the pretreatment with the inhibitor of NF-κB. Our findings demonstrated that curcumol and curcumin could reduce the release of intracellular ROS from macrophages, inhibit the NF-κB signaling pathway, and downregulate the release of proinflammatory factor. Curcumol and curcumin inhibited the TGF-β1/Smads signaling pathway and downregulated the release of fibrotic factors. Curcumin showed no anti-inflammatory effect in CSE-treated cells after the inhibition of NF-κB. Curcumol and curcumin showed an anti-inflammatory effect by inhibiting the NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Vitamin K 2 (VK2), found to act to treat hypertension, has been widely used in the food and pharmaceutical industries nowadays. However, the potential targets and molecular mechanisms of VK2 for salt-sensitive hypertension have not been fully investigated. Therefore, the study aimed to investigate the potential molecular mechanisms of VK2 for salt-sensitive hypertension using network pharmacology and 16S rRNA sequencing strategy. The network pharmacology-based findings from KEGG enrichment analysis revealed that VK2-treated salt-sensitive hypertension was mechanically associated with the complement and coagulation cascades, calcium signaling pathway, renin-angiotensin system, etc. A total of 29 different bacteria in an animal experiment after VK2 supplementation were screened and functionally enriched using PICRUSt2. Additionally, 10 signaling pathways were identified in which the renin-angiotensin system was found to be the potential molecular mechanisms with the greatest change in multiple and statistical significance. Moreover, the results of the renin-angiotensin system-related protein expression exhibited VK2-inhibited renin-angiotensin system in salt-induced hypertensive mice, which significantly verified the previous biological and functional prediction analysis. Finally, spearman correlation analysis showed the different bacteria such as Dubosiella, Ileibacterium , etc., had a positive or negative correlation with renin-angiotensin system-related proteins in salt-induced mice. In conclusion, the potential molecular mechanisms of VK2 for salt-sensitive hypertension may be beneficially achieved by the specific inhibition of the renin-angiotensin system, contributing to the development for a new preventive strategy of salt-sensitive hypertension., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Chen, Tu, Liang, Tao, Jin, Xiao and Chen.)

Needle knife therapy, a form of acupuncture and moxibustion, has been widely used in the clinical treatment of knee osteoarthritis (KOA). However, the mechanism is not clear. Therefore, we studied the mechanisms of action of needle knife intervention on KOA in rabbits, with the PERK-eIF2 α -CHOP pathway as a starting point, in order to determine the mechanism underlying knee joint chondrocyte apoptosis. Apoptosis and ultrastructural changes in the articular cartilage were examined by pathological study and transmission electron microscopy, and PERK, eIF2 α , and CHOP mRNA and protein levels were detected by qRT-PCR and western blot, respectively. PERK, eIF2 α , and CHOP protein levels were significantly higher in the model group than in the normal group ( P < 0.01) and were considerably downregulated in the needle knife and the medicine groups compared to the model group ( P < 0.01). The eIF2 α , p-eIF2 α , and CHOP protein levels were not significantly different between the needle knife and medicine groups. The PERK, eIF2 α , and CHOP mRNA levels in the drug group were higher than those in the needle knife group ( P < 0.01). Needle knife therapy can regulate PERK-eIF2 α -CHOP signaling pathway, which could be one of the mechanisms by which it affects chondrocyte apoptosis in KOA rabbits.

E-Zhu ( Curcuma zedoaria ) is known as a classical traditional Chinese medicine and widely used in the treatment of cancers, cardiovascular disease, inflammation, and other diseases. Its main components include curcumol and curcumin, which have anti-inflammatory and antifibrosis effects. Here we established an in vitro inflammatory injury model by stimulating RAW246.7 cells with cigarette smoke extract (CSE) and detected the intervention effects of curcumin and curcumol on CSE-treated Raw246.7 macrophage cells to explore whether the two compounds inhibited the expression of inflammatory cytokines by inhibiting the NF- κ B signaling pathway. We detected the antifibrosis effects of curcumin and curcumol via TGF- β 1 /Smads signaling pathways. The model of macrophage damage group was established by CSE stimulation. Curcumol and curcumin were administered to Raw246.7 macrophage cells. The efficacy of curcumol and curcumin was evaluated by comparing the activation of proinflammatory factors, profibrotic factors, and NF- κ B and TGF- β 1 /Smads signaling pathway. In addition, CSE-treated group was employed to detect whether the efficacy of curcumol and curcumin was dependent on the NF- κ B signaling via the pretreatment with the inhibitor of NF- κ B. Our findings demonstrated that curcumol and curcumin could reduce the release of intracellular ROS from macrophages, inhibit the NF- κ B signaling pathway, and downregulate the release of proinflammatory factor. Curcumol and curcumin inhibited the TGF- β 1 /Smads signaling pathway and downregulated the release of fibrotic factors. Curcumin showed no anti-inflammatory effect in CSE-treated cells after the inhibition of NF- κ B. Curcumol and curcumin showed an anti-inflammatory effect by inhibiting the NF- κ B signaling pathway.

Aim: To investigate whether silencing Fas-associated phosphatase 1 (FAP-1) expression enhances the efficiency of chemotherapy for colon carcinoma with oxaliplatin., Methods: Expression of FAP-1 in mRNA and protein was detected by reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry. Small interfering RNA (siRNA) was designed according to the FAP-1 mRNA sequence. Cell proliferation was evaluated by methyl thiazolyl tetrazolium (MTT) assay. Anenxin V- and propidine iodine (PI) were assayed by flow cytometry for the detection of apoptosis., Results: The expression of FAP-1 was increased in SW480 cells after chemotherapy with oxaliplatin. Transfection of FAP-1 siRNA into SW480 cells silenced the expression of FAP-1 and consequently abolished the inhibitory function of Fas/FasL-mediated apoptosis pathway, thus increasing the efficacy of chemotherapy for colon carcinoma with oxaliplatin., Conclusion: RNA interference combined with conventional chemotherapy is more effective against colon cancer.

Objective: To screen the molecular markers for refractory anemia with excess blasts in transformation (RAEB) in myelodysplastic syndromes (MDS) by serum proteome profiling., Methods: The serum protein were isolated from patients with RAEB, acute myeloid leukemia or normal subjects by 2-dimensional electrophoresis (2-DE), and the electrophoresis gels were obtained to identify the differentially reacting protein spots. The replica gels of the differentially reacting proteins were analyzed to locate the matching protein spots, which were identified by peptide mass fingerprint based on matrix-assisted laser desorption/ionization time of-flight mass spectrometry (MALDI-TOF-MS) and database searching., Results: Seven differentially expressed proteins in RAEB were found by 2-DE. Of the 7 proteins, 4 were identified by MALDI-TOF-MS to have significantly differential expression in RAEB, including dipeptidyl peptidase (DPP/CD26), polymerase (DNA directed) kappa, PRO2044 and an albumin-like protein., Conclusion: 2-DE-based serum proteome profiling helps identify serum proteomic biomarkers related to MDS. DDP/CD26 has increased expression in the serum in RAEB subtype MDS, suggesting its possible role in advanced MDS.

Objective: To investigate the factors that affect the prognosis of primary gastrointestinal non-Hodgkin's lymphoma (PGI-NHL)., Methods: The clinical data of 116 patients with pathologically confirmed PGI-NHL we treated from January 1993 to December 2003 were analyzed retrospectively. Kaplan-Meier survival analysis was used for analyzing the survival of the patients, and Log-rank test was performed to compare the survival rates in relation to different prognostic factors., Results: The 3-year and 5-year survival rates of the patients were 63.8% (74/116) and 48.2% (40/83), respectively. Univariate analysis revealed that the factors affecting the prognosis of the patients included the presence of B symptom, tumor size, clinical stage, pathological type, depth of invasion, and treatment methods. The patients with B symptom, tumor size no less than 10 cm, advanced clinical stage (stages III(E) and IV(E)), T-cell type, and invasion beyond the serosa who received only surgical management had poorer prognosis than those free of B symptom with tumor size <10 cm, early clinical stage (stages I(E) and II(E)), B-cell type, and submucosal or serosal invasion managed with chemotherapy alone or in combination with surgery. Multivariate analysis showed that B symptom, tumor size no less than 10 cm, advanced clinical stage (stages III(E) and IV(E)), T-cell type, invasion beyond the serosa, and surgery alone were independently associated with poor prognosis., Conclusion: The tumor size, clinical stage, pathological type, treatment methods are the independent factors affecting the prognosis of patients with PGI-NHL.

Objective: To assess the therapeutic efficacy and adverse effects of endogenetic field hyperthermia (EFH) in combination with L-OHP /LV / 5-FU in the treatment of advanced gastric cancer., Methods: This study included 147 surgical patients with stage II-IV gastric cancer, who received postoperative chemotherapy with FOLFOX (L-OHP 85 mg /m square, 3 h intravenous infusion, followed by infusion of LV at 200 mg /m square in 2 h, intravenous injection of 5-Fu at 400 mg /m square, and intravenous infusion of 5-FU at 3000 mg /m square in 48 h). Eight treatment cycles (each lasting for 14 days) were administered. In 68 cases randomly selected from the cohort, EFH was performed on the first and third days (treatment group), but not in the other 79 cases (control group)., Results: The response rate was 68.4% in the treatment group and 36.4% in the control group, showing significant difference between them (P<0.05). The 1-year survival rate was 88.2% in the treatment group, similar to the rate of 81.0% in the control group (P< 0.05), but the 3, 5-year survival rates in treatment group (67.6% and 30.9%) was significantly higher than those in the control group (47.6% and 15.4%, P<0.05). The adverse effects were similar between the two groups., Conclusion: EFH combined with the chemotherapeutic regimen FOLFOX might improve the therapeutic effect of stage II-IV gastric cancer without obviously increasing the adverse effects.

Background & Objective: CAF regimen [Cytoxan+ Adriamycin+5-fluorouracil (5-FU)] and TP regimen (paclitaxel+cisplatin) were effective to advanced breast cancer (ABC). But TP regimen was expensive and the administration was complicated. So the authors evaluated the clinical results of CAF and TP regimens., Methods: A total of 117 ABC patients proved pathologically were divided into CAF and TP groups. Patients in both groups were well matched with baseline disease characteristics (P >0.05). CAF group (66 cases):received Cytoxan 600 mg/m(2), i.v. drip d(1), Adriamycin 60 mg/m(2) i.v. drip d(1) and 5-FU 600 mg/m(2), i.v. drip d(1,8); TP group (51 cases): received paclitaxel 135 mg/m(2) by i.v. drip for 3 hours and cisplatin 60 mg/m(2), i.v. drip d(2-3) The treatments were repeated every 3 weeks. All patients received two cycles of the treatment at least., Results: In CAF group, the response rates (RR) of the initial treatment cases, the retreatment cases, and the whole cases were 54.8% (17/31), 31.4% (11/35), and 42.4% (28/66), respectively. The median time to progression (TTP) was 7.8 months (95%CI:5.3-10.8 months) and the median survival was 17.8 months (95%CI:13.3-22.5%). Whereas in TP group, the RR of the initial treatment cases, the retreatment cases, and the whole cases were 62.5%(15/24), 59.3%(16/27), and 60.8%(31/51), respectively. The median TTP and the median survival were 8.6 months (95%CI:6.5-12 months) and 19 months (95%CI:15-25.5 months), respectively. There were significant differences between two groups in the RR of retreatment cases and the whole cases (P< 0.05, Chi-square test). However, there was no significant difference in the RR of the initial treatment cases, the median TTP and median survival (for RR, P >0.05, Chi-square test; for median TTP and median survival, P >0.05, Log-rank test). Diarrhea was more serious in CAF group than in TP group; however, myodynia, peripheral neuropathy,and skin exanthem were more serious in TP group than in CAF group(P< 0.05,Wilcoxon rank sum test). There was no significant difference in the other side effects between the two groups. All side effects were tolerable., Conclusion: CAF regimen was still a firstly selected regimen for the patients with ABC.