Aluminum phytotoxicity in acidic environments: A comprehensive review of plant tolerance and adaptation strategies.

Aluminum (Al), a non-essential metal for plant growth, exerts significant phytotoxic effects, particularly on root growth. Anthropogenic activities would intensify Al's toxic effects by releasing Al3+ into the soil solution, especially in acidic soils with a pH lower than 5.5 and rich mineral content. The severity of Al-induced phytotoxicity varies based on factors such as Al concentration, ionic form, plant species, and growth stages. Al toxicity leads to inhibited root and shoot growth, reduced plant biomass, disrupted water uptake causing nutritional imbalance, and adverse alterations in physiological, biochemical, and molecular processes. These effects collectively lead to diminished plant yield and quality, along with reduced soil fertility. Plants employ various mechanisms to counter Al toxicity under stress conditions, including sequestering Al in vacuoles, exuding organic acids (OAs) like citrate, oxalate, and malate from root tip cells to form Al-complexes, activating antioxidative enzymes, and overexpressing Al-stress regulatory genes. Recent advancements focus on enhancing the exudation of OAs to prevent Al from entering the plant, and developing Al-tolerant varieties. Gene transporter families, such as ATP-Binding Cassette (ABC), Aluminum-activated Malate Transporter (ALMT), Natural resistance-associated macrophage protein (Nramp), Multidrug and Toxic compounds Extrusion (MATE), and aquaporin, play a crucial role in regulating Al toxicity. This comprehensive review examined recent progress in understanding the cytotoxic impact of Al on plants at the cellular and molecular levels. Diverse strategies developed by both plants and scientists to mitigate Al-induced phytotoxicity were discussed. Furthermore, the review explored recent genomic developments, identifying candidate genes responsible for OAs exudation, and delved into genome-mediated breeding initiatives, isolating transgenic and advanced breeding lines to cultivate Al-tolerant plants.

First report of Nigrospora oryzae causing wilt in summer cypress (Bassia scoparia) in Pakistan.

Summer Cypress (Bassia scoparia) is a large annual herb belonging to the family Amaranthaceae native to Eurasia. It has been introduced in many other countries of the world. In Pakistan, summer cypress is also known as kochia and grown as an ornamental plant for its red fall foliage for landscapes. During October, 2017 a survey was conducted in Punjab Province, Pakistan, where 100 wilted plant samples were collected from 30 different plantations of Faisalabad district. Up to 50% loss of plantation was noted in all visited locations. Lower parts of the plants were affected first presenting with necrosis of leaf tips surrounded by a chlorotic zone (Fig. 1. A). Then necrosis of apical margins of the plant parts occurred, followed by stem discoloration and wilting of entire herbaceous branches, leading to the partial wilting of the plants. Ultimately, whole plant wilted and died, (Fig. 1. B) appearing as though they had been scorched. Diseased tissues from lower stem (crown portion) were sampled, surface sterilized in 70 % ethanol for 30 s, and cultured on to Potato Dextrose Agar (PDA) medium. Petri dishes were incubated at 25 ˚C with alternating 12-hour periods of light and dark. Frequently observed, fast growing whitish grey fungal cultures with black pin head points were obtained after 7 days (Fig. 1. C). Young conidia were one-celled, yellow to orange in color and turned brown to black (Fig. 1. D & E), ranged in size from 11 µm to 16 µm x 9.5 µm to 12 µm (Fig. 1. F), and were ellipsoidal at maturity (Fig. 2. A). Hyphae were branched, septate and dark brown in color while conidiophores were flexuous, branched and ranged between 3.5 µm to 4.5 µm in diameter and 14.5 µm to 26.5 µm in length. Based on morphology (Ellis, 1971), the pathogen was identified as Nigrospora oryzae and submitted to the Westerdijk Collection of Fungi, Netherland (CBS 146145/RNOEG30). Total DNA of isolate EG30 was extracted and portions of the Internal transcribed spacer (ITS) region and beta-tubulin (ßt) gene were amplified using the universal primers ITS1F and ITS4 (White et al., 1990) and ßt2a and ßt2b (Glass and Donaldson, 1995). The generated ITS (GenBank Accession No. MG745331.1 491 bp) and ßt (GenBank Accession No. MN629896 408 bp) sequences were searched against GenBank using BLASTn and were 99% homologous to ITS (KX986074 525 bp ; MN341493 550 bp) and 100% homologous to ßt (MK262852 409 bp) gene region from Nigrospora oryzae (Wang et al., 2017; Zhang, 2019). For pathogenicity tests, ten healthy two-month-old summer cypress plants were inoculated by soil drenching of a spore suspension (106-107 spores/mL) of the fungal isolate EG30 while five plants were treated with sterilized water and used as control treatments. Plants were incubated at 60 to 75% relative humidity (RH) and 25 ˚C in a greenhouse. Leaf necrosis and partial to whole plant witling (Fig. 2. B & C) were observed in the inoculated plants after 21 days. No symptoms appeared in control plants. A fungus was re-isolated from the lower stem (crown portion) parts of the inoculated plants that was identical in morphology to isolate EG30. No fungus resembling EG30 was isolated from the control plants. To the best of our knowledge, this is the first report of summer cypress wilt caused by Nigrospora oryzae (Berk. and Broome) Petch, a known pathogen of several important crops in China, Australia, India, Canada, and Pakistan (Sharma et al., 2013).

Modulation of ABCG2 surface expression by Rab5 and Rab21 to overcome multidrug resistance in cancer cells.

Human ABCG2 is a half transporter implicated in drug efflux and development of multidrug resistance (MDR) in cancer cells. Here we present the regulatory effects of early endocytic Rab GTPases, Rab5A and Rab21 on ABCG2.ABCG2 was stably expressed in MCF-7 cells (MCF-7/G2). Rab5A and Rab21 were manipulated in MCF-7/G2 cells by co-expression or siRNA knockdown and their effect on ABCG2-mediated drug efflux was quantified using fluorescence microscopy.The ectopically expressed ABCG2 was predominantly confined to the plasma membrane and was capable of drug efflux. Expression of constitutively active Rab5A-Q79L mutant in MCF-7/G2 cells decreased the cell surface expression of ABCG2, resulting in the reduction of ABCG2-mediated drug efflux. In contrast, expression of inactive Rab5A-S34N mutant enhanced cell surface expression of ABCG2 and drug efflux. Moreover, reduction in endogenous Rab21 levels in MCF-7/G2 cells by siRNA knockdown, increased the surface localisation of ABCG2. Consequently, efflux ability of cells increased and intracellular retention of doxorubicin and Hoechst 33342; substrates of ABCG2, decreased significantly.These findings suggest that Rab5A and Rab21 play important roles in regulating ABCG2 surface localisation and turnover and can be exploited as a potential strategy to overcome MDR in cancer cells.

Porous Eleocharis@MnPE Layered Hybrid for Synergistic Adsorption and Catalytic Biodegradation of Toxic Azo Dyes from Industrial Wastewater.

The effective treatment of industrial wastewater to protect freshwater reserves for the survival of life is a primary focus of current research. Herein, a multicomponent Eleocharis-manganese peroxidase enzyme (Eleocharis@MnPE) layered hybrid with high surface area (1200 m2/m3), with a strong synergistic adsorption and catalytic biodegradation (SACB), has been developed through a facile method. A combination of outer porous (Eleocharis) and inner catalytically active (MnPE) components of the hybrid resulted in highly efficient SACB system, evidenced by high removal rate of 15 kg m-3 day-1 (100%) and complete degradation of toxic Orange II (OR) azo dye into nontoxic products (gases and weak acids). The Eleocharis@MnPE layered hybrid efficiently degraded both OR in synthetic wastewater and also other azo dyes (red, pink, and yellow dyes) present in three different textile industrial effluents. For the industrial effluents, these were evidenced by the color disappearance and reduction in biological oxygen demand (BOD), chemical oxygen demand (COD), and total organic carbon (TOC) of up to 97%, 92%, and 76%, respectively. Furthermore, reduced toxicity of treated wastewater was confirmed by decreased cell toxicity to 0.1%-1% and increased cell viability to 90%. We believe that designing a hybrid system with strong ability of SACB could be highly effective for industrial-scale treatment of wastewater.

Sequence variants in four genes underlying Bardet-Biedl syndrome in consanguineous families.

PURPOSE: To investigate the molecular basis of Bardet-Biedl syndrome (BBS) in five consanguineous families of Pakistani origin. METHODS: Linkage in two families (A and B) was established to BBS7 on chromosome 4q27, in family C to BBS8 on chromosome 14q32.1, and in family D to BBS10 on chromosome 12q21.2. Family E was investigated directly with exome sequence analysis. RESULTS: Sanger sequencing revealed two novel mutations and three previously reported mutations in the BBS genes. These mutations include two deletions (c.580_582delGCA, c.1592_1597delTTCCAG) in the BBS7 gene, a missense mutation (p.Gln449His) in the BBS8 gene, a frameshift mutation (c.271_272insT) in the BBS10 gene, and a nonsense mutation (p.Ser40*) in the MKKS (BBS6) gene. CONCLUSIONS: Two novel mutations and three previously reported variants, identified in the present study, further extend the body of evidence implicating BBS6, BBS7, BBS8, and BBS10 in causing BBS.

Evaluation of DNA vaccines encoding M. Tb gene Bfrb and Mpt32 in mice model.

Tuberculosis (TB) is a life threatening infectious disease which is prevalent throughout the world. Mycobacterium bovis based Bacille Calmette-Gue´rin (BCG) is the only vaccine available against TB however, this (single) vaccine is not enough to eradicate it. Furthermore, numbers of researches from different parts of the World have shown its efficacy as variable. Hence other (better) vaccines like DNA vaccines are needed in addition to BCG in order to achieve desired goal of TB eradication. The current study was aimed to develop subunit based DNA vaccines against TB and to check their efficacy. Two constructs Bfrb-pND14 and Mpt32-pND14 were made and used as DNA vaccines. Endotoxin free DNA preparations were made and used in immunization studies. Twenty Balb/c female mice of age eight weeks were used in trial. Two experimental groups each comprising eight animals were used to inoculate Mpt32-pND14 and Bfrb-pND14 vaccines respectively. A group of four animals was used as negative control. Animals were bled through tail periodically and finally through cardiac puncture before euthanization. Antibodies were confirmed through dot blot and Agar Gel Immuno Diffusion test (AGID). All the animals immunized with both vaccines were found positive as tested through dot blot and AGID. The results of this study have indicated that both the M. tb genes have produced strong immune response in mice model through pND14 vector and proved themselves as good subunit based DNA vaccines.

Development of biocatalytic microbial ecosystem (FPUS@RODMs@In-PAOREs) for rapid and sustainable degradation of various refractory organics.

The removal of diverse refractory organics from complex industrial wastewater continues to be a challenge. Although biological treatments are commonly employed, only partial degradation and increasing emergence of nitrogenous compounds, i.e., nitrate (NO3) and nitrite (NO2) would pose severe toxicity to the intact microbes. Herein, an efficient biocatalytic microbial ecosystem (BCME) was designed over a porous bio-carrier made of a functional polyurethane sponge (FPUS). The BCME comprised a unique set of organisms (RODMs) with novel metabolism, efficiently degrading highly-concentrated aromatics. Strategic enzyme immobilization was utilized to introduce in-situ production and aggregation of the oxidation and reduction enzymes (In-PAOREs) onto the FPUS, thereby ensuing sustained functions of the RODMs community. The developed FPUS@RODMs@In-PAOREs system was found to enhance the refractory organics removal rate to 4 kg/m3/day, and it would be attributed to the enzymatic catalysis of refractory organics (2000 mg/L) accompanied by the removal of COD (1200 mg/L) and nitrogenous compounds (200 mg/L). Besides, the fluctuating concentration of extra polymeric substances (EPS) played a dual role through enhancing adhesion, promoting the development of a functional microbial ecosystem, and creating an EPS gradient within the FPUS bio-carrier. This differential distribution of enzymes was established to significantly boost biocatalysis activity reaching 400 U/g VSS.

Strategic analysis on development of simultaneous adsorption and catalytic biodegradation over advanced bio-carriers for zero-liquid discharge of industrial wastewater.

With rapid industrial development, millions of tons of industrial wastewater are produced that contain highly toxic, carcinogenic, mutagenic compounds. These compounds may consist of high concentration of refractory organics with plentiful carbon and nitrogen. To date, a substantial proportion of industrial wastewater is discharged directly to precious water bodies due to the high operational costs associated with selective treatment methods. For example, many existing treatment processes rely on activated sludge-based treatments that only target readily available carbon using conventional microbes, with limited capacity for nitrogen and other nutrient removal. Therefore, an additional set-up is often required in the treatment chain to address residual nitrogen, but even after treatment, refractory organics persist in the effluents due to their low biodegradability. With the advancements in nanotechnology and biotechnology, novel processes such as adsorption and biodegradation have been developed, and one promising approach is integration of adsorption and biodegradation over porous substrates (bio-carriers). Regardless of recent focus in a few applied researches, the process assessment and critical analysis of this approach is still missing, and it highlights the urgency and importance of this review. This review paper discussed the development of the simultaneous adsorption and catalytic biodegradation (SACB) over a bio-carrier for the sustainable treatment of refractory organics. It provides insights into the physico-chemical characteristics of the bio-carrier, the development mechanism of SACB, stabilization techniques, and process optimization strategies. Furthermore, the most efficient treatment chain is proposed, and its technical aspects are critically analysed based on updated research. It is anticipated that this review will contribute to the knowledge of academia and industrialist for sustainable upgradation of existing industrial wastewater treatment plants.

Enhanced Solar Photocatalytic Activity of Thermally Stable I:ZnO/Glass Beads for Reduction of Cr(VI) in Tannery Effluent.

Chromium (VI) in tannery effluent is one of the major environmental concerns for the environmentalists due to the hazardous nature of Cr(VI) ions. To reduce Cr(VI) to Cr(III) as an innocuous moiety, pure and I-doped ZnO was grafted over the etched surface of glass beads by successive ionic layer adsorption and reaction (SILAR). Powdered, pure, and I-doped ZnO scrapped from the surface of glass beads was characterized for crystallinity, morphology, and elemental composition by XRD, SEM, TEM, and EDX. The optical properties of both photocatalysts revealed that owing to optimized iodine doping of ZnO, reduction in the bandgap was observed from 3.3 to 2.9 eV. The crystalline nano-bricks of I:ZnO adhered to glass beads were investigated to have remarkable capability to harvest sunlight in comparison to intrinsic ZnO nanodiscs. The thermal stability of I:ZnO was also found to be much improved due to doping of ZnO. The photocatalytic activities of ZnO/GB and I:ZnO/GB were compared by extent of reduction of Cr(VI) under direct natural sunlight (600-650 KWh/m2). The disappearance of absorbance peaks associated with Cr(VI) after treatment with I:ZnO/GB confirmed higher photocatalytic activity of I:ZnO/GB. The reaction parameters of solar photocatalytic reduction, i.e., initial pH (5-9), initial concentration of Cr(VI) (10-50 ppm), and solar irradiation time (1-5 h) were optimized using response surface methodology. The solar photocatalytic reduction of Cr(VI) to Cr(III) present in real tannery effluent was examined to be 87 and 98%, respectively, by employing ZnO/GB and I:ZnO/GB as solar photocatalysts. The extent of reduction was also confirmed by complexation of Cr(VI) and Cr(III) present in treated and untreated tannery waste with 1, 5-diphenylcarbazide. The results of AAS and UV/vis spectroscopy for the decrease in concentration of Cr also supported the evidence of higher efficiency of I:ZnO/GB for reduction of Cr(VI) in tannery effluent. Reusability of the fabricated photocatalyst was assessed for eight cycles, and magnificent extent of reduction of Cr(VI) indicated its high efficiency. Conclusively, I:ZnO/GB is a potential and cost-effective candidate for Cr(VI) reduction in tannery effluent under natural sunlight.

On-Site Application of Solar-Activated Membrane (Cr-Mn-Doped TiO2@Graphene Oxide) for the Rapid Degradation of Toxic Textile Effluents.

Solar-activated water treatment has become an emerging research field due to its eco-friendly nature and the economic feasibility of green photocatalysis. Herein, we synthesized promising, cost-effective, and ultralong-semiconductor TiO2 nanowires (NW), with the aim to degrade toxic azo dyes. The band gap of TiO2 NW was tuned through transition metals, i.e., chromium (Cr) and manganese (Mn), and narrowed by conjugation with high surface area graphene oxide (GO) sheets. Cr-Mn-doped TiO2 NWs were chemically grafted onto GO nanosheets and polymerized with sodium alginate to form a mesh network with an excellent band gap (2.6 eV), making it most suitable to act as a solar photocatalytic membrane. Cr-Mn-doped TiO2 NW @GO aerogels possess high purity and crystallinity confirmed by Energy Dispersive X-ray spectroscopy and X-ray diffraction pattern. A Cr-Mn-doped TiO2 NW @GO aerogels membrane was tested for the photodegradation of Acid Black 1 (AB 1) dye. The synthesized photocatalytic membrane in the solar photocatalytic reactor at conditions optimized by response surface methodology (statistical model) and upon exposure to solar radiation (within 180 min) degraded 100% (1.44 kg/m3/day) AB 1dye into simpler hydrocarbons, confirmed by the disappearance of dye color and Fourier transform infrared spectroscopy. An 80% reduction in water quality parameters defines Cr-Mn-doped TiO2 NW @GO aerogels as a potential photocatalytic membrane to degrade highly toxic pollutants.

Development of Iron Sequester Antioxidant Quercetin@ZnO Nanoparticles with Photoprotective Effects on UVA-Irradiated HaCaT Cells.

BACKGROUND: Solar ultraviolet radiation A (UVA, 320-400 nm) is a significant risk factor leading to various human skin conditions such as premature aging or photoaging. This condition is enhanced by UVA-mediated iron release from cellular iron proteins affecting huge populations across the globe. PURPOSE: Quercetin-loaded zinc oxide nanoparticles (quercetin@ZnO NPs) were prepared to examine its cellular iron sequestration ability to prevent the production of reactive oxygen species (ROS) and inflammatory responses in HaCaT cells. METHODS: Quercetin@ZnO NPs were synthesized through a homogenous precipitation method, and the functional groups were characterized by Fourier transform infrared (FTIR) spectroscopy, whereas scanning electron microscopy (SEM) described the morphologies of NPs. MTT and qRT-PCR assays were used to examine cell viability and the expression levels of various inflammatory cytokines. The cyclic voltammetry (CV) was employed to evaluate the redox potential of quercetin-Fe3+/quercetin-Fe2+ complexes. RESULTS: The material characterization results supported the loading of quercetin molecules on ZnO NPs. The CV and redox potential assays gave Fe-binding capability of quercetin at 0.15 mM and 0.3 mM of Fe(NO3)3. Cytotoxicity assays using quercetin@ZnO NPs with human HaCaT cells showed no cytotoxic effects and help regain cell viability loss following UVA (150 kJ/m2). CONCLUSION: Quercetin@ZnO NPs showed that efficient quercetin release action is UV-controlled, and the released quercetin molecules have excellent antioxidant, anti-inflammatory, and iron sequestration potential. Quercetin@ZnO NPs have superior biocompatibility to provide UVA protection and medication at once for antiphotoaging therapeutics.

Efficient pyrolysis of ginkgo biloba leaf residue and pharmaceutical sludge (mixture) with high production of clean energy: Process optimization by particle swarm optimization and gradient boosting decision tree algorithm.

Production of sustainable clean energy can be achieved by co-pyrolysis of agricultural residues and wastewater sludge. Herein, non-additive thermal behaviour of co-pyrolysis of pharmaceutical sludge and ginkgo biloba leaf residues was investigated. Synergistic effect of co-pyrolysis was not obvious at elevated temperatures. Further, kinetics of co-pyrolysis was studied by fitting Coats-Redfern integration method to thermogravimetric (TG) curve. The change of heat and mass transfer in the reactor caused the change of dynamic parameters. Moreover, hybrid particle swarm optimization and gradient boosting decision tree (PSO-GBDT) algorithm was designed to boost the energy production at full-scale pyrolysis plant by monitoring TG curves. PSO-GBDT model well predicts mass loss rate of the mixture at different heating rates confirming that co-pyrolysis of PS and GBLR can results in high energy production by increasing PS pyrolysis. Designing PSO-GBDT model help to reduced waste production by resourceful treatment of waste in to energy.

Novel heterozygous sequence variant in the GLI1 underlies postaxial polydactyly.

Polydactyly is one of the most common congenital abnormal phenotype of autopod, which is characterized by extra supernumerary digit in hands/feet with or without well-developed bony structure within the digits. Preaxial polydactyly (PPD), postaxial polydactyly (PAP), and meso-axial (central) polydactyly are three different isoforms of polydactyly. Genetically, at least 10 genes have been identified causing nonsyndromic polydactyly. In the present study, we have investigated a large family segregating autosomal dominant form of nonsyndromic polydactyly. Whole exome sequencing followed by Sanger sequencing revealed a novel heterozygous missense variant (NM_005269.3; c.1064C>A; p.(Thr355Asn) in the gene GLI1 segregating with the disease phenotype within the family. This study presents first familial case of autosomal dominant form of polydactyly caused by the GLI1 variant.

Variants in GLI3 Cause Greig Cephalopolysyndactyly Syndrome.

Background: Greig cephalopolysyndactyly syndrome (GCPS) is a disorder of autopod and craniofacial abnormalities. Autopod anomalies include preaxial and/or postaxial polydactyly together with or without syndactyly while craniofacial features include hypertelorism and macrocephaly. GCPS is inherited in an autosomal dominant manner and is caused by sequence variants in GLI3. Methodology and Results: In this study, we examined four unrelated families with GCPS segregating in an autosomal dominant manner. Sanger sequencing revealed three novel (p.Tyr146Leufs*19, p.Glu99Serfs*60, and p.Thr541Arg) and one previously reported non-sense variant (p.Arg792*) in GLI3. Conclusion: The study expands the spectrum of the variants in the GLI3 gene linked to GCPS, and should also facilitate genetic counseling of GCPS patients in the Pakistani population.

In Vivo and In Vitro Monitoring of Amyloid Aggregation via BSA@FGQDs Multimodal Probe.

Early detection of peptide aggregate intermediates is quite challenging because of their variable and complex nature as well as due to lack of reliable sensors for diagnosis. Herein, we report the detection of monomers and oligomers using specified fluorescence and a magnetic resonance imaging (MRI) multimodal probe based on bovine-serum-albumin-capped fluorine functionalized graphene quantum dots (BSA@FGQDs). This probe enables in vitro fluorescence-based monitoring of human islet amyloid polypeptide (hIAPP), insulin, and amyloid ß(1-42) (Aß42) monomers and oligomers during the fibrillogenesis dynamic. Up to 90% fluorescence quenching of BSA@FGQDs probe upon addition of amyloid monomers/oligomers was observed due to static quenching and nonradiative energy transfer. Moreover, the BSA@FGQDs probe shows 10 times higher signals in detecting amyloid intermediates and fibrils than that of conventional thioflavin dye. A negative Δ G° value (-36.21 kJ/mol) indicates spontaneous interaction of probe with the peptide. These interactions are hydrogen bonding and hydrophobic as proved by thermodynamic parameters. Visual binding clues of BSA@FGQDs with different morphological states of amyloid protein was achieved through electron microscopy. Furthermore, intravenous and intracranial injection of BSA@FGQDs probe in Alzheimer model mice brain enabled in vivo detection of amyloid plaques in live mice brain by 19F MRI through contrast enhancement. Our proposed probe not only effectively monitors in vitro fibrillation kinetics of number of amyloid proteins with higher sensitivity and specificity than thioflavin dye, but also, the presence of a 19F center makes BSA@FGQDs an effective probe as a noninvasive and nonradiative in vivo detection probe for amyloid plaques.

Dual effect of PEG-PE micelle over the oligomerization and fibrillation of human islet amyloid polypeptide.

The oligomerization and fibrillation of human islet amyloid polypeptide (hIAPP) play a central role in the pathogenesis of type 2 diabetes. Strategies for remodelling the formation of hIAPP oligomers and fibrils have promising application potential in type 2 diabetes therapy. Herein, we demonstrated that PEG-PE micelle could inhibit hIAPP oligomerization and fibrillation through blocking the hydrophobic interaction and the conformational change from random coil to ß-sheet structures of hIAPP. In addition, we also found that PEG-PE micelle could remodel the preformed hIAPP fibrils allowing the formation of short fibrils and co-aggregates. Taken together, PEG-PE micelle could rescue hIAPP-induced cytotoxicity by decreasing the content of hIAPP oligomers and fibrils that are related to the oxidative stress and cell membrane permeability. This study could be beneficial for the design and development of antiamyloidogenic agents.

Fluorine Functionalized Graphene Quantum Dots as Inhibitor against hIAPP Amyloid Aggregation.

Fibrillar deposits of the human islet amyloid polypeptide (hIAPP) are considered as a root of Type II diabetes mellitus. Fluorinated graphene quantum dots (FGQDs) are new carbon nanomaterials with unique physicochemical properties containing highly electronegative F atoms. Herein we report a single step synthesis method of FGQDs with an inhibitory effect on aggregation and cytotoxicity of hIAPP in vitro. Highly fluorescent and water dispersible FGQDs, less than 3 nm in size, were synthesized by the microwave-assisted hydrothermal method. Efficient inhibition capability of FGQDs to amyloid aggregation was demonstrated. The morphologies of hIAPP aggregates were observed to change from the entangled long fibrils to short thin fibrils and amorphous aggregates in the presence of FGQDs. In thioflavin T fluorescence analysis, inhibited aggregation with prolonged lag time and reduced fluorescence intensity at equilibrium were observed when hIAPP was incubated together with FGQDs. Circular dichroism spectrum results reveal that FGQDs could inhibit conformational transition of the peptide from native structure to ß-sheets. FGQDs could also rescue the cytotoxicity of INS-1 cells induced by hIAPP in a dose dependent manner. This study could be beneficial for design and preparation of inhibitors for amyloids, which is important for prevention and treatment of amyloidosis.

Anti-tumor activity of nanomicelles encapsulating CXCR4 peptide antagonist E5.

Cancer is the leading cause of death worldwide, and metastasis is the main attribute to cancer death. CXCR4 and its natural ligand CXCL12 have been known to play a critical role in tumorigenesis, angiogenesis and metastasis. Therefore, designing a new CXCR4 antagonist to prevent tumor metastasis will be of great significance. Herein, a novel chemically synthesized peptide (E5) that has an ability to target CXCR4/CXCL12 axis was loaded in micelle glycol-phosphatidylethanolamine (PEG-PE) block copolymer to form micelle-encapsulated E5 (M-E5). We demonstrated that M-E5 exhibited higher affinity for CXCR4-overexpressing MCF-7 and HepG2 tumor cells as compared to free E5, and efficiently inhibited the tumor cells migration. Mechanistic studies implied that PEG-PE micelle can encapsulate E5 and improve E5 targeting efficiency for CXCR4 by accumulating E5 on the tumor cell membrane. Furthermore, through encapsulation of chemotherapeutic drug doxorubicin (Dox) in PEG-PE micelle, we proved that PEG-PE micelle could serve as a co-carrier for both E5 and Dox (M-E5-Dox). M-E5 enhanced the efficiency of Dox by down-regulating the phosphorylation level of Akt, Erk and p38/MAPK proteins. In conclusion, PEG-PE micelle demonstrated a promising delivery system for E5, and M-E5 is expected to be a potential therapeutic agent that will help to improve the clinical benefits in current therapies used for solid tumors.