Physical exercise reverses immuno-cold tumor microenvironment via inhibiting SQLE in non-small cell lung cancer

Dear Editor,Physical exercise has been shown to be associated with reduced cancer incidence and cancer-associated mortality[1,2],but the underlying mechanisms are obscure.Immunometabolic regulation has emerged as one of the most prominent mechanisms explaining the effects of exercise on cancer[1,2].Physical exercise primarily lowers blood cholesterol and triglycerides,and protects against cardiovascular diseases[3].However,whether physical exercise can modulate cholesterol metabolism in tumor cells is currently unknown.

Optimized timing of using infliximab in perianal fistulizing Crohn's disease

Infliximab(IFX),as a drug of first-line therapy,can alter the natural progression of Crohn’s disease(CD),promote mucosal healing and reduce complications,hospitalizations,and the incidence of surgery.Perianal fistulas are responsible for the refractoriness of CD and represent a more aggressive disease.IFX has been demonstrated as the most effective drug for the treatment of perianal fistulizing CD.Unfortunately,a significant proportion of patients only partially respond to IFX,and optimization of the therapeutic strategy may increase clinical remission.There is a significant association between serum drug concentrations and the rates of fistula healing.Higher IFX levels during induction are associated with a complete fistula response in these patients.Given the apparent relapse of perianal fistulizing CD,maintenance therapy with IFX over a longer period seems to be more beneficial.It appears that patients without deep remission are at an increased risk of relapse after stopping anti-tumor necrosis factor agents.Thus,only patients in prolonged clinical remission should be considered for withdrawal of IFX treatment when biomarker and endoscopic remission is demonstrated,especially when the hyperintense signals of fistulas on T2-weighed images have disappeared on magnetic resonance imaging.Fundamentally,the optimal timing of IFX use is highly individualized and should be determined by a multidisciplinary team.

Kartogenin and Its Application in Regenerative Medicine

Regenerative medicine refers to the possibility of replacing aged/daniaged cells with genetically similar young and functional cells to restore or establish normal function.Kartogenin(KGN),a small heterocyclic,drug-like compound was discovered in 2012,which is strongly associated with regenerative medicine.KGN has been applied in many regenerative fields,including cartilage regeneration and protection,tendon-bone healing,wound healing,and limb devclopmcnt.KGN could facilitate cartilage repair,promote fonnation of cartilage-like transition zone in tendon-bone junctions,stimulate collagen synthesis for wound healing,and regulate limb development in a coordinated manner.Considering the related mechanism,filamin A/CBFβ/RUNX1,Ihh,and TGFβ/Smad pathways have been reported to involve KGN.Therefore,KGN is proven a promising agent in regenerative medicine;however,studies conducted on the effect of KGN are limited to date and not convictive for Iong-term use.Further studies are recommended to explore the long-term effect and poteniial molecular mechanisms of KGN.Our investigations may motivate researchers to expand its applications in different forms and fields.

Divergent trajectories of lean vs obese non-alcoholic steatohepatitis patients from listing to post-transplant:A retrospective cohort study

BACKGROUND Non-alcoholic steatohepatitis(NASH)cirrhosis is the second most common indication for liver transplantation(LT).The role of body mass index(BMI)on outcomes of NASH cirrhosis has been conflicting.AIM To compare the longitudinal trajectories of patients with lean vs obese NASH cirrhosis,from listing up to post-transplant,having adjusted their BMI for ascites.METHODS We retrospectively reviewed all adult NASH patients listed for LT in our program from 2012 to 2019.Fine-Gray Competing Risk analyses and Cox Proportional-Hazard Models were performed to examine the cumulative incidence of transplant and survival outcomes respectively.RESULTS Out of 265 NASH cirrhosis listed patients,176 were included.Median age was 61.0 years;46%were females.111 patients underwent LT.Obese robust patients had better waitlist survival[hazard ratio(HR):0.12;95%CI:0.05–0.29,P<0.0001]with higher instantaneous rate of transplant(HR:5.71;95%CI:1.26–25.9,P=0.02).Lean NASH patients had a substantially higher risk of graft loss within 90 d post-LT(1.2%vs 13.8%,P=0.032)and death post-LT(2.4%vs 17.2%,P=0.029).1-3-and 5-year graft survival was poor for lean NASH(78.6%,77.3%and 41.7%vs 98.6%,96%and 85%respectively).Overall patient survival post-LT was significantly worse in lean NASH(HR:0.17;95%CI:0.03–0.86,P=0.0142)with 83%lower instantaneous rate of death in obese group.CONCLUSION Although lean NASH is considered to be more benign than obese NASH,our study suggests a paradoxical correlation of lean NASH with waitlist outcomes,and graft and patient survival post-LT.

Long head of biceps tendon transposition for massive and irreparable rotator cuff tears:A systematic review and meta-analysis

BACKGROUND Superior capsular reconstruction(SCR)with long head of biceps tendon(LHBT)transposition was developed to massive and irreparable rotator cuff tears(MIRCTs);however,the outcomes of this technique remain unclear.AIM To perform a systematic review of biomechanical outcomes and a meta-analysis of clinical outcomes after LHBT transposition for MIRCTs.METHODS We performed a systematic electronic database search on PubMed,EMBASE,and Cochrane Library.Studies of SCR with LHBT transposition were included according to the inclusion and exclusion criteria.Biomechanical studies were assessed for main results and conclusions.Included clinical studies were evaluated for quality of methodology.Data including study characteristics,cohort demographics,and outcomes were extracted.A meta-analysis was conducted of the clinical outcomes.RESULTS According to our inclusion and exclusion criteria,a total of six biomechanical studies were identified and reported an overall improvement in subacromial contact pressures and prevention of superior humeral migration without limiting range of motion(ROM)after LHBT transposition for MIRCTs.A total of five clinical studies were included in the meta-analysis of LHBT transposition outcomes,consisting of 253 patients.The results indicated that compared to other surgical methods for MIRCTs,LHBT transposition had advantages of more significant improvement in ROM(forward flexion mean difference[MD]=6.54,95%confidence interval[CI]:3.07-10.01;external rotation[MD=5.15,95%CI:1.59-8.17];the acromiohumeral distance[AHD][MD=0.90,95%CI:0.21-1.59])and reducing retear rate(odds ratio=0.27,95%CI:0.15-0.48).No significant difference in American Shoulder and Elbow Surgeons score,visual analogue scale score,and University of California at Los Angles score was demonstrated between these two groups for MIRCTs.CONCLUSION In general,SCR with LHBT transposition was a reliable and economical technique for treating MIRCTs,both in terms of biomechanical and clinical outcomes,with comparable clinical outcomes,improved ROM,AHD,and reduced the retear rates compared to conventional SCR and other established techniques.More high-quality randomized controlled studies on the long-term outcomes of SCR with LHBT transposition are required to further assess.

Bone marrow mesenchymal stem cell-derived exosomal microRNAs target PI3K/Akt signaling pathway to promote the activation of fibroblasts

BACKGROUND Fibroblast plays a major role in tendon-bone healing.Exosomes derived from bone marrow mesenchymal stem cells(BMSCs)can activate fibroblasts and promote tendon-bone healing via the contained microRNAs(miRNAs).However,the underlying mechanism is not comprehensively understood.Herein,this study aimed to identify overlapped BMSC-derived exosomal miRNAs in three GSE datasets,and to verify their effects as well as mechanisms on fibroblasts.AIM To identify overlapped BMSC-derived exosomal miRNAs in three GSE datasets and verify their effects as well as mechanisms on fibroblasts.METHODS BMSC-derived exosomal miRNAs data(GSE71241,GSE153752,and GSE85341)were downloaded from the Gene Expression Omnibus(GEO)database.The candidate miRNAs were obtained by the intersection of three data sets.TargetScan was used to predict potential target genes for the candidate miRNAs.Functional and pathway analyses were conducted using the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases,respectively,by processing data with the Metascape.Highly interconnected genes in the protein-protein interaction(PPI)network were analyzed using Cytoscape software.Bromodeoxyuridine,wound healing assay,collagen contraction assay and the expression of COL I andα-smooth muscle actin positive were applied to investigate the cell proliferation,migration and collagen synthesis.Quantitative real-time reverse transcription polymerase chain reaction was applied to determine the cell fibroblastic,tenogenic,and chondrogenic potential.RESULTS Bioinformatics analyses found two BMSC-derived exosomal miRNAs,has-miR-144-3p and hasmiR-23b-3p,were overlapped in three GSE datasets.PPI network analysis and functional enrichment analyses in the GO and KEGG databases indicated that both miRNAs regulated the PI3K/Akt signaling pathway by targeting phosphatase and tensin homolog(PTEN).In vitro experiments confirmed that miR-144-3p and miR-23b-3p stimulated proliferation,migration and collagen synthesis of NIH3T3 fibroblasts.Interfering with PTEN affected the phosphorylation of Akt and thus activated fibroblasts.Inhibition of PTEN also promoted the fibroblastic,tenogenic,and chondrogenic potential of NIH3T3 fibroblasts.CONCLUSION BMSC-derived exosomes promote fibroblast activation possibly through the PTEN and PI3K/Akt signaling pathways,which may serve as potential targets to further promote tendon-bone healing.

纳米粒子交联类玻璃高分子材料的动力学行为和流变行为研究

研究了纳米粒子动态交联端羧基聚丁二烯的动力学行为.除了利用传统的熔融重塑以及应力松弛行为来研究其动态行为和可加工性,着重通过线性和非线性动态流变学,研究揭示了粒子交联类玻璃高分子材料与分子交联类玻璃高分子、粒子填充高分子复合材料的差异.与分子交联体系相比,粒子交联体系末端区的松弛主要来源于粒子的扩散运动,可逆共价网络对模量的贡献较弱,但减慢了粒子扩散的速度.与粒子填充体系相比,在粒子交联体系中,粒子需要在动态共价键解离之后才能从粒子笼中逃出.

Evaluating the Phylogenetic Position of Chinese Tree Shrew(Tupaia belangeri chinensis) Based on Complete Mitochondrial Genome:Implication for Using Tree Shrew as an Alternative Experimental Animal to Primates in Biomedical Research

Tree shrew （Tupaia belangeri） is currently placed in Order Scandentia and has a wide distribution in Southeast Asia and Southwest China. Due to its unique characteristics, such as small body size, high brain-to-body mass ratio, short reproductive cycle and life span, and low-cost of maintenance, tree shrew has been proposed to be an alternative experimental animal to primates in biomedical research. However, there are some debates regarding the exact phylogenetic affinity of tree shrew to primates. In this study, we determined the mtDNA entire genomes of three Chinese tree shrews （T. belangeri chinensis） and one Malayan flying lemur （Galeopterus variegatus）. Combined with the published data for species in Euarchonta, we intended to diseen] the phylogenetic relationship among representative species of Dermoptera, Scandentia and Primates. The mtDNA genomes of Chinese tree shrews and Malayan flying lemur shared similar gene organization and structure with those of other mammals. Phylogenetic analysis based on 12 concatenated mitochondrial proteinencoding genes revealed a closer relationship between species of Scandentia and Glires, whereas species of Dermoptera were clustered with Primates. This pattern was consistent with previously reported phylogeny based on mtDNA data, but differed from the one reconstructed on the basis of nuclear genes. Our result suggested that the matrilineal affinity of tree shrew to primates may not be as close as we had thought. The ongoing project for sequencing the entire genome of Chinese tree shrew will provide more information to clarify this important issue.

Species authentication of commercial beef jerky based on PCR-RFLP analysis of the mitochondrial 12S rRNA gene

In this study, we determined species-specific variations by analyzing the mitochondrial 12S rRNA gene sequence variation （-440 bp） in 17 newly obtained sequences and 90 published cattle, yak, buffalo, goat, and pig sequences, which represent 62 breeds and 17 geo- graphic regions. Based on the defined species-specific variations, two endonucleases, Alu I and Bfa I, were selected for species authentication using raw meat/tissue samples and the PCR-RFLP method. Goat and pig were identified using the Alu I enzyme, while cattle, yak, and buffalo were identified by digestion with Bfa I. Our approach had relatively high detection sensitivity of cattle DNA in mixed cattle and yak products, with the lowest detectable threshold equaling 20% of cattle DNA in a mixed cattle/yak sample. This method was successfully used to type commercial beef jerky products, which were produced by different companies utilizing various processing technologies. Our results show that several yak jerky products might be implicated in commercial fraud by using cattle meat instead of yak meat.

Navigability of the Northern Sea Route for Arc7 ice-class vessels during winter and spring sea-ice conditions

Sea ice hinders the navigability of the Arctic,especially in winter and spring.However,three Arc7 ice-class Liquefied Natural Gas carrying vessels safely transited the Northern Sea Route(NSR)without icebreaker assistance in January 2021.More and more Arc7 ice-class vessels are putting into the transit services in the NSR.Therefore,it is necessary to analyze sea-ice conditions and their impact on navigation during wintertime,and the future navigability of Arc7 ice-class vessels along the NSR during winter and spring.Based on sea ice datasets from satellite observations and a model using data assimilation,we explored the sea-ice conditions and their impact during the first three successful commercial voyages through the NSR in winter.In addition,we analyzed the sea ice variation and estimated navigability for Arc7 ice-class vessels in the NSR from January to June of the years 2021–2050 using future projections of the sea-ice cover by the Coupled Model Inter-comparison Project Phase 6(CMIP6)models under two emission scenarios(SSP2-4.5 and SSP5-8.5).The results reveal lower sea ice thickness and similar sea ice concentration during these three transits relative to the past 42 years(from 1979 to 2020).We found the thickness has a larger impact on the vessels’speeds than sea ice concentration.Very likely sea ice thickness played a larger role than the sea ice concentration for the successful transit of the NSR in winter 2021.Future projections suggest sea ice thickness will decrease further in most regions of the NSR from January to June under all scenarios enabling increased navigability of the NSR for Arc7 ice-class vessels.Such vessels could transit through the NSR from January to June under all scenarios by 2050,while some areas near the coast of East Siberian Sea remain inaccessible for Arc7 ice-class vessels in spring(April and May).These findings can support the strategic planning of shipping along the NSR in winter and spring.