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1.
mBio ; : e0108824, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38953634

RESUMO

Numerous host factors, in addition to human angiotensin-converting enzyme 2 (hACE2), have been identified as coreceptors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demonstrating broad viral tropism and diversified druggable potential. We and others have found that antihistamine drugs, particularly histamine receptor H1 (HRH1) antagonists, potently inhibit SARS-CoV-2 infection. In this study, we provided compelling evidence that HRH1 acts as an alternative receptor for SARS-CoV-2 by directly binding to the viral spike protein. HRH1 also synergistically enhanced hACE2-dependent viral entry by interacting with hACE2. Antihistamine drugs effectively prevent viral infection by competitively binding to HRH1, thereby disrupting the interaction between the spike protein and its receptor. Multiple inhibition assays revealed that antihistamine drugs broadly inhibited the infection of various SARS-CoV-2 mutants with an average IC50 of 2.4 µM. The prophylactic function of these drugs was further confirmed by authentic SARS-CoV-2 infection assays and humanized mouse challenge experiments, demonstrating the therapeutic potential of antihistamine drugs for combating coronavirus disease 19.IMPORTANCEIn addition to human angiotensin-converting enzyme 2, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can utilize alternative cofactors to facilitate viral entry. In this study, we discovered that histamine receptor H1 (HRH1) not only functions as an independent receptor for SARS-CoV-2 but also synergistically enhances ACE2-dependent viral entry by directly interacting with ACE2. Further studies have demonstrated that HRH1 facilitates the entry of SARS-CoV-2 by directly binding to the N-terminal domain of the spike protein. Conversely, antihistamine drugs, primarily HRH1 antagonists, can competitively bind to HRH1 and thereby prevent viral entry. These findings revealed that the administration of repurposable antihistamine drugs could be a therapeutic intervention to combat coronavirus disease 19.

2.
Clin Chim Acta ; 561: 119828, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38909979

RESUMO

OBJECTIVE: To explore Cytomegalovirus (CMV) antigen-specific multi-cytokine immune responses in patients with rheumatic disease (RD) under different CMV infection status. METHODS: A total of 60 RD patients in our center from March 2023 to August 2023 were enrolled. The patients were divided into latent CMV infection and active CMV infection, the latter was classified as subclinical CMV infection or CMV disease based on presence or absence of symptoms related to CMV. Whole blood was collected and stimulated with QuantiFERON-CMV antigen. The levels of IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10, IL-17 and CXCL-2 in supernatant were measured by Luminex Assays. The receiver operating characteristic curve was used to evaluate the diagnostic accuracy of cytokine for distinguishing different CMV infection status. RESULTS: The proportion of patients with severe lymphopenia was lowest in the latent CMV infection group, while there were no significant differences in medication usage in different CMV infection status. After stimulation with QF-CMV antigens, the levels of IFN-γ, TNF-α and IL-2 in the CMV disease group were significantly lower than those in the latent CMV infection group. CMV antigen-specific IFN-γ, TNF-α levels and severe lymphopenia together provided the best discriminatory performance for distinguishing between latent and either active CMV infection patients (AUC = 0.854) or CMV disease patients (AUC = 0.935). CONCLUSION: Noninvasive peripheral blood biomarkers (the combination of CMV antigen-specific IFN-γ, TNF-α levels and severe lymphopenia) may have the potential to diferentiate different status of CMV infection in RD population.

3.
Clin Lung Cancer ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38879393

RESUMO

OBJECTIVES: Lorlatinib, a brain-penetrant, third-generation anaplastic lymphoma kinase (ALK) inhibitor, demonstrated robust overall and intracranial antitumor activity in patients with advanced ALK-positive non-small cell lung cancer (NSCLC) previously treated with an ALK inhibitor in a global phase 1/2 study (NCT01970865) and a multicenter phase 2 study conducted in China (NCT03909971). We report updated 3-year follow-up data from the phase 2 study. MATERIALS AND METHODS: Chinese patients with locally advanced or metastatic ALK-positive NSCLC that progressed after crizotinib as the only prior ALK inhibitor (cohort 1) or after 1 non-crizotinib ALK inhibitor (cohort 2), were enrolled in the study. All patients received lorlatinib 100 mg once daily. RESULTS: At data cutoff, of 109 enrolled patients, the median duration of follow-up for progression-free survival (PFS) was 35.8 months in cohort 1 (n = 67) and 33.1 months in cohort 2 (n = 42). Median PFS (95% CI) per independent central review was 26.3 months (16.6-35.9) and 5.6 months (2.9-12.4), respectively. The median duration of follow-up for overall survival (OS) was 36.4 months and 37.5 months, respectively. Median OS (95% CI) was not reached (NR; NR-NR) and 21.9 months (11.9-NR), respectively. Median intracranial time to progression (95% CI) was NR (NR-NR) and NR (9.7 months-NR), respectively. No new safety signals emerged with long-term treatment. CONCLUSION: The long-term data confirm robust overall and intracranial clinical activity of lorlatinib, with no new safety signals emerging. These results support using lorlatinib in Chinese patients with previously treated ALK-positive NSCLC with or without brain metastases. CLINICALTRIALS: gov NCT03909971.

4.
J Mater Chem B ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38904428

RESUMO

Intracellular oxidative protection mechanisms and adverse systemic toxicity are major obstacles for the success of chemodynamic therapy (CDT)/chemotherapy (CT) synergistic therapy. To tackle the fundamental challenges of current CDT and circumvent the side effects of conventional CT, we developed a copper peroxide (CP) and disulfiram (DSF)-loaded 3-aminotriazole (3-AT) doped ZIF-8 (MAF) with partial sequence-specificity using hyaluronic acid (HA) and triphenylphosphine (TPP) in this study. Upon intravenous administration, CP@MAF-DSF@PEG-TPP@HA (CPMDTH) nanoparticles (NPs) were enriched in tumor tissues through HA-mediated endocytosis, followed by enhanced accumulation in mitochondria by the TPP target. The acidic tumor environment (TME) triggered the decomposition of MAF to release CP, DSF and 3-AT. Cu2+ and H2O2 hydrated from CP NPs produced ˙OH via a Fenton-like reaction. CAT activity inhibition and GSH consumption induced by 3-AT dramatically amplified mitochondrial oxidative stress, thereby promoting the overproduction of ˙OH. In addition, the accumulation of DSF and Cu2+ led to the formation of a cytotoxic bis(N,N-diethyldithiocarbamate) copper(II) complex (Cu(DTC)2) in situ, achieving efficient CT. CPMDTH NPs demonstrated significantly improved antitumor efficiency and excellent biosafety both in vitro and in vivo. This study offers a promising therapeutic strategy for CDT/CT synergistic oncotherapy.

5.
Talanta ; 277: 126363, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38850806

RESUMO

Serotonin, a pivotal neurotransmitter regulating various physiological functions, plays a crucial role in disease diagnosis, necessitating precise monitoring of its levels in biological fluids for accurate assessment. Aptamers, known for their high specificity and affinity, have emerged as innovative molecular probes for serotonin analysis. However, existing serotonin aptamer sensing platforms exhibit limitations in terms of portability and rapid detection capabilities. In this study, we introduce a novel, portable, label-free serotonin aptamer sensor utilizing a dye replacement strategy, achieving a short sample-to-result turnaround time and convenient signal readout through a smartphone. The performance of this aptamer sensor was thoroughly assessed across diverse physiological media, demonstrating robust stability in buffer, urine, and serum. Importantly, the detection limit was in the nanomolar range, emphasizing its suitability for the rapid, sensitive, and user-friendly detection of serotonin. This research pioneers an approach for the development of a point-of-care testing (POCT) system for serotonin with practical implications, particularly in resource-limited settings.

6.
J Vis Exp ; (208)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38912821

RESUMO

Retinal organoids (ROs) are a three-dimensional culture system mimicking human retinal features that have differentiated from induced pluripotent stem cells (iPSCs) under specific conditions. Synapse development and maturation in ROs have been studied immunocytochemically and functionally. However, the direct evidence of the synaptic contact ultrastructure is limited, containing both special ribbon synapses and conventional chemical synapses. Transmission electron microscopy (TEM) is characterized by high resolution and a respectable history elucidating retinal development and synapse maturation in humans and various species. It is a powerful tool to explore synaptic structure in ROs and is widely used in the research field of ROs. Therefore, to better explore the structure of RO synaptic contacts at the nanoscale and obtain high-quality microscopic evidence, we developed a simple and repeatable method of RO TEM sample preparation. This paper describes the protocol, reagents used, and detailed steps, including RO fixation preparation, post fixation, embedding, and visualization.


Assuntos
Microscopia Eletrônica de Transmissão , Organoides , Retina , Organoides/ultraestrutura , Organoides/citologia , Retina/citologia , Retina/ultraestrutura , Microscopia Eletrônica de Transmissão/métodos , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/ultraestrutura , Animais , Sinapses/ultraestrutura
7.
Chemistry ; : e202402085, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926940

RESUMO

We described a copper(I)-catalyzed atom economic and selective hydroamination-cyclization of alkynyl-tethered quinazolinones to prepare a variety of indole-fused pyrazino[1,2-a]quinazolinones in good to excellent yields ranging from 39% to 99% under mild reaction conditions. Control experiments revealed that coordination-directed method of quinazolinone moiety with copper(I) was important for the selective hydroamination-cyclization of alkynes at the N1-atom instead of N3-atom of quinazolinone. The reaction could be easily performed at gram scales and some prepared indole-fused pyrazino[1,2-a]quinazolinones with donating groups on the indole moiety showed a distinct fluorescence emission wavelength with blue shift under the acid conditions.

8.
Angew Chem Int Ed Engl ; 63(29): e202403391, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38717757

RESUMO

Room temperature phosphorescence (RTP) materials have garnered significant attention owing to its distinctive optical characteristics and broad range of potential applications. However, the challenge remains in producing RTP materials with more simplicity, versatility, and practicality on a large scale, particularly in achieving chiral signals within a single system. Herein, we show that a straightforward and effective combination of wet spinning and twisting technique enables continuously fabricating RTP fibers with twisting-induced helical chirality. By leveraging the hydrogen bonding interactions between polyvinyl alcohol (PVA) and quinoline derivatives, along with the rigid microenvironment provided by PVA chains, typically, Q-NH2@PVA fiber demonstrates outstanding phosphorescent characteristics with RTP lifetime of 1.08 s and phosphorescence quantum yield of 24.6 %, and the improved tensile strength being 1.7 times than pure PVA fiber (172±5.82 vs 100±5.65 MPa). Impressively, the transformation from RTP to circularly polarized room temperature phosphorescence (CP-RTP) is readily achieved by imparting left- or right-hand helical structure through simply twisting, enabling large-scale production of chiral Q-NH2@PVA fiber with dissymmetry factor of 10-2. Besides, an array of displays and encryption patterns are crafted by weaving or seaming to exemplify the promising applications of these PVA-based fibers with outstanding adaptivity in cutting-edge anti-counterfeiting technology.

9.
Anal Chem ; 96(23): 9666-9675, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38815126

RESUMO

Epigenetic modification plays an indispensable role in regulating routine molecular signaling pathways, yet it is rarely used to modulate molecular self-assembly networks. Herein, we constructed a bioorthogonal demethylase-stimulated DNA circuitry (DSC) system for high-fidelity imaging of microRNA (miRNA) in live cells and mice by eliminating undesired off-site signal leakage. The simple and robust DSC system is composed of a primary cell-specific circuitry regulation (CR) module and an ultimate signal-transducing amplifier (SA) module. After the modularly designed DSC system was delivered into target live cells, the DNAzyme of the CR module was site-specifically activated by endogenous demethylase to produce fuel strands for the subsequent miRNA-targeting SA module. Through the on-site and multiply guaranteed molecular recognitions, the lucid yet efficient DSC system realized the reliably amplified in vivo miRNA sensing and enabled the in-depth exploration of the demethylase-involved signal pathway with miRNA in live cells. Our bioorthogonally on-site-activated DSC system represents a universal and versatile biomolecular sensing platform via various demethylase regulations and shows more prospects for more different personalized theragnostics.


Assuntos
DNA Catalítico , MicroRNAs , MicroRNAs/análise , MicroRNAs/metabolismo , DNA Catalítico/metabolismo , DNA Catalítico/química , Animais , Camundongos , Humanos , Metilação de DNA , Imagem Óptica
10.
Sci Total Environ ; 938: 173530, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38815818

RESUMO

Microbial fuel cells (MFCs), known for their low energy consumption, high efficiency, and environmental friendliness, have been widely utilized for removing antibiotics from wastewater. Compared to conventional wastewater treatment methods, MFCs produce less sludge while exhibiting superior antibiotic removal capacity, effectively reducing the spread of antibiotic resistance genes (ARGs). This study investigates 1) the mechanisms of ARGs generation and proliferation in MFCs; 2) the influencing factors on the fate and removal of antibiotics and ARGs; and 3) the fate and mitigation of ARGs in MFC and MFC-coupled systems. It is indicated that high removal efficiency of antibiotics and minimal amount of sludge production contribute the mitigation of ARGs in MFCs. Influencing factors, such as cathode potential, electrode materials, salinity, initial antibiotic concentration, and additional additives, can lead to the selection of tolerant microbial communities, thereby affecting the abundance of ARGs carried by various microbial hosts. Integrating MFCs with other wastewater treatment systems can synergistically enhance their performance, thereby improving the overall removal efficiency of ARGs. Moreover, challenges and future directions for mitigating the spread of ARGs using MFCs are suggested.


Assuntos
Antibacterianos , Fontes de Energia Bioelétrica , Resistência Microbiana a Medicamentos , Eliminação de Resíduos Líquidos , Águas Residuárias , Eliminação de Resíduos Líquidos/métodos , Resistência Microbiana a Medicamentos/genética , Águas Residuárias/microbiologia , Poluentes Químicos da Água
11.
Brain Struct Funct ; 229(5): 1279-1298, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38703218

RESUMO

ß-synuclein, a member of the synuclein family, is frequently co-expressed with α-synuclein in the neural system, where it serves to inhibit abnormal aggregation of α-synuclein in neurodegenerative diseases. Beyond its role in pathological conditions, ß-synuclein plays various functions independently of α-synuclein. In our investigation, we discovered a broader expression of ß-synuclein in the mouse retina compared to α-synuclein. This widespread pattern implies its potential significance in the retina. Through detailed examination via light- and electron-microscopic immunocytochemistry, we identified ß-synuclein expression from the inner segment (IS) and outer segment (OS) of photoreceptor cells to the ganglion cell layer (GCL). Our findings unveiled unique features, including ß-synuclein immunoreactive IS and OS of cones, higher expression in cone pedicles than in rod spherules, absence in horizontal cells, limited expression in cone bipolar dendrites and somas, higher expression in cone bipolar terminals, presence in most amacrine cells, and expression in almost majority of somas in GCL with an absence in intrinsically photosensitive retinal ganglion cell (ipRGCs) processes. Notably, all cholinergic amacrine cells express high ß- but not α-synuclein, while dopaminergic amacrine cells express α-synuclein exclusively. These distinctive expression patterns offer valuable insights for further exploration into the functions of ß-synuclein and its potential role in synuclein pathology within the retina.


Assuntos
Camundongos Endogâmicos C57BL , Retina , Células Ganglionares da Retina , alfa-Sinucleína , beta-Sinucleína , Animais , Masculino , Camundongos , alfa-Sinucleína/metabolismo , Células Amácrinas/metabolismo , beta-Sinucleína/metabolismo , Retina/metabolismo , Células Bipolares da Retina/metabolismo , Células Ganglionares da Retina/metabolismo
12.
Ultrasound Med Biol ; 50(8): 1134-1142, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38692941

RESUMO

BACKGROUND: Intracardiac or pulmonary right-to-left shunt (RLS) is a common cardiac anomaly associated with an increased risk of neurological disorders, specifically cryptogenic stroke. Saline-contrasted transthoracic echocardiography (scTTE) is often used for RLS diagnosis. However, the identification of saline microbubbles in the left heart can be challenging for novice residents, potentially leading to a delay in diagnosis and treatment. In this study, we proposed an artificial intelligence (AI)-based algorithm designed to automatically detect microbubbles in scTTE images and evaluate right-to-left shunt grades. This tool aims to support residency training and decrease the workload of cardiologists. METHODS: A dataset of 23,665 scTTE images obtained from 174 individuals was included in this study. This dataset was partitioned into a training set (n = 20,475) and an internal validation set (n = 3,190) on a patient-level basis. An additional cohort of 33 patients diagnosed with cryptogenic ischemic stroke was enrolled as an external validation set. The proposed algorithm for right-to-left shunt degree classification employed the EfficientNet-b4 model, and the model's performance was evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity, and compared to the performance of residents. RESULTS: Our AI model demonstrated robust performance with an accuracy of 0.926, sensitivity of 0.827, and specificity of 0.951 on the internal testing dataset. In the external validation set, our AI model exhibited diagnostic accuracy, sensitivity, and specificity of 0.864, 0.818, and 0.909, respectively. In comparison, residents achieved values of 0.727, 0.636, and 0.818, respectively. CONCLUSION: Our AI model provides a swift, precise, and easily deployable methodology for grading the degree of right-to-left shunt in scTTE, carrying substantial implications for routine clinical practice. Residents can benefit from our artificial intelligence-based algorithm, enhancing both the accuracy and efficiency of RLS diagnosis.


Assuntos
Inteligência Artificial , Ecocardiografia , Humanos , Feminino , Ecocardiografia/métodos , Masculino , Pessoa de Meia-Idade , Adulto , Solução Salina , Idoso , Algoritmos , Meios de Contraste , Adolescente , Adulto Jovem
13.
ACS Biomater Sci Eng ; 10(6): 3946-3957, 2024 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-38701357

RESUMO

Elevated levels of ROS, bacterial infection, inflammation, and improper regeneration are the factors that need to be addressed simultaneously for achieving effective wound healing without scar formation. This study focuses on the fabrication of electrospun ROS-responsive selenium-containing polyurethane nanofibers incorporating deferoxamine mesylate (Def), indomethacin (Indo), and gold nanorods (AuNRs) as proangiogenesis, anti-inflammatory, and antibacterial agents for synchronized delivery to a full-thickness wound in vivo. The structure of the fabricated nanofibers was analyzed by various techniques. Toxicity was checked by CCK-8 and hemolytic assays. The efficiency of wound healing in vitro was verified by a transwell assay and cell scratch assay. The wound healing efficiency of the nanofibers was assayed in full-thickness wounds in a rat model. The multifunctional nanofibers had a porous structure, enhanced antioxidation, antibacterial activity, and promoted wound healing. They eradicated TNF-α and IL-6, increased IL-10 expression, and revealed the angiogenic potential by increased expression of HIF-1α, VEGF, and CD31.


Assuntos
Ouro , Nanofibras , Poliuretanos , Espécies Reativas de Oxigênio , Selênio , Cicatrização , Cicatrização/efeitos dos fármacos , Poliuretanos/química , Poliuretanos/farmacologia , Animais , Nanofibras/química , Selênio/química , Selênio/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Ouro/química , Ouro/farmacologia , Ratos , Nanotubos/química , Antibacterianos/farmacologia , Antibacterianos/química , Desferroxamina/farmacologia , Desferroxamina/química , Ratos Sprague-Dawley , Humanos , Indometacina/farmacologia , Masculino , Neovascularização Fisiológica/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química
14.
Nano Lett ; 24(22): 6465-6473, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38767853

RESUMO

Neutrophilic superhalide-anion-triggered chalcogen conversion-based Zn batteries, despite latent high-energy merit, usually suffer from a short lifespan caused by dendrite growth and shuttle effect. Here, a superhalide-anion-motivator reforming strategy is initiated to simultaneously manipulate the anode interface and Se conversion intermediates, realizing a bipolar regulation toward longevous energy-type Zn batteries. With ZnF2 chaotropic additives, the original large-radii superhalide zincate anion species in ionic liquid (IL) electrolytes are split into small F-containing species, boosting the formation of robust solid electrolyte interphases (SEI) for Zn dendrite inhibition. Simultaneously, ion radius reduced multiple F-containing Se conversion intermediates form, enhancing the interion interaction of charged products to suppress the shuttle effect. Consequently, Zn||Se batteries deliver a ca. 20-fold prolonged lifespan (2000 cycles) at 1 A g-1 and high energy/power density of 416.7 Wh kgSe-1/1.89 kW kgSe-1, outperforming those in F-free counterparts. Pouch cells with distinct plateaus and durable cyclability further substantiate the practicality of this design.

15.
J Plant Physiol ; 297: 154262, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38703548

RESUMO

Aluminum (Al) is the major limiting factor affecting plant productivity in acidic soils. Al3+ ions exhibit increased solubility at a pH below 5, leading to plant root tip toxicity. Alternatively, plants can perceive very low concentrations of Al3+, and Al triggers downstream signaling even at pH 5.7 without causing Al toxicity. The ALUMINUM-ACTIVATED-MALATE-TRANSPORTER (ALMT) family members act as anion channels, with some regulating the secretion of malate from root apices to chelate Al, which is a crucial mechanism for plant Al resistance. To date, the role of the ALMT gene family within the legume Medicago species has not been fully characterized. In this study, we investigated the ALMT gene family in M. sativa and M. truncatula and identified 68 MsALMTs and 18 MtALMTs, respectively. Phylogenetic analysis classified these genes into five clades, and synteny analysis uncovered genuine paralogs and orthologs. The real-time quantitative reverse transcription PCR (qRT-PCR) analysis revealed that MtALMT8, MtALMT9, and MtALMT15 in clade 2-2b are expressed in both roots and root nodules, and MtALMT8 and MtALMT9 are significantly upregulated by Al in root tips. We also observed that MtALMT8 and MtALMT9 can partially restore the Al sensitivity of Atalmt1 in Arabidopsis. Moreover, transcriptome analysis examined the expression patterns of these genes in M. sativa in response to Al at both pH 5.7 and pH 4.6, as well as to protons, and found that Al and protons can independently induce some Al-resistance genes. Overall, our findings indicate that MtALMT8 and MtALMT9 may play a role in Al resistance, and highlight the resemblance between the ALMT genes in Medicago species and those in Arabidopsis.


Assuntos
Alumínio , Perfilação da Expressão Gênica , Filogenia , Proteínas de Plantas , Alumínio/toxicidade , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Família Multigênica , Medicago truncatula/genética , Medicago truncatula/efeitos dos fármacos , Medicago truncatula/metabolismo , Medicago sativa/genética , Medicago sativa/efeitos dos fármacos , Medicago sativa/fisiologia , Raízes de Plantas/genética , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Genoma de Planta , Transportadores de Ânions Orgânicos/genética , Transportadores de Ânions Orgânicos/metabolismo , Medicago/genética , Medicago/fisiologia
16.
BMC Genom Data ; 25(1): 43, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38710997

RESUMO

BACKGROUND: Cadmium (Cd) is extremely toxic and non-essential for plants. Different soybean varieties differ greatly in their Cd accumulation ability, but little is known about the underlying molecular mechanisms. RESULTS: Here, we performed transcriptomic analysis using Illumina pair-end sequencing on root tissues from two soybean varieties (su8, high-Cd-accumulating (HAS) and su7, low Cd-accumulating (LAS)) grown with 0 or 50 µM CdSO4. A total of 18.76 million clean reads from the soybean root samples were obtained after quality assessment and data filtering. After Cd treatment, 739 differentially expressed genes (DEGs; 265 up and 474 down) were found in HAS; however, only 259 DEGs (88 up and 171 down) were found in LAS, and 64 genes were same between the two varieties. Pathway enrichment analysis suggested that after cadmium treatment, the DEGs between LAS and HAS were mainly enriched in glutathione metabolism and plant-pathogen interaction pathways. KEGG analysis showed that phenylalanine metabolism responding to cadmium stress in LAS, while ABC transporters responding to cadmium stress in HAS. Besides we found more differential expressed heavy metal transporters such as ABC transporters and zinc transporters in HAS than LAS, and there were more transcription factors differently expressed in HAS than LAS after cadmium treatment in two soybean varieties, eg. bHLH transcription factor, WRKY transcription factor and ZIP transcription factor. CONCLUSIONS: Findings from this study will shed new insights on the underlying molecular mechanisms behind the Cd accumulation in soybean.


Assuntos
Cádmio , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Glycine max , Estresse Fisiológico , Glycine max/genética , Glycine max/efeitos dos fármacos , Glycine max/metabolismo , Cádmio/toxicidade , Cádmio/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Estresse Fisiológico/genética , Genótipo , Transcriptoma/efeitos dos fármacos , Raízes de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética
17.
Front Neurol ; 15: 1364952, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38699054

RESUMO

Background: Timely intravenous thrombolysis (IVT) is crucial for improving outcomes in acute ischemic stroke (AIS) patients. This study evaluates the effectiveness of the Acute Stroke Care Map (ASCaM) initiative in Shenyang, aimed at reducing door-to-needle times (DNT) and thus improving the timeliness of care for AIS patients. Methods: An retrospective cohort study was conducted from April 2019 to December 2021 in 30 hospitals participating in the ASCaM initiative in Shenyang. The ASCaM bundle included strategies such as EMS prenotification, rapid stroke triage, on-call stroke neurologists, immediate neuroimaging interpretation, and the innovative Pre-hospital Emergency Call and Location Identification feature. An interrupted time series analysis (ITSA) was used to assess the impact of ASCaM on DNT, comparing 9 months pre-intervention with 24 months post-intervention. Results: Data from 9,680 IVT-treated ischemic stroke patients were analyzed, including 2,401 in the pre-intervention phase and 7,279 post-intervention. The ITSA revealed a significant reduction in monthly DNT by -1.12 min and a level change of -5.727 min post-ASCaM implementation. Conclusion: The ASCaM initiative significantly reduced in-hospital delays for AIS patients, demonstrating its effectiveness as a comprehensive stroke care improvement strategy in urban settings. These findings highlight the potential of coordinated care interventions to enhance timely access to reperfusion therapies and overall stroke prognosis.

18.
ACS Appl Mater Interfaces ; 16(21): 27794-27803, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38748448

RESUMO

The development of optical humidity detection has been of considerable interest in highly integrated wearable electronics and packaged equipment. However, improving their capacities for color recognition at ultralow humidity and response-recovery rate remains a significant challenge. Herein, we propose a type of hybrid water-harvesting channel to construct brand-new passive fluorescence humidity sensors (PFHSs). Specifically, the hybrid water-harvesting channels involve porous metal-organic frameworks and a hydrophilic poly(acrylic acid) network that can capture water vapors from the ambient environment even at ultralow humidity, into which polar-responsive aggregation-induced emission molecules are doped to impart humidity-sensitive luminescence colors. As a result, the PFHSs exhibit clearly defined fluorescence signals within 0-98% RH coupling with desirable performances such as a fast response rate, precise quantitative feedback, and durable reversibility. Given the flexible processability of this system, we further upgrade the porous structure via electrostatic spinning to furnish a kind of Nano-PFHSs, demonstrating an impressive response time (<100 ms). Finally, we validate the promising applications of these sensors in electronic humidity monitoring and successfully fabricate a portable and rapid humidity indicator card.

19.
J Chem Phys ; 160(17)2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38748027

RESUMO

The design of heterogeneous catalysts generally involves optimizing the reactivity descriptor of adsorption energy, which is inevitably governed by the structure of surface-active sites. A prerequisite for understanding the structure-properties relationship is the precise identification of real surface-active site structures, rather than relying on conceived structures derived from bulk alloy properties. However, it remains a formidable challenge due to the dynamic nature of nanoalloys during catalytic reactions and the lack of accurate and efficient interatomic potentials for simulations. Herein, a generalizable deep-learning potential for the Ag-Pd-F system is developed based on a dataset encompassing the bulk, surface, nanocluster, amorphous, and point defected configurations with diverse compositions to achieve a comprehensive description of interatomic interactions, facilitating precise prediction of adsorption energy, surface energy, formation energy, and diffusion energy barrier and is utilized to investigate the structural evolutions of AgPd nanoalloys during fluorination. The structural evolutions involve the inward diffusion of F, the outward diffusion of Ag in Ag@Pd nanoalloys, the formation of surface AgFx species in mixed and Janus AgPd nanoalloys, and the shape deformation from cuboctahedron to sphere in Ag and Pd@Ag nanoalloys. Moreover, the effects of atomic diffusion and dislocation formation and migration on the reconstructing pathway of nanoalloys are highlighted. It is demonstrated that the stress relaxation upon F adsorption serves as the intrinsic driving factor governing the surface reconstruction of AgPd nanoalloys.

20.
Health Informatics J ; 30(2): 14604582241255818, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38779978

RESUMO

Mycoplasma pneumonia may lead to hospitalizations and pose life-threatening risks in children. The automated identification of mycoplasma pneumonia from electronic medical records holds significant potential for improving the efficiency of hospital resource allocation. In this study, we proposed a novel method for identifying mycoplasma pneumonia by integrating multi-modal features derived from both free-text descriptions and structured test data in electronic medical records. Our approach begins with the extraction of free-text and structured data from clinical records through a systematic preprocessing pipeline. Subsequently, we employ a pre-trained transformer language model to extract features from the free-text, while multiple additive regression trees are used to transform features from the structured data. An attention-based fusion mechanism is then applied to integrate these multi-modal features for effective classification. We validated our method using clinic records of 7157 patients, retrospectively collected for training and testing purposes. The experimental results demonstrate that our proposed multi-modal fusion approach achieves significant improvements over other methods across four key performance metrics.


Assuntos
Registros Eletrônicos de Saúde , Pneumonia por Mycoplasma , Humanos , Pneumonia por Mycoplasma/diagnóstico , Registros Eletrônicos de Saúde/estatística & dados numéricos , Criança , Estudos Retrospectivos , Mycoplasma pneumoniae/patogenicidade , Feminino , Masculino , Pré-Escolar
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