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1.
Nature ; 602(7898): 657-663, 2022 02.
Article in English | MEDLINE | ID: mdl-35016194

ABSTRACT

The SARS-CoV-2 B.1.1.529 (Omicron) variant contains 15 mutations of the receptor-binding domain (RBD). How Omicron evades RBD-targeted neutralizing antibodies requires immediate investigation. Here we use high-throughput yeast display screening1,2 to determine the profiles of RBD escaping mutations for 247 human anti-RBD neutralizing antibodies and show that the neutralizing antibodies can be classified by unsupervised clustering into six epitope groups (A-F)-a grouping that is highly concordant with knowledge-based structural classifications3-5. Various single mutations of Omicron can impair neutralizing antibodies of different epitope groups. Specifically, neutralizing antibodies in groups A-D, the epitopes of which overlap with the ACE2-binding motif, are largely escaped by K417N, G446S, E484A and Q493R. Antibodies in group E (for example, S309)6 and group F (for example, CR3022)7, which often exhibit broad sarbecovirus neutralizing activity, are less affected by Omicron, but a subset of neutralizing antibodies are still escaped by G339D, N440K and S371L. Furthermore, Omicron pseudovirus neutralization showed that neutralizing antibodies that sustained single mutations could also be escaped, owing to multiple synergetic mutations on their epitopes. In total, over 85% of the tested neutralizing antibodies were escaped by Omicron. With regard to neutralizing-antibody-based drugs, the neutralization potency of LY-CoV016, LY-CoV555, REGN10933, REGN10987, AZD1061, AZD8895 and BRII-196 was greatly undermined by Omicron, whereas VIR-7831 and DXP-604 still functioned at a reduced efficacy. Together, our data suggest that infection with Omicron would result in considerable humoral immune evasion, and that neutralizing antibodies targeting the sarbecovirus conserved region will remain most effective. Our results inform the development of antibody-based drugs and vaccines against Omicron and future variants.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Immune Evasion/immunology , Neutralization Tests , SARS-CoV-2/immunology , Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/classification , Antibodies, Viral/classification , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/immunology , Cells, Cultured , Convalescence , Epitopes, B-Lymphocyte/chemistry , Epitopes, B-Lymphocyte/immunology , Humans , Immune Sera/immunology , Models, Molecular , Mutation , SARS-CoV-2/chemistry , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism
2.
PLoS Pathog ; 20(5): e1012230, 2024 May.
Article in English | MEDLINE | ID: mdl-38776321

ABSTRACT

While macrophage is one of the major type I interferon (IFN-I) producers in multiple tissues during viral infections, it also serves as an important target cell for many RNA viruses. However, the regulatory mechanism for the IFN-I response of macrophages to respond to a viral challenge is not fully understood. Here we report ADAP, an immune adaptor protein, is indispensable for the induction of the IFN-I response of macrophages to RNA virus infections via an inhibition of the conjugation of ubiquitin-like ISG15 (ISGylation) to RIG-I. Loss of ADAP increases RNA virus replication in macrophages, accompanied with a decrease in LPS-induced IFN-ß and ISG15 mRNA expression and an impairment in the RNA virus-induced phosphorylation of IRF3 and TBK1. Moreover, using Adap-/- mice, we show ADAP deficiency strongly increases the susceptibility of macrophages to RNA-virus infection in vivo. Mechanically, ADAP selectively interacts and functionally cooperates with RIG-I but not MDA5 in the activation of IFN-ß transcription. Loss of ADAP results in an enhancement of ISGylation of RIG-I, whereas overexpression of ADAP exhibits the opposite effect in vitro, indicating ADAP is detrimental to the RNA virus-induced ISGylation of RIG-I. Together, our data demonstrate a novel antagonistic activity of ADAP in the cell-intrinsic control of RIG-I ISGylation, which is indispensable for initiating and sustaining the IFN-I response of macrophages to RNA virus infections and replication.


Subject(s)
Adaptor Proteins, Signal Transducing , DEAD Box Protein 58 , Interferon Type I , Macrophages , Mice, Knockout , RNA Virus Infections , Ubiquitins , Animals , Macrophages/virology , Macrophages/metabolism , Macrophages/immunology , Mice , RNA Virus Infections/immunology , RNA Virus Infections/metabolism , Ubiquitins/metabolism , Ubiquitins/genetics , DEAD Box Protein 58/metabolism , Interferon Type I/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Cytokines/metabolism , Mice, Inbred C57BL , Humans , Receptors, Immunologic/metabolism , Interferon-beta/metabolism , RNA Viruses/immunology , Interferon Regulatory Factor-3/metabolism
3.
Nucleic Acids Res ; 52(9): 4969-4984, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38452206

ABSTRACT

Proteasome-mediated degradation of chromatin-bound NF-κB is critical in terminating the transcription of pro-inflammatory genes and can be triggered by Set9-mediated lysine methylation of the RelA subunit. However, the E3 ligase targeting methylated RelA remains unknown. Here, we find that two structurally similar substrate-recognizing components of Cullin-RING E3 ligases, WSB1 and WSB2, can recognize chromatin-bound methylated RelA for polyubiquitination and proteasomal degradation. We showed that WSB1/2 negatively regulated a subset of NF-κB target genes via associating with chromatin where they targeted methylated RelA for ubiquitination, facilitating the termination of NF-κB-dependent transcription. WSB1/2 specifically interacted with methylated lysines (K) 314 and 315 of RelA via their N-terminal WD-40 repeat (WDR) domains, thereby promoting ubiquitination of RelA. Computational modeling further revealed that a conserved aspartic acid (D) at position 158 within the WDR domain of WSB2 coordinates K314/K315 of RelA, with a higher affinity when either of the lysines is methylated. Mutation of D158 abolished WSB2's ability to bind to and promote ubiquitination of methylated RelA. Together, our study identifies a novel function and the underlying mechanism for WSB1/2 in degrading chromatin-bound methylated RelA and preventing sustained NF-κB activation, providing potential new targets for therapeutic intervention of NF-κB-mediated inflammatory diseases.


Subject(s)
Chromatin , Proteasome Endopeptidase Complex , Transcription Factor RelA , Ubiquitination , Humans , Chromatin/metabolism , HEK293 Cells , Lysine/metabolism , Methylation , NF-kappa B/metabolism , Proteasome Endopeptidase Complex/metabolism , Protein Binding , Proteolysis , Transcription Factor RelA/metabolism , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics
4.
Plant J ; 2024 May 11.
Article in English | MEDLINE | ID: mdl-38733630

ABSTRACT

Skin color is an important trait that determines the cosmetic appearance and quality of fruits. In cucumber, the skin color ranges from white to brown in mature fruits. However, the genetic basis for this important trait remains unclear. We conducted a genome-wide association study of natural cucumber populations, along with map-based cloning techniques, on an F2 population resulting from a cross between Pepino (with yellow-brown fruit skin) and Zaoer-N (with creamy fruit skin). We identified CsMYB60 as a candidate gene responsible for skin coloration in mature cucumber fruits. In cucumber accessions with white to pale yellow skin color, a premature stop mutation (C to T) was found in the second exon region of CsMYB60, whereas light yellow cucumber accessions exhibited splicing premature termination caused by an intronic mutator-like element insertion in CsMYB60. Transgenic CsMYB60c cucumber plants displayed a yellow-brown skin color by promoting accumulation of flavonoids, especially hyperoside, a yellow-colored flavonol. CsMYB60c encodes a nuclear protein that primarily acts as a transcriptional activator through its C-terminal activation motif. RNA sequencing and DNA affinity purification sequencing assays revealed that CsMYB60c promotes skin coloration by directly binding to the YYTACCTAMYT motif in the promoter regions of flavonoid biosynthetic genes, including CsF3'H, which encodes flavonoid 3'-hydroxylase. The findings of our study not only offer insight into the function of CsMYB60 as dominantly controlling fruit coloration, but also highlight that intronic DNA mutations can have a similar phenotypic impact as exonic mutations, which may be valuable in future cucumber breeding programs.

5.
Plant J ; 115(2): 414-433, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37036138

ABSTRACT

Sensory plastids are important in plant responses to environmental changes. Previous studies show that MutS HOMOLOG 1 (MSH1) perturbation in sensory plastids induces heritable epigenetic phenotype adjustment. Previously, the PsbP homolog DOMAIN-CONTAINING PROTEIN 3 (PPD3), a protein of unknown function, was postulated to be an interactor with MSH1. This study investigates the relationship of PPD3 with MSH1 and with plant environmental sensing. The ppd3 mutant displays a whole-plant phenotype variably altered in growth rate, flowering time, reactive oxygen species (ROS) modulation and response to salt, with effects on meristem growth. Present in both chloroplasts and sensory plastids, PPD3 colocalized with MSH1 in root tips but not in leaf tissues. The suppression or overexpression of PPD3 affected the plant growth rate and stress tolerance, and led to a heritable, heterogenous 'memory' state with both dwarfed and vigorous growth phenotypes. Gene expression and DNA methylome data sets from PPD3-OX and derived memory states showed enrichment in growth versus defense networks and meristem effects. Our results support a model of sensory plastid influence on nuclear epigenetic behavior and ppd3 as a second trigger, functioning within meristem plastids to recalibrate growth plasticity.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Arabidopsis/genetics , Plastids/genetics , Plastids/metabolism , Chloroplasts/metabolism , Epigenesis, Genetic , Gene Expression Regulation, Plant , MutS DNA Mismatch-Binding Protein/genetics , MutS DNA Mismatch-Binding Protein/metabolism
6.
EMBO J ; 39(2): e102201, 2020 01 15.
Article in English | MEDLINE | ID: mdl-31762063

ABSTRACT

The innate immune sensor NLRP3 assembles an inflammasome complex with NEK7 and ASC to activate caspase-1 and drive the maturation of proinflammatory cytokines IL-1ß and IL-18. NLRP3 inflammasome activity must be tightly controlled, as its over-activation is involved in the pathogenesis of inflammatory diseases. Here, we show that NLRP3 inflammasome activation is suppressed by a centrosomal protein Spata2. Spata2 deficiency enhances NLRP3 inflammasome activity both in the macrophages and in an animal model of peritonitis. Mechanistically, Spata2 recruits the deubiquitinase CYLD to the centrosome for deubiquitination of polo-like kinase 4 (PLK4), the master regulator of centrosome duplication. Deubiquitination of PLK4 facilitates its binding to and phosphorylation of NEK7 at Ser204. NEK7 phosphorylation in turn attenuates NEK7 and NLRP3 interaction, which is required for NLRP3 inflammasome activation. Pharmacological or shRNA-mediated inhibition of PLK4, or mutation of the NEK7 Ser204 phosphorylation site, augments NEK7 interaction with NLRP3 and causes increased NLRP3 inflammasome activation. Our study unravels a novel centrosomal regulatory pathway of inflammasome activation and may provide new therapeutic targets for the treatment of NLRP3-associated inflammatory diseases.


Subject(s)
Centrosome/immunology , Deubiquitinating Enzyme CYLD/metabolism , Inflammasomes/immunology , NIMA-Related Kinases/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Protein Serine-Threonine Kinases/metabolism , Proteins/physiology , Animals , Centrosome/metabolism , Cytokines/metabolism , Deubiquitinating Enzyme CYLD/genetics , Disease Models, Animal , Inflammasomes/metabolism , Macrophages/immunology , Macrophages/metabolism , Macrophages/pathology , Mice , Mice, Inbred C57BL , Mice, Knockout , NIMA-Related Kinases/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Peritonitis/immunology , Peritonitis/metabolism , Peritonitis/pathology , Phosphorylation , Protein Serine-Threonine Kinases/genetics , Signal Transduction , Ubiquitination
7.
Funct Integr Genomics ; 24(4): 116, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38910225

ABSTRACT

Chloroplasts are not only critical photosynthesis sites in plants, but they also participate in plastidial retrograde signaling in response to developmental and environmental signals. MEcPP (2-C-Methyl-D-erythritol-2,4-cyclopyrophosphate) is an intermediary in the methylerythritol phosphate (MEP) pathway in chloroplasts. It is a critical precursor for the synthesis of isoprenoids and terpenoid derivatives, which play crucial roles in plant growth and development, photosynthesis, reproduction, and defense against environmental constraints. Accumulation of MEcPP under stressful conditions triggers the expression of IMPα-9 and TPR2, contributing to the activation of abiotic stress-responsive genes. In this correspondence, we discuss plastidial retrograde signaling in support of a recently published paper in Molecular Plant (Zeng et al. 2024). We hope that it can shed more insight on the retrograde signaling cascade.


Subject(s)
Chloroplasts , Stress, Physiological , Chloroplasts/metabolism , Gene Expression Regulation, Plant , Signal Transduction , Arabidopsis/genetics , Arabidopsis/metabolism , Erythritol/metabolism , Erythritol/analogs & derivatives , Arabidopsis Proteins/metabolism , Arabidopsis Proteins/genetics , Sugar Phosphates/metabolism , MAP Kinase Kinase Kinase 5/metabolism , MAP Kinase Kinase Kinase 5/genetics
8.
Anal Chem ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38953491

ABSTRACT

The Tn antigen, an immature truncated O-glycosylation, is a promising biomarker for cancer detection and diagnosis. However, reliable methods for analyzing O-GalNAcylation and complex O-glycosylation are lacking. Here, we develop a novel method, MOTAI, for the sequential analysis of O-glycosylation using different O-glycoproteases. MOTAI conjugates glycopeptides on a solid support and releases different types of O-glycosylation through sequential enzymatic digestion by O-glycoproteases, including OpeRATOR and IMPa. Because OpeRATOR has less activity on O-GalNAcylation, MOTAI enriches O-GalNAcylation for subsequent analysis. We demonstrate the effectiveness of MOTAI by analyzing fetuin O-glycosylation and Jurkat cell lines. We then apply MOTAI to analyze colorectal cancer and benign colorectal polyps. We identify 32 Tn/sTn-glycoproteins and 43 T/sT-glycoproteins that are significantly increased in tumor tissues. Gene Ontology analysis reveals that most of these proteins are ECM proteins involved in the adhesion process of the intercellular matrix. Additionally, the protein disulfide isomerase CRELD2 has a significant difference in Tn expression, and the abnormally glycosylated T345 and S349 O-glycosylation sites in cancer group samples may promote the secretion of CRELD2 and ultimately tumorigenesis through ECM reshaping. In summary, MOTAI provides a powerful new tool for the in-depth analysis of O-GalNAcylation and complex O-glycosylation. It also reveals the upregulation of Tn/sTn-glycoproteins in colorectal cancer, which may provide new insights into cancer biology and biomarker discovery.

9.
Plant Biotechnol J ; 22(5): 1325-1334, 2024 May.
Article in English | MEDLINE | ID: mdl-38213067

ABSTRACT

Cytoplasmic male sterility (CMS), encoded by the mitochondrial open reading frames (ORFs), has long been used to economically produce crop hybrids. However, the utilization of CMS also hinders the exploitation of sterility and fertility variation in the absence of a restorer line, which in turn narrows the genetic background and reduces biodiversity. Here, we used a mitochondrial targeted transcription activator-like effector nuclease (mitoTALENs) to knock out ORF138 from the Ogura CMS broccoli hybrid. The knockout was confirmed by the amplification and re-sequencing read mapping to the mitochondrial genome. As a result, knockout of ORF138 restored the fertility of the CMS hybrid, and simultaneously manifested a cold-sensitive male sterility. ORF138 depletion is stably inherited to the next generation, allowing for direct use in the breeding process. In addition, we proposed a highly reliable and cost-effective toolkit to accelerate the life cycle of fertile lines from CMS-derived broccoli hybrids. By applying the k-mean clustering and interaction network analysis, we identified the central gene networks involved in the fertility restoration and cold-sensitive male sterility. Our study enables mitochondrial genome editing via mitoTALENs in Brassicaceae vegetable crops and provides evidence that the sex production machinery and its temperature-responsive ability are regulated by the mitochondria.


Subject(s)
Brassica , Infertility, Male , Male , Humans , Brassica/genetics , Transcription Activator-Like Effector Nucleases , Plant Breeding , Mitochondria/genetics , Fertility/genetics , Plant Infertility/genetics
10.
Mol Ecol ; 33(4): e17246, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38153177

ABSTRACT

Acclimatization through phenotypic plasticity represents a more rapid response to environmental change than adaptation and is vital to optimize organisms' performance in different conditions. Generally, animals are less phenotypically plastic than plants, but reef-building corals exhibit plant-like properties. They are light dependent with a sessile and modular construction that facilitates rapid morphological changes within their lifetime. We induced phenotypic changes by altering light exposure in a reciprocal transplant experiment and found that coral plasticity is a colony trait emerging from comprehensive morphological and physiological changes within the colony. Plasticity in skeletal features optimized coral light harvesting and utilization and paralleled significant methylome and transcriptome modifications. Network-associated responses resulted in the identification of hub genes and clusters associated to the change in phenotype: inter-partner recognition and phagocytosis, soft tissue growth and biomineralization. Furthermore, we identified hub genes putatively involved in animal photoreception-phototransduction. These findings fundamentally advance our understanding of how reef-building corals repattern the methylome and adjust a phenotype, revealing an important role of light sensing by the coral animal to optimize photosynthetic performance of the symbionts.


Subject(s)
Anthozoa , Animals , Anthozoa/genetics , Epigenome , Adaptation, Physiological , Phenotype , Transcriptome/genetics , Coral Reefs , Acclimatization/genetics
11.
Plant Physiol ; 193(2): 1001-1015, 2023 09 22.
Article in English | MEDLINE | ID: mdl-37394925

ABSTRACT

Cucumber (Cucumis sativus L.) flesh is typically colorless or pale green. Flesh with yellow or orange pigment, determined mainly by carotenoid content and composition, is mostly found in semi-wild Xishuangbanna cucumber, which has a very narrow genetic background. Here, we identified a spontaneous cucumber mutant with yellow flesh (yf-343), which accumulated more ß-cryptoxanthin and less lutein than regular cultivated European glasshouse-type cucumbers. Genetic analysis revealed that the yellow flesh phenotype was controlled by a single recessive gene. Through fine mapping and gene sequencing, we identified the candidate gene C. sativus yellow flesh 2 (Csyf2), encoding an abscisic acid (ABA) 8'-hydroxylase. Overexpression and RNAi-silencing of Csyf2 in cucumber hairy roots produced lower and higher ABA contents than in non-transgenic controls, respectively. Further, RNA-seq analysis suggested that genes related to ABA signal transduction were differentially expressed in fruit flesh between yf-343 and its wild type, BY, with white flesh. The carotenoid biosynthesis pathway was specifically enriched in fruit flesh at 30 days after pollination when yf-343 fruit flesh turns yellow. Our findings highlight a promising target for gene editing to increase carotenoid content, expanding our genetic resources for pigmented cucumber flesh breeding for improving the nutritional quality of cucumber.


Subject(s)
Cucumis sativus , Cucumis sativus/genetics , Plant Breeding , Plant Proteins/genetics , Plant Proteins/metabolism , Carotenoids/metabolism , Fruit/genetics
12.
Opt Express ; 32(3): 3308-3315, 2024 Jan 29.
Article in English | MEDLINE | ID: mdl-38297555

ABSTRACT

Mechanical strain can be used to tune the optical properties of monolayer transition metal dichalcogenides (1L-TMDs). Here, upconversion photoluminescence (UPL) from 1L-WSe2 flakes is tuned with biaxial strain induced by cruciform bending and indentation method. It is found that the peak position of UPL is redshifted by around 24 nm as the applied biaxial strain increases from 0% to 0.51%. At the same time, the UPL intensity increases exponentially for the upconversion energy difference that lies within a broad range between -157 meV to -37 meV. The observed linear and sublinear power dependence of UPL emission in 1L-WSe2 with and without biaxial strain at three different excitation wavelengths of 784 nm, 800 nm, and 820 nm indicates the multiphonon-assisted one-photon upconversion emission process. The results of strain-dependent UPL emission from 1L-TMDs pave a unique path to the advances in photon upconversion applications and optoelectronic devices.

13.
Opt Express ; 32(11): 20136-20145, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38859130

ABSTRACT

Integrating phase-change materials in metasurfaces has emerged as a powerful strategy to realize optical devices with tunable electromagnetic responses. Here, phase-change chiral metasurfaces based on GST-225 material with the designed trapezoid-shaped resonators are demonstrated to achieve tunable circular dichroism (CD) responses in the infrared regime. The asymmetric trapezoid-shaped resonators are designed to support two chiral plasmonic resonances with opposite CD responses for realizing switchable CD between negative and positive values using the GST phase change from amorphous to crystalline. The electromagnetic field distributions of the chiral plasmonic resonant modes are analyzed to understand the chiroptical responses of the metasurface. Furthermore, the variations in the absorption spectrum and CD value for the metasurface as a function of the baking time during the GST phase transition are analyzed to reveal the underlying thermal tuning process of the metasurface. The demonstrated phase-change metasurfaces with tunable CD responses hold significant promise in enabling many applications in the infrared regime such as chiral sensing, encrypted communication, and thermal imaging.

14.
J Exp Bot ; 75(10): 2951-2964, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38426564

ABSTRACT

Vessel traits contribute to plant water transport from roots to leaves and thereby influence how plants respond to soil water availability, but the sources of variation in fine root anatomical traits remain poorly understood. Here, we explore the variations of fine root vessel traits along topological orders within and across tropical tree species. Anatomical traits were measured along five root topological orders in 80 individual trees of 20 species from a tropical forest in southwestern China. We found large variations for most root anatomical traits across topological orders, and strong co-variations between vessel traits. Within species, theoretical specific xylem hydraulic conductivity (Kth) increased with topological order due to increased mean vessel diameter, size heterogeneity, and decreased vessel density. Across species, Kth was associated with vessel fraction in low-order roots and correlated with mean vessel diameter and vessel density in high-order roots, suggesting a shift in relative anatomical contributors to Kth from the second- to fifth-order roots. We found no clear relationship between Kth and stele: root diameter ratios. Our study shows strong variations in root vessel traits across topological orders and species, and highlights shifts in the anatomical underpinnings by varying vessel-related anatomical structures for an optimized water supply.


Subject(s)
Plant Roots , Trees , Xylem , Plant Roots/anatomy & histology , Plant Roots/physiology , Trees/physiology , Trees/anatomy & histology , Xylem/physiology , Xylem/anatomy & histology , Water/metabolism , Water/physiology , Tropical Climate , China
15.
Environ Sci Technol ; 58(10): 4691-4703, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38323401

ABSTRACT

The negative effects of air pollution, especially fine particulate matter (PM2.5, particles with an aerodynamic diameter of ≤2.5 µm), on human health, climate, and ecosystems are causing significant concern. Nevertheless, little is known about the contributions of emerging pollutants such as plastic particles to PM2.5 due to the lack of continuous measurements and characterization methods for atmospheric plastic particles. Here, we investigated the levels of fine plastic particles (FPPs) in PM2.5 collected in urban Shanghai at a 2 h resolution by using a novel versatile aerosol concentration enrichment system that concentrates ambient aerosols up to 10-fold. The FPPs were analyzed offline using the combination of spectroscopic and microscopic techniques that distinguished FPPs from other carbon-containing particles. The average FPP concentrations of 5.6 µg/m3 were observed, and the ratio of FPPs to PM2.5 was 13.2% in this study. The FPP sources were closely related to anthropogenic activities, which pose a potential threat to ecosystems and human health. Given the dramatic increase in plastic production over the past 70 years, this study calls for better quantification and control of FPP pollution in the atmosphere.


Subject(s)
Air Pollutants , Humans , Air Pollutants/analysis , Ecosystem , Environmental Monitoring/methods , China , Particulate Matter/analysis , Seasons , Aerosols/analysis
16.
Phys Chem Chem Phys ; 26(11): 8842-8849, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38426259

ABSTRACT

The metal-semiconductor (M-S) contact is usually an Ohmic contact or a Schottky contact, which greatly affects the electronic properties of devices, and it remains a huge challenge to realize a low-resistance Ohmic contact in a metal-semiconductor junction (MSJ). Herein, we systematically studied the band structures, electrostatic potential, charge transfer, Schottky barrier height of carriers, effective carrier masses, and tunneling probability of carriers of a germanene (Ge)/GaAs MSJ. The transition from the Schottky to the Ohmic contact can be caused by applying certain biaxial strains or electric fields, which weakens the Fermi level pinning (FLP) effect and reduces contact resistance. Meanwhile, the electron injection efficiency of Ge/(GaAs)As MSJ (PTB > 27%) is far superior to that of other two-dimensional (2D) vdW MSJs. This work indicates that Ge/GaAs heterostructures are the most compatible for applying high-effective 2D electronic nanodevices under controllable conditions.

17.
Langenbecks Arch Surg ; 409(1): 154, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714551

ABSTRACT

BACKGROUND: In recent years, there has been an increasing prevalence of patients with papillary thyroid microcarcinoma (PTMC) without lymph node involvement in medical centers worldwide. For patients who are unable to undergo active surveillance (AS) and are afraid of postoperative complications, conformal thyroidectomy may be a suitable option to ensure both preservation of function and complete removal of the tumor. METHODS: The patients in the cohort during 2010 to 2015 were retrospectively enrolled strictly following the inclusion and exclusion criteria. The observation and control groups were defined based on the surgical approach, with patients in the observation group undergoing conformal thyroidectomy and patients in the control group undergoing lobectomy. Event-free survival (EFS), the interval from initial surgery to the detection of recurrent or metastatic disease, was defined as the primary observation endpoint. RESULTS: A total of 319 patients were included in the study, with 124 patients undergoing conformal thyroidectomy and 195 patients undergoing lobectomy. When compared to lobectomy, conformal thyroidectomy demonstrated reduced hospital stays, shorter operative times, and lower rates of vocal cord paralysis and hypoparathyroidism. Furthermore, the mean bleeding volume during the operation and the rate of permanent hypothyroidism were also lower in the conformal thyroidectomy group than in the lobectomy group. However, there was no statistically significant difference observed in the 5- and 10-year EFS between the two groups. CONCLUSIONS: Conformal thyroidectomy had advantages in perioperative management and short-term complication rates, with an EFS that was not inferior to that of lobectomy. Thus, conformal thyroidectomy is a feasible option for low-risk PTMC patients.


Subject(s)
Carcinoma, Papillary , Thyroid Neoplasms , Thyroidectomy , Humans , Thyroidectomy/methods , Thyroidectomy/adverse effects , Female , Male , Thyroid Neoplasms/surgery , Thyroid Neoplasms/pathology , Thyroid Neoplasms/mortality , Retrospective Studies , Middle Aged , Carcinoma, Papillary/surgery , Carcinoma, Papillary/pathology , Carcinoma, Papillary/mortality , Adult , Follow-Up Studies , Feasibility Studies , Cohort Studies , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Treatment Outcome , Operative Time
18.
BMC Musculoskelet Disord ; 25(1): 213, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38481217

ABSTRACT

Osteoporosis is caused by the imbalance of osteoblasts and osteoclasts. The regulatory mechanisms of differentially expressed genes (DEGs) in pathogenesis of osteoporosis are of significant and needed to be further investigated. GSE100609 dataset downloaded from Gene Expression Omnibus (GEO) database was used to identified DEGs in osteoporosis patients. KEGG analysis was conducted to demonstrate signaling pathways related to enriched genes. Osteoporosis patients and the human mesenchymal stem cells (hMSCs) were obtained for in vivo and in vitro resaerch. Lentivirus construction and viral infection was used to knockdown genes. mRNA expression and protein expression were detected via qRT-PCR and western blot assay separately. Alkaline phosphatase (ALP) activity detection, alizarin Red S (ARS) staining, and expression of bone morphogenetic protein 2 (BMP2), osteocalcin (OCN) and Osterix were evaluated to determine osteoblast differentiation capacity. UL-16 binding protein 1 (ULBP1) gene was upregulated in osteoporosis and downregulated in differentiated hMSCs. Knockdown of ULBP1 increased ALP activity, mineralization ability evaluated by ARS staining, expression of BMP2, OCN and Osterix in differentiated hMSCs. Furthermore, rescue experiment demonstrated that suppressed ULBP1 boosted osteoblast differentiation by activating TNF-ß signaling pathway. Knockdown of ULBP1 gene could promoted osteoblast differentiation by activating TNF-ß signaling pathway in differentiated hMSCs. ULBP1 may be a the Achilles' heel of osteoporosis, and suppression of ULBP1 could be a promising treatment for osteoporosis.


Subject(s)
Mesenchymal Stem Cells , Osteoporosis , Humans , Carrier Proteins/metabolism , Cell Differentiation/genetics , Cells, Cultured , Lymphotoxin-alpha/metabolism , Mesenchymal Stem Cells/metabolism , Osteoblasts/metabolism , Osteocalcin/metabolism , Osteogenesis/genetics , Osteoporosis/genetics , Smad2 Protein/metabolism
19.
J Integr Neurosci ; 23(5): 93, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38812381

ABSTRACT

BACKGROUND: Magnetoencephalography (MEG) is a non-invasive imaging technique for directly measuring the external magnetic field generated from synchronously activated pyramidal neurons in the brain. The optically pumped magnetometer (OPM) is known for its less expensive, non-cryogenic, movable and user-friendly custom-design provides the potential for a change in functional neuroimaging based on MEG. METHODS: An array of OPMs covering the opposite sides of a subject's head is placed inside a magnetically shielded room (MSR) and responses evoked from the auditory cortices are measured. RESULTS: High signal-to-noise ratio auditory evoked response fields (AEFs) were detected by a wearable OPM-MEG system in a MSR, for which a flexible helmet was specially designed to minimize the sensor-to-head distance, along with a set of bi-planar coils developed for background field and gradient nulling. Neuronal current sources activated in AEF experiments were localized and the auditory cortices showed the highest activities. Performance of the hybrid optically pumped magnetometer-magnetoencephalography/electroencephalography (OPM-MEG/EEG) system was also assessed. CONCLUSIONS: The multi-channel OPM-MEG system performs well in a custom built MSR equipped with bi-planar coils and detects human AEFs with a flexible helmet. Moreover, the similarities and differences of auditory evoked potentials (AEPs) and AEFs are discussed, while the operation of OPM-MEG sensors in conjunction with EEG electrodes provides an encouraging combination for the exploration of hybrid OPM-MEG/EEG systems.


Subject(s)
Auditory Cortex , Electroencephalography , Evoked Potentials, Auditory , Magnetoencephalography , Humans , Magnetoencephalography/instrumentation , Evoked Potentials, Auditory/physiology , Auditory Cortex/physiology , Electroencephalography/instrumentation , Electroencephalography/methods , Adult , Male
20.
BMC Surg ; 24(1): 108, 2024 Apr 13.
Article in English | MEDLINE | ID: mdl-38615003

ABSTRACT

BACKGROUND: Postoperative hypoparathyroidism caused by parathyroid injury is a problem faced by thyroid surgeons. The current technologies for parathyroid imaging all have some defects. METHODS: Patients with differentiated thyroid carcinoma (DTC) who underwent unilateral thyroidectomy plus ipsilateral central lymph node dissection were recruited. We dissected the main trunk of the superior thyroid artery entering the thyroid gland and placed the venous indwelling tube into the artery. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated. RESULTS: A total of 132 patients enrolled in this single-arm clinical trial, 105 of them completed retrograde catheterization via the superior artery. The sensitivity was 69.23 and 83.33% respectively. The specificity was 72.91 and 64.89%. The accuracy was 72.91 and 64.89%. The PPV was 85.71 and 81.08%. The NPV was 22.58 and 45.45%. There were no patients with allergic reactions to the methylene blue, or methylene blue toxicity. CONCLUSIONS: Retrograde injection of methylene blue via the superior thyroid artery is an effective and safe method to visualize parathyroid glands. This method can accurately locate the target organ by ultraselecting the blood vessel and injecting the contrast agent while avoiding background contamination and reducing the amount of contrast agent. TRIAL REGISTRATION: Clinical trial registration numbers and date of registration: ChiCTR2300077263、02/11/2023.


Subject(s)
Parathyroid Glands , Thyroid Gland , Humans , Arteries , Contrast Media , Methylene Blue , Parathyroid Glands/diagnostic imaging , Parathyroid Glands/surgery , Thyroid Gland/diagnostic imaging , Thyroid Gland/surgery
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