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Diabetes mellitus has become a global health problem, and the number of patients with diabetic foot ulcers (DFU) is rapidly increasing. Currently, DFU still poses great challenges to physicians, as the treatment is complex, with high risks of infection, recurrence, limb amputation, and even death. Therefore, a comprehensive understanding of DFU pathogenesis is of great importance. In this review, we summarized recent findings regarding the DFU development from the perspective of single-nucleotide variations (SNVs). Studies have shown that SNVs located in the genes encoding C-reactive protein, interleukin-6, tumor necrosis factor-alpha, stromal cell-derived factor-1, vascular endothelial growth factor, nuclear factor erythroid-2-related factor 2, sirtuin 1, intercellular adhesion molecule 1, monocyte chemoattractant protein-1, endothelial nitric oxide synthase, heat shock protein 70, hypoxia inducible factor 1 alpha, lysyl oxidase, intelectin 1, mitogen-activated protein kinase 14, toll-like receptors, osteoprotegerin, vitamin D receptor, and fibrinogen may be associated with the development of DFU. However, considering the limitations of the present investigations, future multi-center studies with larger sample sizes, as well as in-depth mechanistic research are warranted.

Deep-red (λem ∼710 nm) thiolated Ag@Au nanoclusters with a quantum yield of ∼18% were rapidly (∼12 min) prepared in aqueous solutions.

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.

Organic–inorganic hybrid perovskite solar cells, one of the most promising photovoltaic devices, have made great progress in their efficiency and preparation technology. In this study, uniform, highly conductive LinNiOx (0 ≤ n ≤ 1; 0< x ≤ 3) films were prepared by electrochemical deposition for a range of Li concentration. Photovoltaic performance for the perovskite solar cells was enhanced through incorporation of the ion pair of Ni3+ ↔ Ni2+ as the interfacial passivation. Depending on the amount of lithium doping, controlled interfacial oxidation was induced by Ni3+. The Li0.32NiOx inhibited charge recombination, reduced the defect density, and enhanced the photocurrent density. A maximum power conversion efficiency of 20.44% was obtained by Li0.32NiOx. Further, in the long-term, in-air stabilities of unencapsulated LinNiOx perovskite solar cells were demonstrated.

The gold standard for identifying pathogens causing osteomyelitis (OM) is intraoperative tissue sampling culture (TSC). However, its positive rate remains inadequate. Here, we evaluated the efficiency of a novel strategy, known as devitalized bone surface culture (BSC), for detecting OM-related microorganisms and compared it to TSC. Between December 2021 and July 2022, patients diagnosed with OM and received both methods for bacterial identification were screened for analysis. In total, 51 cases were finally recruited for analysis. The mean age was 43.6 years, with the tibia as the top infection site. The positive rate of BSC was relatively higher than that of TSC (74.5% vs. 58.8%, p = 0.093), though no statistical difference was achieved. Both BSC and TSC detected definite pathogens in 29 patients, and their results were in accordance with each other. The most frequent microorganism identified by the BSC method was Staphylococcus aureus. Moreover, BSC took a significantly shorter median culture time than TSC (1.0 days vs. 3.0 days, p < 0.001). In summary, BSC may be superior to TSC for identifying OM-associated pathogens, with a higher detectable rate and a shorter culture time.

The pathogenesis of the osteoarthritis (OA) is complex. Abnormal subchondral bone metabolism is an important cause of this disease. Further understanding on the pathology of the subchondral bone in OA may provide a new therapy. This research is about to investigate the role of SDF-1 in the subchondral bone during the pathological process of OA. In vitro, Transwell was used to test the migratory ability of bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs). Western blot presented the protein level after SDF-1 treatment in BMSCs and HUVESs. Alizarin red was used to assess the ability of osteogenic differentiation. To inhibit SDF-1 signaling pathway in vivo, AMD3100 (SDF-1 receptor blocker) was continuously delivered via miniosmotic pump for 4 weeks in mice after performing anterior cruciate ligament transaction surgery. Micro-CT, histology staining, immunofluorescence, immunohistochemistry, and TRAP staining were used to assess the role of SDF-1 on osteogenesis and angiogenesis in the subchondral bone. Our results showed that SDF-1 could recruit BMSCs, activate the p-ERK pathway, and enhance osteogenic differentiation. SDF-1 promoted the ability of proliferation, migration and tube formation of HUVECs by activating the ERK and AKT signaling pathways. In an animal study, inhibition of SDF-1/CXCR4 axis could significantly reduce subchondral osteogenesis differentiation and H-type vessel formation. Furthermore, the AMD3100-treated group showed less cartilage destruction and bone resorption. Our research shows that SDF-1 alters the microenvironment of the subchondral bone by promoting osteoid islet formation and abnormal H-type angiogenesis in the subchondral bone, resulting in articular cartilage degeneration.

The over-use of antibiotics has caused a number of problems such as contamination of antibiotic residues and virus resistance, and therefore has attracted global attention. In this study, spectroscopic techniques and molecular docking were employed to predict conformational changes and binding interaction between two cephalosporins (cefaclor and cefixime) and calf thymus DNA (ctDNA). Fluorescence and UV-vis spectra suggested that static quenching was predominant and cephalosporin bound to the groove region of ctDNA. Binding parameters calculated by the Stern-Volmer and Scatchard equations showed that cephalosporin bound to ctDNA with a binding affinity in the order of 103 L mol-1 . Thermodynamic parameters further indicated that the reaction was a spontaneous process driven by enthalpy and entropy, and that the main binding force was an electrostatic force. The effects of iodide, denaturant, thermal denaturation and pH on a cephalosporin-Hoechst-DNA complex were also studied, and the results confirmed that cephalosporin bound to the groove area of DNA. Finally, these results were further confirmed by molecular docking and electrochemical studies.

Graphene quantum dots (GQDs) could be regarded as graphene with a lateral dimension less than 100 nm. Compared with graphene, GQDs not only possess the excellent properties of graphene but also have been proven to have low toxicity, high fluorescence stability, strong water solubility, as well as better biocompatibility. In this work, an amide bond-based, N-doped graphene quantum dot was synthesized using a simple hydrothermal method. When the reaction time was 4 h and the temperature was 180°C, fluorescence excitation and emission peaks of the product were 340 nm and 450 nm, respectively. Its interaction with human serum albumin (HSA) was investigated using spectroscopy, gel electrophoresis, and molecular simulation. Gel electrophoresis showed that the product did not cause complete scission of the peptide chain in HSA, indicating good biocompatibility. The results of molecular docking showed that the product tended to bind to site III of HSA. This paper provides a meaningful reference for design and development in nanomedicine.

3-Fluorooxindole has been shown to be a biologically active structural unit, novel derivative containing 3-fluorooxindole unit has been successfully constructed using 3-fluorooxindole as a substrate in previous work. Here, the interactions between novel 3-fluorooxindole derivatives and ctDNA were explored through molecular docking, multi-spectral and NMR methods, and the dependence of the binding mechanism on the structure was revealed by combined physical chemistry and organic chemistry. Firstly, molecular docking indicated that the planarity of the molecule enhances the binding strength to ctDNA. UV absorption result showed a weak binding effect. Fluorescence spectroscopy suggested the binding mechanism of 3-fluorooxindoles and ctDNA via groove binding. Moreover, the binding mechanism of 3-fluorooxindoles to ctDNA was further confirmed by

The development of new drugs especially novel anti-cancer drugs has become a hot-spot issue that catches scholars’ attention in every field. Here a IAP antagonist analogue (IAPA) was synthesized and characterized by NMR and HRMS spectra. Its interaction with proteins, including bovine serum albumin (BSA) and human serum albumin (HSA), were investigated by spectral methods and molecular simulation. Fluorescence quenching, together with UV absorption spectrum and time-resolved fluorescence spectrums indicated a static process in BSA/HSA-IAPA system. Thermodynamic parameters including ΔH and ΔS calculated by Vant't Hoff equation were all positive, showing that hydrophobic force was the major force in the interaction of compound IAPA and BSA/HSA. Site marker competitive displacement experiments proved that IAPA bound to site I at BSA/HSA. Synchronous fluorescence spectrum and three-dimensional fluorescence spectrum were also used to investigate the conformational changes of BSA/HSA after binding with compound IAPA. The above results were further verified by molecular docking.

Nisoldipine represents a compound with diverse pharmacological activities. The interaction between nisoldipine and human serum albumin (HSA) was investigated using various methods, including UV–vis, three-dimensional fluorescence, synchronous fluorescence, electrochemical methods and molecular docking. The decreased quenching constant upon increasing temperatures and UV–vis absorption difference spectrum revealed that there was a static quenching mechanism rather than a dynamic quenching mechanism in the interaction of nisoldipine with human serum albumin. The thermodynamic parameters demonstrated that the binding of nisoldipine to human serum albumin was spontaneous and hydrogen bonding, hydrophobic interactions as well as electrostatic interactions played major roles in the binding process. The binding distance was 2.31 nm, indicating the presence of fluorescence energy transfer. Site marker competitive experiments and molecular docking demonstrated that the binding site of nisoldipine in human serum albumin was site I (subdomain IIA). In addition, three-dimensional fluorescence as well as synchronous fluorescence spectra suggested conformational changes of HSA due to the interaction with nisoldipine.

Carbon dots (CDs) have been widely applied in bioimaging, drug delivery and nanomedicine. In this study, the interaction binding mechanism of CDs with calf thymus DNA (ctDNA) has been investigated. A bottom-up synthetic route was selected at low temperature and a one-pot green synthesis of CDs was applied with ascorbic acid as carbon precursor and a water phase reflow at 90 °C under stirring for 3.5 h. The resulting as-synthesized CDs exhibited a green-yellow color, different than what has already been reported for this product with ascorbic acid as carbon precursor. The quantum yield of CDs was 13.3% and the fluorescence decay was 3.19 ns. Analytic methods such as UV-vis absorbance, fluorescence spectroscopy, circular dichroism spectroscopy and electrochemical approaches were used to study the binding mechanism between the CDs and ctDNA. Overall, the results indicated that the binding mode between CDs and ctDNA was intercalation. Moreover, the CDs exhibited specific properties that may be useful in the replacement of other, often toxic fluorescent dyes that are commonly used for organ imaging. CDs may therefore represent a promising fluorescence probe of ctDNA.

Here we synthesized four 3-fluorooxindole derivatives and investigated their affinity interactions with serum albumin by using multi-spectral, electrochemical, and molecular docking. Fluorescence spectroscopy results revealed the affinity of 3-fluorooxindole derivatives and serum albumin. UV spectroscopy showed the type of quenching for both were static quenching, which was proved by temperature dependence experiments and time-resolved fluorescence. Electrochemical experiment results suggested the binding constant of 3-fluorooxindole derivatives and serum albumin was 103–104 by the order of magnitude. Synchronous fluorescence spectroscopy and infrared spectroscopy demonstrated the effect on the secondary structure of serum albumin in the presence of 3-fluorooxindole units. Furthermore, molecular docking and site competition experiments result determined that 3-fluorooxindole derivatives bind to site I of serum albumin. Finally, the interactions between 3-fluorooxindole derivatives and serum albumin were investigated by various methods and summarized the effects of substituents in 3-fluorooxindole derivatives on serum albumin interactions. These results provide a reference for the design of subsequent synthesis of 3-fluorooxindole derivatives and theoretical support for the development of related fluorine-containing drugs.

In order to clarify the mitochondrial toxicity mechanism of the organic arsenical MOPIMP (2-methoxy-4-(((4-(oxoarsanyl) phenyl) imino) methyl) phenol), research was carried out at the sub-cell level based on the previous finding that the compound MOPIMP can damage the mitochondria by triggering a burst of ROS. After investigating its influence on isolated mitochondria in vitro, it was demonstrated that a high dose of MOPIMP with short-term exposure can induce mitochondrial swelling, decrease the membrane potential, enhance the permeability of H+ and K+, and induce membrane lipid peroxidation, indicating that it can result in an MPT process in a ROS-mediated and Ca2+-independent manner. Additionally, MPT was also aggravated as a result of impairment of the membrane integrity and membrane fluidity. In addition, short-term incubation between mitochondria and compound MOPIMP promoted the inhibition of respiratory chain complexes I, II, III and IV, as well as damage to the respiration process, which supported the previous finding about the burst of ROS. On the other hand, after long-term exposure by the organic arsenical MOPIMP, mitochondrial metabolic dysfunction was triggered, which was in accordance with perturbation of the respiratory chain complexes as well as the respiration process. This work systematically sheds light on the mitochondrial toxicity mechanism of the organic arsenical MOPIMP, including induction of the MPT process and inhibition of respiratory metabolism, which provides a potential target for organic arsenicals as anti-tumor drugs.

Considering the vital role of cellular redox state, more and more researches focus on the design of drugs targeting thioredoxin reductase (TrxR), an important enzyme in maintaining the balance of cellular redox. Here two organic arsenicals, 2-(((4-(1,3,2-dithiarsinan-2-yl) phenyl) imino) methyl) phenol (PIM-PAO-PDT) and N-(4-(1,3,2-dithiarsinan-2-yl) phenyl)-2-hydroxybenzamide (PAM-PAO-PDT), bearing the S-As-S chemical scaffold and different linking groups have been synthesized, and both of them show the better inhibitory activity and selectivity towards HL-60 cells. Importantly, it is illustrated that they can target TrxR selectively and inhibit its activity via the disturbance for Cys83 and Cys88 located in conserved active sites. Afterwards, the cells suffer from the burst of ROS, consumption of antioxidants and high sensitivity for oxidants, which further damage the mitochondria leading to dysfunction including the collapse of membrane potential, ATP level decline, mitochondrial membrane swelling, MPTP opening, Ca2+ and cytochrome c release. Then the mitochondria-dependent apoptosis is triggered by PIM-PAO-PDT and PAM-PAO-PDT, which can also be deterred in the presence of NAC, DTT or LA. Although the organic arsenicals can suppress TrxR activity, the following oxidative stress and mitochondrial dysfunction are the main causes for apoptosis.

The pollution of Hg2+ is one of the most serious problems to human health due to their high toxicity, mobility, difficulty in degradation and ability of accumulation in ecological systems. Thus, it is of great importance to develop highly selective and sensitive probe for detecting Hg2+ in aquatic ecosystems. Here we propose a new turn-on strategy for specific recognition and detection of Hg2+. Mn-doped ZnSe quantum dots (QDs) with small size (2.1 nm) were prepared and adopted as probe, the small size of doped QDs makes the replacement of Mn2+ by Hg2+ accessible, which eliminates the fluorescence quenching effect of superficial Mn2+ on Mn-doped ZnSe QDs. Different from traditional semiconductor nanocrystals based turn-off probe for detecting Hg2+, we realize a turn-on strategy for the selective detection of Hg2+ by Hg2+-Mn2+ replacement using semiconductor nanocrystals (Mn-doped ZnSe QDs). This turn-on mechanism was verified by fluorescence spectra, ICP-AES and XPS. In the absence of Hg2+, Mn-doped ZnSe QDs possessed low fluorescence intensity. With the addition of Hg2+, the fluorescence intensity around 600 nm increased dramatically. Our Mn-doped ZnSe QDs exhibits excellent selectivity and sensitivity for Hg2+. The limit of detection is 7.0 nM, which is lower than the mercury toxic level defined by the U.S. Environmental Protection Agency (10 nM). The result of Hg2+ detection in real samples indicates the feasibility and sensitivity of our probe for application in environmental samples.

Methotrexate (MTX), as one of the most significant controlling anti-rheumatism and antineoplastic medicine, which are of interest diverse pharmacological and biological activities. In this work, we determined the molecular interactions between MTX and deoxyribonucleic acid (DNA) based on the berberine (BH) as a fluorescent probe. UV–Vis spectroscopy and fluorescence studies suggested that this interaction process is predominantly a static process and intercalation of MTX into the double helix of hsDNA. The calculated negative values of enthalpy (− 60.43 kJ mol− 1) and entropy (− 127.62 J mol− 1 K− 1) revealed that the binding reaction was predominantly driven by hydrogen bonds and van der Waals interactions. The effects of iodide quenching studies, thermal denaturation and pH on DNA-BH-MTX system were studied to support the intercalative binding of MTX with hsDNA. Furthermore, molecular docking methods further confirmed the selective binding mode between MTX and hsDNA. These findings here are expected to benefit the pharmacological testing of MTX as well as clinical research and drug screening in vitro.

Contamination of antibiotic residues in food and water is an understudied safety concern and is increasingly gaining importance worldwide due to the rising rates of drug resistant organisms. As a class of antibiotics targeting β -lactam, cephalosporin is frequently used in treatment of bacterial infections. In this study, molecular modeling approaches in combination with absorbance, fluorescence and circular dichroism spectroscopy was employed to investigate the interactions of four cephalosporins (cefalexin, cefaclor, cefixime and cefepime) with human serum albumin (HSA). In the mechanism discussion, it was proved that the fluorescence quenching of HSA by cephalosporin is a result of the formation of cephalosporin-HSA complex. Binding parameters calculating from Stern-Volmer method and Scatchard method showed that cephalosporin bind to HSA with the binding affinities of the order 10 3 –10 4 L·mol − 1 . The thermodynamic parameters studies revealed that the binding was characterized by negative enthalpy and negative entropy changes and the hydrogen bonds and van der Waals interactions may play major role in complex formation. Furthermore, the investigated result indicates that azyl served as a hydrophilic group to change the chemical property for drug, the chlorine atom on the R 1 -group of cefaclor weakened the overall molecular polarity or hydrophilicity, while the binding site on HSA was determined by the carboxylate of cefepime. Some other structural characteristics for four kind of cephalosporins were also exhibited in this paper.

Cephalosporins belong the largest class of antibiotics used in the treatment of a wide range of infectious diseases caused by susceptible organisms. In the present study, we chose two typical antibiotics cefalexin/cefixime based on their structure, and investigated the interaction of cephalexin/cefixime with bovine serum albumin (BSA) using UV-vis absorption spectra, fluorescence spectroscopy, circular dichroism (CD) spectroscopy and molecular modeling approaches. Spectroscopic experiments revealed the formation of a BSA - cefalexin/cefixime complex. The binding parameters calculated using a modified Stern - Volmer method and the Scatchard method reached 103 -104 L·mol-1 . Thermodynamic parameter studies revealed that binding characteristics by negative enthalpy and positive entropy changes, and electrostatic interactions play a major role. Site marker competitive displacement experiments and molecular modeling approaches demonstrated that cefalexin and cefixime bind with appropriate affinity to site I (subdomain IIA) of BSA. Furthermore, synchronous fluorescence spectra, CD spectra and molecular modeling results indicated that the secondary structure of BSA was changed in the presence of cefalexin and cefixime. Additionally, the effects of metal ions on the BSA - cefalexin/cefixime system were also assessed.

Currently, animal models used in research on implant-associated osteomyelitis primarily use intramedullary fixation and initial inoculum of planktonic bacterial cells. However, these techniques have certain limitations, including lack of rotational stability and instable inoculation. To improve these models, the present study aimed to establish a novel rabbit model of implant-associated osteomyelitis using biofilm as the initial inoculum following plate fixation of the femoral fracture. A total of 24 New Zealand White rabbits were randomly divided into two equal groups. Osteotomy was performed at the right femoral shaft using a wire saw following fixation with a 5-hole stainless steel plate. The plates were not colonized with bacteria in group 1, but colonized with a biofilm of Staphylococcus aureus (American Type Culture Collection, 25923) in group 2. All the rabbits were sacrificed after 21 days for clinical, X-ray, micro-computed tomography and histological assessments of the severity of osteomyelitis. Scanning electron microscopy and confocal laser scanning microscopy were used for biofilm assessment. In group 2, pus formation, periosteal reaction, cortical destruction and absorption were observed in all the rabbits and biofilm formation was observed on all the plates. However, no pus formation was observed except for a slight inflammatory response and all the plates appeared clean without infection in group 1. The differences between the two groups were statistically significant regarding histologic scores and semi-quantification of the bacteria on the plates (P

Two mitochondria-targeted fluorescent probes (TPP- and TEA-BODIPY) were rationally designed and easily synthesized. These probes can specifically stain mitochondria in living cells with superior brightness, low cytotoxicity and high photostability, thus are quite promising as mitochondrial tracking probes.

Cefixime is a third generation orally administered cephalosporin that is frequently used as a broad spectrum antibiotic against various gram-negative and gram-positive bacteria. In this study, a simple and sensitive fluorescent sensor for the determination of the cefixime and ctDNA was established based on the CdTe:Zn2+ quantum dots (QDs). The fluorescence of CdTe:Zn2+ QDs can be effectively quenched by cefixime in virtue of the surface binding of cefixime on CdTe:Zn2+ QDs and the subsequent photoinduced electron transfer process from CdTe:Zn2+ QDs to cefixime, in particular, the high sensitivity of QDs fluorescence emission to cefixime at the micromole per liter level, which render the cefixime-CdTe:Zn2+ QDs system into fluorescence "OFF" status, then turn on in the presence of ctDNA. Furthermore, the Fourier transform infrared (FTIR) spectra of characteristic bands of C-N and N-H groups of cefixime endow evidence for the interaction of cefixime with CdTe:Zn2+ QDs. The relative electrochemical behavior of the affinity of CdTe:Zn2+ QDs for cefixime and ctDNA reveals the potential molecular binding mechanism.

Background: The coronavirus 2019 (COVID-19) pandemic has led to national school closures Fortunately, at the time of writing, most schools have begun to reopen

Based on the potential therapeutic value in targeting mitochondria and the fluorophore tracing ability, a fluorescent mitochondria-targeted organic arsenical PDT-PAO-F16 was fabricated, which not only visualized the cellular distribution, but also exerted anti-cancer activity in vitro and in vivo via targeting pyruvate dehydrogenase complex (PDHC) and respiratory chain complexes in mitochondria. In details, PDT-PAO-F16 mainly accumulated into mitochondria within hours and suppressed the activity of PDHC resulting in the inhibition of ATP synthesis and thermogenesis disorder. Moreover, the suppression of respiratory chain complex I and IV accelerated the mitochondrial dysfunction leading to caspase family-dependent apoptosis. In vivo, the acute promyelocytic leukemia was greatly alleviated in the PDT-PAO-F16 treated group in APL mice model. Our results demonstrated the organic arsenical precursor with fluorescence imaging and target-anticancer efficacy is a promising anticancer drug.