Summary
Viruses can affect microbial dynamics, metabolism and biogeochemical cycles in aquatic ecosystems. However, viral diversity and functions in agricultural soils are poorly known, especially in ...the rhizosphere. We used virome analysis of eight rhizosphere and bulk soils to study viral diversity and potential biogeochemical impacts in an agro‐ecosystem. The order Caudovirales was the predominant viral type in agricultural soils, with Siphoviridae being the most abundant family. Phylogenetic analysis of the terminase large subunit of Caudovirales identified high viral diversity and three novel groups. Viral community composition differed significantly between bulk and rhizosphere soils. Soil pH was the main environmental driver of the viral community structure. Remarkably, abundant auxiliary carbohydrate‐active enzyme (CAZyme) genes were detected in viromes, including glycoside hydrolases, carbohydrate esterases and carbohydrate‐binding modules. These results demonstrate that virus‐encoded putative auxiliary metabolic genes or metabolic genes that may change bacterial metabolism and indirectly contribute to biogeochemical cycling, especially carbon cycling, in agricultural soil.
Chimeric antigen receptor (CAR) T cell therapy has demonstrated proven efficacy in some hematologic cancers. We evaluated the safety and efficacy of LCAR-B38M, a dual epitope-binding CAR T cell ...therapy directed against 2 distinct B cell maturation antigen epitopes, in patients with relapsed/refractory (R/R) multiple myeloma (MM).
This ongoing phase 1, single-arm, open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM. Lymphodepletion was performed using cyclophosphamide 300 mg/m
. LCAR-B38M CAR T cells (median CAR+ T cells, 0.5 × 10
cells/kg range, 0.07 to 2.1 × 10
) were infused in 3 separate infusions. The primary objective is to evaluate the safety of LCAR-B38M CAR T cells; the secondary objective is to evaluate the antimyeloma response of the treatment based on the general guidelines of the International Myeloma Working Group.
At data cutoff, 57 patients had received LCAR-B38M CAR T cells. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were reported in 37/57 patients (65%); most common were leukopenia (17/57; 30%), thrombocytopenia (13/57; 23%), and aspartate aminotransferase increased (12/57; 21%). Cytokine release syndrome occurred in 51/57 patients (90%); 4/57 (7%) had grade ≥ 3 cases. One patient reported neurotoxicity of grade 1 aphasia, agitation, and seizure-like activity. The overall response rate was 88% (95% confidence interval CI, 76 to 95); 39/57 patients (68%) achieved a complete response, 3/57 (5%) achieved a very good partial response, and 8/57 (14%) achieved a partial response. Minimal residual disease was negative for 36/57 (63%) patients. The median time to response was 1 month (range, 0.4 to 3.5). At a median follow-up of 8 months, median progression-free survival was 15 months (95% CI, 11 to not estimable). Median overall survival for all patients was not reached.
LCAR-B38M CAR T cell therapy displayed a manageable safety profile and demonstrated deep and durable responses in patients with R/R MM.
ClinicalTrials.gov , NCT03090659 ; Registered on March 27, 2017, retrospectively registered.
Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers. We performed exome sequencing on 113 tumor-normal pairs, yielding a mean of 82 non-silent mutations per tumor, and 8 cell ...lines. The mutational profile of ESCC closely resembles those of squamous cell carcinomas of other tissues but differs from that of esophageal adenocarcinoma. Genes involved in cell cycle and apoptosis regulation were mutated in 99% of cases by somatic alterations of TP53 (93%), CCND1 (33%), CDKN2A (20%), NFE2L2 (10%) and RB1 (9%). Histone modifier genes were frequently mutated, including KMT2D (also called MLL2; 19%), KMT2C (MLL3; 6%), KDM6A (7%), EP300 (10%) and CREBBP (6%). EP300 mutations were associated with poor survival. The Hippo and Notch pathways were dysregulated by mutations in FAT1, FAT2, FAT3 or FAT4 (27%) or AJUBA (JUB; 7%) and NOTCH1, NOTCH2 or NOTCH3 (22%) or FBXW7 (5%), respectively. These results define the mutational landscape of ESCC and highlight mutations in epigenetic modulators with prognostic and potentially therapeutic implications.
Cross-species transmission of viruses from wildlife animal reservoirs poses a marked threat to human and animal health
. Bats have been recognized as one of the most important reservoirs for emerging ...viruses and the transmission of a coronavirus that originated in bats to humans via intermediate hosts was responsible for the high-impact emerging zoonosis, severe acute respiratory syndrome (SARS)
. Here we provide virological, epidemiological, evolutionary and experimental evidence that a novel HKU2-related bat coronavirus, swine acute diarrhoea syndrome coronavirus (SADS-CoV), is the aetiological agent that was responsible for a large-scale outbreak of fatal disease in pigs in China that has caused the death of 24,693 piglets across four farms. Notably, the outbreak began in Guangdong province in the vicinity of the origin of the SARS pandemic. Furthermore, we identified SADS-related CoVs with 96-98% sequence identity in 9.8% (58 out of 591) of anal swabs collected from bats in Guangdong province during 2013-2016, predominantly in horseshoe bats (Rhinolophus spp.) that are known reservoirs of SARS-related CoVs. We found that there were striking similarities between the SADS and SARS outbreaks in geographical, temporal, ecological and aetiological settings. This study highlights the importance of identifying coronavirus diversity and distribution in bats to mitigate future outbreaks that could threaten livestock, public health and economic growth.
Besides genome editing, CRISPR-Cas12a has recently been used for DNA detection applications with attomolar sensitivity but, to our knowledge, it has not been used for the detection of small ...molecules. Bacterial allosteric transcription factors (aTFs) have evolved to sense and respond sensitively to a variety of small molecules to benefit bacterial survival. By combining the single-stranded DNA cleavage ability of CRISPR-Cas12a and the competitive binding activities of aTFs for small molecules and double-stranded DNA, here we develop a simple, supersensitive, fast and high-throughput platform for the detection of small molecules, designated CaT-SMelor (CRISPR-Cas12a- and aTF-mediated small molecule detector). CaT-SMelor is successfully evaluated by detecting nanomolar levels of various small molecules, including uric acid and p-hydroxybenzoic acid among their structurally similar analogues. We also demonstrate that our CaT-SMelor directly measured the uric acid concentration in clinical human blood samples, indicating a great potential of CaT-SMelor in the detection of small molecules.
Summary
Plants harbour highly diverse mycobiomes which sustain essential functions for host health and productivity. However, ecological processes that govern the plant–mycobiome assembly, ...interactions and their impact on ecosystem functions remain poorly known. Here we characterized the ecological role and community assembly of both abundant and rare fungal taxa along the soil–plant continuums (rhizosphere, phyllosphere and endosphere) in the maize–wheat/barley rotation system under different fertilization practices at two contrasting sites. Our results indicate that mycobiome assembly is shaped predominantly by compartment niche and host species rather than by environmental factors. Moreover, crop‐associated fungal communities are dominated by few abundant taxa mainly belonging to Sordariomycetes and Dothideomycetes, while the majority of diversity within mycobiomes are represented by rare taxa. For plant compartments, the abundant sub‐community is mainly determined by stochastic processes. In contrast, the rare sub‐community is more sensitive to host selection and mainly governed by deterministic processes. Furthermore, our results demonstrate that rare taxa play an important role in fungal co‐occurrence network and ecosystem functioning like crop yield and soil enzyme activities. These results significantly advance our understanding of crop mycobiome assembly and highlight the key role of rare taxa in sustaining the stability of crop mycobiomes and ecosystem functions.
Covalent organic frameworks (COFs), connecting different organic units into one system through covalent bonds, are crystalline organic porous materials with 2D or 3D networks. Compared with ...conventional porous materials such as inorganic zeolite, active carbon, and metal‐organic frameworks, COFs are a new type of porous materials with well‐designed pore structure, high surface area, outstanding stability, and easy functionalization at the molecular level, which have attracted extensive attention in various fields, such as energy storage, gas separation, sensing, photoluminescence, proton conduction, magnetic properties, drug delivery, and heterogeneous catalysis. Herein, the recent advances in metal‐free COFs as a versatile platform for heterogeneous catalysis in a wide range of chemical reactions are presented and the synthetic strategy and promising catalytic applications of COF‐based catalysts (including photocatalysis) are summarized. According to the types of catalytic reactions, this review is divided into the following five parts for discussion: achiral organic catalysis, chiral organic conversion, photocatalytic organic reactions, photocatalytic energy conversion (including water splitting and the reduction of carbon dioxide), and photocatalytic pollutant degradation. Furthermore, the remaining challenges and prospects of COFs as heterogeneous catalysts are also presented.
Covalent organic frameworks (COFs) as a new type of organic porous materials have aroused great interest in the field of heterogeneous catalysis. Herein, the applications of metal‐free COFs in organic catalysis, photocatalysis, energy conversion, and pollutant degradation are systematically summarized. In addition, the main challenges in this area and the potential prospects for future work are also discussed.
Summary
Plant microbiomes are essential to host health and productivity but the ecological processes that govern crop microbiome assembly are not fully known.
Here we examined bacterial communities ...across 684 samples from soils (rhizosphere and bulk soil) and multiple compartment niches (rhizoplane, root endosphere, phylloplane, and leaf endosphere) in maize (Zea mays)‐wheat (Triticum aestivum)/barley (Hordeum vulgare) rotation system under different fertilization practices at two contrasting sites.
Our results demonstrate that microbiome assembly along the soil‐plant continuum is shaped predominantly by compartment niche and host species rather than by site or fertilization practice. From soils to epiphytes to endophytes, host selection pressure sequentially increased and bacterial diversity and network complexity consequently reduced, with the strongest host effect in leaf endosphere. Source tracking indicates that crop microbiome is mainly derived from soils and gradually enriched and filtered at different plant compartment niches. Moreover, crop microbiomes were dominated by a few dominant taxa (c. 0.5% of bacterial phylotypes), with bacilli identified as the important biomarker taxa for wheat and barley and Methylobacteriaceae for maize.
Our work provides comprehensive empirical evidence on host selection, potential sources and enrichment processes for crop microbiome assembly, and has important implications for future crop management and manipulation of crop microbiome for sustainable agriculture.
Recently, sensors that can imitate human skin have received extensive attention. Capacitive sensors have a simple structure, low loss, no temperature drift, and other excellent properties, and can be ...applied in the fields of robotics, human–machine interactions, medical care, and health monitoring. Polymer matrices are commonly employed in flexible capacitive sensors because of their high flexibility. However, their volume is almost unchanged when pressure is applied, and they are inherently viscoelastic. These shortcomings severely lead to high hysteresis and limit the improvement in sensitivity. Therefore, considerable efforts have been applied to improve the sensing performance by designing different microstructures of materials. Herein, two types of sensors based on the applied forces are discussed, including pressure sensors and strain sensors. Currently, five types of microstructures are commonly used in pressure sensors, while four are used in strain sensors. The advantages, disadvantages, and practical values of the different structures are systematically elaborated. Finally, future perspectives of microstructures for capacitive sensors are discussed, with the aim of providing a guide for designing advanced flexible and stretchable capacitive sensors via ingenious human‐made microstructures.
The advantages, disadvantages, and practical applications of several popular microstructures that are widely employed in capacitive sensors are summarized. A microstructured dielectric layer or electrode can improve sensor sensitivity, reduce hysteresis, and endow the rigid electronic device with excellent elastic stretchability, which is an essential part of next‐generation wearable devices and soft robots.
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