King Abdulaziz City for Science and Technology

Zhang Q., Bastard P., Liu Z., Le Pen J., Moncada-Velez M., Chen J., Ogishi M., Sabli I.K., Hodeib S., Korol C., Rosain J., Bilguvar K., Ye J., Bolze A., Bigio B., et. al.

The genetics underlying severe COVID-19 The immune system is complex and involves many genes, including those that encode cytokines known as interferons (IFNs). Individuals that lack specific IFNs can be more susceptible to infectious diseases. Furthermore, the autoantibody system dampens IFN response to prevent damage from pathogen-induced inflammation. Two studies now examine the likelihood that genetics affects the risk of severe coronavirus disease 2019 (COVID-19) through components of this system (see the Perspective by Beck and Aksentijevich). Q. Zhang et al. used a candidate gene approach and identified patients with severe COVID-19 who have mutations in genes involved in the regulation of type I and III IFN immunity. They found enrichment of these genes in patients and conclude that genetics may determine the clinical course of the infection. Bastard et al. identified individuals with high titers of neutralizing autoantibodies against type I IFN-α2 and IFN-ω in about 10% of patients with severe COVID-19 pneumonia. These autoantibodies were not found either in infected people who were asymptomatic or had milder phenotype or in healthy individuals. Together, these studies identify a means by which individuals at highest risk of life-threatening COVID-19 can be identified. Science, this issue p. eabd4570, p. eabd4585; see also p. 404 A large immunological and genomics study of COVID-19 patients reveals excess mutations in the type I IFN pathway. INTRODUCTION Clinical outcomes of human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection range from silent infection to lethal coronavirus disease 2019 (COVID-19). Epidemiological studies have identified three risk factors for severe disease: being male, being elderly, and having other medical conditions. However, interindividual clinical variability remains huge in each demographic category. Discovering the root cause and detailed molecular, cellular, and tissue- and body-level mechanisms underlying life-threatening COVID-19 is of the utmost biological and medical importance. RATIONALE We established the COVID Human Genetic Effort (www.covidhge.com) to test the general hypothesis that life-threatening COVID-19 in some or most patients may be caused by monogenic inborn errors of immunity to SARS-CoV-2 with incomplete or complete penetrance. We sequenced the exome or genome of 659 patients of various ancestries with life-threatening COVID-19 pneumonia and 534 subjects with asymptomatic or benign infection. We tested the specific hypothesis that inborn errors of Toll-like receptor 3 (TLR3)– and interferon regulatory factor 7 (IRF7)–dependent type I interferon (IFN) immunity that underlie life-threatening influenza pneumonia also underlie life-threatening COVID-19 pneumonia. We considered three loci identified as mutated in patients with life-threatening influenza: TLR3, IRF7, and IRF9. We also considered 10 loci mutated in patients with other viral illnesses but directly connected to the three core genes conferring influenza susceptibility: TICAM1/TRIF, UNC93B1, TRAF3, TBK1, IRF3, and NEMO/IKBKG from the TLR3-dependent type I IFN induction pathway, and IFNAR1, IFNAR2, STAT1, and STAT2 from the IRF7- and IRF9-dependent type I IFN amplification pathway. Finally, we considered various modes of inheritance at these 13 loci. RESULTS We found an enrichment in variants predicted to be loss-of-function (pLOF), with a minor allele frequency

Chaves A., Azadani J.G., Alsalman H., da Costa D.R., Frisenda R., Chaves A.J., Song S.H., Kim Y.D., He D., Zhou J., Castellanos-Gomez A., Peeters F.M., Liu Z., Hinkle C.L., Oh S., et. al.

Semiconductors are the basis of many vital technologies such as electronics, computing, communications, optoelectronics, and sensing. Modern semiconductor technology can trace its origins to the invention of the point contact transistor in 1947. This demonstration paved the way for the development of discrete and integrated semiconductor devices and circuits that has helped to build a modern society where semiconductors are ubiquitous components of everyday life. A key property that determines the semiconductor electrical and optical properties is the bandgap. Beyond graphene, recently discovered two-dimensional (2D) materials possess semiconducting bandgaps ranging from the terahertz and mid-infrared in bilayer graphene and black phosphorus, visible in transition metal dichalcogenides, to the ultraviolet in hexagonal boron nitride. In particular, these 2D materials were demonstrated to exhibit highly tunable bandgaps, achieved via the control of layers number, heterostructuring, strain engineering, chemical doping, alloying, intercalation, substrate engineering, as well as an external electric field. We provide a review of the basic physical principles of these various techniques on the engineering of quasi-particle and optical bandgaps, their bandgap tunability, potentials and limitations in practical realization in future 2D device technologies.

Hanikel N., Prévot M.S., Yaghi O.M.

The advancement of additional methods for freshwater generation is imperative to effectively address the global water shortage crisis. In this regard, extraction of the ubiquitous atmospheric moisture is a powerful strategy allowing for decentralized access to potable water. The energy requirements as well as the temporal and spatial restrictions of this approach can be substantially reduced if an appropriate sorbent is integrated in the atmospheric water generator. Recently, metal–organic frameworks (MOFs) have been successfully employed as sorbents to harvest water from air, making atmospheric water generation viable even in desert environments. Herein, the latest progress in the development of MOFs capable of extracting water from air and the design of atmospheric water harvesters deploying such MOFs are reviewed. Furthermore, future directions for this emerging field, encompassing both material and device improvements, are outlined. The latest progress in the development of metal–organic frameworks and their integration in an apparatus for water harvesting are reviewed.

El-Saber Batiha G., Magdy Beshbishy A., G. Wasef L., Elewa Y.H., A. Al-Sagan A., Abd El-Hack M.E., Taha A.E., M. Abd-Elhakim Y., Prasad Devkota H.

Medicinal plants have been used from ancient times for human healthcare as in the form of traditional medicines, spices, and other food components. Garlic (Allium sativum L.) is an aromatic herbaceous plant that is consumed worldwide as food and traditional remedy for various diseases. It has been reported to possess several biological properties including anticarcinogenic, antioxidant, antidiabetic, renoprotective, anti-atherosclerotic, antibacterial, antifungal, and antihypertensive activities in traditional medicines. A. sativum is rich in several sulfur-containing phytoconstituents such as alliin, allicin, ajoenes, vinyldithiins, and flavonoids such as quercetin. Extracts and isolated compounds of A. sativum have been evaluated for various biological activities including antibacterial, antiviral, antifungal, antiprotozoal, antioxidant, anti-inflammatory, and anticancer activities among others. This review examines the phytochemical composition, pharmacokinetics, and pharmacological activities of A. sativum extracts as well as its main active constituent, allicin.

Levy O., Kuai R., Siren E.M., Bhere D., Milton Y., Nissar N., De Biasio M., Heinelt M., Reeve B., Abdi R., Alturki M., Fallatah M., Almalik A., Alhasan A.H., Shah K., et. al.

To realize the potential of MSCs, bioengineering is needed to boost potency and control heterogeneity.

Khan S., Naushad M., Govarthanan M., Iqbal J., Alfadul S.M.

Wastewater is contaminated water that must be treated before it may be transferred into other rivers and lakes in order to prevent further groundwater pollution. Over the last decade, research has been conducted on a wide variety of contaminants, but the emerging contaminants are those caused primarily by micropollutants, endocrine disruptors (EDs), pesticides, pharmaceuticals, hormones, and toxins, as well as industrially-related synthetic dyes and dye-containing hazardous pollutants. Most emerging pollutants did not have established guidelines, but even at low concentrations they could have harmful effects on humans and aquatic organisms. In order to combat the above ecological threats, huge efforts have been done with a view to boosting the effectiveness of remediation procedures or developing new techniques for the detection, quantification and efficiency of the samples. The increase of interest in biotechnology and environmental engineering gives an opportunity for the development of more innovative ways to water treatment remediation. The purpose of this article is to provide an overview of emerging sources of contaminants, detection technologies, and treatment strategies. The goal of this review is to evaluate adsorption as a method for treating emerging pollutants, as well as sophisticated and cost-effective approaches for treating emerging contaminants.

Jie X., Li W., Slocombe D., Gao Y., Banerjee I., Gonzalez-Cortes S., Yao B., AlMegren H., Alshihri S., Dilworth J., Thomas J., Xiao T., Edwards P.

The ubiquitous challenge of plastic waste has led to the modern descriptor plastisphere to represent the human-made plastic environment and ecosystem. Here we report a straightforward rapid method for the catalytic deconstruction of various plastic feedstocks into hydrogen and high-value carbons. We use microwaves together with abundant and inexpensive iron-based catalysts as microwave susceptors to initiate the catalytic deconstruction process. The one-step process typically takes 30–90 s to transform a sample of mechanically pulverized commercial plastic into hydrogen and (predominantly) multiwalled carbon nanotubes. A high hydrogen yield of 55.6 mmol  $${\mathrm{g}}_{\mathrm{plastic}}^{ - 1}$$ is achieved, with over 97% of the theoretical mass of hydrogen being extracted from the deconstructed plastic. The approach is demonstrated on widely used, real-world plastic waste. This proof-of-concept advance highlights the potential of plastic waste itself as a valuable energy feedstock for the production of hydrogen and high-value carbon materials. The valorisation of plastic waste is highly desirable from an environmental perspective but generally yields low-value products. Now a method is disclosed to deconstruct plastic feedstocks into high-value hydrogen and carbon materials by means of an iron-based catalyst under microwave irradiation.

Wheeler M.A., Clark I.C., Tjon E.C., Li Z., Zandee S.E., Couturier C.P., Watson B.R., Scalisi G., Alkwai S., Rothhammer V., Rotem A., Heyman J.A., Thaploo S., Sanmarco L.M., Ragoussis J., et. al.

Multiple sclerosis is a chronic inflammatory disease of the CNS1. Astrocytes contribute to the pathogenesis of multiple sclerosis2, but little is known about the heterogeneity of astrocytes and its regulation. Here we report the analysis of astrocytes in multiple sclerosis and its preclinical model experimental autoimmune encephalomyelitis (EAE) by single-cell RNA sequencing in combination with cell-specific Ribotag RNA profiling, assay for transposase-accessible chromatin with sequencing (ATAC–seq), chromatin immunoprecipitation with sequencing (ChIP–seq), genome-wide analysis of DNA methylation and in vivo CRISPR–Cas9-based genetic perturbations. We identified astrocytes in EAE and multiple sclerosis that were characterized by decreased expression of NRF2 and increased expression of MAFG, which cooperates with MAT2α to promote DNA methylation and represses antioxidant and anti-inflammatory transcriptional programs. Granulocyte–macrophage colony-stimulating factor (GM-CSF) signalling in astrocytes drives the expression of MAFG and MAT2α and pro-inflammatory transcriptional modules, contributing to CNS pathology in EAE and, potentially, multiple sclerosis. Our results identify candidate therapeutic targets in multiple sclerosis. Single-cell RNA sequencing of cells from humans with multiple sclerosis and mice with a model of the disease identifies a population of disease-promoting astrocytes in which anti-oxidant and anti-inflammatory proteins are suppressed.

Ji Z., Wang H., Canossa S., Wuttke S., Yaghi O.M.

AbstractThe pores in metal–organic frameworks (MOFs) can be functionalized by placing chemical entities along the backbone and within the backbone. This chemistry is enabled by the architectural, thermal, and chemical robustness of the frameworks and the ability to characterize them by many diffraction and spectroscopic techniques. The pore chemistry of MOFs is articulated in terms of site isolation, coupling, and cooperation and relate that to their functions in guest recognition, catalysis, ion and electron transport, energy transfer, pore‐dynamic modulation, and interface construction. It is envisioned that the ultimate control of pore chemistry requires arranging functionalities into defined sequences and developing techniques for reading and writing such sequences within the pores.

Ali Z., Aman R., Mahas A., Rao G.S., Tehseen M., Marsic T., Salunke R., Subudhi A.K., Hala S.M., Hamdan S.M., Pain A., Alofi F.S., Alsomali A., Hashem A.M., Khogeer A., et. al.

• RT-LAMP coupled with CRISPR-Cas12 provides a sensitive and specific virus detection platform. • iSCAN sensitivity and specificity are comparable with RT-qPCR. • iSCAN is a 1 h detection module that can help in testing in low resource areas. • iSCAN can be developed as a one-pot assay. • iSCAN reagents can be produced locally and deployed for SARS-CoV2 detection. The COVID-19 pandemic caused by SARS-CoV-2 affects all aspects of human life. Detection platforms that are efficient, rapid, accurate, specific, sensitive, and user friendly are urgently needed to manage and control the spread of SARS-CoV-2. RT-qPCR based methods are the gold standard for SARS-CoV-2 detection. However, these methods require trained personnel, sophisticated infrastructure, and a long turnaround time, thereby limiting their usefulness. Reverse transcription-loop-mediated isothermal amplification (RT-LAMP), a one-step nucleic acid amplification method conducted at a single temperature, has been used for colorimetric virus detection. CRISPR-Cas12 and CRISPR-Cas13 systems, which possess collateral activity against ssDNA and RNA, respectively, have also been harnessed for virus detection. Here, we built an efficient, rapid, specific, sensitive, user-friendly SARS-CoV-2 detection module that combines the robust virus amplification of RT-LAMP with the specific detection ability of SARS-CoV-2 by CRISPR-Cas12. Furthermore, we combined the RT-LAMP-CRISPR-Cas12 module with lateral flow cells to enable highly efficient point-of-care SARS-CoV-2 detection. Our iSCAN SARS-CoV-2 detection module, which exhibits the critical features of a robust molecular diagnostic device, should facilitate the effective management and control of COVID-19.