Search

Tobacco is one of the important cash crops in China. It is sensitive to low temperature, especially in the early stage of tobacco seed germination and seedling growth. Low temperature stress directly affects the germination of tobacco seeds, leading to irregular emergence and slow growth of seedlings. Therefore, it is important to improve the vigor and cold tolerance of tobacco. In this study, two cold-sensitive tobacco varieties were primed individually with ZnSO 4 , FeSO 4 and Na 2 SeO 3 to test the effects of different microelements priming on seed germination. The results showed that under low temperature (11 °C), all three elements could improve tobacco seed vigor and promote seed germination, with selenium priming exhibiting the best effect. Selenium priming significantly increased the seed vigor index of YY97 by 29.60 % and of YY85 by 47.57 %. Moreover, selenium priming could effectively enhance POD activity in seeds, promote the oxidation of phenolic substances and enhance the activities of G-6-PDH and 6-P-GDH in the process of scavenging ROS and converting H 2 O 2 to ·O 2 - . The results suggested that selenium played an important role in promoting tobacco seed germination under low temperature., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Silver Diamine Fluoride (SDF) is effective for arresting dental caries, presenting a valuable non-invasive treatment option in dentistry. Despite its therapeutic advantages, a significant drawback is the tooth discoloration that follows its application, which can affect patient acceptance. Addressing this aesthetic concern without diminishing the treatment's efficacy remains challenging in dental practice. This study explores strategies to improve the aesthetic outcomes of SDF treatments., Methods: This in vitro study assessed the efficacy of Zinc in reducing SDF-induced discoloration on dentin blocks and examined its impact on the physical properties of dentin, including hardness and roughness. Dentin blocks were pre-treated with various concentrations of Zinc, followed by SDF application. Color changes were analyzed using Image J software, and cytotoxicity was evaluated using the CytoTox-ONE™ Homogeneous Membrane Integrity Assay. Dentin surface characteristics, including micro-hardness and roughness, were assessed using scanning electron microscopy., Results: The study results revealed a dose-dependent efficacy of Zinc in reducing discoloration caused by SDF on dentin, with higher Zinc concentrations showing better improvement in color outcomes. The application of a 20 M Zinc solution prior to SDF treatment significantly reduced discoloration compared to SDF alone, measured on day 14. Additionally, no significant changes in the hardness or roughness of etched dentin were observed in Zinc + SDF group compared to the SDF alone group. Zinc treatments demonstrated a desirable outcome on mucosal cytotoxicity, comparable to that of the negative control., Conclusion: Zinc significantly reduced SDF-induced tooth discoloration in a dose-dependent manner without affecting the etched dentin's micro-hardness and roughness, potentially improving patient acceptance, especially in visible areas of the mouth. Further research is warranted to validate the effectiveness of this zinc-enhanced treatment protocol in vivo., Clinical Significance: Zinc-enhanced SDF treatments could enhance patient acceptance, especially in visible areas of the mouth, offering an improved option for caries management., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The rapid repair of bone defects remains a significant clinical challenge to this day. To address this issue, a 3D-printed biphasic calcium phosphate (BCP) scaffold consisting of 40 wt % hydroxyapatite (HA) and 60 wt % β-tricalcium phosphate (β-TCP) was created. Silicon and zinc were incorporated into HA and β-TCP, respectively, to enhance the angiogenic and osteogenic properties of the BCP scaffold. The physicochemical properties, in vitro cell responses, and bone defect repair efficacy of the modified BCP scaffold were comprehensively investigated. Results showed that the fabricated scaffold possessed a 3D interconnected pore structure. Zinc doping enhanced the sintering of the BCP scaffold, increased its density and strength, but decreased its degradation rate. Conversely, silicon doping had the opposite effect. The modified scaffold was capable of a gradual release of zinc/silicon ions, which promoted the proliferation and differentiation of cells. Specifically, the scaffold doped with zinc significantly promoted the osteogenic differentiation of stem cells. Moreover, co-doping with silicon and zinc synergistically promoted in vitro angiogenesis, with BCP-3 (doped with 2.5 mol % zinc and 4 mol % silicon) exhibiting the best pro-angiogenic activity. BCP-3 significantly induced regeneration of blood vessels and bone tissue in vivo , indicating its potential to accelerate the process of bone defect repair.

Seed coating with fungicides is a common practice in controlling seed-borne diseases, but conventional methods often result in high toxicity to plants and soil. In this study, a nanoparticle formulation was successfully developed using the metal-organic framework UiO-66 as a carrier of the fungicide ipconazole (IPC), with a tannic acid (TA)-Zn II coating serving as a protective layer. The IPC@UiO-66-TA-Zn II nanoparticles provided a controlled release, triggered and regulated by environmental factors such as pH and temperature. This formulation efficiently controlled the proliferation of Fusarium fujikuroi spores, with high penetration into both rice roots and fungal mycelia. The product exhibited high antifungal activity, achieving control efficacy rates of 84.09% to 93.10%, low biotoxicity, and promoted rice growth. Compared to the IPC flowable suspension formula, IPC@UiO-66-TA-Zn II improved the physicochemical properties and enzymatic activities in soil. Importantly, it showed potential for mitigating damage to beneficial soil bacteria. This study provides a promising approach for managing plant diseases using nanoscale fungicides in seed treatment., Competing Interests: Declarations Ethics approval and consent to participate We confirmed that all methods involving the plant and its material adhered with the relevant institutional, national, and international guidelines and legislation. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Rapid regeneration of the injured tissue or organs is necessary to achieve the usual functionalities of the damaged parts. However, bacterial infections delay the regeneration process, a severe challenge in the personalized healthcare sector. To overcome these challenges, 3D-printable multifunctional hydrogels of Zn/tannic acid-reinforced glycol functionalized chitosan for rapid wound healing were developed. Polyphenol strengthened intermolecular connections, while glutaraldehyde stabilized 3D-printed structures. The hydrogel exhibited enhanced viscoelasticity (G'; 1.96 × 10 4  Pa) and adhesiveness (210 kPa). The dual-crosslinked scaffolds showed remarkable antibacterial activity against Bacillus subtilis (∼81 %) and Escherichia coli (92.75 %). The hydrogels showed no adverse effects on human dermal fibroblasts (HDFs) and macrophages (RAW 264.7), indicating their superior biocompatibility. The Zn/TA-reinforced hydrogels accelerate M2 polarization of macrophages through the activation of anti-inflammatory transcription factors (Arg-1, VEGF, CD163, and IL-10), suggesting better immunomodulatory effects, which is favorable for rapid wound regeneration. Higher collagen deposition and rapid re-epithelialization occurred in scaffold-treated rat groups vis-à-vis controls, demonstrating superior wound healing. Taken together, the developed multifunctional hydrogels have great potential for rapidly regenerating bacteria-infected wounds in the personalized healthcare sector., Competing Interests: Declaration of competing interest The authors declare that no conflicts of financial interests or personal relationships have influenced the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Antimicrobial resistant bacteria can occur in the primary food production environment. The emergence and dissemination of antimicrobial resistance (AMR) in the environment can be influenced by several factors, including the presence of heavy metals. The aim of this study was to examine the presence and characteristics of antimicrobial resistant Enterobacterales in soils and spinach grown in soils with and without zinc amendment. A total of 160 samples (92 soil and 68 spinach) were collected from two locations, in which some plots had been amended with zinc. Samples were cultured on selective agars for detection of extended-spectrum beta-lactamase-producing Enterobacterales (ESBL), carbapenem-resistant Enterobacterales and ciprofloxacin-resistant Enterobacterales. Samples were also cultured for enumeration of total Enterobacterales. Isolates were identified by MALDI-TOF. Antimicrobial susceptibility testing was carried out in accordance with EUCAST and CLSI criteria. The whole genome sequence (WGS) of selected isolates was determined. Inductively coupled plasma atomic emission spectrometry was also performed on soil samples in order to measure the concentration of zinc. In total 20 antimicrobial resistant Enterobacterales were isolated from the soil (n = 8) and spinach samples (n = 12). In both sample types, Serratia fonticola (n = 16) was the dominant species, followed by Escherichia coli (n = 1), Citrobacter freundii (n = 1) and Morganella morganii (n = 1) detected in spinach samples, and Enterobacter cloacae (n = 1) detected in a soil sample. The WGS identified genes conferring resistance to different antimicrobials in agreement with the phenotypic results; 14 S. fonticola isolates were confirmed as ESBL producers and harboured the bla FONA gene. Genes that encoded for zinc resistance and multidrug efflux pumps, transporters that can target both antimicrobials and heavy metals, were also identified. Overall, the findings of this study suggest the presence of zinc did not influence the AMR Enterobacterales in soil or spinach samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The amphibian-killing fungus Batrachochytrium dendrobatidis (Bd) has caused substantial declines in Bd-susceptible amphibian species worldwide. However, some populations of Bd-susceptible frogs have managed to survive at existing metal-polluted sites, giving rise to the hypothesis that frogs might persist in the presence of Bd if Bd is inhibited by metals at concentrations that frogs can tolerate. We tested this hypothesis by measuring the survival of Bd zoospores, the life stage that infects amphibians, and calculated the LC 50 after exposure to environmentally-relevant elevated concentrations of copper (Cu), zinc (Zn), and their combination (Cu + Zn) in two repeated 4-day acute exposure runs. We also measured the chronic sensitivity of Bd to these metals over three generations by measuring the number of colonies and live zoospores and calculating EC 50 concentrations after 42 days of exposure. We then compared acute and chronic sensitivity of Bd with amphibian sensitivities by constructing species sensitivity distributions (SSDs) using LC 50 and EC 50 data obtained from the literature. Acute sensitivity data showed that Bd zoospore survival decreased with increasing metal concentrations and exposure durations relative to the control, with the highest LC 50 values for Cu and Zn being 2.5 μg/L and 250 μg/L, respectively. Chronic exposures to metals resulted in decreased numbers of Bd colonies and live zoospores after 42 days, with EC 50 values of 0.75 μg/L and 1.19 μg/L for Cu and Zn, respectively. Bd zoospore survival was 10 and 8 times more sensitive to Cu and Zn, respectively in acute, and 2 and 5 times more sensitive to Cu and Zn in chronic exposure experiments than the most sensitive amphibian species recorded. Our findings are consistent with the hypothesis that metals in existing metal-polluted sites may have a greater impact on Bd relative to amphibians' performance, potentially enabling Bd-susceptible amphibians to persist with Bd at these sites., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Treating psoriasis presents a major clinical challenge because of the limitations associated with traditional topical glucocorticoid therapy. This study introduced a drug delivery system utilizing zinc-doped mesoporous silica nanoparticle (Zn-MSN) and microneedle (MN), designed to enhance drug utilization for prolonged anti-inflammatory and anti-itch effects. The MN system facilitated the transdermal delivery of betamethasone dipropionate (BD), allowing its slow release. The BD@Zn-MSN-MN system promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype, achieving superior anti-inflammatory effects compared to the clinically used BD cream. Additionally, this study demonstrated that BD@Zn-MSN-MN could further alleviate itching in psoriasis-afflicted mice by decreasing the excitability of the transient receptor potential vanilloid V1 (TRPV1) ion channel positive neurons and reducing the release of calcitonin gene-related peptide (CGRP) in the dorsal root ganglion (DRG). These findings offer new insights and effective therapeutic options for the future design of transdermal drug delivery for psoriasis., Competing Interests: Declarations Ethics approval and consent to participate The animal experiments were approved by the Ethics Committee for Experimental Use of Animals of the Shanghai Jiao Tong University School of Medicine (approval code: #SYXK-2013-0050). Consent for publication All authors agree for publication. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

In the context of acute brain injuries, where zinc neurotoxicity and oxidative stress are acknowledged contributors to neuronal damage, we investigated the pivotal role of lysosomes as a potential protective mechanism. Our research commenced with an exploration of epidermal growth factor (EGF) and its impact on lysosomal dynamics, particularly its neuroprotective potential against zinc-induced cytotoxicity. Using primary mouse cerebrocortical cultures, we observed the rapid induction of EGFR endocytosis triggered by EGF, resulting in a transient increase in lysosomal vesicles. Furthermore, EGF stimulated lysosomal biogenesis, evident through elevated expression of lysosomal-associated membrane protein 1 (LAMP-1) and the induction and activation of prominent lysosomal proteases, particularly cathepsin B (CTSB). This process of EGFR endocytosis was found to promote lysosomal augmentation, thus conferring protection against zinc-induced lysosomal membrane permeabilization (LMP) and subsequent neuronal death. Notably, the neuroprotective effects and lysosomal enhancement induced by EGF were almost completely reversed by the inhibition of clathrin-mediated and caveolin-mediated endocytosis pathways, along with the disruption of retrograde trafficking. Furthermore, tyrosine kinase inhibition of EGFR nullified EGFR endocytosis, resulting in the abrogation of EGF-induced lysosomal upregulation and neuroprotection. An intriguing aspect of our study is the successful replication of EGF's neuroprotective effects through the overexpression of LAMP-1, which significantly reduced zinc-induced LMP and cell death, demonstrated in both primary mouse cerebrocortical neuronal cultures and human embryonic kidney (HEK) cells. Our research extended beyond zinc-induced neurotoxicity, as we observed EGF's protective effects against other oxidative stressors linked to intracellular zinc release, including hydrogen peroxide (H 2 O 2 ) and 1-methyl-4-phenylpyridinium ion (MPP + ). Collectively, our findings unveil the intricate interplay between EGF-triggered EGFR endocytosis, lysosomal upregulation, an increase in the regulatory capacity for zinc homeostasis, and the subsequent alleviation of zinc-induced neurotoxicity. These results present promising avenues for therapeutic interventions to enhance neuroprotection by targeting lysosomal augmentation., Competing Interests: Competing interests The authors declare no competing interests. Ethics approval This study was approved by the Animal Care and Use Committee of Sejong University. (Approval No. SJ-20230119-02)., (© 2024. The Author(s).)

Hydrogel composites are water-swollen and three-dimensional materials that have been investigated for various biological applications, including controlled drug delivery and tissue engineering, owing to the similarity between their mechanical, electrical, and chemical properties with biological tissues. The hydrogel composites can provide a superior replication of living tissue compared to their single components. In this regard, Fe-BTC, Cu-BTC, and Zn-BTC MOFs were synthesized and modified with gallic acid (GA). The MOFs-based hydrogel composites (M-BTC-GA@PVA-CS) were finally fabricated by freezing-thawing the as-synthesized MOFs, gallic acid, chitosan, and poly(vinyl alcohol) mixture. The obtained hydrogels were characterized using techniques such as FTIR, XRD, UV-vis, SEM, EDS, and TEM. Additionally, their antibacterial activity against E. coli and S. aureus and biocompatibility were investigated. The results showed that the surface modification of M-BTC MOFs with GA improves the antibacterial performance of hydrogels and increases their biocompatibility and cell viability. Among the as-prepared M-BTC MOF-based composites, the Cu-BTC MOF-loaded hydrogels showed the highest antibacterial activity. In contrast, the lowest antibacterial effect was observed for the hydrogels with Fe-BTC MOFs. Furthermore, the H&E staining exhibited improved vascularization in Zn-BTC-GA@PVA-CS and Cu-BTC-GA@PVA-CS scaffolds compared to the Fe-BTC-GA@PVA-CS hydrogel. These MOFs-loaded hydrogels may be suitable for utilization in biological applications such as skin treatment, drug delivery, and cosmetics owing to their excellent antibacterial activity and low cytotoxicity.

The aggregation of amyloid β peptide (Aβ) in the presence of elevated levels of transition-metal ions, e.g. , Fe 3+ , Cu 2+ , Zn 2+ , is accountable for enhanced cellular toxicity in Alzheimer's disease. Many strategies are reported to inhibit either Cu 2+ , Zn 2+ , or Fe 3+ -induced Aβ fibrillation, focused on one metal. Herein, a taurine-containing adaptable metal sequestering peptide (AMSP) has been developed as the modulator of any of the cited metal-induced Aβ-aggregation in vitro . We designed the peptide conjugate comprising VFFA as a recognition motif and a taurine moiety coupled with a pendant chain of glutamic acid such that the -SO 3 H groups of taurine lie nearby 13 His and 14 His of Aβ, and sequester such metal ions that construct the salt bridge preponderantly via 13 His-metal- 14 His composition as well as bridges with 6 His of Aβ. We checked the modulation of fibrillar aggregates of Aβ in the presence of metal ions by monitoring the fibril accumulation using several biophysical methods. The results established that non-aggregating AMSP sequesters Zn 2+ preferably, along with Fe 3+ and Cu 2+ ions from the metal-Aβ complex at the physiological condition, efficiently inhibiting Aβ aggregation. While such adaptable metal binders that can chelate various metals are new, AMSP inhibits aggregation through selective recognition and metal scavenging.

Selenium@zinc nanoparticles, or Se@Zn NPs, are extensively employed in various environmental, industrial and biological domains. However, the biological potential of Se@Zn NPs has not been thoroughly investigated. This study focused on fabricating Se@Zn NPs from algae using an aqueous extract of Champia parvula seaweed. Analytical techniques were used to describe the successfully synthesized Se@Zn NPs. In addition, a biological function analysis of the Se@Zn NPs was conducted. The Ultraviolet-visible spectroscopy (UV-vis) spectrum showed a specific absorbance peak for the Se@Zn NPs at 350-400 nm. The biomolecules involved in forming Se@Zn NPs were identified by their potential functional groups, as revealed by Fourier transform infrared spectroscopy (FTIR). By scanning electron microscopy (SEM) and transmission electron microscopy (TEM), Se@Zn NPs were shown to be spherical and to have a diameter range of 100-200 nm. NPs with a crystallite diameter of 54.8 nm and chemical compositions of zinc and selenium (1:1.5 ratio) were revealed by X-ray diffraction analysis (XRD) and energy dispersive x-ray spectroscopy (EDS). IC 50 values were determined for the anticancer activity against A549, MCF-7 and HeLa cells. Cell morphological changes in fluorescence microscopy and apoptosis mechanisms by flow cytometry analysis were investigated, which show that Se@Zn NPs induced apoptosis in various cancer cells. DNA fragmentation and ROS levels were studied by fluorescence microscopy. In conclusion, conditions required for therapeutic and preventative applications may be met by the green synthesis of Se@Zn NPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

PANoptosis has recently emerged as a potential approach to improve the immune microenvironment. However, current methods for inducing PANoptosis are limited. Herein, through biological screening, the rational use of the nutrient metal ions Cu 2+ and Zn 2+ had great potential to induce PANoptosis. Inspired by these findings, we successfully developed hydrazided hyaluronic acid-modified zinc copper oxide (HZCO) nanoparticles as a PANoptosis inducer to potentiate immunotherapy. Bioactive HZCO actively delivered Cu 2+ and Zn 2+ while disrupting the cellular intrinsic ion metabolism pathway, resulting in double-stranded DNA release and organelle damage in cancer cells. Simultaneously, this process triggered the formation of PANoptosome and the activation of PANoptosis. HZCO-induced PANoptosis inhibited tumor growth and activated potent antitumor immune response, thereby enhancing the effectiveness of anti-programmed cell death 1 therapy. Overall, our work provides an insight into the development of PANoptosis inducers and the design of synergistic immunotherapy strategies.

Respiratory syncytial virus (RSV) is a common pathogen that causes respiratory infections in infants and children worldwide, significantly impacting hospitalization rates in this age group. Zinc ions are considered to have broad-spectrum antiviral potential against RNA viruses, including RSV. However, poor organism absorption and low intracellular accumulation of zinc require repeated high-dose supplementation, which may lead to unnecessary toxic side effects. In this research, a Zn 2+ -mediated glycyrrhizinic acid (GA)-based hydrogel (ZnGA Gel) was introduced and potentially developed to be a clinically available drug candidate for RSV therapy. ZnGA Gel was fabricated based on the cooperation of two potential RSV inhibiting molecules (Zn 2+ and GA), where Zn 2+ promoted self-assembly of GA and reduced its gel concentration and GA promoted zinc absorption and distribution in lung tissue in vivo. The facile construction of supramolecular hydrogel by the self-assembled coordination complex made it an injectable, temperature-sensitive, and pH-responsive controlled-release drug delivery for Zn 2+ . Most importantly, GA was observed to enhance organism absorption and intracellular accumulation of Zn 2+ and was identified as a zinc ionophore for the first time. GA can colonize on the cell membrane and disturb cell membrane potential, resulting in an enhanced cell membrane permeability. In the presence of GA, more than 4.7-fold increasing Zn 2+ concentrations materialized in the intracellular cytoplasm, compared to Zn 2+ alone administration. This intracellular Zn 2+ accumulation directly boosted the antiviral activities through improved inhibition of RSV replication-associated proteins and significantly inhibited RSV replication. Oral administration of ZnGA Gel on the RSV-infected mice model achieved an ideal therapeutic effect by effectively lowering viral load in the lungs, alleviating lung injury symptoms, and reducing inflammatory cell infiltration at pathological sites. The mechanism involved the inhibition of RSV replication-related proteins, aligning with our in vitro results. Additionally, ZnGA Gel had demonstrated biocompatibility, and reasonable supplementation of zinc was acceptable and effective for infants and children in clinical practice. Hence, the ZnGA Gel developed by us holds promise as an effective anti-RSV medicine in the future.

Three novel complexes of deprotonated diflunisal ( dif ) with neocuproine ( neo ) were synthesized and characterized via elemental, spectral (UV-vis, FTIR, fluorescence, and mass spectrometry), and single-crystal X-ray diffraction analyses. Although the compounds shared a similar composition of [MCl( dif )( neo )], where M represents Zn(II) (1), Co(II) (2) and Cu(II) (3), only 1 and 2 were isostructural, while 3 differed in both the molecular and supramolecular structures. In all three complex molecules, the central atom is coordinated by two nitrogen atoms of neo in a bidentate chelate mode, and one chlorido ligand and dif is bonded in either a monodentate mode via one oxygen atom of the carboxylate in 1 and 2 or in a bidentate chelate mode via both carboxylate oxygen atoms in 3. All three compounds demonstrated remarkable antiproliferative activity against human prostate (PC-3), colon (HCT116) and breast (MDA-MB-468) cancer cell lines with IC 50 values in the nanomolar range, with the lowest values observed in the case of PC-3 and MDA-MB-468 with 2 (20.0 nM) and 3 (31.1 nM), respectively. Moreover, complex 2, as the most active, was further investigated for its potential to induce perturbations in the cell cycle of PC-3 cells. The results indicated an induction of caspase-independent apoptosis. The interaction of the complexes with genomic DNA isolated from the respective cancer cell lines was evaluated for the intercalative mode, with binding strength correlated with the antiproliferative activity against PC-3 and MDA-MB-468 cancer cell lines.

Hydroxyapatite (HAp) and hydroxyapatite-based materials show promising potential in the healthcare sector due to their distinctive properties such as biocompatibility, antimicrobial efficacy, non-toxicity, and robust mechanical characteristics. This makes HAp materials play an important role in hindering infection spreading in healthcare provider institutions. This study assesses the antimicrobial efficacy of the developed hydroxyapatite-based composites incorporating copper, zinc, and silver nanoparticles. The synthesized HAp and its modified composite variants (Cu/HAp, Zn/HAp, and Ag/HAp) with varying ratios ranging from 0 to 15% (wt) were characterized using XRD, XPS, SEM, and TEM analyses. Furthermore, the antibacterial and antifungal properties of the synthesized HAp and HAp-based composites were evaluated. The antibacterial effectiveness of the HAp and its composites was evaluated using a modified disc diffusion test, where the resulting inhibition zones on the agar surface were observed. All the HAp and HAp-based composites (HAp, Cu/HAp, Zn/HAp, and Ag/HAp materials) elicited in the formation of inhibitory zones. The most substantial inhibition values were observed for the 5% Ag/HAp formulation, with values of 19.7 and 13.8, against E. coli and S. aureus, respectively. The 5% Ag/HAp concentration may strike an ideal balance, providing high antimicrobial activity without adverse effects on biocompatibility or material stability. These findings underscore the recommendation of the proposed HAp-based composites for infection control measures through their application on medical instruments, textiles, healthcare personnel attire, and patient garments., (© 2024. The Author(s).)

Zinc nanoparticles (ZnNPs) are a viable option in a number of disciplines, including cancer treatment, due to their special features. Among the several techniques for synthesizing ZnNP, biosynthesis with natural extracts is a highly effective and environmentally benign method, especially for uses in biomedicine. Using an aqueous extract of the marine red seaweed Jania rubens, we created a unique biosynthetic technique in this study to manufacture ZnNPs. The produced ZnNPs have a characteristic flower-like form, as seen by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The effective production of ZnNPs and the involvement of biomolecules in the synthesis process were validated by energy-dispersive X-ray spectroscopy (EDAX) and Fourier transform infrared spectroscopy (FTIR) techniques. Using the MTT assay, the cytotoxic effects of the biosynthesized ZnNPs were evaluated, indicating their ability to inhibit MCF-7 breast cancer cells. Furthermore, ZnNPs' cytotoxicity against MCF-7 cells was validated by live/dead imaging experiments, which supported the MTT results., (© 2024 John Wiley & Sons Ltd.)

Environmental pollution caused by arsenic or its compounds is called arsenic pollution. Arsenic pollution mainly comes from people mining and smelting arsenic compounds. In addition, arsenic compounds' widespread use and production of arsenic-containing pesticides, arsenic-rich water used to irrigate farms, or high arsenic levels in foods caused by coal burning are all sources of arsenic contamination. Arsenic contamination poses a significant threat to global public health. It is reported that exposure to arsenic can induce severe renal injury. However, the underlying mechanism needs to be clarified. In this study, the arsenic exposure model in vivo and in vitro was used to explore the mechanism of arsenic-induced renal injury, especially the role of ferroptosis and its regulatory mechanism, and then to evaluate its anti-pollution effect by supplementing zinc. The results showed that arsenic significantly induced ferroptosis, characterized by up-regulating the expression of YAP and TFR in kidney and CIK cells and then increasing the levels of Fe 2+ and ROS, lipid peroxidation, and iron metabolism. Microscopic observation revealed the shrinkage of mitochondria and the increase in membrane density. In addition, molecular docking and inhibitor experiments further confirmed that arsenic is involved in the process of ferroptosis by activating YAP and TFR. These results clarify the harmful effects of arsenic on carp kidneys and its mechanism and highlight the critical interactions between the YAP-TFR pathway, ROS, and ferroptosis. Importantly, this study found that zinc can reduce ferroptosis caused by the arsenic-activated YAP-TFR pathway by inhibiting YAP activation and lipid peroxidation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Northern corn leaf blight is a devastating disease caused by Setosphaeria turcica (S. turcica), leading to significant yield losses in maize. S. turcica initiates infection through a specialized structure known as the appressorium, which only forms on conducive substrates. In this study, we introduce a semi‑silicone water polyurethane resin (Si-PUD) that induces only germ tube formation from S. turcica conidia. A mixed coating of Si-PUD and polytetrafluoroethylene successfully triggers appressorium formation. Both coatings maintain optical transparency, chemical resistance, and thermal stability, which facilitate microscopic observations and the development of high-throughput systems. These coatings also demonstrate similar effects on Bipolaris maydis (B. maydis), suggesting their potential universal applicability. Utilizing coating-induced synchronous appressorium formation and proteomic analyses, we identified five genes essential for S. turcica appressorium development. Functional analyses of two zinc binuclear cluster domain-containing transcription factors, StTF1 and StTF2, revealed their critical roles in appressorium development and pathogenicity. This study not only develops a novel method for inducing appressorium formation but also lays the groundwork for rapid screening of environmentally-friendly fungicides that inhibit appressorium development., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Molecular cloning and functional characterization of Nemopilema nomurai venom metalloproteinases have provided deeper insights into the pathogenesis of jellyfish dermatitis. This study reports a new cDNA clone from N. nomurai tentacle venom (Transcript sequence: ID469) encoding 362 amino acid residues, belonged to astacin family and capable of disrupting the cell matrix. The N. nomurai metalloproteinase 469 (NnM469) comprises a signal peptide and propeptide, followed by metalloproteinase domain containing a zinc-binding motif, and two ShKT domains. Notably, NnM469 features a zinc-binding motif (HEXXH) at the active site, within an extended sequence of HEXXHXXGFXHE, which is unique to astacin. Immunocytochemistry revealed that NnM469 is located in the stab tube and envelope of jellyfish nematocysts. Western blot and LC-MS/MS analysis confirmed that the NnM469 protein was successfully expressed using the Pichia pastoris expression system. The recombinant NnM469 could degrade the cell matrix, resulting in the death of HaCaT cells with an IC 50 of 26.34 μg/mL. Finally, I-TASSER-generated structure and function predictions indicated that conserved Asp 53 , His 168 , His 172 , His 178 , and Tyr 227 serve as key amino acid residues for the Zn 2+ ion binding in the catalytic center. In summary, the study of the molecular characteristics and function of NnM469 presents an opportunity to develop therapeutic interventions for jellyfish venom-induced dermatitis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The distinctive composition and functions of osteochondral structures result in constrained regeneration. Insufficient healing processes may precipitate the emergence of tissue growth disorders or excessive subchondral bone formation, which can culminate in the deterioration and failure of osteochondral tissue repair. To overcome these limitations, materials designed for osteochondral repair must provide region-specific modulation of the microenvironment and mechanical compatibility. To address these challenges, we propose a method to create continuous hydrogels with distinct structural and functional properties by a precise cross-linking method. We have developed an innovative polyurethane enriched with dimethylglyoxime, facilitating the coordinated loading and precise release of Zn 2+ . This strategy enables the meticulous control of alginate cross-linking, resulting in an elastic gradient hydrogel that closely resembles the osteochondral interface. The SeSe within the hydrogel effectively modulates the inflammatory microenvironment and fosters the M2 polarization of macrophages. The hydrogel's lower layer is designed to rapidly release Zn 2+ , thereby enhancing bone regeneration. The upper layer is intended to prevent bone overgrowth and stimulate chondrogenic differentiation. This dual-layer strategy allows targeted stimuli to each region, promoting the seamless integration of neoosteochondral tissue. Our study demonstrates the potential of this stratified hydrogel in achieving uniform and smooth osteochondral tissue regeneration., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the authors., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Copper (Cu) and zinc (Zn) are both oxidation-reducing metal elements that are necessary for plant growth, and their effect often depends on their concentration. However, there are few studies that have investigated how plants are stressed and affected when the two ions are present simultaneously, especially when one ion is beneficial due to a low concentration and the other is detrimental due to a high concentration. To address this question, we treated Arabidopsis plants with either high or/and low concentrations of the two ions and investigated their mutual effects and the underlying molecular mechanism, focusing on photosynthetic function. The results showed that the photosynthetic pigment content and the performance of photosynthetic systems were most affected when both metal ions were present at detrimental concentrations (60 μM Cu for Cu 60 and 350 μM Zn for Zn 350 ). These include the effective openness of the photoreaction center, the electron transport rate and efficiency of photosystem II (PSII), the NPQ-dependent energy dissipation and the activity of photosystem I (PSI). However, when the harmful concentration of one of the two metals is combined with the beneficial concentration of the other metal (Cu 5 +Zn 350 or Zn 50 +Cu 60 ), these photosynthetic indicators are compensated to different degrees but the negative effects of copper ions at high dose are more difficult to eliminate than zinc ions. These results were also confirmed by gene expression analysis, which provides a clue to understanding the interaction between heavy metal ions, reducing metal toxicity and improving the tolerance of plants to heavy metals in practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

This study elucidates the impact of element dose during nanoparticle (NPs) synthesis on plant growth indices. Novel NPs containing two essential micro-nutrients, zinc (Zn) and manganese (Mn), were co-doped on cerium oxide (CeO 2 ) (ZnMnCe) with different ratios (1, 2, and 3%). The synthesized NPs were characterized by advanced analytical techniques (EDX, TEM, SEM, XPS, and XRD) and hydroponically applied to barley (Hordeum vulgare L.). The impact of ZnMnCe NPs on growth indices and plant nutrients was examined. SEM, HRTEM, and confocal microscopy were used to show the morphological and structural influences of ZnMnCe NPs. Results showed that the plant growth indices (root/leaf length, chlorophyll fluorescence, pigmentation, and biomass) were remarkably improved with a 1% Mn/Zn addition. Conversely, growth retardation, cell membrane damage, root morphology deformation, and genotoxicity were apparent by 3% of Mn/Zn addition. Overall, a significant improvement in growth was revealed when Mn and Zn were included at 1%. However, increasing concentrations (2% and 3%) impaired the growth. These results show that the element ratio used in NPs synthesis is essential in the plant's physiological response. Precise adjustment of element dosage during NPs synthesis determines whether the NPs are beneficial or harmful. This must be well-balanced for nanofertilizer production and plant applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

To fulfill the nutritional requirements of poultry, effective Zn supplementation is required due to Zn deficiency in basic feed. In this study, we investigated the effects of DMY-Zn (dihydromyricetin zinc chelate) on the growth performance, morphology, and biochemical indices; the expression of intestinal barrier-related genes; the intestinal microflora; and the cecum metabolome of Magang geese. A total of 300 14-day-old Magang geese (equal number of males and females) with an average body weight of 0.82 ± 0.08 kg were randomly divided into five groups and fed a basal diet; these groups were given DMY-Zn (low, medium, or high level of DMY-Zn with 30, 55, or 80 mg/kg Zn added to the basal diet) or ZnSO 4 (80 mg/kg Zn added) for 4 weeks. Our results revealed that DMY-Zn significantly impacts growth and biochemical indices and plays a significant role in regulating the intestinal barrier and microflora. DMY-Zn is involved in the upregulation of intestinal barrier gene (ZO1 and MUC2) expression, as well as upregulated Zn-related gene expression (ZIP5). On the other hand, a low concentration of DMY-Zn increased the ɑ diversity index and the abundance of Lactobacillus and Faecalibacterium. Additionally, a cecal metabolomics study showed that the main metabolic pathways affected by DMY-Zn were the pentose phosphate pathway, the biosynthesis of different alkaloids, and the metabolism of sphingolipids. In conclusion, DMY-Zn can reduce feed intake, increase the expression of intestinal barrier-related genes, help maintain the intestinal microflora balance, and increase the abundance of beneficial bacteria in the intestine to improve intestinal immunity., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Severe bleeding and bacterial infections pose significant challenges to the global public health. Effective hemostatic materials have the potential to be used for rapid control of bleeding at the wound site. In this study, mesoporous silica nanoparticles (MSN) were doped with zinc ions (MSN@Zn) and subsequently functionalized with carboxyl (-COOH) groups through post-grafting, resulting in (MSN@Zn-COOH). The results demonstrated the successful functionalization of carboxyl groups on the surface of MSN@Zn mesoporous materials with minimal impact on the morphology. The released zinc ions showed potent antibacterial activity (above ∼80 %) against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In vitro and in vivo assessments of MSN@Zn-COOH revealed excellent hemostatic effects and favorable blood compatibility. Hemolysis percentages associated with MSN@Zn-COOH exhibited noteworthy reductions in comparison to MSN. Furthermore, a decrease in APTT (a test evaluating the intrinsic coagulation pathway) of modified MSN@Zn indicated enhanced hemostasis, supported by their negative zeta potential (∼ -14 to -43 mV). Importantly, all samples showed no cytotoxicity. This work underscores the potential of MSN@Zn-COOH, with its combined hemostatic performance and antibacterial activity, for emergency clinical applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The long-term use of tripterygium glycosides (TG) can lead to male reproductive damage. Research indicates that zinc and selenium exhibit a synergistic effect in the male reproductive system, with the combined preparation demonstrating superior therapeutic effects compared to individual preparations. The purpose of this study was to explore the specific mechanism by which zinc and selenium mitigate reproductive toxicity induced by TG in male rats. Rats were randomly assigned to three groups: control group (C group), model group (M group, receiving TG at 30 mg/kg/day), and model + zinc + selenium group (ZS group). The ZS group was also given TG gavage for the first 4 weeks. Starting from the fifth week until the conclusion of the eighth week, the ZS group received an additional protective treatment of 10 mg/kg/day Zn and 0.1 mg/kg/day Se 4 h after TG administration. Following euthanasia, blood samples, rat testis, and epididymis tissues were collected for further experiments. Combined zinc-selenium treatment corrects the imbalance of zinc-selenium homeostasis in testicular tissue induced by TG. This is achieved by upregulating the expression of metal transcription factor (MTF1) and zinc transporters ZIP8 and ZIP14 and downregulating the expression of ZnT10. Improvement of zinc and selenium homeostasis enhanced the expression of zinc-containing enzymes (ADH, LDH, and ALP) and selenoproteins (GPx1 and SELENOP) in the testis. At the same time, zinc and selenium mitigate TG-induced reproductive damage by promoting the activity of antioxidant enzymes and upregulating the expression of proteins associated with the oxidative stress pathway, including Nrf2, Keap1, HO-1, PI3K, and p-AKT., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Zinc plays a pivotal role in tissue regeneration and maintenance being as a central cofactor in a plethora of enzymatic activities. Hypozincemia is commonly seen with chronic liver disease and is associated with an increased risk of liver fibrosis development and hepatocellular carcinoma. Previously favorable effects of zinc supplementation on liver fibrosis have been shown. However, the underlying mechanism of this effect is not elucidated. Liver fibrosis was induced in mice by using CCl 4 injection, followed by treatment with zinc chloride (ZnCl 2 ) both at fibrotic and sham groups, and their hepatocytes were isolated. Our results showed that the administration of ZnCl 2 restored the depleted cytosolic zinc levels in the hepatocytes isolated from the fibrotic group. Also, alpha-smooth muscle actin (αSMA) expression in hepatocytes was decreased, indicating a reversal of the fibrotic process. Notably, ZIP14 expression significantly increased in the fibrotic group following ZnCl 2 treatment, whereas in the sham group ZIP14 expression decreased. Chromatin immunoprecipitation (ChIP) experiments revealed an increased binding percentage of Metal-regulatory transcription factor 1 (MTF1) on ZIP14 promoter in the hepatocytes isolated from fibrotic mice compared to the sham group after ZnCl 2 administration. In the same group, the binding percentage of the histone deacetylase HDAC4 on ZIP14 promoter decreased. Our results suggest that the ZnCl 2 treatment ameliorates liver fibrosis by elevating intracellular zinc levels through MTF1-mediated regulation of ZIP14 expression and the reduction of ZIP14 deacetylation via HDAC4. The restoration of intracellular zinc concentrations and the modulation of ZIP14 expression by zinc orchestrated through MTF1 and HDAC4, appear to be essential determinants of the therapeutic response in hepatic fibrosis. These findings pave the way for potential novel interventions targeting zinc-related pathways for the treatment of liver fibrosis and associated conditions., (© 2024. The Author(s).)

Biodegradable polymer microspheres in bone tissue engineering have become appealing as their non-invasive advantages in irregular damage bone repair. However, current microspheres used in BTE still lack sufficient osteogenic capacity to induce effective bone regeneration. In this study, we developed osteogenic composite microspheres concurrently loaded with magnesium oxide (MgO) and zinc oxide (ZnO), both of which are osteogenic active substances, using a facile and scalable emulsification method. The osteogenic composite microspheres exhibited a sequential yet complementary release profile characterized by a rapid release of Mg 2+ and a gradual release of Zn 2+ in a physiological environment, thereby maintaining the concentration of bioactive ions at a sustained high level. As a result, the combination of Mg 2+ and Zn 2+ in the composite microspheres led to a synergistic enhancement in biomimetic mineralization and the upregulation in the expression of osteogenic-related genes and proteins at the cellular level. Through a critical-sized calvarial rate defect model, the osteogenic composite microspheres were demonstrated to have strong osteogenic ability to promote new bone formation via ultrasonic imaging, histological and immunohistochemical evaluations. In sum, these osteogenic composite microspheres as microcarriers of Mg 2+ and Zn 2+ have great potential in the delivery of therapeutic ions for treating bone defects., Competing Interests: Declaration of competing interest The authors declared no financial or personal conflict of interest that could affect their objectivity or inappropriately influence their actions., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Tightly sealed peri-implant gingival tissue provides a barrier against oral bacterial invasion, protecting the alveolar bone and maintaining long-term implant survival. To investigate if zinc can enhance the integration between peri-implant gingival tissue and abutment surface, we herein present novel zinc/chitosan/gelatin (Zn/CS/Gel) coatings prepared using the electrophoretic deposition (EPD) technique. The effect of these coatings on human gingival fibroblasts (hGFs) was investigated by culturing these cells on top of the EPD coatings. Surface characterization demonstrated that Zn 2+ were released in a sustained and pH-responsive manner. The preclinical cell culture evaluation of these coatings indicated that the zinc-containing coatings enhanced cell migration, adhesion and collagen secretion of hGFs. Moreover, the zinc-containing coatings exhibited antibacterial efficacy by inhibiting the growth of Porphyromonas gingivalis and reducing attachment of Staphylococcus aureus. Notably, zinc-free CS/Gel coatings prevented attachment of P. gingivalis as well. The coatings were also shown to be cytocompatible with epithelial cells and osteoblasts, which are other relevant cell types which surround dental implants after clinical placement. Based on our findings, it can be concluded that Zn-containing coatings hold promise to enhance the adhesion of gingival tissue to the implant surface, which may potentially contribute to the formation of a robust peri-implant soft sealing counteracting bacterial invasion., (© 2024 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

The emerging antibiotic-resistant bacteria, especially the "ESKAPE" pathogens, pose a continuous threat to global health. In this study, we explored metalloantibiotics as promising therapeutics and innovative antimicrobial agents. The role of metal in the antimicrobial activity of chloroxine (5,7-dichloro-8-hydroxyquinoline), as a metalloantibiotic, was investigated by minimal inhibit concentration (MIC) assay and a series of assays, including growth curve, time-killing, and UV-visible spectroscopy and PAR (4-(2-pyridylazo)-resorcinol) competition assays. Both chloroxine and its structural analogues exhibited increased antibacterial potency against Gram-positive bacteria compared to Gram-negative bacteria. The introduction of exogenous manganese or zinc ions significantly boosted chloroxine's antibacterial efficacy against Gram-negative bacteria, including the notorious ESKAPE pathogens. However, the enhanced antibacterial activity induced by zinc ions could be negated in the presence of copper or ferrous iron ions, as well as changes in oxygen availability, highlighting the involvement of proton motive force, oxidative and antioxidative systems. Notably, chloroxine effectively inhibited the enzymatic activity of superoxide dismutase (SOD). In addition, chloroxine could reverse polymyxin and carbapenem resistance in E. coli in vitro. Therefore, these results suggested that chloroxine with zinc ions are promising therapeutics and antibiotics potentiator to combat multidrug-resistant ESKAPE pathogens., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Introduction: fat tissue is an organ with endocrine function, where the hormone leptin (LEP) is identified. This peptide regulates appetite, the immune system, vascular functions and insulin sensitivity. Zinc (Zn) and resveratrol (RES) have potential effects on adipose tissue. Objective: to know if the combined administration of Zn and RES has any effect on blood leptin quantification in obese people. Methods: longitudinal experimental study, controlled clinical trial design, randomized, double blind. Randomized formation of four groups: T1 (Zn 50 mg), T2 (control), T3 (RES 500 mg), T4 (Zn 50 mg and RES 500 mg) with a supplementation period of 60 days. Blood samples were taken and glucose (GLU), leptin (LEP) and lipids (HDL, LDL, TGL) were quantified before and after exposure to the study elements. Results: age 34 (± 7) years. In T-tests, significance in GLU (p = 0.04) and LEP (p = 0.055). By exposure groups: GLU at T1 (p = 0.03) and T2 (p = 0.031); at LEP at T4 (p = 0.024). Lipids by groups: HDL at T3 (p = 0.039) and T4 (p = 0.014). ANOVA, HDL (p = 0.06). Pearson, HDL (p = 0.07) and LDL (p = 0.09). Conclusion: zinc and resveratrol showed promise as agents in modulating leptin and glucose signaling, confirming that they work in a proportional manner and provide benefits for cardiac health, but more exposure time is needed to see if they impact energy balance homeostasis.

Background: Zinc (Zn), a fundamental trace element in human biology, exhibits pivotal roles in sustaining vital physiological processes and regulating metabolic homeostasis. Insufficient zinc intake has been linked to deleterious consequences on growth, reproductive functions, metabolic activities, and immune responses in both humans and animals. Oral zinc supplementation is usually performed to meet zinc requirement. Previous studies have shown that long-term supplementation of zinc in mice impaired AKT signaling and induced adipocyte hypertrophy in visceral adipose tissue., Methods: The presented study was conducted to investigate the role and mechanism of short-term zinc supplementation on lipids metabolism. Zinc sulfate was supplemented in the drinking water of C57/BL6J male mice at 30 ppm or 90 ppm for one week. Water consumption, food intake, and body weight were analyzed, adipose tissue and serum profile of metabolites were investigated, and the key genes related to lipid metabolism were analyzed., Results: Short-term zinc supplementation decreased visceral adipose tissue weight and adipocyte size compared to the control group, but no difference was observed in food intake, water consumption, and body weight between the two groups. Further studies revealed that short-term zinc supplementation significantly increased the serum insulin level while decreasing the serum NEFA content. In addition, zinc supplementation increased the expression of Atgl and Hsl in the visceral adipose tissue compared with the control mice. Furthermore, the phosphorylation level of HSL and protein level of PPARg in the epididymal adipose tissue increased by zinc supplementation compared with the control mice. In comparison, the protein level of FASN was down-regulated by short-term zinc supplementation in the epididymal adipose tissue, although the expression of lipogenic genes was not changed. The expression of F4/80 and Tnfa were increased in zinc-supplemented adipose tissue as compared with the control group., Conclusions: Our findings suggest that short-term zinc supplementation might reduce fat deposition by enhancing lipolysis in mice. Future studies could focus on the effect of intermittent zinc supplementation on fat reduction in both animal models and humans., Competing Interests: The authors declare that they have no competing interests.

The rising incidence of infections caused by multidrug-resistant bacteria highlights the urgent need for innovative bacterial eradication strategies. Metal ions, such as Zn 2+ and Co 2+ , have bactericidal effects by disrupting bacterial cell membranes and interfering with essential cellular processes. This has led to increased attention toward metal-organic frameworks (MOFs) as potential nonantibiotic bactericidal agents. However, the uniform and enhanced localized release of bactericidal metal ions remains a challenge. Herein, we introduce a nanoscale multipatterned Zn,Co-ZIF@FeOOH, featuring a multipod-like morphology with spiky corners, and dual-bactericidal metal ions. Compared to pure Zn,Co-ZIF, the multipod-like morphology of Zn,Co-ZIF@FeOOH exhibits enhanced adhesion toward bacterial surfaces via topological and multiple interactions of electrostatic interaction, significantly increasing the local release of Zn 2+ and Co 2+ . Additionally, the spiky corners of the spindle-shaped FeOOH nanorods physically penetrate bacterial membranes, causing damage and further enhancing adhesion to bacteria. Nine Gram-negative and one Gram-positive bacteria were selected for in vitro test. Notably, the nanoscale multipatterned Zn,Co-ZIF@FeOOH exhibited high bactericidal efficacy against various multidrug-resistant bacteria, including extended-spectrum β-lactamase-producing (ESBL+) bacteria and carbapenem-resistant bacteria, performing well in both acidic and neutral environments. The wound healing activity of Zn,Co-ZIF@FeOOH was further demonstrated using female Balb/c mouse models infected with bacteria, where the materials show robust antibacterial efficacy and commendable biocompatibility. This study showcases the assembly of metal oxide/MOF composites for nanoscale multipatterning, aims at synergistic bacterial eradication and offers insights into developing nanomaterial-based strategies against multidrug-resistant bacteria.

Immunotherapy holds significant promise for cancer treatment. However, the highly immunosuppressive nature of solid tumors limits its effectiveness. Herein, we developed bioactive zinc-nickel hydroxide (ZnNi(OH) 4 ) nanosheets (NSs) that can effectively initiate the paraptosis-pyroptosis positive feedback cycle through synergistic ionic effect, thereby mitigating the immunosuppression of solid tumors and enhancing the efficacy of immunotherapy. The acid-sensitive ZnNi(OH) 4 NSs releases Ni 2+ and Zn 2+ in the weakly acidic tumor microenvironment. The released Ni 2+ alleviated pyroptosis inhibition by inducing paraptosis and inhibiting autophagic flux. Concurrently, Ni 2+ triggered release of endogenous Zn 2+ within the cell through a coordination competition mechanism, further amplifying zinc overload-mediated pyroptosis. Interestingly, pyroptosis-associated oxidative stress and endoplasmic reticulum stress further promote Ni 2+ -mediated paraptosis, forming a positive feedback loop between pyroptosis and paraptosis. This process not only effectively kills tumor cells but also stimulates a strong inflammatory response, enhancing the antitumor immune response and immunotherapy efficacy. Overall, this study proposes an effective paraptosis-pyroptosis induction strategy based on metal ions and demonstrates the effectiveness of the positive feedback loop of paraptosis-pyroptosis in potentiating immunotherapy.

This study investigates novel zinc and indium phthalocyanines with Schiff base and sulphur moieties, focusing on their potential for cancer therapy and antimicrobial applications. It explores the effectiveness of photochemical and sono-photochemical methods to enhance singlet oxygen production, which is crucial for photodynamic therapy. The synthesized complexes in this study demonstrated high singlet oxygen quantum yields, with D3 (ZnPc) and D4 (InPc) showing Φ ΔPDT values of 0.71 and 0.75, and Φ ΔSPDT values of 0.91 and 0.94, respectively. Furthermore, the evaluation for biological properties revealed that both D3 and D4 exhibit significant antidiabetic properties, DPPH radical scavenging activity, DNA cleavage, antimicrobial activity, biofilm inhibition, and microbial cell viability impacts, both with and without photodynamic therapy. Notably, D3 and D4 achieved antimicrobial cell viability inhibition rates of 84.67 ± 4.67% and 98.32 ± 5.96%, respectively, showcasing their effectiveness in photodynamic antimicrobial therapy. Overall, the study highlights the potential of these phthalocyanine complexes as advanced photosensitizers, with strong singlet oxygen generation and promising biological activities, paving the way for future therapeutic applications.

Humans use dietary supplements for several intended effects, such as supplementing malnutrition. While these compounds have been developed for host end benefits, their ancillary impact on the gut microbiota remains unclear. The human gut has been proposed as a reservoir for the prevalent lateral transfer of antimicrobial resistance and virulence genes in bacteria through plasmid conjugation. Here, we studied the effect of dietary zinc supplements on the incidence of plasmid conjugation in vitro . Supplement effects were analyzed through standardized broth conjugation assays. The avian pathogenic Escherichia coli (APEC) strain APEC-O2-211 was a donor of the multidrug resistance plasmid pAPEC-O2-211A-ColV, and the human commensal isolate E. coli HS-4 was the plasmid-free recipient. Bacterial strains were standardized and mixed 1:1 and supplemented 1:10 with water, or zinc derived from either commercial zinc supplements or zinc gluconate reagent at varying concentrations. We observed a significant reduction in donors, recipients, and transconjugant populations in conjugations supplemented with zinc, with a dose-dependent relationship. Additionally, we observed a significant reduction ( P < 0.05) in log conjugation efficiency in zinc-treated reactions. Upregulation of the mRNA for the plasmid replication initiation gene repA and the subset of transfer genes M , J , E , K , B , P , C , W , U , N , F , Q , D , I , and X was observed. Furthermore, we observed a downregulation of the conjugal propilin gene traA and the entry exclusion gene traS . This study demonstrates the effect of dietary zinc supplements on the conjugal transfer of a multidrug resistance plasmid between pathogenic and commensal bacteria during in vitro conditions.IMPORTANCEThis study identifies dietary zinc supplementation as a potential novel intervention for mitigating the emergence of multidrug resistance in bacteria, thus preventing antibiotic treatment failure and death in patients and animals. Further studies are required to determine the applicability of this approach in an in vivo model., Competing Interests: The authors declare no conflict of interest.

Wound healing presents a formidable challenge for global healthcare systems. We aimed to address this challenge by designing a multifunctional wound dressing tailored to meet diverse therapeutic needs. Arginine (Arg), selected for its ability to promote wound healing, is grafted onto aldehyde-modified regenerated cellulose (DAC) via Schiff base bonds for a reversible controlled release. At the same time, DAC provides hemostatic function, while Zn 2+ plays an antibacterial role and strengthens cross-linking within the dressing matrix. The hydrogels were characterized by FTIR, XRD, SEM, and EDS. Mechanical strength, adhesion, swelling, water retention, oxygen permeability, hemostasis, antioxidant capacity, and antibacterial activity were all rigorously evaluated to demonstrate the superior properties of the dressing, which promotes accelerated wound healing. The skin of injured mice has been shown to recover almost completely within 13 days of dressing treatment. These findings highlight the potential of this innovative multifunctional wound dressing to address complex wound management challenges.

Acquired drug resistance is a major challenge in the management of cancer, which underscores the need for discovery and development of novel therapeutic strategies. We report here the mechanism of the anti-cancer activity of a small coordinate complex composed of the rare earth metal praseodymium (Pr) and mercaptopyridine oxide (MPO; pyrithione). Exposure of cancer cells to relatively low concentrations of the conjugate Pr-MPO (5 µM) significantly impairs cell survival in a p53-independent manner and irrespective of the drug resistant phenotype. Mechanistically, Pr-MPO-induced cell death is caspase-independent, not inhibitable by necrostatin, but associated with the appearance of autophagy markers. However, further analysis revealed incomplete autophagic flux, thus suggesting altered integrity of lysosomal machinery. Supporting the lysosomal targeting activity are data demonstrating increased lysosomal Ca 2+ accumulation and alkalinization, which coincides with cytosolic acidification (drop in pH c from 7.75 to 7.00). In parallel, an increase in lysosomal activity of glycosidase alpha acid (GAA), involved in passive glycogen breakdown, correlates with rapid depletion of glucose stores upon Pr-MPO treatment. This is associated with swift cataplerosis of TCA cycle intermediates, loss of NAD + /NADH and increase in pyruvate dehydrogenase (PDH) activity to compensate for pyruvate loss. Addition of exogenous pyruvate rescued cell survival. Notably, lysosomal impairment and metabolic catastrophe triggered by Pr-MPO are suggestive of Zn 2+ -mediated cytotoxicity, which is confirmed by the ability of Zn 2+ chelator TPEN to block Pr-MPO-mediated anti-tumor activity. Together, these results highlight the ability of the small molecule lanthanide conjugate to target the cells' waste clearing machinery as well as mitochondrial metabolism for Zn 2+ -mediated execution of cancer cells, which could have therapeutic potential against cancers with high metabolic activity., (© 2024. The Author(s).)

Background: The use of lanthanum (La) as a rare element has increased in agriculture. Summer savory (Satureja hortensis L.) is an herbaceous and medicinal plant that has received attention recently. The present study aimed to investigate the effects of foliar application of zinc (Zn), copper (Cu), manganese (Mn), and La at different growth stages, including vegetative, reproductive, and vegetative to harvest on morphological and physiological traits of S. hortensis under hydroponic and soil conditions in the greenhouse. The study was arranged in a factorial experiment based on a completely randomized design (CRD) with three replications., Results: Results of hydroponic condition showed that foliar application of Cu, Zn, and Mn were the most effective treatments to improve the measured morphological and physiological traits. Moreover, La was not more appropriate in increasing the quantitative and qualitative characteristics. Also, results showed that in soil cultivation, foliar application of micronutrient elements increased the ratio of leaf-to-stems, antioxidant compounds, and the percentage of essential oils, while the application of Mn, Cu, Zn, and La did not have positive effects on the increase in vegetative characteristics in all three stages of foliar application compared with the control treatment., Conclusions: Cu, Zn, and Mn in appropriate concentrations can increase growth and physiological characteristics of summer savory in hydroponic systems., (© 2024. The Author(s).)

In patients with abdominal or pelvic tumors, radiotherapy can result in radiation-induced intestinal injury (RIII), a potentially severe complication for which there are few effective therapeutic options. Sitagliptin (SI) is an oral hypoglycemic drug that exhibits antiapoptotic, antioxidant, and anti-inflammatory activity, but how it influences RIII-associated outcomes has yet to be established. In this study, a pH-responsive metal-organic framework-based nanoparticle platform was developed for the delivery of SI (SI@ZIF-8@MS NP). These NPs incorporated mPEG-b-PLLA (MS) as an agent capable of resisting the effects of gastric acid, and are capable of releasing Zn 2+ ions. MS was able to effectively shield these SI@ZIF-8 NPs from rapid degradation when exposed to an acidic environment, enabling the subsequent release of SI and Zn 2+ within the intestinal fluid. Notably, SI@ZIF-8@MS treatment was able to mitigate radiation-induced intestinal dysbiosis in these mice. restored radiation-induced changes in bacterial composition. In summary, these data demonstrate the ability of SI@ZIF-8@MS to protect against WAI-induced intestinal damage in mice, suggesting that these NPs represent a multimodal targeted therapy that can effectively be used in the prevention or treatment of RIII., (© 2024. The Author(s).)

The regulation of intracellular ionic homeostasis to trigger antigen-specific immune responses has attracted extensive interest in tumor therapy. In this study, we developed a dual-pathway nanoreactor, Au-Cu 2-x Se@ZIF-8@P18 NPs (ACS-Z-P NPs), which targets danger-associated molecular patterns (DAMPs) and releases Zn 2+ and reactive oxygen species (ROS) within the tumor microenvironment (TME). Zn 2+ released from the metal-organic frameworks (MOFs) was deposited in the cytoplasm, leading to aberrant transcription levels of intracellular zinc-regulated proteins and DNA damage, thereby inducing pyroptosis and immunogenic cell death (ICD) dependent on caspase1/gasdermin D (GSDMD) pathway. Furthermore, upon laser irradiation, ACS-Z-P NPs could break through the limitations of inherent defects of immunosuppression in TME, enhance ROS generation through a Fenton-like reaction cascade, which subsequently triggered the activation of inflammatory vesicles and the release of damage-associated molecular patterns (DAMPs). This cascade effect led to the amplification of pyroptosis and immunogenic cell death (ICD), thereby remodeling the immunosuppressed TME. Consequently, this process improved dendritic cell (DC) antigen presentation and augmented anti-tumor T-cell responses, effectively initiating antigen-specific immune responses and further enhancing pyroptosis and ICD. This study explores the therapeutic properties of these mechanisms in detail. STATEMENT OF SIGNIFICANCE: The synthesized Au-Cu 2-x Se@ZIF-8@P18 nanoparticles (ACS-Z-Ps) can effectively enhance the body's immune response by regulating zinc ion levels within cells. This regulation leads to abnormal levels of zinc-regulated protein transcription and DNA damage, which induces cellular pyroptosis. As a result, antigen presentation to dendritic cells (DCs) is improved, and anti-tumor T-cell responses are enhanced. The ACS-Z-P NPs overcome the limitations of ROS deficiency and immunosuppression in the tumor microenvironment by using H 2 O 2 in the tumor microenvironment through a Fenton-like reaction. This leads to an increased production of ROS and O 2 , remodeling of the immunosuppressed tumor microenvironment, and enhanced induction of cell pyroptosis and immunogenic cell death. ACS-Z-P NPs targeted B16 cells using the photosensitizer P18 in combination with PDT treatment. This approach significantly inhibited the proliferation of B16 cells and effectively inhibited tumor growth., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The necessity to move away from conventional antibiotic therapy has sparked interest in antimicrobial peptides (AMPs). One fascinating example is human CCL-28 chemokine produced by acinar epithelial cells in the salivary glands. It can also be released into the oral cavity with saliva, playing a crucial role in oral protection. The C-terminal domain of CCL-28 possesses antifungal and antibacterial properties, which are likely linked to membrane disruption and enzyme leakage. Studies suggest that AMPs can become more potent after they have bound Cu(II) or Zn(II). In many cases, these ions are essential for maximizing effectiveness by altering the peptides' physicochemical properties, such as their local charge or structure. The examined peptide binds Cu(II) and Zn(II) ions very effectively, forming equimolar complexes. Metal ion binding affinity, coordination mode, and antimicrobial activity strongly depend on the pH of the environment. Coordination modes have been proposed based on the results of potentiometric titrations, spectroscopic studies (UV-visible, electron paramagnetic resonance and circular dichroism at different path lengths), and mass spectrometry. The antimicrobial properties of the Cu(II) and Zn(II) complexes with the C-terminal fragment of CCL-28 chemokine have been assessed against fungal and bacterial strains, demonstrating exceptional activity against Candida albicans at pH 5.4. Moreover, the complex with Zn(II) ions shows the same activity against the Streptococcus mutans bacterium as chloramphenicol, a commonly used antibiotic. Cyclic voltammetry proposed a probable antimicrobial mechanism of the studied Cu(II) complex through the formation of reactive oxygen species, which was also confirmed by tests with ascorbic acid in UV-vis and fluorescence spectroscopic studies.

Background: In diabetic wounds, hyperglycemia-induced cytotoxicity and impaired immune microenvironment plasticity directly hinder the wound healing process. Regulation of the hyperglycemic microenvironment and remodeling of the immune microenvironment are crucial., Results: Here, we developed a nanozymatic functionalized regenerative microenvironmental regulator (AHAMA/CS-GOx@Zn-POM) for the effective repair of diabetic wounds. This novel construct integrated an aldehyde and methacrylic anhydride-modified hyaluronic acid hydrogel (AHAMA) and chitosan nanoparticles (CS NPs) encapsulating zinc-based polymetallic oxonate nanozyme (Zn-POM) and glucose oxidase (GOx), facilitating a sustained release of release of both enzymes. The GOx catalyzed glucose to gluconic acid and (H₂O₂), thereby alleviating the effects of the hyperglycemic microenvironment on wound healing. Zn-POM exhibited catalase and superoxide dismutase activities to scavenge reactive oxygen species and H₂O₂, a by-product of glucose degradation. Additionally, Zn-POM induced M1 macrophage reprogramming to the M2 phenotype by inhibiting the MAPK/IL-17 signaling diminishing pro-inflammatory cytokines, and upregulating the expression of anti-inflammatory mediators, thus remodeling the immune microenvironment and enhancing angiogenesis and collagen regeneration within wounds. In a rat diabetic wound model, the application of AHAMA/CS-GOx@Zn-POM enhanced neovascularization and collagen deposition, accelerating the wound healing process., Conclusions: Therefore, the regenerative microenvironment regulator AHAMA/CS-GOx@Zn-POM can achieve the effective conversion of a pathological microenvironment to regenerative microenvironment through integrated control of the hyperglycemic-immune microenvironment, offering a novel strategy for the treatment of diabetic wounds., (© 2024. The Author(s).)

Here, we show particle size-dependent therapeutic efficacy with a Zn-based metal-organic framework (MOF). The size of MOFs was tuned in specific ranges (∼100, 200, and 300 nm) built upon the manipulation of synthetic conditions. X-ray photoelectron spectroscopy, infrared, PXRD, and dynamic light scattering and scanning electron microscopy analyses were used to identify the synthesized structures. The various analyses revealed minimal changes in the molecular properties of these structures regardless of their size, confirming our hypothesis regarding the preservation of the identity of MOF nanoparticles despite size variation. The synthesized carriers undergo structure relative destruction in response to a weak acidic tumor microenvironment, and this relative degradation allows the release of the Nimesulide drug into the environment. Interestingly, anticancer studies resulting in SKBR3 (Human breast cancer cell) cells indicate that the different sizes resulted in various inhibition capacities against cancer cells. This work shows the importance of optimizing the geometry of the drug carrier, such as size and shape, to achieve the highest cellular uptake and therapeutic performance. Besides, theoretical studies were carried out using B3LYP/6-31G (d,p) and density functional theory methods to more consider the drug adsorption mechanism.

P53 is a transcription factor that controls a variety of genes, primarily involved in cell cycle and other processes related to cell survival and death. We have isolated peptides targeting P53 (protein and domains) using the "phage display" technique. Interestingly, adding ZnCl2 at 5-10 mM in panning solutions helped to recover more plaque-forming units at least at round one of the screening. Subtractive docking analyses were designed by using a pool of common redundant peptides known as parasites. This rationale helped us differentiate between possibly specific and non-specific bindings. We found notable differences in docking characteristics between different sets of peptides either related to different targets or related to zinc-conditions. The set of zinc-related peptides shows advantageous docking profiles: sharper binding for some positions and distinct exclusive bound residues, including the relevant R248 and R273. Zinc would have modulating/helping role in the targeting of protein P53 by phage displayed peptides in addition to an enhancement action on bacterial infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ben Abid et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Bone defect repair and postoperative infections are among the most challenging issues faced by orthopedic surgeons. Thus, the antibacterial agent Cu and the osteogenic promoter Sr have been widely incorporated into biodegradable alloys separately. However, to the best of our knowledge, the synergistic effects of Cu and Sr on zinc alloys have not been investigated. Therefore, we have developed a series of novel Zn-4Cu-xSr (x = 0.05, 0.1, and 0.3 wt %) alloys. Our results showed that the addition of Cu and Sr significantly increased the strength of pure zinc while maintaining a certain level of ductility. Plastic deformation further enhanced the strength and ductility of the alloys. The tensile strength of HR Zn-4Cu-xSr alloys remains between 233.34 ± 1.31 MPa and 235.81 ± 3.0 MPa, with elongation values ranging from 45.7 ± 1.56% to 49.6 ± 6.22%. The HE Zn-4Cu-0.05Sr alloy exhibits a high elongation of 95.05 ± 11.1%. Furthermore, the HE Zn-4Cu-0.1Sr alloy demonstrates the best overall mechanical performance with ultimate tensile strength ( σ uts ), yield strength ( σ ys ), and elongation (ε) values of 252.73 ± 0.12 MPa, 181.0 ± 0.79 MPa, and 42.8 ± 1.13%, respectively. The corrosion rate of HE Zn-4Cu-xSr alloys increases with an increase in Sr content. All samples exhibit satisfactory cytocompatibility with the cells displaying a healthy spindle-like morphology. In vitro antibacterial tests show that the HE Zn-4Cu-xSr alloys exhibit significant antibacterial effects against Staphylococcus aureus ( S. aureus ) and Escherichia coli ( E. coli ), with the antibacterial properties strengthening as the Sr content increases. Therefore, this study demonstrates the tremendous potential application of Zn-4Cu-xSr alloys in biodegradable zinc alloys for bone fracture fixation and repair.

The comparative efficacy of silicon (Si) and zinc (Zn) nanoparticles (NPs) in mitigating drought stress in fennel (Foeniculum vulgare ) remains largely unexplored. This study evaluated the impact of Si NPs and Zn NPs on enhancing plant growth and physiological-biochemical attributes of fennel under varying irrigation regimes. The 2-year study was a split-pot design with irrigation at three irrigation levels (100, 75, and 50% field capacity, FC) and five treatments of foliar application of Si and Zn NPs (control, 1mM Si NP, 2mM Si NP, 1mM Zn NP, 2mM Zn NP). Results showed that drought stress reduced plant performance. Increases in superoxide dismutase (SOD, 131%) and catalase (CAT, 276%) were seen after a 50% FC drought without the use of Si and Zn NPs. Conversely, biological yield (34%), seed yield (44%), chlorophyll a +b (26%), relative water content (RWC, 21%), and essential oil (EO) yield (50%) were all reduced. However, application of Zn and Si, particularly 1mM Si and 2mM Zn, greatly mitigated drought stress via lowering CAT and SOD activity and enhancing plant yield, chlorophyll content, RWC, and EO. The composition of the EO consisted primarily of anethole, followed by limonene, fenchone, and estragole. During drought conditions, monoterpene hydrocarbons increased while oxygenated monoterpenes decreased. The opposite trend was observed for Si and Zn NPs. Our results suggest that applying Zn NPs at 2mM followed by Si NPs at 1mM improved plant resilience and EO yield in fennel plants under water stress.

Zinc is one of the essential divalent cations in the human body and a fundamental microelement involved in the regulation of many cellular and subcellular functions. Experimental studies reported that zinc deficiency is associated with renal damage and could increase blood pressure. It was proposed that zinc dietary supplementation plays a renoprotective role. Our study aimed to investigate the effects of zinc on intracellular signaling in renal cells and explore the correlation between dietary zinc and the progression of salt-induced hypertension. The impact of extracellular zinc concentrations on two different kidney epithelial cell types, podocytes and principal cells of the cortical collecting duct (CCD), was tested. In podocytes, a rise in extracellular zinc promotes TRPC6 channel-mediated calcium entry but not altered intracellular zinc levels. However, we observe the opposite effect in CCD cells with no alteration in calcium levels and steady-state elevation in intracellular zinc. Moreover, prolonged extracellular zinc exposure leads to cytotoxic insults in CCD cells but not in podocytes, characterized by increased cell death and disrupted cytoskeletal organization. Next, we tested if dietary zinc plays a role in the development of hypertension in Dahl salt-sensitive rats. Neither zinc-rich nor deficient diets impact the regular development of salt-sensitive hypertension. These results suggest specialized roles for zinc in renal function, implicating its involvement in proliferation and apoptosis in CCD cells and calcium signaling and cytoskeletal dynamics modulation in podocytes. Further research is required to elucidate the detailed mechanisms of zinc action and its implications in renal health and disease., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Published by Elsevier Inc.)

Guided bone-regeneration membrane (GBRM) is commonly used in bone-repair surgery because it blocks fibroblast proliferation and provides spatial support in bone-defect spaces. However, the need for removal surgery and the lack of antibacterial properties of conventional GBRM limit its therapeutic applicability for alveolar bone defects. Here we developed a GBRM for alveolar bone-repair and -regeneration applications through double-sided electrospinning of polycaprolactone and chitosan layers on a Zn mesh surface (denoted DSZM). The DSZM showed a UTS of ∼25.6 MPa, elongation of ∼16.1%, strength-elongation product of ∼0.413 GPa%, and ultrahigh spatial maintenance ability, and the UTS was over 6 times higher than that of commercial Bio-Gide membrane. The DSZM exhibited a corrosion rate of ∼17 µm/y and a Zn ion concentration of ∼0.23 µg/ml after 1 month of immersion in Hanks' solution. The DSZM showed direct and indirect cytocompatibility with exceptional osteogenic differentiation and calcium deposition toward MC3T3-E1 cells. Further, the DSZM showed strongly sustained antibacterial activity against S. aureus and osteogenesis in a rat critical-sized maxillary defect model. Overall, the DSZM fits the requirements for alveolar bone-repair and -regeneration applications as a biodegradable GBRM material due to its spatial support, suitable degradability, cytocompatibility, and antibacterial and osteogenic capabilities. STATEMENT OF SIGNIFICANCE: This work reports the mechanical properties, antibacterial ability and osteogenic properties of electrospun PCL-CS nanofiber on Zn mesh as biodegradable guided bone-regeneration membrane for alveolar bone-repair applications. Our findings demonstrate that the DSZM prepared by double-sided electrospinning of PCL-CS layers on Zn mesh showed a UTS of ∼25.6 MPa, elongation of ∼16.1%, strength-elongation product of ∼0.413 GPa%, and ultrahigh spatial maintenance ability, and the UTS was over 6 times greater than that of commercial Bio-Gide® membrane. The DSZM showed direct and indirect cytocompatibility with exceptional osteogenic differentiation and calcium deposition toward MC3T3-E1 cells. Further, the DSZM showed strongly sustained antibacterial activity against S. aureus and osteogenesis in a rat critical-sized maxillary defect model., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In addition to the essential structural and catalytic functions of zinc, evolution has adopted synaptic zinc as a neuromodulator. In the brain, synaptic zinc is released primarily from glutamatergic neurons, notably in the neocortex, hippocampus, amygdala, and auditory brainstem. In these brain areas, synaptic zinc is essential for neuronal and sensory processing fine-tuning. But what niche does zinc fill in neural signaling that other neuromodulators do not? Here, we discuss the evolutionary history of zinc as a signaling agent and its eventual adoption as an essential neuromodulator in the mammalian brain. We then attempt to describe the unique roles that zinc has carved out of the vast and diverse landscape of neuromodulators.