Synthesis and Antioxidant Activity of(E)ω-Formylcamphene-Based Thiazole Hydrazone Derivatives

(E)ω-formylcamphene was synthesized fromα-pinene,the main component of turpentine,and then reacted with thiosemicarbazide to obtain(E)ω-formylcamphene thiosemicarbazide 3,which was reacted with 14α-bromoace-tophenone compounds to obtain 14(E)ω-formylcamphene thiazole hydrazone compounds 5a–5n;the yields were all above 80%.The structures of the target compounds were characterized by IR,^(1)H-NMR,^(13)C-NMR,and HR-MS analyses.Then,500,250,125,62.5,and 31.25 mg/L drug solutions were prepared.Free radical scavenging experi-ments of 1,1-diphenyl-2-picrylhydrazyl(DPPH)and 2,2-bis(3-ethyl-benzothiazole-6-sulfonic acid)diammonium salt(ABTS)were carried out with Trolox and L-ascorbic acid as the control samples.The scavenging rates of 14 compounds for DPPH and ABTS free radicals were obtained;the IC_(50) values of scavenging free radicals were fitted using SPSS software.The results show that 14(E)ω-formylcamphene-based thiazole hydrazone compounds exhibited good scavenging effects on the two free radicals,especially when the concentration of the drug solution was 125 and 62.5 mg/L;most compounds exceeded the scavenging efficiency of Trolox and L-ascorbic acid.

对分课堂下本科生医学遗传学自主学习能力的培养

医学遗传学是一门衔接基础和临床的桥梁学科,是医学专业学生必须掌握的重要基础课程之一。为了培养学生的自主学习能力,提高医学遗传学的教学质量,在医学遗传学教学中采用对分课堂教学模式。在教学设置中,给予学生自主学习的流程和时间保障,并在讲授、讨论和作业等环节,积极引导学生自主学习。大学生自主学习量表测评显示,学生在学习动机和学习策略方面较教学实施前均有增强,测评总分明显增加,自主学习能力得到提升,取得满意的教学效果。

Scalability and efficiency challenges for the exascale supercomputing system:practice of a parallel supporting environment on the Sunway exascale prototype system

With the continuous improvement of supercomputer performance and the integration of artificial intelligence with traditional scientific computing,the scale of applications is gradually increasing,from millions to tens of millions of computing cores,which raises great challenges to achieve high scalability and efficiency of parallel applications on super-large-scale systems.Taking the Sunway exascale prototype system as an example,in this paper we first analyze the challenges of high scalability and high efficiency for parallel applications in the exascale era.To overcome these challenges,the optimization technologies used in the parallel supporting environment software on the Sunway exascale prototype system are highlighted,including the parallel operating system,input/output(I/O)optimization technology,ultra-large-scale parallel debugging technology,10-million-core parallel algorithm,and mixed-precision method.Parallel operating systems and I/O optimization technology mainly support largescale system scaling,while the ultra-large-scale parallel debugging technology,10-million-core parallel algorithm,and mixed-precision method mainly enhance the efficiency of large-scale applications.Finally,the contributions to various applications running on the Sunway exascale prototype system are introduced,verifying the effectiveness of the parallel supporting environment design.

Oncolytic adenoviruses expressing checkpoint inhibitors for cancer therapy

Despite the remarkable success of immune checkpoint inhibitors(ICIs),primary resistance to ICIs causes only subsets of patients to achieve durable responses due to the complex tumor microenvironment(TME).Oncolytic viruses(OVs)can overcome the immunosuppressive TME and promote systemic antitumor immunity in hosts.Engineered OVs armed with ICIs would likely have improved effectiveness as a cancer therapy.According to the diverse immune cell landscapes among different types of tumors,we rationally and precisely generated three recombinant oncolytic adenoviruses(OAds):OAd-SIRPα-Fc,OAd-Siglec10-Fc and OAd-TIGIT-Fc.These viruses were designed to locally deliver SIRPα-Fc,Siglec10-Fc or TIGIT-Fc fusion proteins recognizing CD47,CD24 or CD155,respectively,in the TME to achieve enhanced antitumor effects.Our results suggested that OAd-SIRPα-Fc and OAd-Siglec10-Fc both showed outstanding efficacy in tumor suppression of macrophage-dominated tumors,while OAd-TIGIT-Fc showed the best antitumor immunity in CD8+T-cell-dominated tumors.Importantly,the recombinant OAds activated an inflammatory immune response and generated long-term antitumor memory.In addition,the combination of OAd-Siglec10-Fc with anti-PD-1 significantly enhanced the antitumor effect in a 4T1 tumor model by remodeling the TME.In summary,rationally designed OAds expressing ICIs tailored to the immune cell landscape in the TME can precisely achieve tumor-specific immunotherapy of cancer.

不再靠买房 中国千禧一代寻找新的致富机会

跟其他数以百万计的中国年轻人一样,Byron Zhang也认为自己错过了时机。对于他父母那一代人来说,投资房地产是通往富裕与安稳的必胜之路。现在,随着房价下跌、人口下滑以及到处都是在建和待售住宅,走这条路发财的梦碎了。

Detection of Prognostic Biomarkers for Hepatocellular Carcinoma through CircRNA-associated CeRNA Analysis

Background and Aims:The prognosis of hepatocellular carcinoma(HCC)is extremely poor;therefore,there is an urgent need for novel prognostic molecular biomarkers of HCC.The current investigation utilized circular(circ)RNA-associated competing endogenous(ce)RNAs analysis in order to identify significant prognostic biomarkers of HCC.Methods:CircRNAs and mRNAs that were differentially expressed between normal and HCC tissues were identi-fied.Their respective functions were predicted with Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.A nomogram was used for model verification.Results:A ceRNA network composed of differentially expressed circRNAs and mRNAs was con-structed.Significant hub nodes in the ceRNA network were hsa_circ_0004662,hsa_circ_0005735,hsa_circ_0006990,hsa_circ_0018403 and hsa_circ_0100609.By using this in-formation,a prognostic risk assessment tool was developed based on the expressions of seven genes(PLOD2,TARS,RNF19B,CCT2,RAN,C5orf30 and MCM10).Furthermore,multivariate Cox regression analysis revealed risk and T-stage parameters as independent prognostic factors.The nomograms that were constructed from risk and T-stage groups were used to further assess the prediction of HCC patient survival rates.The nomogram,which consisted of risk and T-stage scores assessment models,was found to be an independent factor for predicting prognosis of HCC.Conclusions:Five circRNAs,including hsa_circ_0004662,hsa_circ_0005735,hsa_circ_0006990,hsa_circ_0018403 and hsa_circ_0100609,that may play key roles in the pro-gression of HCC were identified.Seven gene signatures were identified,which were associated with the aforemen-tioned circRNAs,including PLOD2,TARS,RNF19B,CCT2,RAN,C5orf30 and MCM10,all of which were significant genes involved in the pathophysiology of HCC.These genes may be used as a prognosticating tool in HCC patients.

Transposon-based screen identifies a XRE family regulator crucial for candicidin biosynthesis in Streptomyces albus J1074

Dear Editor,Polyene macrolides are a group of natural products with potent antifungal activity (Caffrey et al., 2016). Candicidin/FR-008, a potent broad-spectrum anti-fungal agent, is produced by several Streptomycetes, including Streptomycetes sp. strain FR-008 (Chen et al., 2003), S. griseus 3570(Campelo and Gil, 2002) and S. albus J1074 (Olano et al.,2014). Due to its medical importance, considerable effort has been applied to elucidate its biosynthetic pathway and identify key regulatory genes (Chen et al., 2003;Zhang et al.,2015).

Outcomes of patients awaiting lung transplantation after the implementation of donation after brain death at a single Chinese center

oluntary contribution has become the only source of donor lungs in China since 2015.To elaborate the outcomes of patients awaiting lung transplantation(LTx)after the implementation of donation after brain death,we performed a retrospective study that encompassed 205 patients with end-stage lung disease who registered for LTx at Shanghai Pulmonary Hospital from January 1,2015 to January 1,2021.A total of 180 patients were enrolled in the study.The median waiting time was 1.25 months.Interstitial lung disease(ILD)(103/180,57.2%)and chronic obstructive pulmonary disease(COPD)(56/180,31.1%)were the most common diseases in our study population.The mean pulmonary artery pressure(mPAP)of patients in the died-waiting group was higher than that of the survivors(53.29+21.71 mmHg vs.42.11+18.58 mmHg,P-0.002).The mortality of patients with ILD(34/103,33.00%)was nearly twice that of patients with COPD(10/56,17.86%)while awaiting LTx(P-0.041).In the died-waiting group,patients with ILD had a shorter median waiting time than patients with COPD after being listed(0.865 months vs.4.720 months,P-0.030).ILD as primary disease and mPAP>35 mmHg were two significant independent risk factors for waitlist mortality,with hazard ratios(HR)of 3.483(95%CI 1.311-9.111;P-0.011)and 3.500(95%CI 1.435-8.536;P=0.006).Hence,LTx is more urgently needed in patients with ILD and pulmonary hypertension.