Antibacterial Chemodynamic Therapy: Materials and Strategies

The wide and frequent use of antibiotics in the treatment of bacterial infection can cause the occurrence of multidrug-resistant bacteria,which becomes a serious health threat.Therefore,it is necessary to develop antibiotic-independent treatment modalities.Chemodynamic therapy(CDT)is defined as the approach employing Fenton and/or Fenton-like reactions for generating hydroxyl radical(•OH)that can kill target cells.Recently,CDT has been successfully employed for antibacterial applications.Apart from the common Fe-mediated CDT strategy,antibacterial CDT strategies mediated by other metal elements such as copper,manganese,cobalt,molybdenum,platinum,tungsten,nickel,silver,ruthenium,and zinc have also been proposed.Furthermore,different types of materials like nanomaterials and hydrogels can be adopted for constructing CDT-involved antibacterial platforms.Besides,CDT can introduce some toxic metal elements and then achieve synergistic antibacterial effects together with reactive oxygen species.Finally,CDT can be combined with other therapies such as starvation therapy,phototherapy,and sonodynamic therapy for achieving improved antibacterial performance.This review first summarizes the advancements in antibacterial CDT and then discusses the present limitations and future research directions in this field,hoping to promote the development of more effective materials and strategies for achieving potentiated CDT.

Influence of Coating Layer on Acoustic Wave Propagation in a Random Complex Medium with Resonant Scatterers

We investigate the influence of coating layer on acoustic wave propagation in a dispersed random medium consisting of coa.ted fibers.In the strong-scattering regime, the characteristics of wave scattering resonances are found to evolve regularly with the properties of the coating layer.By theoretical calculation,frequency gaps are found in acoustic excitation spectra in a random medium.The scattering cross section results present the evolution of scattering resonances with the properties of the coating layer,which offers a good explanation for the change of the frequency gaps.The velocity of the propagation quasi-mode is also shown to depend on the filling fraction of the coating layer.We use the generalized coherent potential-approximation approach to solve acoustic wave dispersion relations in a complicated random medium consisting of coating-structure scatterers.It is shown that our model reveals subtle changes in the behavior of the acoustic wave propagating quasi-modes.

Impact of incident direction on neutron-induced single-bit and multiple-cell upsets in 14 nm FinFET and 65 nm planar SRAMs

Based on the BL09 terminal of China Spallation Neutron Source(CSNS),single event upset(SEU)cross sections of14 nm fin field-effect transistor(FinFET)and 65 nm quad data rate(QDR)static random-access memories(SRAMs)are obtained under different incident directions of neutrons:front,back and side.It is found that,for both technology nodes,the“worst direction”corresponds to the case that neutrons traverse package and metallization before reaching the sensitive volume.The SEU cross section under the worst direction is 1.7-4.7 times higher than those under other incident directions.While for multiple-cell upset(MCU)sensitivity,side incidence is the worst direction,with the highest MCU ratio.The largest MCU for the 14 nm FinFET SRAM involves 8 bits.Monte-Carlo simulations are further performed to reveal the characteristics of neutron induced secondary ions and understand the inner mechanisms.

Frist-principles Band Structures Calculation of Tin-phthalocyanine

We adopt the density function theory with generalized approximation by the Beeke exchange plus Lee-Yang-Parr correlation functional to calculate the electronic first-principles band structure of tin-phthalocyanine （SnPc）. The intermolecular interaction related to transport behavior was analyzed from the F-point wave function as well as from the bandwidths and band gaps. From the calculated bandwidths of the frontier bands as well as the effective masses of the electron and hole, it can be concluded that the mobility of the electron is about two times larger than that of the hole. Furthermore, when several bands near the Fermi surface are taken into account, we find that the interband gaps within the unoccupied bands are generally smaller than those of the occupied bands, indicating that the electron can hop from one band to another which is much easier than the hole. This may happen through electron-phonon coupling for instance, thus effectively yielding an even larger mobility for the electron than for the hole. These facts indicate that in SnPc the electrons are the dominant carriers in transport, in contrast to most organic materials.

Antibacterial gas therapy: Strategies, advances, and prospects

One of the challenges posed by current antibacterial therapy is that the expanded and massive use of antibiotics endows bacteria with the ability to resist almost all kinds of antibiotics.Therefore,developing alternative strategies for efficient antibacterial treatment is urgently needed.Antibacterial gas therapy has attracted much attention in the past decade.Nitric oxide(NO),carbon monoxide(CO),sulfur dioxide(SO2),hydrogen sulfide(H_(2)S),and hydrogen(H_(2))are not only known as endogenous signaling molecules,but also play critical roles in many pathological processes.These gases are considered as attractive bactericidal agents because they are able to kill bacteria,disperse biofilms,and promote bacteria-infected wound healing while avoiding resistance.In this review,we discuss the bactericidal properties of these gases,as well as the recent advances of gas-involving systems in antibacterial,antibiofilm,and wound treatment applications.Moreover,we summarize various gas donors utilized in antibacterial treatment.We hope this review will shed new light on the future design and applications of advanced antibacterial gas therapy.

Exploring three-dimensional biological tissues with new chemical labels

Three-dimensional(3D)histology has exhibited tremendous potential in fundamental research and clini-cal disease grading,but compatible labeling techniques are still lacking.Recently in Science Advances,Pac et al.report a new histological technique termed 3DNFC,which realizes 3D fluorescence imaging of thick tissues via citrate-based in situ fluorophore formation.

Investigating the cellular functions of β-Glucosidases for synthesis of lignocellulose-degrading enzymes in Trichoderma reesei

β-glucosidases play an important role in the synthesis of cellulase in fungi,but their molecular functions and mechanisms remain unknown.We found that the 10 putativeβ-glucosidases investigated in Trichoderma ree-sei facilitate cellulase production,with cel3j being the most crucial.Transcriptional analysis revealed that the most affected biological processes in△cel3j strain were cellulase synthesis,ribosome biogenesis,and RNA poly-merases.Moreover,CEL3J was unconventionally transported through the endoplasmic reticulum,bypassing the Golgi apparatus,whereas cel3j overexpression altered cellulase secretion from conventional to unconventional,likely owing to the activated unconventional protein secretion pathway(UPS),as indicated by the upregulation of genes related to UPS.The mTORC1-GRASP55 signaling axis may modulate the unconventional secretion of CEL3J and cellulase.The transcriptional levels of genes associated with DNA replication,the cell cycle,and meiosis were noticeably affected by overexpressing cel3j.These data give new clues for exploring the roles ofβ-glucosidases and the molecular mechanisms of their unconventional secretion in fungi.

Metal–Phenolic Network-Facilitated“Foe-to-Friend”Conversion of Melittin for Cancer Immunotherapy with Boosted Abscopal Effect

As a naturally occurring cytolytic peptide,melittin(Mel)has strong cytolytic activity and is a potent therapeutic peptide for cancer therapy.However,the serious hemolytic activity of Mel largely impedes its clinical applications.In this work,based on the strong interactions between proteins/peptides and polyphenols,we develop a tannic acid–Fe^(3+)metal–phenolic network(MPN)-based strategy that can convert Mel from foe to friend via shielding its positive charges and reducing its hemolytic activity.Besides,an immune adjuvant resiquimod(R848)is also introduced for immunostimulation,affording the final Mel-and R848-coloaded nanodrug.The Mel-caused membrane disruption can induce immunogenic cell death for immunostimulation,R848 can act as an immune adjuvant to further facilitate the immunostimulatory effect,and the tannic acid–Fe^(3+)MPN-mediated Fenton reaction can produce reactive oxygen species for cancer treatment.Further experiments reveal that the nanodrug can effectively cause immunogenic cell death of tumor cells and arouse robust intratumoral and systemic antitumor immunostimulation.In the bilateral tumor-bearing mouse models,the nanodrug considerably destroys the primary tumor and also boosts the abscopal effect to ablate the distant tumor.Collectively,the MPN-facilitated“foe-to-friend”strategy may promote the practical applications of Mel and foster the development of cancer immunotherapeutics.

Low-Temperature Photothermal Therapy:Strategies and Applications

Although photothermal therapy(PTT)with the assistance of nanotechnology has been considered as an indispensable strategy in the biomedical field,it still encounters some severe problems that need to be solved.Excessive heat can induce treated cells to develop thermal resistance,and thus,the efficacy of PTT may be dramatically decreased.In the meantime,the uncontrollable diffusion of heat can pose a threat to the surrounding healthy tissues.Recently,low-temperature PTT(also known as mild PTT or mild-temperature PTT)has demonstrated its remarkable capacity of conquering these obstacles and has shown excellent performance in bacterial elimination,wound healing,and cancer treatments.Herein,we summarize the recently proposed strategies for achieving low-temperature PTT based on nanomaterials and introduce the synthesis,characteristics,and applications of these nanoplatforms.Additionally,the combination of PTT and other therapeutic modalities for defeating cancers and the synergistic cancer therapeutic effect of the combined treatments are discussed.Finally,the current limitations and future directions are proposed for inspiring more researchers to make contributions to promoting low-temperature PTT toward more successful preclinical and clinical disease treatments.

Mitochondrion-and nucleus-acting polymeric nanoagents for chemo-photothermal combination therapy

Developing intrinsically mitochondria-targetable nanosystems for subcellular structure-oriented precise cancer therapy is highly desirable.Here,we conjugate the cluster determinant 44(CD44)-targetable hyaluronic acid(HA)with cholesterol-poly(ethylene glycol)2 k-NH2 and mitochondria-acting IR825-NH2(a cyanine dye)to construct a self-assembled nanostructure(abbreviated as HA-IR825-Chol)for photothermal therapy.The HA-IR825-Chol exhibits improved photostability and desirable photothermal properties,and can rapidly and substantially enter CD44-overexpressed cancer cells and selectively accumulate in the mitochondria of the cells.Upon near-infrared laser irradiation,it can induce severe mitochondrial damage,which causes cytochrome c release and triggers cell apoptosis.Furthermore,we demonstrate the feasibility of loading the chemotherapeutics 10-hydroxycamptothecin(HCPT)into the hydrophobic cores of HA-IR825-Chol NPs for combined chemophotothermal therapy.HCPT encapsulated within HA-IR825-Chol achieves significantly increased cellular uptake and simultaneous mitochondrial and nuclear localization,leading to the release of cytochrome c from mitochondria and upregulation of cleaved caspase-3,both of which contribute to the cell apoptosis/death.In vivo experiments reveal the excellent tumor-targeting ability of HA-IR825-Chol/HCPT,ensuring the efficient tumor eradication by the chemo-photothermal therapy.This work exemplifies the development of an intrinsically mitochondria-targetable nanocarrier for precise subcellular structure-localized drug delivery,and the Chol-mediated rapid and massive endocytosis of the nanoagents may represent a robust strategy for enhancing the efficacies of nanomedicines.

Bacterial Template Synthesis of Multifunctional Nanospindles for Glutathione Detection and Enhanced Cancer-Specific Chemo-Chemodynamic Therapy

Biological synthetic methods of nanoparticles have shown great advantages,such as environmental friendliness,low cost,mild reaction conditions,and enhanced biocompatibility and stability of products.Bacteria,as one of the most important living organisms,have been utilized as bioreducing nanofactories to biosynthesize many metal nanoparticles or compounds.Here,inspired by the disinfection process of KMnO_(4),we for the first time introduce bacteria as both the template and the reducing agent to construct a novel tumor microenvironment-responsive MnO_(x)-based nanoplatform for biomedical applications in various aspects.It is found that the bacterium/MnO_(x)-based nanospindles(EM NSs)can efficiently encapsulate the chemotherapeutic agent doxorubicin(DOX),leading to the fluorescence quenching of the drug.The as-formed DOX-loaded EM NSs(EMD NSs)are proven to be decomposed by glutathione(GSH)and can simultaneously release DOX and Mn^(2+)ions.The former can be utilized for sensitive fluorescence-based GSH sensing with a limit of detection as low as 0.28μM and selective cancer therapy,while the latter plays important roles in GSH-activated magnetic resonance imaging and chemodynamic therapy.We also demonstrate that these nanospindles can generate oxygen in the presence of endogenous hydrogen peroxide to inhibit P-glycoprotein expression under hypoxia and can achieve excellent tumor eradication and tumor metastasis inhibition performance.Taken together,this work designs a multifunctional bacterially synthesized nanomissile for imaging-guided tumor-specific chemo-chemodynamic combination therapy and will have implications for the design of microorganism-derived smart nanomedicines.

Fluorescent quantum dots for microbial imaging

Quantum dots（QDs）, with several unique optical and chemical features, are becoming desirable fluorescent tags for the biological applications that require long-term and highly sensitive imaging.Besides, the conjugation of various functional biomolecules to QDs has enabled wide applications of QDs in biological imaging. This review focuses on the following four types of QDs： semiconductor quantum dots（semiconductor QDs）, carbon nanodots（CDs）, silicon quantum dots（SiQDs）, and polymer dots（Pdots）, and summarizes the recent advancements of using these QDs in imaging microorganisms including viruses, bacteria, and fungi. We hope that this review will promote the development of new fluorescent QDs for microbial imaging and extend the applications of QD-based imaging techniques in cell biology and beyond.

Ultrasmall green-emitting carbon nanodots with 80%photoluminescence quantum yield for lysosome imaging

Carbon-based fluorescent nanomaterials have gained much attention in recent years.In this work,greenphotoluminescent carbon nanodots(CNDs;also termed carbon dots,CDs)with amine termination were synthesized via the hydrothermal treatment of amine-containing spermine and rose bengal(RB)molecules.The CNDs have an ultrasmall size of~2.2 nm and present bright photoluminescence with a high quantum yield of~80%which is possibly attributed to the loss of halogen atoms(Cl and I)during the hydrothermal reaction.Different from most CNDs which have multicolor fluorescence emission,the asprepared CNDs possess excitation-independent emission property,which can avoid fluorescence overlap with other fluorescent dyes.Moreover,the weakly basic amine-terminated surface endows the CNDs with the acidotropic effect.As a result,the CNDs can accumulate in the acidic lysosomes after cellular internalization and can serve as a favorable agent for lysosome imaging.Besides,the CNDs have a negligible impact on the lysosomal morphology even after 48 h incubation and exhibit excellent biocompatibility in the used cell models.

SERS-encoded nanocomposites for dual pathogen bioassay

Surface-enhanced Raman spectroscopy(SERS)has been successfully applied to detect various biomolecules,but it is still in challenge to assay living cells or bacteria sensitively,selectively and quantitatively in complex environments.In this paper,4-ATP and DTNB are assembled on Ag nanoparticle(NP)-decorated poly(styrene-co-acrylic acid)(PSA)nanospheres and then sealed by silica shells to form sensitive SERS labels based on the localized surface plasmon resonance of Ag NPs and large light scattering cross-sections of PSA nanospheres.They are further developed as encoding tags for dual detection of S.aureus and E.coli after assembling corresponding aptamers,which demonstrate ultralow detection limits of 8 cell L-1 for S.aureus and 2 cell L-1 for E.coli.Such a bioassay indicates a point-of-care strategy of ultrasensitively biomedical detections by encoding specific SERS tags.