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1.
Nucleic Acids Res ; 51(16): 8348-8366, 2023 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-37439331

RESUMO

Genomic and transcriptomic image data, represented by DNA and RNA fluorescence in situ hybridization (FISH), respectively, together with proteomic data, particularly that related to nuclear proteins, can help elucidate gene regulation in relation to the spatial positions of chromatins, messenger RNAs, and key proteins. However, methods for image-based multi-omics data collection and analysis are lacking. To this end, we aimed to develop the first integrative browser called iSMOD (image-based Single-cell Multi-omics Database) to collect and browse comprehensive FISH and nucleus proteomics data based on the title, abstract, and related experimental figures, which integrates multi-omics studies focusing on the key players in the cell nucleus from 20 000+ (still growing) published papers. We have also provided several exemplar demonstrations to show iSMOD's wide applications-profiling multi-omics research to reveal the molecular target for diseases; exploring the working mechanism behind biological phenomena using multi-omics interactions, and integrating the 3D multi-omics data in a virtual cell nucleus. iSMOD is a cornerstone for delineating a global view of relevant research to enable the integration of scattered data and thus provides new insights regarding the missing components of molecular pathway mechanisms and facilitates improved and efficient scientific research.


Assuntos
Multiômica , Proteômica , Hibridização in Situ Fluorescente , Genômica/métodos , Perfilação da Expressão Gênica
2.
Mol Biol Evol ; 40(6)2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37279580

RESUMO

Predator-prey arms races are ideal models for studying the natural selection and adaptive evolution that drive the formation of biological diversity. For venomous snakes, venom is a key bridge linking snakes with their prey, but whether and how venom evolves under the selection of diet remains unclear. Here, we focused on two closely related sea snakes, Hydrophis cyanocinctus and Hydrophis curtus, which show significant differences in prey preferences. Data-independent acquisition (DIA)-based proteomic analysis revealed different degrees of homogeneity in the venom composition of the two snakes, which was consistent with the differential phylogenetic diversity of their prey. By investigating the sequences and structures of three-finger toxins (3FTx), a predominant toxin family in elapid venom, we identified significant differences between the two sea snakes in the binding activity of 3FTx to receptors from different prey populations, which could explain the trophic specialization of H. cyanocinctus. Furthermore, we performed integrated multiomic profiling of the transcriptomes, microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and proteomes of the venom glands; constructed venom-related mRNA-miRNA-lncRNA networks; and identified a series of noncoding RNAs involved in the regulation of toxin gene expression in the two species. These findings are highly informative for elucidating the molecular basis and regulatory mechanisms that account for discrepant venom evolution in response to divergent diets in closely related snakes, providing valuable evidence for the study of coselection and coevolution in predator-prey ecosystems.


Assuntos
Hydrophiidae , Animais , Filogenia , Ecossistema , Proteômica , Multiômica , Venenos Elapídicos/química , Venenos Elapídicos/genética
3.
J Transl Med ; 22(1): 206, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38414027

RESUMO

BACKGROUND: The global cellular landscape of the tumor microenvironment (TME) combining primary and metastatic liver tumors has not been comprehensively characterized. METHODS: Based on the scRNA-seq and spatial transcriptomic data of non-tumor liver tissues (NTs), primary liver tumors (PTs) and metastatic liver tumors (MTs), we performed the tissue preference, trajectory reconstruction, transcription factor activity inference, cell-cell interaction and cellular deconvolution analyses to construct a comprehensive cellular landscape of liver tumors. RESULTS: Our analyses depicted the heterogeneous cellular ecosystems in NTs, PTs and MTs. The activated memory B cells and effector T cells were shown to gradually shift to inhibitory B cells, regulatory or exhausted T cells in liver tumors, especially in MTs. Among them, we characterized a unique group of TCF7+ CD8+ memory T cells specifically enriched in MTs that could differentiate into exhausted T cells likely driven by the p38 MAPK signaling. With regard to myeloid cells, the liver-resident macrophages and inflammatory monocyte/macrophages were markedly replaced by tumor-associated macrophages (TAMs), with TREM2+ and UBE2C+ TAMs enriched in PTs, while SPP1+ and WDR45B+ TAMs in MTs. We further showed that the newly identified WDR45B+ TAMs exhibit an M2-like polarization and are associated with adverse prognosis in patients with liver metastases. Additionally, we addressed that endothelial cells display higher immune tolerance and angiogenesis capacity, and provided evidence for the source of the mesenchymal transformation of fibroblasts in tumors. Finally, the malignant hepatocytes and fibroblasts were prioritized as the pivotal cell populations in shaping the microenvironments of PTs and MTs, respectively. Notably, validation analyses by using spatial or bulk transcriptomic data in clinical cohorts concordantly emphasized the clinical significance of these findings. CONCLUSIONS: This study defines the ontological and functional heterogeneities in cellular ecosystems of primary and metastatic liver tumors, providing a foundation for future investigation of the underlying cellular mechanisms.


Assuntos
Células Endoteliais , Neoplasias Hepáticas , Humanos , Ecossistema , Neoplasias Hepáticas/genética , Perfilação da Expressão Gênica , Microambiente Tumoral
4.
New Phytol ; 242(2): 558-575, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38396374

RESUMO

Black wolfberry (Lycium ruthenicum Murr.) contains various bioactive metabolites represented by flavonoids, which are quite different among production regions. However, the underlying regulation mechanism of flavonoid biosynthesis governing the bioactivity of black wolfberry remains unclear. Presently, we compared the bioactivity of black wolfberry from five production regions. Multi-omics were performed to construct the regulation network associated with the fruit bioactivity. The detailed regulation mechanisms were identified using genetic and molecular methods. Typically, Qinghai (QH) fruit exhibited higher antioxidant and anti-inflammatory activities. The higher medicinal activity of QH fruit was closely associated with the accumulation of eight flavonoids, especially Kaempferol-3-O-rutinoside (K3R) and Quercetin-3-O-rutinoside (rutin). Flavonoid biosynthesis was found to be more active in QH fruit, and the upregulation of LrFLS, LrCHS, LrF3H and LrCYP75B1 caused the accumulation of K3R and rutin, leading to high medicinal bioactivities of black wolfberry. Importantly, transcription factor LrMYB94 was found to regulate LrFLS, LrCHS and LrF3H, while LrWRKY32 directly triggered LrCYP75B1 expression. Moreover, LrMYB94 interacted with LrWRKY32 to promote LrWRKY32-regulated LrCYP75B1 expression and rutin synthesis in black wolfberry. Transgenic black wolfberry overexpressing LrMYB94/LrWRKY32 contained higher levels of K3R and rutin, and exhibited high medicinal bioactivities. Importantly, the LrMYB94/LrWRKY32-regulated flavonoid biosynthesis was light-responsive, showing the importance of light intensity for the medicinal quality of black wolfberry. Overall, our results elucidated the regulation mechanisms of K3R and rutin synthesis, providing the basis for the genetic breeding of high-quality black wolfberry.


Assuntos
Lycium , Lycium/genética , Melhoramento Vegetal , Flavonoides , Antioxidantes , Rutina , Frutas/genética
5.
Ann Surg Oncol ; 31(2): 783-791, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37991582

RESUMO

BACKGROUND: There is an ongoing debate over the prognostic value of the number of examined lymph nodes (ELNs) in cases of gastric signet-ring cell cancer (GSRCC). In this study, we sought to evaluate the correlation between the number of ELNs and the prognosis of GSRCC and identify the optimal number of ELNs. METHODS: A total of 1020 patients diagnosed with GSRCC between 2011 and 2018 in the National Cancer Center database were identified. Clinicopathological characteristics were retrospectively collected, and optimal cutoff values of ELNs were calculated by using X-tile. The impact of different ELNs on overall survival (OS) was compared by using Kaplan-Meier curves. We used univariate and multivariate Cox and subgroup analyses to explore the relationship between ELNs and OS. Furthermore, nonlinear correlations were investigated by using restricted cubic splines (RCSs). RESULTS: X-tile showed that the optimal cutoff value of ELNs was 22. The 5-year OS was higher for patients with ELNs > 22 (vs. ELNs ≤ 22, 66.9% vs. 74.9%, P = 0.026). Multivariate Cox analyses showed that high ELNs were associated with superior OS (hazard ratio = 0.56, 95% confidence interval 0.43-0.74, P < 0.001). In subgroup analyses, the significant association between tumor size > 4 cm, and TNM III stage was still observed. The RCS regression model showed a U-shaped dose-response nonlinear relationship between ELNs and OS; the inflection point, as well as the lowest risk points, corresponded to 44-52 ELNs. CONCLUSIONS: A U-shaped, nonlinear correlation with inflection points of 44-52 ELNs between ELNs and prognosis in GSRCC was identified.


Assuntos
Carcinoma de Células em Anel de Sinete , Neoplasias Gástricas , Humanos , Estadiamento de Neoplasias , Estudos Retrospectivos , Linfonodos/cirurgia , Linfonodos/patologia , Prognóstico , Neoplasias Gástricas/patologia , Carcinoma de Células em Anel de Sinete/cirurgia , Carcinoma de Células em Anel de Sinete/patologia
6.
J Gastroenterol Hepatol ; 39(5): 908-919, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38323685

RESUMO

BACKGROUND AND AIM: A growing number of studies have demonstrated that neoadjuvant chemotherapy can improve the prognosis of patients with resectable colorectal liver metastases (CRLM). However, the routine use of postoperative adjuvant chemotherapy (POAC) for patients with CRLM after simultaneous resection remains controversial. This retrospective study investigated the impact of POAC on outcomes in patients with CRLM who underwent simultaneous resection of colorectal cancer tumors and liver metastases using propensity score matching (PSM) analysis. METHODS: From January 2009 to November 2020, patients with CRLM who underwent simultaneous resection were retrospectively enrolled. The confounding factors and selection bias were adjusted by 2:1 PSM. Patients were stratified into the POAC and non-POAC groups. Kaplan-Meier curves were utilized to compare overall survival (OS) and progression-free survival (PFS) between the groups. Univariate and multivariate Cox regression analyses were used to identify independent clinicopathological factors before and after PSM analysis. The utility of the model was evaluated using receiver operating characteristic (ROC) and calibration curves after PSM analysis. RESULTS: In total, 478 patients with resectable CRLM were enrolled and assigned to the POAC (n = 212, 60.9%) or non-POAC group (n = 136, 39.1%). After 2:1 PSM, there was no significant bias between the groups. Kaplan-Meier survival analysis revealed a significant effect of POAC on OS (P < 0.001) but not PFS. Multivariate Cox regression analysis identified T stage (T3-T4), lymph node metastasis, radiofrequency ablation during surgery, operative time ≥ 325 min, and the receipt of postoperative adjuvant chemotherapy (hazard ratio = 0.447, 95% confidence interval = 0.312-0.638, P < 0.001) as independent prognostic factors for OS. The areas under the ROC curves for the nomogram model for predicting 1-, 3-, and 5-year survival were 0.653, 0.628, and 0.678, respectively. Subgroups analysis suggested that POAC can enhance OS in patients with resectable CRLM with either low (1-2, P < 0.001) or high clinical risk scores (3-5, P = 0.020). CONCLUSIONS: Overall, this study identified POAC as a prognostic factor to predict OS in patients with CRLM undergoing simultaneous resection.


Assuntos
Neoplasias Colorretais , Hepatectomia , Neoplasias Hepáticas , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/mortalidade , Quimioterapia Adjuvante , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Pontuação de Propensão , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
7.
Appl Opt ; 63(2): 525-534, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38227250

RESUMO

Sky-bionic polar co-ordinate navigation is an effective means of providing navigational information in the absence of a priori information. Polar co-ordinate navigation during clear daytime conditions has been studied, but there has been a lack of research of it at night due to problems with noise. Therefore, in this paper, a short-wave infrared polarimetric sensor system is designed, which is capable of acquiring atmospheric polarimetric information in low illumination environments at night, compared with traditional visible band sensors. Additionally, based on the statistics of polarization angle information, an algorithm for removing noise and starlight is proposed to solve the influence of starlight and noise on the polarization information at night. After many outdoor experiments, we found that the method can output the heading angle stably and accurately, and its standard deviation is controlled to be 0.42° in a clear night.

8.
Nucleic Acids Res ; 50(D1): D950-D955, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34723317

RESUMO

The rapid development of single-molecule long-read sequencing (LRS) and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) technologies presents both challenges and opportunities for the annotation of noncoding variants. Here, we updated 3DSNP, a comprehensive database for human noncoding variant annotation, to expand its applications to structural variation (SV) and to implement variant annotation down to single-cell resolution. The updates of 3DSNP include (i) annotation of 108 317 SVs from a full spectrum of functions, especially their potential effects on three-dimensional chromatin structures, (ii) evaluation of the accessible chromatin peaks flanking the variants across 126 cell types/subtypes in 15 human fetal tissues and 54 cell types/subtypes in 25 human adult tissues by integrating scATAC-seq data and (iii) expansion of Hi-C data to 49 human cell types. In summary, this version is a significant and comprehensive improvement over the previous version. The 3DSNP v2.0 database is freely available at https://omic.tech/3dsnpv2/.


Assuntos
Cromatina/química , Bases de Dados Genéticas , Anotação de Sequência Molecular , RNA não Traduzido/genética , Software , Adulto , Linhagem da Célula/genética , Cromatina/metabolismo , Mapeamento Cromossômico , Células Eucarióticas/citologia , Células Eucarióticas/metabolismo , Feto , Genoma Humano , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Internet , Polimorfismo de Nucleotídeo Único , RNA não Traduzido/classificação , RNA não Traduzido/metabolismo , Imagem Individual de Molécula/métodos , Análise de Célula Única/métodos
9.
Nucleic Acids Res ; 50(4): 2081-2095, 2022 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-35150283

RESUMO

The shelterin protein complex is required for telomere protection in various eukaryotic organisms. In mammals, the shelterin subunit TRF2 is specialized in preventing ATM activation at telomeres and chromosome end fusion in somatic cells. Here, we demonstrate that the zebrafish ortholog of TRF2 (encoded by the terfa gene) is protecting against unwanted ATM activation genome-wide. The terfa-compromised fish develop a prominent and specific embryonic neurodevelopmental failure. The heterozygous fish survive to adulthood but exhibit a premature aging phenotype. The recovery from embryonic neurodevelopmental failure requires both ATM inhibition and transcriptional complementation of neural genes. Furthermore, restoring the expression of TRF2 in glial cells rescues the embryonic neurodevelopment phenotype. These results indicate that the shelterin subunit TRF2 evolved in zebrafish as a general factor of genome maintenance and transcriptional regulation that is required for proper neurodevelopment and normal aging. These findings uncover how TRF2 links development to aging by separate functions in gene expression regulation and genome stability control.


Assuntos
Proteína 2 de Ligação a Repetições Teloméricas , Peixe-Zebra , Envelhecimento/genética , Animais , Mamíferos/genética , Complexo Shelterina , Telômero , Proteína 2 de Ligação a Repetições Teloméricas/genética , Peixe-Zebra/genética
10.
Nucleic Acids Res ; 50(13): 7493-7510, 2022 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-35819196

RESUMO

Cellular senescence triggers various types of heterochromatin remodeling that contribute to aging. However, the age-related mechanisms that lead to these epigenetic alterations remain elusive. Here, we asked how two key aging hallmarks, telomere shortening and constitutive heterochromatin loss, are mechanistically connected during senescence. We show that, at the onset of senescence, pericentromeric heterochromatin is specifically dismantled consisting of chromatin decondensation, accumulation of DNA breakages, illegitimate recombination and loss of DNA. This process is caused by telomere shortening or genotoxic stress by a sequence of events starting from TP53-dependent downregulation of the telomere protective protein TRF2. The resulting loss of TRF2 at pericentromeres triggers DNA breaks activating ATM, which in turn leads to heterochromatin decondensation by releasing KAP1 and Lamin B1, recombination and satellite DNA excision found in the cytosol associated with cGAS. This TP53-TRF2 axis activates the interferon response and the formation of chromosome rearrangements when the cells escape the senescent growth arrest. Overall, these results reveal the role of TP53 as pericentromeric disassembler and define the basic principles of how a TP53-dependent senescence inducer hierarchically leads to selective pericentromeric dismantling through the downregulation of TRF2.


Assuntos
Senescência Celular , Centrômero , Heterocromatina , Encurtamento do Telômero , Proteína Supressora de Tumor p53/metabolismo , Linhagem Celular , Cromatina , Dano ao DNA , Regulação para Baixo , Células HeLa , Humanos , Telômero/genética , Proteína 2 de Ligação a Repetições Teloméricas/metabolismo
11.
Proc Natl Acad Sci U S A ; 118(8)2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33558418

RESUMO

The expansion of anatomically modern humans (AMHs) from Africa around 65,000 to 45,000 y ago (ca. 65 to 45 ka) led to the establishment of present-day non-African populations. Some paleoanthropologists have argued that fossil discoveries from Huanglong, Zhiren, Luna, and Fuyan caves in southern China indicate one or more prior dispersals, perhaps as early as ca. 120 ka. We investigated the age of the human remains from three of these localities and two additional early AMH sites (Yangjiapo and Sanyou caves, Hubei) by combining ancient DNA (aDNA) analysis with a multimethod geological dating strategy. Although U-Th dating of capping flowstones suggested they lie within the range ca. 168 to 70 ka, analyses of aDNA and direct AMS 14C dating on human teeth from Fuyan and Yangjiapo caves showed they derive from the Holocene. OSL dating of sediments and AMS 14C analysis of mammal teeth and charcoal also demonstrated major discrepancies from the flowstone ages; the difference between them being an order of magnitude or more at most of these localities. Our work highlights the surprisingly complex depositional history recorded at these subtropical caves which involved one or more episodes of erosion and redeposition or intrusion as recently as the late Holocene. In light of our findings, the first appearance datum for AMHs in southern China should probably lie within the timeframe set by molecular data of ca. 50 to 45 ka.


Assuntos
Arqueologia , Cavernas/química , DNA Antigo/análise , Fósseis , Sedimentos Geológicos/análise , Migração Humana/história , Datação Radiométrica/métodos , China , História Antiga , Humanos
12.
Chemistry ; 29(66): e202301771, 2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-37665775

RESUMO

Qubits are the basic unit of quantum information and computation. To realize quantum computing and information processing, the decoherence times of qubits must be long enough. Among the studies of molecule-based electron spin qubits, most of the work focused on the ions with the spin S=1/2, where only single-bit gates can be constructed. However, quantum operations require the qubits to interact with each other, so people gradually carry out relevant research in ions or systems with S>1/2 and multilevel states. In this work, a two-dimensional (2D) oxygen-coordinated GdIII NaI -based oxamato supramolecular coordination framework, Na[Gd(4-HOpa)4 (H2 O)] ⋅ 2H2 O (1, 4-HOpa=N-4-hydroxyphenyloxamate), was selected as a possible carrier of qubit. The field-induced slow magnetic relaxation shows this system has phonon bottleneck (PB) effect at low temperatures with a very weak magnetic anisotropy. The pulse electron paramagnetic resonance studies show the spin-lattice and spin-spin relaxation times are T1 =1.66 ms at 4 K and Tm =4.25 µs at 8 K for its diamagnetically diluted sample (1Gd0.12 %). It suggested that the relatively long decoherence time is mainly ascribed to its near isotropic and the PB effect from resonance phonon trapped for pure sample, while the dilution further improves its qubit performance.

13.
Bioorg Med Chem ; 92: 117420, 2023 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-37573821

RESUMO

Overexpression of tumor necrosis factor-α (TNF-α) is implicated in many inflammatory diseases, including septic shock, hepatitis, asthma, insulin resistance and autoimmune diseases, such as rheumatoid arthritis and Crohn's disease. The TNF-α signaling pathway is a valuable target, and anti-TNF-α drugs are successfully used to treat autoimmune and inflammatory diseases. Here, we study anti-inflammatory activity of an anti-TNF-α peptide (SN1-13, DEFHLELHLYQSW). In the cellular level assessment, SN1-13 inhibited TNF-α-induced cytotoxicity and blocks TNF-α-triggered signaling activities (IC50 = 15.40 µM). Moreover, the potential binding model between SN1-13 and TNF-α/TNFRs conducted through molecular docking revealed that SN1-13 could stunt TNF-α mediated signaling thought blocking TNF-α and its receptor TNFR1 and TNFR2. These results suggest that SN1-13 would be a potential lead peptide to treat TNF-α-mediated inflammatory diseases.


Assuntos
NF-kappa B , Fator de Necrose Tumoral alfa , Humanos , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Simulação de Acoplamento Molecular , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Inflamação/tratamento farmacológico , Peptídeos/farmacologia , Peptídeos/uso terapêutico
14.
Sensors (Basel) ; 23(9)2023 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-37177420

RESUMO

An accurate, easy setup, low-cost, and time-saving method for measuring glucose concentration was proposed. An all-grating-based glucose concentration measurement system contained moving-grating-based heterodyne interferometry and a grating-based self-align sensor. By combining the first-order diffraction lights from two separated moving gratings by a polarization beam splitter and creating S- and P-polarized light interference by an analyzer, the interference signal could be a heterodyne light source with a heterodyne frequency depending on the relative velocities of the two moving gratings. Next, a grating-based self-align sensor was used to make the optical configuration setup easy and accurate. Moreover, the sensor was deposited on GOx film to improve the measurement sensitivity and specificity for glucose. Finally, the phase change induced by the reaction of the sensor and glucose solutions was detected. The validity of this method was proved, and the measurement resolution can reach 2 mg/dL.

15.
Molecules ; 28(5)2023 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-36903328

RESUMO

The abuse of antibiotics and lack of new antibacterial drugs has led to the emergence of superbugs that raise fears of untreatable infections. The Cathelicidin family of antimicrobial peptide (AMP) with varying antibacterial activities and safety is considered to be a promising alternative to conventional antibiotics. In this study, we investigated a novel Cathelicidin peptide named Hydrostatin-AMP2 from the sea snake Hydrophis cyanocinctus. The peptide was identified based on gene functional annotation of the H. cyanocinctus genome and bioinformatic prediction. Hydrostatin-AMP2 showed excellent antimicrobial activity against both Gram-positive and Gram-negative bacteria, including standard and clinical Ampicillin-resistant strains. The results of the bacterial killing kinetic assay demonstrated that Hydrostatin-AMP2 had faster antimicrobial action than Ampicillin. Meanwhile, Hydrostatin-AMP2 exhibited significant anti-biofilm activity including inhibition and eradication. It also showed a low propensity to induce resistance as well as low cytotoxicity and hemolytic activity. Notably, Hydrostatin-AMP2 apparently decreased the production of pro-inflammatory cytokines in the LPS-induced RAW264.7 cell model. To sum up, these findings indicate that Hydrostatin-AMP2 is a potential peptide candidate for the development of new-generation antimicrobial drugs fighting against antibiotic-resistant bacterial infections.


Assuntos
Anti-Infecciosos , Hydrophiidae , Animais , Catelicidinas/química , Antibacterianos/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/farmacologia , Bactérias , Ampicilina , Testes de Sensibilidade Microbiana
16.
J Neurophysiol ; 127(5): 1438-1444, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35443136

RESUMO

Accumulating evidence has demonstrated that histone deacetylase 1 (HDAC1) expression is statistically correlated with the severity of traumatic brain injury (TBI). However, the specific role of HDAC1 in the occurrence and development of TBI remains unclear. The lateral fluid percussion injury (LFPI) was used to conduct TBI mouse model in C57BL/6J and C57BL/6J-Hdac1em1cyagen mice. Western blot and qRT-PCR were performed to estimate the expression of HDAC1 and nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in brain tissues. Modified neurological severity score (mNSS) and brain water content were analyzed to detect the neurological deficit. Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) were used to detect the oxidative stress. Oxidative stresses, HDAC1, and NOX4 expression were upregulated in the lesioned cortices tissues after TBI. HDAC1 protein expression was positively correlated with the NOX4 in TBI mouse. Hdac1 knockout attenuated brain edema and neurological dysfunction caused by TBI in mice. Hdac1 knockout inhibited the expressions of NOX4 induced by TBI and attenuated TBI-induced oxidative stress. HDAC1 expression is positively correlated with to NOX4-mediated oxidative stress in a TBI mouse model.NEW & NOTEWORTHY Traumatic brain injury causes increased oxidative stresses, histone deacetylase 1, and nicotinamide adenine dinucleotide phosphate oxidase 4 expression. Hdac1 knockout could attenuate the brain damage caused by traumatic brain injury. The results suggest that histone deacetylase 1 may be a therapeutic target for the treatment of traumatic brain injury.


Assuntos
Lesões Encefálicas Traumáticas , Histona Desacetilase 1/metabolismo , Animais , Lesões Encefálicas Traumáticas/metabolismo , Modelos Animais de Doenças , Histona Desacetilase 1/genética , Camundongos , Camundongos Endogâmicos C57BL , NADP/metabolismo , NADP/uso terapêutico , NADPH Oxidase 4/genética , NADPH Oxidase 4/metabolismo , Estresse Oxidativo
17.
Mol Biol Evol ; 38(11): 4867-4883, 2021 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-34320652

RESUMO

True sea snakes (Hydrophiini) are among the last and most successful clades of vertebrates that show secondary marine adaptation, exhibiting diverse phenotypic traits and lethal venom systems. To better understand their evolution, we generated the first chromosome-level genomes of two representative Hydrophiini snakes, Hydrophis cyanocinctus and H. curtus. Through comparative genomics we identified a great expansion of the underwater olfaction-related V2R gene family, consisting of more than 1,000 copies in both snakes. A series of chromosome rearrangements and genomic structural variations were recognized, including large inversions longer than 30 megabase (Mb) on sex chromosomes which potentially affect key functional genes associated with differentiated phenotypes between the two species. By integrating multiomics we found a significant loss of the major weapon for elapid predation, three-finger toxin genes, which displayed a dosage effect in H. curtus. These genetic changes may imply mechanisms that drove the divergent evolution of adaptive traits including prey preferences between the two closely related snakes. Our reference-quality sea snake genomes also enrich the repositories for addressing important issues on the evolution of marine tetrapods, and provide a resource for discovering marine-derived biological products.


Assuntos
Hydrophiidae , Animais , Venenos Elapídicos/genética , Evolução Molecular , Genoma , Hydrophiidae/genética , Fenótipo
18.
Opt Lett ; 47(4): 921-924, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-35167559

RESUMO

In this study, a hybrid method for high-quality rapid drilling of transparent hard materials which combines femtosecond laser (fs-laser) Bessel beam modifying materials and selective wet etching is presented. Using this method, micro-holes with no taper of different sizes (from 10 to 35 µm) and shapes (square, triangle, circular, and pentagram) are fabricated. Bessel beams of different lengths can be generated flexibly by loading different computer-generated holograms (CGHs) into the spatial light modulator (SLM) and the maximum length of light interacting with materials can reach 320 µm, leading to a reduction of the laser scanning time by two orders of magnitude. Moreover, a set of three-dimensional multi-layer submicron through-holes in crystal materials is also realized, with an aspect ratio of more than 1000 for each hole. These results indicate that this method has broad application potential in chip packaging, aviation manufacturing, single particle catalysis, and other fields.

19.
Phys Chem Chem Phys ; 24(31): 18684-18690, 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35895316

RESUMO

Due to its low electrochemical potential and high theoretical specific energy, lithium-metal batteries (LMBs) have been considered as a promising advanced energy storage system for portable applications such as electric vehicles (EVs). However, the uncontrolled growth of lithium dendrites during cycling has remained a challenge. By utilizing an inert solvent to "dilute" the high concentration electrolytes, the concept of localized high-concentration electrolytes (LHCEs) has recently been demostrated as an effective solution to enable the dendrite-free cycling of LMBs. In this work, we investigated the reactions of 2 M lithium bis(fluorosulfonyl)imide (LiFSI) in a mixture of dimethoxyethane (DME)/tris(2,2,2-trifluoroethyl) orthoformate (TFEO) electrolyte at a Li metal anode. The SEI formation mechanism is investigated using a hybrid ab initio and reactive force field (HAIR) method. The 1n reactive HAIR trajectory reveals the important initial reduction reactions of LiFSI, TFEO, and DME. Particularly, both FSI anions and TFEO decompose quickly to release a considerable amount of F-, which leads to a LiF-rich SEI inorganic inner layer (IIL). Furthermore, TFEO produces a significant amount of unsaturated carbon products, such as thiophene, which can potentially increase the conductivity of SEI to increase the battery performance. Meanwhile, XPS analysis is utilized to further investigate the evolution of the atomic environment in SEI. Future designs of better electrolytes can be greatly aided by these results.

20.
Int Orthop ; 46(12): 2853-2857, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36088415

RESUMO

PURPOSE: To study the efficacy of three kinds of surgery for trigger thumb. METHODS: A total of 60 cases of trigger thumb (Quinnell Grade IV) were randomly divided into three groups. The A1 pulley was disconnected at the middle in Group A, at the extreme radial side in Group B, excised in Group C. The following indicators were recorded pre-operatively (D0), and at one (D1), three (D3), seven (D7), 14 (D14), and 28 (D28) days post-operatively: 1. the pain visual analogue score (VAS) when flexing the affected thumb; 2. range of motion (ROM) of the interphalangeal joint with pain tolerance; 3. the time of pain disappearance when flexing the affected thumb. RESULTS: The differences of VAS and ROM between D1 and D0, D3 and D1, D7 and D3, D14 and D7, D28 and D14 were statistically significant (P < 0.05). There was no significant difference in changes of VAS (or ROM) at D1 or D28 in contrast to D0 among the three groups. The differences of VAS (or ROM) changes at D3, D7, and D14 in contrast to D0 among the three groups were statistically significant (P < 0.05). The difference of the time when the pain disappearing in the normal range of motion among the three groups were statistically significant (P < 0.05). CONCLUSION: Disconnecting the A1-pulley at the extreme radial side is better than another two methods for treating the trigger thumb (Quinnell Grade IV). It has been shown to effectively accelerate postoperative pain relief and functional recovery. TRIAL REGISTRATION: Clinical trial registry number: ChiCTR2100051193.


Assuntos
Dedo em Gatilho , Humanos , Dedo em Gatilho/cirurgia , Polegar/cirurgia , Amplitude de Movimento Articular , Recuperação de Função Fisiológica , Dor
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