Publications by authors named "Ke Wu"

368 Publications

Development of a Vaccine against SARS-CoV-2 Based on the Receptor-Binding Domain Displayed on Virus-Like Particles.

Vaccines (Basel) 2021 Apr 16;9(4). Epub 2021 Apr 16.

International Immunology Centre, Anhui Agricultural University, Hefei 230036, China.

The ongoing coronavirus disease (COVID-19) pandemic is caused by a new coronavirus (severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)) first reported in Wuhan City, China. From there, it has been rapidly spreading to many cities inside and outside China. Nowadays, more than 110 million cases with deaths surpassing 2 million have been recorded worldwide, thus representing a major health and economic issues. Rapid development of a protective vaccine against COVID-19 is therefore of paramount importance. Here, we demonstrated that the recombinantly expressed receptor-binding domain (RBD) of the spike protein can be coupled to immunologically optimized virus-like particles derived from cucumber mosaic virus (CuMV). The RBD displayed CuMV bound to ACE2, the viral receptor, demonstrating proper folding of RBD. Furthermore, a highly repetitive display of the RBD on CuMV resulted in a vaccine candidate that induced high levels of specific antibodies in mice, which were able to block binding of the spike protein to ACE2 and potently neutralize SARS-CoV-2 virus in vitro.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/vaccines9040395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073353PMC
April 2021

A chromatography-free and aqueous waste-free process for thioamide preparation with Lawesson's reagent.

Beilstein J Org Chem 2021 9;17:805-812. Epub 2021 Apr 9.

College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310032, P.R. China.

After completing the thio-substitution with Lawesson's reagent, ethanol was found to be effective in the decomposition of the inherent stoichiometric six-membered-ring byproduct from the Lawesson's reagent to a highly polarized diethyl thiophosphonate. The treatment significantly simplified the following chromatography purification of the desired thioamide in a small scale preparation. As scaling up the preparation of two pincer-type thioamides, we have successfully developed a convenient process with ethylene glycol to replace ethanol during the workup, including a traditional phase separation, extraction, and recrystallization. The newly developed chromatography-free procedure did not generate P-containing aqueous waste, and only organic effluents were discharged. It is believed that the optimized procedure offers the great opportunity of applying the Lawesson's reagent for various thio-substitution reactions on a large scale.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3762/bjoc.17.69DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042485PMC
April 2021

Laparoscopic anatomic liver resection of segment 7 using a caudo-dorsal approach to the right hepatic vein.

Surg Oncol 2021 Apr 18;38:101575. Epub 2021 Apr 18.

Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Army Medical University, Chongqing, China. Electronic address:

Background: Laparoscopic anatomic liver resection of segment 7 (S7) is technically challenging because of the posterosuperior location and the lack of clear anatomical landmarks [1-4]. Here, we introduce a caudo-dorsal approach, which may offer a benefit for the difficult procedure.

Methods: The patient was a 53-year-old man with hepatocellular carcinoma located in S7 of the liver. After the transection of caudate process, the Glissonean pedicle of S7 (G7) extending from the right posterior Glissonean pedicle was identified on the liver dorsal side. The demarcation line was noted by isolating and clamping G7. The intraoperative ultrasound was then used to assess the extent of the tumor. The right hepatic vein was approached from the dorsal side and continuously exposed in a caudal-cranial direction along the anterior surface of inferior vena cava after isolating and cutting the venous branches draining S7. Following the dissection of G7, the liver parenchymal transection was proceeded along the ischemic line between segment 6 and 7 with the ventral cutting plane extended to join the dorsal one. The liver parenchyma of the ventral side of the exposed right hepatic vein (RHV) was further transected from the dorsal side toward the root side of RHV. The resection of S7 was completed with perihepatic ligaments dissection.

Results: The intermittent Pringle maneuver (15 min occlusion and 5 min reperfusion) was applied when necessary with a total time of 45 min. The operation time was 200 min, the estimated blood loss was 300 ml, and no transfusion was required. Pathology confirmed moderately differentiated HCC with negative surgical margin. The patient was discharged on postoperative day 8 with no complications and has been followed up for 8 months without recurrence.

Conclusion: This caudo-dorsal approach for laparoscopic anatomical S7 segmentectomy is easy and feasible when performed by experienced surgeons at experienced centers in well-selected patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.suronc.2021.101575DOI Listing
April 2021

Application of endoscopic technique in completely occluded anastomosis with anastomotic separation after radical resection of colon cancer: a case report and literature review.

BMC Surg 2021 Apr 20;21(1):201. Epub 2021 Apr 20.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Background: Anastomosis-related complications are common after the radical resection of colon cancer. Among such complications, severe stenosis or completely occluded anastomosis (COA) are uncommon in clinical practice, and the separation of the anastomosis is even rarer. For such difficult problems as COA or anastomotic separation, clinicians tend to adopt surgical interventions, and few clinicians try to solve them through endoscopic operations.

Case Presentation: In this article, we present a case of endoscopic treatment of anastomotic closure and separation after radical resection for sigmoid carcinoma. After imaging examination and endoscopic evaluation, we found that the patient had a COA accompanied by a 3-4 cm anastomotic separation. With the aid of fluoroscopy, we attempted to use the titanium clip marker as a guide to perform an endoscopic incision and successfully achieved recanalization. We used a self-expanding covered metal stent to bridge the intestinal canal to resolve the anastomotic separation. Finally, the patient underwent ileostomy takedown, and the postoperative recovery was smooth. The follow-up evaluation results showed that the anastomotic stoma was unobstructed.

Conclusions: We reported the successful application of endoscopic technique in a rare case of COA and separation after colon cancer surgery, which is worth exploring and verifying through more clinical studies in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12893-021-01202-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056686PMC
April 2021

CD45ROCD8 T cell-derived exosomes restrict estrogen-driven endometrial cancer development via the ERβ/miR-765/PLP2/Notch axis.

Theranostics 2021 11;11(11):5330-5345. Epub 2021 Mar 11.

Laboratory for Reproductive Immunology, NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200080, People's Republic of China.

Estrogen-dependent cancers (e.g., breast, endometrial, and ovarian cancers) are among the leading causes of morbidity and mortality in women worldwide. Recently, exosomes released by tumor-infiltrating CD8 T cells have been under the spotlight in the field of cancer immunotherapy. Our study aims at elucidating the underlying mechanisms of the crosstalk between estrogen signaling and CD8 T cells, and possible intervention values in uterine corpus endometrial cancer (UCEC). Micro RNA-seq was conducted to screen differentially expressed micro RNA in UCEC. Bioinformatic analysis was processed to predict the target of miR-765. RNA silencing or overexpressing and pharmacologic inhibitors were used to assess the functions of ERβ/miR-765/PLP2/Notch axis in UCEC cell proliferation and invasion and . imaging was performed to evaluate the metastasis of tumor in mice. Combined fluorescent hybridization for miR-765 and immunofluorescent labeling for CD8 was carried out to prove the co-localization between miR-765 and CD8 T cells. Exosomes derived from CD45ROCD8 T cells were isolated to detect the regulatory effects on UCEC. miR-765 is characterized as the most downregulated miRNA in UCEC, and there is a negative correlation between miR-765 and Proteolipid protein 2 (PLP2) in UCEC lesion. Estrogen significantly down-regulates miR-765 level, and facilitates the development of UCEC by estrogen receptor (ER) β. Mechanistically, this process is mediated through the miRNAs (e.g., miR-3584-5p, miR-7-5p, miR-150-5p, and miR-124-3p) cluster-controlled regulation of the PLP2, which further regulates Ki-67 and multiple epithelial-mesenchymal transition (EMT)-related molecules (e.g, E-cadherin and Vimentin) in a Notch signaling pathway-dependent manner. Interestingly, the selective ER degrader Fulvestrant alleviates estrogen-mediated miR-765/PLP2 expression regulation and UCEC development in ERβ-dependent and -independent manners. Additionally, CD45ROCD8 T cell-derived exosomes release more miR-765 than that from CD45ROCD8 T cells. In therapeutic studies, these exosomes limit estrogen-driven disease development via regulation of the miR-765/PLP2 axis. This observation reveals novel molecular mechanisms underlying estrogen signaling and CD8 T cell-released exosomes in UCEC development, and provides a potential therapeutic strategy for UCEC patients with aberrant ERβ/miR-765/PLP2/Notch signaling axis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/thno.58337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039953PMC
March 2021

Rapid Acquisition of High-Quality SARS-CoV-2 Genome via Amplicon-Oxford Nanopore Sequencing.

Virol Sin 2021 Apr 13. Epub 2021 Apr 13.

CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China.

Genome sequencing has shown strong capabilities in the initial stages of the COVID-19 pandemic such as pathogen identification and virus preliminary tracing. While the rapid acquisition of SARS-CoV-2 genome from clinical specimens is limited by their low nucleic acid load and the complexity of the nucleic acid background. To address this issue, we modified and evaluated an approach by utilizing SARS-CoV-2-specific amplicon amplification and Oxford Nanopore PromethION platform. This workflow started with the throat swab of the COVID-19 patient, combined reverse transcript PCR, and multi-amplification in one-step to shorten the experiment time, then can quickly and steadily obtain high-quality SARS-CoV-2 genome within 24 h. A comprehensive evaluation of the method was conducted in 42 samples: the sequencing quality of the method was correlated well with the viral load of the samples; high-quality SARS-CoV-2 genome could be obtained stably in the samples with Ct value up to 39.14; data yielding for different Ct values were assessed and the recommended sequencing time was 8 h for samples with Ct value of less than 20; variation analysis indicated that the method can detect the existing and emerging genomic mutations as well; Illumina sequencing verified that ultra-deep sequencing can greatly improve the single read error rate of Nanopore sequencing, making it as low as 0.4/10,000 bp. In summary, high-quality SARS-CoV-2 genome can be acquired by utilizing the amplicon amplification and it is an effective method in accelerating the acquisition of genetic resources and tracking the genome diversity of SARS-CoV-2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12250-021-00378-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043101PMC
April 2021

A polymer controlled nucleation route towards the generalized growth of organic-inorganic perovskite single crystals.

Nat Commun 2021 Apr 1;12(1):2023. Epub 2021 Apr 1.

Institute of Microstructure and Property of Advanced Materials, Faculty of Materials and Manufacturing, Beijing University of Technology, Beijing, China.

Recently, there are significant progresses in the growth of organic-inorganic lead halide perovskite single crystals, however, due to their susceptible nucleation and growth mechanisms and solvent requirements, the efficient and generalized growth for these single crystals is still challenging. Here we report the work towards this target with a polymer-controlled nucleation process for the highly efficient growth of large-size high-quality simple ternary, mixed-cations and mixed-halide perovskite single crystals. Among them, the carrier lifetime of FAPbBr single crystals is largely improved to 10199 ns. Mixed MA/FAPbBr single crystals are synthesized. The crucial point in this process is suggested to be an appropriate coordinative interaction between polymer oxygen groups and Pb, greatly decreasing the nuclei concentrations by as much as 4 orders of magnitudes. This polymer-controlled route would help optimizing the solution-based OIHPs crystal growth and promoting applications of perovskite single crystals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-22193-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016843PMC
April 2021

Primary and secondary postoperative hemorrhage in pediatric tonsillectomy.

World J Clin Cases 2021 Mar;9(7):1543-1553

Department of Radiology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou 310052, Zhejiang Province, China.

Background: Tonsillectomy is the most common procedure for treatment of pediatric recurrent acute tonsillitis and tonsillar enlargement that contributes to obstructive sleep apnea hypopnea syndrome. Postoperative hemorrhage of tonsillectomy is a life-threatening complication.

Aim: To identify the risk factors that may contribute to primary and secondary post-operative hemorrhage in pediatric tonsillectomy.

Methods: The clinical data from 5015 children, 3443 males and 1572 females, aged 1.92-17.08 years, with recurrent tonsillitis and/or tonsil hypertrophy who underwent tonsillectomy in our hospital from January 2009 to December 2018 were retrospectively collected. The variables including sex, age, time of onset, diagnosis, method of tonsillectomy, experience of surgeon, time when the surgery started and monthly average air temperature were abstracted. The patients with postoperative hemorrhage were classified into two groups, the primary bleeding group and the secondary bleeding group, and their characteristics were compared with those of the nonbleeding group separately. Statistical analysis was performed by chi-square test with SPSS 20.

Results: Ninety-two patients had post-tonsillectomy hemorrhage, and the incidence rate of post-tonsillectomy hemorrhage was 1.83%. The mean age was 5.75 years. Cases of primary hemorrhage accounted for approximately 33.70% (31/92), and cases of secondary hemorrhage occurred in 66.30% (61/92). The rate of reoperation for bleeding was 0.92%, and the rate of rehospitalization for bleeding was 0.88% in all patients. Multiple hemostasis surgery was performed in 6.52% (3/46) of patients. The method of tonsillectomy (coblation tonsillectomy) and experience of the surgeon (junior surgeon with less than 5 years of experience) were significantly associated with primary hemorrhage ( = 5.830, = 0.016, = 6.621, = 0.010, respectively). Age (over 6 years old) and time of onset (more than a 1-year history) were significantly associated with secondary hemorrhage (= 15.242, = 0.000, =4.293, = 0.038, respectively). There was no significant difference in sex, diagnosis, time when the surgery started or monthly average air temperature. There was a significant difference in the intervention measures between the primary bleeding group and the secondary bleeding group (= 10.947, = 0.001). The lower pole and middle portion were the common bleeding sites, followed by the upper pole and palatoglossal arch.

Conclusion: The incidence rate of post-tonsillectomy hemorrhage is low. Coblation tonsillectomy and less than 5 years' experience of surgeon contribute to the tendency for primary hemorrhage. Age and time of onset are responsible for secondary hemorrhage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12998/wjcc.v9.i7.1543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942054PMC
March 2021

Kirscner wire fixation versus suture anchor technique for mallet finger: A meta-analysis.

Medicine (Baltimore) 2021 Mar;100(11):e24996

Department of Hand Surgery, Wuxi 9th People's Hospital Affiliated to Soochow University, Wuxi, China.

Purpose: Though the previous studies had described various surgical techniques for the treatment of mallet finger injuries, consensus on which technique was the most effective and appropriate surgical methods had not yet reached. This review aimed to systematically compare the effectiveness and safety of the treatment for mallet finger injuries via Kirschner wire fixation versus suture anchor technique to recommend an optimum option.

Methods: All literatures published until December 31, 2019 compared Kirschner wire fixation versus suture anchor technique to treat mallet finger were acquired through a comprehensive search in multiple databases. A meta-analysis was performed by the Cochrane Collaboration's RevMan 5.3 software.

Results: A total of 8 trials with 362 cases consisted of 4 randomized controlled trials and 4 prospective studies. The results suggested that the groups treated with kirschner wire fixation experienced more significant advantage in less complications than suture anchor groups (P  < .05). On the other hand, no significant differences were found in terms of the total active range motion of the distal interphalangeal joint, the average distal interphalangeal joint extensor lag, Visual Analogue Scale scores, recurrence, as well as functional assessment at the final follow-up (P > .05, respectively) between the two surgical procedures.

Conclusions: No obvious superiority were shown for the effectiveness between the two surgical interventions based on the above results. But in view of the less economic spending and complications, Kirschner wire fixation should be a better alternative relative to the suture anchor technique for inevitable surgical treatment of mallet finger lesions. However, a prudent attitude is still necessary to choose the two operative managements before a large sample and high-quality randomized controlled trials had been performed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000024996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982224PMC
March 2021

Construction and validation of a machine learning-based nomogram: A tool to predict the risk of getting severe coronavirus disease 2019 (COVID-19).

Immun Inflamm Dis 2021 Mar 13. Epub 2021 Mar 13.

Shanghai Medical Aid Team in Wuhan, Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.

Background: Identifying patients who may develop severe coronavirus disease 2019 (COVID-19) will facilitate personalized treatment and optimize the distribution of medical resources.

Methods: In this study, 590 COVID-19 patients during hospitalization were enrolled (Training set: n = 285; Internal validation set: n = 127; Prospective set: n = 178). After filtered by two machine learning methods in the training set, 5 out of 31 clinical features were selected into the model building to predict the risk of developing severe COVID-19 disease. Multivariate logistic regression was applied to build the prediction nomogram and validated in two different sets. Receiver operating characteristic (ROC) analysis and decision curve analysis (DCA) were used to evaluate its performance.

Results: From 31 potential predictors in the training set, 5 independent predictive factors were identified and included in the risk score: C-reactive protein (CRP), lactate dehydrogenase (LDH), Age, Charlson/Deyo comorbidity score (CDCS), and erythrocyte sedimentation rate (ESR). Subsequently, we generated the nomogram based on the above features for predicting severe COVID-19. In the training cohort, the area under curves (AUCs) were 0.822 (95% CI, 0.765-0.875) and the internal validation cohort was 0.762 (95% CI, 0.768-0.844). Further, we validated it in a prospective cohort with the AUCs of 0.705 (95% CI, 0.627-0.778). The internally bootstrapped calibration curve showed favorable consistency between prediction by nomogram and the actual situation. And DCA analysis also conferred high clinical net benefit.

Conclusion: In this study, our predicting model based on five clinical characteristics of COVID-19 patients will enable clinicians to predict the potential risk of developing critical illness and thus optimize medical management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/iid3.421DOI Listing
March 2021

Synchronous reduction-fixation of reducible heavy metals from aqueous solutions: Application of novel mesoporous MFT/SBA-15 composite materials.

Chemosphere 2021 Mar 1;276:130112. Epub 2021 Mar 1.

National-Regional Joint Engineering Research Center for Soil Pollution Control and Remediation in South China, Guangdong Key Laboratory of Integrated Agro-environmental Pollution Control and Management, Institute of Eco-environmental and Soil Sciences, Guangdong Academy of Sciences, Guangzhou, 510650, China. Electronic address:

The usual treatment for Cr(VI)-contaminated wastewater primarily included reduction, adsorption, and the subsequent separation of the Cr-laden adsorbent. Among these factors, the adsorbent is the most critical factor in determining Cr removal efficiency. In this study, a novel melamine-formaldehyde-thiourea (MFT) chelating resin/mesoporous silica composite material (MFT/SBA-15) was synthesized via a co-condensation method and used for the reduction and fixation of Cr(VI)-contaminated water. Cr(VI) adsorption onto MFT/SBA-15 obeyed the pseudo-second-order model, and the chemical adsorption was the rate-limiting step in the adsorption process. Also it followed the Langmuir adsorption model, with single molecular layer adsorption characteristics. The organic components within MFT/SBA-15 were the core functional groups for Cr(VI) adsorption, and the formation of a coordination bond (CS→Cr) between the lone electron pairs of the S atom and Cr during the adsorption process led to the synchronous reduction-fixation processes of Cr(VI). These synchronous effects were further demonstrated for other reducible heavy metals, including As(V) and Cu(II), but negligibly observed in chemically stable elements, such as Zn(II), Ni(II), Pb(II), Cd(II), and As(III). The novel mesoporous MFT/SBA-15 materials combine the advantages of the chelating resin and mesoporous silica and have excellent potential for the wastewater treatment of reducible heavy metals through synchronous reduction-fixation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2021.130112DOI Listing
March 2021

Recovery of Acid and Base from Sodium Sulfate Containing Lithium Carbonate Using Bipolar Membrane Electrodialysis.

Membranes (Basel) 2021 Feb 22;11(2). Epub 2021 Feb 22.

Collaborative Innovation Center for Environmental Pollution Precaution and Ecological Rehabilitation of Anhui, School of Biology, Food and Environment Engineering, Hefei University, Hefei 230601, China.

Lithium carbonate is an important chemical raw material that is widely used in many contexts. The preparation of lithium carbonate by acid roasting is limited due to the large amounts of low-value sodium sulfate waste salts that result. In this research, bipolar membrane electrodialysis (BMED) technology was developed to treat waste sodium sulfate containing lithium carbonate for conversion of low-value sodium sulfate into high-value sulfuric acid and sodium hydroxide. Both can be used as raw materials in upstream processes. In order to verify the feasibility of the method, the effects of the feed salt concentration, current density, flow rate, and volume ratio on the desalination performance were determined. The conversion rate of sodium sulfate was close to 100%. The energy consumption obtained under the best experimental conditions was 1.4 kWh·kg. The purity of the obtained sulfuric acid and sodium hydroxide products reached 98.32% and 98.23%, respectively. Calculated under the best process conditions, the total process cost of BMED was estimated to be USD 0.705 kg NaSO, which is considered low and provides an indication of the potential economic and environmental benefits of using applying this technology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/membranes11020152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927085PMC
February 2021

Mutation analysis and prenatal diagnosis of a family with congenital contractural arachnodactyly.

Mol Genet Genomic Med 2021 Feb 27:e1638. Epub 2021 Feb 27.

Key Laboratory of Medical Genetics, Wenzhou Central Hospital, Wenzhou, China.

Background: Congenital contractural arachnodactyly (CCA) is a rare autosomal dominant condition caused by mutations in the fibrillin 2 gene (FBN2). The primary clinical symptoms of CCA include multiple flexion contractures, arachnodactyly, dolichostenomelia, scoliosis, abnormal pinnae, muscular hypoplasia, and crumpled ears.

Methods: We used whole-exome sequencing technology to examine an arthrogryposis multiplex congenita and used Sanger sequencing technology to genetically confirm its family.

Results: FBN2 c.3344A>T(p.D1115V) was identified in this family with CCA in a pedigree. Prenatal diagnosis and counseling were carried out simultaneously to avoid the birth of the sick fetus.

Conclusion: The study is on FBN2 variant in CCA, which potentially having implications for genetic counseling and clinical management, our study may provide new insights into the cause and diagnosis of CCA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mgg3.1638DOI Listing
February 2021

Partial substitution of organic nitrogen with synthetic nitrogen enhances rice yield, grain starch metabolism and related genes expression under the dual cropping system.

Saudi J Biol Sci 2021 Feb 17;28(2):1283-1296. Epub 2020 Nov 17.

Key Laboratory of Crop Cultivation and Farming Systems College of Agriculture, Guangxi University Nanning 530004, China.

Improving grain filling in the presernt farming systems is crucial where grain filling is a concern due to the extreme use of chemical fertilizers (CF). A field experiment was conducted at the experimental station of Guangxi University, China in 2019 to test the hypothesis that cattle manure (CM) and poultry manure (PM) combined with CF could improve rice grain filling rate, yield, biochemical and qualitative attributes. A total of six treatments, i.e., no fertilizer (T), 100% CF (T), 60% CM + 40% CF (T), 30% CM + 70% CF (T), 60% PM + 40% CF (T), and 30% PM + 70% CF (T) were used in this study. Results showed that the combined treatment Tincreased starch metabolizing enzymes activity (SMEs), such as ADP-glucose phosphorylase (ADGPase) by 8 and 12%, soluble starch synthase (SSS) by 7 and 10%, granule bound starch synthesis (GBSS) by 7 and 9%, and starch branching enzyme (SBE) by 14 and 21% in the early and late seasons, respectively, compared with T. Similarly, higher rice grain yield, grain filling rate, starch, and amylose content were also recorded in combined treatments. In terms of seasons, higher activity of SMEs , grain starch, and amylose content was noted in the late-season compared to the early season. The increment in these traits was mainly attributed to a lower temperature in the late season during the grain filling period. Furthermore, our results suggested that an increment in starch accumulation and grain filling rate were mainly associated with the enhanced sink capacity by regulating key enzyme activities involved in Suc-to-starch conversion. In-addition, RT-qPCR analysis showed higher expression levels of  and  genes, which resultantly increased the activities of SMEs during the grain filling period under combined treatments. Linear regression analysis revealed that the activity of ADGPase, SSS, GBSS, and SBE were highly positively correlated with starch and amylose accumulation. Thus, we concluded that a combination of 30% N from PM or CM with 70% N from CF is a promising option in terms of improving rice grain yield and quality. Our study provides a sustainable fertilizer management strategy to enhance rice grain yield and quality at the lowest environmental cost.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.sjbs.2020.11.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878691PMC
February 2021

Functional expression and purification of recombinant full-length human ATG7 protein with HIV-1 Tat peptide in Escherichia coli.

Protein Expr Purif 2021 Jun 13;182:105844. Epub 2021 Feb 13.

Beijing Key Laboratory of Radiation Biology (No. BZ0325) and Department of Experimental Pathology, Beijing Institute of Radiation Medicine, Beijing, 100850, China. Electronic address:

The human autophagy-related protein ATG7 (hATG7), an E1-like ubiquitin enzyme, activates two ubiquitin-like proteins, LC3 (Atg8) and Atg12, and promotes autophagosome formation. While hATG7 plays an essential role for the autophagy conjugation system, the production of full-length functional hATG7 in bacterial systems remains challenging. Previous studies have demonstrated that the HIV-1 virus-encoded Tat peptide ('GRKKRRQRRR') can increase the yield and solubility of heterologous proteins. Here, functional full-length hATG7 was expressed using the pET28b-Tat expression vector in the Escherichia coli BL21 (DE3) strain. Recombinant hATG7 protein aggregated as inclusion bodies while expressed with widely used prokaryotic expression plasmids. In contrast, the solubility of Tat-tagged hATG7 increased significantly with prolonged time compared to Tat-free hATG7. The recombinant proteins were purified to >90% homogeneity under native conditions with a single step of affinity chromatography purification. The results of in vitro pull-down and LC3B-I lipidation assays showed that Tat-tagged hATG7 directly interacted with LC3B-I and promoted LC3B-I lipidation, suggesting that Tat-tagged hATG7 has significant catalytic activity. Overall, this study provides a novel method for improving the functional expression of full-length hATG7 in bacterial systems by fusion with the Tat peptide, a process which may be applied in future studies of hATG7 structure and function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pep.2021.105844DOI Listing
June 2021

Small-Conductance Ca-Activated K Channels 2 in the Hypothalamic Paraventricular Nucleus Precipitates Visceral Hypersensitivity Induced by Neonatal Colorectal Distension in Rats.

Front Pharmacol 2020 27;11:605618. Epub 2021 Jan 27.

Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China.

Visceral hypersensitivity is one of the pivotal pathophysiological features of visceral pain in irritable bowel syndrome (IBS). Small-conductance Ca-activated K channel (SK) is critical for a variety of functions in the central nervous system (CNS), nonetheless, whether it is involved in the pathogenesis of visceral hypersensitivity remain elusive. In this study, we examined mechanism of SK2 in hypothalamic paraventricular nucleus (PVN) in the pathogenesis of visceral hypersensitivity induced by neonatal colorectal distension (CRD). Rats undergoing neonatal CRD presented with visceral hypersensitivity as well as downregulated membrane SK2 channel and p-PKA. Intra-PVN administration of either the membrane protein transport inhibitor dynasore or the SK2 activator 1-EBIO upregulated the expression of membrane SK2 in PVN and mitigated visceral hypersensitivity. In addition, 1-EBIO administration reversed the increase in neuronal firing rates in PVN in rats undergoing neonatal CRD. On the contrary, intra-PVN administration of either the SK2 inhibitor apamin or PKA activator 8-Br-cAMP exacerbated the visceral hypersensitivity. Taken together, these findings demonstrated that visceral hypersensitivity is related to the downregulation of membrane SK2 in PVN, which may be attributed to the activation of PKA; pharmacologic activation of SK2 alleviated visceral hypersensitivity, which brings prospect of SK2 activators as a new intervention for visceral pain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2020.605618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873043PMC
January 2021

The design of X-band EPR cavity with narrow detection aperture for in vivo fingernail dosimetry after accidental exposure to ionizing radiation.

Sci Rep 2021 Feb 8;11(1):2883. Epub 2021 Feb 8.

Beijing Institute of Radiation Medicine, Beijing Key Laboratory of Radiation Biology (No. BZ0325), Beijing, 100850, China.

For the purpose of assessing the radiation dose of the victims involved in the nuclear emergency or radiation accident, a new type of X-band EPR resonant cavity for in vivo fingernail EPR dosimetry was designed and a homemade EPR spectrometer for in vivo fingernail detection was constructed. The microwave resonant mode of the cavity was rectangular TE101, and there was a narrow aperture for fingernail detection opened on the cavity's wall at the position of high detection sensitivity. The DPPH dot sample and the fingernail samples were measured based on the in vivo fingernail EPR spectrometer. The measurements of the DPPH dot sample verified the preliminary functional applicable of the EPR spectrometer and illustrated the microwave power and modulation response features. The fingernails after irradiation by gamma-ray were measured and the radiation-induced signal was acquired. The results indicated that the cavity and the in vivo EPR dosimeter instrument was able to detect the radiation-induced signal in irradiated fingernail, and preliminarily verified the basic function of the instrument and its potential for emergency dose estimate after a radiation accident.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-82462-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870891PMC
February 2021

Ni-catalyzed reductive decyanation of nitriles with ethanol as the reductant.

Chem Commun (Camb) 2021 Mar;57(18):2273-2276

College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310032, P. R. China and State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, The Chinese Academy of Sciences, Lanzhou 730000, P. R. China.

A nickel-catalyzed reductive decyanation of aromatic nitriles has been developed, in which the readily available and abundant ethanol was applied as the hydride donor. Various functional groups on the aromatic rings, such as alkoxyl, amino, imino and amide, were compatible in this catalytic protocol. Heteroaryl, benzylic and alkenyl nitriles were also tolerated. Mechanistic investigation indicated that ethanol provided hydride efficiently via β-hydride elimination in this reductive decyanation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0cc07743gDOI Listing
March 2021

Efficacy and safety of apatinib combined with transarterial chemoembolization (TACE) in treating patients with recurrent hepatocellular carcinoma.

Ann Transl Med 2020 Dec;8(24):1677

Department of Hepatobiliary Surgery, Xinqiao Hospital, Army Medical University, Chongqing, China.

Background: Apatinib, a vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitor, has shown promising therapeutic effect for hepatocellular carcinoma (HCC). This prospective clinical study was implemented to evaluate the efficacy and safety of apatinib combined with transarterial chemoembolization (TACE) versus TACE alone in treating patients with recurrent HCC after hepatectomy.

Methods: Eligible patients with postoperative recurrent HCC from January 2018 to January 2020 were enrolled at the Xinqiao Hospital of Army Medical University. Patients were randomized 1:1 into TACE plus apatinib group or TACE-alone group. The clinical information of patients was collected, and the patients were followed up until untreatable progression or the end of the study. Adverse events (AEs), overall survival (OS) and progression-free survival (PFS) between the two groups were evaluated. In addition, the objective response rate (ORR) and the disease control rate (DCR) were determined according to the modified Response Evaluation Criteria In Solid Tumors (mRECIST). Among those indexes, PFS was the primary endpoint.

Results: This study enrolled 80 patients with recurrent HCC, and the demographics and primary tumor characteristics were balanced between the two groups. However, TACE plus apatinib treatment could significantly improve the median PFS of patients when compared with the TACE-alone group (17.2 12.5 months, P=0.041). The 1- and 2-year overall survival (OS) rates showed a tendency of improving in the TACE plus apatinib group, but not significantly (95.0% 85.0%, and 90.0% 75.0%; both P>0.05). Furthermore, the TACE plus apatinib treatment did significantly increase the short-term ORR and DCR when compared with the TACE-alone group (all P<0.05). And no unexpected toxicity or procedure-related mortality was occurred during this study.

Conclusions: The combination treatment of apatinib and TACE might be safe and of potential benefit on patients with intrahepatic recurrent HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm-20-7244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812192PMC
December 2020

Bioinformatic gene analysis for possible biomarkers and therapeutic targets of hypertension-related renal cell carcinoma.

Transl Androl Urol 2020 Dec;9(6):2675-2687

Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Renal cell carcinoma (RCC) is one of the most prevalent malignant tumors of the urinary system. Hypertension can cause hypertensive nephropathy (HN). Meanwhile, Hypertension is considered to be related to kidney cancer. We analyzed co-expressed genes to find out the relationship between hypertension and RCC and show possible biomarkers and novel therapeutic targets of hypertension-related RCC.

Methods: We identified the differentially expressed genes (DEGs) of HN and RCC through analyzing Gene Expression Omnibus (GEO) datasets GSE99339, GSE99325, GSE53757 and GSE15641 by means of bioinformatics analysis, respectively. Then we evaluated these genes with protein-protein interaction (PPI) networks, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and CTD database. Subsequently, we verified co-expressed DEGs with Gene Expression Profiling Interactive Analysis (GEPIA) database. Finally, corresponding predicted miRNAs of co-expressed DEGs were identified and verified via mirDIP database and Starbase, respectively.

Results: We identified 9 co-expressed DEGs, including , , , , , , , , and . and and their corresponding predicted miRNAs, especially hsa-miR-221-5p, hsa-miR-205-5p, hsa-miR-152-3p and hsa-miR-137 may be notably related to hypertension-related RCC.

Conclusions: and genes have great potential to become novel biomarkers and therapeutic targets concerning hypertension-related RCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/tau-20-817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807377PMC
December 2020

Astragaloside IV alleviates silica‑induced pulmonary fibrosis via inactivation of the TGF‑β1/Smad2/3 signaling pathway.

Int J Mol Med 2021 03 15;47(3). Epub 2021 Jan 15.

Department of Respiratory Medicine, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250033, P.R. China.

The aim of the present study was to investigate the anti‑fibrotic effects of astragaloside IV (ASV) in silicosis rats, and to further explore the potential underlying molecular mechanisms. A silica‑induced rat model of pulmonary fibrosis was successfully constructed. Hematoxylin and eosin and Masson's trichrome staining were performed to observe the pathological changes in lung tissues. Immunohistochemical analysis was used to assess the expression levels of Collagen I, fibronectin and α‑smooth muscle actin (α‑SMA). A hemocytometer and Giemsa staining were used to evaluate the cytological characteristics of the bronchoalveolar lavage fluid. ELISA was used to detect the levels of the inflammatory cytokines tumor necrosis factor‑α, interleukin (IL)‑1β and IL‑6. Reverse transcription‑quantitative PCR and western blotting were performed to detect the mRNA and protein expression levels of genes associated with the transforming growth factor (TGF)‑β1/Smad signaling pathway. ASV alleviated silica‑induced pulmonary fibrosis, and reduced the expression of collagen I, fibronectin and α‑SMA. In addition, the results of the present study suggested that the ASV‑mediated anti‑pulmonary fibrosis response may involve reduction of inflammation and oxidative stress. More importantly, ASV suppressed silica‑induced lung fibroblast fibrosis via the TGF‑β1/Smad signaling pathway, thereby inhibiting the progression of silicosis. In conclusion, the present study indicated that ASV may prevent silicosis‑induced fibrosis by reducing the expression of Collagen I, fibronectin and α‑SMA, and reducing the inflammatory response and oxidative stress, and these effects may be mediated by inhibiting the activation of the TGF‑β1/Smad signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ijmm.2021.4849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834968PMC
March 2021

Application of arterial spin labeling and susceptibility weighted imaging in the diagnosis of ischemic cerebrovascular diseases.

Int J Clin Exp Pathol 2020 1;13(12):3052-3059. Epub 2020 Dec 1.

Department of Medical Imaging, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University Jinan 250012, China.

Objective: To investigate the application value of arterial spin labeling (ASL) and susceptibility weighted imaging (SWI) in the diagnosis of acute ischemic cerebrovascular disease (CVDs).

Methods: A total of 124 patients who received fluid attenuated inversion recovery (FLAIR), diffusion weighted imaging (DWI), ASL, time of flight magnetic resonance angiography (TOF-MRA) and SWI scan sequentially were included in this study. The area of the abnormal perfusion region was compared with that of the restricted diffusion region. The cerebral blood flow (CBF) value and apparent diffusion coefficient (ADC) value were compared in ischemic penumbra (IP), infarct core and mirror region. The susceptibility vessel sign (SVS) detection rate was compared with the major vessel severe stenosis or occlusion rate as revealed by MRA. A receiver operating characteristic curve (ROC) was used to analyze the value of SVS as revealed by SWI.

Results: In total, 124 cases were included in this study, and 77 cases showed acute cerebral infarction. Among the 77 cases, 59 cases showed an IP. There were significant differences in ADC and CBF values between the infarct core and mirror region (P < 0.01). There was no significant difference in ADC value between IP and mirror region (P = 0.176), but there was significant difference in CBF value between IP and mirror region (P < 0.01). There was no significant difference in SVS detection rate compared with the vessel severe stenosis or occlusion rate in MRA (P = 0.111). Based on the MRA standards, the area under curve (AUC) of ROC for the SVS as revealed by SWI was 0.86 (95% CI: 0.753-0.962).

Conclusions: ASL combined with DWI contributed to IP evaluation of acute cerebral infarction. SWI showed higher diagnostic value for intravascular thrombus in acute cerebral infarction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791372PMC
December 2020

Transplanting -silenced bone marrow mesenchymal stem cells promote neurological function recovery in TBI mice.

Aging (Albany NY) 2020 12 19;13(2):2822-2850. Epub 2020 Dec 19.

Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.

Bone marrow mesenchymal stem cells (BMMSCs)-based therapy has emerged as a promising novel therapy for Traumatic Brain Injury (TBI). However, the therapeutic quantity of viable implanted BMMSCs necessary to initiate efficacy is still undetermined. Increased oxidative stress following TBI, which leads to the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase signaling pathway, has been implicated in accounting for the diminished graft survival and therapeutic effect. To prove this assertion, we silenced the expression of NADPH subunits (p22-phox, p47-phox, and p67-phox) and small GTPase Rac1 in BMMSCs using shRNA. Our results showed that silencing these proteins significantly reduced oxidative stress and cell death/apoptosis, and promoted implanted BMMSCs proliferation after TBI. The most significant result was however seen with silencing, which demonstrated decreased expression of apoptotic proteins, enhanced survival ratio, reduction in TBI lesional volume and significant improvement in neurological function post shRac1-BMMSCs transplantation. Additionally, two RNA-seq hub genes ( and ) were identified to play critical roles in shRac1-mediated cell survival. In summary, we propose that knockdown of gene could significantly boost cell survival and promote the recovery of neurological functions after BMMSCs transplantation in TBI mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.202334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880331PMC
December 2020

Improvement in Signal-to-Noise Ratio of Liquid-State NMR Spectroscopy via a Deep Neural Network DN-Unet.

Anal Chem 2021 01 30;93(3):1377-1382. Epub 2020 Dec 30.

Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Department of Electronic Science, State Key Laboratory for Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen 361005, China.

Nuclear magnetic resonance (NMR) is one of the most powerful analytical tools and is extensively applied in many fields. However, compared to other spectroscopic techniques, NMR has lower sensitivity, impeding its wider applications. Using data postprocessing techniques to increase the NMR spectral signal-to-noise ratio (SNR) is a relatively simple and cost-effective method. In this work, a deep neural network, termed as DN-Unet, is devised to suppress noise in liquid-state NMR spectra to enhance SNR. It combines structures of encoder-decoder and convolutional neural network. Different from traditional deep learning training strategy, M-to-S strategy is developed to enhance DN-Unet capability that multiple noisy spectra (inputs) correspond to a same single noiseless spectrum (label) in the training stage. The trained 1D model can be used for denoising not only 1D but also high dimension spectra, further improving DN-Unet's performance. 1D, 2D, and 3D NMR spectra were utilized to evaluate DN-Unet performance. The results suggest that DN-Unet provides larger than 200-fold increase in SNR with weak peaks hidden in noise perfectly recovered and spurious peaks suppressed well. Since DN-Unet developed here to increase SNR is based on data postprocessing, it is universal for a variety of samples and NMR platforms. The great SNR enhancement and extreme excellence in differentiating signal and noise would greatly promote various liquid-state NMR applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.analchem.0c03087DOI Listing
January 2021

Relationship between tumor heterogeneity and volume in cervical cancer: Evidence from integrated fluorodeoxyglucose 18 PET/MR texture analysis.

Nucl Med Commun 2021 May;42(5):545-552

Department of Radiology, Shengjing Hospital of China Medical University.

Objective: The aim of this study was to evaluate the effect of cervical cancer volume on PET/magnetic resonance (MR) texture heterogeneity.

Materials And Methods: We retrospectively analyzed the PET/MR images of 138 patients with pathologically diagnosed cervical squamous cell carcinoma, including 50 patients undergoing surgery and 88 patients receiving concurrent chemoradiotherapy. Fluorodeoxyglucose 18 (18FDG)-PET/MR examination were performed for each patient before treatment, and the PET and MR texture analysis were undertaken. The texture features of the tumor based on gray-level co-occurrence matrices were extracted, and the correlation between tumor texture features and volume parameters was analyzed using Spearman's rank correlation coefficient. Finally, the variation trend of tumor texture heterogeneity was analyzed as tumor volumes increased.

Results: PET texture features were highly correlated with metabolic tumor volume (MTV), including entropy-log2, entropy-log10, energy, homogeneity, dissimilarity, contrast, correlation, and the correlation coefficients (rs) were 0.955, 0.955, -0.897, 0.883, -0.881, -0.876, and 0.847 (P < 0.001), respectively. In the range of smaller MTV, the texture heterogeneity of energy, entropy-log2, and entropy-log10 increases with an increase in tumor volume, whereas the texture heterogeneity of homogeneity, dissimilarity, contrast, and correlation decreases with an increase in tumor volume. Only homogeneity, contrast, correlation, and dissimilarity had high correlation with tumor volume on MRI. The correlation coefficients (rs) were 0.76, -0.737, 0.644, and -0.739 (P < 0.001), respectively. The texture heterogeneity of MRI features that are highly correlated with tumor volume decreases with increasing tumor volume.

Conclusion: In the small tumor volume range, the heterogeneity variation trend of PET texture features is inconsistent as the tumor volume increases, but the variation trend of MRI texture heterogeneity is consistent, and MRI texture heterogeneity decreases as tumor volume increases. These results suggest that MRI is a better imaging modality when compared with PET in determining tumor texture heterogeneity in the small tumor volume range.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MNM.0000000000001354DOI Listing
May 2021

In Situ Determination of Nitrate in Water Using Fourier Transform Mid-Infrared Attenuated Total Reflectance Spectroscopy Coupled with Deconvolution Algorithm.

Molecules 2020 Dec 10;25(24). Epub 2020 Dec 10.

The State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science Chinese Academy of Sciences, Nanjing 210008, China.

Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy has been used to determine the nitrate content in aqueous solutions. However, the conventional water deduction algorithm indicated considerable limits in the analysis of samples with low nitrate concentration. In this study, FTIR-ATR spectra of nitrate solution samples with high and low concentrations were obtained, and the spectra were then pre-processed with deconvolution curve-fitting (without water deduction) combined with partial least squares regression (PLSR) to predict the nitrate content. The results show that the typical absorption of nitrate (1200-1500 cm) did not clearly align with the conventional algorithm of water deduction, while this absorption was obviously observed through the deconvolution algorithm. The first principal component of the spectra, which explained more than 95% variance, was linearly related to the nitrate content; the correlation coefficient () of the PLSR model for the high-concentration group was 0.9578, and the ratio of the standard deviation of the prediction set to that of the calibration set () was 4.22, indicating excellent prediction performance. For the low-concentration group model, and were 0.9865 and 3.15, respectively, which also demonstrated significantly improved prediction capability. Therefore, FTIR-ATR spectroscopy combined with deconvolution curve-fitting can be conducted to determine the nitrate content in aqueous solutions, thus facilitating rapid determination of nitrate in water bodies with varied concentrations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules25245838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764078PMC
December 2020

Comp34 displays potent preclinical antitumor efficacy in triple-negative breast cancer via inhibition of NUDT3-AS4, a novel oncogenic long noncoding RNA.

Cell Death Dis 2020 12 11;11(12):1052. Epub 2020 Dec 11.

Division of Cancer Research and Training, Department of Internal Medicine, Charles Drew University of Medicine and Science, David Geffen UCLA School of Medicine and UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA, 90095, USA.

The abnormal PI3K/AKT/mTOR pathway is one of the most common genomic abnormalities in breast cancers including triple-negative breast cancer (TNBC), and pharmacologic inhibition of these aberrations has shown activity in TNBC patients. Here, we designed and identified a small-molecule Comp34 that suppresses both AKT and mTOR protein expression and exhibits robust cytotoxicity towards TNBC cells but not nontumorigenic normal breast epithelial cells. Mechanically, long noncoding RNA (lncRNA) AL354740.1-204 (also named as NUDT3-AS4) acts as a microRNA sponge to compete with AKT1/mTOR mRNAs for binding to miR-99s, leading to decrease in degradation of AKT1/mTOR mRNAs and subsequent increase in AKT1/mTOR protein expression. Inhibition of lncRNA-NUDT3-AS4 and suppression of the NUDT3-AS4/miR-99s association contribute to Comp34-affected biologic pathways. In addition, Comp34 alone is effective in cells with secondary resistance to rapamycin, the best-known inhibitor of mTOR, and displays a greater in vivo antitumor efficacy and lower toxicity than rapamycin in TNBC xenografted models. In conclusion, NUDT3-AS4 may play a proproliferative role in TNBC and be considered a relevant therapeutic target, and Comp34 presents promising activity as a single agent to inhibit TNBC through regulation of NUDT3-AS4 and miR-99s.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-020-03235-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733521PMC
December 2020

Behavioural Effects and Market Dynamics in Field and Laboratory Experimental Asset Markets.

Entropy (Basel) 2020 Oct 20;22(10). Epub 2020 Oct 20.

Institute of Risk Analysis, Prediction and Management (Risks-X), Academy for Advanced Interdiscplinary Studies, Southern University of Science and Technology (SUSTech), Shenzhen 518055, China.

A vast literature investigating behavioural underpinnings of financial bubbles and crashes relies on laboratory experiments. However, it is not yet clear how findings generated in a highly artificial environment relate to the human behaviour in the wild. It is of concern that the laboratory setting may create a confound variable that impacts the experimental results. To explore the similarities and differences between human behaviour in the laboratory environment and in a realistic natural setting, with the same type of participants, we translate a field study conducted by reference (Sornette, D.; et al. , , 1-53) with trading rounds each lasting six full days to a laboratory experiment lasting two hours. The laboratory experiment replicates the key findings from the field study but we observe substantial differences in the market dynamics between the two settings. The replication of the results in the two distinct settings indicates that relaxing some of the laboratory control does not corrupt the main findings, while at the same time it offers several advantages such as the possibility to increase the number of participants interacting with each other at the same time and the number of traded securities. These findings pose important insights for future experiments investigating human behaviour in complex systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/e22101183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597354PMC
October 2020

Proteasome inhibitors attenuates mitoxantrone-triggered immunogenic cell death in prostate cancer cells.

Med Oncol 2020 Nov 19;37(12):116. Epub 2020 Nov 19.

Institute of Precision Medicine, Jining Medical University, Jining, 272067, China.

Both mitoxantrone (MTX) and proteasome inhibitors efficiently trigger immunogenic cell death (ICD) in cancer cells. However, whether the combination of MTX and proteasome inhibitors can synergistically enhance ICD remains unknown. In this study, we showed that the proteasome inhibitors bortezomib (BZM) and carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG132) impaired MTX-induced ICD in prostate cancer cells, as measured using ICD biomarkers and dendritic cell activation in vitro. Mice vaccinated with RM-1 mouse prostate cancer cell line treated with BZM or MG132 in combination with MTX showed enhanced tumor growth, and shortened tumor-free, and worse overall survival compared with those treated with MTX alone. In conclusion, we demonstrated that proteasome inhibitors (BZM or MG132) attenuated MTX-induced ICD, suggesting that proteasome activation was required for MTX-induced ICD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12032-020-01445-yDOI Listing
November 2020

NEAT1/miR-200b-3p/SMAD2 axis promotes progression of melanoma.

Aging (Albany NY) 2020 11 16;12(22):22759-22775. Epub 2020 Nov 16.

Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.

Melanoma is a skin malignancy with a high mutation frequency of genetic alterations. MicroRNA (miR)-200b-3p is involved in various cancers, while in melanoma its bio-function remains unknown. In this study, we found that miR-200b-3p was down-regulated in melanoma tissues and cell lines compared to benign nevus cells. Overexpression of miR-200b-3p significantly inhibited the proliferation and invasion of melanoma cells. According to bioinformatics analysis and sequencing data, we supposed that SMAD family member 2 (SMAD2) was the target gene and nuclear enriched abundant transcript 1 (NEAT1) was the upstream long non-coding RNA (lncRNA) of miR-200b-3p. These predictions were verified by western blotting and quantitative real-time reverse transcription PCR (RT-qPCR). Luciferase reporter assays revealed that NEAT1 up-regulated SMAD2 by directly sponging miR-200b-3p. and , we demonstrated that both NEAT1 and SMAD2 could promote the proliferation and invasion of melanoma cells, and these effects were reversed by up-regulating miR-200b-3p. In addition, NEAT1/miR-200b-3p/SMAD2 axis promoted melanoma progression by activating EMT signaling pathway and immune responses. Taken together, the NEAT1/miR-200b-3p/SMAD2 signaling pathway promotes melanoma via activation of EMT, cell invasion and is related with immune responses, which provides new insights into the molecular mechanisms and therapeutic targets for melanoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.103909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746346PMC
November 2020