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1.
Mol Biol Evol ; 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38885310

ABSTRACT

Large-scale genomic projects and ancient DNA innovations have ushered in a new paradigm for exploring human evolutionary history. However, the genetic legacy of spatiotemporally diverse ancient Eurasians within Chinese paternal lineages remains unresolved. Here, we report an integrated Y-chromosome genomic database encompassing 15,563 individuals from both modern and ancient Eurasians, including 919 newly reported individuals, to investigate Chinese paternal genomic diversity. The high-resolution, time-stamped phylogeny reveals multiple diversification events and extensive expansions in the early and middle Neolithic. We identify four major ancient population movements, each associated with technological innovations, that have shaped the Chinese paternal landscape. Firstly, the expansion of early East Asians and millet farmers from the Yellow River Basin, predominantly carrying O2/D subclades, significantly influenced the formation of the Sino-Tibetan people and facilitated the permanent settlement of the Tibetan Plateau. Secondly, the dispersal of rice farmers from the Yangtze River Valley, carrying O1 and certain O2 sublineages, reshapes the genetic makeup of southern Han Chinese, as well as the Tai-Kadai, Austronesian, Hmong-Mien, and Austroasiatic people. Thirdly, Neolithic Siberian Q/C paternal lineages originated and proliferated among hunter-gatherers on the Mongolian Plateau and the Amur River Basin, leaving a significant imprint on the gene pools of northern China. Fourthly, J/G/R paternal lineages derived from western Eurasia, which were initially spread by Yamnaya-related steppe pastoralists, maintain their presence primarily in northwestern China. Overall, our research provides comprehensive genetic evidence elucidating the significant impact of interactions with culturally distinct ancient Eurasians on the patterns of paternal diversity in modern Chinese populations.

2.
BMC Genomics ; 25(1): 611, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38890579

ABSTRACT

BACKGROUND: Ancient northern East Asians (ANEA) from the Yellow River region, who pioneered millet cultivation, play a crucial role in understanding the origins of ethnolinguistically diverse populations in modern China and the entire landscape of deep genetic structure and variation discovery in modern East Asians. However, the direct links between ANEA and geographically proximate modern populations, as well as the biological adaptive processes involved, remain poorly understood. RESULTS: Here, we generated genome-wide SNP data for 264 individuals from geographically different Han populations in Shandong. An integrated genomic resource encompassing both modern and ancient East Asians was compiled to examine fine-scale population admixture scenarios and adaptive traits. The reconstruction of demographic history and hierarchical clustering patterns revealed that individuals from the Shandong Peninsula share a close genetic affinity with ANEA, indicating long-term genetic continuity and mobility in the lower Yellow River basin since the early Neolithic period. Biological adaptive signatures, including those related to immune and metabolic pathways, were identified through analyses of haplotype homozygosity and allele frequency spectra. These signatures are linked to complex traits such as height and body mass index, which may be associated with adaptations to cold environments, dietary practices, and pathogen exposure. Additionally, allele frequency trajectories over time and a haplotype network of two highly differentiated genes, ABCC11 and SLC10A1, were delineated. These genes, which are associated with axillary odor and bilirubin metabolism, respectively, illustrate how local adaptations can influence the diversification of traits in East Asians. CONCLUSIONS: Our findings provide a comprehensive genomic dataset that elucidates the fine-scale genetic history and evolutionary trajectory of natural selection signals and disease susceptibility in Han Chinese populations. This study serves as a paradigm for integrating spatiotemporally diverse ancient genomes in the era of population genomic medicine.


Subject(s)
Genetics, Population , Haplotypes , Polymorphism, Single Nucleotide , Humans , China , Genomics , Evolution, Molecular , Gene Frequency , Asian People/genetics , Genome, Human
3.
PLoS One ; 19(4): e0300662, 2024.
Article in English | MEDLINE | ID: mdl-38630758

ABSTRACT

PURPOSE: To explore the feasibility and validity of machine learning models in determining causality in medical malpractice cases and to try to increase the scientificity and reliability of identification opinions. METHODS: We collected 13,245 written judgments from PKULAW.COM, a public database. 963 cases were included after the initial screening. 21 medical and ten patient factors were selected as characteristic variables by summarising previous literature and cases. Random Forest, eXtreme Gradient Boosting (XGBoost) and Light Gradient Boosting Machine (LightGBM) were used to establish prediction models of causality for the two data sets, respectively. Finally, the optimal model is obtained by hyperparameter tuning of the six models. RESULTS: We built three real data set models and three virtual data set models by three algorithms, and their confusion matrices differed. XGBoost performed best in the real data set, with a model accuracy of 66%. In the virtual data set, the performance of XGBoost and LightGBM was basically the same, and the model accuracy rate was 80%. The overall accuracy of external verification was 72.7%. CONCLUSIONS: The optimal model of this study is expected to predict the causality accurately.


Subject(s)
Malpractice , Orthopedics , Humans , Reproducibility of Results , China , Machine Learning
4.
Heliyon ; 10(5): e26712, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38434364

ABSTRACT

The aims of this study were to explore the protective effect of Xiaochaihu decoction in mice with sepsis induced by intraperitoneal injection; to explore its anti-inflammatory effect on the TLR4-MyD88-NF-κB signalling pathway; and to explore the main material basis of the anti-inflammatory effect of Xiaochaihu decoction, with the aim of supplementing and expanding the associated research and providing a scientific foundation for the clinical use of the decoction. The effects of Xiaochaihu decoction on septic mice were analysed by measurements of white blood cells (WBC) and Platelets (PLT); Nitric Oxide (NO) level in serum; IL-6, IL-1ß and TNF-α levels in serum; RT-PCR; Haematoxylin-Eosin (HE) immunohistochemistry; western blotting (WB). The results showed the excellent in vivo anti-inflammatory effects of Xiaochaihu decoction in LPS-induced septic mice, through down regulation of the gene and protein expression of TLR4, MYD88, TRAF6, IKK, IKBα and p65 and the subsequent reduction in the release of inflammatory mediators IL-6, IL-1ß, TNF-α and NO. Moreover, significant anti-septic effect was observed from high and medium doses of Xiaochaihu decoction, but not from the low dose.

5.
Anal Chem ; 96(11): 4657-4664, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38456390

ABSTRACT

Polyvinyl alcohol (PVA) with abundant hydroxyl groups (-OH) has been widely used for membranes, hydrogels, and films, and its function is largely affected by the alcoholysis degree. Therefore, the development of rapid and accurate methods for alcoholysis degree determination in PVAs is important. In this contribution, we have proposed a novel fluorescence-based platform for probing the alcoholysis degree of PVA by using the (E)-N-(4-methoxyphenyl)-1-(quinolin-2-yl)methanimine (QPM)-Zn2+ complex as the reporter. The mechanism study disclosed that the strong coordination between -OH and Zn2+ induced the capture of the QPM-Zn2+ complex and promoted its subsequent immobilization into the noncrystalline area. The immobilization of the QPM-Zn2+ complex restricted its molecular rotation and reduced the nonirradiative transition, thus yielding bright emissions. In addition, the practical applications of this proposed method were further validated by the accurate alcoholysis degree determination of blind PVA samples with the confirmation of the National Standard protocol. It is expected that the developed fluorescence approach in this work might become an admissive strategy for screening the alcoholysis degree of PVA.

6.
Environ Sci Pollut Res Int ; 31(8): 11622-11632, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38221561

ABSTRACT

Identification of the transport of sulfonamide antibiotics in soils facilitates a better understanding of the environmental fate and behaviors of these ubiquitous contaminants. In this study, the mobility properties of sulfanilamide (SNM, a typical sulfonamide antibiotic) through saturated soils with different physicochemical characteristics were investigated. The results showed that the physicochemical characteristics controlled SNM mobility. Generally, the mobility of SNM was positively correlated with CEC values and soil organic matter content, which was mainly related to the interactions between the organic matter in soils and SNM molecules via π-π stacking, H-bonding, ligand exchange, and hydrophobic interaction. Furthermore, higher clay mineral content and lower sand content were beneficial for restraining SNM transport in the soils. Unlike Na+, Cu2+ ions could act as bridging agents between the soil grains and SNM molecules, contributing to the relatively weak transport of SNM. Furthermore, the trend of SNM mobility in different soil columns was unaffected by solution pH (5.0-9.0). Meanwhile, for a given soil, the SNM mobility was promoted as the solution pH values increased, which was caused by the enhanced electrostatic repulsion between SNM- species and soil particles as well as the declined hydrophobic interaction between SNM and soil organic matter. The obtained results provide helpful information for the contribution of soil physicochemical characteristics to the transport behaviors of sulfonamide antibiotics in soil-water systems.


Subject(s)
Soil Pollutants , Soil , Sulfanilamide , Soil/chemistry , Porosity , Soil Pollutants/analysis , Anti-Bacterial Agents/chemistry , Sulfonamides , Adsorption
7.
Anal Chim Acta ; 1287: 342059, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38182367

ABSTRACT

BACKGROUND: The selective recognition of drugs and its metabolism or decomposition products is significant to drug development and drug resistance research. Fluorescence-based techniques provide satisfying sensitivity by target-triggered chemical reaction. However, the interference from the matrix or additives usually restricts the specific detection. It is highly desirable to explore specific chemical reactions for achieving selective perception of these species. RESULTS: We report a specific m-aminophenol (MAP)-dopamine (DA) reaction, which generates highly fluorescent azamonardine-like products. Based on this reaction, fluorometric and indirect detection of p-aminosalicylic acid (typical antituberculosis drug, PAS) can be realized using the DA-based probe with high sensitivity. The acid induces the decarboxylation of PAS and produces MAP, which reacts with DA and generates fluorescent azamonardine-like products. The practical application of the proposed method is validated by the accurate PAS analysis in urine samples and Pasinazid tablets. Interestingly, none of additives in the Pasinazid tablets contribute comparable fluorescence variation. SIGNIFICANCE: This work discovers a new MAP-DA reaction for the first time, it not only explores sensitive PAS drug detection probe, but also demonstrates the feasibility of the development of novel drug analysis platform by recognizing decomposition product with specific reaction. Thus, new avenues for the exploration of simple and rapid spectrophotometric probes toward various drug analytes with high specify and sensitivity based on this tactic might be possible in analytical and drug-related fields.


Subject(s)
Aminosalicylic Acid , Dopamine , Spectrophotometry , Fluorometry , Biological Assay , Coloring Agents
8.
ACS Catal ; 13(24): 15977-15990, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38125976

ABSTRACT

The development of selective catalysts for direct conversion of ammonia into nitrous oxide, N2O, will circumvent the conventional five-step manufacturing process and enable its wider utilization in oxidation catalysis. Deviating from commonly accepted catalyst design principles for this reaction, reliant on manganese oxide, we herein report an efficient system comprised of isolated chromium atoms (1 wt %) stabilized in the ceria lattice by coprecipitation. The latter, in contrast to a simple impregnation approach, ensures firm metal anchoring and results in stable and selective N2O production over 100 h on stream up to 79% N2O selectivity at full NH3 conversion. Raman, electron paramagnetic resonance, and in situ UV-vis spectroscopies reveal that chromium incorporation enhances the density of oxygen vacancies and the rate of their generation and healing. Accordingly, temporal analysis of products, kinetic studies, and atomistic simulations show lattice oxygen of ceria to directly participate in the reaction, establishing the cocatalytic role of the carrier. Coupled with the dynamic restructuring of chromium sites to stabilize intermediates of N2O formation, these factors enable catalytic performance on par with or exceeding benchmark systems. These findings demonstrate how nanoscale engineering can elevate a previously overlooked metal into a highly competitive catalyst for selective ammonia oxidation to N2O, paving the way toward industrial implementation.

9.
J Genet Genomics ; 2023 Oct 11.
Article in English | MEDLINE | ID: mdl-37827489

ABSTRACT

Tibeto-Burman (TB) people have endeavored to adapt to the hypoxic, cold, and high-UV high-altitude environments in the Tibetan Plateau and complex disease exposures in lowland rainforests since the late Paleolithic period. However, the full landscape of genetic history and biological adaptation of geographically diverse TB-speaking people, as well as their interaction mechanism, remain unknown. Here, we generate a whole-genome meta-database of 500 individuals from 39 TB-speaking populations and present a comprehensive landscape of genetic diversity, admixture history, and differentiated adaptative features of geographically different TB-speaking people. We identify genetic differentiation related to geography and language among TB-speaking people, consistent with their differentiated admixture process with incoming or indigenous ancestral source populations. A robust genetic connection between the Tibetan-Yi corridor and the ancient Yellow River people supports their Northern China origin hypothesis. We finally report substructure-related differentiated biological adaptative signatures between highland Tibetans and Loloish speakers. Adaptative signatures associated with the physical pigmentation (EDAR and SLC24A5) and metabolism (ALDH9A1) are identified in Loloish people, which differed from the high-altitude adaptative genetic architecture in Tibetan. TB-related genomic resources provide new insights into the genetic basis of biological adaptation and better reference for the anthropologically informed sampling design in biomedical and genomic cohort research.

10.
J Nanobiotechnology ; 21(1): 331, 2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37715178

ABSTRACT

Although photothermal therapy (PTT) employing nanozymes has shown excellent antibacterial potential, excessive heating generally harms host cells and hinders recovery. Herein, we report an innovative technique for acquiring the programmed temperature by managing the catalytic activity of nanozymes. The photothermal system of CeO2 + F- + TMB can obtain precise photothermal temperature by adjusting the concentration of fluoride ions under near-infrared irradiation. At the optimized photothermal temperature, the photothermal system affords fine photothermal antibacterial treatment with high-efficiency antibacterial effects against Staphylococcus aureus and Escherichia coli in vitro. In vivo wound healing experiments confirm that the system can effectively promote fibroblast proliferation, angiogenesis and collagen deposition with remarkable wound healing efficiency. This strategy offers a novel design concept for creating a new generation of PTT and opens the way for the creation of alternative antibiotics.


Subject(s)
Diathermy , Fluorides , Wound Healing , Anti-Bacterial Agents/pharmacology , Bacteria , Escherichia coli
11.
Materials (Basel) ; 16(12)2023 Jun 14.
Article in English | MEDLINE | ID: mdl-37374569

ABSTRACT

Transformers, reactors and other electrical equipment often work under harmonics and DC-bias working conditions. It is necessary to quickly and accurately simulate the hysteresis characteristics of soft magnetic materials under various excitation conditions in order to achieve accurate calculations of core loss and the optimal design of electrical equipment. Based on Preisach hysteresis model, a parameter identification method for asymmetric hysteresis loop simulation is designed and applied to the simulation of hysteresis characteristics under bias conditions of oriented silicon steel sheets. In this paper, the limiting hysteresis loops of oriented silicon steel sheets are obtained through experiments under different working conditions. The first-order reversal curves(FORCs) with asymmetric characteristics is generated numerically, and then the Everett function is established under different DC bias conditions. The hysteresis characteristics of the oriented silicon steel sheets under harmonics and DC bias are simulated by improving FORCs identification method of the Preisach model. By comparing the results of simulation and experiment, the effectiveness of the proposed method is verified, so as to provide an important reference for material production and application.

12.
Front Med (Lausanne) ; 10: 1304369, 2023.
Article in English | MEDLINE | ID: mdl-38188339

ABSTRACT

Background: Gram-negative bacteria is a global public health problem. Treatment options include novel beta-lactamase inhibitors. Objectives: The objective of this study was to collect information on the efficacy and safety of novel ß-lactamase inhibitor combinations such as imipenem-cilastatin/relebactam (IMI/REL). Methods: In order to comprehensively evaluate the clinical, microbiological, and adverse events outcomes, a meta-analysis was conducted on clinical trials comparing novel ß-lactamase inhibitor combinations with existing comparator therapies. Results: Four studies comprising 948 patients were included in the analysis. IMI/REL therapy demonstrated similar clinical responses to comparators across various treatment visits, including discontinuation of intravenously administered therapy visits [DCIV, RR = 1.00 (0.88, 1.12)], early follow-up visits [EFU, RR = 1.00 (0.89, 1.14)], late follow-up visits [LFU, RR = 1.00 (0.88, 1.13)]. Moreover, no significant difference in the microbiologic response of MITT patients was observed between IMI/REL and comparators across DCIV [RR = 0.99 (0.89, 1.11)], EFU [RR = 1.01 (0.95, 1.07)], and LFU visits [RR = 1.00 (90.94, 1.07)]. In terms of safety, therapy with IMI/REL and comparators exhibited similar risks of at least one adverse event (AE), drug-related AEs, and discontinuation due to AEs. The incidence of serious AEs (SAEs) was significantly lower in the IMI/REL group compared to the comparison groups. The predominant AEs were gastrointestinal disorders, with no significant difference observed between the IMI/REL group and comparators. Conclusion: The clinical and microbiologic response to IMI/REL in the treatment of bacterial infection was comparable to that of the comparator. Furthermore, the incidence of AEs and the tolerability of IMI/REL were similar among the comparators. Based on these findings, IMI/REL can be considered as a viable alternative treatment option.

13.
Cells ; 11(24)2022 12 12.
Article in English | MEDLINE | ID: mdl-36552777

ABSTRACT

Dynein axonemal heavy chain 5 (DNAH5) is the most mutated gene in primary ciliary dyskinesia (PCD), leading to abnormal cilia ultrastructure and function. Few studies have revealed the genetic characteristics and pathogenetic mechanisms of PCD caused by DNAH5 mutation. Here, we established a child PCD airway organoid directly from the bronchoscopic biopsy of a patient with the DNAH5 mutation. The motile cilia in the organoid were observed and could be stably maintained for an extended time. We further found abnormal ciliary function and a decreased immune response caused by the DNAH5 mutation through single-cell RNA sequencing (scRNA-Seq) and proteomic analyses. Additionally, the directed induction of the ciliated cells, regulated by TGF-ß/BMP and the Notch pathway, also increased the expression of inflammatory cytokines. Taken together, these results demonstrated that the combination of multiomics analysis and organoid modelling could reveal the close connection between the immune response and the DNAH5 gene.


Subject(s)
Axonemal Dyneins , Kartagener Syndrome , Child , Humans , Axonemal Dyneins/genetics , Kartagener Syndrome/genetics , Transforming Growth Factor beta , Multiomics , Proteomics , Organoids , Cell Differentiation/genetics
14.
ACS Appl Bio Mater ; 2022 Aug 15.
Article in English | MEDLINE | ID: mdl-35969274

ABSTRACT

Traditional Chinese herbal medicine (TCHM) is the naturally available pharmaceutical with millennia of evolution from ancient China, capable of a superior therapeutic index and minimized unwanted effects on the human body. This work presents a therapeutic microrobotic platform based on pollen typhae (PT), a typical type of TCHM, fabricated by coating porous PT microspheres with Fe3O4 nanoparticles (PT robots) via electrostatic adsorption. The PT robots exhibit effective and controllable motion in various biological media upon external magnetic control and, meanwhile, preserve the inherent hemostasis property of PT. The blood clotting capacity of PT robots is attributed to their stimulation of the endogenous blood coagulation pathway and platelets with increased counts, which could be further improved by their effective magnetic propulsion. The remote magnetic control also allows the manipulation of PT robots in mice stomach, inducing enhanced binding and prolonged retention of PT robots in stomach mucosa. Moreover, PT robots upon magnetic control show an enhanced hemostatic effect in treating the mice bearing acute gastric bleeding compared with other passive groups. This work offers a facile and feasible route to integrate TCHM with manmade micromachines possessing the innate curative features of TCHM. Such a design expanded the versatility of microrobots and can be generalized to vast types of TCHM for broader biomedical applications.

15.
Adv Mater ; 34(26): e2201042, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35452560

ABSTRACT

A unique robotic medical platform is designed by utilizing cell robots as the active "Trojan horse" of oncolytic adenovirus (OA), capable of tumor-selective binding and killing. The OA-loaded cell robots are fabricated by entirely modifying OA-infected 293T cells with cyclic arginine-glycine-aspartic acid tripeptide (cRGD) to specifically bind with bladder cancer cells, followed by asymmetric immobilization of Fe3 O4 nanoparticles (NPs) on the cell surface. OA can replicate in host cells and induce cytolysis to release the virus progeny to the surrounding tumor sites for sustainable infection and oncolysis. The asymmetric coating of magnetic NPs bestows the cell robots with effective movement in various media and wireless manipulation with directional migration in a microfluidic device and bladder mold under magnetic control, further enabling steerable movement and prolonged retention of cell robots in the mouse bladder. The biorecognition of cRGD and robust, controllable propulsion of cell robots work synergistically to greatly enhance their tissue penetration and anticancer efficacy in the 3D cancer spheroid and orthotopic mouse bladder tumor model. Overall, this study integrates cell-based microrobots with virotherapy to generate an attractive robotic system with tumor specificity, expanding the operation scope of cell robots in biomedical community.


Subject(s)
Oncolytic Viruses , Robotics , Urinary Bladder Neoplasms , Adenoviridae/genetics , Animals , Cell Line, Tumor , Magnetic Phenomena , Mice , Urinary Bladder Neoplasms/therapy
16.
Angew Chem Int Ed Engl ; 61(22): e202116517, 2022 May 23.
Article in English | MEDLINE | ID: mdl-35244964

ABSTRACT

Alkali metal promoters have been widely employed for preparation of heterogeneous catalysts used in many industrially important reactions. However, the fundamentals of their effects are usually difficult to access. Herein, we unravel mechanistic and kinetic aspects of the role of alkali metals in CO2 hydrogenation over Fe-based catalysts through state-of-the-art characterization techniques, spatially resolved steady-state and transient kinetic analyses. The promoters affect electronic properties of iron in iron carbides. These carbide characteristics determine catalyst ability to activate H2 , CO and CO2 . The Allen scale electronegativity of alkali metal promoter was successfully correlated with the rates of CO2 hydrogenation to higher hydrocarbons and CH4 as well as with the rate constants of individual steps of CO or CO2 activation. The derived knowledge can be valuable for designing and preparing catalysts applied in other reactions where such promoters are also used.

17.
Nucleic Acids Res ; 50(11): e66, 2022 06 24.
Article in English | MEDLINE | ID: mdl-35288753

ABSTRACT

Alternative polyadenylation increases transcript diversities at the 3' end, regulating biological processes including cell differentiation, embryonic development and cancer progression. Here, we present a Bayesian method SCAPE, which enables de novo identification and quantification of polyadenylation (pA) sites at single-cell level by utilizing insert size information. We demonstrated its accuracy and robustness and identified 31 558 sites from 36 mouse organs, 43.8% (13 807) of which were novel. We illustrated that APA isoforms were associated with miRNAs binding and regulated in tissue-, cell type-and tumor-specific manners where no difference was found at gene expression level, providing an extra layer of information for cell clustering. Furthermore, we found genome-wide dynamic changes of APA usage during erythropoiesis and induced pluripotent stem cell (iPSC) differentiation, suggesting APA contributes to the functional flexibility and diversity of single cells. We expect SCAPE to aid the analyses of cellular dynamics and diversities in health and disease.


Subject(s)
Induced Pluripotent Stem Cells , MicroRNAs , 3' Untranslated Regions/genetics , Animals , Bayes Theorem , Cell Differentiation/genetics , Induced Pluripotent Stem Cells/metabolism , Mice , MicroRNAs/genetics , MicroRNAs/metabolism , Polyadenylation
18.
ACS Appl Mater Interfaces ; 13(49): 58382-58392, 2021 Dec 15.
Article in English | MEDLINE | ID: mdl-34860489

ABSTRACT

Utilizing spermatozoa as the engine unit of robotic systems at a microscale has brought revolutionized inspirations and strategies to the biomedical community. However, the motility of sperms is impaired by the surrounding threats. For example, the antisperm antibody (AsA) can specifically bind with surface antigens on the sperm membrane and adversely affect their propulsion, hindering the operation of sperm-based microrobots in practical environments. In the present work, we report a biohybrid sperm microrobot by encapsulating sperm cells within metal-organic frameworks (MOFs) and zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (NPs) (ZIFSpermbot), capable of active drug delivery and cytoprotection from the biological threats of AsA. ZIF-8 NPs can be facilely coated on the sperm membrane through complexation with tannic acid. Such cell surface engineering has a negligible impact on sperm motility under optimized conditions. The selective permeability of the resulting porous ZIF-8 wrappings protects ZIFSpermbots from the specific binding of AsA, enabling the preservation of intrinsic propulsion of the sperm engine. Besides, ZIF-8 wrappings sustainably release zinc ions and attenuate the oxidative damage generated in sperm cells, allowing the maintenance of sperm movement. Combining the effective protection of sperm propulsion with the drug-loading capacity of ZIF-8 NPs provides new applicability to ZIFSpermbots in risky surroundings with AsA, exhibiting rapid migration in a microfluidic device for active drug delivery with enhanced therapeutic efficacy due to their retained effective propulsion. Imparting bioengine-based microrobots with multifunctional wrappings holds great promise for designing adaptive cell robots that endure harsh environments toward locally extended and diverse operations, facilitating their use in practical and clinical applications.


Subject(s)
Antibiotics, Antineoplastic/pharmacology , Doxorubicin/pharmacology , Drug Delivery Systems , Exoskeleton Device , Metal-Organic Frameworks/pharmacology , Sperm Motility/drug effects , Antibiotics, Antineoplastic/chemistry , Doxorubicin/chemistry , Humans , Lab-On-A-Chip Devices , Male , Materials Testing , Metal-Organic Frameworks/chemistry , Optical Imaging
19.
Opt Lett ; 46(20): 5284-5287, 2021 Oct 15.
Article in English | MEDLINE | ID: mdl-34653173

ABSTRACT

We proposed a nonconservative coupling scheme based on the add-drop filter configuration, in which a high Q factor passive microtoroid resonator is indirectly driven by an active unit, thus providing an additional coupling which might be comparable to a mode decay rate. Extraordinary scattering points are predicted when one of the supermodes becomes lossless. Specifically, when the inherent coupling strength is set at half of the mode's total decay rate, controllable transmission peaks can be realized by tuning the nonconservative coupling strength and phase delay. Our theoretic research might find potential application in tunable light steering based on non-Hermitian resonator systems.

20.
Cell Host Microbe ; 29(3): 489-502.e8, 2021 03 10.
Article in English | MEDLINE | ID: mdl-33548198

ABSTRACT

The SARS-CoV-2 virus, the causative agent of COVID-19, is undergoing constant mutation. Here, we utilized an integrative approach combining epidemiology, virus genome sequencing, clinical phenotyping, and experimental validation to locate mutations of clinical importance. We identified 35 recurrent variants, some of which are associated with clinical phenotypes related to severity. One variant, containing a deletion in the Nsp1-coding region (Δ500-532), was found in more than 20% of our sequenced samples and associates with higher RT-PCR cycle thresholds and lower serum IFN-ß levels of infected patients. Deletion variants in this locus were found in 37 countries worldwide, and viruses isolated from clinical samples or engineered by reverse genetics with related deletions in Nsp1 also induce lower IFN-ß responses in infected Calu-3 cells. Taken together, our virologic surveillance characterizes recurrent genetic diversity and identified mutations in Nsp1 of biological and clinical importance, which collectively may aid molecular diagnostics and drug design.


Subject(s)
COVID-19/immunology , COVID-19/virology , Interferon Type I/immunology , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Viral Nonstructural Proteins/genetics , A549 Cells , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Base Sequence , COVID-19/blood , Cell Line , Child , Child, Preschool , Chlorocebus aethiops , Female , Gene Deletion , Genomics , HEK293 Cells , Humans , Infant , Interferon Type I/blood , Interferon-beta/blood , Interferon-beta/metabolism , Male , Middle Aged , Molecular Epidemiology , Reverse Genetics , Vero Cells , Viral Nonstructural Proteins/immunology , Young Adult
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