Transcriptome and carotenoid profiling of different varieties of Coffea arabica provides insights into fruit color formation

The processability and ultimate quality of coffee(Coffea arabica)are determined by the composition of the matured fruits.The basis of genetic variation in coffee fruit quality could be explained by studying color formation during fruit maturation.Transcriptome profiling was conducted on matured fruits of four C.arabica varieties(orange colored fruits(ORF);purple colored fruits(PF);red colored fruits(RF)and yellow colored fruits(YF))to identify key color-regulating genes,biosynthesis pathways and transcription factors implicated in fruit color formation.A total of 39,938 genes were identified in the transcriptomes of the four C.arabica varieties.In all,2745,781 and 1224 differentially expressed genes(DEGs)were detected in YF_vs_PF,YF_vs_RF and YF_vs_ORF,respectively,with 1732 DEGs conserved among the three pairwise groups.Functional annotation of the DEGs led to the detection of 28 and 82 key genes involved in the biosynthesis of carotenoids and anthocyanins,respectively.Key transcription factors bHLH,MYB,NAC,MADS,and WRKY implicated in fruit color regulation were detected.The high expression levels of gene-LOC113688784(PSY),gene-LOC113730013(b-CHY),gene-LOC113728842(CCD7),gene-LOC113689681(NCED)and gene-LOC113729473(ABA2)in YF may have accounted for the yellow coloration.The differential expression of several anthocyanin and carotenoid-specific genes in the fruits substantially account for the purple(PF),red(RF),and orange(ORF)colorations.This study provides important insights into fruit color formation and variations in C.arabica and will help to develop coffee varieties with specific color and quality traits.

A multidimensional platform of patient-derived tumors identifies drug susceptibilities for clinical lenvatinib resistance

Lenvatinib,a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer,facing limitations due to drug resistance.Here,we applied a multidimensional,high-throughput screening platform comprising patient-derived resistant liver tumor cells(PDCs),organoids(PDOs),and xenografts(PDXs)to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings.Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment,expediting drug repurposing screens.Pharmacological screening identified romidepsin,YM155,apitolisib,NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models.Notably,romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway.A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models.Collectively,our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer,providing a feasible multidimensional platform for personalized medicine.

Pharmacological inhibition of BAP1 recruits HERC2 to competitively dissociate BRCA1-BARD1, suppresses DNA repair and sensitizes CRC to radiotherapy

Radiotherapy is widely used in the management of advanced colorectal cancer(CRC).However,the clinical efficacy is limited by the safe irradiated dose.Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation.The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination(HR)DSB repair,and its functions may be affected by HERC2 or BAP1.Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes;however,the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn’t been defined.Through activity-based profiling,we identified PT33 as an active entity for HR repair suppression.Subsequently,we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen.Mechanistically,pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction,interrupting HR repair.Consequently,PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo.Overall,these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.

Enhanced separation of tetrafluoropropanol from water via carbon nanotubes membranes:insights from molecular dynamics simulations

Fluorinated alcohols exhibit promising prospects in chemical industry because of their special structure and many exciting properties,in which tetrafluoropropanol(TFP)is extensive applied in synthesis of pesticides,dyestuffs,variety of solvents and detergents.However,the presence of TFP in water garners increasing attention globally because of their intrinsic potential to threat ecosystems and human health.Carbon nanotubes(CNTs)membranes are burgeoning candidates for TFP-water separation owing to well-endowed extraordinary structural and transport properties.However,a grand challenge lies in the rational design of CNTs for improving separation performance.Herein,molecular dynamics(MD)simulations were performed to investigate the effects of various parameters on the separation of TFP-water mixtures including feed temperature,CNTs pore diameters,and fluorine functionalization position.It was found that TFP was pre-selected in CNTs ranging from 9.48 to 18.98Ådue to preferential adsorption and diffusion mechanism.Excellent separation factor of 16 was achieved by(7,7)CNTs and the mass fraction of TFP was purified from 75%to 97.51%.Fluorine modified CNTs separated TFP and water by preferentially permeating water due to hydrogen bonding interaction.Simulation results showed that CNTs modified at both the entrance and interior had better separation performance than CNT modified only at one of these positions.The 100wt%water content in permeate was achieved by(11,11)CNTs modified with fluorine at the entrance and interior.These findings provide valuable insights for designing potential candidates for fluorinated alcohol-water azeotropic mixtures membrane separation,and promise extensive application aspects for the reclamation of fluorinated alcohol.

Tuning the luminous properties and optical thermometry of Cs_(2)SnCl_(6) phosphor microcrystals via Bi and Sb codoping

The toxicity and instability of lead halide perovskite seriously limit its commercial application in lighting,although it has high photoluminescence(PL)efficiency and adjustable emission.Here,lead-free bismuth(Bi)and antimony(Sb)codoped Cs_(2)SnCl_(6)(BSCSC)microcrystals(MCs)are prepared successfully by a solvothermal method.The PL spectrum is composed of dual emission bands with the peak at 485 and 650 nm,of which relative intensity can be tunable through the change of Bi and Sb feeding contents,respectively.Because of the phonon–electron interaction,the PL intensity is enhanced as the temperature rises within the range of 80–260 K.Then,the nonradiative transition is intensified until 380 K,which results in decrease in PL intensity.Simultaneously,combining with time-resolved PL,it is concluded that the emission peak at 485 nm is attributed to the[Bi_(Sn)+V_(Cl)]as the luminescent centers with the lifetime of hundreds of nanoseconds,and the emission peak at 650 nm is attributed to microsecond-timescale self-trapped excitons.The maximum values of relative sensitivity(S_(R))and absolute sensitivity(S_(A))values obtained are 3.82%K^(-1) and 5.11 ns·K^(-1),which for the first time to our knowledge demonstrate that BSCSC MCs can be novel luminescent materials for developing better optical thermometry.Whitelight-emitting diodes(WLEDs)are constructed using BSCSC MCs only combined with an LED chip,the Commission Internationale de L’Eclairage color coordinates of which are(0.30,0.37).It provides a novel scheme for the lighting field to realize WLEDs without adding additional commercial phosphors.