Design of eco-friendly antifreeze peptides as novel inhibitors of gas-hydration kinetics.

In this study, peptides designed using fragments of an antifreeze protein (AFP) from the freeze-tolerant insect Tenebrio molitor, TmAFP, were evaluated as inhibitors of clathrate hydrate formation. It was found that these peptides exhibit inhibitory effects by both direct and indirect mechanisms. The direct mechanism involves the displacement of methane molecules by hydrophobic methyl groups from threonine residues, preventing their diffusion to the hydrate surface. The indirect mechanism is characterized by the formation of cylindrical gas bubbles, the morphology of which reduces the pressure difference at the bubble interface, thereby slowing methane transport. The transfer of methane to the hydrate interface is primarily dominated by gas bubbles in the presence of antifreeze peptides. Spherical bubbles facilitate methane migration and potentially accelerate hydrate formation; conversely, the promotion of a cylindrical bubble morphology by two of the designed systems was found to mitigate this effect, leading to slower methane transport and reduced hydrate growth. These findings provide valuable guidance for the design of effective peptide-based inhibitors of natural-gas hydrate formation with potential applications in the energy and environmental sectors.

Prediction of lncRNA and disease associations based on residual graph convolutional networks with attention mechanism.

LncRNAs are non-coding RNAs with a length of more than 200 nucleotides. More and more evidence shows that lncRNAs are inextricably linked with diseases. To make up for the shortcomings of traditional methods, researchers began to collect relevant biological data in the database and used bioinformatics prediction tools to predict the associations between lncRNAs and diseases, which greatly improved the efficiency of the study. To improve the prediction accuracy of current methods, we propose a new lncRNA-disease associations prediction method with attention mechanism, called ResGCN-A. Firstly, we integrated lncRNA functional similarity, lncRNA Gaussian interaction profile kernel similarity, disease semantic similarity, and disease Gaussian interaction profile kernel similarity to obtain lncRNA comprehensive similarity and disease comprehensive similarity. Secondly, the residual graph convolutional network was used to extract the local features of lncRNAs and diseases. Thirdly, the new attention mechanism was used to assign the weight of the above features to further obtain the potential features of lncRNAs and diseases. Finally, the training set required by the Extra-Trees classifier was obtained by concatenating potential features, and the potential associations between lncRNAs and diseases were obtained by the trained Extra-Trees classifier. ResGCN-A combines the residual graph convolutional network with the attention mechanism to realize the local and global features fusion of lncRNA and diseases, which is beneficial to obtain more accurate features and improve the prediction accuracy. In the experiment, ResGCN-A was compared with five other methods through 5-fold cross-validation. The results show that the AUC value and AUPR value obtained by ResGCN-A are 0.9916 and 0.9951, which are superior to the other five methods. In addition, case studies and robustness evaluation have shown that ResGCN-A is an effective method for predicting lncRNA-disease associations. The source code for ResGCN-A will be available at https://github.com/Wangxiuxiun/ResGCN-A .

Membrane-Anchored Aggregation-Induced Emission Luminogens: Accurate Labeling and Efficient Photodynamic Inactivation of Streptococcus mutans in Anticaries Therapy.

Dental caries is a widespread bacterial infectious disease that imposes a significant public health burden globally. The primary culprits in caries development are cariogenic bacteria, notably Streptococcus mutans (S. mutans), due to their robust biofilm-forming capabilities. To address this issue, a series of cationic pyridinium-substituted photosensitizers with aggregation-induced emission have been designed. All of these aggregation-induced emission luminogens (AIEgens) exhibit outstanding microbial visualization and photodynamic killing of S. mutans, thanks to their luminous fluorescence and efficient singlet oxygen generation ability. Notably, one of the membrane-anchored AIEgens (TDTPY) can inactivate planktic S. mutans and its biofilm without causing significant cytotoxicity. Importantly, application of TDTPY-mediated photodynamic treatment on in vivo rodent models has yielded commendable imaging results and effectively slowed down caries progression with assured biosafety. Unlike traditional single-mode anticaries materials, AIEgens integrate the dual functions of detecting and removing S. mutans and are expected to build a new caries management diagnosis and treatment platform. To the best of our knowledge, this is also the first report on the use of AIEgens for anticaries studies both in vitro and in vivo.

Covalent organic framework membrane reactor for boosting catalytic performance.

Membrane reactors are known for their efficiency and superior operability compared to traditional batch processes, but their limited diversity poses challenges in meeting various reaction requirements. Herein, we leverage the molecular tunability of covalent organic frameworks (COFs) to broaden their applicability in membrane reactors. Our COF membrane demonstrates an exceptional ability to achieve complete conversion in just 0.63 s at room temperature-a benchmark in efficiency for Knoevenagel condensation. This performance significantly surpasses that of the corresponding homogeneous catalyst and COF powder by factors of 176 and 375 in turnover frequency, respectively. The enhanced concentration of reactants and the rapid removal of generated water within the membrane greatly accelerate the reaction, reducing the apparent activation energy. Consequently, this membrane reactor enables reactions that are unattainable using both COF powders and homogeneous catalysts. Considering the versatility, our findings highlight the substantial promise of COF-based membrane reactors in organic transformations.

Dealuminated Beta zeolite reverses Ostwald ripening for durable copper nanoparticle catalysts.

Copper nanoparticle-based catalysts have been extensively applied in industry, but the nanoparticles tend to sinter into larger ones in the chemical atmospheres, which is detrimental to catalyst performance. In this work, we used dealuminated Beta zeolite to support copper nanoparticles (Cu/Beta-deAl) and showed that these particles become smaller in methanol vapor at 200°C, decreasing from ~5.6 to ~2.4 nanometers in diameter, which is opposite to the general sintering phenomenon. A reverse ripening process was discovered, whereby migratable copper sites activated by methanol were trapped by silanol nests and the copper species in the nests acted as new nucleation sites for the formation of small nanoparticles. This feature reversed the general sintering channel, resulting in robust catalysts for dimethyl oxalate hydrogenation performed with supported copper nanoparticles for use in industry.

Treatment and prognosis analysis of 488 patients with FIGO 2018 stage Ⅲc squamous cervical cancer / 中华妇产科杂志

Objective: To analyze the treatment and prognosis of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage Ⅲc cervical squamous cell carcinoma. Methods: A total of 488 patients at Zhejiang Cancer Hospital between May, 2013 to May, 2015 were enrolled. The clinical characteristics and prognosis were compared according to the treatment mode (surgery combined with postoperative chemoradiotherapy vs radical concurrent chemoradiotherapy). The median follow-up time was (96±12) months ( range time from 84 to 108 months). Results: (1) The data were divided into surgery combined with chemoradiotherapy group (surgery group) and concurrent chemoradiotherapy group (radiotherapy group), including 324 cases in the surgery group and 164 cases in the radiotherapy group. There were significant differences in Eastern Cooperation Oncology Group (ECOG) score, FIGO 2018 stage, large tumors (≥4 cm), total treatment time and total treatment cost between the two groups (all P<0.01). (2) Prognosis: ① for stage Ⅲc1 patients, there were 299 patients in the surgery group with 250 patients survived (83.6%). In the radiotherapy group, 74 patients survived (52.9%). The difference of survival rates between the two groups was statistically significant (P<0.001). For stage Ⅲc2 patients, there were 25 patients in surgery group with 12 patients survived (48.0%). In the radiotherapy group, there were 24 cases, 8 cases survived, the survival rate was 33.3%. There was no significant difference between the two groups (P=0.296). ② For patients with large tumors (≥4 cm) in the surgery group, there were 138 patients in the Ⅲc1 group with 112 patients survived (81.2%); in the radiotherapy group, there were 108 cases with 56 cases survived (51.9%). The difference between the two groups was statistically significant (P<0.001). Large tumors accounted for 46.2% (138/299) vs 77.1% (108/140) in the surgery group and radiotherapy group. The difference between the two groups was statistically significant (P<0.001). Further stratified analysis, a total of 46 patients with large tumors of FIGO 2009 stage Ⅱb in the radiotherapy group were extracted, and the survival rate was 67.4%, there was no significant difference compared with the surgery group (81.2%; P=0.052). ③ Of 126 patients with common iliac lymph node, 83 patients survived, with a survival rate of 65.9% (83/126). In the surgery group, 48 patients survived and 17 died, with a survival rate of 73.8%. In the radiotherapy group, 35 patients survived and 26 died, with a survival rate of 57.4%. There were no significant difference between the two groups (P=0.051). (3) Side effects: the incidence of lymphocysts and intestinal obstruction in the surgery group were higher than those in the radiotherapy group, and the incidence of ureteral obstruction and acute and chronic radiation enteritis were lower than those in the radiotherapy group, and there were statistically significant differences (all P<0.01). Conclusions: For stage Ⅲc1 patients who meet the conditions for surgery, surgery combined with postoperative adjuvant chemoradiotherapy and radical chemoradiotherapy are acceptable treatment methods regardless of pelvic lymph node metastasis (excluding common iliac lymph node metastasis), even if the maximum diameter of the tumor is ≥4 cm. For patients with common iliac lymph node metastasis and stage Ⅲc2, there is no significant difference in the survival rate between the two treatment methods. Based on the duration of treatment and economic considerations, concurrent chemoradiotherapy is recommended for the patients.

Design and synthesis of anti-HCV drug sofosbuvir:research advances / 国际药学研究杂志

Sofosbuvir is a new type of direct-acting antiviral(DAA)drugs against hepatitis C.By competitive combination to NS5B polymerase activity sites,sofosbuvir can terminate genome synthesis of newly born virus,and finally inhibit the replication of hepatitis C virus(HCV).The research and development process of sofosbuvir is based on the principles of nucleoside antiviral drug metabolism.The subtle structure modification improves the drug′s structure stability and absorption process,which makes sofosbuvir a liver targeted anti-HCV drug.Sofosbuvir has become a clinical fundamental drug for anti-HCV infection,and then used alone or in combination with other drugs,with higher recovery rate,better safety and anti-drug resistance.This article reviews the research back?ground,development process,clinical application and synthetic methods for sofosbuvir.

Feasibility of unilateral or bilateral nerve-sparing radical hysterectomy in patients with cervical cancer and evaluation of the post-surgery recovery of the bladder and rectal function / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the feasibility of unilateral or bilateral nerve-sparing radical hysterectomy and evaluate the recovery of bladder and bowel function postoperatively.</p><p><b>METHODS</b>From August 2008 to October 2009, sixty-one patients with cervical cancer stage Ib1 to IIa underwent radical hysterectomy (33 cases) and nerve-sparing radical hysterectomy (28 cases). Unilateral nerve-sparing radical hysterectomy was performed in 10 patients, and bilateral nerve-sparing radical hysterectomy (BNS) was performed in 18 patients. The data of operation time, blood loss, postoperative hospital stay days, residual urine volume, and postoperative complications were collected. The postoperative recovery of bladder and bowel function was evaluated.</p><p><b>RESULTS</b>There were no significant differences between nerve-sparing radical hysterectomy (NSRH) and radical hysterectomy (RH) groups in operation time [NSRH: (224.5 ± 40.0) min, RH: (176.4 ± 30.0 min)], blood loss [NSRH: (464.3 ± 144.0) ml, RH: (374.2 ± 138.7) ml], postoperative hospital stay days [NSRH: (8.4 ± 2.0) d, RH: (9.2 ± 1.8) d, and residual urine volume [NSRH: (64.8 ± 16.9) ml, RH: (70.6 ± 16.0) ml]. There were also no significant differences between UNSRH and BNSRH groups in operation time [UNSRH: (208.5 ± 28.5) min, BNSRH: (233.3 ± 43.1) min], blood loss [UNSRH: (440.0 ± 104.9) ml, BNSRH: (477.8 ± 162.90) ml], postoperative hospital stay days [UNSRH: 9.1 ± 1.8) d, BNSRH: (8.7 ± 2.1 d], and the residual urine volume [UNSRH: (68.3 ± 12.5) ml, BNSRH: (62.8 ± 20.0) ml]. There was a significant difference in the time of the Foley catheter removal between NSRH [(12.4 ± 5.2) d] and RH [(22.4 ± 9.7) d] groups. There was a significant difference in the time of the Foley catheter removal between UNSRH [(18.2 ± 3.6) d] and BNSRH [(9.1 ± 2.0) d] groups. During the postoperative 3 weeks follow-up, the patients in the NSRH group had a higher rate of satisfaction at urination and defecation (100%, 75%) than the RH group (54.5%, 24.2%).</p><p><b>CONCLUSION</b>UNSRH and BNSRH are safe and feasible techniques for early stage cervical cancer, and may significantly improve the recovery of bladder and rectal function.</p>

Reversing effect of exogenous WWOX gene expression on malignant phenotype of primary cultured lung carcinoma cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Whether WW domain containing oxidoreductase (WWOX) gene is a tumor-suppressor is still controversial. Some researchers found that the transcription of the WWOX gene was lacking not only in tumor tissues but also in non-tumorous tissues and sometimes in normal tissues. Hence it is important to explore the role of the expression of the exogenous WWOX gene in the proliferation and apoptosis of primary cultured lung carcinoma cells.</p><p><b>METHODS</b>Lipofection technique was used to determine primary cultured lung carcinoma cells containing the highly expressed exogenous WWOX gene and primary cultured cells with vectors as controls. An animal model of lung cancer was made by subcutaneous implantation of tumor cells into nude mice. RT-PCR, Western blotting, flow cytometry, and TUNEL were used to detect the transcription, expression of the exogenous gene and the effect of the expression of targeted genes on the proliferation and apoptosis of the primary cultured lung carcinoma cells.</p><p><b>RESULTS</b>The growth, clone formation rate (CFR) ((5.33 +/- 1.53)%) of the primary lung cancer cells transfected with the WWOX gene, tumor size and weight were significantly lower than those of the non-transfected lung cancer cells (CFR: (14.33 +/- 1.53)%) and the primary lung cancer cells transfected with blank plasmids (CFR: (11.00 +/- 1.73)%, P < 0.05). The apoptosis level of primary lung cancer cells transfected with the WWOX gene ((40.72 +/- 5.20)%) was significantly higher than that of the non-transfected lung cancer cells ((2.76 +/- 0.02)%) and the primary lung cancer cells transfected with blank plasmids ((2.72 +/- 0.15)%, P < 0.05).</p><p><b>CONCLUSION</b>The expression of the exogenous WWOX gene can significantly inhibit the proliferation of lung cancer cells and induce their apoptosis, suggesting that the WWOX gene possesses tumor-suppressing effect.</p>