A Unique Hybridization Route to Access Hydrazylnaphthalimidols as Novel Structural Scaffolds of Multitargeting Broad-Spectrum Antifungal Candidates.

This study developed a class of novel structural antifungal hydrazylnaphthalimidols (HNs) with multitargeting broad-spectrum potential via multicomponent hybridization to confront increasingly severe fungal invasion. Some prepared HNs exhibited considerable antifungal potency; especially nitrofuryl HN 4a (MIC = 0.001 mM) exhibited a potent antifungal activity against Candida albicans, which is 13-fold higher than that of fluconazole. Furthermore, nitrofuryl HN 4a displayed low cytotoxicity, hemolysis and resistance, as well as a rapid fungicidal efficacy. Preliminary mechanistic investigations revealed that nitrofuryl HN 4a could inhibit lactate dehydrogenase to decrease metabolic activity and promote the accumulation of reactive oxygen species, leading to oxidative stress. Moreover, nitrofuryl HN 4a did not exhibit membrane-targeting ability; it could embed into DNA to block DNA replication but could not cleave DNA. These findings implied that HNs are promising as novel structural scaffolds of potential multitargeting broad-spectrum antifungal candidates for treating fungal infection.

One-step growth of Cu-doped carbon dots in amino-modified carbon nanotube-modified electrodes for sensitive electrochemical detection of BPA.

Copper-doped carbon dots and aminated carbon nanotubes (Cu-CDs/NH2-CNTs) nanocomposites were synthesized by a one-step growth method, and the composites were characterized for their performance. An electrochemical sensor for sensitive detection of bisphenol A (BPA) was developed for using Cu-CDs/NH2-CNTs nanocomposites modified with glassy carbon electrodes (GCE). The sensor exhibited an excellent electrochemical response to BPA in 0.2 M PBS (pH 7.0) under optimally selected conditions. The linear range of the sensor for BPA detection was 0.5-160 µM, and the detection limit (S/N = 3) was 0.13 µM. Moreover, the sensor has good interference immunity, stability and reproducibility. In addition, the feasibility of the practical application of the sensor was demonstrated by the detection of BPA in bottled drinking water and Liu Yang River water.

Sterically Hindered Oleogel-Based Underwater Adhesive Enabled by Mesh-Tailoring Strategy.

Underwater adhesives hold significant relevance in daily life and numerous industrial applications. Despite considerable efforts, developing scalable, high-performance underwater adhesives through a simple and effective method remains a formidable challenge. This study presents a novel mesh-tailoring strategy for in situ, rapid, and ultrastrong oleogel-based underwater adhesives (OUA), which comprises a highly crosslinked polyurethane network with a matching mesh size (≈2.22 nm) that precisely entraps bio-based epoxidized soybean oil (ESO) molecules (≈2.31 nm) by steric hindrance effect. This oleogel exhibits unprecedented robust mechanical properties (≈35 MPa) and maintains stability under extreme conditions, including high temperatures (100 °C), high pressures (30 MPa), and immersion in various solvents (water, ethanol, or ESO). In particular, this oleogel displays high hydrophobicity, rapid curing, and strong interface affinity, resulting in ultrahigh underwater adhesion strength (up to 2.13 MPa) and exceptional substrate universality. Moreover, the remarkable environmental adaptability and stability of OUA enable its use in harsh aqueous environments, including acidic/alkaline, saline, and extreme temperature solutions. The comprehensive capabilities of the OUA underscore its potential for building underwater structures, repairing leaky containers, and sealing broken submarine pipelines. This research establishes the foundation for the designing of next-generation underwater adhesives and offers fresh perspectives for exploring oleogel-based materials.

Platelet-rich plasma promotes skeletal muscle regeneration and neuromuscular functional reconstitution in a concentration-dependent manner in a rat laceration model.

Abnormal function of injured muscle with innervation loss is a challenge in sports medicine. The difficulty of rehabilitation is regenerating and reconstructing the skeletal muscle tissue and the neuromuscular junction (NMJ). Platelet-rich plasma (PRP) releases various growth factors that may provide an appropriate niche for tissue regeneration. However, the specific mechanism of the PRP's efficacy on muscle healing remains unknown. In this study, we injected PRP with different concentration gradients (800, 1200, 1600 × 109 pl/L) or saline into a rat gastrocnemius laceration model. The results of histopathology and neuromyography show that PRP improved myofibers regeneration, facilitated electrophysiological recovery, and reduced fibrosis in a concentration-dependent manner. Furthermore, we found that PRP promotes the activity of satellite cells by upregulating the expression of the myogenic regulatory factor (MyoD, myogenin). Meanwhile, PRP promotes the regeneration and maturation of acetylcholine receptor (AChR) clusters of the Neuromuscular junction (NMJ) on the regenerative myofibers. Finally, we found that the expression of the Agrin, LRP4, and MuSK was upregulated in the PRP-treated groups, which may contribute to AChR cluster regeneration and functional recovery. The conclusions proposed a hypothesis for PRP treatment's efficacy and mechanism in muscle injuries, indicating promising application prospects.

Design, Synthesis, and Insecticidal and Fungicidal Activities of Ether/Oxime-ether Containing Isoxazoline Derivatives.

The existing agricultural insecticides have developed drug resistance from long-term use. Isoxazoline derivatives are new insecticides discovered in the 21st century. Because of their unique insecticidal mechanism, high selectivity, safety, and no significant cross resistance with the existing pesticides on the market, they have become a hot spot in the field of pesticide research. Herein, a series of novel isoxazoline derivatives containing ether and oxime-ether structures were designed and synthesized by a scaffold-hopping strategy using the pesticide fluralaner as a template structure. Through the investigation of insecticidal activity and the systematic structure-activity relationship, a series of compounds with high insecticidal activities were found, and compounds I-4, II-9, and II-13 with LC50 values of 0.00008-0.00036 mg/L against diamondback moth emerged as novel insecticide candidates. These compounds also exhibited broad spectrum fungicidal activities against 14 plant fungi. The current work provides a reference for the design of new isoxazoline compounds based on the scaffold-hopping strategy.

Non-isocyanate Polyurethane Coating with High Hardness, Superior Flexibility, and Strong Substrate Adhesion.

Flexible hard coatings with strong adhesion are critical requirements for several foldable devices and marine applications; however, only a few such coatings have been reported. Herein, we report a non-isocyanate polyurethane (NIPU) coating prepared by the epoxy-oligosiloxane nanocluster-amine curing reaction and cyclic carbonate-amine polyaddition, where the former provides the coating with ceramic-like hardness and polymer-like flexibility while the latter polymerization results in NIPU with strong substrate adhesion. The coating is transparent (>92% transmittance), hard (5-7 H), and flexible (2 mm bending diameter). It has strong adhesion to various substrates including aluminum alloy, titanium, steel, glass, ceramic, epoxy, and polyethylene terephthalate (2-8 MPa), which can be attributed to the high density of polar groups in NIPU. Moreover, we can facilely endow the coating with anti-icing, self-cleaning, and anti-smudge capabilities by incorporating amine-terminated low-surface-tension polydimethylsiloxane (PDMS) to replace a part of the amine curing agent. Particularly, the mechanical properties of NIPU coatings are only slightly affected by the introduction of low-content PDMS since it intends to enrich on the surface. The novel coating has promising future for use in fields of foldable devices and marine applications.

Clinical usefulness of linked color imaging in identifying Helicobacter pylori infection: A systematic review and meta-analysis.

BACKGROUND: Accurate diagnosis of Helicobacter pylori (H. pylori) infection status is a crucial premise for eradication therapy, as well as evaluation of risk for gastric cancer. Recent progress on imaging enhancement endoscopy (IEE) made it possible to not only detect precancerous lesions and early gastrointestinal cancers but also to predict H. pylori infection in real time. As a novel IEE modality, linked color imaging (LCI) has exhibited its value on diagnosis of lesions of gastric mucosa through emphasizing minor differences of color tone. AIM: To compare the efficacy of LCI for H. pylori active infection vs conventional white light imaging (WLI). METHODS: PubMed, Embase, Embase and Cochrane Library were searched up to the end of April 11, 2022. The random-effects model was adopted to calculate the diagnostic efficacy of LCI and WLI. The calculation of sensitivity, specificity, and likelihood ratios were performed; symmetric receiver operator characteristic (SROC) curves and the areas under the SROC curves were computed. Quality of the included studies was chosen to assess using the quality assessment of diagnostic accuracy studies-2 tool. RESULTS: Seven original studies were included in this study. The pooled sensitivity, specificity, positive likelihood rate, and negative likelihood rate of LCI for the diagnosis of H. pylori infection of gastric mucosa were 0.85 [95% confidence interval (CI): 0.76-0.92], 0.82 (95%CI: 0.78-0.85), 4.71 (95%CI: 3.7-5.9), and 0.18 (95%CI: 0.10-0.31) respectively, with diagnostic odds ratio = 26 (95%CI: 13-52), SROC = 0.87 (95%CI: 0.84-0.90), which showed superiority of diagnostic efficacy compared to WLI. CONCLUSION: Our results showed LCI can improve efficacy of diagnosis on H. pylori infection, which represents a useful endoscopic evaluation modality for clinical practice.

Identification of Novel Antifungal Skeleton of Hydroxyethyl Naphthalimides with Synergistic Potential for Chemical and Dynamic Treatments.

The invasion of pathogenic fungi poses nonnegligible threats to the human health and agricultural industry. This work exploited a family of hydroxyethyl naphthalimides as novel antifungal species with synergistic potential of chemical and dynamic treatment to combat the fungal resistance. These prepared naphthalimides showed better antifungal potency than fluconazole towards some tested fungi including Aspergillus fumigatus, Candida tropicalis and Candida parapsilosis 22019. Especially, thioether benzimidazole derivative 7f with excellent anti-Candida tropicalis efficacy (MIC = 4 µg/mL) possessed low cytotoxicity, safe hemolysis level and less susceptibility to induce resistance. Biochemical interactions displayed that 7f could form a supramolecular complex with DNA to block DNA replication, and constitute a biosupermolecule with cytochrome P450 reductase (CPR) from Candida tropicalis to hinder CPR biological function. Additionally, 7f presented strong lipase affinity, which facilitated its permeation into cell membrane. Moreover, 7f with dynamic antifungal potency promoted the production and accumulation of reactive oxygen species (ROS) in cells, which destroyed the antioxidant defence system, led to oxidative stress with lipid peroxidation, loss of glutathione, membrane dysfunction and metabolic inactivation, and eventually caused cell death. The chemical and dynamic antifungal synergistic effect initiated by hydroxyethyl naphthalimides was a reasonable treatment window for prospective development.

An unanticipated discovery of novel naphthalimidopropanediols as potential broad-spectrum antibacterial members.

Constructing a new antibacterial structural framework is an effective strategy to combat drug resistance. This work discovered a class of naphthalimidopropanediols (NIOLs) as a novel structural type of potential broad-spectrum antibacterial agents. Especially, NIOLs 9u, 12i, 15 against Staphylococcus aureus and NIOLs 9l, 13a against Pseudomonas aeruginosa showed excellent inhibitory activities, and they displayed high membrane selectivity from an electrostatic distinction on the membranes between bacteria and mammalian cells. These highly active NIOLs could effectually inhibit the bacterial growths, and relieve the resistance developments. Moreover, the facts of membrane depolarization, outer/inner membrane permeabilization and leakage of intracellular materials, demonstrated that these NIOLs could target and destroy the S. aureus or P. aeruginosa membranes. In particular, they could disrupt the antioxidant defense systems of S. aureus or P. aeruginosa through up-regulation of reactive oxygen species. Simultaneously, they could render the metabolic inactivation of the tested strains, and eradicate the formed biofilms and efficiently kill the strains within the biofilms. The in vitro and in vivo cytotoxicity assay indicated that these compounds possessed low toxicity. These findings of novel NIOLs as potential broad-spectrum antibacterial members provided a bright hope for conquering drug resistance.

[Experimental study on the regulation of subchondral bone plate osteoprotegerin/receptor activator of nuclear factor kappa-B ligand system by berberine to retard the development of osteoarthritis in rabbits].

OBJECTIVE: To investigate the effect of intra-articular berberine injection on the structural remodeling of subchondral bone plate and osteoprotegerin/receptor activator of nuclear factor kappa-B ligand(OPG/RANKL) system expression in rabbits with osteoarthritis(OA). METHODS: Forty 12-month-old male rabbits with an average of(2.73±0.18) kg of body weight, underwent left anterior cruciate ligament transection(ACLT), and were divided into berberine group and placebo groups after operation, 20 rabbits in each group. The berberine group received intra-articular injection of 100 µmol/L berberine 0.3 ml every week for 6 weeks. In placebo group, the same dose of 0.9% sodium chloride injection was injected into the left knee joint cavity every week for 6 weeks. Another 20 12-month-old male rabbits, weighing (2.68±0.18) kg, underwent sham operation on the left knee joint without intra-articular injection intervention (sham operation group). On the last day of the sixth week after operation, three groups of animals were sacrificed to obtain knee joint specimens. The femoral medial condyle samples were obtained for histological evaluation of cartilage and subchondral bone, Mankin scoring system was used to evaluate articular cartilage structure. Image-Pro Plus(IPP) software was used to evaluate subchondral bone plate bone volume(BV), bone volume/total volume(BV/TV), trabecular circumference(TC), mean trabecular thickness (Tb.Th). Real-time quantitative reverse transcription polymerization Enzyme chain reaction(reverse transcription-polymerase chain reaction, RT-PCR) was used to detect the mRNA expression levels of OPG and RANKL in subchondral bone tissue at 6 weeks after operation. RESULTS: The cartilage structure evaluation showed that the surface of cartilage tissue in the sham operation group was smooth and flat, and the safranin coloration was full in the full thickness of the cartilage;the cartilage tissue in the berberine group showed uneven surface layer, and the staining of safranin O was mildly decreased;the surface layer fibrosis was seen in placebo group, Safranin O faded significantly. The Mankin score in the berberine group was lower than that in placebo group(P<0.01), but higher than that in sham operation group(P<0.01). The structural evaluation of subchondral bone plate showed that the trabecular bone in sham-operated group was densely arranged;after berberine intervention, the trabeculae were closely arranged;the subchondral bone trabeculae in placebo group were relatively sparse, and the distance between trabeculae was wider. Subchondral bone plate IPP software evaluation showed that BV, BV/TV, TC, Tb.Th in berberine group were higher than those in placebo group(P<0.01), BV, BV/TV, TC, Tb.Th in berberine group were higher than those in placebo group(P<0.01), while lower than the sham operation group (P<0.01). PCR test results showed that the expression of OPG mRNA in the berberine group was significantly higher than that in placebo group(P<0.01), and OPG mRNA in the berberine group was lower than that in sham operation group (P<0.01). There was no significant difference in mRNA expression of RANKL among three groups(P>0.05);the ratio of OPG/RANKL in berberine group was higher than that in placebo group(P<0.01), but lower than that in sham operation group(P<0.01). CONCLUSION: Intra-articular injection of berberine can effectively inhibit the resorption of subchondral bone in the early stage of OA and delay the development of the disease. The specific mechanism may be that berberine maintains the balance of OPG/RANKL system by up-regulating the expression of OPG gene in subchondral bone.

Tumor microenvironment-responsive nanohybrid for hypoxia amelioration with photodynamic and near-infrared II photothermal combination therapy.

Phototherapy, particularly photothermal therapy (PTT) and photodynamic therapy (PDT), has been widely investigated for tumor treatment. However, the limited tissue penetration depth of light in the near-infrared I (NIR-I) region and the hypoxic tumor microenvironment (TME) severely constrain their clinical applications. To address these challenges, in the present study, we developed a chlorin e6 (Ce6) and MnO2-coloaded, hyaluronic acid (HA)-coated single-walled carbon nanohorns (SWNHs) nanohybrid (HA-Ce6-MnO2@SWNHs) for PDT and PTT combination therapy of tumor. HA-Ce6-MnO2@SWNHs responded to the mild acidic TME to ameliorate tumor hypoxia, thus enhancing tumor PDT. Moreover, HA-Ce6-MnO2@SWNHs had a high photothermal conversion efficiency at 1064 nm (55.48%), which enabled deep tissue penetration (3.05 cm) and allowed for highly efficient tumor PTT in near-infrared II (NIR-II) window. PDT and PTT combination therapy with HA-Ce6-MnO2@SWNHs achieved a good therapeutic efficacy on 4T1 tumor-bearing mice, eradicating the primary tumors and suppressing cancer recurrence. Our study provides a promising strategy for developing a hypoxia relief and deep tissue penetration phototherapy platform by using SWNHs for highly effective tumor PDT and NIR-II PTT combination therapy. STATEMENT OF SIGNIFICANCE: The hypoxic tumor microenvironment (TME) and the limited penetration of the NIR-I light in biological tissues compromise the efficacy of photothermal therapy (PTT) and photodynamic therapy (PDT) on tumors. Here, we developed a chlorin e6 (Ce6) and MnO2-coloaded, hyaluronic acid (HA)-coated single-walled carbon nanohorns (SWNHs) nanohybrid (HA-Ce6-MnO2@SWNHs) for PDT and PTT combination therapy of tumors. The nanohybrid could efficiently accumulate in tumors through CD44-mediated active targeting. The sequential MnO2-enhanced PDT and efficient NIR-II PTT had a remarkable therapeutic effect by eliminating the primary tumor and simultaneously inhibiting tumor recurrence.

Coumarin thiazoles as unique structural skeleton of potential antimicrobial agents.

A novel type of coumarin thiazoles as unique multi-targeting antimicrobial agents were developed through four steps including cyclization, nucleophilic substitution and condensation starting from commercial resorcine. Most of the prepared coumarin thiazoles displayed favorable inhibitory potency against the tested strains. Noticeably, methyl oxime V-a exerted potent inhibitory efficacy against methicillin-resistant Staphylococcus aureus (MRSA) at low concentration (1 µg/mL) and showed broad antimicrobial spectrum. Medicinal bioevaluations revealed that the active molecule V-a exhibited low toxicity toward mammalian cells, rapidly killing effect, good capability of eradicating MRSA biofilms and unobvious probability to engender drug resistance. Chemical biological methods were employed to investigate preliminary mechanism, which indicated that compound V-a was able to damage the integrity of membrane to trigger leakage of protein, insert into MRSA DNA to block its replication and induce the generation of reactive oxygen species (ROS) to inhibit bacterial growth. Computational study manifested that low HOMO-LUMO energy gap of molecule V-a was favorable to exert high antimicrobial activity.

Novel metronidazole-derived three-component hybrids as promising broad-spectrum agents to combat oppressive bacterial resistance.

The dreadful bacterial resistance to clinical drugs calls for the development of novel antibacterials. This work developed a class of unique metronidazole-derived three-component hybrids as promising antibacterial therapeutic alternatives. Bioactive assay discovered that p-chlorophenylhydrazone derivative 6b possessed excellent ability to suppress the growth of drug-resistant E. coli (MIC = 0.5 µg/mL), being 16 folds more potent than norfloxacin (MIC = 8 µg/mL). The active molecule 6b with imperceptible hemolysis could effectively retard the development of bacterial drug resistance within 30 passages. Moreover, compound 6b displayed a favorable inhibitory effect on E. coli biofilms and could act rapidly in bactericidal efficacy. Subsequent exploration of mechanism revealed that 6b could destruct the bacterial cytoplasmic membrane, leading to the leakage of intracellular protein. The inactivation of lactate dehydrogenase, metabolic stagnation and the accumulation of reactive oxygen species caused by 6b were observed. Furthermore, molecule 6b could form a supramolecular complex with DNA to obstruct DNA replication. These results demonstrated that metronidazole-derived three-component hybrids provided a large potential for deep development as prospective antibacterial agents.

Design, synthesis, and insecticidal and fungicidal activities of quaternary ammonium salt derivatives of a triazolyphenyl isoxazoline insecticide.

BACKGROUND: Insect pests seriously decrease the yield and quality of agricultural crops. Resistance to commonly used insecticides is increasingly undermining their effectiveness, and therefore the development of agents with novel modes of action is desirable. Isoxazolines are a new class of insecticides that act on γ-aminobutyric acid (GABA) gated chloride channels. In this work, we used the highly active 4-triazolyphenyl isoxazoline DP-9 as a parent structure to design and synthesize a series of quaternary ammonium salt (QAS) derivatives, and we systematically evaluated their insecticidal and antifungal activities. RESULTS: Many of the synthesized QASs exhibit insecticidal activities equivalent to or higher than that of DP-9. In particular, compounds I-31 (93%, 0.00005 mg/L) and I-34 (80%, 0.00001 mg/L) showed insecticidal activities against diamondback moth larvae that were 2-10 times higher than those of fluralaner (70%, 0.0001 mg/L) and DP-9 (80%, 0.0001 mg/L), in addition to showing excellent activities against oriental armyworm, fall armyworm, cotton bollworm, corn borer, and mosquito larvae. Furthermore, all of the synthesized compounds also showed broad-spectrum fungicidal activities. CONCLUSION: The insecticidal activities of QAS derivatives of DP-9 were the same as or better than the activity of DP-9. Compounds I-31 and I-34 showed better insecticidal activities against diamondback moth larvae than fluralaner and DP-9, and thus are promising new candidates for insecticide research.

Discovery of unique thiazolidinone-conjugated coumarins as novel broad spectrum antibacterial agents.

Unique coumarin conjugates with thiazolidinone as novel structural antibacterial modulators were exploited to combat the lethal multidrug-resistant bacterial infections. Bioactivity evaluation identified that indole-incorporated coumarin thiazolidinone conjugate 14a with low cytotoxicity to mammalian cells showed a broad antibacterial spectrum and exerted potent inhibition efficiencies to the tested germs at low concentrations (0.25-2 µg/mL). Moreover, the favorable performance of 14a in eradicating bacterial biofilm was beneficial to avert developing drug resistance. Mechanistic explorations revealed that molecule 14a was able to destroy cell membrane, leading to the leakage of intracellular materials and metabolism inhibition. The accumulation of excess reactive oxygen species (ROS) mediated by compound 14a could impede glutathione (GSH) activity and induce lipid peroxidation to suppress bacteria growth. Furthermore, compound 14a could not only intercalate into DNA base pair but also take part in non-covalent interaction with DNA gyrase B to hinder their biological function. Quantum chemical study indicated that molecule 14a had low HOMO-LUMO energy gap, which resulted in more stabilizing interactions and was conducive to displaying better antibacterial activity. ADMET analysis manifested that 14a possessed promising pharmacokinetic properties.

An unanticipated discovery towards novel naphthalimide corbelled aminothiazoximes as potential anti-MRSA agents and allosteric modulators for PBP2a.

Available therapeutic strategies are urgently needed to conquer multidrug resistance of MRSA. A visible effort was guided towards the advancement of novel antibacterial framework of naphthalimide corbelled aminothiazoximes, and desired to assert some insight on the conjunction of individual pharmacophore with distinct biological activities and unique action mechanism. Preliminary assessment displayed that dimethylenediamine derivative 13d presented a wonderful inhibition on MRSA (MIC = 0.5 µg/mL), and showed excellent membrane selectivity (HC50 > 200 µg/mL) from an electrostatic distinction of the electronegative bacterial membranes and the electroneutral mammalian membranes. Moreover, 13d could effectually relieve the development of MRSA resistance. Investigations into explaining the mechanism of anti-MRSA disclosed that 13d displayed strong lipase affinity, which facilitated its permeation into cell membrane, causing membrane depolarization, leakage of cytoplasmic contents and lactate dehydrogenase (LDH) inhibition. Meanwhile, 13d could exert interaction with DNA to hinder biological function of DNA, and disrupt the antioxidant defense system of MRSA through up-regulation of ROS subjected the strain to oxidative stress. In particular, the unanticipated mechanism for naphthalimide corbelled aminothiazoximes that 13d could suppress the expression of PBP2a by inducing allosteric modulation of PBP2a and triggering the open of the active site, was discovered for the first time. These findings of naphthalimide corbelled aminothiazoximes as a small-molecule class of anti-MRSA agents held promise in strategies for treatment of MRSA infections.

Identification of a novel antifungal backbone of naphthalimide thiazoles with synergistic potential for chemical and dynamic treatment.

Aim: The high incidence and prevalence of fungal infections call for new antifungal drugs. This work was to develop naphthalimide thiazoles as potential antifungal agents. Results & methodology: These compounds showed significant antifungal potency toward some tested fungi. Especially, naphthalimide thiazole 4h with excellent anti-Candida tropicalis efficacy possessed good hemolysis level, low toxicity and no obvious resistance. Deciphering the mechanism showed that 4h interacted with DNA and disrupted the antioxidant defense system of C. tropicalis. Compound 4h also triggered membrane depolarization, leakage of cytoplasmic contents and LDH inhibition. Simultaneously, 4h rendered metabolic inactivation and eradicated the formed biofilms of C. tropicalis. Conclusion: The multifaceted synergistic effect initiated by naphthalimide thiazoles is a reasonable treatment window for prospective development.

One-pot synthesis of 68Ga-doped ultrasmall gold nanoclusters for PET/CT imaging of tumors.

Gold nanoclusters (AuNCs) have attracted much attention for tumor theranostics in recent years because of their ability of renal clearance and to escape the reticuloendothelial system (RES) sequestration. In this study, we presented a novel method to synthesize 68Ga-doped (labeled) AuNCs by simultaneous reduction of 68GaCl3 and HAuCl4 by glutathione. As synthesized 68Ga-doped, glutathione-coated AuNCs (68Ga-GSH@AuNCs) were ultrasmall in size (<2 nm), highly stable under physiological conditions and renally clearable, and had high efficiency for tumor targeting. To demonstrate the universality of this 68Ga labeling method and further enhance tumor targeting efficiency, arginine-glycine-aspartate (RGD)-containing peptide was introduced as co-reductant to synthesize RGD peptide and glutathione co-coated, 68Ga-labeled AuNCs (68Ga-RGD-GSH@AuNCs). Introduction of RGD peptide did not interfere the synthesis process but significantly enhanced the tumor targeting efficiency of the AuNCs. Our study demonstrated that it was feasible to label AuNCs with gallium-68 by direct reduction of the radioisotope and HAuCl4 with reductant peptides, holding a great potential for clinical translation for PET/CT detection of tumors.

Molecular design and preparation of 2-aminothiazole sulfanilamide oximes as membrane active antibacterial agents for drug resistant Acinetobacter baumannii.

A series of 2-aminothiazole sulfanilamide oximes were developed as new membrane active antibacterial agents to conquer the microbial infection. Benzoyl derivative 10c was preponderant for the treatment of drug-resistant A. baumannii infection in contrast to norfloxacin and exerted excellent biocompatibility against mammalian cells including erythrocyte and LO2 cell line. Meanwhile, it had ability to eradicate established biofilm to alleviate the resistance burden. Mechanism investigation elucidated that compound 10c was able to disturb the membrane effectively and inhibit lactic dehydrogenase, which led to cytoplasmic content leakage. The cellular redox homeostasis was interfered via the production of reactive oxygen and nitrogen species (RONS), which further contributed to respiratory pathway inactivation and reduction of GSH activity. This work indicated that 2-aminothiazole sulfanilamide oximes could be a promising start for the exploitation of novel antibacterial agents against pathogens.

Neuroprotective effects of Ginkgo biloba dropping pills in Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world; however, it lacks effective and safe treatments. Ginkgo biloba dropping pill (GBDP), a unique Chinese G. biloba leaf extract preparation, exhibits antioxidant and neuroprotective effects and has a potential as an alternative therapy for PD. Thus, the aims of this study were to evaluate the effects of GBDP in in vitro and in vivo PD models and to compare the chemical constituents and pharmacological activities of GBDP and the G. biloba extract EGb 761. Using liquid chromatography tandem-mass spectrometry, 46 GBDP constituents were identified. Principal component analysis identified differences in the chemical profiles of GBDP and EGb 761. A quantitative analysis of 12 constituents showed that GBDP had higher levels of several flavonoids and terpene trilactones than EGb 761, whereas EGb 761 had higher levels of organic acids. Moreover, we found that GBDP prevented 6-hydroxydopamine-induced dopaminergic neuron loss in zebrafish and improved cognitive impairment and neuronal damage in methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mice. Although similar effects were observed after EGb 761 treatment, the neuroprotective effects were greater after GBDP treatment on several endpoints. In addition, in vitro results suggested that the Akt/GSK3ß pathway may be involved in the neuroprotective effects of GBDP. These findings demonstrated that GBDP have potential neuroprotective effects in the treatment of PD.