The nuclear pore complex (NPC), one of the largest protein complexes in eukaryotes, serves as a physical gate to regulate nucleocytoplasmic transport. Here, we determined the 8 Å resolution cryo-electron microscopic (cryo-EM) structure of the outer rings containing nuclear ring (NR) and cytoplasmic ring (CR) from the Xenopus laevis NPC, with local resolutions reaching 4.9 Å. With the aid of AlphaFold2, we managed to build a pseudoatomic model of the outer rings, including the Y complexes and flanking components. In this most comprehensive and accurate model of outer rings to date, the almost complete Y complex structure exhibits much tighter interaction in the hub region. In addition to two copies of Y complexes, each asymmetric subunit in CR contains five copies of Nup358, two copies of the Nup214 complex, two copies of Nup205 and one copy of newly identified Nup93, while that in NR contains one copy of Nup205, one copy of ELYS and one copy of Nup93. These in-depth structural features represent a great advance in understanding the assembly of NPCs.
Animals ; Artificial Intelligence ; Cryoelectron Microscopy ; Nuclear Pore/ultrastructure* ; Oocytes/metabolism* ; Xenopus laevis

Chemotherapy has been a major option in clinic treatment of malignant tumors. However, single chemotherapy faces some drawbacks, such as multidrug resistance, severe side effects, which hinder its clinic application in tumor treatment. Multifunctional nanoparticles loading with chemotherapeutic agent and photosensitizer could be a promising way to efficiently conduct tumor combination therapy. In the current study, a novel pH-sensitive and bubble-generating mesoporous silica-based drug delivery system (denoted as M(a)D@PI-PEG-RGD) was constructed. Ammonium bicarbonate (NH

Malignant tumors are the second most important cause of death after cardiovascular and cerebrovascular diseases. Chemotherapeutic drugs for tumor treatment have strong toxic side effects. The common solution is to use nanoparticle as a carrier that can deliver drugs to tumor issues so as to kill the tumor cells. However, most of the current drug-carriers have a serious drug loss before reaching the tumor area, which makes the difficult control of drug release. Multi-stimulus responsive nano-carrier systems can overcome these drawbacks and make drug release controllable. pH/redox dual sensitive nano-carrier systems are currently hot research direction. In this paper, the research progress of pH/redox dual sensitive nano-carrier systems in recent years was reviewed in order to provide reference for relative researches.

In recent years, mesoporous silica nanoparticles (MSNs) have been widely used in the construction of various intelligent drug delivery systems due to their unique and excellent properties. The stimuli-responsive drug delivery system based on mesoporous silica nanoparticles can effectively load anticancer drugs and target them to tumor cells, and then responsively release anticancer drugs under the action of specific stimulation signals. The method of specifically delivering anticancer drugs to target sites not only can greatly improvethe drug efficacy, but also effectively reduce the side effects of anticancer drugs on normal tissues and organs. Thereby the advantages of anticancer drugs in tumor therapy are improved. In this paper, the applications and developments of stimuliresponsive mesoporous silica nano drug delivery systems in tumor therapy were summarized.

Objective: To investigate the efficacy and safety of IA regimen which contains idarubicin (IDA) 8 mg/m², 10 mg/m² or 12 mg/m² as induction chemotherapy for adult patients with de-novo acute myeloid leukemia (AML) . Methods: A total of 1 215 newly diagnosed adult AML patients, ranging from May 2011 to March 2015 in the First Affiliated Hospital of Soochow University and other 36 clinical blood centers in China were enrolled in the multicenter, single-blind, non-randomized, clinical controlled study. To compare the response rate of complete remission (CR) , adverse events between different dose idarubicin combined with cytarabine (100 mg/m²) as induction chemotherapy in newly diagnosed patients of adult AML. Results: Of 1 207 evaluable AML patients were assigned to this analysis of CR rate. The CR rates of IDA 8 mg/m² group, IDA 10 mg/m² group and IDA 12 mg/m² group were 73.6% (215/292) , 84.1% (662/787) and 86.7% (111/128) , respectively (P<0.001) . After adjusted for age, blast ratio of bone marrow, FAB classification and risk stratification, the odds ratios (95% CI) of IDA 10 mg/m² group and IDA 12 mg/m² group were 0.49 (0.34-0.70) and 0.36 (0.18-0.71) , as compared with the IDA 8 mg/m² group (P<0.001, P=0.003) . In the intermediate and favorable groups, CR rates was 76.5% (163/213) , 86.9% (506/582) and 86.1% (68/79) in different doses of IDA (P=0.007) . Interestingly, IA regimen with IDA 10 mg/m² was the only beneficial factor affecting CR in this group after adjusted for age, blast ratio of bone marrow and FAB classification[OR=0.47 (95% CI 0.31-0.71) , P<0.001]. CR rates in adverse group was 50.0% (18/36) , 60.6% (43/71) and 81.8% (18/22) respectively (P=0.089) . However, the odds ratios (95% CI) of IDA 12 mg/m² when compared with the IDA 8 mg/m² was 0.22 (0.06-0.80) , after adjusted for age, blast ratio of bone marrow and FAB classification. The median time (days) of neutrophil count less than 0.5×10⁹/L in IDA 8 mg/m² group, IDA 10 mg/m² group and IDA 12 mg/m² group were 14 (11-18) , 15 (11-20) and 18 (14-22) , respectively (P=0.012) and of platelet count lower than 20×10⁹/L were 14 (7-17) , 15 (11-20) and 17 (15-21) , respectively (P=0.001) . The incidences of lung infection in the three groups were 9.8%, 13.5% and 25.2%, respectively (P<0.001) . Conclusions For young adult patients (aged 18-60 years) with AML in China, intensifying induction therapy with idarubicin 10 mg/m² is clinically superior to IDA 8 mg/m² and IDA 12 mg/m² in favorable intermediate AML subgroup. However, idarubicin 12 mg/m² is more suitable to adverse AML subgroup.

To confirm the etiology of a dead case for a 6 year-old female Ailurus fulgens,one strain of the predominant bacteria from pathologic tissues(heart,liver,spleen,lung and other samples) of the dead Ailurus fulgens were examined and isolated.The isolate was named R1 and no other bacteria were isolated.The bacterial etiological examination(morphological characteristics,biochemical characteristics and 16S rDNA gene detection)of R1 showed that it was identifed as K.peneumoniae.Artificial infection to mice about R1 was also conducted in this study.R1 had strong pathogenicity to mice and the LD50 is 6.5 × 104 CFU/mL.Moreover,the clinical and pathological features of the dead mice were consistent with that of the Ailurus fulgens.To find effective therapeutic drugs of curing other Ailurus fulgens,antibiotic sensitivity test of R1 was conducted,and the results revealed that R1 was highly sensitive to cefotaxime et al,moderately sensitive to amikacin and resistant to penicillin.These data showed that K.peneumoniae was bacterial pathogen leading to death of the Ailurus fulgens and it had strong resistance to penicillins,macrolides and virginiamycin and it had broad drug resistance spectrum.However,R1 is sensitive to cephalosporins and aminoglycoside antibiotics.

Objective Henoch-Sch?nlein purpura(HSP)is a common multisystemic vasculitis in children ,but the exact pathogenesis remains unknown. Pentraxin 3(PTX3),a new kind of inflammatory cytokines,has a strong inflammatory effect,and is involved in occurrence and develop-ment of a variety of autoimmune diseases. The objective of this study is to evaluate the expression of PTX3,interleukin-8(IL-8),tumor necrosis fac-tor-α(TNF-α)and high sensitivity C-reactive protein(hs-CRP)in children with HSP,and explore the clinical significance of PTX3 in HSP devel-opment. Methods Thirty-six children(HSP group)and 17 healthy children(control group)were enrolled in the study. Serum levels of PTX3,IL-8 and TNF-α were detected by enzyme-linked immunosorbent assay. Serum hs-CRP levels were measured by automatic biochemical analyzer. Re-sults The serum levels of PTX3,IL-8,TNF-α,and hs-CRP were up-regulated in HSP group compared with the control group(P<0.05). The levels of PTX3,IL-8,TNF-α,and hs-CRP in patients with joint symptoms,or/and gastrointestinal symptoms,or/and kidney injury were significant-ly higher than those patients without joint symptoms,or/and gastrointestinal symptoms,or/and kidney injury(P<0.05). The expression of PTX3 was positively correlated with the expression of IL-8 and TNF-α(r=0.514,0.833,all P<0.05),but there was no correlation between PTX3 and hs-CRP(r=0.292,P>0.05). The expression of PTX3,IL-8,TNF-α and hs-CRP in HSP patients had no gender difference(all P>0.05). Con-clusion The high expression of PTX3 is related to the degree of inflammation in children with HSP. The up-regulated expression of PTX3 may play an important role in pathogenesis of HSP in children.

Objective To investigate the effect of anti-apoptotic protein HSP-90 in human multiple myeloma cell line U266 cells after bertezomib interaction. Methods The HSP-90 mRNA expression in the U266 cells was tested by reverse transcription polymerase chain reaction (RT-PCR) after 4 hours of treatment of bertezomib by different concentration. Results With the of increased concentration of bortezomib, the expression level of HSP-90 αmRNA was also increased in U266 cells. Respectively, quantitative results of HSP-90α are 0.343±0.017, 0.505±0.039, 0.640±0.029, 0.760±0.059, 0.963±0.054 from the low to high concentration of bertezomib groups. And there are statistical difference between each group(P <0.05). However, the HSP-90β quantitative results in 0 nmol/L concentration of bertezomib (0.61±0.022) have statistical difference between 50, 150, 200 nmol/L groups(P <0.05). HSP-90β quantitative results in 50(0.765±0.050)and 100 nmol/L(0.645±0.052) nmol/L groups are different(P <0.05). Compared with 100 nmol/L concentration of bortezomib group, statistical difference also exists in 150 (0.770±0.059) and 200 nmol/L (0.790±0.027)groups (P <0.05). Although there is no obvious increase in the mRNA expression of HSP-90β from the chart, statistical difference existed in the whole data (P <0.05). Conclusion Bortezomib can increase the level expression of HSP-90 mRNA, and especially increase the level expression of HSP-90α mRNA.

0 (P<0.01).Conclusions HERG1 was over expressed in PANC1 cells and tissues of human pancreatic cancer.The HERG1 K+ channel was related to the proliferation,migration and invasion of PANC1.

目的观察带锁髓内钉固定结合自体骨髓移植治疗长管状骨骨折和骨折不愈合的疗效。方法对12例股骨、胫骨长管状骨骨折和骨折不愈合患者行带锁髓内钉固定、复位,同时行自体骨髓移植治疗(每2周移植1次,共移植3—6次)。结果所有病例均未出现骨折延迟愈合或不愈合,于10—18个月时取出髓内钉,未出现断钉、关节功能障碍、骨密度明显降低等。结论带锁髓内钉固定结合自体骨髓移植是一种可行的治疗长管状骨骨折与骨折不愈合的有效方法。