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
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
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
HighlightsA novel conjugative plasmid pHJ90-cfr carrying the multiresistance gene cfr was characterized in Proteus vulgaris.A new IS5-family member,ISPmi4,was identified for the first time.Both plasmids and ICEs were ...HighlightsA novel conjugative plasmid pHJ90-cfr carrying the multiresistance gene cfr was characterized in Proteus vulgaris.A new IS5-family member,ISPmi4,was identified for the first time.Both plasmids and ICEs were vital mobile genetic elements for horizontal transmission of cfr gene in Proteus species.展开更多
The fluorescence imaging (FLI) in the second near-infrared window (NIR-II, 1000–1700nm) has attracted considerable attention in the past decade. In contrast to conventional NIR-I window excitation (808nm/980nm), FLI ...The fluorescence imaging (FLI) in the second near-infrared window (NIR-II, 1000–1700nm) has attracted considerable attention in the past decade. In contrast to conventional NIR-I window excitation (808nm/980nm), FLI with NIR-II window excitation (1064nm/other wavelength beyond 1000nm) can afford deeper tissue penetration depth with high clarity due to the merits of suppressed photon scattering and diminished autofluorescence. In this review, we have summarized NIR-II window excitable/emissive organic/polymeric fluorophores recently developed. The characteristics of these fluorophores such as chemical structures and photophysical properties have also been critically discussed. Furthermore, the latest development of noninvasive in vivo FLI with NIR-II excitation was highlighted. The ideal imaging results emphasized the importance of NIR-II excitation of these fluorophores in enabling deep tissue penetration and high-resolution imaging. Finally, a perspective on the challenges and prospects of NIR-II excitable/emissive organic/polymeric fluorophores was also discussed. We expected this review will be served as a source of inspiration for researchers, stimulating the creation of novel NIR-II excitable fluorophores and fostering the development of bioimaging applications.展开更多
The light-driven CO_(2)reduction reaction(CO_(2)RR)to CO is a very effective way to address global warming.To avoid competition with water photolysis,metal-free gas-solid CO_(2)RR catalysts should be investigated.Cova...The light-driven CO_(2)reduction reaction(CO_(2)RR)to CO is a very effective way to address global warming.To avoid competition with water photolysis,metal-free gas-solid CO_(2)RR catalysts should be investigated.Covalent organic frameworks(COFs)offer a promising approach for CO_(2)transformation but lack high efficiency and selectivity in the absence of metals.Here,we have incorporated a pyridine nitrogen component into the imine-COF conjugated structure(Tp Pym).This innovative system has set a record of producing a CO yield of 1565μmol g^(-1)within 6 h.The soft X-ray absorption fine structure measurement proves that Tp Pym has both better conjugation and electron cloud enrichment.The electronic structure distribution delays the charge-carrier recombination,as evidenced by femtosecond transient absorption spectroscopy.The energy band diagram and theoretical calculation show that the conduction-band potential of Tp Pym is lower and the reduction reaction of CO_(2)to CO is more likely to occur.展开更多
Tactile perception plays a vital role for the human body and is also highly desired for smart prosthesis and advanced robots.Compared to active sensing devices,passive piezoelectric and triboelectric tactile sensors c...Tactile perception plays a vital role for the human body and is also highly desired for smart prosthesis and advanced robots.Compared to active sensing devices,passive piezoelectric and triboelectric tactile sensors consume less power,but lack the capability to resolve static stimuli.Here,we address this issue by utilizing the unique polarization chemistry of conjugated polymers for the first time and propose a new type of bioinspired,passive,and bio-friendly tactile sensors for resolving both static and dynamic stimuli.Specifically,to emulate the polarization process of natural sensory cells,conjugated polymers(including poly(3,4-ethylenedioxythiophen e):poly(styrenesulfonate),polyaniline,or polypyrrole)are controllably polarized into two opposite states to create artificial potential differences.The controllable and reversible polarization process of the conjugated polymers is fully in situ characterized.Then,a micro-structured ionic electrolyte is employed to imitate the natural ion channels and to encode external touch stimulations into the variation in potential difference outputs.Compared with the currently existing tactile sensing devices,the developed tactile sensors feature distinct characteristics including fully organic composition,high sensitivity(up to 773 mV N^(−1)),ultralow power consumption(nW),as well as superior bio-friendliness.As demonstrations,both single point tactile perception(surface texture perception and material property perception)and two-dimensional tactile recognitions(shape or profile perception)with high accuracy are successfully realized using self-defined machine learning algorithms.This tactile sensing concept innovation based on the polarization chemistry of conjugated polymers opens up a new path to create robotic tactile sensors and prosthetic electronic skins.展开更多
In this paper,we propose a three-term conjugate gradient method for solving unconstrained optimization problems based on the Hestenes-Stiefel(HS)conjugate gradient method and Polak-Ribiere-Polyak(PRP)conjugate gradien...In this paper,we propose a three-term conjugate gradient method for solving unconstrained optimization problems based on the Hestenes-Stiefel(HS)conjugate gradient method and Polak-Ribiere-Polyak(PRP)conjugate gradient method.Under the condition of standard Wolfe line search,the proposed search direction is the descent direction.For general nonlinear functions,the method is globally convergent.Finally,numerical results show that the proposed method is efficient.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
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
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 demand for enhanced optical properties in advanced fluorescence technologies has driven research into the structure-property relationship of fluorophores.In this paper,we use naphthalene fluorophores Na DC-Aze and...The demand for enhanced optical properties in advanced fluorescence technologies has driven research into the structure-property relationship of fluorophores.In this paper,we use naphthalene fluorophores Na DC-Aze and PhDO-Aze as a case study to emphasize the pivotal role of cross conjugation in tuning the optical structure-property relationship.Na DC-Aze and PhDO-Aze,formed by hybridizing two distinct conjugated systems in a single naphthalene molecule,exhibit spectral characteristics from both conjugated systems.Experimental data and theoretical calculations demonstrate the coexistence of two electron-delocalization systems in a cross-conjugation manner in both Na DC-Aze and PhDO-Aze.The cross-conjugation fluorophores exhibit high brightness,large Stokes shift,and a broad absorption wavelength range by combining distinct spectral properties from its parent fluorophores.These spectral properties will be advantageous for certain applications(i.e.,panchromatic absorption in organic solar cells,and fluorophores compatible with a wide range of excitation wavelengths).展开更多
Antibody-drug conjugates(ADCs)represent a promising approach in targeted cancer therapy,combining the tar-geted precision of antibodies with the potency of cytotoxic payloads to selectively target tumour cell whilst m...Antibody-drug conjugates(ADCs)represent a promising approach in targeted cancer therapy,combining the tar-geted precision of antibodies with the potency of cytotoxic payloads to selectively target tumour cell whilst min-imising off-target effects.This review provides a comprehensive analysis of ADCs,encompassing their structural components,mechanisms of action,and clinical applications.It also examines recent technological advancements,particularly in antibody engineering and linker design,aimed at enhancing therapeutic efficacy and safety.The current clinical landscape is outlined,highlighting approved ADCs and promising candidates in clinical trials,while also addressing key challenges such as stability,half-life,and systemic toxicity.This review is based on an extensive literature survey from major databases such as Scopus and Web of Science,with a focus on keywords like“antibody-drug conjugates”,“ADC advancements”,and“next-generation ADC technologies”.By integrating insights from both preclinical and clinical perspectives,we highlight the transformative potential of ADCs in advancing modern cancer therapy.展开更多
π-Conjugated donor-acceptor-donor-acceptor-donor(D-A-D-A-D)type pyrenoviologens(PyV^(2+)),with the 2,7 positions of pyrene serving as connection bridges,were synthesized through SN2 reactions.Specifically,pyrenoviolo...π-Conjugated donor-acceptor-donor-acceptor-donor(D-A-D-A-D)type pyrenoviologens(PyV^(2+)),with the 2,7 positions of pyrene serving as connection bridges,were synthesized through SN2 reactions.Specifically,pyrenoviologen 3c was modified with a methylnaphthalene group,while 3a and 3b were modified with methyl and benzyl groups,respectively,for comparison.These pyrenoviologens exhibit reversible redox properties and strong fluorescence emission.Electrochromic devices(ECDs)were prepared using pyrenoviologens as the active materials.Notably,naphthalene-containing pyrenoviologen 3c,with its DA-D-A-D conjugated structure,possesses more stable free radicals,enabling it to maintain the radical color for a longer duration after power loss.A series of color-changing devices were successfully assembled.Due to the strong fluorescence of pyrenoviologens and the unique electron transfer effect between them and picric acid(PA),a sensor film with good selectivity and high sensitivity for PA in aqueous solution was prepared using pyrenoviologens as the fluorescent probe.Specifically,3c exhibited the highest sensitivity to PA due to its lowest energy gap.The introduction of the D-A-D-A-D structure is a strategic approach to enhancing photoelectric performance and broadening the application of viologens.展开更多
Sonodynamic therapy(SDT)is garnering considerable attention as a promising treatment for deep-seated tumors because of its strong tissue penetration ability,non-invasiveness,and controllability.However,the SDT efficie...Sonodynamic therapy(SDT)is garnering considerable attention as a promising treatment for deep-seated tumors because of its strong tissue penetration ability,non-invasiveness,and controllability.However,the SDT efficiency of traditional sonosensitizers including porphyrins and their derivatives are limited due to their poor water dissolubility,high aggregation,and low reactive oxygen species(ROS)production efficiency.Consequently,it is crucial to develop novel sonosensitizers with high yields of ROS,outstanding water solubility,and good biocompatibility.Herein,we constructed a new platform for SDT based on unimolecular porphyrin derivatives OPV-C_(3)-TPP.The probe OPV-C_(3)-TPP was synthesized by covalently linking conjugated oligomers(OPV)with 5,10,15,20-tetra(4-aminophenyl)porphyrin(TAPP).The introduction of OPV greatly improves the water solubility of the porphyrins and reduces the self-aggregation of the porphyrins.In addition,OPV-C_(3)-TPP has good intramolecular energy transfer efficiency,thus enhancing the yield of ROS.The experimental results show that OPV-C_(3)-TPP exhibits excellent ROS generation capacity under ultrasound(US)irradiation,which leads to apoptosis and necrosis of tumor cells.In vivo tumor growth is also significantly inhibited in the OPV-C_(3)-TPP t US group,exhibiting better SDT effects than TAPP.Therefore,the unimolecular OPV-C_(3)-TPP can be used as a potential sonosensitizer,providing a promising SDT for deep-tissue tumors.展开更多
Chemical modification of native peptides and proteins is a versatile strategy to facilitate late-stage diversification for functional studies.Among the proteogenic amino acids,lysine is extensively involved in posttra...Chemical modification of native peptides and proteins is a versatile strategy to facilitate late-stage diversification for functional studies.Among the proteogenic amino acids,lysine is extensively involved in posttranslational modifications and the binding of ligands to target proteins,making its selective modification attractive.However,lysine’s high natural abundance and solvent accessibility,as well as its relatively low reactivity to cysteine,necessitate addressing chemoselectivity and regioselectivity for the Lys modification of native proteins.Although Lys chemoselective modification methods have been well developed,achieving site-selective modification of a specific Lys residue remains a great challenge.In this review,we discussed the challenges of Lys selective modification,presented recent examples of Lys chemoselective modification,and summarized the currently known methods and strategies for Lys site-selective modification.We also included an outlook on potential solutions for Lys site-selective labeling and its potential applications in chemical biology and drug development.展开更多
Diradicaloid polycyclic hydrocarbons(PHs)own unique open-shell electronic structures and exhibit potential utility in the fields of organic electronics and spintronics.Herein,we disclose precise fusion of B/O-heterocy...Diradicaloid polycyclic hydrocarbons(PHs)own unique open-shell electronic structures and exhibit potential utility in the fields of organic electronics and spintronics.Herein,we disclose precise fusion of B/O-heterocycles onto PHs for control over their electronic structures and diradical properties.We designed and synthesized four B/O-containing diradicaloid isomers that feature the fluoreno[3,2-b]fluorene and fluoreno[2,1-a]fluoreneπ-skeletons,respectively.The precise B/O-heterocycle fusion modes along with the changed conjugation patterns lead to their modulated electronic structures and properties,such as diradical and aromatic structures,energy levels and band gaps,as well as magnetic,electrochemical and photophysical properties.Notably,the mode A may decrease the open-shell extent,whereas the mode B can enhance the diradical nature,leading to their well-tuned diradical characters in the range of0.46-0.70.Moreover,the mode A stabilizes the LUMOs and the mode B obviously increases the HOMO levels,which are remarkably contributed by the B and O atoms,respectively,further giving rise to the decreased band gaps and redshifted absorptions.This study clearly illustrates the electronic effects of B/O-heterocycle fusion on PHs and gains insight into B/O-type organic diradicaloids.These findings will provide an important guideline for the design of more fascinating heteroatom-containing diradicaloids.展开更多
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.
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.
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supported by the National Key Research and Development Program of China(2022YFF0710505)the Central Public-interest Scientific Institution Basal Research Fund,China(1610302022001)。
文摘HighlightsA novel conjugative plasmid pHJ90-cfr carrying the multiresistance gene cfr was characterized in Proteus vulgaris.A new IS5-family member,ISPmi4,was identified for the first time.Both plasmids and ICEs were vital mobile genetic elements for horizontal transmission of cfr gene in Proteus species.
基金supported by the National Nature Science Foundation of China(Nos.62075079,62305127,61975200)the Natural Science Foundation of Jilin Province(20230508135RC)the Science and Technology Development Foundation of Changchun City(23GZZ15).
文摘The fluorescence imaging (FLI) in the second near-infrared window (NIR-II, 1000–1700nm) has attracted considerable attention in the past decade. In contrast to conventional NIR-I window excitation (808nm/980nm), FLI with NIR-II window excitation (1064nm/other wavelength beyond 1000nm) can afford deeper tissue penetration depth with high clarity due to the merits of suppressed photon scattering and diminished autofluorescence. In this review, we have summarized NIR-II window excitable/emissive organic/polymeric fluorophores recently developed. The characteristics of these fluorophores such as chemical structures and photophysical properties have also been critically discussed. Furthermore, the latest development of noninvasive in vivo FLI with NIR-II excitation was highlighted. The ideal imaging results emphasized the importance of NIR-II excitation of these fluorophores in enabling deep tissue penetration and high-resolution imaging. Finally, a perspective on the challenges and prospects of NIR-II excitable/emissive organic/polymeric fluorophores was also discussed. We expected this review will be served as a source of inspiration for researchers, stimulating the creation of novel NIR-II excitable fluorophores and fostering the development of bioimaging applications.
基金supported by the National Natural Science Foundation of China(Nos.22375031,22202037,22472023)the Fundamental Research Funds for the Central Universities(Nos.2412023YQ001,2412023QD019,2412024QD014)+1 种基金supported by grants from the seventh batch of Jilin Province Youth Science and Technology Talent Lifting Project(No.QT202305)Science and Technology Development Plan Project of Jilin Province,China(No.20240101192JC)。
文摘The light-driven CO_(2)reduction reaction(CO_(2)RR)to CO is a very effective way to address global warming.To avoid competition with water photolysis,metal-free gas-solid CO_(2)RR catalysts should be investigated.Covalent organic frameworks(COFs)offer a promising approach for CO_(2)transformation but lack high efficiency and selectivity in the absence of metals.Here,we have incorporated a pyridine nitrogen component into the imine-COF conjugated structure(Tp Pym).This innovative system has set a record of producing a CO yield of 1565μmol g^(-1)within 6 h.The soft X-ray absorption fine structure measurement proves that Tp Pym has both better conjugation and electron cloud enrichment.The electronic structure distribution delays the charge-carrier recombination,as evidenced by femtosecond transient absorption spectroscopy.The energy band diagram and theoretical calculation show that the conduction-band potential of Tp Pym is lower and the reduction reaction of CO_(2)to CO is more likely to occur.
基金financially supported by the Sichuan Science and Technology Program(2022YFS0025 and 2024YFFK0133)supported by the“Fundamental Research Funds for the Central Universities of China.”。
文摘Tactile perception plays a vital role for the human body and is also highly desired for smart prosthesis and advanced robots.Compared to active sensing devices,passive piezoelectric and triboelectric tactile sensors consume less power,but lack the capability to resolve static stimuli.Here,we address this issue by utilizing the unique polarization chemistry of conjugated polymers for the first time and propose a new type of bioinspired,passive,and bio-friendly tactile sensors for resolving both static and dynamic stimuli.Specifically,to emulate the polarization process of natural sensory cells,conjugated polymers(including poly(3,4-ethylenedioxythiophen e):poly(styrenesulfonate),polyaniline,or polypyrrole)are controllably polarized into two opposite states to create artificial potential differences.The controllable and reversible polarization process of the conjugated polymers is fully in situ characterized.Then,a micro-structured ionic electrolyte is employed to imitate the natural ion channels and to encode external touch stimulations into the variation in potential difference outputs.Compared with the currently existing tactile sensing devices,the developed tactile sensors feature distinct characteristics including fully organic composition,high sensitivity(up to 773 mV N^(−1)),ultralow power consumption(nW),as well as superior bio-friendliness.As demonstrations,both single point tactile perception(surface texture perception and material property perception)and two-dimensional tactile recognitions(shape or profile perception)with high accuracy are successfully realized using self-defined machine learning algorithms.This tactile sensing concept innovation based on the polarization chemistry of conjugated polymers opens up a new path to create robotic tactile sensors and prosthetic electronic skins.
基金Supported by the Science and Technology Project of Guangxi(Guike AD23023002)。
文摘In this paper,we propose a three-term conjugate gradient method for solving unconstrained optimization problems based on the Hestenes-Stiefel(HS)conjugate gradient method and Polak-Ribiere-Polyak(PRP)conjugate gradient method.Under the condition of standard Wolfe line search,the proposed search direction is the descent direction.For general nonlinear functions,the method is globally convergent.Finally,numerical results show that the proposed method is efficient.
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supported by the National Natural Science Foundation of China(Nos.22225806,22078314,21908216,22378385)Dalian Institute of Chemical Physics(Nos.DICPI202142,DICPI202436)+1 种基金Agency for Science,Technology and Research(No.A*STAR,Singapore)under its Advanced Manufacturing and Engineering Program(No.A2083c0051)SUTD Kickstarter Initiative(No.SKI 2021_03_10)。
文摘The demand for enhanced optical properties in advanced fluorescence technologies has driven research into the structure-property relationship of fluorophores.In this paper,we use naphthalene fluorophores Na DC-Aze and PhDO-Aze as a case study to emphasize the pivotal role of cross conjugation in tuning the optical structure-property relationship.Na DC-Aze and PhDO-Aze,formed by hybridizing two distinct conjugated systems in a single naphthalene molecule,exhibit spectral characteristics from both conjugated systems.Experimental data and theoretical calculations demonstrate the coexistence of two electron-delocalization systems in a cross-conjugation manner in both Na DC-Aze and PhDO-Aze.The cross-conjugation fluorophores exhibit high brightness,large Stokes shift,and a broad absorption wavelength range by combining distinct spectral properties from its parent fluorophores.These spectral properties will be advantageous for certain applications(i.e.,panchromatic absorption in organic solar cells,and fluorophores compatible with a wide range of excitation wavelengths).
基金supported by the UCSI University under the Research Excellence and Innovation Grant(REIG)(grant numbers:REIG-FAS-2023/006,REIG-FAS-2024/001).
文摘Antibody-drug conjugates(ADCs)represent a promising approach in targeted cancer therapy,combining the tar-geted precision of antibodies with the potency of cytotoxic payloads to selectively target tumour cell whilst min-imising off-target effects.This review provides a comprehensive analysis of ADCs,encompassing their structural components,mechanisms of action,and clinical applications.It also examines recent technological advancements,particularly in antibody engineering and linker design,aimed at enhancing therapeutic efficacy and safety.The current clinical landscape is outlined,highlighting approved ADCs and promising candidates in clinical trials,while also addressing key challenges such as stability,half-life,and systemic toxicity.This review is based on an extensive literature survey from major databases such as Scopus and Web of Science,with a focus on keywords like“antibody-drug conjugates”,“ADC advancements”,and“next-generation ADC technologies”.By integrating insights from both preclinical and clinical perspectives,we highlight the transformative potential of ADCs in advancing modern cancer therapy.
基金supported by the Shaanxi Province Technological Innovation Guidance Special(No.2022QFY08-01)the National Key Research and Development Program of China(No.2021YFB3200702)+5 种基金Natural Science Foundation of China(Nos.22201228,22205172,52203240 and 22175138)China Postdoctoral Science Foundation(Nos.2022M712530,2023T160506,and 2022M712497)Fundamental Research Funds for the Central Universities(No.xzy012022017)Young Talent Fund of Association for Science and Technology in Shaanxi(No.20230624)Shaanxi Province Postdoctoral Science Foundation(No.2023b SHTBZZ04)the Youth Innovation Team of Shaanxi Universities。
文摘π-Conjugated donor-acceptor-donor-acceptor-donor(D-A-D-A-D)type pyrenoviologens(PyV^(2+)),with the 2,7 positions of pyrene serving as connection bridges,were synthesized through SN2 reactions.Specifically,pyrenoviologen 3c was modified with a methylnaphthalene group,while 3a and 3b were modified with methyl and benzyl groups,respectively,for comparison.These pyrenoviologens exhibit reversible redox properties and strong fluorescence emission.Electrochromic devices(ECDs)were prepared using pyrenoviologens as the active materials.Notably,naphthalene-containing pyrenoviologen 3c,with its DA-D-A-D conjugated structure,possesses more stable free radicals,enabling it to maintain the radical color for a longer duration after power loss.A series of color-changing devices were successfully assembled.Due to the strong fluorescence of pyrenoviologens and the unique electron transfer effect between them and picric acid(PA),a sensor film with good selectivity and high sensitivity for PA in aqueous solution was prepared using pyrenoviologens as the fluorescent probe.Specifically,3c exhibited the highest sensitivity to PA due to its lowest energy gap.The introduction of the D-A-D-A-D structure is a strategic approach to enhancing photoelectric performance and broadening the application of viologens.
基金supported by the National Natural Science Foundation of China(22274095 and 21974084)the Fundamental Research Funds for the Central Universities(GK202302004).
文摘Sonodynamic therapy(SDT)is garnering considerable attention as a promising treatment for deep-seated tumors because of its strong tissue penetration ability,non-invasiveness,and controllability.However,the SDT efficiency of traditional sonosensitizers including porphyrins and their derivatives are limited due to their poor water dissolubility,high aggregation,and low reactive oxygen species(ROS)production efficiency.Consequently,it is crucial to develop novel sonosensitizers with high yields of ROS,outstanding water solubility,and good biocompatibility.Herein,we constructed a new platform for SDT based on unimolecular porphyrin derivatives OPV-C_(3)-TPP.The probe OPV-C_(3)-TPP was synthesized by covalently linking conjugated oligomers(OPV)with 5,10,15,20-tetra(4-aminophenyl)porphyrin(TAPP).The introduction of OPV greatly improves the water solubility of the porphyrins and reduces the self-aggregation of the porphyrins.In addition,OPV-C_(3)-TPP has good intramolecular energy transfer efficiency,thus enhancing the yield of ROS.The experimental results show that OPV-C_(3)-TPP exhibits excellent ROS generation capacity under ultrasound(US)irradiation,which leads to apoptosis and necrosis of tumor cells.In vivo tumor growth is also significantly inhibited in the OPV-C_(3)-TPP t US group,exhibiting better SDT effects than TAPP.Therefore,the unimolecular OPV-C_(3)-TPP can be used as a potential sonosensitizer,providing a promising SDT for deep-tissue tumors.
基金the National Natural Science Foundation of China(Nos.82373722,22077144)Hunan Provincial Natural Science Foundation of China(No.2023JJ30527)+2 种基金Guangdong Basic and Applied Basic Research Foundation(No.2023B1515040006)Guangdong Provincial Key Laboratory of Construction Foundation(No.2023B1212060022)Key Research and Development Program of Guangdong Province(No.2020B1111110003).
文摘Chemical modification of native peptides and proteins is a versatile strategy to facilitate late-stage diversification for functional studies.Among the proteogenic amino acids,lysine is extensively involved in posttranslational modifications and the binding of ligands to target proteins,making its selective modification attractive.However,lysine’s high natural abundance and solvent accessibility,as well as its relatively low reactivity to cysteine,necessitate addressing chemoselectivity and regioselectivity for the Lys modification of native proteins.Although Lys chemoselective modification methods have been well developed,achieving site-selective modification of a specific Lys residue remains a great challenge.In this review,we discussed the challenges of Lys selective modification,presented recent examples of Lys chemoselective modification,and summarized the currently known methods and strategies for Lys site-selective modification.We also included an outlook on potential solutions for Lys site-selective labeling and its potential applications in chemical biology and drug development.
基金supported by National Natural Science Foundation of China(Nos.52373182 and 22175074)Jilin Scientific and Technological Development Program(No.20220101054JC)Department of Education of Jilin Province(No.JJKH20221046KJ)。
文摘Diradicaloid polycyclic hydrocarbons(PHs)own unique open-shell electronic structures and exhibit potential utility in the fields of organic electronics and spintronics.Herein,we disclose precise fusion of B/O-heterocycles onto PHs for control over their electronic structures and diradical properties.We designed and synthesized four B/O-containing diradicaloid isomers that feature the fluoreno[3,2-b]fluorene and fluoreno[2,1-a]fluoreneπ-skeletons,respectively.The precise B/O-heterocycle fusion modes along with the changed conjugation patterns lead to their modulated electronic structures and properties,such as diradical and aromatic structures,energy levels and band gaps,as well as magnetic,electrochemical and photophysical properties.Notably,the mode A may decrease the open-shell extent,whereas the mode B can enhance the diradical nature,leading to their well-tuned diradical characters in the range of0.46-0.70.Moreover,the mode A stabilizes the LUMOs and the mode B obviously increases the HOMO levels,which are remarkably contributed by the B and O atoms,respectively,further giving rise to the decreased band gaps and redshifted absorptions.This study clearly illustrates the electronic effects of B/O-heterocycle fusion on PHs and gains insight into B/O-type organic diradicaloids.These findings will provide an important guideline for the design of more fascinating heteroatom-containing diradicaloids.
