EPAS1 prevents telomeric damage-induced senescence by enhancing transcription of TRF1,TRF2,and RAD50

Telomeres are nucleoprotein structures located at the end of each chromosome,which function in terminal protection and genomic stability.Telomeric damage is closely related to replicative senescence in vitro and physical aging in vivo.As relatively long-lived mammals based on body size,bats display unique telomeric patterns,including the upregulation of genes involved in alternative lengthening of telomeres(ALT),DNA repair,and DNA replication.At present,however,the relevant molecular mechanisms remain unclear.In this study,we performed cross-species comparison and identified EPAS1,a well-defined oxygen response gene,as a key telomeric protector in bat fibroblasts.Bat fibroblasts showed high expression of EPAS1,which enhanced the transcription of shelterin components TRF1 and TRF2,as well as DNA repair factor RAD50,conferring bat fibroblasts with resistance to senescence during long-term consecutive expansion.Based on a human single-cell transcriptome atlas,we found that EPAS1 was predominantly expressed in the human pulmonary endothelial cell subpopulation.Using in vitro-cultured human pulmonary endothelial cells,we confirmed the functional and mechanistic conservation of EPAS1 in telomeric protection between bats and humans.In addition,the EPAS1 agonist M1001 was shown to be a protective compound against bleomycin-induced pulmonary telomeric damage and senescence.In conclusion,we identified a potential mechanism for regulating telomere stability in human pulmonary diseases associated with aging,drawing insights from the longevity of bats.

Phylogenomic relationships and molecular convergences to subterranean life in rodent family Spalacidae

All extant species in the rodent family Spalacidae are subterranean and have evolved various traits for underground life.However,the phylogenomic relationships among its three subfamilies(Myospalacinae,Spalacinae,and Rhizomyinae)and the molecular basis underlying their adaptations to underground life remain poorly understood.Here,we inferred the phylogenomic relationships among these subfamilies based on de novo sequencing the genome of the hoary bamboo rat(Rhizomys pruinosus).Analyses showed that 50%of the identified 11028 one-to-one orthologous protein-coding genes and the concatenated sequences of these orthologous genes strongly supported a sister relationship between Myospalacinae and Rhizomyinae.

Pneumonia and ocular disease as the primary presentations of Takayasu arteritis:a case report

Dear Editor,Takayasu arteritis(TA)is a rare,idiopathic,granulomatous,large-vessel vasculitis,with preferential involvement of the aorta,its main branches,and pulmonary arteries[1].It has been reported that the ocular involvements were found in 8.1%–68%[2],non-specific arthralgia or myalgia in 13%–41%,aortic regurgitation in 5%–55%.

Cochlear hair cells of echolocating bats are immune to intense noise

Exposure to intense noise can damage cochlear hair cells,leading to hearing loss in mammals.To avoid this constraint,most mammals have evolved in relatively quiet environments.Echolocating bats,however,are naturally exposed to continuous intense sounds from their own and neighboring sonar emissions for maintaining sonar directionality and range.Here,we propose the presence of intense noise resistance in cochlear hair cells of echolocating bats against noise-induced hearing loss(NIHL).To test this hypothesis,we performed noise exposure experiments for laboratory mice,one nonecholocating bat species,and five echolocating bat species.Contrary to nonecholocating fruit bats and mice,the hearing and the cochlear hair cells of echolocating bats remained unimpaired after continuous intense noise exposure.The comparative analyses of cochleae transcriptomic data showed that several genes protecting cochlear hair cells from intense sounds were overexpressed in echolocating bats.Particularly,the experimental examinations revealed that ISL1 overexpression significantly improved the survival of cochlear hair cells.Our findings support the existence of protective effects in cochlear hair cells of echolocating bats against intense noises,which provides new insight into understanding the relationship between cochlear hair cells and intense noises,and preventing or ameliorating NIHL in mammals.

Triterpenoid Saponins from Pulsatilla cernua （Thunb.） Bercht. et Opiz.

To investigate saponins from the roots of Pulsatilla cernua （Thunb.） Bercht. et Opiz., two new compounds together with five known trlterpenold saponins were isolated. The structures of the two new trlterpenoid saponins, named cernuasides A and B, were elucidated as 3-O-[β-D-xylopyranosyl（1-）2）]-[α-L-rhamnopyranosyl（1-）4）]-α-L- arablnopyranosyl hederagenin 28-O-β-D-glucopyranosyl ester （compound 1） and 3-O-[α-L-arabinopyranosyl（1→）3）]- [α-L-rhamnopyranosyl （1→）2）]-α-L-arabinopyranosyl hederagenin 28-O-β-D-glucopyranosyl ester （compound 2） by 1D, 2D-NMR techniques, ESIMS analysis, as well as chemical methods.

Influence of process parameters on interracial tensile strength of crosswedge rolling of 42CrMo/Q235 laminated shafts

Through rolling experiments and interfacial tensile strength tests of cross-wedge rolled laminated shafts of 42CrMo/Q235 composites, the influence of process parameters, including forming angle, spreading angle, area reduction, rolling temperature and core material diameter on the interfacial shear strength was analyzed. The results show that the sequence of process parameters in order of greatest influence on interfacial tensile strength was rolling temperature, area reduction, core material diameter, forming angle and spreading angle. At the interface of the combined materials, tensile strength decreased as forming angle and spreading angle increased, whereas the tensile strength first increased and then decreased as area reduction, rolling temperature and core material diameter increased.