Wastewater treatment plants (WWTPs) are recognized as hotspots for horizontal gene transfer (HGT) of antibiotic resistance genes (ARGs). Despite our understanding of the composition and distribution ...of ARGs in WWTPs, the genetic location, host, and fate of ARGs remain largely unknown.
In this study, we combined Oxford Nanopore and Illumina metagenomics sequencing to comprehensively uncover the resistome context of influent, activated sludge, and effluent of three WWTPs and simultaneously track the hosts of the ARGs. The results showed that most of the ARGs detected in all compartments of the WWTPs were carried by plasmids. Transposons and integrons also showed higher prevalence on plasmids than on the ARG-carrying chromosome. Notably, integrative and conjugative elements (ICEs) carrying five types of ARGs were detected, and they may play an important role in facilitating the transfer of ARGs, particularly for tetracycline and macrolide-lincosamide-streptogramin (MLS). A broad spectrum of ARGs carried by plasmids (29 subtypes) and ICEs (4 subtypes) was persistent across the WWTPs. Host tracking showed a variety of antibiotic-resistant bacteria in the effluent, suggesting the high potential for their dissemination into receiving environments. Importantly, phenotype-genotype analysis confirmed the significant role of conjugative plasmids in facilitating the survival and persistence of multidrug-resistant bacteria in the WWTPs. At last, the consistency in the quantitative results for major ARGs types revealed by Nanopore and Illumina sequencing platforms demonstrated the feasibility of Nanopore sequencing for resistome quantification.
Overall, these findings substantially expand our current knowledge of resistome in WWTPs, and help establish a baseline analysis framework to study ARGs in the environment.
Class 1 integrase intI1 has been considered as a good proxy for anthropogenic pollution because of being linked to genes conferring resistance to antibiotics. The gene cassettes of class 1 integrons ...could carry diverse antibiotic resistance genes (ARGs) and conduct horizontal gene transfer among microorganisms. The present study applied high-throughput sequencing technique combined with an intI1 database and genome assembly to quantify the abundance of intI1 in 64 environmental samples from 8 ecosystems, and to investigate the diverse arrangements of ARG-carrying gene cassettes (ACGCs) carried by class 1 integrons. The abundance of detected intI1 ranged from 3.83 × 10–4 to 4.26 × 10° intI1/cell. High correlation (Pearson’s r = 0.852) between intI1 and ARG abundance indicated that intI1 could be considered as an important indicator of ARGs in environments. Aminoglycoside resistance genes were most frequently observed on gene cassettes, carried by 57% assembled ACGCs, followed by trimethoprim and beta-lactam resistance genes. This study established the pipeline for broad monitoring of intI1 in various environmental samples and scanning the ARGs carried by integrons. These findings supplemented our knowledge on the distribution of class 1 integrons and ARGs carried on mobile genetic elements, benefiting future studies on horizontal gene transfer of ARGs.
An efficient and reconfigurable rectifier circuit, with the capability of automatically switching from low-power to high-power operation mode, is presented in this paper. The new topology allows the ...rectifier to convert RF power to dc power efficiently over an extended input power range. The circuit consists of diodes as rectifying elements and of n-channel field effect transistor in a depletion mode acting as the automated switch. Without using an external dc source, the circuit directly uses the rectified output dc voltage to bias the transistor, allowing high conversion efficiency over a wide input power range. This results in a compact and self-contained circuit. A total of two prototypes optimized for near-field and far-field wireless power transfer systems are fabricated and the measured results show that the performance exceeds that of the conventional rectifier circuit, which can only stay efficient over a limited range of the input power. The proposed design can maintain more than 50% of conversion efficiency over more than 25-dB range of the input power, with peak efficiency of 88% and 80% for near-field and far-field rectifiers, respectively. A system-level validation also confirms the improvement of the proposed rectifier design.
Catechins from green tea are one of the most effective natural compounds for cancer chemoprevention and have attracted extensive research. Cancer cell‐selective apoptosis‐inducing properties of ...catechins depend on efficient intracellular delivery. However, the low bioavailability limits the application of catechins. Herein, a nano‐scaled micellar composite composed of catechin‐functionalized cationic lipopolymer and serum albumin is constructed. Cationic liposomes tend to accumulate in the pulmonary microvasculature due to electrostatic effects and are able to deliver the micellar system intracellularly, thus improving the bioavailability of catechins. Albumin in the system acts as a biocompatible anti‐plasma absorbent, forming complexes with positively charged lipopolymer under electrostatic interactions, contributing to prolonged in vivo retention. The physicochemical properties of the nano‐micellar complexes are characterized, and the antitumor properties of catechin‐functionalized materials are confirmed by reactive oxygen species (ROS), caspase‐3, and cell apoptosis measurements. The role of each functional module, cationic polymeric liposome, and albumin is revealed by cell penetration, in vivo animal assays, etc. This multicomponent micellar nanocomposite has the potential to become an effective vehicle for the treatment of lung diseases such as pneumonia, lung tumors, sepsis‐induced lung injury, etc. This study also demonstrates that it is a great strategy to create a delivery system that is both tissue‐targeted and biologically active by combining cationic liposomes with the native bioactive compound catechins.
A multicomponent nano‐scaled micellar composite, Ac/Pc, consisting of catechin functionalized cationic lipopolymer (Pc) and serum albumin (Ac) is the focus of this work. The use of grafting catechins on polyelectrolyte macromolecules has resulted in the construction of a carrier with lung‐targeted, effective delivery of catechins intracellularly, giving the carrier the properties of catechins, i.e., cancer cell‐selective apoptosis‐induction and normal cell protection. Cationic liposomes, Pc, tend to accumulate in the pulmonary microvasculature due to electrostatic effects, as well as are able to deliver the micellar system intracellularly. Albumin in the system acts as a biocompatible anti‐plasma absorbent and can form complexes with positively charged Pc under electrostatic interactions, prolonging the in vivo retention time and reducing side effects.
Other than a few avascular tissues, almost all human tissues are connected to the systemic circulation via blood vessels that promote metabolism and function. Accordingly, engineered vascularization ...is a vital goal in tissue engineering for regenerative medicine. Endothelial cells (ECs) play a central role in vascularization with two significant specificities: physical interfaces between vascular stroma and blood, and phenotypic organ-specificity. Biomaterial scaffolding technologies that address these unique properties of ECs have been developed to promote the vascularization of various engineered tissues, and these have advanced from mimicking vascular architectures ex situ towards promoting spontaneous angiogenic remodeling in situ. Simultaneously, endothelial progenitor cells (EPCs) and organ-specific ECs are attracting more and more attention with the increasing awareness of the diversity of ECs in different organs.
ECs physically interface between the vascular stroma and blood. ECs not only provide instructive signals for organogenesis but also have organ-specific phenotypes.
Biomaterials that can promote spontaneous angiogenic remodeling in situ have been developed to address these unique properties of ECs. In response to physical or biochemical cues from scaffolds, host blood vessels grow into engineered tissues and form functional vascular networks in situ.
Because vascularization occurs where engineered tissues are engrafted, in situ angiogenic remodeling ensures that the regenerated vascular networks are organ-specific.
Simultaneous, organ-specific vascularization can also be established by vascularizing engineered tissues with endothelial progenitor cells that can differentiate into various endothelial phenotypes or organ-specific ECs.
A complete solution from parameter extraction to large-signal electrothermal model generation for gallium nitride (GaN) HEMTs is presented in this paper with the consideration of trapping deduced ...gate and drain lag effects. The extrinsic parasitic parameters are extracted by multibias hot-FET optimization using artificial bee colony algorithm. New terminal charge (Q gs , Q gd , and Q ds ) models with temperature dependence are proposed to better characterize the GaN devices. Physical mechanisms of the electrothermal and trapping effects have been investigated, and the artificial neural network (ANN) is exploited to construct the drain current based on pulsed I-V (PIV) measurements. Besides the instantaneous terminal voltages, additional three auxiliary variables are employed to describe the memory effects of GaN HEMT: channel temperature, gate trapping state, and drain trapping state. These variables are identified from PIVs to compose the input layer of the ANN, while in the simulator, they are captured by the thermal and two envelop tracking subcircuits. These physical auxiliary variables together with the ANN technology enable unlimited fitting sets of PIVs with satisfying accuracy. Singletone and two-tone on-wafer measurements are conducted for the verification, and a good agreement has been achieved between the measurements and simulations.
During femtosecond laser fabrication, photons are mainly absorbed by electrons, and the subsequent energy transfer from electrons to ions is of picosecond order. Hence, lattice motion is negligible ...within the femtosecond pulse duration, whereas femtosecond photon-electron interactions dominate the entire fabrication process. Therefore, femtosecond laser fabrication must be improved by controlling localized transient electron dynamics, which poses a challenge for measuring and controlling at the electron level during fabrication processes. Pump-probe spectroscopy presents a viable solution, which can be used to observe electron dynamics during a chemical reaction. In fact, femtosecond pulse durations are shorter than many physical/chemical characteristic times, which permits manipulating, adjusting, or interfering with electron dynamics. Hence, we proposed to control localized transient electron dynamics by temporally or spatially shaping femtosecond pulses, and further to modify localized transient materials properties, and then to adjust material phase change, and eventually to implement a novel fabrication method. This review covers our progresses over the past decade regarding electrons dynamics control (EDC) by shaping femtosecond laser pulses in micro/nanomanufacturing: (1) Theoretical models were developed to prove EDC feasibility and reveal its mechanisms; (2) on the basis of the theoretical predictions, many experiments are conducted to validate our EDC-based femtosecond laser fabrication method. Seven examples are reported, which proves that the proposed method can significantly improve fabrication precision, quality, throughput and repeatability and effectively control micro/nanoscale structures; (3) a multiscale measurement system was proposed and developed to study the fundamentals of EDC from the femtosecond scale to the nanosecond scale and to the millisecond scale; and (4) As an example of practical applications, our method was employed to fabricate some key structures in one of the 16 Chinese National S&T Major Projects, for which electron dynamics were measured using our multiscale measurement system.
In addition to proteins and nucleic acids, polysaccharides are an important type of biomacromolecule widely distributed in plants, animals, and microorganisms. Polysaccharides are considered as ...promising biomaterials due to their significant bioactivities, natural abundance, immunoactivity, and chemical modifiability for tissue engineering (TE) applications. Due to the similarities of the biochemical properties of polysaccharides and the extracellular matrix of human bodies, polysaccharides are increasingly recognized and accepted. Furthermore, the degradation behavior of these macromolecules is generally nontoxic. Certain delicate properties, such as remarkable mechanical properties and tunable tissue response, can be obtained by modifying the functional groups on the surface of polysaccharide molecules. The applications of polysaccharide-based biomaterials in the TE field have been growing intensively in recent decades, for example, bone/cartilage regeneration, cardiac regeneration, neural regeneration, and skin regeneration. This review summarizes the main essential properties of polysaccharides, including their chemical properties, crosslinking mechanisms, and biological properties, and focuses on the association between their structures and properties. The recent progress in polysaccharide-based biomaterials in various TE applications is reviewed, and the prospects for future studies are addressed as well. We intend this review to offer a comprehensive understanding of and inspiration for the research and development of polysaccharide-based materials in TE. Impact statement Polysaccharides are promising biomaterials due to their significant bioactivities, natural abundance, immunoactivity, and chemical modifiability for tissue engineering (TE) applications. As an important natural macromolecule, polysaccharide has attracted much attention both in academia and industry for several biomedical applications. Compared with synthetic materials, polysaccharides have unique biological properties; it is self-evident that polysaccharides will always be the research hotspot in fabricating various biomaterials for different TE. However, most researches about polysaccharides-based materials are still far from practical treatment. This review summarizes the main essential properties of polysaccharides, providing the basic information about chemical properties, crosslinking mechanisms, and biological properties. Recent researches about design and fabrication of polysaccharides-based materials are summarized.
Background
Non‐small cell lung cancer (NSCLC) is one of the most common human malignancies and the leading cause of cancer‐related death. Over the past few decades, genomic alterations of cancer ...driver genes have been identified in NSCLC, and molecular testing and targeted therapies have become standard care for lung cancer patients. Here we studied the unique genomic profile of driver genes in Chinese patients with NSCLC by next‐generation sequencing (NGS) assay.
Materials and Methods
A total of 1,200 Chinese patients with NSCLC were enrolled in this study. The median age was 60 years (range: 26–89), and 83% cases were adenocarcinoma. NGS‐based genomic profiling of major lung cancer‐related genes was performed on formalin‐fixed paraffin‐embedded tumor samples and matched blood.
Results
Approximately 73.9% of patients with NSCLC harbored at least one actionable alteration recommended by the National Comprehensive Cancer Network guideline, including epidermal growth factor receptor (EGFR), ALK, ERBB2, MET, BRAF, RET, and ROS1. Twenty‐seven patients (2.2%) harbored inherited germline mutations of cancer susceptibility genes. The frequencies of EGFR genomic alterations (both mutations and amplification) and ALK rearrangement were identified as 50.1% and 7.8% in Chinese NSCLC populations, respectively, and significantly higher than the Western population. Fifty‐six distinct uncommon EGFR mutations other than L858R, exon19del, exon20ins, or T790M were identified in 18.9% of patients with EGFR‐mutant NSCLC. About 7.4% of patients harbored both sensitizing and uncommon mutations, and 11.6% of patients harbored only uncommon EGFR mutations. The uncommon EGFR mutations more frequently combined with the genomic alterations of ALK, CDKN2A, NTRK3, TSC2, and KRAS. In patients <40 years of age, the ALK‐positive percentage was up to 28.2%. Moreover, 3.2% of ALK‐positive patients harbored multi ALK rearrangements, and seven new partner genes were identified.
Conclusion
More unique features of cancer driver genes in Chinese NSCLC were identified by next‐generation sequencing. These findings highlighted that NGS technology is more feasible and necessary than other molecular testing methods, and suggested that the special strategies are needed for drug development and targeted therapy for Chinese patients with NSCLC.
Implications for Practice
Molecular targeted therapy is now the standard first‐line treatment for patients with advanced non‐small cell lung cancer (NSCLC). Samples of 1,200 Chinese patients with NSCLC were analyzed through next‐generation sequencing to characterize the unique feature of uncommon EGFR mutations and ALK fusion. The results showed that 7.4% of EGFR‐mutant patients harbored both sensitizing and uncommon mutations and 11.6% harbored only uncommon mutations. Uncommon EGFR mutations more frequently combined with the genomic alterations of ALK, CDKN2A, NTRK3, TSC2, and KRAS. ALK fusion was more common in younger patients, and the frequency decreased monotonically with age. 3.2% of ALK‐positive patients harbored multi ALK rearrangement, and seven new partner genes were identified.
Lung cancer is the most fatal malignancy in China. This study assessed genomic alterations of driver genes in a cohort of Chinese patients with non‐small cell lung cancer. This article reports the resulting analysis of germline mutations, EGFR variations, and ALK rearrangements, the most common and important driver genes in Chinese NSCLC population.
Microsphere technology serves as an efficient and effective platform for cell applications ( in vitro cell culture and in vivo cell delivery) due to its mimicry of the 3D native environment, high ...surface area:volume ratio, and ability to isolate the entrapped cells from the environment. Properties of cell-laden microspheres are determined by the type of application and the cell. While high cell densities are preferable for large-scale therapeutic biomolecule production in vitro , an immunoprotective barrier is most important for allogeneic pancreatic islet transplantation into patients. Furthermore, the biological cells require a suitable microenvironment in terms of its physical and biochemical properties. Here, we discuss applications of cell-laden microspheres and their corresponding design parameters.
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