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1.
Nature ; 627(8003): 313-320, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38480964

RESUMO

Intrinsically stretchable electronics with skin-like mechanical properties have been identified as a promising platform for emerging applications ranging from continuous physiological monitoring to real-time analysis of health conditions, to closed-loop delivery of autonomous medical treatment1-7. However, current technologies could only reach electrical performance at amorphous-silicon level (that is, charge-carrier mobility of about 1 cm2 V-1 s-1), low integration scale (for example, 54 transistors per circuit) and limited functionalities8-11. Here we report high-density, intrinsically stretchable transistors and integrated circuits with high driving ability, high operation speed and large-scale integration. They were enabled by a combination of innovations in materials, fabrication process design, device engineering and circuit design. Our intrinsically stretchable transistors exhibit an average field-effect mobility of more than 20 cm2 V-1 s-1 under 100% strain, a device density of 100,000 transistors per cm2, including interconnects and a high drive current of around 2 µA µm-1 at a supply voltage of 5 V. Notably, these achieved parameters are on par with state-of-the-art flexible transistors based on metal-oxide, carbon nanotube and polycrystalline silicon materials on plastic substrates12-14. Furthermore, we realize a large-scale integrated circuit with more than 1,000 transistors and a stage-switching frequency greater than 1 MHz, for the first time, to our knowledge, in intrinsically stretchable electronics. Moreover, we demonstrate a high-throughput braille recognition system that surpasses human skin sensing ability, enabled by an active-matrix tactile sensor array with a record-high density of 2,500 units per cm2, and a light-emitting diode display with a high refreshing speed of 60 Hz and excellent mechanical robustness. The above advancements in device performance have substantially enhanced the abilities of skin-like electronics.


Assuntos
Desenho de Equipamento , Pele , Transistores Eletrônicos , Dispositivos Eletrônicos Vestíveis , Humanos , Silício , Nanotubos de Carbono , Tato
3.
Clin Infect Dis ; 2024 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-38552199

RESUMO

Precision daptomycin dosing faces clinical implementation barriers despite known exposure-safety concerns with the use of twice the regulatory-approved doses. We propose achieving a single 7-11 hour post-dose plasma target concentration of 30 mg/L to 43 mg/L to be a practical starting point to facilitate precision daptomycin dosing.

4.
Planta ; 260(1): 5, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38777878

RESUMO

MAIN CONCLUSION: Trace amounts of epibrassinolide (EpiBL) could partially rescue wheat root length inhibition in salt-stressed situation by scavenging ROS, and ectopic expression of TaDWF4 or TaBAK1 enhances root salt tolerance in Arabidopsis by balancing ROS level. Salt stress often leads to ion toxicity and oxidative stress, causing cell structure damage and root development inhibition in plants. While prior research indicated the involvement of exogenous brassinosteroid (BR) in plant responses to salt stress, the precise cytological role and the function of BR in wheat root development under salt stress remain elusive. Our study demonstrates that 100 mM NaCl solution inhibits wheat root development, but 5 nM EpiBL partially rescues root length inhibition by decreasing H2O2 content, oxygen free radical (OFR) content, along with increasing the peroxidase (POD) and catalase (CAT) activities in salt-stressed roots. The qRT-PCR experiment also shows that expression of the ROS-scavenging genes (GPX2 and CAT2) increased in roots after applying BR, especially during salt stress situation. Transcriptional analysis reveals decreased expression of BR synthesis and root meristem development genes under salt stress in wheat roots. Differential expression gene (DEG) enrichment analysis highlights the significant impact of salt stress on various biological processes, particularly "hydrogen peroxide catabolic process" and "response to oxidative stress". Additionally, the BR biosynthesis pathway is enriched under salt stress conditions. Therefore, we investigated the involvement of wheat BR synthesis gene TaDWF4 and BR signaling gene TaBAK1 in salt stress responses in roots. Our results demonstrate that ectopic expression of TaDWF4 or TaBAK1 enhances salt tolerance in Arabidopsis by balancing ROS (Reactive oxygen species) levels in roots.


Assuntos
Brassinosteroides , Homeostase , Raízes de Plantas , Espécies Reativas de Oxigênio , Tolerância ao Sal , Esteroides Heterocíclicos , Triticum , Triticum/genética , Triticum/fisiologia , Triticum/metabolismo , Triticum/crescimento & desenvolvimento , Triticum/efeitos dos fármacos , Brassinosteroides/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/fisiologia , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Tolerância ao Sal/genética , Esteroides Heterocíclicos/farmacologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Estresse Salino , Estresse Oxidativo , Arabidopsis/genética , Arabidopsis/fisiologia , Arabidopsis/efeitos dos fármacos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Catalase/metabolismo
5.
Int J Legal Med ; 138(2): 561-570, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37801116

RESUMO

Species identification of biological specimens can provide the valuable clues and accelerate the speed of prosecution material processing for forensic investigation, especially when the case scene is inaccessible and the physical evidence is cumbersome. Thus, establishing a rapid, simple, and field-adapted species identification method is crucial for forensic scientists, particularly as first-line technology at the crime scene for initial rapid screening. In this study, we established a new field-adapted species identification method by combining multiplex multienzyme isothermal rapid amplification (MIRA), lateral flow dipstick (LFD) system, and universal primers. Universal primers targeting COX I and COX II genes were used in multiplex MIRA-LFD system for seven species identification, and a dedicated MIRA-LFD system primer targeting CYT B gene was used to detect the human material. DNA extraction was performed by collecting DNA directly from the centrifuged supernatant. Our study found that the entire amplification process took only 15 min at 37 °C and the results of LFDs could be visually observed after 10 min. The detection sensitivity of human material could reach 10 pg, which is equivalent to the detection of single cell. Different common animal samples mixed at the ratio of 1 ng:1 ng, 10 ng:1 ng, and 1 ng:10 ng could be detected successfully. Furthermore, the damaged and degraded samples could also be detected. Therefore, the convenient, feasible, and rapid approach for species identification is suitable for popularization as first-line technology at the crime scene for initial rapid screening and provides a great convenient for forensic application.


Assuntos
DNA , Técnicas de Amplificação de Ácido Nucleico , Animais , Humanos , Técnicas de Amplificação de Ácido Nucleico/métodos , Sensibilidade e Especificidade , Primers do DNA/genética , Reação em Cadeia da Polimerase/métodos
6.
Int J Legal Med ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38858273

RESUMO

Monozygotic (MZ) twins cannot be distinguished using conventional forensic STR typing because they present identical STR genotypings. However, MZ twins do not always live in the same environment and often have different dietary and other lifestyle habits. Metabolic profiles are deyermined by individual characteristics and are also influenced by the environment in which they live. Therefore, they are potential markers capable of identifying MZ twins. Moreover, the production of proteins varies from organism to organism and is influenced by both the physiological state of the body and the external environment. Hence, we used metabolomics and proteomics to identify metabolites and proteins in peripheral blood to discriminate MZ twins. We identified 1749 known metabolites and 622 proteins in proteomic analysis. The metabolic profiles of four pairs of MZ twins revealed minor differences in intra-MZ twins and major differences in inter-MZ twins. Each pair of MZ twins exhibited distinct characteristics, and four metabolites-methyl picolinate, acesulfame, paraxanthine, and phenylbenzimidazole sulfonic acid-were observed in all four MZ twin pairs. These four differential exogenous metabolites conincidently show that the different external environments and life styles can be well distinguished by metabolites, considering that twins do not all have the same eating habits and living environments. Moreover, MZ twins showed different protein profiles in serum but not in whole blood. Thus, our results indicate that differential metabolites provide potential biomarkers for the personal identification of MZ twins in forensic medicine.

7.
J Chem Inf Model ; 64(10): 4322-4333, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38733561

RESUMO

Revealing the mechanisms that influence transcription factor binding specificity is the key to understanding gene regulation. In previous studies, DNA double helix structure and one-hot embedding have been used successfully to design computational methods for predicting transcription factor binding sites (TFBSs). However, DNA sequence as a kind of biological language, the method of word embedding representation in natural language processing, has not been considered properly in TFBS prediction models. In our work, we integrate different types of features of DNA sequence to design a multichanneled deep learning framework, namely MulTFBS, in which independent one-hot encoding, word embedding encoding, which can incorporate contextual information and extract the global features of the sequences, and double helix three-dimensional structural features have been trained in different channels. To extract sequence high-level information effectively, in our deep learning framework, we select the spatial-temporal network by combining convolutional neural networks and bidirectional long short-term memory networks with attention mechanism. Compared with six state-of-the-art methods on 66 universal protein-binding microarray data sets of different transcription factors, MulTFBS performs best on all data sets in the regression tasks, with the average R2 of 0.698 and the average PCC of 0.833, which are 5.4% and 3.2% higher, respectively, than the suboptimal method CRPTS. In addition, we evaluate the classification performance of MulTFBS for distinguishing bound or unbound regions on TF ChIP-seq data. The results show that our framework also performs well in the TFBS classification tasks.


Assuntos
Fatores de Transcrição , Fatores de Transcrição/metabolismo , Fatores de Transcrição/química , Sítios de Ligação , Aprendizado Profundo , DNA/química , DNA/metabolismo , Biologia Computacional/métodos , Redes Neurais de Computação
8.
J Nematol ; 56(1): 20240016, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38737093

RESUMO

Nematodes play a vital ecological role in soil and marine ecosystems, but there is limited information about their dietary diversity and feeding habits. Due to methodological challenges, the available information is based on inference rather than confirmed observations. The lack of correct dietary requirements also hampers rearing experiments. To achieve insight into the prey of mononchid nematodes, this study employed high-throughput Illumina paired-end sequencing using universal eukaryotic species 18S primers on 10 pooled mononchid nematode species, namely Mylonchulus brachyuris, M. brevicaudatus, Mylonchulus sp., Clarkus parvus, Prionchulus sp. M. hawaiiensis, M. sigmaturellus, M. vulvapapillatus, Anatonchus sp. and Miconchus sp. The results indicate that mononchids are associated with a remarkable diversity of eukaryotes, including fungi, algae, and protists. While the metabarcoding approach, first introduced here for mononchids, proved to be a simple and rapid method, it has several limitations and crucial methodological challenges that should be addressed in future studies. Ultimately, such methods should be able to evaluate the dietary complexity of nematodes and provide a valuable avenue for unraveling the dietary requirements of previously unculturable nematodes. This can contribute to the methodology of understanding their feeding habits and contributions to ecosystem dynamics.

9.
J Cell Physiol ; 238(2): 366-378, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36548450

RESUMO

In this study, we investigated the effects of long noncoding RNA (lncRNA) SND1-IT1 on human microglia (HMC3 cells) delivered by intracerebral hemorrhage (ICH)-derived exosomes (ICH-exos) as well as a competitive endogenous RNA (ceRNA) network. Exosomes obtained from ICH plasma were characterized by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and western blot. RNA sequencing was performed to study the lncRNA transcriptome from ICH-exos and the healthy control-derived exosomes (HC-exos) and differentially expressed lncRNAs (DE-lncRNAs) were identified. HMC3 cells were treated with ICH-exos or transfected with pcDNA3.1-SND1-IT1, and then cell viability and apoptosis were measured. The ceRNA network (lncRNA SND1-IT1/miR-124-3p/messenger RNA MTF1) was chosen for further investigation. NTA, TEM, and western blot showed that exosomes were successfully separated and could be absorbed by HMC3 cells. The expression of lncRNA SND1-IT1 in ICH-exos was significantly higher than that of HC-exos (p < 0.05). In addition, lncRNA SND1-IT1 overexpression and ICH-exos significantly inhibited cell viability and enhanced apoptosis. A total of 162 DE-lncRNAs were identified by sequencing, and a ceRNA network was constructed. The dual-luciferase reporter gene indicated that lncRNA SND1-IT1, miR-124-3p, and MTF1 interacted with each other. Cell experiments showed that lncRNA SND1-IT1 affected the growth of HMC3 cells through miR-124-3p/MTF1. In conclusion, ICH-exos delivered lncRNA SND1-IT1 to HMC3 cells, and exosomal lncRNA SND1-IT1 can regulate cell viability and apoptosis to influence HMC3 cell growth via the SND1-IT1/miR-124-3p/MTF1 axis.


Assuntos
Exossomos , MicroRNAs , RNA Longo não Codificante , Humanos , Proliferação de Células , Endonucleases/metabolismo , Exossomos/genética , Microglia/metabolismo , MicroRNAs/genética , RNA Longo não Codificante/genética , Fator MTF-1 de Transcrição
10.
Antimicrob Agents Chemother ; 67(11): e0082023, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37850741

RESUMO

Echinocandins like anidulafungin are first-line therapies for candidemia and invasive candidiasis, but their dosing may be suboptimal in obese patients. Our objective was to quantify anidulafungin exposure in a cohort of adults across a wide body size range to test if body size affects anidulafungin pharmacokinetics (PK). We enrolled 20 adults between the ages of 18 and 80 years, with an equal distribution of patients above and below a body mass index of 30 kg/m2. A single 100-mg dose of anidulafungin was administered, followed by intensive sampling over 72 h. Population PK analysis was used to identify and compare covariates of anidulafungin PK parameters. Monte Carlo simulations were performed to compute the probability of target attainment (PTA) based on alternative dosing regimens. Participants (45% males) had a median (range) age of 45 (21-78) years and a median (range) weight of 82.7 (42.4-208.3) kg. The observed median (range) of AUC0-∞ was 106.4 (51.9, 138.4) mg∙h/L. Lean body weight (LBW) and adjusted body weight (AdjBW) were more influential than weight as covariates of anidulafungin PK parameters. The conventional 100 mg daily maintenance is predicted to have a PTA below 90% in adults with an LBW > 55 kg or an AdjBW > 75 kg. A daily maintenance dose of 150-200 mg is predicted in these heavier adults. Anidulafungin AUC0-∞ declines with increasing body size. A higher maintenance dose will increase the PTA compared to the current approach in obese patients.


Assuntos
Antifúngicos , Candidíase Invasiva , Adulto , Masculino , Humanos , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Anidulafungina/uso terapêutico , Antifúngicos/farmacocinética , Obesidade/tratamento farmacológico , Peso Corporal , Candidíase Invasiva/tratamento farmacológico , Tamanho Corporal , Método de Monte Carlo
11.
Plant Biotechnol J ; 21(12): 2625-2640, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37594728

RESUMO

High light stress is an important factor limiting crop yield. Light receptors play an important role in the response to high light stress, but their mechanisms are still poorly understood. Here, we found that the abundance of GmPLP1, a positive blue light receptor protein, was significantly inhibited by high light stress and mainly responded to high blue light. GmPLP1 RNA-interference soybean lines exhibited higher light energy utilization ability and less light damage and reactive oxygen species (ROS) accumulation in leaves under high light stress, while the phenotype of GmPLP1:GmPLP1-Flag overexpression soybean showed the opposite characteristics. Then, we identified a protein-protein interaction between GmPLP1 and GmVTC2, and the intensity of this interaction was primarily affected by sensing the intensity of blue light. More importantly, overexpression of GmVTC2b improved soybean tolerance to high light stress by enhancing the ROS scavenging capability through increasing the biosynthesis of ascorbic acid. This regulation was significantly enhanced after interfering with a GmPLP1-interference fragment in GmVTC2b-ox soybean leaves, but was weakened when GmPLP1 was transiently overexpressed. These findings demonstrate that GmPLP1 regulates the photosynthetic capacity and ROS accumulation of soybean to adapt to changes in light intensity by sensing blue light. In summary, this study discovered a new mechanism through which GmPLP1 participates in high light stress in soybean, which has great significance for improving soybean yield and the adaptability of soybean to high light.


Assuntos
Glycine max , Fotossíntese , Espécies Reativas de Oxigênio/metabolismo , Glycine max/genética , Glycine max/metabolismo , Fotossíntese/genética , Luz , Folhas de Planta/genética , Folhas de Planta/metabolismo
12.
New Phytol ; 239(2): 606-623, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37161722

RESUMO

Allopolyploidization may initiate rapid evolution due to heritable karyotypic changes. The types and extents of these changes, the underlying causes, and their effects on phenotype remain to be fully understood. Here, we designed experimental populations suitable to address these issues using a synthetic allotetraploid wheat. We show that extensive variation in both chromosome number (NCV) and structure (SCV) accumulated in a selfed population of a synthetic allotetraploid wheat (genome Sb Sb DD). The combination of NCVs and SCVs generated massive organismal karyotypic heterogeneity. NCVs and SCVs were intrinsically correlated and highly variable across the seven sets of homoeologous chromosomes. Both NCVs and SCVs stemmed from meiotic pairing irregularity (presumably homoeologous pairing) but were also constrained by homoeologous chromosome compensation. We further show that homoeologous meiotic pairing was positively correlated with sequence synteny at the subtelomeric regions of both chromosome arms, but not with genic nucleotide similarity per se. Both NCVs and SCVs impacted phenotypic traits but only NCVs caused significant reduction in reproductive fitness. Our results implicate factors influencing meiotic homoeologous chromosome pairing and reveal the type and extent of karyotypic variation and its immediate phenotypic manifestation in synthetic allotetraploid wheat. This has relevance for our understanding of allopolyploid evolution.


Assuntos
Cromossomos de Plantas , Triticum , Triticum/genética , Cromossomos de Plantas/genética , Poaceae/genética , Cariótipo , Cariotipagem , Pareamento Cromossômico/genética
13.
Environ Sci Technol ; 57(6): 2495-2505, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36719139

RESUMO

Understanding fossil-fuel/food production and consumption patterns is the first step toward reducing the climate impacts of associated methane (CH4) emissions but remains unclear in China. Here, based on the bottom-up method, whole-industrial-chain CH4 emission in China (CH4-CHINA) is developed to track CH4 emissions from production to use and finally to disposal. The estimated Chinese national CH4 emissions in 2020 are 39288.3 Gg (25,230.8-53,345.7 Gg), with 50.4 and 49.6% emissions generated from fossil-fuel and food systems, respectively. ∼130,000 point sources are included to achieve a highly resolved inventory of CH4 emissions, which account for ∼53.5% of the total anthropogenic CH4 emissions in 2020. Our estimate is 36% lower than the Chinese inventory reported to the UNFCCC and 40% lower than EDGAR v6.0, mainly driven by lower emissions from rice cultivation, waste management, and coal supply chain in this study. Based on the emission flow, we observe that previous studies ignored the emissions from natural gas vehicles and residential appliances, coke production, municipal solid waste predisposal, septic tanks, biogas digesters, and food sewage treatment, which totally contribute ∼12.4% of the national anthropogenic CH4 emissions. The results discussed in this study provide critical insights to design and formulate effective CH4 emission mitigation strategies.


Assuntos
Metano , Gerenciamento de Resíduos , Metano/análise , Gás Natural , Carvão Mineral , China
14.
Environ Sci Technol ; 57(31): 11510-11519, 2023 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-37489803

RESUMO

Accurately tracking carbon flows is the first step toward reducing the climate impacts of the iron and steel industry (ISI), which is still lacking in China. In this study, we track carbon flows from coal/mineral mines to end steel users by coupling the cross-process material and energy flow model, point-based emission inventory, and interprovincial trade matrices. In 2020, ISI emitted 2288 Tg of CO2 equivalent (CO2eq, including CH4 and CO2), 96% of which came from energy use and 4% from raw material decomposition. Often overlooked off-gas use and CH4 leakage in coal mines account for 25% of life-cycle emissions. Due to limited scrap resources and a high proportion of pig iron feed, the life-cycle emission intensity of the electric arc furnace (EAF) (1.15 t CO2eq/t steel) is slightly lower than the basic oxygen furnace (BOF) (1.58 t CO2eq/t steel) in China. In addition, over 49% of producer-based emissions are driven by interprovincial coal/coke/steel trade. In particular, nearly all user-based emissions in Zhejiang and Beijing are transferred to steelmaking bases. Therefore, we highlight the need for life-cycle and spatial shifts in user-side carbon management.


Assuntos
Poluentes Atmosféricos , Ferro , Animais , Suínos , Poluentes Atmosféricos/análise , Carbono , Aço , Dióxido de Carbono/análise , Carvão Mineral , China
15.
Environ Sci Technol ; 57(4): 1551-1567, 2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36661479

RESUMO

Toxic trace elements (TEs) can pose serious risks to ecosystems and human health. However, a comprehensive understanding of atmospheric emission inventories for several concerning TEs has not yet been developed. In this study, we systematically reviewed the status and progress of existing research in developing atmospheric emission inventories of TEs focusing on global, regional, and sectoral scales. Multiple studies have strengthened our understanding of the global emission of TEs, despite attention being mainly focused on Hg and source classification in different studies showing large discrepancies. In contrast to those of developed countries and regions, the officially published emission inventory is still lacking in developing countries, despite the fact that studies on evaluating the emissions of TEs on a national scale or one specific source category have been numerous in recent years. Additionally, emissions of TEs emitted from waste incineration and traffic-related sources have produced growing concern with worldwide rapid urbanization. Although several studies attempt to estimate the emissions of TEs based on PM emissions and its source-specific chemical profiles, the emission factor approach is still the universal method. We call for more extensive and in-depth studies to establish a precise localization national emission inventory of TEs based on adequate field measurements and comprehensive investigation to reduce uncertainty.


Assuntos
Poluentes Atmosféricos , Mercúrio , Oligoelementos , Humanos , Oligoelementos/análise , Poluentes Atmosféricos/análise , Ecossistema , Monitoramento Ambiental/métodos , Mercúrio/análise
16.
Int Arch Occup Environ Health ; 96(6): 785-796, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37079056

RESUMO

OBJECTIVE: Antineoplastic drugs (ADs) are widely used in clinical practice and have been demonstrated to be effective in treating malignant tumors. However, they carry a risk of cytogenotoxicity for healthcare workers. Studies have reported that genotoxic biomarkers can be applied to assess the occupational health status of healthcare workers at an early stage, but results of different studies are variable. The objectives of the review were examine the association between long-term exposure to ADs and cytogenetic damage to healthcare workers. METHODS: We systematically reviewed studies between 2005 and 2021 using PubMed, Embase and Web of Science databases that used cytogenetic biomarkers to assess occupational exposure to ADs in healthcare workers. We used RevMan5.4 to analyze the tail length parameters of the DNA, frequency of the chromosomal aberrations, sister chromatid exchanges and micronuclei. A total of 16 studies were included in our study. The studies evaluate the quality of the literature through the Agency for Healthcare Research and Quality. RESULTS: The results revealed that under the random-effects model, the estimated standard deviation was 2.37 (95% confidence interval [CI] 0.92-3.81, P = 0.001) for the tail length parameters of the DNA, 1.48 (95% CI 0.71-2.25, P = 0.0002) for the frequency of chromosomal aberrations, 1.74 (95% CI 0.49-2.99, P = 0.006) for the frequency of sister chromatid exchanges and 1.64 (95% CI 0.83-2.45, P < 0.0001) for the frequency of micronuclei. CONCLUSIONS: The results indicate that there is a significant association between occupational exposure to ADs and cytogenetic damage, to which healthcare workers should be alerted.


Assuntos
Antineoplásicos , Exposição Ocupacional , Humanos , Antineoplásicos/efeitos adversos , Aberrações Cromossômicas/induzido quimicamente , Pessoal de Saúde , Exposição Ocupacional/efeitos adversos , Biomarcadores , Troca de Cromátide Irmã , Análise Citogenética
17.
Int J Mol Sci ; 25(1)2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38203196

RESUMO

In pig production, pigs often show more aggressive behavior after mixing, which adversely affects animal welfare and growth performance. The Jumonji and structural domain-rich AT interaction domain 2 (JARID2) gene plays an important role in neurodevelopment in mice and various psychiatric disorders in humans. The JARID2 gene may impact the aggressive behavior of pigs. By observing the behavior of 500 weaned pigs during the first 72 h after mixing, the ear tissue samples of the 12 most aggressive and 12 least aggressive pigs were selected for DNA resequencing based on the intensity of their aggressive behavior. Large group correlation analysis indicated that the rs3262221458 site located in the 3'-UTR region of the porcine JARID2 gene has a strong relationship with the aggressive behavior of weaned pigs. Pigs with the mutant TT genotype of rs3262221458 have more aggressive behavior than those pigs with the GG and GT genotypes. The dual luciferase assay indicated that the luciferase activity of the plasmids containing the G allele of rs326221458 was significantly less than that of plasmids containing the T allele of rs326221458 and control groups. The binding ability of miR-9828-3p to sequences containing the T allele was less than that of sequences containing the G allele. The overexpression of miR-9828-3p in porcine neuroglial cells (PNGCs) and PK15 cells significantly decreased the mRNA and protein levels of the JARID2 gene. In addition, miR-9828-3p inhibited the proliferation of PNGCs. After inhibiting miR-9828-3p, the mRNA and protein expression levels of JARID2 increased, and the proliferation of PNGCs showed an opposite trend to the cells that forced the expression of miR-9828-3p. In addition, interference with the JARID2 gene by siRNA can effectively inhibit the proliferation of PNGCs. In summary, we found that the rs326221458 locus regulates the expression of the JARID2 gene by affecting the binding of miR-9828-3p and the JARID2 gene, thereby affecting the aggressive behavior of weaned pigs after mixing.


Assuntos
MicroRNAs , Polimorfismo de Nucleotídeo Único , Humanos , Suínos/genética , Animais , Camundongos , Regiões 3' não Traduzidas , RNA Mensageiro , Luciferases , MicroRNAs/genética , Complexo Repressor Polycomb 2
18.
Am J Transplant ; 22(9): 2246-2253, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35373451

RESUMO

Thrombospondin-1 (TSP-1) is a key mediator of renal ischemia-reperfusion injury (IRI), a major cause of kidney dysfunction under various disease conditions and a risk factor of renal allograft rejection. In this study, we developed a nanotechnology-based therapy targeting TSP-1 to prevent renal IRI. A biocompatible nanoparticle (NP) capable of specific binding to TSP-1 was prepared by conjugating NPs with TSP-1-binding (LSKL) peptides. LSKL/NPs not only effectively adsorbed recombinant TSP-1 proteins in vitro, but also efficiently neutralized TSP-1 in mice undergoing renal IRI. IRI-induced elevation of TSP-1 in the kidney was significantly inhibited by post-IR treatment with LSKL/NPs, but not free LSKL or NPs. Furthermore, TSP-1 proteins adsorbed on LSKL/NPs were functionally inactive and unable to induce apoptosis in renal tubular epithelial cells. Importantly, LSKL/NPs induced strong protection against renal IRI, as shown by markedly diminished serum creatinine levels and improved histological lesions of the kidney. Thus, LSKL/NPs provide a useful means of depleting and inactivating TSP-1 and a potential therapy for renal IRI.


Assuntos
Transplante de Rim , Nanopartículas , Traumatismo por Reperfusão , Animais , Apoptose , Rim/patologia , Transplante de Rim/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Trombospondina 1/antagonistas & inibidores , Trombospondina 1/metabolismo , Trombospondina 1/farmacologia
19.
BMC Cancer ; 22(1): 909, 2022 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-35986311

RESUMO

BACKGROUND: HuR/ELAVL1 (embryonic lethal abnormal vision 1) was a downstream target of miR-29b in some cancer cells. HuR protein exerts important prognostic effects of involving in the pathogenesis and development of acute myeloid leukemia (AML). This study aims to investigate the role of miR-29b-3p in biological behaviors of AML cells by targeting HuR and the involvement of the NF-κB and JAK/STAT signaling pathways. METHODS: The expressions of HuR and miR-29b-3p in AML cells were determined using RT-qPCR and Western blot, and the association between them was analyzed using the Spearman method. Next, the target relationship between HuR and miR-29b-3p was predicted by biological information databases and verified by the dual-luciferase reporter gene assay. MTS, methyl cellulose, flow cytometry and transwell assay were employed to detect the cell proliferation, clone formation, cell cycle and apoptosis, invasion and migration respectively, the effect of miR-29b-3p targeted HuR on the biological behaviors of AML cells was explored after over- /down-expression of miR-29b-3p and rescue experiment. Then, immunofluorescence assay and western blot were employed to detect location expression and phosphorylation levels of NF-κB and JAK/STAT signaling pathways related molecules respectively. RESULTS: HuR was negatively correlated with miR-29b-3p, and was the downstream target of miR-29b-3p in AML cells. When miR-29b-3p was overexpressed in AML cells, HuR was down-regulated, accompanied by cell viability decreased, cell cycle arrest, apoptosis increased, invasion and migration weakened. Moreover, the opposite result appeared after miR-29b-3p was down-regulated. The rescue experiment showed that miR-29b-3p inhibitor could reverse the biological effect of HuR down-regulation in AML cells. Molecular pathway results showed that miR-29b-3p could inhibit p65 expression in nucleus and phosphorylation levels of p65, IκBα, STAT1, STAT3 and STAT5. CONCLUSION: miR-29b-3p can inhibit malignant biological behaviors of AML cells via the inactivation of the NF-κB and JAK/STAT signaling pathways by targeting HuR. miR-29b-3p and its target HuR can be used as a new potential molecular for AML treatment.


Assuntos
Leucemia Mieloide Aguda , MicroRNAs , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Humanos , Leucemia Mieloide Aguda/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Transdução de Sinais/genética
20.
World J Urol ; 40(4): 973-982, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35064801

RESUMO

PURPOSE: The present study introduces a modified surgical procedure, extraperitoneal laparoscopic simple prostatectomy (LSP) with urethra preservation using urethral initiation as the entry point, and evaluates its feasibility, safety, and efficacy in the treatment of benign prostatic obstruction (BPO). MATERIALS AND METHODS: A total of 50 patients with BPO underwent modified LSP from January 2018 to December 2020. The main surgical procedures performed were as follows: transversely incision of prostate surgical capsule at the urethral initiation; creating of the subcapsular plane and the space between urethra and adenoma; removal of lobes with preservation of urethra followed by suturing of capsule. Preoperative, perioperative, follow-up parameters, and complications were recorded and analyzed. RESULTS: Operative time was (106.34 ± 28.00) min and intraoperative blood loss was (98.80 ± 130.58) ml. Continuous bladder irrigation (CBI) was not performed routinely, catheterization duration was (5.26 ± 2.99) days, and postoperative hospital stay was (5.42 ± 1.62) days. Significant improvements were observed in functional outcomes, whereas no retrograde ejaculation, urinary incontinence, and urethral stricture occurred. Urethral rupture was not significantly influenced by operative time, intraoperative blood loss, and prostate volume. However, it prolonged CBI duration, drainage tube retention time, catheterization duration, and postoperative hospital stay. Operative time decreased with an increase in the number of cases, and the surgeon achieved proficiency level after handling 21-25 cases. CONCLUSION: Extraperitoneal LSP with urethra preservation using urethral initiation as the entry point is a feasible, repeatable, safe, and effective surgical procedure, which is suitable for treating BPO.


Assuntos
Laparoscopia , Hiperplasia Prostática , Obstrução Uretral , Perda Sanguínea Cirúrgica , Humanos , Laparoscopia/métodos , Masculino , Prostatectomia/métodos , Hiperplasia Prostática/cirurgia , Uretra/cirurgia , Obstrução Uretral/cirurgia
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