The NOD-like receptor protein 3 (NLRP3) inflammasome is essential in innate immune-mediated inflammation, with its overactivation implicated in various autoinflammatory, metabolic, and neurodegenerative diseases. Pharmacological inhibition of NLRP3 offers a promising treatment strategy for inflammatory conditions, although no medications targeting the NLRP3 inflammasome are currently available. This study demonstrates that clioquinol (CQ), a clinical drug with chelating properties, effectively inhibits NLRP3 activation, resulting in reduced cytokine secretion and cell pyroptosis in both human and mouse macrophages, with a half maximal inhibitory concentration (IC₅₀) of 0.478 μM. Additionally, CQ mitigates experimental acute peritonitis, gouty arthritis, sepsis, and colitis by lowering serum levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Mechanistically, CQ covalently binds to Arginine 335 (R335) in the NACHT domain, inhibiting NLRP3 inflammasome assembly and blocking the interaction between NLRP3 and its component protein. Collectively, this study identifies CQ as an effective natural NLRP3 inhibitor and a potential therapeutic agent for NLRP3-driven diseases.

Objective:To explore the application of on-demand teaching in the teaching of newly recruited nurses in the Class-A tertiary hospital.Methods:A total of 84 newly recruited nurses from Beijing Shijitan Hospital Affiliated to Capital Medical University from August 2017 to August 2018 were selected as the control group, and routine teaching was used. In addition, 116 new nurses from August 2019 to August 2020 were selected as the observation group, and on-demand teaching was adopted. The results of theory and practical operation, comprehensive ability and teaching satisfaction of the two groups were compared. The software SPSS 22.0 was used for t-test. Results:The nurses in the observation group had higher scores than the control group in theory [(96.38±2.14) vs. (91.56±3.75)] and practice [(95.49±2.23) vs. (90.91±4.02)]. The scores of nurses in the observation group were higher than those in the control group in accurate implementation of doctor's orders, emergency response ability, ability to observe illness, operation level, communication ability, professional image of nurses, cooperation satisfaction with doctors and harmony with nurses ( P<0.05). The nurses in the observation group scored higher than those in the control group in teaching content, teaching method, teaching attitude, and teaching effect satisfaction ( P<0.05). Conclusion:The application of on-demand teaching in the teaching of newly recruited nurses in the Class-A tertiary hospital can significantly improve their theoretical and practical skills, and improve their comprehensive ability and teaching satisfaction.

Human cytosolic sulfotransferase 2A1 (SULT2A1) is an important phase II metabolic enzyme. The detection of SULT2A1 is helpful for the functional characterization of SULT2A1 and diagnosis of its related diseases. However, due to the overlapping substrate specificity among members of the sulfotransferase family, it is difficult to develop a probe substrate for selective detection of SULT2A1. In the present study, through characterization of the sulfation of series of bufadienolides, arenobufagin (AB) was proved as a potential probe substrate for SULT2A1 with high sensitivity and specificity. Subsequently, the sulfation of AB was characterized by experimental and molecular docking studies. The sulfate-conjugated metabolite was identified as AB-3-sulfate. The sulfation of AB displayed a high selectivity for SULT2A1 which was confirmed by reaction phenotyping assays. The sulfation of AB by human liver cytosols and recombinant SULT2A1 both obeyed Michaelis-Menten kinetics, with similar kinetic parameters. Molecular docking was performed to understand the interaction between AB and SULT2A1, in which the lack of interaction with Met-137 and Tyr-238 of SULT2A1 made it possible to eliminate substrate inhibition of AB sulfation. Finally, the probe was successfully used to determine the activity of SULT2A1 and its isoenzymes in tissue preparations of human and laboratory animals.

ABSTRACT:Objective To explore the changes of serum cytokine interleukin-17 (IL-17)in patients with chronic hepatitis B of different clinical types and its clinical significance.Methods We selected 30 cases of mild chronic hepatitis B,34 cases of moderate one,29 cases of severe one,38 cases of liver cirrhosis,and 21 cases of acute on chronic liver failure.Another 30 cases over the same period served as the healthy control group.Cytokine IL-1 7 level in peripheral blood was detected in each group,and all the groups except the control group were detected for liver function and HBV-DNA.These related serum markers were detected and the results were statistically analyzed.Results ① IL-17 in the peripheral blood was (8.103±2.061)ng/mL in healthy control group;(25.551 ±7.078)ng/mL,(45.442±18.358)ng/mL and (75.378±19.05)ng/mL in the groups with mild,moderate and severe chronic hepatitis B;and (97.16±17.066)ng/mL in acute on chronic liver failure group.Its levels gradually increased with the severity;and there were significantly different among the five groups and between every two groups (P<0.01).The peripheral blood level of IL-17 was (8.103±2.061)ng/mL in the healthy control group, (34.517±8.905)ng/mL in compensatory cirrhosis group,and (45.615±15.623)ng/mL in the decompensated cirrhosis group.These three groups had pairwise comparison,and the difference between every two groups was significant (P<0 .0 1 ).The peripheral blood level of IL-1 7 in the decompensated cirrhosis group increased compared with that in the compensatory group.③ In the 1 5 2 cases detected,serum IL-1 7 level and serum ALT,AST,TBIL,HBV-DNA levels were positively correlated,and serum PTA had negative correlation with the level of IL-1 7 .④ In the 2 1 cases of acute on chronic liver failure,the peripheral blood level of IL-1 7 did not significantly differ between antigen-e positive and negative groups (P=0.654).⑤ In 21 patients with chronic on acute liver failure,the level of IL-1 7 in peripheral serum and MELD scores showed a positive correlation by Pearson correlation analysis (r=0.533,P=0.013).Conclusion In patients with chronic hepatitis B,the level of IL-17 in peripheral serum increased with disease severity.Moreover,the level of IL-1 7 in peripheral blood may play a role in promoting the progression of cirrhosis and the development of acute on chronic liver failure.

OBJECTIVETo investigate the therapeutic effect of facial artery perforator flap for the soft tissue defects at nose, lip and cheek.

METHODSThe facial artery perforator adjacent to the defect was identified by Doppler ultrasonography. The perforator flap was designed according to the defect location, size and shape. The subcutaneous tissue around the perforator was kept as much as possible to protect the venous drainage.

RESULTSFrom Oct. 2012 to Oct.2013, 26 cases were treated with facial artery perforator flaps, with 9 cases of nasal defects, 10 cases of lip defects and 7 cases of buccal defects. The defects size ranged from 1.5 cm x 2.0 cm to 3.0 cm x 3.0 cm and the flaps size ranged from 2.0 cm x 2.5 cm to 3.5 cm x 3. 5 cm. Superficial necrosis(3mm in width) happened at the end of one flap. All the other 25 flaps survived completely. 16 cases were followed up for 3 months to 2 years with no relapse and satisfactory cosmetic and functional results were achieved.

CONCLUSIONSBoth cosmetic and functional effect can be achieved with facial artery perforator flap for defects at nose, lip and cheek.

Arteries ; Cheek ; surgery ; Graft Survival ; Humans ; Lip ; surgery ; Nose ; surgery ; Perforator Flap ; blood supply ; transplantation ; Rhinoplasty ; methods

Protein A and protein G are two well-defined immunoglobulin (Ig)-binding proteins (IBPs), which show affinity for specific sites on Ig of mammalian hosts. Protein A and protein G contained several highly homologous IgG-binding domains which had been demonstrated to have function to bind to IgG. Whether combinations of Ig-binding domains of various IBPs could produce useful novel binding properties remains interesting. We constructed a combinatorial phage library which displayed randomly-rearranged A, B, C, D and E domains of protein A, B2 and B3 domains of protein G. Four rounds molecular evolution of this library directed by all four human IgG subclasses respectively generated a common arrangement of D-C respectively which didn't exist in SpA. The dynamic loss of control phages and increase of the phages displaying two or more binding domains, especially the selective enrichment of D-C and strict selection of its linking peptides demonstrated the efficient molecular evolutions and the significance of the selected D-C arrangement. The phage binding assays confirmed that D-C possessed a binding advantage with four human IgG subclasses compared to SpA. In this work, a novel combination of Ig-binding domains, D-C, was obtained and presented the novel Ig binding properties which provided a novel candidate molecule for the purification, production and detection of IgG antibodies and a new approach for the further study of structures and functions of IBPs.
Amino Acid Sequence ; Antibody Specificity ; Bacterial Proteins ; immunology ; metabolism ; Binding Sites ; Binding, Competitive ; Evolution, Molecular ; Immunoglobulin G ; immunology ; metabolism ; Molecular Sequence Data ; Peptide Library ; Sequence Alignment ; Staphylococcal Protein A ; immunology ; metabolism

Objective To study the mechanism of tear trough deformity and palabromalar groove deformity.Methods Four old cadavers (2 male,2 female,an average age of 67.2 years) with obvious tear trough deformity and palpbromalar groove deformity and 4 young cadavers (2 male,2 female,an average age of 23.5 years) without tear trough deformity and palpbromalar groove deformity were selected and dissected and histological observation were performed on lower eyelid and periorbital region.Results Compared to young specimens,the skin and orbicularis oculi muscle of old specimens were atrophy and relaxed.Tear trough deformity and palabromalar groove deformity overlaid the junction of thinner eyelid skin and thicker cheek skin.The superior border of the malar fat pad covered the junction of the palpebral and orbital portions of the orbicularis muscle,and correlated with the tear trough and palpbromalar groove,but the superior border of the malar fat pad in young cadavers was found above the tear trough and palpbromalar groove line.The orbicularis retaining ligament arose from the orbital rim and caudal to the junction of the palpebral and orbital portions of the orbicularis muscle,and it was relaxed in old group than that in young group.Conclusions Tear trough deformity and palabromalar groove deformity result from combination of age-related relaxation,atrophy and descent of layers of tissues.The orbital septal and the orbicularis retaining ligament prevent tissues from descending,which makes tear trough deformity and palabromalar groove deformity more visible.

We constructed a phage-displayed random mutation library of Tat38-61(51N/55N), for studying the molecular evolution screening of HIV-1 Tat38-61 epitope. We used primers containing the random nucleotide sequences, and introduced the random mutations at the sites of 51 and 55 amino acids coding sequences into full-length Tat sequences by overlapping PCR. With the randomly mutated full-length Tat as template, the Tat38-61(51N/55N) mutants which contained recognition sequences for the Xba I in both ends were amplified by PCR using the designed primers. The mutants were cloned into Xba I site in the phagemid vector pCANTAB5S, then the recombinants were transformed into E. coli TG1, a phage-displayed the random mutation library of Tat38-61(51N/55N) was constructed by the rescue of help virus M13KO7. The results showed that the library consisted of about 5.0 x 10(6) colonies and the phage library titer was 2.65 x 10(12) TU/mL. More than 56.50% colonies in the library were positive for insertion. Sequence analysis showed that the nucleotides encoding amino acids at the sites of 51 and 55 distributed randomly. The constructed mutation library could meet the requirements for the following molecular evolution screening, and might prepare the Tat mutants for the further study of new Tat vaccine candidates.
AIDS Vaccines ; immunology ; Escherichia coli ; genetics ; metabolism ; HIV-1 ; genetics ; Humans ; Mutation ; Peptide Fragments ; biosynthesis ; genetics ; immunology ; Peptide Library ; Recombinant Proteins ; biosynthesis ; genetics ; immunology ; tat Gene Products, Human Immunodeficiency Virus ; biosynthesis ; genetics ; immunology