This study focuses on an ad hoc machine-learning method for locating archaeological sites in arid environments. Pleiades (P1B) were uploaded to the cloud asset of the Google Earth Engine (GEE) environment because they are not yet available on the platform. The average of the SAR data was combined with the P1B image in the selected study area called Blad Talh at Gafsa, which is located in southern Tunisia. This pre-desert region has long been investigated as an important area of Roman civilization (106 BCE). The results show an accurate probability map with an overall accuracy and Kappa coefficient of 0.93 and 0.91, respectively, when validated with field survey data. The results of this research demonstrate, from the perspective of archaeologists, the capability of satellite data and machine learning to discover buried archaeological sites. This work shows that the area presents more archaeological sites, which has major implications for understanding the archaeological significance of the region. Remote sensing combined with machine learning algorithms provides an effective way to augment archaeological surveys and detect new cultural deposits.

2D transition-metal dichalcogenides of chromium are technologically important due to their diverse electrical and magnetic properties. Herein this study, 1T-CrS2 nanosheets as thin as 2?nm are successfully synthesized by an atmospheric pressure space-confined chemical vapor deposition method. The prepared CrS2 nanosheets are stable at room temperature. Electrical measurement shows a quasi n-type semiconductor behavior. In addition, terahertz characterizations on 1T-CrS2 reveal its potential to integrate with the ultrathin infrared sensor platforms.

Global concerns towards potentially toxic elements (PTEs) are steadily increasing due to the significant threats that PTEs pose to human health and environmental quality. This calls for immediate, effective and efficient remediation solutions. Earthworms, the 'ecosystem engineers', can modify and improve soil health and enhance plant productivity. Recently, considerable attention has been paid to the potential of earthworms, alone or combined with other soil organisms and/or soil amendments, to remediate PTEs contaminated soils. However, the use of earthworms in the remediation of PTEs contaminated soil (i.e., vermiremediation) has not been thoroughly reviewed to date. Therefore, this review discusses and provides comprehensive insights into the suitability of earthworms as potential candidates for bioremediation of PTEs contaminated soils and mitigating environmental and human health risks. Specifically, we reviewed and discussed: i) the occurrence and abundance of earthworms in PTEs contaminated soils; ii) the influence of PTEs on earthworm communities in contaminated soils; iii) factors affecting earthworm PTEs accumulation and elimination, and iv) the dynamics and fate of PTEs in earthworm amended soils. The technical feasibility, knowledge gaps, and practical challenges have been worked out and critically discussed. Therefore, this review could provide a reference and guidance for bio-restoration of PTEs contaminated soils and shall also help developing innovative and applicable solutions for controlling PTEs bioavailability for the remediation of contaminated soils and the mitigation of the environment and human risks.

SummaryBackground
The 2015 Lancet Commission on global surgery identified surgery and anaesthesia as indispensable parts of holistic health-care systems. However, COVID-19 exposed the fragility of planned surgical services around the world, which have also been neglected in pandemic recovery planning. This study aimed to develop and validate a novel index to support local elective surgical system strengthening and address growing backlogs.
Methods
First, we performed an international consultation through a four-stage consensus process to develop a multidomain index for hospital-level assessment (surgical preparedness index; SPI). Second, we measured surgical preparedness across a global network of hospitals in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) to explore the distribution of the SPI at national, subnational, and hospital levels. Finally, using COVID-19 as an example of an external system shock, we compared hospitals' SPI to their planned surgical volume ratio (SVR; ie, operations for which the decision for surgery was made before hospital admission), calculated as the ratio of the observed surgical volume over a 1-month assessment period between June 6 and Aug 5, 2021, against the expected surgical volume based on hospital administrative data from the same period in 2019 (ie, a pre-pandemic baseline). A linear mixed-effects regression model was used to determine the effect of increasing SPI score.
Findings
In the first phase, from a longlist of 103 candidate indicators, 23 were prioritised as core indicators of elective surgical system preparedness by 69 clinicians (23 [33%] women; 46 [67%] men; 41 from HICs, 22 from MICs, and six from LICs) from 32 countries. The multidomain SPI included 11 indicators on facilities and consumables, two on staffing, two on prioritisation, and eight on systems. Hospitals were scored from 23 (least prepared) to 115 points (most prepared). In the second phase, surgical preparedness was measured in 1632 hospitals by 4714 clinicians from 119 countries. 745 (45·6%) of 1632 hospitals were in MICs or LICs. The mean SPI score was 84·5 (95% CI 84·1–84·9), which varied between HIC (88·5 [89·0–88·0]), MIC (81·8 [82·5–81·1]), and LIC (66·8 [64·9–68·7]) settings. In the third phase, 1217 (74·6%) hospitals did not maintain their expected SVR during the COVID-19 pandemic, of which 625 (51·4%) were from HIC, 538 (44·2%) from MIC, and 54 (4·4%) from LIC settings. In the mixed-effects model, a 10-point increase in SPI corresponded to a 3·6% (95% CI 3·0–4·1; p<0·0001) increase in SVR. This was consistent in HIC (4·8% [4·1–5·5]; p<0·0001), MIC (2·8 [2·0–3·7]; p<0·0001), and LIC (3·8 [1·3–6·7%]; p<0·0001) settings.
Interpretation
The SPI contains 23 indicators that are globally applicable, relevant across different system stressors, vary at a subnational level, and are collectable by front-line teams. In the case study of COVID-19, a higher SPI was associated with an increased planned surgical volume ratio independent of country income status, COVID-19 burden, and hospital type. Hospitals should perform annual self-assessment of their surgical preparedness to identify areas that can be improved, create resilience in local surgical systems, and upscale capacity to address elective surgery backlogs.
Funding
National Institute for Health Research (NIHR) Global Health Research Unit on Global Surgery, NIHR Academy, Association of Coloproctology of Great Britain and Ireland, Bowel Research UK, British Association of Surgical Oncology, British Gynaecological Cancer Society, and Medtronic.

Biochar is a solid material obtained from the pyrolytic carbonization of biomass in an oxygen-free/limited environment. Sulfur-containing biochar has a wide range of applications, such as adsorptive removal of pollutants (e.g., Hg, Cd, and Ni) and acting as a solid acid catalyst or as an electrode of Li-S battery. To date, many methods have been developed to strengthen the function of biochar by introducing sulfur-containing groups to promote the application and commercialization of biochar. This review aims to present the formation, analysis, engineering, and application of sulfur-functional groups in biochar. The sulfur-functional groups such as organic sulfur (e.g., C–S, –C–S–C–, CS, thiophene, and sulfone) and inorganic sulfur (e.g., sulfate, sulfide, sulfite, and elemental S) can be determined through Fourier transform infrared spectrometry (FTIR), X-ray photoelectron spectroscopy (XPS), and X-ray absorption near edge structure (XANES). The sulfur-functional groups can be obtained through selecting biomass composition, pyrolysis process, S-doping, and post-treatment of biochar, but the engineering is challenging. The positive effect of sulfur-functional groups in the application is also analyzed in this paper, such as the complexation and electron transfer between sulfur-functional groups and heavy metal (e.g., Hg, Cd, and Ni) on improving biochar adsorption capacity. However, there are still challenges in directional synthesis, precise determination, and regulation of application performance. Based on the research gaps identified, future prospective investigation directions on analysis, engineering, and application of biochar S-functional groups were presented in this review.

Two-dimensional (2D) ferromagnets with out-of-plane (OOP) magnetic anisotropy are potential candidates for realizing the next-generation memory devices with ultra-low power consumption and high storage density. However, a scalable approach to synthesize 2D magnets with OOP anisotropy directly on the complimentary metal-oxide semiconductor (CMOS) compatible substrates has not yet been mainly explored, which hinders the practical application of 2D magnets. This work demonstrates a cascaded space confined chemical vapor deposition (CS-CVD) technique to synthesize 2D FexGeTe2 ferromagnets. The weight fraction of iron (Fe) in the precursor controls the phase purity of the as-grown FexGeTe2. As a result, high-quality Fe3GeTe2 and Fe5GeTe2 flakes have been grown selectively using the CS-CVD technique. Curie temperature (TC) of the as-grown FexGeTe2 can be up to ∼ 280 K, nearly room temperature. The thickness and temperature-dependent magnetic studies on the Fe5GeTe2 reveal a 2D Ising to 3D XY behavior. Also, Terahertz spectroscopy experiments on Fe5GeTe2 display the highest conductivity among other FexGeTe2 2D magnets. The results of this work indicate a scalable pathway for the direct growth and integration of 2D ternary magnets on CMOS-based substrates to develop spintronic memory devices.

Dielectric constant (ε, epsilon) is one of the basic physical parameters for materials, determining the response of materials to electromagnetic waves or electrical field; its value is generally positive. In fact, dielectric constant can also be negative, regarded as supernormal performance to some degree. The negative dielectric property has become research hotspot as an essential key for constructing metamaterials, showing unique and exotic electromagnetic properties not existing in naturally occurring materials, such as negative refraction, perfect troubles, and reverse Doppler effect. Recently, the feasibility is demonstrated to achieve negative dielectric property in conventional heterogeneous composites rather than periodic artificial arrays; drawing great attention from researchers in material science and engineering, many advances have been made and can promote the development of metamaterials and conventional electromagnetic functional materials. Here, we reviewed the recent advances in negative dielectric property designed in some heterogeneous composites, including metal composites, carbon composites, ceramic composites, conducting polymer. Besides, various strategies, including designing different microstructures, changing the working temperatures, choosing flexible matrix or fillers, electro-magnetic coupling, were summarized to precisely adjust negative dielectric property. Finally, the question unsolved and perspectives about negative dielectric property are put forward; we expect to shed light on the mechanism of negative dielectric property as well as its relationship with the material design in composition and microstructure.

Diphenyleneiodonium (DPI) has long been evaluated as an anticancer drug inhibiting NADPH oxidase, the IC in several cancer cell lines was reported 10 µM, which is too high for efficacy. In this study, we employed miPS-Huh7cmP cells, which we previously established as a cancer stem cell (CSC) model from induced pluripotent stem cells, to reevaluate the efficacy of DPI because CSCs are currently one of the main foci of therapeutic strategy to treat cancer, but generally considered resistant to chemotherapy. As a result, the conventional assay for the cell growth inhibition by DPI accounted for an IC at 712 nM that was not enough to define the effectiveness as an anticancer drug. Simultaneously, the wound-healing assay revealed an IC of approximately 500 nM. Comparatively, the IC values shown on sphere formation, colony formation, and tube formation assays were 5.52, 12, and 8.7 nM, respectively. However, these inhibitory effects were not observed by VAS2780, also a reputed NADPH oxidase inhibitor. It is noteworthy that these three assays are evaluating the characteristic of CSCs and are designed in the three-dimensional (3D) culture methods. We concluded that DPI could be a suitable candidate to target mitochondrial respiration in CSCs. We propose that the 3D culture assays are more efficient to screen anti-CSC drug candidates and better mimic tumor microenvironment when compared to the adherent monolayer of 2D culture system used for a conventional assay, such as cell growth inhibition and wound-healing assays.

Human Cripto-1 is a member of the epidermal growth factor (EGF)-Cripto-FRL-1-Cryptic (CFC) family family and performs critical roles in cancer and various pathological and developmental processes. Recently we demonstrated that a soluble form of Cripto-1 suppresses the self-renewal and enhances the differentiation of cancer stem cells (CSCs). A functional form of soluble Cripto-1 was found to be difficult to obtain because of the 12 cysteine residues in the protein which impairs the folding process. Here, we optimized the protocol for a T7 expression system, purification from inclusion bodies under denatured conditions refolding of a His-tagged Cripto-1 protein. A concentrations of 0.2-0.4 mM isopropyl β-D-1-thiogalactopyranoside (IPTG) at 37°C was found to be the optimal concentration for Cripto-1 expression while imidazole at 0.5 M was the optimum concentration to elute the Cripto-1 protein from a Ni-column in the smallest volume. Cation exchange column chromatography of the Cripto-1 protein in the presence of 8 M urea exhibited sufficient elution profile at pH 5, which was more efficient at recovery. The recovery of the protein reached to more than 26.6% after refolding with arginine. The purified Cripto-1 exhibited high affinity to the anti-ALK-4 antibody and suppressed sphere forming ability of CSCs at high dose and induced cell differentiation.

Viruses evade the innate immune response by suppressing the production or activity of cytokines such as type I interferons (IFNs). Here we report the discovery of a mechanism by which the SARS-CoV-2 virus coopts an intrinsic cellular machinery to suppress the production of the key immunostimulatory cytokine IFN-β. We reveal that the SARS-CoV-2 encoded nonstructural protein 2 (NSP2) directly interacts with the cellular GIGYF2 protein. This interaction enhances the binding of GIGYF2 to the mRNA cap-binding protein 4EHP, thereby repressing the translation of the

Duckling short beak and dwarfism syndrome virus (SBDSV), an emerging goose parvovirus, has caused short beak and dwarfism syndrome (SBDS) in Chinese duck flocks since 2015. Presently, there is no commercial vaccine against SBDS. In the present study, a virus-like particle (VLP)-based candidate vaccine was developed against this disease. A baculovirus expression system was used to express the SBDSV VP2 protein in Sf9 cells. Immunofluorescence assay, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting were used to confirm protein expression. Furthermore, transmission electron microscopy was used to observe the formation of VLPs. VLPs were formulated into an oil-adjuvanted maternal vaccine to evaluate humoral responses in breeding ducks via latex particle agglutination inhibition assay (LPAI) and microneutralization assay. The offspring were challenged with SBDSV to test the protective efficacy. A single dose of SBDSV was able to induce the high level of LPAI antibodies in ducks, with LPAI and neutralization peak titres of 4.9 ± 1.20 log2 and 7.1 ± 1.20 log2, respectively, at 4 weeks post-vaccination (wpv). The average LPAI titre of yolk antibodies in duck eggs receiving 2 doses (first and boost doses) of the vaccine was 5.3 ± 1.09 log2 at 4 weeks post-boost. The protective efficacy of the maternal vaccine was 87.5%-100%. These results indicate that SBDSV VLPs can be a promising vaccine candidate for controlling SBDS.

Polymeric nanoparticles (NPs) are produced using bio-compatible and bio-degradable materials such as PLGA (Poly(lactic-co-glycolic acid)). This technology provides a valuable tool to deliver molecules to the subcellular level with a relatively low risk of cytotoxicity. However their use in the field of reproductive biotechnology is not yet scientifically substantiated. The aim of the present study was to test if PLGA NPs can be taken-up by cumulus-enclosed oocytes as a first step towards potential oocyte-targeted applications to enhance oocyte quality and fertility. We conducted a series of experiments using bovine in vitro oocyte maturation as a model to study FITC-conjugated PLGA internalization (using laser-scanning confocal microscopy) and the effect of some important physical (particle size) and chemical (conjugation with PEG) modifications. We show evidence that PLGA NPs can be taken-up by cumulus cells and to a less extent by the enclosed oocytes regardless of the NP size. The NP transfer to the oocyte appear to be transcellular (via cumulus cells and transzonal projections) and paracellular (via zona pellucida). The PLGA NPs were detected in the vicinity of the oocyte as quick as 2 h post-exposure in a protein-free medium and did not compromise cumulus cell viability nor subsequent early embryo development or embryo quality. These results suggest that PLGA NPs may have promising applications as carriers for drug or molecule delivery targeting cumulus cells and oocytes.

The availability of fresh frozen (FF) tissue is a barrier for implementing RNA sequencing (RNA-seq) in the clinic. The majority of clinical samples are stored as formalin-fixed, paraffin-embedded (FFPE) tissues. Exome capture platforms have been developed for RNA-seq from FFPE samples. However, these methods have not been systematically compared. We performed transcriptomic analysis of 32 FFPE tumor samples from 11 patients using three exome capture-based methods: Agilent SureSelect V6, TWIST NGS Exome, and IDT XGen Exome Research Panel. We compared these methods to the TruSeq RNA-seq of fresh frozen (FF-TruSeq) tumor samples from the same patients. We assessed the recovery of clinically relevant biological features. The Spearman’s correlation coefficients between the global expression profiles of the three capture-based methods from FFPE and matched FF-TruSeq were high (rho = 0.72–0.9, p < 0.05). A significant correlation between the expression of key immune genes between individual capture-based methods and FF-TruSeq (rho = 0.76-0.88, p < 0.05) was observed. All exome capture-based methods reliably detected outlier expression of actionable gene transcripts, including ERBB2, MET, NTRK1 , and PPARG . In urothelial cancer samples, the Agilent assay was associated with the highest molecular subtype concordance with FF-TruSeq (Cohen’s k = 0.7, p < 0.01). The Agilent and IDT assays detected all the clinically relevant fusions that were initially identified in FF-TruSeq. All FFPE exome capture-based methods had comparable performance and concordance with FF-TruSeq. Our findings will enable the implementation of RNA-seq in the clinic to guide precision oncology approaches.

Abstract We describe the convergent synthesis of a 5-O-?-D-ribofuranosyl-based apramycin derivative (apralog) that displays significantly improved antibacterial activity over the parent apramycin against wild-type ESKAPE pathogens. In addition, the new apralog retains excellent antibacterial activity in the presence of the only aminoglycoside modifying enzyme (AAC(3)-IV) acting on the parent, without incurring susceptibility to the APH(3?) mechanism that disables other 5-O-?-D-ribofuranosyl 2-deoxystreptamine type aminoglycosides by phosphorylation at the ribose 5-position. Consistent with this antibacterial activity, the new apralog has excellent 30?nM activity (IC50) for the inhibition of protein synthesis by the bacterial ribosome in a cell-free translation assay, while retaining the excellent across-the-board selectivity of the parent for inhibition of bacterial over eukaryotic ribosomes. Overall, these characteristics translate into excellent in?vivo efficacy against E. coli in a mouse thigh infection model and reduced ototoxicity vis à vis the parent in mouse cochlear explants.

SummaryBackground
Risk of mortality following surgery in patients across Africa is twice as high as the global average. Most of these deaths occur on hospital wards after the surgery itself. We aimed to assess whether enhanced postoperative surveillance of adult surgical patients at high risk of postoperative morbidity or mortality in Africa could reduce 30-day in-hospital mortality.
Methods
We did a two-arm, open-label, cluster-randomised trial of hospitals (clusters) across Africa. Hospitals were eligible if they provided surgery with an overnight postoperative admission. Hospitals were randomly assigned through minimisation in recruitment blocks (1:1) to provide patients with either a package of enhanced postoperative surveillance interventions (admitting the patient to higher care ward, increasing the frequency of postoperative nursing observations, assigning the patient to a bed in view of the nursing station, allowing family members to stay in the ward, and placing a postoperative surveillance guide at the bedside) for those at high risk (ie, with African Surgical Outcomes Study Surgical Risk Calculator scores ≥10) and usual care for those at low risk (intervention group), or for all patients to receive usual postoperative care (control group). Health-care providers and participants were not masked, but data assessors were. The primary outcome was 30-day in-hospital mortality of patients at low and high risk, measured at the participant level. All analyses were done as allocated (by cluster) in all patients with available data. This trial is registered with ClinicalTrials.gov, NCT03853824.
Findings
Between May 3, 2019, and July 27, 2020, 594 eligible hospitals indicated a desire to participate across 33 African countries; 332 (56%) were able to recruit participants and were included in analyses. We allocated 160 hospitals (13 275 patients) to provide enhanced postoperative surveillance and 172 hospitals (15 617 patients) to provide standard care. The mean age of participants was 37·1 years (SD 15·5) and 20 039 (69·4%) of 28 892 patients were women. 30-day in-hospital mortality occurred in 169 (1·3%) of 12 970 patients with mortality data in the intervention group and in 193 (1·3%) of 15 242 patients with mortality data in the control group (relative risk 0·96, 95% CI 0·69–1·33; p=0·79). 45 (0·2%) of 22 031 patients at low risk and 309 (5·6%) of 5500 patients at high risk died. No harms associated with either intervention were reported.
Interpretation
This intervention package did not decrease 30-day in-hospital mortality among surgical patients in Africa at high risk of postoperative morbidity or mortality. Further research is needed to develop interventions that prevent death from surgical complications in resource-limited hospitals across Africa.
Funding
Bill & Melinda Gates Foundation and the World Federation of Societies of Anaesthesiologists.
Translations
For the Arabic, French and Portuguese translations of the abstract see Supplementary Materials section.