Neural substrates for regulating self-grooming behavior in rodents. / 啮齿动物自我梳理行为调控的神经基质.

Grooming, as an evolutionarily conserved repetitive behavior, is common in various animals, including humans, and serves essential functions including, but not limited to, hygiene maintenance, thermoregulation, de-arousal, stress reduction, and social behaviors. In rodents, grooming involves a patterned and sequenced structure, known as the syntactic chain with four phases that comprise repeated stereotyped movements happening in a cephalocaudal progression style, beginning from the nose to the face, to the head, and finally ending with body licking. The context-dependent occurrence of grooming behavior indicates its adaptive significance. This review briefly summarizes the neural substrates responsible for rodent grooming behavior and explores its relevance in rodent models of neuropsychiatric disorders and neurodegenerative diseases with aberrant grooming phenotypes. We further emphasize the utility of rodent grooming as a reliable measure of repetitive behavior in neuropsychiatric models, holding promise for translational psychiatry. Herein, we mainly focus on rodent self-grooming. Allogrooming (grooming being applied on one animal by its conspecifics via licking or carefully nibbling) and heterogrooming (a form of grooming behavior directing towards another animal, which occurs in other contexts, such as maternal, sexual, aggressive, or social behaviors) are not covered due to space constraints.

Electroacupuncture pretreatment inhibits ferroptosis and inflammation after middle cerebral artery occlusion in rats by activating Nrf2.

OBJECTIVE: Electroacupuncture (EA) pretreatment can effectively increase the tolerance of the brain to ischemic stroke. The mechanism of ischemic tolerance induced by EA is related to Nrf2, but its specific mechanism has not been elucidated. This paper was designed to explore the effect of EA pretreatment on brain injury and the related mechanisms. METHODS: Rats were pretreated with EA before middle cerebral artery occlusion (MCAO) modeling. The symptoms of neurological deficit and the volume of cerebral infarction were measured. The levels of inflammatory factors, oxidative stress-related factors, LPO, ROS, and Fe2+ were evaluated by the corresponding kits. Cell apoptosis was determined through TUNEL staining. The mRNA expression of inflammatory factors was examined by RT-qPCR, and the protein expression of ferroptosis-related factors, pyroptosis-related proteins, Keap1, Nrf2, HO-1, and NQO1 by western blotting. RESULTS: EA pretreatment improved the symptoms of neurological deficit and reduced the volume of cerebral infarction. EA pretreatment significantly inhibited oxidative stress, inflammatory response, ferroptosis, pyroptosis, and apoptosis in brain tissues of MCAO rats. Mechanistically, EA pretreatment could activate Nrf2 expression and reduce Keap1 expression. CONCLUSION: EA pretreatment reduced inflammation and oxidative stress and inhibited ferroptosis by activating Nrf2 expression, ultimately delaying the development of ischemic stroke.

Re-Engineering Fungal Nonribosomal Peptide Synthetases by Module Dissection and Duplicated Thiolation Domains.

Unnatural product (uNP) nonribosomal peptides promise to be a valuable source of pharmacophores for drug discovery. However, the extremely large size and complexity of the nonribosomal peptide synthetase (NRPS) enzymes pose formidable challenges to the production of such uNPs by combinatorial biosynthesis and synthetic biology. Here we report a new NRPS dissection strategy that facilitates the engineering and heterologous production of these NRPSs. This strategy divides NRPSs into "splitting units", each forming an enzyme subunit that contains catalytically independent modules. Functional collaboration between the subunits is then facilitated by artificially duplicating, at the N-terminus of the downstream subunit, the linker - thiolation domain - linker fragment that is resident at the C-terminus of the upstream subunit. Using the suggested split site that follows a conserved motif in the linker connecting the adenylation and the thiolation domains allows cognate or chimeric splitting unit pairs to achieve productivities that match, and in many cases surpass those of hybrid chimeric enzymes, and even those of intact NRPSs, upon production in a heterologous chassis. Our strategy provides facile options for the rational engineering of fungal NRPSs and for the combinatorial reprogramming of nonribosomal peptide production.

Structure-activity relationship between gold nanoclusters and human serum albumin: Effects of ligand isomerization.

The interactions between gold nanoclusters (AuNCs) and proteins have been extensively investigated. Nevertheless, the structure-activity relationship between gold nanoclusters and proteins in terms of ligand isomerization remained unclear. Here, interactions between Au25NCs modified with para-, inter- and ortho-mercaptobenzoic acid (p/m/o-MBA-Au25NCs) and human serum albumin (HSA) were analyzed. The results of the multispectral approach showed that all three gold nanoclusters bound to the site I in dynamic modes to increase the stability of HSA. There were significant differences in the binding intensity, thermodynamic parameters, main driving forces, and binding ratios between these three gold nanoclusters and HSA, which might be related to the existence forms of the three ligands on the surface of AuNCs. Due to the different polarities of AuNCs themselves, the impact of three AuNCs on the microenvironment of amino acid residues in HSA was also different. It could be seen that ligand isomerization significantly affected the interactions between gold nanoclusters and proteins. This work will provide theoretical guidance for ligand selection and biological applications of metal nanoclusters.

Vestibular Rehabilitation of Patient with Hypertrophic Olivary Degeneration: A Case Report.

Background Hypertrophic olivary degeneration (HOD) is a rare disorder that typically develops in the weeks to months following a structural brainstem or cerebellar lesion in the Guillain-Mollaret triangle (GMT). Clinically, patients with HOD present with palatal myoclonus and nystagmus, which are difficult to treat and rarely resolve. Purpose The purpose of this case is to present the results of vestibular and balance assessments of a patient with bilateral HOD before and after vestibular rehabilitation. Methods This case report describes a 43-year-old trucker who presented with dizziness, blurred vision, and balance problems for more than 10 months, accompanied by new-onset tremors and ataxia for more than 6 months. The patient's characteristic clinical manifestations were palatal myoclonus and nystagmus. Magnetic resonance imaging (MRI) revealed bilateral HOD after an acute pontine hemorrhage. Comprehensive vestibular and balance assessments were performed. Results Vestibular and balance assessments demonstrated nystagmus, impaired vestibulo-ocular reflex (VOR), optokinetic reflex (OKR), and balance function. Following 4 months of vestibular rehabilitation, the patient's eye symptoms and balance function were improved. Conclusions The case presented here highlights the rare clinical manifestations of HOD after pontine hemorrhage. Vestibular rehabilitation training may be beneficial for the recovery of patients with HOD.

Modified Selective Dorsal Rhizotomy Exposure Method for Adults With Spastic Paralysis of the Lower Limbs.

BACKGROUND AND OBJECTIVES: Spinal deformities are a common complication after selective dorsal rhizotomy (SDR). In this article, we introduce a more minimally invasive SDR procedure in adult patients with spastic paralysis of the lower limbs. METHODS: In this retrospective analysis of SDR in 8 adult patients with spastic paralysis of the lower limbs, a modified exposure method was used during the surgery. Only the lower part of the L1 spinous process, upper part of the L2 spinous process, and part of the lamina were resected through L1-2 interlaminar approaches. The motor and sensory roots were found to be completely dependent on electrophysiological monitoring. The sensory roots of the target muscle groups were partially transected. All patients were followed up for 2-4 years. The degree of lower extremity spasm was assessed using the Gross Motor Function Classification Scale, Ashworth grading, Gross Motor Function Measure-66, joint range of motion, and electromyography analysis. RESULTS: All 8 patients were successfully operated with the help of intraoperative electrophysiological monitoring. The Ashworth score of the target muscles, Gross Motor Function Measure-66 score, and range of motion of the joints improved significantly after surgery. Two patients achieved cross-grade improvement in their Gross Motor Function Classification Scale scores. No persistent incision pain or spinal deformities were observed during follow-up. CONCLUSION: The interspinous process approach provides sufficient surgical space and reduced the damage to the bone structure of the spine. The electrophysiological monitoring protocol is suitable for adult patients with lower extremity spasm.

Nocardioides cremeus sp. nov., Nocardioides abyssi sp. nov. and Nocardioides oceani sp. nov., three actinobacteria isolated from Western Pacific Ocean sediment.

Three Gram-stain-positive, non-motile, short rod-shaped, catalase-positive and oxidase-negative actinomycete strains (SOB44T, SOB72T and SOB77T) were isolated from a deep-sea sediment sample collected from the Western Pacific Ocean. Cells of the three strains showed optimum growth at 30 °C and pH 7.0. Strains SOB44T, SOB72T and SOB77T could tolerate up to 10, 9 and 9 % (w/v) NaCl concentration and grow at pH 5.0-12.0, 5.0-11.0 and 5.0-11.0, respectively. Phylogenetic results based on 16S rRNA gene sequences showed that the three isolates belonged to the genus Nocardioides and were identified as representing three novel species based on 78.0-93.1 % average nucleotide identity and 21.3-50.0 % DNA-DNA hybridization values with closely related reference strains. Strains SOB44T, SOB72T and SOB77T showed highest 16S rRNA gene sequence similarity to Nocardioides salarius CL-Z59T (99.2 %), Nocardioides deserti SC8A-24T (99.2 %) and Nocardioides marmotae zg-579T (98.5 %), respectively. All three strains had MK-8(H4) as the respiratory quinone, iso-C16 : 0 as the major fatty acid, and phosphatidylglycerol, diphosphatidylglycerol and phosphatidylinositol as the major polar lipids. The diagnostic diamino acid in the cell-wall peptidoglycan of all three isolates was ll-diaminopimelic acid. The DNA G+C contents of strains SOB44T, SOB72T and SOB77T were 71.1, 72.9 and 72.9 mol%, respectively. Based on the phenotypic, phylogenetic and genotypic data, strains SOB44T, SOB72T and SOB77T clearly represent three novel taxa within the genus Nocardioides, for which the names Nocardioides cremeus sp. nov. (type strain SOB44T=JCM 35774T= MCCC M28400T), Nocardioides abyssi sp. nov. (type strain SOB72T=JCM 35775T=MCCC M28318T) and Nocardioides oceani sp. nov. (type strain SOB77T=JCM 35776T=MCCC M28544T) are proposed.

A polycistronic system for multiplexed and precalibrated expression of multigene pathways in fungi.

Synthetic biology requires efficient systems that support the well-coordinated co-expression of multiple genes. Here, we discover a 9-bp nucleotide sequence that enables efficient polycistronic gene expression in yeasts and filamentous fungi. Coupling polycistronic expression to multiplexed, markerless, CRISPR/Cas9-based genome editing, we develop a strategy termed HACKing (Highly efficient and Accessible system by CracKing genes into the genome) for the assembly of multigene pathways. HACKing allows the expression level of each enzyme to be precalibrated by linking their translation to those of host proteins with predetermined abundances under the desired fermentation conditions. We validate HACKing by rapidly constructing highly efficient Saccharomyces cerevisiae cell factories that express 13 biosynthetic genes, and produce model endogenous (1,090.41 ± 80.92 mg L-1 squalene) or heterologous (1.04 ± 0.02 mg L-1 mogrol) terpenoid products. Thus, HACKing addresses the need of synthetic biology for predictability, simplicity, scalability, and speed upon fungal pathway engineering for valuable metabolites.

Revealing the effects of ligands of silver nanoclusters on the interactions between them and ctDNA: Abstraction to visualization.

Silver nanoclusters (AgNCs) have been widely applied in the field of biology, drug therapy and cell imaging in the last decade. In order to study the biosafety of AgNCs, GSH-AgNCs and DHLA-AgNCs were synthesized using glutathione (GSH) and dihydrolipoic acid (DHLA) as ligands, and their interactions with calf thymus DNA (ctDNA) from abstraction to visualization were studied. The results of spectroscopy, viscometry and molecular docking demonstrated that GSH-AgNCs mainly bound to ctDNA in a groove mode, while DHLA-AgNCs were both groove and intercalation binding. Fluorescence experiments suggested that the quenching mechanism of both AgNCs to the emission of ctDNA-probe were both in static mode, and thermodynamic parameters demonstrated that the main forces between GSH-AgNCs and ctDNA were hydrogen bonds and van der Waals forces, while hydrogen bonds and hydrophobic forces contributed to the binding of DHLA-AgNCs to ctDNA. The binding strength demonstrated that DHLA-AgNCs bound to ctDNA more strongly than that of GSH-AgNCs. The results of circular dichroism (CD) spectroscopy reflected small effects of both AgNCs on the structure of ctDNA. This study will support the theoretical foundation for the biosafety of AgNCs and have a guiding significance for the preparation and application of AgNCs.

Affinity binding of COVID-19 drug candidates (chloroquine/hydroxychloroquine) and serum albumin: Based on photochemistry and molecular docking.

Chloroquine (CQ) and hydroxychloroquine (HCQ) show good efficacy in the treatment of SARS-CoV-2 in the early stage, while they are no longer recommended due to their side effects. As an important drug delivery carrier, serum albumin (SA) is closely related to the efficacy of drugs. Here, the affinity behaviour of chloroquine and hydroxychloroquine with two SA were investigated through the multispectral method of biochemistry and computer simulation. The results showed that the intrinsic emission of both SA was quenched by CQ and HCQ in a spontaneous exothermic entropy reduction static process, which relied mainly on hydrogen bonding and van der Waals forces. The lower binding constants suggested weak binding between the two drugs and SA, which might lead to differences in efficacy and possibly even to varying side effects. Binding site recognition demonstrated that CQ preferred to bind to the two sites of both SA, while HCQ tended to bind to site I of SA. The results of conformational studies demonstrated that CQ and HCQ could affect the structure of both SA by slightly increasing the α-helix content of SA. Finally, we combine the results from experimental start with molecular simulations to suggest drug modifications to guide the design of drugs. This work has important implications for guiding drug design improvements to select CQ derivatives with fewer side effects for the treatment of COVID-19.

Mucus- and pH-mediated controlled release of core-shell chitosan nanoparticles in the gastrointestinal tract for diabetes treatment.

For the successful oral delivery of peptide drugs, considerable barriers created by the harsh environment of the gastrointestinal tract, mucus, and epithelial cells must be overcome. This study was to establish a core-shell structure with chitosan (CS) nanoparticles (NP) as the core and poly-N-(2-hydroxypropyl) methacrylamide (pHPMA) as the intelligent escape shell to overcome pH and mucus barriers and improve the delivery efficiency of peptide drugs. A core-shell system (COS) composed of pHPMA-AT-1002-cys-chitosan (LRA-PA-CNPs) was prepared and used for the treatment of type 2 diabetes mellitus with the large-molecule peptide drug liraglutide (LRA). The complete COS system was observed through electron microscopy; the particle size of the LRA-PA-CNPs was approximately 160 nm; the encapsulation efficiency was approximately 69% ± 5%; the zeta potential was close to neutral; the mucus and epithelial penetration of the COS system were increased; and animal experiments showed that the COS system enhanced the oral hypoglycaemic effect of LRA.HIGHLIGHTSIntelligent escape material of poly-N-(2-hydroxypropyl) methacrylamide as the shell.Core-shell nanoparticles penetrate the mucus layer and exposing the chitosan core.Overcome pH and mucus barriers to improve the delivery efficiency of peptide drugs.

Design and construction of competitive, noncompetitive and uncompetitive nano inhibitors of enzymes.

Three common types of reversible inhibitors, namely competitive, noncompetitive and uncompetitive inhibitors, were designed and constructed by using enzymes with different surface charges and gold nanoparticles with different surface ligands and particle sizes. To our knowledge, it is the first time that an uncompetitive nano inhibitor has been discovered.

Chemometrics and genome mining reveal an unprecedented family of sugar acid-containing fungal nonribosomal cyclodepsipeptides.

Xylomyrocins, a unique group of nonribosomal peptide secondary metabolites, were discovered in Paramyrothecium and Colletotrichum spp. fungi by employing a combination of high-resolution tandem mass spectrometry (HRMS/MS)-based chemometrics, comparative genome mining, gene disruption, stable isotope feeding, and chemical complementation techniques. These polyol cyclodepsipeptides all feature an unprecedented d-xylonic acid moiety as part of their macrocyclic scaffold. This biosynthon is derived from d-xylose supplied by xylooligosaccharide catabolic enzymes encoded in the xylomyrocin biosynthetic gene cluster, revealing a novel link between carbohydrate catabolism and nonribosomal peptide biosynthesis. Xylomyrocins from different fungal isolates differ in the number and nature of their amino acid building blocks that are nevertheless incorporated by orthologous nonribosomal peptide synthetase (NRPS) enzymes. Another source of structural diversity is the variable choice of the nucleophile for intramolecular macrocyclic ester formation during xylomyrocin chain termination. This nucleophile is selected from the multiple available alcohol functionalities of the polyol moiety, revealing a surprising polyspecificity for the NRPS terminal condensation domain. Some xylomyrocin congeners also feature N-methylated amino acid residues in positions where the corresponding NRPS modules lack N-methyltransferase (M) domains, providing a rare example of promiscuous methylation in the context of an NRPS with an otherwise canonical, collinear biosynthetic program.

Sevoflurane ameliorates LPS-induced inflammatory injury of HK-2 cells through Sirtuin1/NF-kB pathway

The anesthetic sevoflurane (SEV) has been shown to protect against organ’s injury during sep-sis. The present study intended to uncover the protective effects of SEV on sepsis-induced acute kidney injury (SI-AKI) and its possible mechanism. Human renal tubular epithelial cell HK-2 was treated with 10 μg/mL lipopolysaccharide (LPS) to construct SI-AKI cell model. LPS-induced HK-2 cells were pretreated with SEV in the absence or presence of EX527, an inhibitor of Sirtuin 1 (SIRT1), after which were the detection of cell viability, lactate dehydrogenase (LDH) release, apoptosis, inflammation, and oxidative stress. Our results demonstrated that LPS caused decreased cell viability, increased LDH release, improved cell apoptosis along with decreased expression of Bcl2 and enhanced expressions of Bax, cleaved PARP and cleaved caspase, enhanced production, and protein expressions of TNF-α, IL-6, and IL-1β, increased generation of reactive oxygen species (ROS) and malondialdehyde (MDA), but contributed to declined activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). LPS inhibited SIRT1 and IκBα expressions but up-regulated p-NF-κB p65 and acetyl-p53 expressions as well. However, SEV pretreatment abolished all above-mentioned effects of LPS on HK-2 cells, while EX527 significantly reversed the effects of SEV. In conclusion, SEV effectively pro-tected HK-2 cells against LPS-induced apoptosis, inflammation, and oxidative stress, and these effects may depend on the increase of SIRT1 expression, thereby inactivating NF-κB signaling.© 2022 Codon Publications. Published by Codon Publications (AU)

Degradation-Kinetics-Controllable and Tissue-Regeneration-Matchable Photocross-linked Alginate Hydrogels for Bone Repair.

Photocross-linked alginate hydrogels, due to their biodegradability, biocompatibility, strong control for gelling kinetics in space and time, and admirable adaptability for in situ polymerization with a minimally invasive approach in surgical procedures, have created great expectations in bone regeneration. However, hydrogels with suitable degradation kinetics that can match the tissue regeneration process have not been designed, which limits their further application in bone tissue engineering. Herein, we finely developed an oxidation strategy for alginate to obtain hydrogels with more suitable degradation rates and comprehensively explored their physical and biological performances in vitro and in vivo to further advance the clinical application for the hydrogels in bone repair. The physical properties of the gels can be tuned via tailoring the degree of alginate oxidation. In particular, in vivo degradation studies showed that the degradation rates of the gels were significantly increased by oxidizing alginate. The activity, proliferation, initial adhesion, and osteogenic differentiation of rat and rabbit bone marrow stromal cells (BMSCs) cultured with/in the hydrogels were explored, and the results demonstrated that the gels possessed excellent biocompatibility and that the encapsulated BMSCs were capable of osteogenic differentiation. Furthermore, in vivo implantation of rabbit BMSC-loaded gels into tibial plateau defects of rabbits demonstrated the feasibility of hydrogels with appropriate degradation rates for bone repair. This study indicated that hydrogels with increasingly controllable and matchable degradation kinetics and satisfactory bioproperties demonstrate great clinical potential in bone tissue engineering and regenerative medicine and could also provide references for drug/growth-factor delivery therapeutic strategies for diseases requiring specific drug/growth-factor durations of action.

Rapid preparation of water-soluble Ag@Au nanoclusters with bright deep-red emission.

Deep-red (λem ∼ 710 nm) thiolated Ag@Au nanoclusters with a quantum yield of ∼18% were rapidly (∼12 min) prepared in aqueous solutions. The effects of pH and silver ions were demonstrated. The surface modification further resulted in nanoclusters with a quantum yield of ∼38%, the highest value ever reported for water-soluble red Au nanoclusters. This will highly facilitate their applications in sensing, bioimaging, etc.

The protective effects of etomidate against interleukin-1ß (IL-1ß)-induced oxidative stress, extracellular matrix alteration and cellular senescence in chondrocytes.

Osteoarthritis (OA) is a common chronic inflammatory disease associated with aging. Etomidate is an intravenous anesthetic with profound antioxidant and anti-inflammatory effects. We speculated that etomidate might exert a beneficial effect on OA. Herein, we explored the effects of etomidate on interleukin-1ß (IL-1ß)- induced chondrocytes. Our results prove that etomidate ameliorated the IL-1ß-induced oxidative stress in C28/12 chondrocytes by decreasing and increasing the reactive oxygen species (ROS) and glutathione peroxidase (GPx) levels, respectively. Etomidate prevented the IL-1ß-induced increase in the expressions of matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-13 (MMP-13) in C28/I2 chondrocytes at both mRNA and protein levels. It also caused a significant reduction in the percentage of senescence-associated-ß-galactosidase (SA-ß-Gal)-stained chondrocytes, while inducing elevated telomerase activity in IL-1ß-treated C28/I2 chondrocytes. The expression levels of senescence regulators, plasminogen activator inhibitor-1 (PAI-1) and p16, were also inhibited by etomidate in IL-1ß-treated C28/I2 chondrocytes. In addition, etomidate caused the activation of Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), along with upregulated expression levels of phosphorylated AMPKα and phosphorylated acetyl-Co A carboxylase (ACC). Moreover, blockage of AMPK using compound C abolished the protective effects of etomidate on IL-1ß-challenged C28/I2 chondrocytes. Taken together, these results demonstrate that etomidate protected C28/I2 chondrocytes from IL-1ß-induced oxidative stress, ECM degradation, and cellular senescence via activating AMPK signaling.

Impedance spectroscopy for identifying tau protein to monitor anesthesia-based issues.

Anesthesia-related drugs cause various side effects and health-related illnesses after surgery. In particular, neurogenerative disorder is a common problem of anesthesia-related drugs. A patient gets anesthesia as a requirement of the preoperative evaluation to diagnose the medical illness, which is caused by anesthetic drug treatment. Different blood-based biomarkers help in identifying the changes appearing in patients after anesthesia treatment. Among them, tau protein is a sensitive biomarker of neurodegenerative diseases, and the fluctuations in tau proteins are highly associated with various diseases. Furthermore, researchers have found unstable levels of tau protein after the anesthesia process. The current research has focused on quantifying tau protein via impedance spectroscopy to identify the problems caused by anesthesia-related drugs. An impedance spectroscopy electrode was modified into a multiwalled carbon nanotube, and an amine-ended aptamer was then attached. This electrode surface was used to quantify the tau protein level and reached the detection limit of 1 fM. The determination coefficient was found to be y = 369.93x + 1144.9, with R2 = 0.9846 in the linear range of 1 fM-1 nM. Furthermore, tau protein spiked human serum was clearly identified on the immobilized aptamer surface, indicating the specific detection.

The regulation of BbLaeA on the production of beauvericin and bassiatin in Beauveria bassiana.

Beauvericin and bassiatin are two valuable compounds with various bioactivities biosynthesized by the supposedly same nonribosomal peptide synthetase BbBEAS in entomopathogenic fungus Beauveria bassiana. To evaluate the regulatory effect of global regulator LaeA on their production, we constructed BbLaeA gene deletion and overexpression mutants, respectively. Deletion of BbLaeA resulted in a decrease of the beauvericin titer, while overexpression of BbLaeA increased its production by 1-2.26 times. No bassiatin could be detected in ΔBbLaeA and wild type strain of B. bassiana, but 4.26-5.10 µg/mL bassiatin was produced in OE::BbLaeA. Furthermore, additional metabolites with increased production in OE::BbLaeA were isolated and identified as primary metabolites. Among them, 4-hydroxyphenylacetic acid showed antibacterial bioactivity against Ralstonia solanacearum. These results indicated that BbLaeA positively regulates the production of beauvericin, bassiatin and various bioactive primary metabolites.

Interactions between Two Kinds of Gold Nanoclusters and Calf Thymus Deoxyribonucleic Acid: Directions for Preparations to Applications.

Gold nanoclusters (AuNCs) have shown promising applications in biotherapy owing to their ultrasmall size and unique molecular-like properties. In order to better guide the preparations and applications of AuNCs, dihydrolipoic acid-protected AuNCs (DHLA-AuNCs) and glutathione-protected AuNCs (GSH-AuNCs) were selected as models and the interactions between them and calf thymus DNA (ctDNA) were studied in detail. The results showed that there was a small difference in the binding mechanisms and forces between both AuNCs and ctDNA. The quenching mechanisms of both AuNCs to (ctDNA-HO) were completely different. The binding constants indicated that the binding strength between DHLA-AuNCs and ctDNA was greater than those of GSH-AuNCs. The conformation investigations showed that GSH-AuNCs had a greater impact on the conformation of ctDNA, and both AuNCs were more inclined to interact with the A-T base pairs of ctDNA. These results indicate that the surface ligand had a significant effect on the interactions between AuNCs and DNA and might also further affect the applications of AuNCs, and these results could guide the preparations of AuNCs. For DHLA-AuNCs, their good biocompatibility made them a potential candidate for application in imaging, drug treatment, sensing, and so on. The resulting base accumulation of ctDNA and weak interactions made GSH-AuNCs have great potential for application in gene therapy, which was consistent with the current reports on the applications of these two AuNCs. This work has pointed out the directions for the preparations and applications of AuNCs.