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Recent Submissions

  • Exploiting machine learning models to identify novel Alzheimer’s disease biomarkers and potential targets

    Alamro, Hind; Thafar, Maha A.; Albaradei, Somayah; Gojobori, Takashi; Essack, Magbubah; Gao, Xin (Scientific Reports, Springer Science and Business Media LLC, 2023-03-27) [Article]
    We still do not have an effective treatment for Alzheimer's disease (AD) despite it being the most common cause of dementia and impaired cognitive function. Thus, research endeavors are directed toward identifying AD biomarkers and targets. In this regard, we designed a computational method that exploits multiple hub gene ranking methods and feature selection methods with machine learning and deep learning to identify biomarkers and targets. First, we used three AD gene expression datasets to identify 1/ hub genes based on six ranking algorithms (Degree, Maximum Neighborhood Component (MNC), Maximal Clique Centrality (MCC), Betweenness Centrality (BC), Closeness Centrality, and Stress Centrality), 2/ gene subsets based on two feature selection methods (LASSO and Ridge). Then, we developed machine learning and deep learning models to determine the gene subset that best distinguishes AD samples from the healthy controls. This work shows that feature selection methods achieve better prediction performances than the hub gene sets. Beyond this, the five genes identified by both feature selection methods (LASSO and Ridge algorithms) achieved an AUC = 0.979. We further show that 70% of the upregulated hub genes (among the 28 overlapping hub genes) are AD targets based on a literature review and six miRNA (hsa-mir-16-5p, hsa-mir-34a-5p, hsa-mir-1-3p, hsa-mir-26a-5p, hsa-mir-93-5p, hsa-mir-155-5p) and one transcription factor, JUN, are associated with the upregulated hub genes. Furthermore, since 2020, four of the six microRNA were also shown to be potential AD targets. To our knowledge, this is the first work showing that such a small number of genes can distinguish AD samples from healthy controls with high accuracy and that overlapping upregulated hub genes can narrow the search space for potential novel targets.
  • Genomics-driven breeding for local adaptation of durum wheat is enhanced by farmers’ traditional knowledge

    Gesesse, Cherinet Alem; Nigir, Bogale; de Sousa, Kauê; Gianfranceschi, Luca; Gallo, Guido Roberto; Poland, Jesse; Kidane, Yosef Gebrehawaryat; Abate Desta, Ermias; Fadda, Carlo; Pè, Mario Enrico; Dell’Acqua, Matteo (Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, 2023-03-27) [Article]
    In the smallholder, low-input farming systems widespread in sub-Saharan Africa, farmers select and propagate crop varieties based on their traditional knowledge and experience. A data-driven integration of their knowledge into breeding pipelines may support the sustainable intensification of local farming. Here, we combine genomics with participatory research to tap into traditional knowledge in smallholder farming systems, using durum wheat (Triticum durum Desf.) in Ethiopia as a case study. We developed and genotyped a large multiparental population, called the Ethiopian NAM (EtNAM), that recombines an elite international breeding line with Ethiopian traditional varieties maintained by local farmers. A total of 1,200 EtNAM lines were evaluated for agronomic performance and farmers’ appreciation in three locations in Ethiopia, finding that women and men farmers could skillfully identify the worth of wheat genotypes and their potential for local adaptation. We then trained a genomic selection (GS) model using farmer appreciation scores and found that its prediction accuracy over grain yield (GY) was higher than that of a benchmark GS model trained on GY. Finally, we used forward genetics approaches to identify marker–trait associations for agronomic traits and farmer appreciation scores. We produced genetic maps for individual EtNAM families and used them to support the characterization of genomic loci of breeding relevance with pleiotropic effects on phenology, yield, and farmer preference. Our data show that farmers’ traditional knowledge can be integrated in genomics-driven breeding to support the selection of best allelic combinations for local adaptation.
  • Tailor-Made White Photothermal Fabrics: a Bridge between Pragmatism and Aesthetic

    Chang, Jian; Shi, Le; Zhang, Miao; Li, Renyuan; Shi, Yifeng; Yu, Xiaowen; Pang, Kanglei; Qu, Liangti; Wang, Peng; Yuan, Jiayin (Advanced Materials, Wiley, 2023-03-27) [Article]
    Maintaining human thermal comfort in cold wild is crucial for diverse outdoor activities, e.g., sports and recreation, health-care, and special occupations. To date, advanced clothes are employed to collect solar energy as heat source to stand cold climates, while their dull dark photothermal coating may hinder pragmatism in wild and visual sense considering fashion. Herein, tailor-made white webs with strong photothermal effect are proposed. With the embedding of Cs<sub>x</sub> WO<sub>3</sub> nanoparticles (NPs) as additive inside nylon nanofibers, these webs are capable of drawing both NIR and UV light in sunlight for heating. Their exceptional photothermal conversion capability enables 2.5-10.5°C warmer than that of a commercial sweatshirt of 6 times thicker under different climates. Remarkably, this smart fabric can increase its photothermal conversion efficiency in a wet state. It is optimal for fast sweat or water evaporation at human comfort temperature (38.5°C) under sunlight, and its role in thermoregulation is equally important to avoid excess heat loss in wilderness survival. Obviously, this smart web with considerable merits of shape retention, softness, safety, breathability, washability and on-demand coloration, provides a revolutionary solution to realize energy-saving outdoor thermoregulatory and simultaneously satisfy the needs of fashion and aesthetics.
  • Bioengineering of air-filled protein nanoparticles by genetic and chemical functionalization.

    Karan, Ram; Renn, Dominik; Nozue, Shuho; Zhao, Lingyun; Habuchi, Satoshi; Allers, Thorsten; Rueping, Magnus (Journal of nanobiotechnology, Springer Science and Business Media LLC, 2023-03-25) [Article]
    Background: Various bacteria and archaea, including halophilic archaeon Halobacterium sp. NRC-1 produce gas vesicle nanoparticles (GVNPs), a unique class of stable, air-filled intracellular proteinaceous nanostructures. GVNPs are an attractive tool for biotechnological applications due to their readily production, purification, and unique physical properties. GVNPs are spindle- or cylinder-shaped, typically with a length of 100 nm to 1.5 μm and a width of 30–250 nm. Multiple monomeric subunits of GvpA and GvpC proteins form the GVNP shell, and several additional proteins are required as minor structural or assembly proteins. The haloarchaeal genetic system has been successfully used to produce and bioengineer GVNPs by fusing several foreign proteins with GvpC and has shown various applications, such as biocatalysis, diagnostics, bioimaging, drug delivery, and vaccine development. Results: We demonstrated that native GvpC can be removed in a low salt buffer during the GVNP purification, leaving the GvpA-based GVNP's shell intact and stable under physiological conditions. Here, we report a genetic engineering and chemical modification approach for functionalizing the major GVNP protein, GvpA. This novel approach is based on combinatorial cysteine mutagenesis within GvpA and genetic expansion of the N-terminal and C-terminal regions. Consequently, we generated GvpA single, double, and triple cysteine variant libraries and investigated the impact of mutations on the structure and physical shape of the GVNPs formed. We used a thiol–maleimide chemistry strategy to introduce the biotechnological relevant activity by maleimide-activated streptavidin–biotin and maleimide-activated SpyTag003-SpyCatcher003 mediated functionalization of GVNPs. Conclusion: The merger of these genetic and chemical functionalization approaches significantly extends these novel protein nanomaterials' bioengineering and functionalization potential to assemble catalytically active proteins, biomaterials, and vaccines onto one nanoparticle in a modular fashion.
  • Nano-Strategies for Lignin Biomaterials towards Cancer Therapy

    Sathasivam, Thenapakiam; Kai, Jing; Sugiarto, Sigit; Yong, Yu; Soo, Debbie Xiang Yun; Zhu, Qiang; Merzaban, Jasmeen; Kai, Dan (Advanced Healthcare Materials, Wiley, 2023-03-25) [Article]
    Lignin is a nontoxic and biocompatible biopolymer with many promising characteristics, including a high tensile strength and antioxidant properties. This natural polymer can be processed through several chemical methods and modified into lignin nanomaterials for potential biomedical applications. This review summarizes the latest developments in nanolignin (NL)-based biomaterials for cancer therapy; various NL applications related to cancer therapy are considered, including drug and gene delivery, biosensing, bioimaging, and tissue engineering. The manuscript also outlines the potential use of these materials to improve the therapeutic potency of chemotherapeutic drugs by decreasing their dose and reducing their adverse effects. Due to its high surface area-to-volume ratio and the easy modification of its chemical components, NL could serve as an appropriate matrix for the binding and controlled release of various pharmaceutical agents. Moreover, the challenges in the utilization of NL-based materials for cancer therapy are discussed, along with the prospects of advances in such nanomaterials for medical research applications.
  • Rice Gene Index (RGI): a comprehensive pan-genome database for comparative and functional genomics of Asian rice.

    Yu, Zhichao; Chen, Yongming; Zhou, Yong; Zhang, Yulu; Li, Mengyuan; Ouyang, Yidan; Chebotarov, Dmytro; Mauleon, Ramil; Zhao, Hu; Xie, Weibo; McNally, Kenneth L; Wing, Rod Anthony; Guo, Weilong; Zhang, Jianwei (Molecular plant, Elsevier BV, 2023-03-24) [Article]
    To integrate the genomic information of the rice pan-genome, we performed comparative analyses and established a user-friendly Rice Gene Index (RGI, platform with 16 platinum standard reference genomes and supplementary transcriptome data. To logically organize and scientifically the index of 744,233 genes among rice accessions, we detected 112,658 Ortholog Gene Indices, and provide ‘GeneCard’ pages to query genomic, transcriptomic, and homology information for each gene. The RGI allows users to search for relationships and comprehensive information of genes in keyword-based, sequence-based, and relationship-based ways. Furthermore, users can visualize these relationships at local and global scales corresponding to ‘Microcollinearity’ and ‘Macrocollinearity’ modules.
  • Cooling Energy and Climate Change Nexus in Arid Climate and the Role of Energy Transition

    Khourchid, Ammar M.; Al-Ansari, Tareq A.; Al-Ghamdi, Sami (Buildings, MDPI AG, 2023-03-23) [Article]
    Buildings are significant contributors to climate change through their energy consumption, particularly in countries with hot and dry climates where cooling services require substantial amounts of energy. Climate change is expected to increase cooling demand, further exacerbating the problem. This study investigates the impact of climate change on cooling demands in different building types in Qatar and evaluates related environmental impacts. Using a high-resolution regional climate model, future climate data were obtained for 2071 and 2100 under the Representative Concentration Pathway (RCP) 4.5. The energy consumption of eight prototype buildings was simulated under baseline and future climates, and the environmental impacts were assessed using Life Cycle Assessment (LCA) for natural gas and solar power as energy sources. The study found that the cooling demand could increase by 13–53% and 19–67% in 2071 and 2100, respectively, with buildings having higher thermal insulation and lower window-to-wall ratio being less affected by climate change. The LCA results showed that replacing natural gas with solar power can reduce cooling energy-associated CO2 emissions by 92%. However, challenges such as human toxicity and metal depletion need to be addressed. The study highlights the importance of considering potential climate change scenarios to develop more resilient buildings and encourages implementing efficient recycling and waste management strategies before implementing PV panels.
  • Updated guidelines for gene nomenclature in wheat

    Boden, S. A.; McIntosh, R. A.; Uauy, C.; Krattinger, Simon G.; Dubcovsky, J.; Rogers, W. J.; Xia, X. C.; Badaeva, E. D.; Bentley, A. R.; Brown-Guedira, G.; Caccamo, M.; Cattivelli, L.; Chhuneja, P.; Cockram, J.; Contreras-Moreira, B.; Dreisigacker, S.; Edwards, D.; González, F. G.; Guzmán, C.; Ikeda, T. M.; Karsai, I.; Nasuda, S.; Pozniak, C.; Prins, R.; Sen, T. Z.; Silva, P.; Simkova, H.; Zhang, Y.; the Wheat Initiative (Theoretical and Applied Genetics, Springer Science and Business Media LLC, 2023-03-23) [Article]
    Key message: Here, we provide an updated set of guidelines for naming genes in wheat that has been endorsed by the wheat research community. The last decade has seen a proliferation in genomic resources for wheat, including reference- and pan-genome assemblies with gene annotations, which provide new opportunities to detect, characterise, and describe genes that influence traits of interest. The expansion of genetic information has supported growth of the wheat research community and catalysed strong interest in the genes that control agronomically important traits, such as yield, pathogen resistance, grain quality, and abiotic stress tolerance. To accommodate these developments, we present an updated set of guidelines for gene nomenclature in wheat. These guidelines can be used to describe loci identified based on morphological or phenotypic features or to name genes based on sequence information, such as similarity to genes characterised in other species or the biochemical properties of the encoded protein. The updated guidelines provide a flexible system that is not overly prescriptive but provides structure and a common framework for naming genes in wheat, which may be extended to related cereal species. We propose these guidelines be used henceforth by the wheat research community to facilitate integration of data from independent studies and allow broader and more efficient use of text and data mining approaches, which will ultimately help further accelerate wheat research and breeding.
  • Engineered production of isoprene from the model green microalga Chlamydomonas reinhardtii

    Yahya, Razan Z.; Wellman, Gordon; Overmans, Sebastian; Lauersen, Kyle J. (Metabolic Engineering Communications, Elsevier BV, 2023-03-23) [Article]
    Isoprene is a clear, colorless, volatile 5-carbon hydrocarbon that is one monomer of all cellular isoprenoids and a platform chemical with multiple applications in industry. Many plants have evolved isoprene synthases (IspSs) with the capacity to liberate isoprene from dimethylallyl diphosphate (DMADP) as part of cellular thermotolerance mechanisms. Isoprene is hydrophobic and volatile, rapidly leaves plant tissues and is one of the main carbon emission sources from vegetation globally. The universality of isoprenoid metabolism allows volatile isoprene production from microbes expressing heterologous IspSs. Here, we compared heterologous overexpression from the nuclear genome and localization into the plastid of four plant terpene synthases (TPs) in the green microalga Chlamydomonas reinhardtii. Using sealed vial mixotrophic cultivation, direct quantification of isoprene production was achieved from the headspace of living cultures, with the highest isoprene production observed in algae expressing the Ipomoea batatas IspS. Perturbations of the downstream carotenoid pathway through keto carotenoid biosynthesis enhanced isoprene titers, which could be further enhanced by increasing flux towards DMADP through heterologous co-expression of a yeast isopentenyl-PP delta isomerase. Multiplexed controlled-environment testing revealed that cultivation temperature, rather than illumination intensity, was the main factor affecting isoprene yield from the engineered alga. This is the first report of heterologous isoprene production from a eukaryotic alga and sets a foundation for further exploration of carbon conversion to this commodity chemical.
  • Bone-Marrow-Derived Mesenchymal Stem Cells, Their Conditioned Media, Protect against Cyclophosphamide-Induced Infertility in Rats

    Ibrabim, Dalia; Abozied, Nadia; Maboud, Samar Abdel; Alzamami, Ahmad; Alturki, Norah; Jaremko, Mariusz; Alanazi, Maram Khalil; Seddek, Asmaa (Frontiers in Pharmacology, Frontiers Media, 2023-03-22) [Article]
    Cancer is a deadly disease characterized by abnormal cell proliferation. Chemotherapy is one tech-nique of cancer treatment. Cyclophosphamide (CYP) is the most powerful chemotherapy medication, yet it has serious adverse effects. It is an antimitotic medicine that regulates cell proliferation and primarily targets quickly dividing cells, and it has been related to varying levels of infertility in hu-mans. In the current study, we assessed the biochemical, histological, and microscopic evaluations of testicular damage following CYP administration. Further, we have explored the potential protective impact of mesenchymal stem cell (MSCs) transplantation. The biochemical results revealed that ad-ministration of CYP increased serum concentrations of follicle-stimulating hormone (FSH) and lu-teinizing hormone (LH), while it decreased serum concentrations of free testosterone hormone (TH), testicular FSH, LH, and free TH concentrations, testicular total antioxidant capacity (TAC), and testicular activity of superoxide dismutase (SOD) enzyme. The histology and sperm examinations revealed that CYP induced destruction to the architectures of several tissues in the testes, which drastically reduced the Johnsen score as well as the spermatogenesis process. Surprisingly, trans-plantation of MSCs after CYP administration altered the deterioration effect of CYP injury on the testicular tissues, as demonstrated by biochemical and histological analysis. Our results indicated alleviation of serum and testicular sex hormones, as well as testicular oxidative stress markers (TAC and SOD activity), and nearly restored the normal appearance of the testicular tissues, Johnsen score, and spermatogenesis process. In conclusion, our work emphasizes the protective pharmacological use of MSCs to mitigate the effects of CYP on testicular tissues that impair the spermatogenesis process following chemotherapy. These findings indicate that transferring MSCs to chemotherapy patients could significantly improve spermatogenesis
  • Unique stratification of biofilm density in heterotrophic membrane-aerated biofilms: An experimental and modeling study

    Li, Mengfei; Perez-Calleja, Patricia; Kim, Bumkyu; Picioreanu, Cristian; Nerenberg, Robert (Chemosphere, Elsevier BV, 2023-03-22) [Article]
    We consistently find a band of high cell density develop within heterotrophic membrane-aerated biofilms. This study reports and attempts to explain this unique behavior. Biofilm density affects volumetric reaction rates, biofilm growth rates, substrate diffusion, and mechanical behavior. Yet the mechanisms and dynamics of biofilm density development are poorly understood. In this study, a membrane-aerated biofilm, where O2 was supplied from the base of the biofilm and acetate from the bulk liquid, was used to explore spatial and temporal patterns of density development. Biofilm density was assessed by optical coherence tomography. After inoculation, the biofilm quickly increased in thickness, with a low density throughout. However, as the biofilm reached a stable thickness of around 1000 μm, a high-density layer developed in the biofilm interior. The layer slowly expanded over time. Oxygen microprofiles in the biofilm showed this layer coincided with the most metabolically active zone, resulting from counter-diffusing O2 and acetate. The formation of this dense layer appeared to be related to changes in growth rates. Initially, high growth rates throughout the biofilm presumably led to fast-growing, low-density biofilms. As the biofilm became thicker, and as substrates became limiting in the biofilm interior, growth rates decreased, resulting in new growth at a higher density. A 1-D mathematical model with variable biofilm density was developed by linking the rates of extracellular polymeric substances (EPS) production to the growth rate. The model captured the initial fast growth at a low density, followed by a slower, substrate-limited growth in the biofilm interior, producing a dense band within the biofilm. Together, these results suggest that low growth rates can lead to high-density zones within the interior of counter-diffusional biofilms. These findings should also be relevant to conventional, co-diffusional biofilms, although differences in density may be less obvious.
  • 3D-Printed disposable nozzles for cost-efficient extrusion-based 3D bioprinting

    Albalawi, Hamed I.; Khan, Zainab N.; H. Rawas, Ranim; U. Valle-Pérez, Alexander; Abdelrahman, Sherin; Hauser, Charlotte (Materials Science in Additive Manufacturing, AccScience Publishing, 2023-03-21) [Article]
    3D bioprinting has significantly impacted tissue engineering with its capability to create intricate structures with complex geometries that were difficult to replicate through traditional manufacturing techniques. Extrusion-based 3D bioprinting methods tend to be limited when creating complex structures using bioinks of low viscosity. However, the capacity for creating multi-material structures that have distinct properties could be unlocked through the mixture of two solutions before extrusion. This could be used to generate architectures with varying levels of stiffness and hydrophobicity, which could be utilized for regenerative medicine applications. Moreover, it allows for combining proteins and other biological materials in a single 3D-bioprinted structure. This paper presents a standardized fabrication method of disposable nozzle connectors (DNC) for 3D bioprinting with hydrogel-based materials. This method entails 3D printing connectors with dual inlets and a single outlet to mix the material internally. The connectors are compatible with conventional Luer lock needles, offering an efficient solution for nozzle replacement. IVZK (Ac-Ile-Val-Cha-Lys-NH2) peptide-based hydrogel materials were used as a bioink with the 3D-printed DNCs. Extrusion-based 3D bioprinting was employed to print shapes of varying complexities, demonstrating potential in achieving high print resolution, shape fidelity, and biocompatibility. Post-printing of human neonatal dermal fibroblasts, cell viability, proliferation, and metabolic activity were observed, which demonstrated the effectiveness of the proposed design and process for 3D bioprinting using low-viscosity bioinks.
  • Tuning anticancer properties and DNA-binding of Pt(ii) complexes via alteration of nitrogen softness/basicity of tridentate ligands

    Al-Rashdi, Kamelah S.; Babgi, Bandar A.; Ali, Ehab M. M.; Jedidi, Abdesslem; Emwas, Abdul-Hamid M.; Davaasuren, Bambar; Jaremko, Mariusz; Humphrey, Mark G. (RSC Advances, Royal Society of Chemistry (RSC), 2023-03-21) [Article]
    Nine tridentate Schiff base ligands of the type (N^N^O) were synthesized from reactions of primary amines {2-picolylamine (Py), N-phenyl-1,2-diaminobenzene (PhN), and N-phenyl-1,2-diaminoethane(EtN)} and salicylaldehyde derivatives {3-ethoxy (OEt), 4-diethylamine (NEt2) and 4-hydroxy (OH)}. Complexes with the general formula Pt(N^N^O)Cl were synthesized by reacting K2PtCl4 with the ligands in DMSO/ethanol mixtures. The ligands and their complexes were characterized by NMR spectroscopy, mass spectrometry and elemental analysis. The DNA-binding behaviours of the platinum(II) complexes were investigated by two techniques, indicating good binding affinities and a two-stage binding process for seven complexes: intercalation followed by switching to a covalent binding mode over time. The other two complexes covalently bond to ct-DNA without intercalation. Theoretical calculations were used to shed light on the electronic and steric factors that lead to the difference in DNA-binding behavior. The reactions of some platinum complexes with guanine were investigated experimentally and theoretically. The binding of the complexes with bovine serum albumin (BSA) indicated a static interaction with higher binding affinities for the ethoxy-containing complexes. The half maximal inhibitory concentration (IC50) values against MCF-7 and HepG2 cell lines suggest that platinum complexes with tridentate ligands of N-phenyl-o-phenylenediamine or pyridyl with 3-ethoxysalicylimine are good chemotherapeutic candidates. Pt-Py-OEt and Pt-PhN-OEt have IC50 values against MCF-7 of 13.27 and 10.97 μM, respectively, compared to 18.36 μM for cisplatin, while they have IC50 values against HepG2 of 6.99 and 10.15 μM, respectively, compared to 19.73 μM for cisplatin. The cell cycle interference behaviour with HepG2 of selected complexes is similar to that of cisplatin, suggesting apoptotic cell death. The current work highlights the impact of the tridentate ligand on the biological properties of platinum complexes.
  • Pan-genome inversion index reveals evolutionary insights into the subpopulation structure of Asian rice.

    Zhou, Yong; Yu, Zhichao; Chebotarov, Dmytro; Chougule, Kapeel; Lu, Zhenyuan; Rivera, Luis F; Kathiresan, Nagarajan; AlBader, Noor Mohammed; Mohammed, Nahed Abdullah; Alsantely, Aseel O.; Mussurova, Saule; Santos, Joao; Thimma, Manjula; Troukhan, Maxim; Fornasiero, Alice; Green, Carl Douglas; Copetti, Dario; Kudrna, Dave; Llaca, Victor; Lorieux, Mathias; Zuccolo, Andrea; Ware, Doreen; McNally, Kenneth; Zhang, Jianwei; Wing, Rod Anthony (Nature communications, Cold Spring Harbor Laboratory, 2023-03-21) [Article]
    Understanding and exploiting genetic diversity is a key factor for the productive and stable production of rice. Here, we utilize 73 high-quality genomes that encompass the subpopulation structure of Asian rice (Oryza sativa), plus the genomes of two wild relatives (O. rufipogon and O. punctata), to build a pan-genome inversion index of 1769 non-redundant inversions that span an average of ~29% of the O. sativa cv. Nipponbare reference genome sequence. Using this index, we estimate an inversion rate of ~700 inversions per million years in Asian rice, which is 16 to 50 times higher than previously estimated for plants. Detailed analyses of these inversions show evidence of their effects on gene expression, recombination rate, and linkage disequilibrium. Our study uncovers the prevalence and scale of large inversions (≥100 bp) across the pan-genome of Asian rice and hints at their largely unexplored role in functional biology and crop performance.
  • An overlooked soil carbon pool in vegetated coastal ecosystems: National-scale assessment of soil organic carbon stocks in coastal shelter forests of China.

    Li, Yuan; Fu, Chuancheng; Wang, Weiqi; Zeng, Lin; Tu, Chen; Luo, Yongming (The Science of the total environment, Elsevier BV, 2023-03-17) [Article]
    Protection and restoration of vegetated coastal ecosystems provide opportunities to mitigate climate change. Coastal shelter forests as one of vegetated coastal ecosystems play vital role on sandy coasts protection, but less attention is paid on their soil organic carbon (OC) sequestration potential. Here, we provide the first national-scale assessment of the soil OC stocks, fractions, sources and accumulation rates from 48 sites of shelter forests and 74 sites of sandy beaches across 22° of latitude in China. We find that, compared with sandy beaches, shelter forest plantation achieves an average soil desalination rate of 92.0 % and reduces the soil pH by 1.3 units. The improved soil quality can facilitate OC sequestration leading to an increase of soil OC stock of 11.8 (0.60–64.2) MgC ha−1 in shelter forests. Particulate OC (POC) is a dominant OC fraction in both sandy beaches and shelter forests, but most sites are >80 % in shelter forests. The low δ13C values and higher C:N ratios, which are more regulated by climate and tree species, together with high POC proportions suggest a substantial contribution of plant-derived OC. Bayesian mixing model indicates that 71.8 (33.5–91.6)% of the soil OC is derived from local plant biomass. We estimate that soil OC stocks in Chinese shelter forests are 20.5 (7.44–79.7) MgC ha−1 and 4.53 ± 0.71 TgC in the top meter, with an accumulation rate of 45.0 (6.90 to 194.1) gC m−2 year−1 and 99.5 ± 44.9 GgC year−1. According to coastal shelter forest afforestation plan, additional 1.72 ± 0.27 TgC with a rate of 37.9 ± 17.1 GgC year−1 can be sequestrated in the future. Our findings suggest that construction of coastal shelter forests can be an effective solution to sequester more soil carbon in coastal ecosystems.
  • Preclinical models for prediction of immunotherapy outcomes and immune evasion mechanisms in genetically heterogeneous multiple myeloma.

    Larrayoz, Marta; Garcia-Barchino, Maria J; Celay, Jon; Etxebeste, Amaia; Jimenez, Maddalen; Perez, Cristina; Ordoñez, Raquel; Cobaleda, Cesar; Botta, Cirino; Fresquet, Vicente; Roa, Sergio; Goicoechea, Ibai; Maia, Catarina; Lasaga, Miren; Chesi, Marta; Bergsagel, P Leif; Larrayoz, Maria J; Calasanz, Maria J; Campos-Sanchez, Elena; Martinez-Cano, Jorge; Panizo, Carlos; Rodriguez-Otero, Paula; Vicent, Silvestre; Roncador, Giovanna; Gonzalez, Patricia; Takahashi, Satoru; Katz, Samuel G; Walensky, Loren D; Ruppert, Shannon M; Lasater, Elisabeth A; Amann, Maria; Lozano, Teresa; Llopiz, Diana; Sarobe, Pablo; Lasarte, Juan J; Planell, Nuria; Gomez-Cabrero, David; Kudryashova, Olga; Kurilovich, Anna; Revuelta, Maria V; Cerchietti, Leandro; Agirre, Xabier; San Miguel, Jesus; Paiva, Bruno; Prosper, Felipe; Martinez-Climent, Jose A (Nature medicine, Springer Science and Business Media LLC, 2023-03-16) [Article]
    The historical lack of preclinical models reflecting the genetic heterogeneity of multiple myeloma (MM) hampers the advance of therapeutic discoveries. To circumvent this limitation, we screened mice engineered to carry eight MM lesions (NF-κB, KRAS, MYC, TP53, BCL2, cyclin D1, MMSET/NSD2 and c-MAF) combinatorially activated in B lymphocytes following T cell-driven immunization. Fifteen genetically diverse models developed bone marrow (BM) tumors fulfilling MM pathogenesis. Integrative analyses of ∼500 mice and ∼1,000 patients revealed a common MAPK–MYC genetic pathway that accelerated time to progression from precursor states across genetically heterogeneous MM. MYC-dependent time to progression conditioned immune evasion mechanisms that remodeled the BM microenvironment differently. Rapid MYC-driven progressors exhibited a high number of activated/exhausted CD8+ T cells with reduced immunosuppressive regulatory T (Treg) cells, while late MYC acquisition in slow progressors was associated with lower CD8+ T cell infiltration and more abundant Treg cells. Single-cell transcriptomics and functional assays defined a high ratio of CD8+ T cells versus Treg cells as a predictor of response to immune checkpoint blockade (ICB). In clinical series, high CD8+ T/Treg cell ratios underlie early progression in untreated smoldering MM, and correlated with early relapse in newly diagnosed patients with MM under Len/Dex therapy. In ICB-refractory MM models, increasing CD8+ T cell cytotoxicity or depleting Treg cells reversed immunotherapy resistance and yielded prolonged MM control. Our experimental models enable the correlation of MM genetic and immunological traits with preclinical therapy responses, which may inform the next-generation immunotherapy trials.
  • Fouling of Polyalkylmethylsiloxane Composite Membranes during Pervaporation Separation of ABE-Fermentation Mixtures

    Rokhmanka, Tatyana N.; Grushevenko, Evgenia A.; Arapova, Olga V.; Bondarenko, Galina N.; Golubev, George S.; Borisov, Ilya L.; Volkov, Alexey V. (Applied Sciences, MDPI AG, 2023-03-16) [Article]
    Production of bio-alcohols is one of the approaches used in the development of alternative energy. Pervaporation is a promising option for the separation of bio-alcohols from the fermentation mixture. A serious problem in the process of continuous extraction of biobutanol from the fermentation broth is the contamination of the membrane, which leads to a decrease in its permeability over time. In this work, the transport properties of composite membranes based on polyheptylmethylsiloxane (PHeptMS), polydecylmethylsiloxane (PDecMS), and a commercial membrane MDK-3 were studied during separation of a real ABE-fermentation broth in vacuum pervaporation mode. The study was performed before and after continuous contact of the membranes with the fermentation broth for one month. Visually and by scanning electron spectroscopy, the presence of membrane surface residue and its effect on the wettability of the membrane selective layer by the components of the ABE broth were determined. The sediment composition was evaluated by energy dispersive analysis and infrared spectroscopy. According to the pervaporation separation of the ABE-broth using PHeptMS, PDecMS, and MDK-3 membranes, the butanol flux was 0.029, 0.012, and 0.054 kg/(m2·h), respectively. The butanol-water partition factor was 41, 22, and 13 for PHeptMS, PDecMS, and MDK-3, respectively. After one month of incubation of the membranes in ABE-fermentation broth during the separation of the model mixture, a decrease of 10 and 5% in permeate flux and separation factor, respectively, was observed for all membranes. Temperature dependences (30–60 °C) of permeate flux, permeability, and selectivity were obtained for the membranes after clogging. The most promising in terms of minimal negative changes as a result of fouling was demonstrated by the PHeptMS membrane. For it, the clogging dynamics during separation of the real fermentation broth for 216 h were investigated. Two characteristic steps of decrease in transport and separation properties were observed, after 28 and 150 h of the experiment. After 216 h of experiment, a 1.28-fold decrease in total flux through the membrane, a 9% decrease in butanol permeability, and a 10% decrease in n-butanol selectivity were found for PHeptMS.
  • Efficient in planta production of amidated antimicrobial peptides that are active against drug-resistant ESKAPE pathogens

    Chaudhary, Shahid; Ali, Zahir; Tehseen, Muhammad; Haney, Evan F.; Pantoja Angles, Aarón; Alshehri, Salwa; Wang, Tiannyu; Clancy, Gerard Jude; Ayach, Maya; Hauser, Charlotte; Hong, Pei-Ying; Hamdan, Samir; Hancock, Robert E. W.; Mahfouz, Magdy M. (Nature Communications, Springer Science and Business Media LLC, 2023-03-16) [Article]
    Antimicrobial peptides (AMPs) are promising next-generation antibiotics that can be used to combat drug-resistant pathogens. However, the high cost involved in AMP synthesis and their short plasma half-life render their clinical translation a challenge. To address these shortcomings, we report efficient production of bioactive amidated AMPs by transient expression of glycine-extended AMPs in Nicotiana benthamiana line expressing the mammalian enzyme peptidylglycine α-amidating mono-oxygenase (PAM). Cationic AMPs accumulate to substantial levels in PAM transgenic plants compare to nontransgenic N. benthamiana. Moreover, AMPs purified from plants exhibit robust killing activity against six highly virulent and antibiotic resistant ESKAPE pathogens, prevent their biofilm formation, analogous to their synthetic counterparts and synergize with antibiotics. We also perform a base case techno-economic analysis of our platform, demonstrating the potential economic advantages and scalability for industrial use. Taken together, our experimental data and techno-economic analysis demonstrate the potential use of plant chassis for large-scale production of clinical-grade AMPs.
  • The Influence of Prenatal Exposure to Methamphetamine on the Development of Dopaminergic Neurons in the Ventral Midbrain

    Alsanie, Walaa F.; Abdelrahman, Sherin; Felimban, Raed I.; Alkhatabi, Heba A.; Gaber, Ahmed; Alosimi, Ebtisam Abdulah; Alhomrani, Majid; Habeeballah, Hamza; Hauser, Charlotte; Alamri, Abdulhakeem S.; Althobaiti, Aiysha; Alsharif, Abdulaziz; Alzahrani, Ahmed S.; Al-Ghamdi, Mohammad S.; Raafat, Bassem M.; Alswat, Khaled A.; Althobaiti, Yusuf S.; Asiri, Yousif A. (International Journal of Molecular Sciences, MDPI AG, 2023-03-16) [Article]
    Methamphetamine, a highly addictive central nervous system (CNS) stimulant, is used worldwide as an anorexiant and attention enhancer. Methamphetamine use during pregnancy, even at therapeutic doses, may harm fetal development. Here, we examined whether exposure to methamphetamine affects the morphogenesis and diversity of ventral midbrain dopaminergic neurons (VMDNs). The effects of methamphetamine on morphogenesis, viability, the release of mediator chemicals (such as ATP), and the expression of genes involved in neurogenesis were evaluated using VMDNs isolated from the embryos of timed-mated mice on embryonic day 12.5. We demonstrated that methamphetamine (10 µM; equivalent to its therapeutic dose) did not affect the viability and morphogenesis of VMDNs, but it reduced the ATP release negligibly. It significantly downregulated Lmx1a, En1, Pitx3, Th, Chl1, Dat, and Drd1 but did not affect Nurr1 or Bdnf expression. Our results illustrate that methamphetamine could impair VMDN differentiation by altering the expression of important neurogenesis-related genes. Overall, this study suggests that methamphetamine use may impair VMDNs in the fetus if taken during pregnancy. Therefore, it is essential to exercise strict caution for its use in expectant mothers.
  • Fully Printed Dual-Layer Depolarizing Chipless RFID Tag for Wearable Applications

    Wang, Renqi; Akhter, Zubair; Li, Weiwei; Shamim, Atif (IEEE Journal of Radio Frequency Identification, Institute of Electrical and Electronics Engineers (IEEE), 2023-03-16) [Article]
    This work presents a cross-polar dual-layer chipless radio-frequency identification (RFID) tag based on a ladder-shaped resonator design. An integrated ground plane enables direct attachment to human skin without performance deterioration. Simulations show that the ladder-shaped resonator provides several advantages over traditional L-shaped and straight resonators, including a strong cross-polar radar cross section (-23.4 dBsm), third-order harmonics, orientation insensitivity, and compact size (0.062 λ2). The effects of the ground plane shape on the surface current distribution are investigated, and a circular tag of 20 mm radius is designed using ladder resonator groups and frequency shift encoding to provide an active area of 96.45 bits/λ2 and a unit frequency of 6.03 bits/GHz. The tag substrate is three-dimensionally (3D) printed with metallic resonator patterns that are subsequently screen-printed on the substrate. The maximum read range is measured at 40 mm using a cross-shaped, dual-polarized Vivaldi antenna connected to a network analyzer. The measured characteristics in free space are in good agreement with the simulation results, and practical on-body performance tests for the manufactured prototype using simulation and direct measurements indicate that the tag performance remains stable for both free space and on-body cases. The fully printed fabrication process makes the proposed tag design suitable for mass production at a low cost.

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