Zinc (Zn) deficiency is a common disorder of humans in developing countries. The effect of Zn biofortification (via application of six rates of Zn fertilizer to soil) on Zn bioavailability in wheat grain and flour and its impacts on human health was evaluated. Zn bioavailability was estimated with a trivariate model that included Zn homeostasis in the human intestine. As the rate of Zn fertilization increased, the Zn concentration increased in all flour fractions, but the percentages of Zn in standard flour (25%) and bran (75%) relative to total grain Zn were constant. Phytic acid (PA) concentrations in grain and flours were unaffected by Zn biofortification. Zn bioavailability and the health impact, as indicated by disability-adjusted life years (DALYs) saved, increased with the Zn application rate and were greater in standard and refined flour than in whole grain and coarse flour. The biofortified standard and refined flour obtained with application of 50 kg/ha ZnSO₄·7H₂O met the health requirement (3 mg of Zn obtained from 300 g of wheat flour) and reduced DALYs by >20%. Although Zn biofortification increased Zn bioavailability in standard and refined flour, it did not reduce the bioavailability of iron, manganese, or copper in wheat flour.

Increasing grain zinc (Zn) concentration of cereals for minimizing Zn malnutrition in two billion people represents an important global humanitarian challenge. Grain Zn in field-grown wheat at the global scale ranges from 20.4 to 30.5 mg kg-1, showing a solid gap to the biofortification target for human health (40 mg kg-1). Through a group of field experiments, we found that the low grain Zn was not closely linked to historical replacements of varieties during the Green Revolution, but greatly aggravated by phosphorus (P) overuse or insufficient nitrogen (N) application. We also conducted a total of 320-pair plots field experiments and found an average increase of 10.5 mg kg-1 by foliar Zn application. We conclude that an integrated strategy, including not only Zn-responsive genotypes, but of a similar importance, Zn application and field N and P management, are required to harvest more grain Zn and meanwhile ensure better yield in wheat-dominant areas.

Although their cost-effectiveness and intrinsic safety, aqueous zinc-ion batteries suffer from notorious side reactions including hydrogen evolution reaction, Zn corrosion and passivation, and Zn dendrite formation on the anode. Despite numerous strategies to alleviate these side reactions have been demonstrated, they can only provide limited performance improvement from a single aspect. Herein, a triple-functional additive with trace amounts, ammonium hydroxide, was demonstrated to comprehensively protect zinc anodes. The results show that the shift of electrolyte pH from 4.1 to 5.2 lowers the HER potential and encourages the in situ formation of a uniform ZHS-based solid electrolyte interphase on Zn anodes. Moreover, cationic NH4+ can preferentially adsorb on the Zn anode surface to shield the "tip effect" and homogenize the electric field. Benefitting from this comprehensive protection, dendrite-free Zn deposition and highly reversible Zn plating/stripping behaviors were realized. Besides, improved electrochemical performances can also be achieved in Zn//MnO2 full cells by taking the advantages of this triple-functional additive. This work provides a new strategy for stabilizing Zn anodes from a comprehensive perspective.

Effect of zinc (Zn) application to soil on root growth and Zn uptake and translocation in winter wheat are poorly understood. This study evaluated the effect of soil Zn fertilization (0, 2.3, 5.7, 11.4, 22.7, 34.1 kg of Zn ha-1) on root growth and distribution, crop Zn uptake, root-to-shoot translocation of Zn, and remobilization of Zn from shoot to grain. Results of this study revealed that Zn application ≤11.4 kg ha-1 significantly increased root dry weight, root length density, and root surface area within 0-30 cm soil depth and higher rates of Zn application caused slight decreases in these root parameters. Shoot biomass and shoot Zn accumulation increased as Zn application rate increased mainly because of improved matching of root growth and enhanced availability of Zn in the topsoil layer. Post-anthesis Zn uptake by shoot increased and translocation of Zn from root to shoot decreased as rate of Zn application increased. The degree to which Zn accumulation in grain resulted from pre-anthesis remobilization vs. post-anthesis shoot uptake depended on Zn availability in soil; post-anthesis shoot uptake dominated at DTPA-Zn concentrations >7.15 mg kg-1, and pre-anthesis remobilization dominated at lower soil Zn levels. In conclusion, Zn uptake, translocation and remobilization to grain were affected by root growth and its matching with the availability of soil Zn. The results suggest that soils similar to the study soil should be fertilized to 30 cm depth with about 11.4 kg ha-1 Zn in order to obtain high yield and grain Zn concentration of wheat.

Background: Many publications have investigated the association between metal ions and the risk of Alzheimer's disease (AD), but the results were ambiguous. Aims: The objective of this study was to assess the association between the serum levels of metals (copper/zinc/iron) and the risk of AD via meta-analysis of case-control studies. Methods: We screened literatures published after 1978 in the Pubmed, Embase, Cochrane library, Web of Science and ClinicalTrials.gov. Electronic databases. By using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, we performed a systematic review of the 407 publications, there are 44 of these publications met all inclusion criteria. The Review Manager 5.3 software was used to calculate available data from each study. Results: Consistent with the conclusions of other meta-analysis, our results demonstrated serum copper levels were significantly higher [MD = 9.27, 95% CI (5.02-13.52); p < 0.0001], and the serum zinc levels were significantly lower in AD patients than in healthy controls [MD = -6.12, 95% CI (-9.55, -2.69); p = 0.0005]. Serum iron levels were significantly lower in AD patients than in healthy controls after excluded two studies [MD = -13.01, 95% CI (-20.75, -5.27); p = 0.001]. Conclusion: The results of our meta-analysis provided rigorous statistical support for the association of the serum levels of metals and the risk of AD, suggesting a positive relationship between the serum copper levels and AD risk, and a negative relationship between the serum zinc/iron levels and AD risk.

CCCH-type zinc finger proteins comprise a large protein family. Increasing evidence suggests that members of this family are RNA-binding proteins with regulatory functions in mRNA processing. Compared with those in animals, functions of CCCH-type zinc finger proteins involved in plant growth and development are poorly understood.

Improving the development of inferior grains is important for increasing maize yield under high-density conditions. However, the effect of micronutrients, especially zinc (Zn), on the development of inferior grains and maize yield under field conditions has not been evaluated to date. A field experiment with six Zn application rates (0, 2.3, 5.7, 11.4, 22.7, and 34.1 kg/ha) was conducted to investigate the effects of soil application of Zn fertilizer on the development of inferior grains. Pollen viability was measured at the tasseling stage. The maize spike was divided into apical (inferior grain), middle, and basal sections for further measurement at harvest. Results showed that soil application of Zn fertilizer increased maize yield by 4.2-16.7% due to increased kernel number and weight in the apical, but not in the middle and basal sections. Zn application also significantly increased pollen viability at the tasseling stage. The critical Zn concentrations in shoots at the tasseling stage for obtaining high pollen viability and high kernel numbers of inferior grains were 31.2 and 35.6 mg/kg, respectively. Zn application also increased the 1,000-kernel weight of inferior grain due to high biomass accumulation. Furthermore, the grain Zn concentration of inferior grain with Zn application increased by 24.3-74.9% compared with no Zn application. Thus, soil application of Zn fertilizer successfully increased grain yield of maize by improving pollen viability, kernel number, and kernel weight of inferior grains (apical section), also contributing to grain Zn biofortification.

Myeloid zinc finger 1 (MZF1) belongs to the Kruppel family of zinc-finger transcription factors. Recent studies have demonstrated that in dorsal root ganglion (DRG) neurons, MZF1 is involved in the development and maintenance of neuropathic pain. However, the role of MZF1 in inflammatory pain still remains unknown. In the present study, the mechanism of MZF1 in chronic inflammatory pain was investigated in rats received an intraplantar injection of complete Freund's adjuvant (CFA). Subsequently, a series of assays including Western blotting, qRT-PCR, immunohistochemistry, and chromatin immunoprecipitation (ChIP) were performed. We found that CFA led to MZF1 upregulation in ipsilateral L4/5 DRGs. Pre- and post-microinjection of MZF1 siRNA into the ipsi-L5 DRG blocked the development of CFA-induced chronic inflammatory pain and alleviated the mechanical allodynia and thermal hyperalgesia in the maintenance phase. CFA also increased MMP-2/9 and Nav1.8 expression but reduced voltage-gated potassium 1.2 (Kv1.2) and Cav1.2 expression in L4/L5 DRGs. Microinjection of MZF1 siRNA into DRG diminished the CFA-induced changes in MMP-2/9 and Kv1.2 expression. However, the expressions of Nav1.8 and Cav1.2 were not changed by the treatment. Double immunofluorescence staining showed that MMP-2/9 and Kv1.2 were co-localized with MZF1 in DRGs. The ChIP-PCR results revealed that MZF1 binds directly to the promoter region of MMP-2/9 gene. Together, the above results imply that upregulation of MZF1 in DRGs might contribute to the development and maintenance of CFA-induced chronic inflammatory pain by regulating MMP-2/9 and Kv1.2 expression. Targeting DRG-localized MZF1 might be a promising therapeutic strategy for the treatment of chronic inflammatory pain in the clinic.

This study aimed to explore relationships between whole blood copper (Cu), zinc (Zn) and Cu/Zn ratio and cardiac dysfunction in patients with septic shock.

Assigning bond orders is a necessary and essential step for characterizing a chemical structure correctly in force field based simulations. Several methods have been developed to do this. They all have advantages but with limitations too. Here, an automatic algorithm for assigning chemical connectivity and bond order regardless of hydrogen for organic molecules is provided, and only three dimensional coordinates and element identities are needed for our algorithm. The algorithm uses hard rules, length rules and conjugation rules to fix the structures. The hard rules determine bond orders based on the basic chemical rules; the length rules determine bond order by the length between two atoms based on a set of predefined values for different bond types; the conjugation rules determine bond orders by using the length information derived from the previous rule, the bond angles and some small structural patterns. The algorithm is extensively evaluated in three datasets, and achieves good accuracy of predictions for all the datasets. Finally, the limitation and future improvement of the algorithm are discussed.

The formidable virulence of methicillin-resistant staphylococcus aureus (MRSA) have thrown great challenges to biomedicine, which mainly derives from their autocrine phenol-soluble modulins (PSMs) toxins, especially the most toxic member termed phenol-soluble modulins α3 (PSMα3). PSMα3 cytotoxicity is attributed to its amyloidal fibrillation and subsequent formation of cross-α sheet fibrils. Inspired by the multiple biological activity of Sappanwood, herein, we adopted brazilin, a natural polyphenolic compound originated from Caesalpinia sappan, as a potential antidote of PSMα3 toxins, and attempted to prove that the regulation of PSMα3 fibrillation was an effective alexipharmic way for MRSA infections. In vitro results revealed that brazilin suppressed PSMα3 fibrillation and disassembled preformed amyloidal fibrils in a dose-dependent manner, in which molar ratio (brazilin: PSMα3) of efficient inhibition and disassembly were both 1:1. These desired regulations dominated by brazilin benefited from its bonding to core fibrils-forming residues of PSMα3 monomers urged by hydrogen bonding and pi-pi stacking, and such binding modes facilitated brazilin-mediated inhibition or disruption of interactions between neighboring PSMα3 monomers. In this context, these inhibited and disassembled PSMα3 assemblies could not easily insert into cell membrane and subsequent penetration, and thus alleviating the membrane disruption, cytoplasmic leakage, and reactive oxygen species (ROS) generation in normal cells. As such, brazilin dramatically decreased the cytotoxicity borne by toxic PSMα3 fibrils. In addition, in vivo experiments affirmed that brazilin relieved the toxicity of PSMα3 toxins and thus promoted the skin wound healing of mice. This study provides a new antidote of PSMα3 toxins, and also confirms the feasibility of the assembly-regulation strategy in development of antidotes against supramolecular fibrillation-dependent toxins.

Artificial intelligence (AI)-based molecular design methods, especially deep generative models for generating novel molecule structures, have gratified our imagination to explore unknown chemical space without relying on brute-force exploration. However, whether designed by AI or human experts, the molecules need to be accessibly synthesized and biologically evaluated, and the trial-and-error process remains a resources-intensive endeavor. Therefore, AI-based drug design methods face a major challenge of how to prioritize the molecular structures with potential for subsequent drug development. This study indicates that common filtering approaches based on traditional screening metrics fail to differentiate AI-designed molecules. To address this issue, we propose a novel molecular filtering method, MolFilterGAN, based on a progressively augmented generative adversarial network. Comparative analysis shows that MolFilterGAN outperforms conventional screening approaches based on drug-likeness or synthetic ability metrics. Retrospective analysis of AI-designed discoidin domain receptor 1 (DDR1) inhibitors shows that MolFilterGAN significantly increases the efficiency of molecular triaging. Further evaluation of MolFilterGAN on eight external ligand sets suggests that MolFilterGAN is useful in triaging or enriching bioactive compounds across a wide range of target types. These results highlighted the importance of MolFilterGAN in evaluating molecules integrally and further accelerating molecular discovery especially combined with advanced AI generative models.

Coronavirus disease 2019 (COVID-19), resulting from infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can cause severe and fatal pneumonia along with other life-threatening complications. The COVID-19 pandemic has taken a heavy toll on the healthcare system globally and has hit the economy hard in all affected countries. As a result, there is an unmet medical need for both the prevention and treatment of COVID-19 infection. Several herbal remedies have claimed to show promising clinical results, but the mechanisms of action are not clear. We set out to identify the anti-viral natural products of these herbal remedies that presumably inhibit the life cycle of SARS-CoV-2. Particularly we chose four key SARS-CoV-2 viral enzymes as targets: Papain-like protease, Main protease, RNA dependent RNA polymerase, and 2'-O-ribose methyltransferase, which were subjected to an unbiased in silico screening against a small molecule library of 33,765 compounds originating from herbs and medicinal plants. The small molecules were then ranked based on their free energy of fitting into the "druggable" pockets on the surface of each target protein. We have analyzed the best "fit" molecules and annotated them according to their plant sources and pharmacokinetic properties. Here we present a list of potential anti-viral ingredients of herbal remedies targeting SARS-CoV-2 and explore the potential mechanisms of action of these compounds as a framework for further development of chemoprophylaxis agents against COVID-19.

Angiogenesis is the growth of new capillaries from existing blood vessels that supply oxygen and nutrients and provide gateways for immune surveillance. Abnormal vessel growth in term of excessive angiogenesis is a hallmark of cancer, inflammatory and eye diseases. VEGFR-2 (vascular endothelial growth factor receptor 2) dominating the process of angiogenesis has led to approval of therapeutic inhibitors and is becoming a promising target for anti-angiogenic drugs. Notwithstanding these successes, the clinical use of current VEGFR-2 blockers is more challenging than anticipated. Taking axitinib as a reference drug, in our study we found three potent VEGFR-2 inhibitors (ZINC08254217, ZINC08254138, and ZINC03838680) from natural derivatives. Each of the three inhibitors acquired a better grid score than axitinib (-62.11) when docked to VEGFR-2. Molecular dynamics simulations demonstrated that ZINC08254217- and ZINC08254138-VEGFR-2 complexes were more stable than axitinib. Similar to bind free energy for axitinib (-54.68 kcal/mol), such for ZINC03838680, ZINC08254217, and ZINC08254138 was -49.37, -43.32, and -32.73 kcal/mol respectively. These results suggested these three compounds could be candidate drugs against angiogenesis, with comparable VEGFR-2 binding affinity of axitinib. Hence findings in our study are able to provide valuable information on discovery of effective anti-angiogenesis therapy.

Polymer membranes, having improved conductivity with enhanced thermal and chemical stability, are desirable for proton exchange membranes fuel cell application. Hence, poly(benzophenone)s membranes (SI-PBP) containing super gas-phase acidic sulfonyl imide groups have been prepared from 2,5-dichlorobenzophenone (DCBP) monomer by C-C coupling polymerization using Ni (0) catalyst. The entirely aromatic C-C coupled polymer backbones of the SI-PBP membranes provide exceptional dimensional stability with rational ion exchange capacity (IEC) from 1.85 to 2.30 mS/cm. The as-synthesized SI-PBP membranes provide enhanced proton conductivity (107.07 mS/cm) compared to Nafion 211® (104.5 mS/cm). The notable thermal and chemical stability of the SI-PBP membranes have been assessed by the thermogravimetric analysis (TGA) and Fenton's test, respectively. The well distinct surface morphology of the SI-PBP membranes has been confirmed by the atomic force microscopy (AFM). These results of SI-PBP membranes comply with all the requirements for fuel cell applications.

Aqueous zinc-ion batteries, in terms of integration with high safety, environmental benignity, and low cost, have attracted much attention for powering electronic devices and storage systems. However, the interface instability issues at the Zn anode caused by detrimental side reactions such as dendrite growth, hydrogen evolution, and metal corrosion at the solid (anode)/liquid (electrolyte) interface impede their practical applications in the fields requiring long-term performance persistence. Despite the rapid progress in suppressing the side reactions at the materials interface, the mechanism of ion storage and dendrite formation in practical aqueous zinc-ion batteries with dual-cation aqueous electrolytes is still unclear. Herein, we design an interface material consisting of forest-like three-dimensional zinc-copper alloy with engineered surfaces to explore the Zn plating/stripping mode in dual-cation electrolytes. The three-dimensional nanostructured surface of zinc-copper alloy is demonstrated to be in favor of effectively regulating the reaction kinetics of Zn plating/stripping processes. The developed interface materials suppress the dendrite growth on the anode surface towards high-performance persistent aqueous zinc-ion batteries in the aqueous electrolytes containing single and dual cations. This work remarkably enhances the fundamental understanding of dual-cation intercalation chemistry in aqueous electrochemical systems and provides a guide for exploring high-performance aqueous zinc-ion batteries and beyond.

Antioxidation is very important in medicine and food. The current evaluation technologies often have many shortcomings. In this work, an improved electrochemical sensing platform for the evaluation of antioxidant activity has been proposed. A hydrogel was prepared based on graphene oxide, zinc ions, and chitosan. Zinc ions play the role of crosslinking agents in hydrogels. The structure of chitosan can be destroyed by injecting hydrogen peroxide into the hydrogel, and the free zinc ions can diffuse to the surface of the electrode to participate in the electrochemical reaction. This electrochemical sensor can evaluate the antioxidant activity by comparing the current difference of zinc reduction before and after adding the antioxidant. With the help of graphene oxide, this hydrogel can greatly enhance the sensing effect. We conducted tests on 10 real samples. This proposed electrochemical platform has been successfully applied for evaluating the antioxidant activity of Scutellaria baicalensis, and the results were compared to those obtained from the 2,2-diphenyl-1-picrylhydrazyl-based traditional analysis technique.

Acute lymphoblastic leukemia (ALL) is the most frequently occurring malignant neoplasm in children. Despite advances in treatment and outcomes for ALL patients, the pathogenesis of the disease remains unclear. Microarray analysis of samples from 100 Chinese children with ALL revealed the up-regulation of CTCF (CCCTC binding factor). CTCF is a highly conserved 11-zinc finger protein that is involved in many human cancers; however, the biological function of CTCF in pediatric ALL is unknown.

Advanced thermoplastic materials, such as polyether-ether-ketone (PEEK) and highly cross-linked polyethylene (HXLPE), have been increasingly used as orthopaedic implant materials. Similar to other implants, PEEK-on-HXLPE prostheses produce debris from polymer wear that may activate the immune response, which can cause osteolysis, and ultimately implant failure. In this study, we examined whether the anti-inflammatory properties of zinc oxide nanoparticles (ZnO NPs) could attenuate polymer wear particle-induced inflammation.

Previous studies have demonstrated that myeloid zinc finger 1 (MZF1) in the dorsal root ganglion (DRG) participates in neuropathic pain induced by chronic-constriction injury (CCI) via regulation of voltage-gated K+ channels (Kv). Emerging evidence indicates that transient receptor potential vanilloid 1 (TRPV1) is involved in the development and maintenance of neuropathic pain. Although it is known that the transcription of TRPV1 is regulated by Kruppel-like zinc-finger transcription factor 7 (Klf7)-and that the structure of TRPV1 is similar to that of Kv-few studies have systematically investigated the relationship between MZF1 and TRPV1 in neuropathic pain. In the present study, we demonstrated that CCI induced an increase in MZF1 and TRPV1 in lumbar-level 4/5 (L4/5) DRGs at 3 days post-CCI and that this increase was persistent until at least 14 days post-CCI. DRG microinjection of rAAV5-MZF1 into the DRGs of naïve rats resulted in a decrease in paw-withdrawal threshold (PWT) and paw-withdrawal latency (PWL) compared with that of the rAAV5-EGFP group, which started at four weeks and lasted until at least eight weeks after microinjection. Additionally, prior microinjection of MZF1 siRNA clearly ameliorated CCI-induced reduction in PWT and PWL at 3 days post-CCI and lasted until at least 7 days post-CCI. Correspondingly, microinjection of MZF1 siRNA subsequent to CCI alleviated the established mechanical allodynia and thermal hyperalgesia induced by CCI, which occurred at 3 days postinjection and lasted until at least 10 days postinjection. Microinjection of rAAV5-MZF1 increased the expression of TRPV1 in DRGs. Microinjection of MZF1 siRNA diminished the CCI-induced increase of TRPV1, but not P2X7R, in DRGs. These findings suggest that MZF1 may contribute to neuropathic pain via regulation of TRPV1 expression in DRGs.