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1.
Immunity ; 57(1): 106-123.e7, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38159573

RESUMO

When the filtrate of the glomerulus flows through the renal tubular system, various microscopic sediment particles, including mineral crystals, are generated. Dislodging these particles is critical to ensuring the free flow of filtrate, whereas failure to remove them will result in kidney stone formation and obstruction. However, the underlying mechanism for the clearance is unclear. Here, using high-resolution microscopy, we found that the juxtatubular macrophages in the renal medulla constitutively formed transepithelial protrusions and "sampled" urine contents. They efficiently sequestered and phagocytosed intraluminal sediment particles and occasionally transmigrated to the tubule lumen to escort the excretion of urine particles. Mice with decreased renal macrophage numbers were prone to developing various intratubular sediments, including kidney stones. Mechanistically, the transepithelial behaviors of medulla macrophages required integrin ß1-mediated ligation to the tubular epithelium. These findings indicate that medulla macrophages sample urine content and remove intratubular particles to keep the tubular system unobstructed.


Assuntos
Cálculos Renais , Rim , Camundongos , Animais , Macrófagos
2.
Immunity ; 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39116878

RESUMO

Hypertension is usually accompanied by elevated sympathetic tonicity, but how sympathetic hyperactivity is triggered is not clear. Recent advances revealed that microglia-centered neuroinflammation contributes to sympathetic excitation in hypertension. In this study, we performed a temporospatial analysis of microglia at both morphological and transcriptomic levels and found that microglia in the hypothalamic paraventricular nucleus (PVN), a sympathetic center, were early responders to hypertensive challenges. Vasculature analyses revealed that the PVN was characterized by high capillary density, thin vessel diameter, and complex vascular topology relative to other brain regions. As such, the PVN was susceptible to the penetration of ATP released from the vasculature in response to hemodynamic disturbance after blood pressure increase. Mechanistically, ATP ligation to microglial P2Y12 receptor was responsible for microglial inflammatory activation and the eventual sympathetic overflow. Together, these findings identified a distinct vasculature pattern rendering vulnerability of PVN pre-sympathetic neurons to hypertension-associated microglia-mediated inflammatory insults.

3.
Nano Lett ; 24(29): 8940-8947, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38989866

RESUMO

Two-dimensional magnet CrI3 is a promising candidate for spintronic devices. Using nonadiabatic molecular dynamics and noncollinear spin time-dependent density functional theory, we investigated hole spin relaxation in two-dimensional CrI3 and its dependence on magnetic configurations, impacted by spin-orbit and electron-phonon interactions. Driven by in-plane and out-of-plane iodine motions, the relaxation rates vary, extending from over half a picosecond in ferromagnetic systems to tens of femtoseconds in certain antiferromagnetic states due to significant spin fluctuations, associated with the nonadiabatic spin-flip in tuning to the adiabatic flip. Antiferromagnetic CrI3 with staggered layer magnetic order notably accelerates adiabatic spin-flip due to enhanced state degeneracy and additional phonon modes. Ferrimagnetic CrI3 shows a transitional behavior between ferromagnetic and antiferromagnetic types as the magnetic moment changes. These insights into the spin dynamics of CrI3 underscore its potential for rapid-response spintronic applications and advance our understanding of two-dimensional materials for spintronics.

4.
BMC Bioinformatics ; 25(1): 164, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664601

RESUMO

Multimodal integration combines information from different sources or modalities to gain a more comprehensive understanding of a phenomenon. The challenges in multi-omics data analysis lie in the complexity, high dimensionality, and heterogeneity of the data, which demands sophisticated computational tools and visualization methods for proper interpretation and visualization of multi-omics data. In this paper, we propose a novel method, termed Orthogonal Multimodality Integration and Clustering (OMIC), for analyzing CITE-seq. Our approach enables researchers to integrate multiple sources of information while accounting for the dependence among them. We demonstrate the effectiveness of our approach using CITE-seq data sets for cell clustering. Our results show that our approach outperforms existing methods in terms of accuracy, computational efficiency, and interpretability. We conclude that our proposed OMIC method provides a powerful tool for multimodal data analysis that greatly improves the feasibility and reliability of integrated data.


Assuntos
Análise de Célula Única , Análise por Conglomerados , Análise de Célula Única/métodos , Biologia Computacional/métodos , Humanos , Algoritmos
5.
J Am Chem Soc ; 146(1): 1167-1173, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38127733

RESUMO

Nonradiative multiphonon transitions play a crucial role in understanding charge carrier dynamics. To capture the non-Condon effect in nonadiabatic molecular dynamics (NA-MD), we develop a simple and accurate method to calculate noncrossing and crossing k-point NA coupling in momentum space on an equal footing and implement it with a trajectory surface hopping algorithm. Multiple k-point MD trajectories can provide sufficient nonzero momentum multiphonons coupled to electrons, and the momentum conservation is maintained during nonvertical electron transition. The simulations of indirect bandgap transition in silicon and intra- and intervalley transitions in graphene show that incorporation of the non-Condon effect is needed to correctly depict these types of charge dynamics. In particular, a hidden process is responsible for the delayed nonradiative electron-hole recombination in silicon: the thermal-assisted rapid trapping of an excited electron at the conduction band minimum by a long-lived higher energy state through a nonvertical transition extends charge carrier lifetime, approaching 1 ns, which is about 1.5 times slower than the direct bandgap recombination. For graphene, intervalley scattering takes place within about 225 fs, which can occur only when the intravalley relaxation proceeds to about 50 fs to gain enough phonon momentum. The intra- and intervalley scattering constitute energy relaxation, which completes within sub-500 fs. All the simulated time scales are in excellent agreement with experiments. The study establishes the underlying mechanisms for a long-lived charge carrier in silicon and valley scattering in graphene and underscores the robustness of the non-Condon approximation NA-MD method, which is suitable for rigid, soft, and large defective systems.

6.
J Am Chem Soc ; 146(28): 19547-19554, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38976802

RESUMO

We simulated hot-electron relaxation in black phosphorus using the nonadiabatic molecular dynamics (NA-MD) approach with a non-Condon effect in momentum space beyond the harmonic approximation. By comparing simulations at the Γ point in a large supercell with those using a few k-points in a smaller supercell─while maintaining the same number of electronic states within the same energy range, we demonstrate that both setups yield remarkably consistent energy relaxation times, regardless of the initial state energy. This consistency arises from the complementary effects of supercell size in real space and the number of k-points in the reciprocal space. This finding confirms that simulations at a single k-point in large size supercells are an effective approximation for NA-MD with a non-Condon effect. This approach offers significant advantages for complex photophysics, such as intervalley scattering and indirect bandgap charge recombination, and is particularly suitable for large systems without the need for a harmonic approximation.

7.
Rapid Commun Mass Spectrom ; 38(14): e9763, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38745395

RESUMO

OBJECTIVE: Carotid atherosclerosis is a chronic progressive vascular disease that can be complicated by stroke in severe cases. Prompt diagnosis and treatment of high-risk patients are quite difficult due to the lack of reliable clinical biomarkers. This study aimed to explore potential plaque metabolic markers of stroke-prone risk and relevant targets for pharmacological intervention. METHOD: Carotid intima and plaque sample tissues were obtained from 20 patients with cerebrovascular symptoms of carotid origin. An untargeted metabolomics approach based on liquid chromatography-tandem mass spectrometry was utilized to characterize the metabolic profiles of the tissues. Multivariate and univariate analysis tools were used. RESULTS: A total of 154 metabolites were significantly altered in carotid plaque when compared with thickened intima. Of these, 62 metabolites were upregulated, whereas 92 metabolites were downregulated. Support vector machines identified the 15 most important metabolites, such as N-(cyclopropylmethyl)-N'-phenylurea, 9(S)-HOTrE, ACar 12:2, quinoxaline-2,3-dithiol, and l-thyroxine, as biomarkers for high-risk plaques. Metabolic pathway analysis showed that abnormal purine and nucleotide metabolism, amino acid metabolism, glutathione metabolism, and vitamin metabolism may contribute to the occurrence and progression of carotid atherosclerotic plaque. CONCLUSIONS: Our study identifies the biomarkers and related metabolic mechanisms of carotid plaque, which is stroke-prone, and provides insights and ideas for the precise prevention and targeted intervention of the disease.


Assuntos
Biomarcadores , Metabolômica , Placa Aterosclerótica , Espectrometria de Massas em Tandem , Humanos , Espectrometria de Massas em Tandem/métodos , Masculino , Feminino , Biomarcadores/análise , Biomarcadores/metabolismo , Pessoa de Meia-Idade , Idoso , Placa Aterosclerótica/química , Placa Aterosclerótica/metabolismo , Metabolômica/métodos , Cromatografia Líquida/métodos , Doenças das Artérias Carótidas/metabolismo , Metaboloma
8.
Proc Natl Acad Sci U S A ; 118(31)2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34330824

RESUMO

Biofilms are aggregates of bacterial cells surrounded by an extracellular matrix. Much progress has been made in studying biofilm growth on solid substrates; however, little is known about the biophysical mechanisms underlying biofilm development in three-dimensional confined environments in which the biofilm-dwelling cells must push against and even damage the surrounding environment to proliferate. Here, combining single-cell imaging, mutagenesis, and rheological measurement, we reveal the key morphogenesis steps of Vibrio cholerae biofilms embedded in hydrogels as they grow by four orders of magnitude from their initial size. We show that the morphodynamics and cell ordering in embedded biofilms are fundamentally different from those of biofilms on flat surfaces. Treating embedded biofilms as inclusions growing in an elastic medium, we quantitatively show that the stiffness contrast between the biofilm and its environment determines biofilm morphology and internal architecture, selecting between spherical biofilms with no cell ordering and oblate ellipsoidal biofilms with high cell ordering. When embedded in stiff gels, cells self-organize into a bipolar structure that resembles the molecular ordering in nematic liquid crystal droplets. In vitro biomechanical analysis shows that cell ordering arises from stress transmission across the biofilm-environment interface, mediated by specific matrix components. Our imaging technique and theoretical approach are generalizable to other biofilm-forming species and potentially to biofilms embedded in mucus or host tissues as during infection. Our results open an avenue to understand how confined cell communities grow by means of a compromise between their inherent developmental program and the mechanical constraints imposed by the environment.


Assuntos
Biofilmes/crescimento & desenvolvimento , Matriz Extracelular/fisiologia , Análise de Célula Única/métodos , Vibrio cholerae/fisiologia
9.
J Am Chem Soc ; 145(47): 25887-25893, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-37966512

RESUMO

Ultrafast charge and spin dynamics have immense effects on the applications of topological insulators (TIs). By performing spin-adiabatic nonadiabatic molecular dynamics simulations in the presence of electron-phonon (e-ph) and spin-phonon couplings, we investigate temperature-dependent intra- and interband charge and spin relaxation dynamics via the bulk and surface paths in the three-dimensional TI Bi2Te3. The e-ph coupling dominates charge relaxation in the bulk path, and the relaxation rate is positively correlated with temperature due to the large energy gaps and weak spin polarization. Conversely, the relaxation dynamics exhibits an opposite temperature dependence in the surface path because of electron re-excitation and spin mismatching induced by spin-phonon coupling, which arises from small energy gaps and strong spin polarization. The two mechanisms rationalize the charge carriers being long-lived in the bulk and surface phases at low and room temperature, respectively. Additionally, strong thermal fluctuations of the topological states' magnetic moments destroy the spin-momentum locking and trigger backscattering at room temperature.

10.
J Environ Manage ; 330: 117214, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36623386

RESUMO

A park that had used reclaimed water as the sole water supply for fourteen years, was selected to analyze the distribution, sources and risks of 16 priority polycyclic aromatic hydrocarbons (PAHs) in waters and sediments. The effects of phytoremediation were investigated in waterbodies classified as phytoremediation, transitional and non-phytoremediation areas. Diagnostic ratio (DR) and principal component analysis (PCA) were used to analyze the sources of PAHs, while risk quotient (RQ) was used as risk assessment tool. Results showed that ∑PAH concentrations in sediments ranged from 29.4 to 1245.6 ng‧g-1, with average of 354.3 ng‧g-1, corresponding to a moderate pollution level. The concentration of PAHs in water ranged from 10.6 to 326.3 ng‧L-1, with average of 147.2 ng‧L-1, corresponding to a low pollution level. The ∑PAHs in sediments showed a downward trend from northwest to southeast along with the water flow direction, with average values of 459.5, 362.9 and 246.1 ng‧L-1 in the upstream, midstream and downstream, respectively. In contrast, PAH concentrations in water were consistent with recreational activities in the urban park area. There were 95% of water samples and 72% of sediment samples obtaining the Ant/(Ant + Phe) > 0.1 and Flu/(Flu + Pyr) > 0.5, indicating that coal combustion was the major source of PAHs in both the water and sediment. The RQ∑PAH(NCs) values in water and sediment were all between 1 and 800, while RQ∑PAH(MPCs) reached equal to 0, suggesting that ∑PAHs presented a low ecological risk. Acenaphthene accounted for 28.4% of RQ(NCs), and became the most risk PAH in water column. Aquatic plants effectively removed high-ring PAHs from water and middle-ring PAHs from sediments, reducing the overall risks posed by PAHs.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Água/análise , Monitoramento Ambiental , Poluentes Químicos da Água/análise , Medição de Risco , China , Sedimentos Geológicos
11.
Microb Pathog ; 152: 104750, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33484808

RESUMO

BACKGROUND: Adherence to the surface of the host cell is the precondition for T. vaginalis parasitism and pathogenicity, causing urogenital infection. The AP65 of T. vaginalis (TvAP65) involves in the process of adhesion. So, the present study was aimed at investigating the molecular characterization and vaccine candidacy of TvAP65 for protecting the host from the onset of Trichomoniasis. METHODS: The open reading frame (ORF) of TvAP65 was amplified and then inserted into pET-32a (+) to clone recombinant TvAP65 (rTvAP65). The immunoblotting determined the immunogenicity and molecular size of TvAP65, while immunofluorescence staining visualized and the precise localization of TvAP65 in T. vaginalis trophozoites. Animal challenge and enzyme-linked immunosorbent assay (ELISA) test were used to evaluate the immunoprotection and the types of the immune response of TvAP65. RESULTS: By the sequence analysis, TvAP65 encoded a 63.13 kDa protein that consisted 567 amino acid residues with a high antigenic index. The western blotting revealed that rTvAP65 and native TvAP65 could interact with the antibodies in the rat serums post hoc rTvAP65 immunization and the serums from the mice that were experimentally infected with T. vaginalis, respectively. Immunofluorescence stained TvAP65 on the surface of T. vaginalis trophozoites. Moreover, following emulsification with Freund's adjuvant, rTvAP65 was subsequently administered to BALB/c mice three times at 0, 2, and 4 weeks and the results from this animal challenge experiments showed significant increases in immunoglobulins of IgG2a, IgG1, and IgG, and cytokine of IFN-γ, and IL-2, and 10. Lastly, rTvAP65 vaccinated animals had a prolonged survival time (26.80 ± 4.05) after challenged by T. vaginalis. CONCLUSIONS: TvAP65 mediated the adhesion of T. vaginalis to the host epithelia for the pathogenesis of the parasite and can be considered as a candidate protein for designing a functional vaccine that induces cell-mediated and humoral immunity against the T. vaginalis infection.


Assuntos
Tricomoníase , Trichomonas vaginalis , Animais , Moléculas de Adesão Celular/genética , Camundongos , Camundongos Endogâmicos BALB C , Proteínas de Protozoários/genética , Ratos , Tricomoníase/prevenção & controle , Trichomonas vaginalis/genética
12.
Glycoconj J ; 38(2): 213-231, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33835347

RESUMO

Pancreatic cancer is a highly malignant tumor of the digestive tract that is difficult to diagnose and treat. It is more common in developed countries and has become one of the main causes of death in some countries and regions. Currently, pancreatic cancer generally has a poor prognosis, partly due to the lack of symptoms in the early stages of pancreatic cancer. Therefore, most cases are diagnosed at advanced stage. With the continuous in-depth research of glycoproteomics in precision medical diagnosis, there have been some reports on quantitative analysis of cancer-related cells, plasma or tissues to find specific biomarkers for targeted therapy. This research is based on the developed complete N-linked glycopeptide database search engine GPSeeker, combined with liquid-mass spectrometry and stable diethyl isotope labeling, providing a benchmark of site- and structure-specific quantitative tissue N-glycoproteomics for discovery of potential N-glycoprotein markers. With spectrum-level FDR ≤1%, 20,038 intact N-Glycopeptides corresponding to 4518 peptide backbones, 228 N-glycan monosaccharide compositions 1026 N-glycan putative structures, 4460 N-glycosites and 3437 intact N-glycoproteins were identified. With the criteria of ≥1.5-fold change and p value<0.05, 52 differentially expressed intact N-glycopeptides (DEGPs) were found in pancreatic cancer tussues relative to control, where 38 up-regulated and 14 down-regulated, respectively.


Assuntos
Glicoproteínas/química , Glicoproteínas/metabolismo , Neoplasias Pancreáticas/metabolismo , Benchmarking , Biomarcadores Tumorais/metabolismo , Bases de Dados de Proteínas , Glicoproteínas/análise , Humanos , Marcação por Isótopo , Proteômica/métodos , Ferramenta de Busca , Espectrometria de Massas em Tandem/métodos
13.
BMC Cancer ; 19(1): 918, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31519156

RESUMO

BACKGROUNDS: A number of circular RNAs (circRNAs) have been identified in various cancer including F-box and WD repeat domain containing 7 (FBXW7) circular RNA (circ-FBXW7), which can suppress glioma cell growth. However, the role of circ-FBXW7 in colorectal cancer (CRC) remains unclear. We aimed to investigate the effect and mechanisms of circ-FBXW7 on CRC progression. METHODS: The expression of circ-FBXW7 in CRC patients was detected by PCR. Stably knockdown of circ-FBXW7 (si circ-FBXW7) cell lines and overexpression of circ-FBXW7 (oe circ-FBXW7) cell lines were constructed by small interfering RNA method and plasmids transfection in CRC SW480 and SW620 cells. The functional experiments including cell proliferation, migration and invasion were carried out by cell counting kit-8 (CCK-8) assay, wound healing assay and trans well assay. The xenograft animal models were established to evaluate the effect and the underlying molecular mechanisms of circ-FBXW7 on CRC progression. RESULTS: CRC samples had a significantly lower level of circ-FBXW7 compared to normal tissue. si circ-FBXW7 notably promoted the proliferation, colony formation, cell migration and invasion of CRC cell in vitro. On contrast, circ-FBXW7 overexpressed significantly suppressed CRC cell proliferation, migration and invasion. Similarly, si circ-FBXW7 stimulated the tumor growth and circ-FBXW7 overexpression repressed the tumor progression in SW480 and SW620 tumor models, which suggested that circ-FBXW7 could serve as a target biomarker of CRC. Further study found that si circ-FBXW7 up-regulated the mRNA and protein expressions of NEK2 and mTOR, and diminished the PTEN expression. Whereas, overexpressed circ-FBXW7 induced the tumor suppression via reversing the expressions of NEK2, mTOR, and PTEN. CONCLUSION: circ-FBXW7 plays a major role in controlling the progression of CRC through NEK2, mTOR, and PTEN signaling pathways and may be a potential therapeutic target for CRC treatment. Circ-FBXW7 controls the progression of CRC through NEK2, mTOR, and PTEN signaling pathways and its overexpression inhibits colorectal cancer cell migration and invasion, suggesting the potential therapeutic target for CRC treatment.


Assuntos
Proteína 7 com Repetições F-Box-WD/genética , Quinases Relacionadas a NIMA/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , RNA Circular , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos
14.
Virol J ; 16(1): 24, 2019 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-30791956

RESUMO

BACKGROUND: As a low pathogenic influenza virus, avian influenza virus subtype H9N2 (H9N2 AIV) often induces high morbidity in association with secondary bacterial infections in chickens or mammals. To explore this phenomenon, the relationship between intestinal microflora changes and bacterial translocations was studied post H9N2 AIV challenge and post AIV infection plus Ageratum-liquid treatment. METHODS: Illumina sequencing, histological examination and Neongreen-tagged bacteria were used in this study to research the microbiota composition, intestinal barrier, and bacterial translocation in six weeks of BALB/c mice. RESULTS: H9N2 AIV infection caused intestinal dysbacteriosis and mucosal barrier damages. Notably, the villus length was significantly reduced (p < 0.01) at 12 dpi and the crypt depth was significantly increased (p < 0.01) at 5 dpi and 12 dpi with infection, resulting in the mucosal regular villus-length/crypt-depth (V/C) was significantly reduced (p < 0.01) at 5 dpi and 12 dpi. Moreover, degeneration and dissolution of the mucosal epithelial cells, loose of the connective tissue and partial glandular atrophy were found in infection group, indicating that intestinal barrier function was weakened. Eventually, intestinal microbiota (Staphylococcus, E. coli, etc.) overrun the intestinal barrier and migrated to liver and lung tissues of the mice at 5 and 12 dpi. Furthermore, the bacteria transferred in mesentery tissue sites from intestine at 36 h through tracking the Neongreen-tagged bacteria. Then the Neongreen-tagged bacteria were isolated from liver at 48 h post intragastrical administration. Simultaneously, Ageratum-liquid could inhibit the intestinal microbiota disorder post H9N2 AIV challenge via the respiratory tract. In addition, this study also illustrated that Ageratum-liquid could effectively prevent intestinal bacterial translocation post H9N2 AIV infection in mice. CONCLUSION: In this study, we report the discovery that H9N2 AIV infection could damage the ileal mucosal barrier and induce the disturbance of the intestinal flora in BALB/c mice resulting in translocation of intestinal bacteria. In addition, this study indicated that Ageratum-liquid can effectively prevent bacterial translocation following H9N2 infection. These findings are of important theoretical and practical significance in prevention and control of H9N2 AIV infection.


Assuntos
Ageratum/química , Infecções Bacterianas/tratamento farmacológico , Translocação Bacteriana/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Mucosa Intestinal/virologia , Infecções por Orthomyxoviridae/tratamento farmacológico , Animais , Coinfecção/tratamento farmacológico , Microbioma Gastrointestinal , Genoma Bacteriano , Vírus da Influenza A Subtipo H9N2/patogenicidade , Vírus da Influenza A Subtipo H9N2/fisiologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Camundongos , Camundongos Endogâmicos BALB C
15.
Int J Biol Macromol ; 268(Pt 1): 131704, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38670198

RESUMO

Mosquitoes form a vital group of vector insects, which can transmit various diseases and filarial worms. The cuticle is a critical structure that protects mosquitoes from adverse environmental conditions and penetration resistance. Thus, cuticle proteins can be used as potential targets for controlling the mosquito population. In the present study, we found that AaCPR100A is a structural protein in the soft cuticle, which has flexibility and elasticity allowing insects to move or fly freely, of Aedes aegypti. RNA interference (RNAi) of AaCPR100A caused high mortality in Aedes aegypti larvae and adults and significantly decreased the egg hatching rate. Transmission electron microscopy (TEM) analysis revealed that the larval microstructure had no recognizable endocuticle in AaCPR100A-deficient mosquitoes. A yeast two-hybrid assay was performed to screen proteins interacting with AaCPR100A. We verified that the G12-like protein had the strongest interaction with AaCPR100A using yeast two-hybrid and GST pull-down assays. Knockdown of G12-like transcription resulted in high mortality in Ae. aegypti larvae, but not in adults. Interestingly, RNAi of G12-like rescued the high mortality of adults caused by decreased AaCPR100A expression. Additionally, adults treated with G12-like dsRNA were found to be sensitive to low temperature, and their eggshell formation and hatching were decreased. Overall, our results demonstrated that G12-like may interacts with AaCPR100A, and both G12-like and AaCPR100A are involved in Ae. aegypti cuticle development and eggshell formation. AaCPR100A and G12-like can thus be considered newly potential targets for controlling the Ae. aegypti mosquito.


Assuntos
Aedes , Proteínas de Insetos , Animais , Aedes/genética , Aedes/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Larva/metabolismo , Larva/crescimento & desenvolvimento , Interferência de RNA , Ligação Proteica , Técnicas do Sistema de Duplo-Híbrido
16.
Front Pharmacol ; 15: 1364160, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694921

RESUMO

Objective: Bioinformatics methods were applied to investigate the pivotal genes and regulatory networks associated with atherosclerotic carotid artery stenosis (ACAS) and provide new insights for the treatment of this disease. Methods: The study utilized five ACAS datasets (GSE100927, GSE11782, GESE28829, GSE41571, and GSE43292) downloaded from the NCBI GEO database. The first four datasets were combined as the training set (n = 99), while GSE43292 (n = 64) was used as the validation set. Difference analysis and functional enrichment analysis were then performed on the training set. The pathogenic targets of ACAS were screened by protein-protein interaction networks and MCODE analyses, combined with three machine learning algorithms. The results were next verified by analysis of inter-group differences and ROC curve analysis. Next, immune-related function and immune cell correlation analyses were performed, and plaques of human ACAS were applied to verify the results via immunohistochemistry (IH) and immunofluorescence (IF). Finally, the competing endogenous RNAs (ceRNA) and transcription factors (TFs) regulatory networks of the characterized genes were constructed. Results: A total of 177 differentially expressed genes were identified, including 67 genes downregulated and 110 genes upregulated. Gene set enrichment analysis revealed that five pathways were active in the experimental group, including xenograft rejection, autoimmune thyroid disease, graft-versus-host disease, leishmaniasis infection, and lysosomes. Four key genes were identified, with C3AR1 being upregulated and FBLN5, PPP1R12A, and TPM1 being downregulated. The analysis of inter-group differences demonstrated that the four characterized genes were differentially expressed in both the control and experimental groups. The ROC analysis showed that they had high AUC values in both the training and validation sets. Therefore, a predictive ACAS patient nomogram model based on the screened genes was established. Correlation analysis revealed a positive correlation between C3AR1 expression and neutrophils, which was further validated in IH and IF. One or multiple lncRNAs may compete with the characterized genes for binding miRNAs. Additionally, each characterized gene interacts with multiple TFs. Conclusion: Four pivotal genes were screened, and relevant ceRNA and TFs were predicted. These molecules may exert a crucial role in ACAS and serve as potential biomarkers and therapeutic targets.

17.
Clin Transl Allergy ; 14(1): e12334, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38282195

RESUMO

BACKGROUND: Chronic rhinosinusitis (CRS) is usually accompanied by mucin hypersecretion that can lead to mucus accumulation and impair nasal mucociliary clearance, thus exacerbating airway inflammation. Abnormal mucin hypersecretion is regulated by different T helper (Th) cytokines, which are associated with different endotype-driven inflammatory responses. Therefore, it is of great significance to understand how these factors regulate mucin hypersecretion to provide precise treatment strategies for different endotypes of CRS. BODY: Thus far, the most common endotypes of CRS are classified as type 1, type 2, or type 3 immune responses based on innate and adaptive cell-mediated effector immunity, and the representative Th cytokines in these immune responses, such as IFN-γ, TNF-α, IL-4, IL-5, IL-13, IL-10, IL-17, and IL-22, play an important regulatory role in mucin secretion. We reviewed all the related literature in the PubMed database to determine the expression of these Th cytokines in CRS and the role they play in the regulation of mucin secretion. CONCLUSION: We believe that the main Th cytokines involved in specific endotypes of CRS play a key role in regulating abnormal mucin secretion, which contributes to better understanding of the pathogenesis of CRS and provides therapeutic targets for airway inflammatory diseases associated with mucin hypersecretion.

18.
Sci Data ; 11(1): 799, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39025902

RESUMO

Callosobruchus maculatus is one of the most competitive stored grain pests, which causes a great loss to agricultural economy. However, due to an inadequacy of high-quality reference genome, the molecular mechanisms for olfactory and hypoxic adaptations to stored environments are unknown and require to be revealed urgently, which will contribute to the detection and prevention of the invasive pests C. maculatus. Here, we presented a high-quality chromosome-level genome of C. maculatus based on Illumina, Nanopore and Hi-C sequencing data. The total size was 1.2 Gb, and 65.17% (797.47 Mb) of it was identified to be repeat sequences. Among assembled chromosomes, chromosome 10 was considered the X chromosome according to the evidence of reads coverage and homologous genes among species. The current version of high-quality genome provides preferable data resources for the adaptive evolution research of C. maculatus.


Assuntos
Besouros , Genoma de Inseto , Animais , Besouros/genética
19.
J Phys Chem Lett ; 14(11): 2715-2721, 2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-36892969

RESUMO

The giant spin-orbit coupling (SOC) of a heavy lead element significantly extends charge carrier lifetimes of lead halide perovskites (LHPs). The physical mechanism remains unclear and requires a quantum dynamics perspective. Taking methylammonium lead iodide (MAPbI3) as a prototypical system and using non-adiabatic molecular dynamics combined with 1/2 electron correction, we show that SOC notably reduces the non-radiative electron-hole (e-h) recombination by decreasing the non-adiabatic coupling (NAC) primarily as a result of SOC decreasing the e-h wave function overlap by reshaping the electron and hole wave functions. Second, SOC causes spin mismatch subject to spin-mixed states, which further decreases NAC. The charge carrier lifetime is about 3-fold longer in the present of SOC relative to the absence of SOC. Our study generates the fundamental understanding of SOC minimizing non-radiative charge and energy losses in LHPs.

20.
J Phys Chem Lett ; 14(23): 5403-5409, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37279169

RESUMO

Ultrafast demagnetization in magnetic metals is the key to spintronics devices. Taking iron as a prototypical system, we investigate the demagnetization mechanism by simulating the charge and spin dynamics using nonadiabatic molecular dynamics in the presence of explicit spin-orbit coupling (SOC). Strong SOC drives ultrafast spin-flip of electrons and holes, which trigger demagnetization and remagnetization, respectively. Their confrontation decreases the demagnetization ratio and finishes the demagnetization within 167 fs, agreeing with the experimental time scale. The joint spin-flip of electrons and holes correlated with the electron-phonon coupling-induced fast electron-hole recombination further decreases the maximum demagnetization ratio, below 5% of experimental value. Although the Elliott-Yafet electron-phonon scattering model can rationalize the ultrafast spin-flip process, it fails to reproduce the experimental maximum demagnetization ratio. The study suggests the key role of SOC on spin dynamics and emphasizes the interplay between SOC and electron-phonon interactions on the ultrafast demagnetization.

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