Targeting telomerase utilizing zeolitic imidazole frameworks as non-viral gene delivery agents across different cancer cell types.

Telomerase, a ribonucleoprotein coded by the hTERT gene, plays an important role in cellular immortalization and carcinogenesis. hTERT is a suitable target for cancer therapeutics as its activity is highly upregulated in most of cancer cells but absent in normal somatic cells. Here, by employing the two Metal-Organic Frameworks (MOFs), viz. ZIF-C and ZIF-8, based biomineralization we encapsulate Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 plasmid system that targets hTERT gene (CrhTERT) in cancer cells. When comparing the two biocomposites, ZIF-C shows the better loading capacity and cell viability. The loaded plasmid in ZIF-C is highly protected against enzymatic degradation. CrhTERT@ZIF-C is efficiently endocytosed by cancer cells and the subcellular release of CrhTERT leads to telomerase knockdown. The resultant inhibition of hTERT expression decreases cellular proliferation and causing cancer cell death. Furthermore, hTERT knockdown shows a significant reduction in tumour metastasis and alters protein expression. Collectively we show the high potential of ZIF-C-based biocomposites as a promising general tool for gene therapy of different types of cancers.

Rumen Parameters, Nutrients Digestibility and Milk Production of Lactating Boer Goats Fed Diets Containing Clay Minerals.

<b>Background and Objective:</b> The inclusion of clay minerals in dairy nutrition is getting attention owing to their proven beneficial effects. The current study aimed to evaluate the effect of dietary supplementation of three different clay minerals (bentonite, zeolite and humic acid) on the performance of lactating Boer goats. <b>Materials and Methods:</b> Twenty lactating Boer goats (having an average body weight ~42.7 kg) were divided into four groups (5 animals each) by using a completely randomized design (CRD). Each group was fed with one of four dietary treatments: Control group with basal ration R1: Consisting of concentrate feed mixture (CFM) and clover hay (50:50%, C:R) on a dry matter (DM) basis, R2: Basal ration plus 1% bentonite, R3: Basal ration plus 1.25% zeolite and R4: Basal ration plus 0.5% humic acid. <b>Results:</b> The results revealed that bentonite and humic acid increased (p<0.05) the nutrient digestibility and nutritive values compared to zeolite and control groups. Ruminal ammonia and total volatile fatty acids (TVFAs) contents increased (p<0.05) with supplementation of bentonite. No effect of clays supplementation was observed on plasma total protein, urea and creatinine, however, it increased (p<0.05) the albumin concentration and albumin/globulin ratios compared to the control while decreasing the plasma globulin contents. Supplementation of humic acid increased (p<0.05) the AST concentrations. Bentonite supplementation recorded the highest milk yield (p<0.05) and composition, while the zeolite group had the lowest values. <b>Conclusion:</b> The present study indicated that the inclusion of clay minerals particularly bentonite (at 1%) can positively affect the performance of lactating Boer goats.

Treatment of secondary urban wastewater with a low ammonium-tolerant marine microalga using zeolite-based adsorption.

The low tolerance of marine microalgae to ammonium and hyposalinity limits their use in urban wastewater (UWW) treatments. In this study, using the marine microalga Amphidinium carterae, it is demonstrated for the first time that this obstacle can be overcome by introducing a zeolite-based adsorption step to obtain a tolerable UWW stream. The maximum ammonium adsorption capacities measured in the natural zeolite used are among the highest reported. The microalga grows satisfactorily in mixtures of zeolite-treated UWW and seawater at a wide range of proportions, both with and without adjusting the salinity, as long as the ammonium concentration is below the threshold tolerated by the microalgae (6.3 mg L-1). A proof of concept performed in 10-L bubble column photobioreactors with different culture strategies, including medium recycling, showed an enhanced biomass yield relative to a control with no UWW. No noticeable effect was observed on the production of specialty metabolites.

Effect of Zeolite Supplementation on Gene Expression in the Intestinal Mucosa in the Context of Immunosafety Support in Poultry.

Zeolite is an effective and non-toxic silicate mineral. Its properties are widely used in industry due to its sorption and ion exchange properties. Due to its excellent chemical properties, it has also great potential in poultry production as a food additive or supplement to bedding. This is of great importance for the biosafety and hygiene of production. The study aimed to analyse the effects of simultaneous application of zeolite to feed and bedding on production parameters and expression of genes related to intestinal tightness, organism defence, and immune response. Male Ross 308 broiler chickens were used in the experiment. In the experimental group, an external factor in the form of a powdery zeolite was used for feed and pelleted bedding. On the day of slaughter, the caecal mucosa was collected for gene expression analysis. We showed no significant changes in the tissue composition of the carcasses, but zeolite had a beneficial effect on the carcass yield. The analysis of the immune gene panel showed a significant increase in the expression of the interleukins and interferons genes. We have demonstrated the effect of zeolite on the improvement of the intestinal barrier and increasing the tightness of the intestines. There were no changes in gene expression related to the host's defence against infections; therefore, based on the obtained results, it was concluded that zeolite can be considered an immunomodulating factor of the immune system.

A biomimetic zeolite-based nanoenzyme contributes to neuroprotection in the neurovascular unit after ischaemic stroke via efficient removal of zinc and ROS.

Zeolite-based nanomaterials have a large number of applications in the field of medicine due to their high porosity, biocompatibility and biological stability. In this study, we designed cerium (Ce)-doped Linde Type A (LTA) zeolite-based nanomaterials (Ce/Zeo-NMs) as a multifunctional mesoporous nanoenzyme to reduce dysfunction of the neurovascular unit (NVU) and attenuate cerebral ischaemia-reperfusion (I/R) injury. Owing to its unique adsorption capacity and mimetic catalytic activities, Ce@Zeo-NMs adsorbed excess zinc ions and exhibited scavenging activity against reactive oxygen species (ROS) induced by acute I/R, thus reshaping the oxidative and zinc microenvironment in the ischaemic brain. In vivo results demonstrated that Ce@Zeo-NMs significantly reduced ischaemic damage to the NVU by decreasing the infarct area, protecting against breakdown of the blood-brain barrier (BBB) via inhibiting the degradation of tight junction proteins (TJPs) and inhibiting activation of microglia and astrocytes in a rat model of middle cerebral artery occlusion-reperfusion (MCAO/R). Taken together, these findings indicated that Ce@Zeo-NMs may serve as a promising dual-targeting therapeutic agent for alleviating cerebral I/R injury. STATEMENT OF SIGNIFICANCE: Cerium (Ce)-doped Linde Type A zeolite-based nanomaterials (Ce/Zeo-NMs) as a multifunctional mesoporous nanoenzyme were designed for inducing neuroprotection after ischaemic stroke by reducing dysfunction of the neurovascular unit (NVU). Ce@Zeo-NMs had the ability to adsorb excessive Zn2+ and showed mimetic enzymatic activities. As a result, Ce@Zeo-NMs protected against cerebral ischaemia and reduced the damage of NVU by improving the integrity of blood brain barrier (BBB) and inhibiting activation of microglia and astrocytes in a rat model of middle cerebral artery occlusion-reperfusion (MCAO/R). These findings indicated that Ce@Zeo-NMs may serve as a therapeutic strategy for neuroprotection and functional recovery upon ischaemic stroke onset.

Mitochondrial Dysfunction and Antioxidation Dyshomeostasis-Enhanced Tumor Starvation Synergistic Chemotherapy Achieved using a Metal-Organic Framework-Based Nano-Enzyme Reactor.

Exploiting zeolitic imidazolate framework (ZIF)-based nanoparticles to synergistically enhance starvation-combined chemotherapy strategies remains an urgent demand. Herein, glucose oxidase (GOX) and doxorubicin (DOX) were facilely incorporated into ZIFs for starvation-combined chemotherapy. The as-prepared DOX/GOX-loaded ZIF (DGZ) exhibited uniform size with good dispersity, effective protection of the GOX activity, and stable delivery of the drugs into tumor. Correspondingly, it could achieve the glucose- and pH-responsive degradation and thus the controllable drug release. As a result, the acidification of glucose accompanied with reactive oxygen species (ROS) production was observed for the starvation-enhanced chemotherapy and the improved degradation. Most importantly, adjustable Zn2+ release was achieved with the biodegradation of DGZ, which thus contributed to an augmented therapeutic outcome via the Zn2+-induced mitochondrial dysfunction and antioxidation dyshomeostasis. These findings, synergized with the enhancement of starvation-combined chemotherapy by inhibiting the mitochondrial energy metabolism and boosting the ROS accumulation using pristine ZIF-based nanoparticles, provide a new insight into the metal-organic framework-based nanomedicine for further cancer treatments.

Immobilization of Escherichia coli cells harboring a nitrilase with improved catalytic properties though polyethylenemine-induced silicification on zeolite.

In the chemical-biological synthesis route of gabapentin, immobilized Escherichia coli cells harboring nitrilase are used to catalyze the biotransformation of intermediate 1-cyanocyclohexaneacetonitile to 1-cyanocyclohexaneacetic acid. Herein, we present a novel cell immobilization method, which is based on cell adsorption using 75 g/L Escherichia coli cells and 6 g/L zeolite, cell crosslinking using 3 g/L polyethylenemine and biomimetic silicification using 18 g/L hydrolyzed tetramethylorthosilicate. The constructed "hybrid biomimetic silica particles (HBSPs)" with core-shell structure showed a specific activity of 147.2 ± 2.3 U/g, 82.6 ± 2.8% recovery of nitrilase activity and a half-life of 19.1 ± 1.9 h at 55 °C. 1-Cyanocyclohexaneacetonitrile (1.0 M) could be completely hydrolyzed by 50 g/L of HBSPs at pH 7.5, 35 °C in 4 h, providing 92.1 ± 3.2% yield of 1-cyanocyclohexaneacetic acid. In batch reactions, the HBSPs could be reused for 13 cycles and maintained 79.9 ± 4.1% residual activity after the 10th batch, providing an average product yield of 92.6% in the first 10 batches with a productivity of 619.3 g/L/day. In addition, multi-layer structures consisting of silica coating and polyethylenemine/glutaraldehyde crosslinking were constructed to enhance the mechanical strength of immobilized cells, and the effects of coating layers on the catalytic properties of immobilized cells was discussed.

Biodegradable Nanocatalyst with Self-Supplying Fenton-like Ions and H2O2 for Catalytic Cascade-Amplified Tumor Therapy.

Therapeutic nanosystems triggered by a specific tumor microenvironment (TME) offer excellent safety and selectivity in the treatment of cancer by in situ conversion of a less toxic substance into effective anticarcinogens. However, the inherent antioxidant systems, hypoxic environment, and insufficient hydrogen peroxide (H2O2) in tumor cells severely limit their efficacy. Herein, a new strategy has been developed by loading the chemotherapy prodrug disulfiram (DSF) and coating glucose oxidase (GOD) on the surface of Cu/ZIF-8 nanospheres and finally encapsulating manganese dioxide (MnO2) nanoshells to achieve efficient DSF-based cancer chemotherapy and dual-enhanced chemodynamic therapy (CDT). In an acidic TME, the nanocatalyst can biodegrade rapidly and accelerate the release of internal active substances. The outer layer of MnO2 depletes glutathione (GSH) to destroy the reactive oxygen defensive mechanisms and achieves continuous oxygen generation, thus enhancing the catalytic efficiency of GOD to burst H2O2. Benefiting from the chelation reaction between the released Cu2+ and DSF, a large amount of cytotoxic CuET products is generated, and the Cu+ are concurrently released, thereby achieving efficient chemotherapy and satisfactory CDT efficacy. Furthermore, the release of Mn2+ can initiate magnetic resonance imaging signals for the tracking of the nanocatalyst.

A Biocatalytic Cascade in an Ultrastable Mesoporous Hydrogen-Bonded Organic Framework for Point-of-Care Biosensing.

Herein, we report the first example of using mesoporous hydrogen-bonded organic frameworks (MHOFs) as the protecting scaffold to organize a biocatalytic cascade. The confined microenvironment of MHOFs has robust and large transport channels, allowing the efficient transport of a wide range of biocatalytic substrates. This new MHOF-confined cascade system shows superior activity, extended scope of catalytic substrates, and ultrahigh stability that enables the operation of complex chemical transformations in a porous carrier. In addition, the advantages of MHOF-confined cascades system for point-of-care biosensing are also demonstrated. This study highlights the advantages of HOFs as scaffold for multiple enzyme assemblies, which has huge potential for mimicking complex cellular transformation networks in a controllable manner.

ATP-triggered mitochondrial cascade reactions for cancer therapy with nanoscale zeolitic imidazole framework-90.

Goals: Chemotherapy, the most conventional modality for cancer therapy, usually brings serious side effects because of the low cancer-therapeutic specificity and bioavailability. It is of great significance for cancer treatment to develop new effective strategies to regulate biochemical reactions in organelles, enhance the specificity of chemotherapeutic drugs and reduce their side effects. Methods: We report herein a zeolitic imidazole framework-90 (ZIF-90) based nanoplatform, which was used to initiate a series of mitochondrial cascade reactions using ATP as a molecular switch for cancer therapy. The thioketal linked camptothecin (camptothecin prodrug, TK-CPT) and 2-Methoxyestradiol (2-ME) were encapsulated into the pores of ZIF-90 nanoparticles using a simple one-pot method, and the nanoplatform was finally coated with a layer of homologous cell membrane. Results: Mitochondrial ATP can efficiently degrade ZIF-90 and then release the loaded 2-ME and CPT prodrugs. 2-ME can inhibit the activity of superoxide dismutase (SOD), which induces the up-regulation of reactive oxygen species (ROS) in situ. The thioketal linkers in CPT prodrug can respond to ROS, thereby achieving subsequent release of parent CPT drug. This cascade of reactions can lead to prolonged high oxidative stress and cause continuous cancer cell apoptosis, due to the increased ROS level and the liberation of CPT. Conclusion: We constructed an ATP-triggered strategy using nanoscale ZIF-90 to initiate mitochondrial cascade reactions for cancer therapy. The ZIF-90 based nanoplatform exhibited low cytotoxicity, good mitochondria-targeting ability, and excellent therapeutic effect. In vivo experiments demonstrated that the growth of tumor can be efficiently inhibited in a mouse model. This ATP-triggered strategy to induce mitochondrial biochemical reactions offers more possibilities for developing organelle-targeted therapeutic platforms.

Asbestos and Zeolites: from A to Z via a Common Ion.

Asbestos and zeolites are silicate-based minerals, linked inextricably via paradoxical similarities and differences which have emanated from different geological epochs. Both have been employed in the service of humanity through millennia: asbestos, for its "inextinguishable" quality of being an insulator against heat and fire; zeolite, a "boiling stone" with its volcanic and marine sedimentary rock origins, for its propensity to adsorb water and remove metals and toxins. Serious adverse health effects observed in asbestos miners as long ago as the 1st Century AD did not halt the rising popularity of asbestos. As the miracle material of the 1900s, asbestos production and consumption exploded, culminating in its ubiquity in ships, vehicles, homes, commercial buildings, and over 3000 different industrial and household products. Through the 1940s and 1950s, epidemiological studies concluded that asbestos was a likely cause of asbestosis, lung cancer, and malignant mesothelioma, and it is now banned in many but far from all countries. The long latency between exposure to asbestos and the occurrence of cancer has obscured the deadly consequences of asbestos exposure for centuries. Even today, a considerable part of the world population is insufficiently aware of the dangers of asbestos, and millions of tons of this carcinogen continue to be mined and used worldwide. Zeolites, both natural and synthetic, are microporous aluminosilicate minerals commonly used in a myriad of processes, in the petrochemical industry, in domestic appliances and cleaning agents, as commercial adsorbents and exchangers for toxins and pollutants, and as catalysts. Zeolites are found in agriculture, veterinary science, and human health. More recently, new materials such as carbon nanotubes are being employed in materials requiring durability and thermal and electrical conductivity, yet nanotubes are now joining the ranks of more established particulates such as asbestos and silica, in causing human disease. In this review, we compare and contrast the similarities and differences of these two groups of silicate minerals and their waxing and waning use in the employ of humanity.

Zeolitic Imidazolate Framework Platform for Combinational Starvation Therapy and Oxygen Self-Sufficient Photodynamic Therapy against a Hypoxia Tumor.

The antitumor efficacy of photodynamic therapy (PDT) is greatly impeded by the nonspecific targeting of photosensitizers and limited oxygen supply in hypoxic tumors. Aiming to overcome the problem, a dual-locked porphyrin/enzyme-loading zeolitic imidazolate framework (ZIF) nanoplatform was constructed for starvation therapy and O2 self-sufficient PDT. The fluorescence recovery and PDT of photosensitizers could be cooperatively triggered by dual pathological parameters, the low pH and overexpressed GSH in tumor tissues, which makes the PDT process conduct precisely in a tumor microenvironment. The cascade catalysis of glucose oxidase and catalase promotes the nanoplatform dissociation, inhibits the energy supply of tumors (starvation therapy), and provides enough O2 to ameliorate the hypoxia and enhance PDT efficacy. In vitro and in vivo studies were performed to confirm the high antitumor efficacy of the porphyrin/enzyme-loading ZIF nanoplatform. Thus, this work offers a path for precise and efficient PDT-based combination therapy against a hypoxia tumor.

Effects of plant on denitrification pathways in integrated vertical-flow constructed wetland treating swine wastewater.

Plant is an important part of constructed wetland (CW), while, its potential effect on nitrogen cycling is complicated. Herein, integrated vertical-flow constructed wetland (IVCW) in pilot-scale planted with Arundo donax (Planted System, PS) was constructed to treat swine wastewater. The removal performance of nitrogen in PS, effects of plant on the microbial community structure and nitrogen related function genes were revealed. Results showed that, Arundo donax planting enhanced the removal rate of TN, compared to unplanted IVCWs, the absolute abundance of Pseudomonas, Acinetobacter and Bacillus in PS was significantly increased, as well as the absolute abundance of functional gene (amoA, nxrA, nirK, nirS and nosZ). The denitrification process was mainly occurred in down-flow cell of PS with significantly higher abundant of nirK and nosZ (P < 0.05). These findings suggested that Arundo donax planting in IVCWs with zeolite as substrate promoted the growth of denitrifying microorganisms under higher pollutant load. In addition, the increased abundant of nosZ and the ratio of nosZ/∑nir indicating a lower genetic potential for N2O release. Our research provides new insight into the potential application of plant on the purification of swine wastewater.

Assessment of H-ß zeolite as an ochratoxin binder for poultry.

Most of the cereal-based ingredients used in poultry feed are contaminated with ochratoxin-A (OTA). We have investigated H-ß zeolite (HBZ) as a new OTA binder for poultry, along with widely used clay mineral-based product (CM), using in vitro and in vivo methods. In vitro binding experiment was carried out using a biphasic assay, consisting of adsorption at pH 3.2 and desorption at pH 6.8. High adsorption (>98%) with less desorption (<5%) was observed for HBZ, whereas CM showed high binding (>98%) and moderate desorption (48%). In the in vitro experiments with the different simulated gastro-intestinal pH buffers, HBZ did not desorb OTA at any of the pH. Desorption of OTA was observed with CM, as the pH increases. From the in vitro kinetic and chemisorption studies, faster, stronger, and higher adsorption was observed for HBZ. Thermodynamic studies showed positive entropy (22.76 KJ/mol K) for HBZ, signifying predominant hydrophobic interactions towards OTA, whereas CM exhibited negative entropy (-3.67 KJ/mol K). The in vivo binding efficacy of HBZ and CM was tested in 5-wk-old broiler chickens. The study consisted of 4 experimental groups, each with 6 replicates having 2 birds per replicate. The groups were control, negative control (no toxin binder), T1 (HBZ at 1 kg/ton of feed), and T2(CM at 1 kg/ton of feed). Except control, all the replicates received 20 µg of OTA in the feed. Excreta samples of T1, T2, and NC contained 11.57, 7.16, and 2.78 µg of OTA respectively, which was significantly different from each other (P < 0.05). A growth performance trial was conducted in broiler chickens for 35 D. A total of 288 one-day-old birds were randomly segregated to 3 treatment groups, each with 8 replicates of 12 birds each. Treatment groups consisted of control, T1, and T2, treated with no toxin binder, HBZ, and CM at 1 kg/ton of feed, respectively. None of the treatment groups including control, affected BW gain, and feed conversion ratio (P > 0.05).

ATP-responsive laccase@ZIF-90 as a signal amplification platform to achieve indirect highly sensitive online detection of ATP in rat brain.

A novel electrochemical online system for indirect, highly sensitive and selective online monitoring of ATP in the cerebral microdialysate is presented based on the particular reaction of ATP with zeolitic imidazole framework-90 (ZIF-90) encapsulated laccase microcrystals (laccase@ZIF-90) and the natural catalytic activity of laccase.

One-pot synthesis of trypsin-based magnetic metal-organic frameworks for highly efficient proteolysis.

Immobilization of enzymes onto metal-organic frameworks (MOFs) through a biomimetic mineralization approach can preserve biological functionality in harsh environments. Despite the success of this approach, the alkaline environment of the reaction system, which is caused by the organic monomers of MOFs, makes it unsuitable for some pH-sensitive enzymes, especially for trypsin. Herein, we reported a facile approach for the one-pot synthesis of trypsin-immobilized magnetic zeolite imidazolate framework-8 (iron oxide@ZIF-8@trypsin), where the growth of ZIF-8 around the citric acid-modified iron oxide and immobilization of trypsin occurred simultaneously when the pH of the reaction system was changed to some extent. With a large specific surface area and a high enzyme loading capacity, the resultant iron oxide@ZIF-8@trypsin exhibited 2.6 times higher enzymatic activity than free trypsin. Moreover, it showed a favourable magnetic response (43 emu g-1) which made the operation and recycling easy and convenient. In addition, iron oxide@ZIF-8@trypsin could be applied as an immobilized enzyme microreactor (IMER) to rapidly and efficiently digest proteins and complex human serum samples with satisfactory results, showing great promise for application in proteomic analysis.

Nanoscale dual-enzyme cascade metal-organic frameworks through biomimetic mineralization as ROS generators for synergistic cancer therapy.

Chemodynamic therapy (CDT) has been critically challenged by insufficient H2O2 in cancer tissues and inefficient reactive oxygen species (ROS) production. Herein, we have reported the facile synthesis of an efficient ROS generator (GOx@Pd@ZIF-8) that exerts synergistic anticancer activity by blocking glucose metabolism and producing ROS. Glucose oxidase (GOx) and palladium (Pd) cube nanozymes were incorporated in zeolitic imidazolate framework-8 (ZIF-8) by biomimetic mineralization. Systematic characterization indicated the successful entrapment and embedding of GOx and Pd during ZIF-8 crystal growth. The GOx@Pd@ZIF-8 composite showed favorable catalytic glucose activity and stable ROS production. In vitro experiments showed that the GOx@Pd@ZIF-8 composite effectively inhibited cancer cell proliferation, invasion, and migration and promoted apoptosis through the ROS-mediated signaling pathway, which was further confirmed by bioinformatics analyses of RNA-seq data obtained from in vitro experiments. Furthermore, the GOx@Pd@ZIF-8 composite inhibited tumor growth with few to no side effects on other tissues in vivo. This work provides a novel antitumor strategy involving the construction of a stable and highly active ROS generator that shows promise for the treatment of solid cancers.

The effect of feed supplementation with Transcarpathian zeolite (clinoptilolite) on the concentrations of acute phase proteins and cytokines in the serum and hepatic tissue of chickens.

The aim of the this study was to determine the effect of different levels of Transcarpathian zeolite (clinoptilolite) on selected indicators of the immune response in chickens by assessing the concentrations of the acute phase proteins haptoglobin, C-reactive protein (CRP), serum amyloid A, transferrin, and alpha-1-acid glycoprotein and the cytokines tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-2, and IL-10 in the serum and hepatic tissues of chickens. The study was conducted on 450 one-day-old male Ross 308 chickens. The total rearing period was 42 D. The samples of blood and liver were collected before the start of the study (day 0) and on day 42, after rearing was completed. ELISA kits specific for chicken CRP, haptoglobin, alpha-1-acid glycoprotein, serum amyloid A, transferrin, TNF-α, IFN-γ, IL-2, and IL-10 were used to determine the levels of acute phase proteins and cytokines in the serum and liver homogenates. The results of immunological tests suggest that for long-term maintenance of homeostasis in chickens, the addition of 2% zeolite as a feed additive is most beneficial. The results indicate that 3% clinoptilolite induce production of Th1 pro-inflammatory cytokines, increasing the synthesis of IL-2, IFN-γ, and TNF-α. The high concentration of IL-10 after the use of zeolite in conjunction with the high concentration of IL-2, TNF-α, and IFN-γ indicates a reduction in the intensity of inflammatory processes, the enhancement of the humoral immune response, and the simultaneous inhibition of the production of Th1-type cytokines. The increase of CRP concentration in conjunction with high concentrations of pro- and anti-inflammatory cytokines in the birds from the group receiving 3% clinoptilolite demonstrates indicates that it can influence the development of local inflammatory processes and enhance immune regulation in birds. Our research has shown that clinoptilolite influences on an increase in birds' resistance to infection, as confirmed by clinical observations and anatomopathological examination and by the increase in the synthesis of acute phase proteins with immunoregulatory properties.

Modulating the Biofunctionality of Metal-Organic-Framework-Encapsulated Enzymes through Controllable Embedding Patterns.

Embedding an enzyme within a MOF as exoskeleton (enzyme@MOF) offers new opportunities to improve the inherent fragile nature of the enzyme, but also to impart novel biofunctionality to the MOF. Despite the remarkable stability achieved for MOF-embedded enzymes, embedding patterns and conversion of the enzymatic biofunctionality after entrapment by a MOF have only received limited attention. Herein, we reveal how embedding patterns affect the bioactivity of an enzyme encapsulated in ZIF-8. The enzyme@MOF can maintain high activity when the encapsulation process is driven by rapid enzyme-triggered nucleation of ZIF-8. When the encapsulation is driven by slow coprecipitation and the enzymes are not involved in the nucleation of ZIF-8, enzyme@MOF tends to be inactive owing to unfolding and competing coordination caused by the ligand, 2-methyl imidazole. These two embedding patterns can easily be controlled by chemical modification of the amino acids of the enzymes, modulating their biofunctionality.