Fatty acid binding protein 5 is a novel therapeutic target for hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is an aggressive subtype of liver cancer and is one of the most common cancers with high mortality worldwide.Reprogrammed lipid metabolism plays crucial roles in HCC cancer cell survival,growth,and evolution.Emerging evidence suggests the importance of fatty acid binding proteins(FABPs)in contribution to cancer progression and metastasis;however,how these FABPs are dysregulated in cancer cells,especially in HCC,and the roles of FABPs in cancer progression have not been well defined.AIM To understand the genetic alterations and expression of FABPs and their associated cancer hallmarks and oncogenes in contributing to cancer malignancies.METHODS We used The Cancer Genome Atlas datasets of pan cancer and liver hepatocellular carcinoma(LIHC)as well as patient cohorts with other cancer types in this study.We investigated genetic alterations of FABPs in various cancer types.mRNA expression was used to determine if FABPs are abnormally expressed in tumor tissues compared to non-tumor controls and to investigate whether their expression correlates with patient clinical outcome,enriched cancer hallmarks and oncogenes previously reported for patients with HCC.We determined the protein levels of FABP5 and its correlated genes in two HCC cell lines and assessed the potential of FABP5 inhibition in treating HCC cells.RESULTS We discovered that a gene cluster including five FABP family members(FABP4,FABP5,FABP8,FABP9 and FABP12)is frequently co-amplified in cancer.Amplification,in fact,is the most common genetic alteration for FABPs,leading to overexpression of FABPs.FABP5 showed the greatest differential mRNA expression comparing tumor with non-tumor tissues.High FABP5 expression correlates well with worse patient outcomes(P<0.05).FABP5 expression highly correlates with enrichment of G2M checkpoint(r=0.33,P=1.1e-10),TP53 signaling pathway(r=0.22,P=1.7e-5)and many genes in the gene sets such as CDK1(r=0.56,P=0),CDK4(r=0.49,P=0),and TP53(r=0.22,P=1.6e-5).Furthermore,FABP5 also correlates well with two co-expressed oncogenes PLK1 and BIRC5 in pan cancer especially in LIHC patients(r=0.58,P=0;r=0.58,P=0;respectively).FABP5high Huh7 cells also expressed higher protein levels of p53,BIRC5,CDK1,CDK2,and CDK4 than FABP5low HepG2 cells.FABP5 inhibition more potently inhibited the tumor cell growth in Huh7 cells than in HepG2 cells.CONCLUSION We discovered that FABP5 gene is frequently amplified in cancer,especially in HCC,leading to its significant elevated expression in HCC.Its high expression correlates well with worse patient outcome,enriched cancer hallmarks and oncogenes in HCC.FABP5 inhibition impaired the cell viability of FABP5high Huh7 cells.All these support that FABP5 is a novel therapeutic target for treating FABP5high HCC.

AI绘画软件的创作特征研究——以绘画软件Novel AI生成的动漫人物形象为例

近年来,随着扩散模型、Lora模型、Controlnet等技术应用于绘画领域,现今的AI绘画软件已经能够生成完整的动漫人物,具备了较高的可控性和精确性。文章通过分析AI绘画软件“Novel AI”生成的动漫人物形象,总结了这一AI软件表现出的绘画创作特征,并在此基础上评估了现今人工智能技术对于动漫创作产生的影响。

Identification and functional analyses of a novel FOXL2 pathogenic variant causing blepharophimosis, ptosis, and epicanthus inversus syndrome

AIM: To discover the molecular pathogenic basis of the blepharophimosis, ptosis, and epicanthus inversus syndrome(BPES), and to predict the clinical subtype according to in vitro experiments, which is significant to the prognosis.METHODS: A 3-year-old sporadic female patient with typical clinical manifestations of BPES was enrolled. The coding region of forkhead box L2(FOXL2) gene was sequenced, and the functional assays were performed in vitro by Western blotting, subcellular localization experiment, luciferase reporter assay, and quantitative realtime polymerase chain reaction.RESULTS: A novel FOXL2 point pathogenic variant(c.274G>T) was detected, resulting in a truncated protein(p.E92*). Functional studies demonstrated that the FOXL2 pathogenic variant induced the subcellular mislocalization and the abnormal transcriptional activity on promoters of the steroidogenic acute regulatory protein(StAR or STARD1) gene and the odd-skipped related 2 transcription factor(OSR2) gene.CONCLUSION: A novel pathogenic variant is identified to expand the spectrum of the known FOXL2 mutations. The in vitro experiments provide reference data and more insights to the molecular pathogenesis of BPES. The predicted high risk of ovarian insufficiency makes it significant for the patient enrolled to have further follow-up and therapy concerning female endocrinology.

Clinical and genetic characteristics of retinoblastoma patients in a single center with four novel RB1 variants

AIM:To assess the clinical and genetic characteristics of children diagnosed with retinoblastoma(RB)at Gazi University Faculty of Medicine’s Department of Pediatric Oncology.METHODS:All cases diagnosed with RB and received treatment and follow-up in the Ophthalmology and Pediatric Oncology Department,October 2016 to May 2021 were evaluated retrospectively.The RB1 gene was analyzed by next-generation sequencing(NGS)technique in DNAs obtained from peripheral blood samples of the patients.RESULTS:This study included 53 cases with 67 RBaffected eyes during the study period.The mean age was 24.6(median:18.5,range:3–151)mo.There were 15(22.3%)Group D eyes and 39(58.2%)Group E eyes.The RB1 gene was sequenced by the NGS method in 19 patients.Heterozygous RB1:NM_000321.3:c.54_76del(p.Glu19AlafsTer4)variant was detected in a 15-month-old female with bilateral RB.Heterozygous RB1:NM_000321.3:c.1814+3A>T variant was detected in a 5.5-month-old male with bilateral RB.The intronic RB1:NM_000321.3:c.1332+4A>G variant was detected in patient 14,a 13-month-old male with unilateral RB.The RB1:NM_000321.3:c.575_576del(p.Lys192SerfsTer10)variant was found in an 18-month-old female with an allele frequency of 37%.These variants have not been reported in the literature and mutation databases.CONCLUSION:Four novel variants are described and one of them is found in two different patients.This data is crucial for assessing prognosis.It serves as a guide for estimating the long-term risk of secondary malignancy as well as the short-term risk of developing additional malignancies in the same eye and the other eye.

Novel combined endoscopic and laparoscopic surgery for advanced T2 gastric cancer:Two case reports

BACKGROUND The standard treatment for advanced T2 gastric cancer(GC)is laparoscopic or surgical gastrectomy(either partial or total)and D2 lymphadenectomy.A novel combined endoscopic and laparoscopic surgery(NCELS)has recently been proposed as a better option for T2 GC.Here we describe two case studies demonstrating the efficacy and safety of NCELS.CASE SUMMARY Two T2 GC cases were both resected by endoscopic submucosal dissection and full-thickness resection and laparoscopic lymph nodes dissection.This method has the advantage of being more precise and minimally invasive compared to current methods.The treatment of these 2 patients was safe and effective with no complications.These cases were followed up for nearly 4 years without recurrence or metastasis.CONCLUSION This novel method provides a minimally invasive treatment option for T2 GC,and its potential indications,effectiveness and safety needs to be further evaluated in controlled studies.

Comprehensive analysis of the full-length transcripts and alternative splicing involved in clubroot resistance in Chinese cabbage

Chinese cabbage is an economically important Brassica vegetable worldwide, and clubroot, which is caused by the soilborne protist plant pathogen Plasmodiophora brassicae is regarded as a destructive disease to Brassica crops. Previous studies on the gene transcripts related to Chinese cabbage resistance to clubroot mainly employed RNA-seq technology,although it cannot provide accurate transcript assembly and structural information. In this study, PacBio RS II SMRT sequencing was used to generate full-length transcriptomes of mixed roots at 0, 2, 5, 8, 13, and 22 days after P. brassicae infection in the clubroot-resistant line DH40R. Overall, 39 376 high-quality isoforms and 26 270 open reading frames(ORFs) were identified from the SMRT sequencing data. Additionally, 426 annotated long noncoding RNAs(lncRNAs),56 transcription factor(TF) families, 1 883 genes with poly(A) sites and 1 691 alternative splicing(AS) events were identified. Furthermore, 1 201 of the genes had at least one AS event in DH40R. A comparison with RNA-seq data revealed six differentially expressed AS genes(one for disease resistance and five for defensive response) that are potentially involved in P. brassicae resistance. The results of this study provide valuable resources for basic research on clubroot resistance in Chinese cabbage.

Full-Length Transcriptome Analysis of Cultivated and Wild Tetraploid Peanut

The high-quality genomes and large-scale full-length cDNA sequences of allotetraploid peanuts have been sequenced and released,which has accelerated the functional genomics and molecular breeding research of peanut.In order to understand the difference in the transcriptional levels of wild and cultivated peanuts.In this study,we integrated of second-and third-generation sequencing technologies to sequence full-length transcriptomes in peanut cv.Pingdu9616 and its putative ancestor Arachis monticola.The RNA extracted from six different tissues(i.e.,roots,stems,leaves,flowers,needles and pods)were sampled at 20 days after flowering.A total of 31,764 and 33,981 high-quality transcripts were obtained from Monticola and Pingdu9616,respectively.The number of alternative splicing,the unit point mutation of variable adenylation,the number of open reading frames and the two-site mutation were identified in Pingdu9616 more than in Monticola,but the three-site mutation in Pingdu9616 was lower than in Monticola.1,691 LncRNAs,and 4,000 bp of maximum length of LncRNA was identified in Monticola and Pingdu9616.Furthermore,comparative analysis between transcript data shown that 56 transcription factor families were involved in Monticola,and Pingdu9616 and the number of transcription factors in Pingdu9616 was higher than that in Monticola,the number of expressed genes estimated in flower,root,young pod and leaf organs was higher in Monticola than Pingdu9616.Over all,our study provided a valuable resource of large-scale full-length transcripts for further research of the molecular breeding and functional analysis of genes.

Novel Deletion in Exon 7 of Betaine Aldehyde Dehydrogenase 2(BADH2)

The fragrance of rice is one of the premium characteristics that breeders want to include in rice varieties due to the higher market value. Nucleotide deletions in exons 2(7 bp) and 7(8 bp) of Betaine Aldehyde Dehydrogenase 2(BADH2) are associated with fragrance in rice. In this study, a new 13 bp deletion in exon 7 of the BADH2 gene was discovered in the Nang Thom Cho Dao(NTCD) variety, and the mutation has been closely related to the genetic background of indica subspecies through the Bayesian phylogenetic approach and haplotype network analysis of the 3 000 Rice Genomes Project. In addition, a set of functional markers(EX07-13F, EX07-13RN, and EX07-13RM) identified the 13 bp deletion only within NTCD(no amplified band) compared with both non-aromatic and other aromatic rice varieties(110 bp band). The deletion of 13 bases instead of 8 bases in exon 7 of BADH2 caused a premature stop codon, which down-regulated the expression of the BADH2 transcript while associated with up-regulation of OsP5CS and the high amount of 2-acetyl-1-pyrroline. It is potential to use the deletion in exon 7 of the BADH2 gene as a novel marker for adulteration and breeding of fragrant rice varieties, particularly for NTCD.

Chinese Sources for AfterWards:From Premodern Poetry,Paintings,and Medical Texts to Modern Novels,Film,and Documentaries

This paper focuses on Chinese sources suggested for a narrative medicine(NM)program,called AfterWards.Dr Lauren Small established AfterWards in 2014 and has been coordinating it since out of the Pediatrics Department at Johns Hopkins Medicine.In early 2019,she started giving a series of lectures and workshops about AfterWards to Chinese medical educators and clinicians in Beijing and Shanghai.She created an AfterWards Facilitator’s Guide based on Western-language sources for workshop participants.She also started to organize with Jiang Yuhong(Peking Union Medical College)a workshop for Chinese colleagues to be held at Johns Hopkins Medicine in October 2019.They invited the author to participate.The idea was hatched then to develop Chinese source materials following the AfterWards structure for an updated Facilitator’s Guide that Dr Small had initially written.A typical one-hour AfterWards session consists of a specific five-part structure:a literary text or artwork,an associated theme,discussion topics,a writing exercise,and shared reflection.While the content of the program always changes from session to session,the basic structure remains the same.This paper summarizes the types of Chinese sources and their related narrative-medicine themes that were originally selected for inclusion in the updated AfterWards Facilitator’s Guide intended for Chinese colleagues.These sources about coping with sick family members,aging,and illness ranged from the textual(classical Chinese poems on aging and diagnostic forms for training students)and visual(premodern Chinese paintings and murals of medical encounters)to the fictive(novels)and performative(contemporary Asian-American film in English and Chinese-language film and documentaries).

Characterization and distribution of novel alleles of the vernalization gene Vrn-A1 in Chinese wheat(Triticum aestivum L.) cultivars

The ability of wheat to adapt to a wide range of environmental conditions is determined mostly by allelic diversity among genes regulating vernalization requirement.Vrn-1 is a major regulator of this requirement.In this study,two novel alleles of Vrn-A1 were discovered in Chinese cultivars:vrn-A1n was identified in two landraces,Jiunong 2 and Ganchun 16,and Vrn-A1o was detected in Duanhongmangmai.Both novel alleles showed a linked duplication in the promoter region.The common copy of these two alleles was identical to the recessive allele vrn-A1.Compared with the recessive allele vrn-A1,the other copy of vrn-A1n contained a 54-bp deletion in the promoter region and the distinct copy of Vrn-A1o contained an11-bp deletion in the promoter region.In segregating populations in the greenhouse under nonvernalizing(20–25°C)and long-day(16 h light)conditions,plants with the novel vrn-A1n allele did not head earlier than those with the recessive vrn-A1 allele.However,plants that were either homozygous or heterozygous for the novel Vrn-A1o allele headed earlier than those with the recessive vrn-A1 allele.To identify the novel allele with the small-sized product and facilitate screening,a DNA marker for the novel dominant allele Vrn-A1o was designed.Analysis of the novel-allele distribution showed that two cultivars carrying the vrn-A1n allele were dispersed in the northwestern spring wheat zone,and 12 cultivars carrying the dominant Vrn-A1o allele were widely distributed in the northwestern spring wheat zone,Xinjiang winter and spring wheat zone,Yellow and Huai River valley winter wheat zone,and QinghaiTibetan Plateau spring and winter wheat zone.Our study identifies useful germplasm and a DNA marker for wheat breeding.

The Influence of Integrated Chinese and Western Medicine Treatment on the Quality of Life and Laboratory Indicators of Patients with Novel Coronavirus Pneumonia

Objective: To investigate the influence of integrated Chinese and Western medicine treatment on the quality of life and laboratory indicators of patients with novel coronavirus pneumonia (COVID-19). Methods: A prospective, self-controlled study was conducted to analyze the changes in corresponding laboratory indicators and quality of life in 75 confirmed COVID-19 patients treated with integrated Chinese and Western medicine in our hospital during the early stage, middle stage, recovery period, and two weeks after discharge. The effectiveness and safety of the treatment regimen were evaluated in conjunction with the time for 2019-nCoV nucleic acid conversion, disease progression, and adverse reactions. Results: The PLT levels in the initial stage were significantly lower than those in the recovery period in 75 patients. The CRP levels in the initial stage were significantly lower than those after discharge for 2 weeks. The TBIL, IBTL, and DHIL levels in the initial stage were significantly lower than those in the middle stage. The K+ levels in the initial stage were significantly lower than those in the recovery period and after discharge for 2 weeks. The LYMGH levels in the initial stage were significantly lower than those in the recovery period and after discharge for 2 weeks. The TP and ALB levels in the initial stage were higher than those in the middle stage and the recovery period. The LDH levels, scores of daily activity limitation, scores of respiratory distress symptoms, scores of psychological emotions, CT imaging scores, and positive rate of nucleic acid were significantly lower than those in the recovery period and after discharge for 2 weeks. The AG, CK, CK-MB, and α-HBDH levels in the initial stage were significantly higher than those in the recovery period. However, the AMY level in the initial stage was significantly lower than that in the recovery period and after discharge for 2 weeks (p Conclusion: Integrated Chinese and Western medicine treatment has a significant impact on laboratory indicators such as PLT, LYMGH, CRP, TBIL, IBTL, DHIL, TP, ALB, K+, AG, LDH, CK, CK-MB, α-HBDH, AMY, CT imaging, and 2019-nCoV nucleic acid in COVID-19 patients. It has good clinical efficacy and safety, and can improve the quality of life of patients.

Exploring Splicing Variants and Novel Genes in Sacred Lotus Based on RNA-seq Data

Sacred lotus(Nelumbo nucifera)is a typical aquatic plant,belonging to basal eudicot plant,which is ideal for genome and genetic evolutionary study.Understanding lotus gene diversity is important for the study of molecular genetics and breeding.In this research,public RNA-seq data and the annotated reference genome were used to identify the genes in lotus.A total of 26,819 consensus and 1,081 novel genes were identified.Meanwhile,a comprehensive analysis of gene alternative splicing events was conducted,and a total of 19,983“internal”alternative splicing(AS)events and 14,070“complete”AS events were detected in 5,878 and 5,881 multi-exon expression genes,respectively.Observations made from the AS events show the predominance of intron retention(IR)subtype of AS events representing 33%.IR is followed by alternative acceptor(AltA),alternative donor(AltD)and exon skipping(ES),highlighting the universality of the intron definition model in plants.In addition,functional annotations of the gene with AS indicated its relationship to a number of biological processes such as cellular process and metabolic process,showing the key role for alternative splicing in influencing the growth and development of lotus.The results contribute to a better understanding of the current gene diversity in lotus,and provide an abundant resource for future functional genome analysis in lotus.

Study on Load Bearing Characteristics of Novel Expandable Deepwater Drilling Conductor Based on Laboratory Experiment and Field Test

A novel expandable conductor was designed and applied in deep-water drilling to improve the vertical and lateral bearing capacity with a significant reduction of conductor jetting depth and soaking time. The vertical and lateral bearing capability of expandable conductors was depicted based on the ultimate subgrade reaction method and pile foundation bearing theory. The load-bearing characteristics of a laboratory-scale expandable conductor were analyzed through laboratory experiments. The serial simulation experiments are accomplished to study the bearing characteristics(vertical ultimate bearing capacity, lateral soil pressure, and lateral displacement) during the conductor soaking process. The laboratory experimental results show that the larger the length and thickness of expandable materials are,the higher the bearing capacity of the wellhead will be. During the conductor soaking process, the soil pressure around the three expandable conductors increases faster, strings representing a stronger squeezing effect and resulting in higher vertical bearing capacity. Furthermore, the lateral displacement of novel expandable conductor is smaller than that of the conventional conductor. All the advantages mentioned above contributed to the reduction of conductor’s jetting depth and soaking time. Lastly, the application workflow of a novel expandable deep-water drilling conductor was established and the autonomous expandable conductor was successfully applied in the South China Sea with a significant reduction of conductor’s jetting depth and soaking time. According to the soil properties and designed installation depth of the surface conductor, the arrangement of expandable materials should be designed reasonably to meet the safety condition and reduce the construction cost of the subsea wellhead.

Full-length transcriptome sequence and SSR marker development for genetic diversity research in yellowfin seabream Acanthopagrus latus

Yellowfin seabream Acanthopagrus latus is an important economic fish in Chinese coastal areas.Given its narrow distribution and overfishing,the genetic diversity of yellowfin seabream has been restricted for artificial breeding and reproduction.We performed full-length transcriptome sequencing and assembly of the genome of yellowfin seabream.A total of 68086 unigenes were obtained,with an N50 of 3391 bp on average length of 2933 bp.A total number of 50593 expressed sequence tags linked to simple sequence repeats(EST-SSR)were identified,among them dinucleotide repeats(40.6%)and AC/GT motifs(38.5%)were the most frequent.Of the 190 EST-SSRs for which PCR primer pairs were designed,150 primer pairs successfully amplified target loci and 15 SSRs showed high polymorphism.The alleles per locus ranged 6-50 on average of 25.3.The expected and observed heterozygosity varied from 0.632 to 0.969 and from 0.519 to 0.953,respectively.The polymorphic index content(PIC)values of each locus ranged 0.587-0.966 on average of 0.851.Among six yellowfin seabream population samples preliminarily tested for genetic diversity and differentiation,the Fangchenggang(FCG)population in Guangxi Province had the highest mean observed heterozygosity(H_(o))value(0.786),whereas the Zhangzhou(ZZ)population in Fujian Province had the lowest(0.678).The pairwise fixation index(Fst)values indicated significant population differentiation among six yellowfin seabream populations.This study provided evidence for the usefulness of the transcriptomic resource information and EST-SSR markers for natural resource conservation,population genetics,and breeding studies of yellowfin seabream in South China.

A novel Ti-5.55Al-6.70Zr-1.50V-0.70Mo-3.41Nb-0.21Si alloy designed using cluster-plus-glue-atom model for laser additive manufacturing

A novel Ti-5.55Al-6.70Zr-1.50V-0.70Mo-3.41Nb-0.21Si alloy was designed using the cluster formula approach(cluster-plus-glue-atom model)and prepared by laser melting deposition(LMD).Its composition formula 12[Al-Ti_(12)](AlTi_(2))+5[Al_(0.8)Si_(0.2)-Ti_(12)Zr_(2)](V_(0.8)Mo_(0.2)Nb_(1)Ti)features an enhancedβ-Ti via co-alloying of Zr,V,Mo,Nb and Si.The experimental results show that the cluster formula ofαandβphases in the novel alloy are respectivelyα-[Al-Ti_(11.5)Zr_(0.5)](Al_(1)Ti_(2))andβ-[Al_(0.8)Si_(0.2)-Ti_(13.2)Zr_(0.8)](V_(1)Mo_(0.4)Nb_(1.6)),both containing Zr elements.The fitted composition via the α andβphase cluster formulas has little difference with the actual alloy composition,suggesting that the validity of cluster-plus-glue-atom model in the alloy composition design.After hot isostatic pressing(HIP),both the Ti-6Al-4V and the novel alloy by LMD are characterized by prior-βcolumnar grains,while the typical<100>texture disappears.Compared with Ti-6Al-4V,Ti-5.55Al-6.70Zr-1.50V-0.70Mo-3.41Nb-0.21Si alloy exhibits a combination of higher strength(1,056 MPa)and higher ductility(14%)at room temperature and higher strength(580 MPa)at 550℃ after HIP,and can potentially serves as LMD materials.

A Novel Approach for Optimum Conjunctive Use Management of Groundwater and Surface Water Resources under Uncertainty

Uncertainty in determining optimum conjunctive water use lies not only on variability of hydrological cycle and climate but also on lack of adequate data and perfect knowledge about groundwater-surface water system interactions, errors in historic data and inherent variability of system parameters both in space and time. Simulation-optimization models are used for conjunctive water use management under uncertain conditions. However, direct application of such approach whereby all realizations are considered at every-iteration of the optimization process leads to a highly computational time-consuming optimization problem as the number of realizations increases. Hence, this study proposes a novel approach—a Retrospective Optimization Approximation (ROA) approach. In this approach, a simulation model was used to determine aquifer system responses (draw-downs) which were assembled as response matrices and incorporated in the optimization model (procedure) as coefficients in the constraints. The sample optimization sub-problems generated, were solved and analyzed through ROA-Active-Set procedure implemented under MATLAB code. The ROA-Active Set procedure solves and evaluates a sequence of sample path optimization sub-problems in an increasing number of realizations. The methodology was applied to a real-world conjunctive water use management problem found in Great Letaba River basin, South Africa. In the River basin, surface water source contributes 87% of the existing un-optimized total conjunctive water use withdrawal rate (6512.04 m3/day) and the remaining 13% is contributed by groundwater source. Through ROA approach, results indicate that the optimum percentages contribution of the surface and subsurface sources to the total water demand are 58% and 42% respectively. This implies that the existing percentage contribution can be increased or reduced by ±29% that is groundwater source can be increased by 29% while the surface water source contribution can be reduced by 29%. This reveals that the existing conjunctive water use practice is unsustainable wherein surface water system is overstressed while groundwater system is under-utilized. Through k-means sampling technique ROA-Active Set procedure was able to attain a converged maximum expected total optimum conjunctive water use withdrawal rate of 4.35 × 104 m3/day within a relatively few numbers of iterations (6 to 8 iterations) in about 2.30 Hrs. In conclusion, results demonstrated that ROA approach is capable of managing real-world regional aquifers sustainable conjunctive water use practice under hydro-geological uncertainty conditions.

A network pharmacology approach to explore the mechanism of action of Yiqi Fumai lyophilized injection in the treatment of novel coronavirus disease

Background:Shengmai decoction,which has been included in the diagnosis and treatment of coronavirus disease 2019(COVID-19),is effective in the early treatment of patients with severe COVID-19.Yiqi Fumai lyophilized injection(YQFM)is a modern Chinese medicine preparation of the Shengmai decoction.The mechanism of its intervention at the molecular level in the severe stage of COVID-19 remains unclear.Therefore,it is necessary to investigate the mechanism of YQFM in the treatment of patients with severe COVID-19.Methods:The corresponding target genes of the main active ingredients in YQFM and COVID-19 were obtained by using multiple databases and literature retrieval.A protein-protein interaction network was constructed,and enrichment analysis of the target was performed using Cytoscape 3.8.1.Lastly,the docking of all the identified compounds with angiotensin-converting enzyme II was confirmed by applying molecular docking technology.Results:YQFM has anti-inflammatory effects on RAW267.4 macrophages.The main active compounds of YQFM are all effective anti-inflammatory agents,and these active compounds also show beneficial physiological functions,such as anti-oxidation,anti-bacterial,and anticancer activities.Gene Ontology analysis showed enrichment in the following pathways:lipopolysaccharides,interleukins,NF-kappa B,interleukin-2 and others,revealing that YQFM may play a role in the treatment of patients with severe COVID-19 through these pathways.Conclusion:YQFM has multicomponent and multitarget characteristics,and it could reduce lung injury by inhibiting inflammatory reactions,promoting antiviral activities,and regulating immunity,among other functions,to treat patients with severe COVID-19.

Access to novel anti-diabetic agents in resource limited settings:A brief commentary

The prevalence of diabetes mellitus is increasing in resource limited settings.Simultaneously,there has been an increase in the number of novel therapies for the management of diabetes mellitus.However,use of novel antidiabetic therapies is limited because of major market access challenges in resource limited settings.Niching products to those patients with the highest absolute risk for major adverse cardiovascular outcomes,and thus most likely to benefit from the therapy,are less likely to have negative budget impact for funders.To improve access,and reduce morbidity and mortality,requires alignment amongst key stakeholders including patient advocacy groups,health care professional councils,national departments of health,the pharmaceutical industry,treasury and finance departments.

AENO:a Novel Reconstruction Method in Conjunction with ADER Schemes for Hyperbolic Equations

In this paper,we present a novel spatial reconstruction scheme,called AENO,that results from a special averaging of the ENO polynomial and its closest neighbour,while retaining the stencil direction decided by the ENO choice.A variant of the scheme,called m-AENO,results from averaging the modified ENO(m-ENO)polynomial and its closest neighbour.The concept is thoroughly assessed for the one-dimensional linear advection equation and for a one-dimensional non-linear hyperbolic system,in conjunction with the fully discrete,high-order ADER approach implemented up to fifth order of accuracy in both space and time.The results,as compared to the conventional ENO,m-ENO and WENO schemes,are very encouraging.Surprisingly,our results show that the L_(1)-errors of the novel AENO approach are the smallest for most cases considered.Crucially,for a chosen error size,AENO turns out to be the most efficient method of all five methods tested.