Enhancing antibacterial properties by regulating valence configurations of copper: a focus on Cu-carboxyl chelates.

Optimizing the antibacterial effectiveness of copper ions while reducing environmental and cellular toxicity is essential for public health. A copper chelate, named PAI-Cu, is skillfully created using a specially designed carboxyl copolymer (a combination of acrylic and itaconic acids) with copper ions. PAI-Cu demonstrates a broad-spectrum antibacterial capability both in vitro and in vivo, without causing obvious cytotoxic effects. When compared to free copper ions, PAI-Cu displays markedly enhanced antibacterial potency, being about 35 times more effective against Escherichia coli and 16 times more effective against Staphylococcus aureus. Moreover, Gaussian and ab initio molecular dynamics (AIMD) analyses reveal that Cu+ ions can remain stable in the carboxyl compound's aqueous environment. Thus, the superior antibacterial performance of PAI-Cu largely stems from its modulation of copper ions between mono- and divalent states within the Cu-carboxyl chelates, especially via the carboxyl ligand. This modulation leads to the generation of reactive oxygen species (˙OH), which is pivotal in bacterial eradication. This research offers a cost-effective strategy for amplifying the antibacterial properties of Cu ions, paving new paths for utilizing copper ions in advanced antibacterial applications.

Mitochondrial-Targeted Metal-Phenolic Nanoparticles to Attenuate Intervertebral Disc Degeneration: Alleviating Oxidative Stress and Mitochondrial Dysfunction.

As intervertebral disc degeneration (IVDD) proceeds, the dysfunctional mitochondria disrupt the viability of nucleus pulposus cells, initiating the degradation of the extracellular matrix. To date, there is a lack of effective therapies targeting the mitochondria of nucleus pulposus cells. Here, we synthesized polygallic acid-manganese (PGA-Mn) nanoparticles via self-assembly polymerization of gallic acid in an aqueous medium and introduced a mitochondrial targeting peptide (TP04) onto the nanoparticles using a Schiff base linkage, resulting in PGA-Mn-TP04 nanoparticles. With a size smaller than 50 nm, PGA-Mn-TP04 possesses pH-buffering capacity, avoiding lysosomal confinement and selectively accumulating within mitochondria through electrostatic interactions. The rapid electron exchange between manganese ions and gallic acid enhances the redox capability of PGA-Mn-TP04, effectively reducing mitochondrial damage caused by mitochondrial reactive oxygen species. Moreover, PGA-Mn-TP04 restores mitochondrial function by facilitating the fusion of mitochondria and minimizing their fission, thereby sustaining the vitality of nucleus pulposus cells. In the rat IVDD model, PGA-Mn-TP04 maintained intervertebral disc height and nucleus pulposus tissue hydration. It offers a nonoperative treatment approach for IVDD and other skeletal muscle diseases resulting from mitochondrial dysfunction, presenting an alternative to traditional surgical interventions.

Injectable nanocomposite hydrogels with enhanced lubrication and antioxidant properties for the treatment of osteoarthritis.

Osteoarthritis (OA) is a chronic inflammatory joint disease characterized by progressive cartilage degeneration, synovitis, and osteoid formation. In order to effectively treat OA, it is important to block the harmful feedback caused by reactive oxygen species (ROS) produced during joint wear. To address this challenge, we have developed injectable nanocomposite hydrogels composed of polygallate-Mn (PGA-Mn) nanoparticles, oxidized sodium alginate, and gelatin. The inclusion of PGA-Mn not only enhances the mechanical strength of the biohydrogel through a Schiff base reaction with gelatin but also ensures efficient ROS scavenging ability. Importantly, the nanocomposite hydrogel exhibits excellent biocompatibility, allowing it to effectively remove ROS from chondrocytes and reduce the expression of inflammatory factors within the joint. Additionally, the hygroscopic properties of the hydrogel contribute to reduced intra-articular friction and promote the production of cartilage-related proteins, supporting cartilage synthesis. In vivo experiments involving the injection of nanocomposite hydrogels into rat knee joints with an OA model have demonstrated successful reduction of osteophyte formation and protection of cartilage from wear, highlighting the therapeutic potential of this approach for treating OA.

Enhanced Mitochondrial Targeting and Inhibition of Pyroptosis with Multifunctional Metallopolyphenol Nanoparticles in Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is a significant contributor to low back pain, characterized by excessive reactive oxygen species generation and inflammation-induced pyroptosis. Unfortunately, there are currently no specific molecules or materials available to effectively delay IVDD. This study develops a multifunctional full name of PG@Cu nanoparticle network (PG@Cu). A designed pentapeptide, bonded on PG@Cu nanoparticles via a Schiff base bond, imparts multifunctionality to the metal polyphenol particles (PG@Cu-FP). PG@Cu-FP exhibits enhanced escape from lysosomal capture, enabling efficient targeting of mitochondria to scavenge excess reactive oxygen species. The scavenging activity against reactive oxygen species originates from the polyphenol-based structures within the nanoparticles. Furthermore, Pyroptosis is effectively blocked by inhibiting Gasdermin mediated pore formation and membrane rupture. PG@Cu-FP successfully reduces the activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 inflammasome by inhibiting Gasdermin protein family (Gasdermin D, GSDMD) oligomerization, leading to reduced expression of Nod-like receptors. This multifaceted approach demonstrates higher efficiency in inhibiting Pyroptosis. Experimental results confirm that PG@Cu-FP preserves disc height, retains water content, and preserves tissue structure. These findings highlight the potential of PG@Cu-FP in improving IVDD and provide novel insights for future research in IVDD treatments.

Harnessing gradient gelatin nanocomposite hydrogels: a progressive approach to tackling antibacterial biofilms.

Infectious wounds pose significant challenges due to their susceptibility to bacterial infections, hindering tissue repair. This study introduces gradient gelatin nanocomposite hydrogels for wound healing and antibacterial biofilm management. These hydrogels, synthesized via UV light polymerization, incorporate copper-doped polydopamine nanoparticles (PDA-Cu) and GelMA (gelatin methacrylate). The hydrogels have a unique structure with a porous upper layer and a denser lower layer, ensuring superior swelling (over than 600%) and effective contact with bacterial biofilms. In vitro experiments demonstrate their remarkable antibacterial properties, inhibiting S. aureus and E. coli biofilms by over 45% and 53%, respectively. This antibacterial action is attributed to the regulation of reactive oxygen species (ROS) production, an alternative mechanism to bacterial cell wall disruption. Moreover, the hydrogels exhibit high biocompatibility with mammalian cells, making them suitable for medical applications. In vivo evaluation in a rat wound infection model shows that the gradient hydrogel treatment effectively controls bacterial biofilm infections and accelerates wound healing. The treated wounds have smaller infected areas and reduced bacterial colony counts. Histological analysis reveals reduced inflammation and enhanced granulation tissue formation in treated wounds, highlighting the therapeutic potential of these gradient nanocomposite hydrogels. In summary, gradient gelatin nanocomposite hydrogels offer promising multifunctional capabilities for wound healing and biofilm-related infections, paving the way for innovative medical dressings with enhanced antibacterial properties and biocompatibility.

Variations in sexual function after laparoendoscopic single-site hysterectomy in women with benign gynecologic diseases.

Laparoendoscopic single-site surgery (LESS) has become a novel minimally invasive approach applied as an option to perform hysterectomy. The aim of the study was to evaluate the influence of LESS hysterectomy on the sexual function in women with benign gynecologic indications. From October 2016 to May 2021, a total of 486 premenopausal, sexually active women were eligible. Female sexual function index (FSFI) was used to assess sexual function preoperatively and 6, 12 months postoperatively. Total FSFI score ≤26.55 indicated female sexual dysfunction (FSD). Compared with pre-operation, each subdomain and total FSFI scores increased at 6 (all p < 0.05) and 12 months (all p < 0.001). Prevalence of FSD decreased at 6 (30 vs 39.9%, p = 0.002) and 12 months (27 vs 39.9%, p < 0.001). In patients with preoperative FSD, each subdomain and total FSFI scores improved at 6 and 12 months (all p < 0.001), while decreased at 6 months (p < 0.001) and had no significant difference at 12 months (p = 0.54) in patients without preoperative FSD. These results suggest that LESS hysterectomy has a significant positive effect on the sexual function in women with benign gynecologic diseases, especially those with preoperative FSD.

Engineered high-strength biohydrogel as a multifunctional platform to deliver nucleic acid for ameliorating intervertebral disc degeneration.

Intervertebral disc degeneration (IVDD) is a leading cause of low back pain. The strategy of using functional materials to deliver nucleic acids provides a powerful tool for ameliorating IVDD. However, the immunogenicity of nucleic acid vectors and the poor mechanical properties of functional materials greatly limit their effects. Herein, antagomir-204-3p (AM) shows low immunogenicity and effectively inhibits the apoptosis of nucleus pulposus cells. Moreover, a high-strength biohydrogel based on zinc-oxidized sodium alginate-gelatin (ZOG) is designed as a multifunctional nucleic acid delivery platform. ZOG loaded with AM (ZOGA) exhibits great hygroscopicity, antibacterial activity, biocompatibility, and biodegradability. Moreover, ZOGA can be cross-linked with nucleus pulposus tissue to form a high-strength collagen network that improves the mechanical properties of the intervertebral disc (IVD). In addition, ZOGA provides an advantageous microenvironment for genetic expression in which AM can play an efficient role in maintaining the metabolic balance of the extracellular matrix. The results of the radiological and histological analyses demonstrate that ZOGA restores the height of the IVD, retains moisture in the IVD, and maintains the tissue structure. The ZOGA platform shows the sustained release of nucleic acids and has the potential for application to ameliorate IVDD, opening a path for future studies related to IVD.

The potential therapeutic impacts of trehalose on cardiovascular diseases as the environmental-influenced disorders: An overview of contemporary findings.

Cardiovascular diseases (CVDs) as environmental-influenced disorders, are a major concern and the leading cause of death worldwide. A range of therapeutic approaches has been proposed, including conventional and novel methods. Natural compounds offer a promising alternative for CVD treatment due to their ability to regulate molecular pathways with minimal adverse effects. Trehalose is natural compound and disaccharide with unique biological functions and cardio-protective properties. The cardio-protective effects of trehalose are generated through its ability to induce autophagy, which is mediated by the transcription factors TFEB and FOXO1. The stimulation of TFEB plays a significant role in regulating autophagy genes and autophagosome formation. Activation of FOXO1 through dephosphorylation of Foxo1 and blocking of p38 mitogen-activated protein kinase (p38 MAPK) also triggers autophagy dramatically. Trehalose has been shown to reduce CVD risk factors, including atherosclerosis, cardiac remodeling after a heart attack, cardiac dysfunction, high blood pressure, and stroke. It also reduces structural abnormalities of mitochondria, cytokine production, vascular inflammation, cardiomyocyte apoptosis, and pyroptosis. This review provides a molecular overview of trehalose's cardioprotective functions, including its mechanisms of autophagy and its potential to improve CVD symptoms based on clinical evidence.

Copper functionalized poly (acrylic acid-co-itaconic acid) nanohydrogel: Its antibacterial properties on oral pathogens and biocompatibility.

Although extensive efforts have been made to explore effective antibiotics, the development of antibiotics lags far behind the emergence of drug-resistant bacteria. Antimicrobial materials as an alternative strategy provide effective functions in aiding in relieving the dose of antibiotics. Herein, we report a novel antibacterial agent with high antibacterial effectivity and low toxicity, which is simply composed of a trace amount of Cu2+ ion and nanoscale biocompatible polymer poly (acrylic acid-co-itaconic acid) (PAI-Cu). The polymer shows greatly enhanced antibacterial activity against various Gram-positive and Gram-negative pathogens compared with equal concentrations of copper ion solution, yet shows nearly no toxicity towards human cells. The antibacterial performance and mechanism of copper ionized polymer hydrogel are evaluated in terms of multiple methods, towards various oral bacteria including Streptococcus mutans, Enterococcus faecalis, Lactobacillus acidophilus, Actinomycetes viscosus, Porphyromonas gingivalis, Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans, and Prevotella intermedia. Bacterial cell membrane and wall damage caused by PAI-Cu nanohydrogel should be regarded as an important antibacterial mechanism. Moreover, PAI-Cu nanohydrogel, as the role of catalytic active center, can activate the surrounding oxygen, and generate hydroxyl radical (·OH), which can destroy the proliferation ability of microbial cells. We suggest that PAI-Cu nanohydrogel is a promising antibacterial agent against dental pathogens and beyond.

Gold nanoparticles with helical surface structure transformed from chiral molecules for SERS-active substrates preparation.

Surface-enhanced Raman scattering (SERS) technique has enlarged the application of Raman spectroscopy, and the most crucial problem is the exploration of SERS-active materials. In the paper, a SERS substrate made of helical gold nanoparticles by the directed synthesis of L-glutathione (L-GSH) was proposed. Because of the large surface specific area and the uneven conduction electrons distribution for sharp tips resulted from the complex concave surface and the symmetry breaking structure, The nanostructure has shown an impressive average enhancement factor (EF) of 2.95 × 105 under off-resonant condition. This phenomenon was explained by the experimental results and finite difference time domain (FDTD) method. Finally, the SERS substrates were used to detect thiram on pear with a limit of detection (LOD) of 0.62 mg/kg and R2 of 0.9772. The proposed SERS substrates suggest the potential application of chiral molecules such as amino acids, peptides et al. in the SERS-active materials fabrication.

Asymmetric barrier membranes based on polysaccharide micro-nanocomposite hydrogel: Synthesis, characterization, and their antibacterial and osteogenic activities.

Guided tissue regeneration (GTR) strategies enable periodontal tissue regeneration, generally by providing barrier membranes. However, currently available membranes have limited osteoconductive and antibacterial potential. To address these challenges, we fabricated a new asymmetric barrier membrane. Agarose hydrogel functions as the main body of the barrier membrane. Hollow carbonated hydroxyapatite (CHA) prepared by hydrothermal method, was sedimented in agarose to exhibit an asymmetrical structure. And ε-poly-lysine (ε-PLL) was chosen as an antimicrobial agent to equip the membrane with long-lasting antibacterial activity. With the increased dose of CHA addition, the barrier membrane shows better biocompatibility, and higher mechanical properties. We demonstrated the osteoconductivity and antibacterial properties of the membrane in vitro and in vivo. In summary, our findings suggest that the barrier membrane has good osteoconductive and antibacterial properties, indicating its potential for periodontal tissue engineering.

Differential Impacts on Bacterial Composition and Abundance in Rhizosphere Compartments between Al-Tolerant and Al-Sensitive Soybean Genotypes in Acidic Soil.

In this study, two soybean genotypes i.e. aluminum-tolerant Baxi 10 (BX10) and aluminum-sensitive Bendi 2 (BD2) were used as plant materials and the acidic red soil was used as growth medium. The soil layers from the inside to the outside of the root are: rhizospheric soil after washing (WRH), rhizospheric soil after brushing (BRH) and rhizospheric soil at two sides (SRH), respectively. The rhizosphere bacterial communities were analyzed by high-throughput sequencing of V4 hypervariable regions of 16S rRNA gene (16S rDNA) amplicons via Illumina MiSeq. The results of alpha diversity showed that the BRH and SRH of BX10 were significantly lower on community richness than that of BD2, while the WRH existed no significant difference between BX10 and BD2. Among the three sampling compartments of the same soybean genotype, WRH had the lowest community richness and diversity while existed the highest coverage. Beta diversity analysis results displayed no significant difference for any compartment between the two genotypes, or among the three different sampling compartments for any same soybean genotype. However, the relative abundance of major bacterial taxa specifically nitrogen-fixating and/or aluminum-tolerant bacteria was significantly different in the compartments of the BRH and/or SRH at phylum and genus levels depicting genotype dependent variations in rhizosphere bacterial community. Strikingly, as compared with BRH and SRH, the WRH within the same genotype (BX10 or BD2) always had an enrichment effect on rhizosphere bacteria associated with nitrogen-fixation.

Sequence isomerism-dependent self-assembly of glycopeptide mimetics with switchable antibiofilm properties.

In biological systems, diverse amino acid sequences and functional decorations endow proteins with specific functions. Functionally modified oligopeptides are attractive building blocks to assemble stimuli-responsive biomimetic superstructures for mimicking soft structures in nature and biomaterial applications. In this work, we selectively synthesized the structurally simplest isomeric tripeptides (i.e., Ala-Gly-Gly-OH, Gly-Ala-Gly-OH and Gly-Gly-Ala-OH) to demonstrate how the subtlest change in sequence isomerism influences the self-assembly of glycopeptides. To impart self-assembly capability and stimuli-responsiveness, the isomeric tripeptides were modified with a hydrophobic n-butylazobenzene tail at the N-terminal. We observed three different self-assembled 1-D morphologies (i.e., nanotwists, nanoribbons and nanofibers) from the azobenzene-glycopeptides (AGPs) under the same conditions when the position of the Ala residue was switched. Experimental methods including transmission electron microscopy (TEM), atomic force microscopy (AFM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy and circular dichroism (CD) spectroscopy were used to characterize the structural details of glycopeptide mimetic assemblies. Martini coarse-grained molecular dynamics (MD) simulations confirmed such structural observations and investigated the differences in assembly mechanisms. Furthermore, the glycopeptide mimetic assemblies showed a reversible disassembly-assembly process in response to temperature, light or host-guest chemistry, and can be used as switchable antibiofilm nanoagents.

Switchable modulation of bacterial growth and biofilm formation based on supramolecular tripeptide amphiphiles.

Design and fabrication of smart supramolecular peptide systems is an effective strategy to develop antibacterial agents that can be selectively activated/inactivated by external stimuli for combating bacterial resistance. In this work, we selectively synthesized isomeric tripeptides (i.e., Ala-Gly-Gly-OH and Gly-Gly-Ala-OH) with the simplest structures to construct a minimalistic dual-responsive supramolecular antibacterial system. To impart stimuli-responsiveness, the tripeptides were modified using a hydrophobic n-butylazobenzene tail at the N-terminal, which benefited the enhancement of the hydrophobicity of the tripeptides and they served as synergistic antibacterial moieties. Two different self-assembled 1-D morphologies (i.e., nanotwists and nanofibers) were observed under the same conditions when the position of the Ala residue was altered. More importantly, the supramolecular tripeptide amphiphiles exhibited a reversible assembly/disassembly process in response to different stimuli (i.e., light and host-guest chemistry). Based on the stimuli-responsiveness, the antibacterial/antibiofilm activities against either Gram-negative or Gram-positive bacteria could be reversibly modulated.

Reversible modulation of plasmonic chiral signals of achiral gold nanorods using a chiral supramolecular template.

We report here the fabrication of a multiple stimuli-responsive chiral plasmonic system based on the reversible self-assembly of phenylboronic acid-capped gold nanorods (PBA-Au NRs) guided by a supramolecular glycopeptide mimetic template. The plasmonic chiral signals of PBA-Au NRs can be reversibly switched on and off by temperature, light, pH and glucose concentration variations.

Performance of P16/Ki67 dual staining in triaging hr-HPV-positive population during cervical Cancer screening in the younger women.

BACKGROUND: Cervical cancer is the most common malignancy from the female reproductive tract, and usually develops from low-grade or high-grade squamous intraepithelial lesions (LSIL or HSIL). Detecting the precancerous lesion during the LSIL-HSIL-invasive cancer sequelae can effectively interrupt the oncogenesis and decrease the incidence of invasive carcinoma. The aim of this study is to evaluate the performance of P16/Ki67 dual staining in triaging hr-HPV-positive population. METHODS: Conventional gynecological examination, cervical cytology and hr-HPV testing were given to all patients. Specimens were collected for cytology examination and HPV genotyping. According to cytology results, patients were divided into cervical cancer group, HSIL group, LSIL group and benign lesion group. Sensitivity and specificity of the dual staining method in each histopathologic group was obtained and compared. RESULTS: Among the108 patients participated in the study, 65 were diagnosed as normal, 15 as LSIL, 20 as HSIL and 8 as CC, by histopathologic examination. Dual staining of p16/Ki67 on cytology specimen provided a positive predictive value of 86% and the negative predictive value of 96%. The sensitivity approached 96.43% when combining ThinPrep cytological test (TCT) with the dual staining, with a specificity of 60% in detecting HSIL. Joint detection of TCT and p16/Ki67 dual staining displayed the highest specificity among all the attempted combinations of detection methods. CONCLUSIONS: This study demonstrated that p16/Ki-67 dual staining represents an effective method for cervical cancer screening. Application of this method could lead to a reduction of unnecessary colposcopy referrals and misdiagnosis.

HOXC13 promotes proliferation of lung adenocarcinoma via modulation of CCND1 and CCNE1.

In this study, we confirmed that HOXC13 might be a potential oncogene in lung adenocarcinoma through an analysis of The Cancer Genome Atlas (TCGA) datasets. Further analysis revealed that the expression of HOXC13 was significantly higher in lung adenocarcinoma tissues than in adjacent normal tissues; importantly, its expression correlated with poor clinical characteristics and worse prognosis. In vitro experiments showed that HOXC13 expression generally increased in lung adenocarcinoma cell lines. Moreover, knockdown of HOXC13 inhibited lung adenocarcinoma cell proliferation, and induced G1-phase arrest via downregulation of CCND1 and CCNE1. Conversely, HOXC13 overexpression promoted lung adenocarcinoma cell proliferation, and decreased the percentage of cells in G1-phase via upregulation of CCND1 and CCNE1. We also found that miR-141 downregulated HOXC13, by directly targeting its 3'UTR, and inhibited proliferation of lung adenocarcinoma cells. Taken together, our results suggest that HOXC13, which is directly targeted by miR-141, is highly expressed in lung adenocarcinoma, and promotes proliferation of lung adenocarcinoma by modulating the expression of CCND1 and CCNE1.

Bioconjugation of Gold Nanobipyramids for SERS Detection and Targeted Photothermal Therapy in Breast Cancer.

Gold nanobipyramids (Au NBPs) with two sharp tips present an extremely strong electric field enhancement, which endows them with more advantages in biomedical photonics than other gold nanostructures. The application of Au NBPs for diagnosis and therapy is now under intensive investigation. Here, we report Au NBPs for surface-enhanced Raman scattering (SERS) detection and photothermal therapy (PTT) of MCF-7 cancer cells both in vitro and in vivo via bioconjugation with Raman reporter 2-naphthalenethiol (2-NAP) and folic acid (FA). The results showed that bioconjugated Au NBPs not only could be used for the quantitative detection of the MCF-7 cells in the range of 5-500 cells/mL, but also lead to the enhanced Raman signal in MCF-7 tumor-bearing nude mice with high specificity. Moreover the bioconjugated Au NBPs exhibited excellent photothermal performance in both in vitro and in vivo therapies, in which the cell viability decreased to 6.44% and the relative volume of MCF-7 tumors treated with bioconjugated Au NBPs reduced to 0.037 under the irradiation of an 808 nm laser. Our results indicate that bioconjugated Au NBPs offer an excellent nanoplatform for PTT and SERS detection in the future.

Anisotropic particles from a one-pot double emulsion induced by partial wetting and their triggered release.

A family of anisotropic particles is synthesized via a facile, scalable, and versatile method based on a conventional double emulsion, which is very well suited for practical production and applications. Partial wetting theory is well established as a powerful instrument to elucidate the controlled phase separation within the double emulsion. This theory is employed to assist the manipulation of the phase separation process for the formation of well-defined nonspherical particles as well as their triggered release.

Controllable and facile fabrication of gold nanostructures for selective metal-assisted etching of silicon.

A method with the combination of organic-vapor-assisted polymer swelling and nanotransfer printing (nTP) is used to manufacture desirable patterns consisting of gold nano-clusters on silicon wafers for Au-assisted etching of silicon. This method remarkably benefits to the size control and regional selection of the deposited Au. By tuning the thickness of the Au films deposited on the polydimethylsiloxane (PDMS) stamps, along with the swelling of PDMS stamps in acetone atmosphere, the Au films are cracked into diverse nanostructures. These nanostructures are covalently transferred onto silicon substrates in a large scale and enable to accelerate the chemical etching of silicon. The etched areas are composed of porous structures which can be readily distinguished from the surroundings on optical microscope. PDMS stamps and the Au clusters provide the control over the feature of the etched areas and the porous silicon, respectively. The silicon surfaces with patterned porous features offer a platform for exploiting new functional templates, for example, they present a diversity of antireflective and fluorescent performance.