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1.
Nature ; 575(7783): 473-479, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31748722

RESUMO

Traditional technologies for virtual reality (VR) and augmented reality (AR) create human experiences through visual and auditory stimuli that replicate sensations associated with the physical world. The most widespread VR and AR systems use head-mounted displays, accelerometers and loudspeakers as the basis for three-dimensional, computer-generated environments that can exist in isolation or as overlays on actual scenery. In comparison to the eyes and the ears, the skin is a relatively underexplored sensory interface for VR and AR technology that could, nevertheless, greatly enhance experiences at a qualitative level, with direct relevance in areas such as communications, entertainment and medicine1,2. Here we present a wireless, battery-free platform of electronic systems and haptic (that is, touch-based) interfaces capable of softly laminating onto the curved surfaces of the skin to communicate information via spatio-temporally programmable patterns of localized mechanical vibrations. We describe the materials, device structures, power delivery strategies and communication schemes that serve as the foundations for such platforms. The resulting technology creates many opportunities for use where the skin provides an electronically programmable communication and sensory input channel to the body, as demonstrated through applications in social media and personal engagement, prosthetic control and feedback, and gaming and entertainment.


Assuntos
Realidade Aumentada , Desenho de Equipamento , Pele , Tato , Interface Usuário-Computador , Realidade Virtual , Tecnologia sem Fio/instrumentação , Comunicação , Epiderme , Retroalimentação , Feminino , Humanos , Masculino , Próteses e Implantes , Robótica , Mídias Sociais , Vibração , Jogos de Vídeo
2.
Proc Natl Acad Sci U S A ; 119(48): e2206829119, 2022 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-36409915

RESUMO

Retinal ganglion cells (RGCs) are heterogeneous projection neurons that convey distinct visual features from the retina to brain. Here, we present a high-throughput in vivo RGC activity assay in response to light stimulation using noninvasive Ca2+ imaging of thousands of RGCs simultaneously in living mice. Population and single-cell analyses of longitudinal RGC Ca2+ imaging reveal distinct functional responses of RGCs and unprecedented individual RGC activity conversions during traumatic and glaucomatous degeneration. This study establishes a foundation for future in vivo RGC function classifications and longitudinal activity evaluations using more advanced imaging techniques and visual stimuli under normal, disease, and neural repair conditions. These analyses can be performed at both the population and single-cell levels using temporal and spatial information, which will be invaluable for understanding RGC pathophysiology and identifying functional biomarkers for diverse optic neuropathies.


Assuntos
Glaucoma , Células Ganglionares da Retina , Animais , Camundongos , Diagnóstico por Imagem , Retina , Glaucoma/diagnóstico por imagem , Encéfalo
3.
Genomics ; 116(5): 110903, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39069233

RESUMO

MicroRNAs (miRNAs) are widely involved in various lipogenic processes, including adipocyte proliferation and differentiation, lipid droplet formation, and adipocyte-specific gene activation. The present study aimed to investigate the gene expression profiles of bovine preadipocytes under high miR-10167-3p expression using the RNA-seq technique and to verify the functions of its downstream target genes on the proliferation and differentiation of bovine preadipocytes. First, RNA-seq identified 573 differentially expressed genes (DEGs), of which 243 were downregulated and 330 were upregulated. Then, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that 15.19% of the DEGs were enriched in pathways related to lipid metabolism. Meanwhile, dual-luciferase reporter gene assay verified the target-binding relationship between miR-10167-3p and TCF7L1. The function of TCF7L1 was assessed using several experiments in adipocytes with high TCF7L1 expression and RNA interference. The mRNA and protein expression of proliferation, differentiation, and apoptosis marker genes were detected using qPCR and western blot, respectively; lipid droplet synthesis was detected using oil red O, Nile red, and bodipy staining; adipocyte proliferation was detected by EdU; and apoptosis was detected using flow cytometry. The results revealed that TCF7L1 overexpression inhibited bovine preadipocyte differentiation and apoptosis and promoted their proliferation, with opposite results obtained with its RNA interference. These results may provide a reference for the subsequent investigation of the molecular mechanism of bovine fat deposition.

4.
Lancet Oncol ; 25(1): 76-85, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38048802

RESUMO

BACKGROUND: Locally advanced cervical cancer constitutes around 37% of cervical cancer cases globally and has a poor prognosis due to limited therapeutic options. Immune checkpoint inhibitors in the neoadjuvant setting could address these challenges. We aimed to investigate the efficacy and safety of neoadjuvant chemo-immunotherapy for locally advanced cervical cancer. METHODS: In this single-arm, phase 2 trial, which was done across eight tertiary hospitals in China, we enrolled patients aged 18-70 years with untreated cervical cancer (IB3, IIA2, or IIB/IIIC1r with a tumour diameter ≥4 cm [International Federation of Gynecology and Obstetrics, 2018]) and an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible patients underwent one cycle of priming doublet chemotherapy (75-80 mg/m2 cisplatin, intravenously, plus 260 mg/m2 nab-paclitaxel, intravenously), followed by two cycles of a combination of chemotherapy (cisplatin plus nab-paclitaxel) on day 1 with camrelizumab (200 mg, intravenously) on day 2, with a 3-week interval between treatment cycles. Patients with stable disease or progressive disease received concurrent chemoradiotherapy, and patients with a complete response or partial response proceeded to radical surgery. The primary endpoint was the objective response rate, by independent central reviewer according to Response Evaluation Criteria in Solid Tumours, version 1.1. Activity and safety were analysed in patients who received at least one dose of camrelizumab. This study is registered with ClinicalTrials.gov, NCT04516616, and is ongoing. FINDINGS: Between Dec 1, 2020, and Feb 10, 2023, 85 patients were enrolled and all received at least one dose of camrelizumab. Median age was 51 years (IQR 46-57) and no data on race or ethnicity were collected. At data cutoff (April 30, 2023), median follow-up was 11·0 months (IQR 6·0-14·5). An objective response was noted in 83 (98% [95% CI 92-100]) patients, including 16 (19%) patients who had a complete response and 67 (79%) who had a partial response. The most common grade 3-4 treatment-related adverse events during neoadjuvant chemo-immunotherapy were lymphopenia (21 [25%] of 85), neutropenia (ten [12%]), and leukopenia (seven [8%]). No serious adverse events or treatment-related deaths occurred. INTERPRETATION: Neoadjuvant chemo-immunotherapy showed promising antitumour activity and a manageable adverse event profile in patients with locally advanced cervical cancer. The combination of neoadjuvant chemo-immunotherapy with radical surgery holds potential as a novel therapeutic approach for locally advanced cervical cancer. FUNDING: National Key Technology Research and Development Program of China and the National Clinical Research Center of Obstetrics and Gynecology.


Assuntos
Trombocitopenia , Neoplasias do Colo do Útero , Feminino , Humanos , Pessoa de Meia-Idade , Cisplatino/efeitos adversos , Terapia Neoadjuvante/efeitos adversos , Neoplasias do Colo do Útero/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Trombocitopenia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
5.
BMC Genomics ; 25(1): 358, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605318

RESUMO

BACKGROUND: Hox gene family is an important transcription factor that regulates cell process, and plays a role in the process of adipocytes differentiation and fat deposition. Previous transcriptome sequencing studies have indicated that the Homeobox A9 gene (HOXA9) is a candidate gene for regulating the process of bovine lipid metabolism, but the function and specific mechanism of action remain unclear. Therefore, this study aims to explore the role of HOXA9 in the proliferation, differentiation and apoptosis of bovine preadipocytes through gain-of-function and lose-of-function. RESULT: It found HOXA9 highly expressed in bovine adipose tissue, and its expression level changed significantly during adipocytes differentiation process. It gave a hint that HOXA9 may be involved in the process of bovine lipid metabolism. The results of HOXA9 gain-of-function experiments indicated that HOXA9 appeared to act as a negative regulator not only in the differentiation but also in the proliferation of bovine preadipocytes, which is mainly reflected that overexpression of HOXA9 down-regulate the mRNA and protein expression level of PPARγ, CEBPα and FABP4 (P < 0.05). The mRNA expression level of CDK1, CDK2, PCNA, CCNA2, CCNB1, CCND1 and CCNE2, as well as the protein expression of CDK2 also significantly decreased. The decrease of lipid droplets content was the main characteristic of the phenotype (P < 0.01), which further supported the evidence that HOXA9 was a negative regulator of preadipocytes differentiation. The decrease of cell proliferation rate and EdU positive rate, as well as the limitation of transition of preadipocytes from G0/G1 phase to S phase also provided evidence for the inhibition of proliferation. Apart from this above, we noted an interesting phenomenon that overexpression of HOXA9 showed in a significant upregulation of both mRNA and protein level of apoptosis markers, accompanied by a significant increase in cell apoptosis rate. These data led us not to refute the fact that HOXA9 played an active regulatory role in apoptosis. HOXA9 loss-of-function experiments, however, yielded the opposite results. Considering that HOXA9 acts as a transcription factor, we predicted its target genes. Dual luciferase reporter assay system indicated that overexpression of HOXA9 inhibits activity of PCNA promoter. CONCLUSION: Taken together, we demonstrated for the first time that HOXA9 played a role as a negative regulatory factor in the differentiation and proliferation of preadipocytes, but played a positive regulatory role in apoptosis, and it may play a regulatory role by targeting PCNA. This study provides basic data for further exploring the regulatory network of intramuscular fat deposition in bovine.


Assuntos
Adipócitos , Genes Homeobox , Animais , Bovinos , Adipócitos/metabolismo , Antígeno Nuclear de Célula em Proliferação/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , Diferenciação Celular/genética , Proliferação de Células , Fatores de Transcrição/metabolismo , Apoptose/genética , RNA Mensageiro/metabolismo , Adipogenia/genética
6.
BMC Med ; 22(1): 317, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39113030

RESUMO

BACKGROUND: The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) serves as a novel composite lipid indicator for atherosclerosis. However, the association between NHHR and mortality in patients with diabetes or prediabetes remains unclear. Consequently, the objective of this study was to investigate the relationship between NHHR and both all-cause and cardiovascular mortality in US adults with diabetes or prediabetes. METHODS: This study included 12,578 adult participants with diabetes or prediabetes from the US National Health and Nutrition Examination Survey (1999-2018). Mortality outcomes were ascertained by linking to the National Death Index (NDI) record up to December 31, 2019. We employed a weighted multivariate Cox proportional hazards model and restricted cubic splines to assess the associations between NHHR and all-cause and cardiovascular mortality. A segmented Cox proportional hazards model was used for evaluating threshold effects. Furthermore, a competing risks analysis was performed to explore the relationship between NHHR and cardiovascular mortality. RESULTS: During a median follow-up period of 8.08 years, 2403 participants encountered all-cause mortality, with 662 of them specifically succumbing to cardiovascular mortality. The restricted cubic splines revealed a U-shaped association between NHHR and all-cause mortality, while an L-shaped association was observed for cardiovascular mortality. The analysis of threshold effects revealed that the inflection points for NHHR and all-cause and cardiovascular mortality were 2.72 and 2.83, respectively. Specifically, when the baseline NHHR was below the inflection points, a negative correlation was observed between NHHR and both all-cause mortality (HR: 0.76, 95% CI: 0.68-0.85) and cardiovascular mortality (HR: 0.70, 95% CI: 0.57-0.85). Conversely, when the baseline NHHR exceeded the inflection points, a positive correlation was observed between NHHR and both all-cause mortality (HR: 1.11, 95% CI: 1.06-1.16) and cardiovascular mortality (HR: 1.08, 95% CI: 1.00-1.16). CONCLUSIONS: Among US adults with diabetes or prediabetes, a U-shaped association was observed between NHHR and all-cause mortality, whereas an L-shaped association was identified with cardiovascular mortality. The inflection points for all-cause and cardiovascular mortality were 2.72 and 2.83, respectively.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus , Inquéritos Nutricionais , Estado Pré-Diabético , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estado Pré-Diabético/sangue , Estado Pré-Diabético/mortalidade , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/sangue , Adulto , Estados Unidos/epidemiologia , Diabetes Mellitus/mortalidade , Diabetes Mellitus/sangue , HDL-Colesterol/sangue , Idoso , Modelos de Riscos Proporcionais , Causas de Morte
7.
Chembiochem ; 25(13): e202400229, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38700379

RESUMO

Photodynamic therapy (PDT) is a newly emerged strategy for disease treatment. One challenge of the application of PDT drugs is the side-effect caused by the non-specificity of the photosensitive molecules. Most of the photosensitizers may invade not only the pathogenic cells but also the normal cells. In recent, people tried to use special cargoes to deliver the drugs into target cells. DNA nanoflowers (NFs) are a kind of newly-emerged nanomaterial which constructed through DNA rolling cycle amplification (RCA) reaction. It is reported that the DNA NFs were suitable materials which have been widely applied as nanocargos for drug delivery in cancer chemotherapeutic treatment. In this paper, we have introduced a new multifunctional DNA NF which could be prepared through an one-pot RCA reaction. This proposed DNA NF contained a versatile AS1411 G-quadruplex moiety, which plays key roles not only for specific recognition of cancer cells but also for near-infrared ray based photodynamic therapy when conjugating with a special porphyrin molecule. We demonstrated that the DNA NF showed good selectivity toward cancer cells, leading to highly efficient photo-induced cytotoxicity. Moreover, the in vivo experiment results suggested this DNA NF is a promising nanomaterial for clinical PDT.


Assuntos
DNA , Nanoestruturas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Humanos , DNA/química , Animais , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/síntese química , Nanoestruturas/química , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Linhagem Celular Tumoral
8.
Plant Cell Environ ; 47(9): 3447-3465, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38725360

RESUMO

Terrestrial water fluxes are substantially mediated by vegetation, while the distribution, growth, health, and mortality of plants are strongly influenced by the availability of water. These interactions, playing out across multiple spatial and temporal scales, link the disciplines of plant ecophysiology and ecohydrology. Despite this connection, the disciplines have provided complementary, but largely independent, perspectives on the soil-plant-atmosphere continuum since their crystallization as modern scientific disciplines in the late 20th century. This review traces the development of the two disciplines, from their respective origins in engineering and ecology, their largely independent growth and maturation, and the eventual development of common conceptual and quantitative frameworks. This common ground has allowed explicit coupling of the disciplines to better understand plant function. Case studies both illuminate the limitations of the disciplines working in isolation, and reveal the exciting possibilities created by consilience between the disciplines. The histories of the two disciplines suggest opportunities for new advances will arise from sharing methodologies, working across multiple levels of complexity, and leveraging new observational technologies. Practically, these exchanges can be supported by creating shared scientific spaces. This review argues that consilience and collaboration are essential for robust and evidence-based predictions and policy responses under global change.


Assuntos
Plantas , Plantas/metabolismo , Fenômenos Fisiológicos Vegetais , Hidrologia , Ecologia , Ecossistema , Água/metabolismo , Água/fisiologia
9.
NMR Biomed ; 37(2): e5051, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37926525

RESUMO

The objective of the current study was to develop and evaluate a DEep learning-based rapid Spiral Image REconstruction (DESIRE) and deep learning (DL)-based segmentation approach to quantify the left ventricular ejection fraction (LVEF) for high-resolution spiral real-time cine imaging, including 2D balanced steady-state free precession imaging at 1.5 T and gradient echo (GRE) imaging at 1.5 and 3 T. A 3D U-Net-based image reconstruction network and 2D U-Net-based image segmentation network were proposed and evaluated. Low-rank plus sparse (L+S) served as the reference for the image reconstruction network and manual contouring of the left ventricle was the reference of the segmentation network. To assess the image reconstruction quality, structural similarity index, peak signal-to-noise ratio, normalized root-mean-square error, and blind grading by two experienced cardiologists (5: excellent; 1: poor) were performed. To assess the segmentation performance, quantification of the LVEF on GRE imaging at 3 T was compared with the quantification from manual contouring. Excellent performance was demonstrated by the proposed technique. In terms of image quality, there was no difference between L+S and the proposed DESIRE technique. For quantification analysis, the proposed DL method was not different to the manual segmentation method (p > 0.05) in terms of quantification of LVEF. The reconstruction time for DESIRE was ~32 s (including nonuniform fast Fourier transform [NUFFT]) per dynamic series (40 frames), while the reconstruction time of L+S with GPU acceleration was approximately 3 min. The DL segmentation takes less than 5 s. In conclusion, the proposed DL-based image reconstruction and quantification techniques enabled 1-min image reconstruction for the whole heart and quantification with automatic reconstruction and quantification of the left ventricle function for high-resolution spiral real-time cine imaging with excellent performance.


Assuntos
Aprendizado Profundo , Volume Sistólico , Imagem Cinética por Ressonância Magnética/métodos , Função Ventricular Esquerda , Imageamento Tridimensional/métodos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética
10.
J Biomed Sci ; 31(1): 55, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38802791

RESUMO

BACKGROUND: Radioresistance is a key clinical constraint on the efficacy of radiotherapy in lung cancer patients. REV1 DNA directed polymerase (REV1) plays an important role in repairing DNA damage and maintaining genomic stability. However, its role in the resistance to radiotherapy in lung cancer is not clear. This study aims to clarify the role of REV1 in lung cancer radioresistance, identify the intrinsic mechanisms involved, and provide a theoretical basis for the clinical translation of this new target for lung cancer treatment. METHODS: The effect of targeting REV1 on the radiosensitivity was verified by in vivo and in vitro experiments. RNA sequencing (RNA-seq) combined with nontargeted metabolomics analysis was used to explore the downstream targets of REV1. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to quantify the content of specific amino acids. The coimmunoprecipitation (co-IP) and GST pull-down assays were used to validate the interaction between proteins. A ubiquitination library screening system was constructed to investigate the regulatory proteins upstream of REV1. RESULTS: Targeting REV1 could enhance the radiosensitivity in vivo, while this effect was not obvious in vitro. RNA sequencing combined with nontargeted metabolomics revealed that the difference result was related to metabolism, and that the expression of glycine, serine, and threonine (Gly/Ser/Thr) metabolism signaling pathways was downregulated following REV1 knockdown. LC-MS/MS demonstrated that REV1 knockdown results in reduced levels of these three amino acids and that cystathionine γ-lyase (CTH) was the key to its function. REV1 enhances the interaction of CTH with the E3 ubiquitin ligase Rad18 and promotes ubiquitination degradation of CTH by Rad18. Screening of the ubiquitination compound library revealed that the ubiquitin-specific peptidase 9 X-linked (USP9X) is the upstream regulatory protein of REV1 by the ubiquitin-proteasome system, which remodels the intracellular Gly/Ser/Thr metabolism. CONCLUSION: USP9X mediates the deubiquitination of REV1, and aberrantly expressed REV1 acts as a scaffolding protein to assist Rad18 in interacting with CTH, promoting the ubiquitination and degradation of CTH and inducing remodeling of the Gly/Ser/Thr metabolism, which leads to radioresistance. A novel inhibitor of REV1, JH-RE-06, was shown to enhance lung cancer cell radiosensitivity, with good prospects for clinical translation.


Assuntos
Neoplasias Pulmonares , Nucleotidiltransferases , Tolerância a Radiação , Ubiquitina-Proteína Ligases , Ubiquitinação , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Ubiquitina Tiolesterase/metabolismo , Ubiquitina Tiolesterase/genética , Linhagem Celular Tumoral , Camundongos , Animais , DNA Polimerase Dirigida por DNA
11.
Biotechnol Bioeng ; 121(1): 206-218, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37747706

RESUMO

The messenger RNA (mRNA) 5'-cap structure is indispensable for mRNA translation initiation and stability. Despite its importance, large-scale production of capped mRNA through in vitro transcription (IVT) synthesis using vaccinia capping enzyme (VCE) is challenging, due to the requirement of tedious and multiple pre-and-post separation steps causing mRNA loss and degradation. Here in the present study, we found that the VCE together with 2'-O-methyltransferase can efficiently catalyze the capping of poly dT media-tethered mRNA to produce mRNA with cap-1 structure under an optimized condition. We have therefore designed an integrated purification and solid-based capping protocol, which involved capturing the mRNA from the IVT system by using poly dT media through its affinity binding for 3'-end poly-A in mRNA, in situ capping of mRNA 5'-end by supplying the enzymes, and subsequent eluting of the capped mRNA from the poly dT media. Using mRNA encoding the enhanced green fluorescent protein as a model system, we have demonstrated that the new strategy greatly simplified the mRNA manufacturing process and improved its overall recovery without sacrificing the capping efficiency, as compared with the conventional process, which involved at least mRNA preseparation from IVT, solution-based capping, and post-separation and recovering steps. Specifically, the new process accomplished a 1.76-fold (84.21% over 47.79%) increase in mRNA overall recovery, a twofold decrease in operation time (70 vs. 140 min), and similar high capping efficiency (both close to 100%). Furthermore, the solid-based capping process greatly improved mRNA stability, such that the integrity of the mRNA could be well kept during the capping process even in the presence of exogenously added RNase; in contrast, mRNA in the solution-based capping process degraded almost completely. Meanwhile, we showed that such a strategy can be operated both in a batch mode and in an on-column continuous mode. The results presented in this work demonstrated that the new on-column capping process developed here can accomplish high capping efficiency, enhanced mRNA recovery, and improved stability against RNase; therefore, can act as a simple, efficient, and cost-effective platform technology suitable for large-scale production of capped mRNA.


Assuntos
Poli T , Ribonucleases , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Capuzes de RNA/química , Capuzes de RNA/genética
12.
Pharmacol Res ; 205: 107236, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38797358

RESUMO

The rapid antidepressant effects of ketamine depend on the N-methyl-D-aspartate (NMDA) receptor containing 2B subunit (NR2B), whose function is influenced by its phosphorylated regulation and distribution within and outside synapses. It remains unclear if ketamine's rapid onset of antidepressant effects relies on the dynamic phosphorylated regulation of NR2B within and outside synapses. Here, we show that ketamine rapidlyalleviated depression-like behaviors and normalized abnormal expression of pTyr1472NR2B and striatal-enriched protein tyrosine phosphatase (STEP) 61 within and outside synapses in the medial prefrontal cortex (mPFC) induced by chronic unpredictable stress (CUS) and conditional knockdown of STEP 61, a key phosphatase of NR2B, within 1 hour after administration Together, our results delineate the rapid initiation of ketamine's antidepressant effects results from the restoration of NR2B phosphorylation homeostasis within and outside synapses. The dynamic regulation of phosphorylation of NR2B provides a new perspective for developing new antidepressant strategies.


Assuntos
Antidepressivos , Depressão , Ketamina , Camundongos Endogâmicos C57BL , Córtex Pré-Frontal , Receptores de N-Metil-D-Aspartato , Receptores de N-Metil-D-Aspartato/metabolismo , Ketamina/farmacologia , Animais , Fosforilação/efeitos dos fármacos , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Masculino , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Depressão/tratamento farmacológico , Depressão/metabolismo , Proteínas Tirosina Fosfatases não Receptoras/metabolismo , Proteínas Tirosina Fosfatases não Receptoras/genética , Tirosina/metabolismo , Camundongos , Estresse Psicológico/metabolismo , Estresse Psicológico/tratamento farmacológico , Sinapses/efeitos dos fármacos , Sinapses/metabolismo , Comportamento Animal/efeitos dos fármacos
13.
Nanotechnology ; 35(18)2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38271735

RESUMO

A single ZnO nanowire device with volatile resistive switching behavior has been prepared. Different from traditional resistive switching devices, such ZnO nanowire devices do not exhibit resistive switching behaviors under a single bias voltage, and appear resistive switching behavior under the combined action of light stimuli and bias voltage. Through the demonstration of the time-dependent hysteresis curve and atmosphere-dependent hysteresis loop of the resistive switching devices, it is believed that under the resistive switching process, ultraviolet illumination can increase the carrier concentration and modulate the barrier depletion structure, and external bias voltage can ionize the surface state. They work together to modulate the switching process of the devices. Such light stimuli and bias voltage dual-modulated resistive switching device enables optical control and may thus be considered for sensory applications or optically tunable memories.

14.
Plant Cell Rep ; 43(5): 125, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38647720

RESUMO

KEY MESSAGE: The interaction network and pathway map uncover the potential crosstalk between sugar and hormone metabolisms as a possible reason for leaf senescence in P. ternata. Pinellia ternata, an environmentally sensitive medicinal plant, undergoes leaf senescence twice a year, affecting its development and yield. Understanding the potential mechanism that delays leaf senescence could theoretically decrease yield losses. In this study, a typical senescent population model was constructed, and an integrated analysis of transcriptomic and metabolomic profiles of P. ternata was conducted using two early leaf senescence populations and two stay-green populations. The result showed that two key gene modules were associated with leaf senescence which were mainly enriched in sugar and hormone signaling pathways, respectively. A network constructed by unigenes and metabolisms related to the obtained two pathways revealed that several compounds such as D-arabitol and 2MeScZR have a higher significance ranking. In addition, a total of 130 hub genes in this network were categorized into 3 classes based on connectivity. Among them, 34 hub genes were further analyzed through a pathway map, the potential crosstalk between sugar and hormone metabolisms might be an underlying reason of leaf senescence in P. ternata. These findings address the knowledge gap regarding leaf senescence in P. ternata, providing candidate germplasms for molecular breeding and laying theoretical basis for the realization of finely regulated cultivation in future.


Assuntos
Regulação da Expressão Gênica de Plantas , Metabolômica , Pinellia , Reguladores de Crescimento de Plantas , Folhas de Planta , Transcriptoma , Folhas de Planta/genética , Folhas de Planta/metabolismo , Folhas de Planta/crescimento & desenvolvimento , Pinellia/genética , Pinellia/metabolismo , Pinellia/fisiologia , Pinellia/crescimento & desenvolvimento , Reguladores de Crescimento de Plantas/metabolismo , Transcriptoma/genética , Senescência Vegetal/genética , Perfilação da Expressão Gênica , Açúcares/metabolismo , Metaboloma/genética , Redes Reguladoras de Genes , Metabolismo dos Carboidratos/genética
15.
Blood Purif ; : 1-12, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38865971

RESUMO

INTRODUCTION: Continuous renal replacement therapy (CRRT) is a primary form of renal support for patients with acute kidney injury in an intensive care unit. Making an accurate decision of discontinuation is crucial for the prognosis of patients. Previous research has mostly focused on the univariate and multivariate analysis of factors in CRRT, without the capacity to capture the complexity of the decision-making process. The present study thus developed a dynamic, interpretable decision model for CRRT discontinuation. METHOD: The study adopted a cohort of 1,234 adult patients admitted to an intensive care unit in the MIMIC-IV database. We used the eXtreme Gradient Boosting (XGBoost) machine learning algorithm to construct dynamic discontinuation decision models across 4 time points. SHapley Additive exPlanation (SHAP) analysis was conducted to exhibit the contributions of individual features to the model output. RESULT: Of the 1,234 included patients with CRRT, 596 (48.3%) successfully discontinued CRRT. The dynamic prediction by the XGBoost model produced an area under the curve of 0.848, with accuracy, sensitivity, and specificity of 0.782, 0.786, and 0.776, respectively. The performance of the XGBoost model was far superior to other test models. SHAP demonstrated that the features that contributed most to the model results were the Sequential Organ Failure Assessment score, serum lactate level, and 24-h urine output. CONCLUSION: Dynamic decision models supported by machine learning are capable of dealing with complex factors in CRRT and effectively predicting the outcome of discontinuation.

16.
BMC Public Health ; 24(1): 2248, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39160497

RESUMO

BACKGROUND: The prevalence of self-injury and suicide is higher than the general population of people living with HIV/AIDS (PLWHA). However, the results reported in existing studies are highly variable in China. The purpose of this systematic review and meta-analysis was to synthesize the currently available high-quality evidence to explore the prevalence and influence factors of self-injury and suicide among PLWHA in China. METHOD: We retrieve literature written in Chinese and English through databases such as PubMed, Embase, Web of Science, Cochrane Library, SinoMed, CNKI, WanFang Database, and CQVIP from inception to 1 September 2022. Sata 16.0 software was used for analysis. RESULTS: A total of 28 studies were included with a sample size of 1,433,971 and had a satisfactory quality score of ≥ 5. The prevalence among PLWHA in China were 30% for suicidal ideation (SI), 5% for suicide attempt (SA), 8% for suicide plan (SP), 7% for attempted suicide (AS), and 3‰ for completed suicide. High stigma (OR = 2.94, 95%CI: 1.90 - 4.57), depression (OR, 3.17; 95%CI, 2.20 - 4.57), anxiety (OR, 3.06; 95%CI, 2.23 - 4.20), low self-esteem (OR, 3.82, 95%CI, 2.22 - 6.57), high HIV related stress (OR, 2.53; 95%CI, 1.36 - 4.72), and unemployment (OR, 2.50; 95%CI, 1.51 - 4.15) are risk factors for SI; high social support (OR, 0.61; 95%CI, 0.44 - 0.84) and spouse infected with HIV (OR, 0.39; 95%CI, 0.21 - 0.74) are protective factors for SI; depression (OR, 1.62; 95%CI, 1.24 - 2.13), high aggression (OR, 4.66; 95%CI, 2.59 - 8.39), and more negative life events (OR, 2.51; 95%CI, 1.47 - 4.29) are risk factors for AS; high level of education (OR, 1.31; 95%CI, 1.21 - 1.43) is risk factor for CS. CONCLUSION: Figures indicate that approximately one-third of PLWHA had suicidal ideation, and three out of 1,000 completed suicide in China. Positive events are protective factors for self-injury and suicide among PLWHA, while negative events are risk factors. This suggests that psychosocial support and risk assessment should be integrated into the care of PLWHA.


Assuntos
Infecções por HIV , Comportamento Autodestrutivo , Suicídio , Humanos , China/epidemiologia , Comportamento Autodestrutivo/epidemiologia , Comportamento Autodestrutivo/psicologia , Infecções por HIV/psicologia , Infecções por HIV/epidemiologia , Suicídio/estatística & dados numéricos , Suicídio/psicologia , Prevalência , Fatores de Risco , Ideação Suicida , Síndrome da Imunodeficiência Adquirida/psicologia , Síndrome da Imunodeficiência Adquirida/epidemiologia , Tentativa de Suicídio/estatística & dados numéricos , Tentativa de Suicídio/psicologia
17.
Artigo em Inglês | MEDLINE | ID: mdl-38870494

RESUMO

Objectives: This study aimed to explore the experiences and caregiving perspectives of mothers from low-income families who have children with asthma,and to establish a foundation for the development of tailored nursing strategies specifically designed for families facing similar circumstances. Method: A descriptive qualitative research method was employed. Fifteen mothers of asthmatic children from low-income families receiving treatment at the Respiratory Centre of Chongqing Children's Hospital were purposefully sampled from June to December 2021. Semi-structured interviews were conducted to gather data on their caregiving experiences, and thematic analysis was utilized to analyze the interview data. Results: The interviewees were 27-42 years old (SD=32.3 years), 33.3% were full-time mothers(A woman who quit work, in order to focus on taking care of the child and the family ), 53.3% had one child, 46.6% had a college degree or higher, and 100% had health insurance. Through in-depth interviews, four main themes and eight sub-themes were identified, including (a) insufficient knowledge about the disease, (b) anxiety and uncertainty, (c) insufficient social support system, and (d) insufficient resources for medical services. The first theme describes a weak willingness to learn and medication discontinuation at will. The second theme describes financial burden and psychological stress, the third theme describes lack of family support and low social participation, and the fourth theme describes insufficient health insurance support and unequal distribution of healthcare resources. Conclusion: Mothers from low-income families with asthmatic children face substantial psychological burdens and familial pressures. It is crucial for healthcare professionals to actively engage with and deepen their understanding of these mothers' caregiving experiences and psychological well-being. By doing so, positive coping strategies can be developed, promoting the physical and mental health of these mothers and improving asthma control in their children.

18.
Ecotoxicol Environ Saf ; 281: 116611, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38909393

RESUMO

Nitrophenols, a versatile intermediate, have been widely used in leather, medicine, chemical synthesis, and other fields. Because these components are widely applied, they can enter the environment through various routes, leading to many hazards and toxicities. There has been a recent surge in the development of simple, rapid, environmentally friendly, and effective techniques for determining these environmental pollutants. This review provides a comprehensive overview of the latest research progress on the pretreatment and analysis methods of nitrophenols since 2017, with a focus on environmental samples. Pretreatment methods include liquid-liquid extraction, solid-phase extraction, dispersive extraction, and microextraction methods. Analysis methods mainly include liquid chromatography-based methods, gas chromatography-based methods, supercritical fluid chromatography. In addition, this review also discusses and compares the advantages/disadvantages and development prospects of different pretreatment and analysis methods to provide a reference for further research.


Assuntos
Poluentes Ambientais , Nitrofenóis , Poluentes Ambientais/análise , Nitrofenóis/análise , Monitoramento Ambiental/métodos , Extração Líquido-Líquido/métodos , Extração em Fase Sólida , Cromatografia Líquida , Cromatografia Gasosa , Cromatografia com Fluido Supercrítico/métodos
19.
Reprod Domest Anim ; 59(1): e14497, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37917556

RESUMO

Milk production traits as the most important economic traits of dairy cows, they directly reflect the benefits of breeding and the economic benefits of pasture. In this study, A disintegrin and metalloproteinase-12 (ADAM12), Parkinson's disease gene 2 (PRKN) and dipeptidyl peptidase-like protein subtype 6 (DPP6) polymorphism in 384 Chinese Holstein cows were detected by time-of-flight mass spectrometry and through statistical analysis using software such as Popgene 32, SAS 9.4 and Origin 2022, the relationship between single nucleotide polymorphisms (SNPs) of three genes with four milk production traits such as daily milk yield (DMY), milk fat percentage (MFP), milk protein percentage (MPP) and somatic cell score (SCS) was verified at molecular level. The results showed that four polymorphic loci (116,467,133, 116,604,487, 116,618,268 and 116,835,111) of DPP6 gene, two polymorphic loci (97,665,052 and 97,159,837) of PRKN gene and two polymorphic loci (45,542,714 and 45,553,888) of ADAM12 gene were detected. PRKN-97665052, DPP6-116467133, ADAM12-45553888, DPP6-116604487 and DPP6-116835111 were all in Hardy-Weinberg equilibrium state (p > .05). ADAM12-45542714, PRKN-97159837 and PRKN-97665052 were moderately polymorphic (0.25 ≤ PIC <0.50) in Holstein. It is evident that the selection potential and genetic variation of these five loci are relatively large, and the genetic richness is relatively high. The correlation analysis of different genotypes between these eight loci and milk production traits of Holstein showed that ADAM12-45542714 and DPP6-116835111 (p < .01) had an extremely significant effects on the DMY of Chinese Holstein in Ningxia, while PRKN-97665052 had an extremely significant effect on MFP (p < .01). The effect of PRKN-97665052 and DPP6-116467133 on MPP of Holstein were extremely significant (p < .01). DPP6-116618268 had an extremely significant effect on the SCS of Holstein in Ningxia (p < .01), and AA genotype individuals showed a higher SCS than GG genotype individuals; the other two loci (ADAM12-45553888 and DPP6-116604487) had no significant effects on milk production traits of Holstein (p > .05). In addition, through the joint analysis of DPP6, PRKN and ADAM12 gene loci, it was found that the interaction effect between the three gene loci could significantly affect the DMY, SCS (p < .01) and MPP (p < .05). In conclusion, several different loci of DPP6, PRKN and ADAM12 genes can affect the milk production traits of Holstein to different degrees. PRKN, DPP6 and ADAM12 genes can be used as potential candidate genes for milk production traits of Holstein for marker-assisted selection, providing theoretical basis for breeding of Holstein.


Assuntos
Lactação , Leite , Polimorfismo de Nucleotídeo Único , Animais , Bovinos/genética , Feminino , Humanos , Proteína ADAM12/genética , Proteína ADAM12/metabolismo , Dipeptidil Peptidases e Tripeptidil Peptidases/análise , Dipeptidil Peptidases e Tripeptidil Peptidases/genética , Dipeptidil Peptidases e Tripeptidil Peptidases/metabolismo , Genótipo , Lactação/genética , Leite/química , Proteínas do Leite , Proteínas do Tecido Nervoso/análise , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Fenótipo , Canais de Potássio/análise , Canais de Potássio/genética , Canais de Potássio/metabolismo , Proteínas/metabolismo , Ubiquitina-Proteína Ligases/genética
20.
J Adv Nurs ; 80(7): 2822-2834, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38186045

RESUMO

AIM: This study aimed to analyse the effects of servant leadership on nurses' emotional failure and compliance with standard precautions and to explore the moderating effect of individual resilience. DESIGN: A cross-sectional survey. METHODS: This descriptive cross-sectional study was conducted from October 9 to November 1, 2022. The convenience sampling method was used to collect questionnaire data from 924 clinical nurses in a third-class general hospital in Chongqing, China. RESULTS: The emotional exhaustion and compliance with standard precautions were at the general level. Servant leadership mediated by emotional exhaustion had a significant positive predictive effect on compliance with standard precautions. Personal resilience played a negative moderating role in the relationship between servant leadership and emotional exhaustion. For nurses with low resilience, servant leadership had a greater impact on emotional exhaustion. CONCLUSION: The current compliance with standard precautions for clinical nurses is not high due to emotional exhaustion. The level of servant leadership can alleviate nurses' emotional exhaustion and improve compliance with standard precautions. Especially for nurses with low personal resilience, the care and support of department leaders are needed. IMPACT: We found that the compliance with standard precautions is not high, and the link between emotional exhaustion, servant leadership and compliance with standard precautions provides a basis for further patient care. NO PATIENT OR PUBLIC CONTRIBUTION: There was no patient or public involvement. IMPACT STATEMENT: Nurses are the key population for hospital infection prevention and control, and their level of compliance with standard precautions is of great significance for hospital infection prevention and control. However, in practice, nurses' compliance with standard precautions is generally low. Most of the previous studies on nurses' compliance with standard precautions were conducted from the perspective of individual nurses, based on the staff's 'knowledge, belief, and action' to study the current status of compliance with standard precautions and the factors affecting adherence, with less attention paid to the influence of psychological, environmental, and organizational factors. Therefore, the study focuses on the impact of servant leadership and emotional exhaustion on standard precautionary adherence, which is of great significance for good care management at the organizational level. It also explored how the impact of servant leadership on emotional exhaustion varies across levels of resilience, which is important for accurately identifying different types of nursing staff and targeting assistance.


Assuntos
Esgotamento Profissional , Fidelidade a Diretrizes , Liderança , Recursos Humanos de Enfermagem Hospitalar , Humanos , Estudos Transversais , Feminino , Adulto , Masculino , Esgotamento Profissional/psicologia , Recursos Humanos de Enfermagem Hospitalar/psicologia , Recursos Humanos de Enfermagem Hospitalar/estatística & dados numéricos , Inquéritos e Questionários , Fidelidade a Diretrizes/estatística & dados numéricos , China , Pessoa de Meia-Idade , Resiliência Psicológica , Exaustão Emocional
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