Bacteria can evolve rapidly by acquiring new traits such as virulence,metabolic properties,and most importantly,antimicrobial resistance,through horizontal gene transfer(HGT).Multidrug resistance in bacteria,especiall...Bacteria can evolve rapidly by acquiring new traits such as virulence,metabolic properties,and most importantly,antimicrobial resistance,through horizontal gene transfer(HGT).Multidrug resistance in bacteria,especially in Gram-negative organisms,has become a global public health threat often through the spread of mobile genetic elements.Conjugation represents a major form of HGT and involves the transfer of DNA from a donor bacterium to a recipient by direct contact.Conjugative plasmids,a major vehicle for the dissemination of antimicrobial resistance,are selfish elements capable of mediating their own transmission through conjugation.To spread to and survive in a new bacterial host,conjugative plasmids have evolved mechanisms to circumvent both host defense systems and compete with co-resident plasmids.Such mechanisms have mostly been studied in model plasmids such as the F plasmid,rather than in conjugative plasmids that confer antimicrobial resistance(AMR)in important human pathogens.A better understanding of these mechanisms is crucial for predicting the flow of antimicrobial resistance-conferring conjugative plasmids among bacterial populations and guiding the rational design of strategies to halt the spread of antimicrobial resistance.Here,we review mechanisms employed by conjugative plasmids that promote their transmission and establishment in Gram-negative bacteria,by following the life cycle of conjugative plasmids.展开更多
Flavobacterium columnare, the etiological agent of colunmaris disease, is one of the most important and widespread bacterial pathogens of freshwater fish. In this study, we constructed two artificial selectable marke...Flavobacterium columnare, the etiological agent of colunmaris disease, is one of the most important and widespread bacterial pathogens of freshwater fish. In this study, we constructed two artificial selectable markers (chloramphenicol and spectinomycin resistance) for gene transfer in F. columnare. These two new artificial selectable markers, which were created by placing the chloramphenicol or spectinomycin resistance gene under the control of the native acs regulatory region of F. columnare, were functional in both F. columnare and Escherichia coli. The integrative/conjugative plasmids constructed by using these markers were introduced into F. columnare G4 via electroporation or conjugation. The integrated plasmid DNA was confirmed by Southern blotting and PCR analysis. These two markers can be employed in future investigations into gene deletion and the pathogenicity of virulence factors in F. columnare.展开更多
Pasteurella multocida(PM)has been infecting a variety of hosts for a long time,causing sustained economic losses worldwide;however,there have been limited studies on its extensive adaptability(Aktories et al.2012).Ana...Pasteurella multocida(PM)has been infecting a variety of hosts for a long time,causing sustained economic losses worldwide;however,there have been limited studies on its extensive adaptability(Aktories et al.2012).Analysis of strains data collected in our laboratory revealed that PM typically acquires foreign genes through transformation and conjugation,rather than transformation and fusion.Integrative and conjugative elements(ICEs)are a crucial mechanism that leads to abrupt changes in niche preferences and enhances environmental adaptability for bacteria,with their number far exceeding the number of plasmids and phages(Wozniak and Waldor 2010;Johnson and Grossman 2015;Botelho and Schulenburg 2021).Previous research has shown that the European bovine-sourced strain Pm36950 contains the experimentally transferable resistant ICEPmu1,which could integrate into the host chromosome or forming a circular intermediate(Michael et al.2012).Additionally,a few studies have suggested that PM strains isolated from European bovine and Asian swine might contain ICEs,but these claims lack experimental verification(Klima et al.2014;Moustafa et al.2015;Kadlec et al.2017;Peng et al.2017;Beker et al.2018;Schink et al.2022).Currently,there is no data available on ICE-carrying PM strains isolated from hosts outside of European cattle or Chinses swine.This letter presents a report on a novel ICE identified in the hypervirulent and multidrug-resistant PM HN141014 strain isolated from Chinese duck.The ICE was specifically analyzed for its resistance genes,transferable capacity and host diversity.展开更多
Antimicrobial susceptibility test was performed on 57 clinical isolates of P. aeruginosa and 36 clinical isolates of Acinetobacter with 11 antimicrobial agents including getamicin, amikacin, ciprofloxacin, ofloxacin, ...Antimicrobial susceptibility test was performed on 57 clinical isolates of P. aeruginosa and 36 clinical isolates of Acinetobacter with 11 antimicrobial agents including getamicin, amikacin, ciprofloxacin, ofloxacin, fleroxacin, piperacillin, cefotaxime, cefoperazone/sulbactam, ceftazidime, cefoperazone and doxycycline. Transferable drug resistance plasmid carrying rates of these clinical isolates were also studied. On the basis of the in vitro activities, 52.63%(30/57) of the isolated strains of P. aeruginosa were susceptible to antimicrobial agents selected (except doxycycline), 41.67%(15/36) of the isolated strains of Acinetobacter were susceptible to 11 antimicrobial agents. The sensitivity rate of P.aeruginosa and Acinetobacter to antimicrobial agents selected was 70% or greater to all except doxycycline. Furthermore, the sensitivity rate of P.aeruginosa to amikacin ciprofloxacin, ceftazidime, cefoperazone, cefoperazone/sulbactam, and that of Acinetobacter to cefoperazone/sulbactam, amikacin was more than 90%,among them amikacin, cefoperazone/sulbactam being the most effective. Plasmid analysis showed that 15.79%(9/57) P.aeruginosa strains and 13.89%(5/36) Acinetobacter strains carried plasmid. Conjugative plasmid carrying rates of P. aeruginosa strains and Acinetobacter strains were 7.02%(4/57), 13.89%(5/36), respectively. Conjugative plasmid didn′t play an important role in the formation and dissemination of drug resistance of P. aeruginosa and Acinetobacter.展开更多
The global dissemination of antibiotic resistance genes(ARGs),especially via plasmid-mediated horizontal transfer,is becoming a pervasive health threat.While our previous study found that herbicides can accelerate the...The global dissemination of antibiotic resistance genes(ARGs),especially via plasmid-mediated horizontal transfer,is becoming a pervasive health threat.While our previous study found that herbicides can accelerate the horizontal gene transfer(HGT)of ARGs in soil bacteria,the underlying mechanisms by which herbicides promote the HGT of ARGs across and within bacterial genera are still unclear.Here,the underlying mechanism associ-ated with herbicide-promoted HGT was analyzed by detecting intracellular reactive oxygen species(ROS)production,extracellular polymeric substance composition,cell membrane integrity and proton motive force combined with genome-wide RNA sequencing.Exposure to herbicides induced a series of the above bacterial responses to promote HGT except for the ROS response,including compact cell-to-cell contact by enhancing pilus-encoded gene expression and decreasing cell surface charge,increasing cell membrane permeability,and enhancing the proton motive force,providing additional power for DNA uptake.This study provides a mechanistic understanding of the risk of bacterial resistance spread promoted by herbicides,which elucidates a new perspective on nonantibiotic agrochemical acceleration of the HGT of ARGs.展开更多
An unmet challenge in radical relay difunctionalization of alkenes is the incorporation of two discrete transient radicals in a regiocontrolled manner under transition-metal-free conditions.Current protocols typically...An unmet challenge in radical relay difunctionalization of alkenes is the incorporation of two discrete transient radicals in a regiocontrolled manner under transition-metal-free conditions.Current protocols typically rely on persistent radicals or organometallic surrogates to trap radical adducts,thereby suppressing the undesired reactions but limiting the diversity.The direct use of two transient radicals remains synthetically elusive.We present a visible-light photoredox catalyzed alkene dialkylation strategy via a kinetically guided conjugative radical–radical coupling.This transition-metal-free approach enables two direct C(sp^(3))–C(sp^(3))bond formations across the C=C double bond using alkyl and allyl or benzyl radicals.Mechanistic investigations reveal the radical nature of the process.The success of this approach hinges on kinetically controlled radical addition to alkene substrates and the steric protection of the resulting radical adducts.This mild and functional-group-tolerant reaction exhibits broad substrate scope and tolerates structurally complex substrates,highlighting its potential for late-stage functionalization.展开更多
The co-occurrence of plasmid-mediated multidrug resistance and hypervirulence in epidemic carbapenem-resistant Klebsiella pneumoniae has emerged as a global public health issue.In this study,an ST23 carbapenem-resista...The co-occurrence of plasmid-mediated multidrug resistance and hypervirulence in epidemic carbapenem-resistant Klebsiella pneumoniae has emerged as a global public health issue.In this study,an ST23 carbapenem-resistant hyper-virulent K.pneumoniae(CR-HvKP)strain VH1-2 was identified from cucumber in China and harbored a novel hybrid plasmid pVH1-2-VIR.The plasmid pVH1-2-VIR carrying both virulence and multidrug-resistance(MDR)genes was likely generated through the recombination of a virulence plasmid and an IncFIIK conjugative MDR plasmid in clinical ST2318622 isolated from a sputum sample.The plasmid pVH1-2-VIR exhibited the capacity for transfer to the clinical ST11 carbapenem-resistant K.pneumoniae(CRKP)strain via conjugation assay.Acquisition of pVH1-2-VIR plasmid directly converted a CRKP into CR-HvKP strain characterized by hypermucoviscosity,heightened virulence for Galleria mellonella larvae,and increased colonization ability in the mouse intestine.The emergence of such a hybrid plasmid may expedite the spread of CR-HvKP strains,posing a significant risk to human health.展开更多
The longitudinal π-extension of carbon nanohoops is one of the most effective bottom-up synthetic strategies toward carbon nanotubes(CNTs).Herein,the precise synthesis of a multi-substituted carbon nanohoop([12]CPP-8...The longitudinal π-extension of carbon nanohoops is one of the most effective bottom-up synthetic strategies toward carbon nanotubes(CNTs).Herein,the precise synthesis of a multi-substituted carbon nanohoop([12]CPP-8PBPy)based on cycloparaphenylenes(CPPs)grafted with eight pyrene-functionalized units was reported.This structurally well-defined nanohoop not only acts as a segment of armchair-type CNTs but also achieves enhanced longitudinal π-extension.The structure of[12]CPP-8PBPy was confirmed by high-resolution mass spectrometry(HRMS)and nuclear magnetic resonance(NMR).The photophysical properties were studied by UV/Vis and photoluminescence spectroscopy.The potential applications of[12]CPP-8PBPy in electron-transport devices were further investigated.展开更多
I. INTRODUCTIONIn the preceding paper we have reported that in a forked conjugative thienylpolyenic system with two electron-attracting groups at one end, the structural
In this paper, the following carbonyl-imino bridged compounds and related analogs havebeen synthesized:X= C1, m = 0); and the structural effect of the carbonyl-imino bridges has been studied by means of the UV and oth...In this paper, the following carbonyl-imino bridged compounds and related analogs havebeen synthesized:X= C1, m = 0); and the structural effect of the carbonyl-imino bridges has been studied by means of the UV and other properties of the compounds. A new conception of conjugative segment is put forward. The structural bases for each of the three π-π* bands of (C) are ascertained and verified by modification on structure of segments, such as eliminating, merging, lengthening or shortening of segments. It is demonstrated that both bridges -CO-and -NH- can block the conjugated polarization of the whole molecule so as to form three segments S, M and L of which the λmax each exhibits relative independence. The electronic absorption peaks resulting from different segments can be readily recognized and the existence of each segment can be ascertained. This may provide a new way for structural analysis of bridged compounds.展开更多
Cancer is the second leading cause of death globally.Its treatment remains a major challenge due to the disease's complexity,heterogeneity,and adaptive nature.Among the array of available treatments,targeted thera...Cancer is the second leading cause of death globally.Its treatment remains a major challenge due to the disease's complexity,heterogeneity,and adaptive nature.Among the array of available treatments,targeted therapy emerges as a paramount approach to address this substantial unmet clinical need,owing to its precise tumor targeting capabilities and potential for mitigating tumor progression risks.Drug conjugates are in high demand for targeted therapy due to their unique ligand specificity and potent cytotoxicity,thereby significantly enhancing therapeutic efficacy and reducing the incidence of adverse effects.Therefore,as a burgeoning field in biomedical research,it is timely to outline the latest advances in drug conjugates-driven cancer treatment.Herein,we aim to present the emerging breakthroughs in this exciting field at the intersection of target ligands,linkers,payloads,and cancer treatments.This review focuses on several drug conjugates-related strategies,including antibody-drug conjugates(ADCs),peptide-drug conjugates(PDCs),small molecule-drug conjugates(SMDCs),aptamer-drug conjugates(ApDCs)and radionuclide-drug conjugates(RDCs).Finally,we discuss the fundamentals behind drug conjugate-based anticancer therapeutics,along with their inherent advantages and associated challenges,as well as recent research advances.展开更多
Five homologous series of bifurcate systems of aliphatic and aromatic polyenic cyano and carboxylic compounds have been prepared and studied. The electronic absorption spectra forthe series and the NMR chemical shifts...Five homologous series of bifurcate systems of aliphatic and aromatic polyenic cyano and carboxylic compounds have been prepared and studied. The electronic absorption spectra forthe series and the NMR chemical shifts for the methyl-, methylene- and beta-protons havebeen found to conform very well to the rule of homologous linearity. The mass spectra forthe α-cyano polyenic ester series show strong peaks for the fragments of M-COOEt but noneof M-CN, indicating that the CN group seems to be in stronger conjugation with the poly-enic chain than the COOEt group does. In all the forked series studided, a red shift in electronic spectra is brought about upon the introduction of an electron-attractive branching group, just like the case of introducing an electron-repelling substituent. This has been taken as an indication of the predominance of themolecular integrality over the group characteristics. By means of the method of similar triangles between a homologous line for a linearseries and that for the corresponding forked compounds, the equivalent △Ns for a branching group may be calculated with accuracy. Based on the value of this equivalent, the substituentnature of the structural effect of the branching group has been inferred. The electronic absorption maxima for four series of the forked compounds have been cal-culated by means of the extended homologous equation for the corresponding linear compounds.With an appropriate correction for the positional effect of the substituent equivalent, the cal-culated wavelengths agree generally with experimental data within ± 7nm.展开更多
The development of solar-driven interfacial evaporation technology is pivotal for addressing global water scarcity.However,it is hindered by the difficulty in synergizing high photothermal conversion with low water ev...The development of solar-driven interfacial evaporation technology is pivotal for addressing global water scarcity.However,it is hindered by the difficulty in synergizing high photothermal conversion with low water evaporation enthalpy into a single material.Herein,we propose an iron-aldehyde-cooperative dynamic covalent anchoring strategy,successfully constructing a covalently locked,hydroxymethyl-functionalized PEDOT-PVA integrated dual-network hydrogel(MEPH).This strategy employs Fe3+to achieve the one-step in situ oxidative polymerization of hydroxymethyl EDOT while concurrently forming a physical hybrid network with PVA,which is subsequently reinforced by covalent cross-linking using glutaraldehyde.This design endows the MEPH with exceptional broadband light absorption(>99%),efficient water transport,and regulated water state within the hydrogel matrix,leading to a reduced evaporation enthalpy of 732 J·g^(−1).The resulting evaporator achieves an ultrahigh evaporation rate of 4.95 kg·m^(−2)·h^(−1)under 1-sun illumination,corresponding to an energy conversion efficiency exceeding 95%,while maintaining stable,salt-resistant operation in high-salinity environments.Outdoor experiments validate its outstanding practicality for seawater and wastewater purification,with the produced freshwater significantly promoting plant growth,highlighting its great potential in sustainable agricultural water cycles.This iron-aldehyde-cooperative dynamic covalent anchoring strategy provides an innovative design paradigm for a new generation of high-performance and robust solar evaporators.展开更多
The extraction of uranium from seawater via membrane adsorption is a promising strategy for ensuring a long-term supply of uranium and the sustainability of nuclear energy.However,this approach has been hindered by th...The extraction of uranium from seawater via membrane adsorption is a promising strategy for ensuring a long-term supply of uranium and the sustainability of nuclear energy.However,this approach has been hindered by the longstanding challenge of identifying sustainable membrane materials.In response,we propose a prototypal hybridization strategy to design a novel series of aminated conjugated microporous polymer(CMPN)@collagen fiber membrane(COLM).These sustainable and low-cost membrane materials allow a rapid and high-affinity kinetic to capture 90%of the uranium in just 30 min from 50 ppm with a high selectivity of Kd>105 mL·g^(−1).They also afford a robustly reusable adsorption capacity as high as 345 mg·g^(−1)that could harvest 1.61 mg·g^(−1)of uranium in a short 7-day real marine engineering in Fujian Province,even though suffered from very low uranium concentration of 3.29μg·L^(−1)and tough influence of salts such as 10.77 g·L^(−1)of Na^(+),1.75μg·L^(−1)of VO_(3)^(−)etc.in the rough seas.The structural evidence from both experimental and theoretical studies confirmed the formation of favorable chelating motifs from the amino group on CMPN-COLM,and the intensification by the synergistic effect from the size-sieving action of CMPN and the capillary inflow effect of COLM.展开更多
Conjugated microporous polymers(CMPs)are a unique class of organic porous materials characterized byπ-conjugated structures and permanent micropores,distinguishing them from non-porous polymers and conventionalπ-con...Conjugated microporous polymers(CMPs)are a unique class of organic porous materials characterized byπ-conjugated structures and permanent micropores,distinguishing them from non-porous polymers and conventionalπ-conjugated polymers.CMPs offer extensive versatility in synthetic approaches,enabling the synthesis of cross-linked and mesoporous structures.Advances in chemical processes,structural design,and synthesis methodologies have been developed,resulting in a diverse range of CMPs with unique configurations and properties,contributing to the fast expansion of the field.CMPs are particularly notable for their ability to enable the competitive utilization ofπ-conjugated structures within mesoporous configurations,making them valuable for investigations across various domains.They have shown considerable promise in addressing fuel and environmental challenges,demonstrated by their exceptional performance in applications such as vapor adsorption,heterogeneous catalysis,light emission,light harvesting,and energy generation.This review examines the chemical engineering principles underlying CMPs,including synthesis approaches,systemic research advancements,multifunctional investigations boundaries,potential applications,and progress in synthesis,dimensionality,and morphology studies.Specifically,it offers a comparative analysis of CMPs and linear polymeric materials,aiding in the development of functional polymers.Furthermore,this review explores the primary fundamental limitations of CMPs in fuel-related domains and discusses alternative strategies,including novel synthesis methods incorporating interactions and morphologies,to address these challenges.Ultimately,this assessment aims to provide a valuable and inspiring resource for professionals in the field of fuel management,guiding future research and development efforts.展开更多
The scalable fabrication of stretchable conjugated polymer films via solution printing is essential for their practical application in largearea wearable electronics.However,the printed conjugated polymer films typica...The scalable fabrication of stretchable conjugated polymer films via solution printing is essential for their practical application in largearea wearable electronics.However,the printed conjugated polymer films typically exhibit high crystallinity,limiting their mechanical deformability.Herein,we propose a plasticizer-assisted printing strategy to simultaneously enhance the stretchability and electrical performance of films based on the conjugated polymer poly(3-(5-(5-methylselenophen-2-yl)thiophen-2-yl)-6-(5-methylthiophen-2-yl)-2,5-bis(4-octyltetradecyl)-2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-dione)(P(TDPP-Se)).The incorporation of a plasticizer trioctyl trimellitate(TOTM)promotes P(TDPP-Se)aggregation in initial solution,facilitates chain alignment under flow field,and shorten solidification process,thereby restricting randomly polymer crystallization.Consequently,a low-crystallinity film with favorable edge-on orientation,strong chain alignment and improved chain dynamics is realized,which effectively alleviates crystallites fragmentation and crack propagation under large strain.The TOTM-plasticized film exhibits approximately 2-fold improvements in fracture strain and charge mobility,along with superior mobility retention under 100%strain in comparison to the neat film.This study provides a feasible approach for microstructure control in printed stretchable conjugated polymer film.展开更多
Pure organic room-temperature phosphorescent(RTP)polymers possess good processability and flexibility over small molecular crystals.However,most of RTP polymers reported so far are based on non-conjugated polymers,and...Pure organic room-temperature phosphorescent(RTP)polymers possess good processability and flexibility over small molecular crystals.However,most of RTP polymers reported so far are based on non-conjugated polymers,and achieving efficient phosphorescent emission in RTP conjugated polymers(CPs)remains a significant challenge.Herein,we developed two RTP CPs(P(PSe ZPh-p-Ph)and P(PSe ZPh-m-Ph))by linking the phenoselenazine units with the para-and meta-phenylene units,respectively,to form the conjugated main chains.The phenylene linker with different lingking mode manipulates the effictiveπ-conjugation of the polymer backbones.Comparing with the para-linked P(PSe ZPh-pPh),meta-linked P(PSe ZPh-m-Ph)exhibit the decreased effectiveπ-conjugation and the enhanced contribution of selenium atoms to the frontier orbitals,leading to the larger spin-orbit coupling(SOC)constants and the accelerated phosphorescence radiative decay process.The P(PSe ZPhm-Ph)achieves a phosphorescence quantum yield of 21.4%in doped polystyrene films,which is among the highest efficiencies reported to date for pure organic RTP CPs.These CPs are applied to construct phosphorescent film sensors for oxygen detection with the high quenching constants(K_(sv))up to 14.80 kPa^(-1)and low detection of limit of 0.84 ppm,demostrating the potential for application in oxygen film sensors.展开更多
The development of synthetic hybrid biological systems integrating photosynthetic organisms with organic-abiotic functional materials holds significant promise for enhancing photosynthetic processes.The artificial reg...The development of synthetic hybrid biological systems integrating photosynthetic organisms with organic-abiotic functional materials holds significant promise for enhancing photosynthetic processes.The artificial regulation of the state transition between photosystem I(PSI)and photosystem II(PSII)represents a strategic and promising approach for improving the efficiency of natural photosynthesis.In this study,we demonstrate that poly(benzimidazolium-phenylthiophene)(CP4)featuring a flexible cationic backbone exhibits superior ultraviolet light-harvesting capability.The polymer CP4 enhanced PSI activity in Chlorella pyrenoidosa(C.pyrenoidosa),subsequently promoting PSII activity and augmenting overall photosynthetic performance.During light-dependent reactions,CP4 significantly accelerated photosynthetic electron transfer,resulting in a 330%increase in the production of oxygen and 93%and 96%increases in the ATP and NADPH contents,respectively.In the context of dark reactions,CP4 facilitated the conversion and utilization of light energy,leading to a 6%increase in both carbohydrate and protein contents.These findings indicate that synthetic light-harvesting polymer materials exhibit considerable application potential in the field of biomass production through enhancement of natural photosynthetic efficiency.展开更多
The development of non-corrosive and efficient anode interlayers(AILs)is pivotal for advancing highperformance organic optoelectronic devices.Conventional materials such as PEDOT:PSS,though widely adopted,suffer from ...The development of non-corrosive and efficient anode interlayers(AILs)is pivotal for advancing highperformance organic optoelectronic devices.Conventional materials such as PEDOT:PSS,though widely adopted,suffer from significant limitations including acidity,corrosion,and poor device stability.Herein,we propose a novel molecular design strategy by introducing p-πconjugation into a p Hneutral conjugated polyelectrolyte(CPE)(PIDT-T)to simultaneously enhance work function(WF)and electrical conductivity.Through doping with polyoxometalate(POM),the optimized PIDT-T:POM achieves a high WF of 4.85 e V,conductivity of 7.25×10^(-3)S cm^(-1),and>98%optical transmittance.In organic solar cells(OSCs),PIDT-T:POM delivers a power conversion efficiency(PCE)of 19.04%,outperforming PEDOT:PSS-based counterparts(18.52%)and representing one of the highest PCEs reported for devices utilizing non-acidic AILs.Moreover,organic light-emitting diodes(OLEDs)incorporating PIDTT:POM exhibit a remarkable reduction in turn-on voltage(from 5.8 to 3.0 V)and enhanced luminous efficiency,demonstrating its dual functionality for both OSCs and OLEDs.These findings establish p-πconjugated polyelectrolytes as a powerful molecular platform for next-generation,high-efficiency,and corrosion-free organic optoelectronic applications.展开更多
Breast cancer is a heterogeneous disease stratified by hormone receptors(HRs)and human epidermal growth factor receptor 2(HER2)status and each subtype has divergent therapeutic needs.Despite the current therapeutic ad...Breast cancer is a heterogeneous disease stratified by hormone receptors(HRs)and human epidermal growth factor receptor 2(HER2)status and each subtype has divergent therapeutic needs.Despite the current therapeutic advances,resistance to standard therapies remains pervasive,underscoring the demand for novel strategies.Antibody-drug conjugates(ADCs)offer a powerful strategy by combining tumor-specific antibodies to potent cytotoxins,enabling selective delivery and minimizing off-target toxicity1.TROP2,a transmembrane glycoprotein broadly overexpressed in breast cancer,has emerged as a promising ADC target.The approval of datopotamab deruxtecan(Dato-DXd)with sacituzumab govitecan(SG)and the incorporation of these ADCs into the National Comprehensive Cancer Network(NCCN)guidelines(v2.2025)highlight the fast penetration of TROP2 ADCs into clinical practice2.This editorial provides timely insights into optimizing TROP2-targeted strategies to improve outcomes across breast cancer subtypes.展开更多
基金the Wellcome Trust,BBSRC,and the National Natural Science Foundation of China(81802065,102908/Z/13/Z).
文摘Bacteria can evolve rapidly by acquiring new traits such as virulence,metabolic properties,and most importantly,antimicrobial resistance,through horizontal gene transfer(HGT).Multidrug resistance in bacteria,especially in Gram-negative organisms,has become a global public health threat often through the spread of mobile genetic elements.Conjugation represents a major form of HGT and involves the transfer of DNA from a donor bacterium to a recipient by direct contact.Conjugative plasmids,a major vehicle for the dissemination of antimicrobial resistance,are selfish elements capable of mediating their own transmission through conjugation.To spread to and survive in a new bacterial host,conjugative plasmids have evolved mechanisms to circumvent both host defense systems and compete with co-resident plasmids.Such mechanisms have mostly been studied in model plasmids such as the F plasmid,rather than in conjugative plasmids that confer antimicrobial resistance(AMR)in important human pathogens.A better understanding of these mechanisms is crucial for predicting the flow of antimicrobial resistance-conferring conjugative plasmids among bacterial populations and guiding the rational design of strategies to halt the spread of antimicrobial resistance.Here,we review mechanisms employed by conjugative plasmids that promote their transmission and establishment in Gram-negative bacteria,by following the life cycle of conjugative plasmids.
基金Supported by the National Basic Research Program of China(973Program)(No.2009CB118703)
文摘Flavobacterium columnare, the etiological agent of colunmaris disease, is one of the most important and widespread bacterial pathogens of freshwater fish. In this study, we constructed two artificial selectable markers (chloramphenicol and spectinomycin resistance) for gene transfer in F. columnare. These two new artificial selectable markers, which were created by placing the chloramphenicol or spectinomycin resistance gene under the control of the native acs regulatory region of F. columnare, were functional in both F. columnare and Escherichia coli. The integrative/conjugative plasmids constructed by using these markers were introduced into F. columnare G4 via electroporation or conjugation. The integrated plasmid DNA was confirmed by Southern blotting and PCR analysis. These two markers can be employed in future investigations into gene deletion and the pathogenicity of virulence factors in F. columnare.
基金supported by the earmarked fund for China Agriculture Research System(CARS-42-17)the Sichuan Veterinary Medicine and Drug Innovation Group of China Agricultural Research System(SCCXTD-2021-18)。
文摘Pasteurella multocida(PM)has been infecting a variety of hosts for a long time,causing sustained economic losses worldwide;however,there have been limited studies on its extensive adaptability(Aktories et al.2012).Analysis of strains data collected in our laboratory revealed that PM typically acquires foreign genes through transformation and conjugation,rather than transformation and fusion.Integrative and conjugative elements(ICEs)are a crucial mechanism that leads to abrupt changes in niche preferences and enhances environmental adaptability for bacteria,with their number far exceeding the number of plasmids and phages(Wozniak and Waldor 2010;Johnson and Grossman 2015;Botelho and Schulenburg 2021).Previous research has shown that the European bovine-sourced strain Pm36950 contains the experimentally transferable resistant ICEPmu1,which could integrate into the host chromosome or forming a circular intermediate(Michael et al.2012).Additionally,a few studies have suggested that PM strains isolated from European bovine and Asian swine might contain ICEs,but these claims lack experimental verification(Klima et al.2014;Moustafa et al.2015;Kadlec et al.2017;Peng et al.2017;Beker et al.2018;Schink et al.2022).Currently,there is no data available on ICE-carrying PM strains isolated from hosts outside of European cattle or Chinses swine.This letter presents a report on a novel ICE identified in the hypervirulent and multidrug-resistant PM HN141014 strain isolated from Chinese duck.The ICE was specifically analyzed for its resistance genes,transferable capacity and host diversity.
文摘Antimicrobial susceptibility test was performed on 57 clinical isolates of P. aeruginosa and 36 clinical isolates of Acinetobacter with 11 antimicrobial agents including getamicin, amikacin, ciprofloxacin, ofloxacin, fleroxacin, piperacillin, cefotaxime, cefoperazone/sulbactam, ceftazidime, cefoperazone and doxycycline. Transferable drug resistance plasmid carrying rates of these clinical isolates were also studied. On the basis of the in vitro activities, 52.63%(30/57) of the isolated strains of P. aeruginosa were susceptible to antimicrobial agents selected (except doxycycline), 41.67%(15/36) of the isolated strains of Acinetobacter were susceptible to 11 antimicrobial agents. The sensitivity rate of P.aeruginosa and Acinetobacter to antimicrobial agents selected was 70% or greater to all except doxycycline. Furthermore, the sensitivity rate of P.aeruginosa to amikacin ciprofloxacin, ceftazidime, cefoperazone, cefoperazone/sulbactam, and that of Acinetobacter to cefoperazone/sulbactam, amikacin was more than 90%,among them amikacin, cefoperazone/sulbactam being the most effective. Plasmid analysis showed that 15.79%(9/57) P.aeruginosa strains and 13.89%(5/36) Acinetobacter strains carried plasmid. Conjugative plasmid carrying rates of P. aeruginosa strains and Acinetobacter strains were 7.02%(4/57), 13.89%(5/36), respectively. Conjugative plasmid didn′t play an important role in the formation and dissemination of drug resistance of P. aeruginosa and Acinetobacter.
基金This work was supported by the National Natural Science Foundation of China(31972521)the Fujian Agriculture and Forest University Program for Distinguished Young Scholar(No.XJQ2017001).
文摘The global dissemination of antibiotic resistance genes(ARGs),especially via plasmid-mediated horizontal transfer,is becoming a pervasive health threat.While our previous study found that herbicides can accelerate the horizontal gene transfer(HGT)of ARGs in soil bacteria,the underlying mechanisms by which herbicides promote the HGT of ARGs across and within bacterial genera are still unclear.Here,the underlying mechanism associ-ated with herbicide-promoted HGT was analyzed by detecting intracellular reactive oxygen species(ROS)production,extracellular polymeric substance composition,cell membrane integrity and proton motive force combined with genome-wide RNA sequencing.Exposure to herbicides induced a series of the above bacterial responses to promote HGT except for the ROS response,including compact cell-to-cell contact by enhancing pilus-encoded gene expression and decreasing cell surface charge,increasing cell membrane permeability,and enhancing the proton motive force,providing additional power for DNA uptake.This study provides a mechanistic understanding of the risk of bacterial resistance spread promoted by herbicides,which elucidates a new perspective on nonantibiotic agrochemical acceleration of the HGT of ARGs.
基金support of the National Natural Science Foundation of China(grant no.22271151)the Natural Science Foundation of Jiangsu Province(grant no.BK20211534)the US National Science Foundation(grant no.CHE-2154593)。
文摘An unmet challenge in radical relay difunctionalization of alkenes is the incorporation of two discrete transient radicals in a regiocontrolled manner under transition-metal-free conditions.Current protocols typically rely on persistent radicals or organometallic surrogates to trap radical adducts,thereby suppressing the undesired reactions but limiting the diversity.The direct use of two transient radicals remains synthetically elusive.We present a visible-light photoredox catalyzed alkene dialkylation strategy via a kinetically guided conjugative radical–radical coupling.This transition-metal-free approach enables two direct C(sp^(3))–C(sp^(3))bond formations across the C=C double bond using alkyl and allyl or benzyl radicals.Mechanistic investigations reveal the radical nature of the process.The success of this approach hinges on kinetically controlled radical addition to alkene substrates and the steric protection of the resulting radical adducts.This mild and functional-group-tolerant reaction exhibits broad substrate scope and tolerates structurally complex substrates,highlighting its potential for late-stage functionalization.
基金supported in part by the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(32121004)Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(2019BT02N054)+4 种基金Laboratory of Lingnan Modern Agriculture Project(NT2021006)Guangdong Major Project of Basic and Applied Basic Research(grant 2020B0301030007)Innovation Team Project of Guangdong University(2019KCXTD001),the 111 Project(grant D20008)Natural Science Foundation of Shandong Province of China(ZR2022MC001)the Scientific and Technological Projects of Qingdao(19‐6‐1‐94‐nsh).
文摘The co-occurrence of plasmid-mediated multidrug resistance and hypervirulence in epidemic carbapenem-resistant Klebsiella pneumoniae has emerged as a global public health issue.In this study,an ST23 carbapenem-resistant hyper-virulent K.pneumoniae(CR-HvKP)strain VH1-2 was identified from cucumber in China and harbored a novel hybrid plasmid pVH1-2-VIR.The plasmid pVH1-2-VIR carrying both virulence and multidrug-resistance(MDR)genes was likely generated through the recombination of a virulence plasmid and an IncFIIK conjugative MDR plasmid in clinical ST2318622 isolated from a sputum sample.The plasmid pVH1-2-VIR exhibited the capacity for transfer to the clinical ST11 carbapenem-resistant K.pneumoniae(CRKP)strain via conjugation assay.Acquisition of pVH1-2-VIR plasmid directly converted a CRKP into CR-HvKP strain characterized by hypermucoviscosity,heightened virulence for Galleria mellonella larvae,and increased colonization ability in the mouse intestine.The emergence of such a hybrid plasmid may expedite the spread of CR-HvKP strains,posing a significant risk to human health.
文摘The longitudinal π-extension of carbon nanohoops is one of the most effective bottom-up synthetic strategies toward carbon nanotubes(CNTs).Herein,the precise synthesis of a multi-substituted carbon nanohoop([12]CPP-8PBPy)based on cycloparaphenylenes(CPPs)grafted with eight pyrene-functionalized units was reported.This structurally well-defined nanohoop not only acts as a segment of armchair-type CNTs but also achieves enhanced longitudinal π-extension.The structure of[12]CPP-8PBPy was confirmed by high-resolution mass spectrometry(HRMS)and nuclear magnetic resonance(NMR).The photophysical properties were studied by UV/Vis and photoluminescence spectroscopy.The potential applications of[12]CPP-8PBPy in electron-transport devices were further investigated.
文摘I. INTRODUCTIONIn the preceding paper we have reported that in a forked conjugative thienylpolyenic system with two electron-attracting groups at one end, the structural
基金Project supported by the National Natural Science Foundation of China.
文摘In this paper, the following carbonyl-imino bridged compounds and related analogs havebeen synthesized:X= C1, m = 0); and the structural effect of the carbonyl-imino bridges has been studied by means of the UV and other properties of the compounds. A new conception of conjugative segment is put forward. The structural bases for each of the three π-π* bands of (C) are ascertained and verified by modification on structure of segments, such as eliminating, merging, lengthening or shortening of segments. It is demonstrated that both bridges -CO-and -NH- can block the conjugated polarization of the whole molecule so as to form three segments S, M and L of which the λmax each exhibits relative independence. The electronic absorption peaks resulting from different segments can be readily recognized and the existence of each segment can be ascertained. This may provide a new way for structural analysis of bridged compounds.
基金the Project of China-Japan Joint International Laboratory of Advanced Drug Delivery System Research and Translation of Liaoning Province(No.2024JH2/102100007)the open fund of National Key Laboratory of Advanced DrugFormulations for Overcoming Delivery Barriers(No.2024-KFB-003)+1 种基金the National Natural Science Foundation of China(No.82104109)Scientific Research Project of Liaoning Department of Education(No.LJ212410163045).
文摘Cancer is the second leading cause of death globally.Its treatment remains a major challenge due to the disease's complexity,heterogeneity,and adaptive nature.Among the array of available treatments,targeted therapy emerges as a paramount approach to address this substantial unmet clinical need,owing to its precise tumor targeting capabilities and potential for mitigating tumor progression risks.Drug conjugates are in high demand for targeted therapy due to their unique ligand specificity and potent cytotoxicity,thereby significantly enhancing therapeutic efficacy and reducing the incidence of adverse effects.Therefore,as a burgeoning field in biomedical research,it is timely to outline the latest advances in drug conjugates-driven cancer treatment.Herein,we aim to present the emerging breakthroughs in this exciting field at the intersection of target ligands,linkers,payloads,and cancer treatments.This review focuses on several drug conjugates-related strategies,including antibody-drug conjugates(ADCs),peptide-drug conjugates(PDCs),small molecule-drug conjugates(SMDCs),aptamer-drug conjugates(ApDCs)and radionuclide-drug conjugates(RDCs).Finally,we discuss the fundamentals behind drug conjugate-based anticancer therapeutics,along with their inherent advantages and associated challenges,as well as recent research advances.
文摘Five homologous series of bifurcate systems of aliphatic and aromatic polyenic cyano and carboxylic compounds have been prepared and studied. The electronic absorption spectra forthe series and the NMR chemical shifts for the methyl-, methylene- and beta-protons havebeen found to conform very well to the rule of homologous linearity. The mass spectra forthe α-cyano polyenic ester series show strong peaks for the fragments of M-COOEt but noneof M-CN, indicating that the CN group seems to be in stronger conjugation with the poly-enic chain than the COOEt group does. In all the forked series studided, a red shift in electronic spectra is brought about upon the introduction of an electron-attractive branching group, just like the case of introducing an electron-repelling substituent. This has been taken as an indication of the predominance of themolecular integrality over the group characteristics. By means of the method of similar triangles between a homologous line for a linearseries and that for the corresponding forked compounds, the equivalent △Ns for a branching group may be calculated with accuracy. Based on the value of this equivalent, the substituentnature of the structural effect of the branching group has been inferred. The electronic absorption maxima for four series of the forked compounds have been cal-culated by means of the extended homologous equation for the corresponding linear compounds.With an appropriate correction for the positional effect of the substituent equivalent, the cal-culated wavelengths agree generally with experimental data within ± 7nm.
基金financially supported by the Natural Science Foundation of Jiangxi Province(No.20232ACB204002)the Jiangxi Provincial Key Laboratory of Flexible Electronics(No.20242BCC32010).
文摘The development of solar-driven interfacial evaporation technology is pivotal for addressing global water scarcity.However,it is hindered by the difficulty in synergizing high photothermal conversion with low water evaporation enthalpy into a single material.Herein,we propose an iron-aldehyde-cooperative dynamic covalent anchoring strategy,successfully constructing a covalently locked,hydroxymethyl-functionalized PEDOT-PVA integrated dual-network hydrogel(MEPH).This strategy employs Fe3+to achieve the one-step in situ oxidative polymerization of hydroxymethyl EDOT while concurrently forming a physical hybrid network with PVA,which is subsequently reinforced by covalent cross-linking using glutaraldehyde.This design endows the MEPH with exceptional broadband light absorption(>99%),efficient water transport,and regulated water state within the hydrogel matrix,leading to a reduced evaporation enthalpy of 732 J·g^(−1).The resulting evaporator achieves an ultrahigh evaporation rate of 4.95 kg·m^(−2)·h^(−1)under 1-sun illumination,corresponding to an energy conversion efficiency exceeding 95%,while maintaining stable,salt-resistant operation in high-salinity environments.Outdoor experiments validate its outstanding practicality for seawater and wastewater purification,with the produced freshwater significantly promoting plant growth,highlighting its great potential in sustainable agricultural water cycles.This iron-aldehyde-cooperative dynamic covalent anchoring strategy provides an innovative design paradigm for a new generation of high-performance and robust solar evaporators.
基金supported by National Natural Science Foundation of China(Grant No.22378066,22108040)Collaboration&Innovation Platform Project of National Independent Innovation Demonstration Zone(Fuzhou,Xiamen&Quanzhou)(Project No:3502ZCQXT2023004).
文摘The extraction of uranium from seawater via membrane adsorption is a promising strategy for ensuring a long-term supply of uranium and the sustainability of nuclear energy.However,this approach has been hindered by the longstanding challenge of identifying sustainable membrane materials.In response,we propose a prototypal hybridization strategy to design a novel series of aminated conjugated microporous polymer(CMPN)@collagen fiber membrane(COLM).These sustainable and low-cost membrane materials allow a rapid and high-affinity kinetic to capture 90%of the uranium in just 30 min from 50 ppm with a high selectivity of Kd>105 mL·g^(−1).They also afford a robustly reusable adsorption capacity as high as 345 mg·g^(−1)that could harvest 1.61 mg·g^(−1)of uranium in a short 7-day real marine engineering in Fujian Province,even though suffered from very low uranium concentration of 3.29μg·L^(−1)and tough influence of salts such as 10.77 g·L^(−1)of Na^(+),1.75μg·L^(−1)of VO_(3)^(−)etc.in the rough seas.The structural evidence from both experimental and theoretical studies confirmed the formation of favorable chelating motifs from the amino group on CMPN-COLM,and the intensification by the synergistic effect from the size-sieving action of CMPN and the capillary inflow effect of COLM.
基金supported by the King Khalid University,Abha,Saudi Arabiathe Deanship of Scientific Research at King Khalid University for funding this work through Large Groups Project under grant number(R.G.P.2/335/46)the Guangdong Office of Research Projects at the Provincial University(No.2024KCXTD064)。
文摘Conjugated microporous polymers(CMPs)are a unique class of organic porous materials characterized byπ-conjugated structures and permanent micropores,distinguishing them from non-porous polymers and conventionalπ-conjugated polymers.CMPs offer extensive versatility in synthetic approaches,enabling the synthesis of cross-linked and mesoporous structures.Advances in chemical processes,structural design,and synthesis methodologies have been developed,resulting in a diverse range of CMPs with unique configurations and properties,contributing to the fast expansion of the field.CMPs are particularly notable for their ability to enable the competitive utilization ofπ-conjugated structures within mesoporous configurations,making them valuable for investigations across various domains.They have shown considerable promise in addressing fuel and environmental challenges,demonstrated by their exceptional performance in applications such as vapor adsorption,heterogeneous catalysis,light emission,light harvesting,and energy generation.This review examines the chemical engineering principles underlying CMPs,including synthesis approaches,systemic research advancements,multifunctional investigations boundaries,potential applications,and progress in synthesis,dimensionality,and morphology studies.Specifically,it offers a comparative analysis of CMPs and linear polymeric materials,aiding in the development of functional polymers.Furthermore,this review explores the primary fundamental limitations of CMPs in fuel-related domains and discusses alternative strategies,including novel synthesis methods incorporating interactions and morphologies,to address these challenges.Ultimately,this assessment aims to provide a valuable and inspiring resource for professionals in the field of fuel management,guiding future research and development efforts.
基金supported by the National Natural Science Foundation of China(No.52433009)the Fundamental Research Funds for the Central Universities(No.GK202501005)the State Key Laboratory of Polymer Science and Technology(No.PST-KF2025-07)。
文摘The scalable fabrication of stretchable conjugated polymer films via solution printing is essential for their practical application in largearea wearable electronics.However,the printed conjugated polymer films typically exhibit high crystallinity,limiting their mechanical deformability.Herein,we propose a plasticizer-assisted printing strategy to simultaneously enhance the stretchability and electrical performance of films based on the conjugated polymer poly(3-(5-(5-methylselenophen-2-yl)thiophen-2-yl)-6-(5-methylthiophen-2-yl)-2,5-bis(4-octyltetradecyl)-2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-dione)(P(TDPP-Se)).The incorporation of a plasticizer trioctyl trimellitate(TOTM)promotes P(TDPP-Se)aggregation in initial solution,facilitates chain alignment under flow field,and shorten solidification process,thereby restricting randomly polymer crystallization.Consequently,a low-crystallinity film with favorable edge-on orientation,strong chain alignment and improved chain dynamics is realized,which effectively alleviates crystallites fragmentation and crack propagation under large strain.The TOTM-plasticized film exhibits approximately 2-fold improvements in fracture strain and charge mobility,along with superior mobility retention under 100%strain in comparison to the neat film.This study provides a feasible approach for microstructure control in printed stretchable conjugated polymer film.
基金supported by the National Natural Science Foundation of China(Nos.22275182,22075272,51973211,51833009,21674111 and 52261135541)the Ministry of Science and Technology of the People’s Republic of China(the National Key R&D Program of China,No.2022YFB4200400)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB0520102)。
文摘Pure organic room-temperature phosphorescent(RTP)polymers possess good processability and flexibility over small molecular crystals.However,most of RTP polymers reported so far are based on non-conjugated polymers,and achieving efficient phosphorescent emission in RTP conjugated polymers(CPs)remains a significant challenge.Herein,we developed two RTP CPs(P(PSe ZPh-p-Ph)and P(PSe ZPh-m-Ph))by linking the phenoselenazine units with the para-and meta-phenylene units,respectively,to form the conjugated main chains.The phenylene linker with different lingking mode manipulates the effictiveπ-conjugation of the polymer backbones.Comparing with the para-linked P(PSe ZPh-pPh),meta-linked P(PSe ZPh-m-Ph)exhibit the decreased effectiveπ-conjugation and the enhanced contribution of selenium atoms to the frontier orbitals,leading to the larger spin-orbit coupling(SOC)constants and the accelerated phosphorescence radiative decay process.The P(PSe ZPhm-Ph)achieves a phosphorescence quantum yield of 21.4%in doped polystyrene films,which is among the highest efficiencies reported to date for pure organic RTP CPs.These CPs are applied to construct phosphorescent film sensors for oxygen detection with the high quenching constants(K_(sv))up to 14.80 kPa^(-1)and low detection of limit of 0.84 ppm,demostrating the potential for application in oxygen film sensors.
基金supported by the National Key R&D Program of China(Nos.2023YFC3404200,2023YFC34042012023YFC3404202)+1 种基金the National Natural Science Foundation of China(No.22575253)the Beijing Natural Science Foundation(No.Z220025)。
文摘The development of synthetic hybrid biological systems integrating photosynthetic organisms with organic-abiotic functional materials holds significant promise for enhancing photosynthetic processes.The artificial regulation of the state transition between photosystem I(PSI)and photosystem II(PSII)represents a strategic and promising approach for improving the efficiency of natural photosynthesis.In this study,we demonstrate that poly(benzimidazolium-phenylthiophene)(CP4)featuring a flexible cationic backbone exhibits superior ultraviolet light-harvesting capability.The polymer CP4 enhanced PSI activity in Chlorella pyrenoidosa(C.pyrenoidosa),subsequently promoting PSII activity and augmenting overall photosynthetic performance.During light-dependent reactions,CP4 significantly accelerated photosynthetic electron transfer,resulting in a 330%increase in the production of oxygen and 93%and 96%increases in the ATP and NADPH contents,respectively.In the context of dark reactions,CP4 facilitated the conversion and utilization of light energy,leading to a 6%increase in both carbohydrate and protein contents.These findings indicate that synthetic light-harvesting polymer materials exhibit considerable application potential in the field of biomass production through enhancement of natural photosynthetic efficiency.
基金the financial support from the Beijing Municipal Science&Technology Commission(2242013)。
文摘The development of non-corrosive and efficient anode interlayers(AILs)is pivotal for advancing highperformance organic optoelectronic devices.Conventional materials such as PEDOT:PSS,though widely adopted,suffer from significant limitations including acidity,corrosion,and poor device stability.Herein,we propose a novel molecular design strategy by introducing p-πconjugation into a p Hneutral conjugated polyelectrolyte(CPE)(PIDT-T)to simultaneously enhance work function(WF)and electrical conductivity.Through doping with polyoxometalate(POM),the optimized PIDT-T:POM achieves a high WF of 4.85 e V,conductivity of 7.25×10^(-3)S cm^(-1),and>98%optical transmittance.In organic solar cells(OSCs),PIDT-T:POM delivers a power conversion efficiency(PCE)of 19.04%,outperforming PEDOT:PSS-based counterparts(18.52%)and representing one of the highest PCEs reported for devices utilizing non-acidic AILs.Moreover,organic light-emitting diodes(OLEDs)incorporating PIDTT:POM exhibit a remarkable reduction in turn-on voltage(from 5.8 to 3.0 V)and enhanced luminous efficiency,demonstrating its dual functionality for both OSCs and OLEDs.These findings establish p-πconjugated polyelectrolytes as a powerful molecular platform for next-generation,high-efficiency,and corrosion-free organic optoelectronic applications.
文摘Breast cancer is a heterogeneous disease stratified by hormone receptors(HRs)and human epidermal growth factor receptor 2(HER2)status and each subtype has divergent therapeutic needs.Despite the current therapeutic advances,resistance to standard therapies remains pervasive,underscoring the demand for novel strategies.Antibody-drug conjugates(ADCs)offer a powerful strategy by combining tumor-specific antibodies to potent cytotoxins,enabling selective delivery and minimizing off-target toxicity1.TROP2,a transmembrane glycoprotein broadly overexpressed in breast cancer,has emerged as a promising ADC target.The approval of datopotamab deruxtecan(Dato-DXd)with sacituzumab govitecan(SG)and the incorporation of these ADCs into the National Comprehensive Cancer Network(NCCN)guidelines(v2.2025)highlight the fast penetration of TROP2 ADCs into clinical practice2.This editorial provides timely insights into optimizing TROP2-targeted strategies to improve outcomes across breast cancer subtypes.