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Bat coronavirus RaTG13 shares about 96.2% nucleotide sequence identity with that of SARS-CoV-2 and uses human and Rhinolophus affinis (Ra) angiotensin-converting enzyme 2 (ACE2) as entry receptors. Whether there are bat species other than R. affinis susceptible to RaTG13 infection remains elusive. Here, we show that, among 18 different bat ACE2s tested, only RaACE2 is highly susceptible to transduction by RaTG13 S pseudovirions, indicating that the bat species harboring RaTG13 might be very limited. RaACE2 has seven polymorphic variants, RA-01 to RA-07, and they show different susceptibilities to RaTG13 S pseudovirions transduction. Sequence and mutagenesis analyses reveal that residues 34, 38, and 83 in RaACE2 might play critical roles in interaction with the RaTG13 S protein. Of note, RaACE2 polymorphisms have minimal effect on S proteins of SARS-CoV-2 and several SARS-CoV-2 related CoVs (SC2r-CoVs) including BANAL-20-52 and BANAL-20-236 in terms of binding, membrane fusion, and pseudovirus entry. Further mutagenesis analyses identify residues 501 and 505 in S proteins critical for the recognition of different RaACE2 variants and pangolin ACE2 (pACE2), indicating that RaTG13 might have not been well adapted to R. affinis bats. While single D501N and H505Y changes in RaTG13 S protein significantly enhance the infectivity and minimize the difference in susceptibility among different RaACE2 variants, an N501D substitution in SARS-CoV-2 S protein displays marked disparity in transduction efficiencies among RaACE2 variants with a significant reduction in infectivity on several RaACE2 variants. Finally, a T372A substitution in RaTG13 S protein not only significantly increases infectivity on all RaACE2 variants, but also markedly enhances entry on several bat ACE2s including R. sinicus YN, R. pearsonii, and R. ferrumeiqunum. However, the T372A mutant is about 4-fold more sensitive to neutralizing sera from mice immunized with BANAL-20-52 S, suggesting that the better immune evasion ability of T372 over A372 might contribute to the natural selective advantage of T372 over A372 among bat CoVs. Together, our study aids a better understanding of coronavirus entry, vaccine design, and evolution.
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COVID-19 , Quirópteros , Animais , Camundongos , Humanos , SARS-CoV-2/metabolismo , Enzima de Conversão de Angiotensina 2 , Glicoproteína da Espícula de Coronavírus/metabolismoRESUMO
Heart failure and cardiac remodeling are both characterized by mitochondrial dysfunction. Healthy mitochondria are required for adequate contractile activity and appropriate regulation of cell survival. In the mammalian heart, enhancement of the mitochondrial unfolded protein response (UPRmt) is cardioprotective under pressure overload conditions. We explored the UPRmt and the underlying regulatory mechanism in terms of hypertension-induced cardiac remodeling and the cardioprotective effect of metformin. Male spontaneously hypertensive rats and angiotensin II-treated neonatal rat cardiomyocytes were used to induce cardiac hypertrophy. The results showed that hypertension induced the formation of aberrant mitochondria, characterized by a reduced mtDNA/nDNA ratio and swelling, as well as lower levels of mitochondrial complexes I to V and inhibition of the expression of one protein subunit of each of complexes I to IV. Such changes eventually enlarged cardiomyocytes and increased cardiac fibrosis. Metformin treatment increased the mtDNA/nDNA ratio and regulated the UPRmt, as indicated by increased expression of activating transcription factor 5, Lon protease 1, and heat shock protein 60, and decreased expression of C/EBP homologous protein. Thus, metformin improved mitochondrial ultrastructure and function in spontaneously hypertensive rats. In vitro analyses revealed that metformin reduced the high levels of angiotensin II-induced mitochondrial reactive oxygen species in such animals and stimulated nuclear translocation of heat shock factor 1 (HSF1). Moreover, HSF1 small-interfering RNA reduced the metformin-mediated improvements in mitochondrial morphology and the UPRmt by suppressing hypertrophic signals and cardiomyocyte apoptosis. These results suggest that HSF1/UPRmt signaling contributes to the beneficial effects of metformin. Metformin-mediated targeting of mitochondrial protein homeostasis and modulation of HSF1 levels have potential therapeutic implications in terms of cardiac remodeling.
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Fatores de Transcrição de Choque Térmico , Metformina , Miócitos Cardíacos , Resposta a Proteínas não Dobradas , Animais , Masculino , Ratos , Angiotensina II/farmacologia , Cardiomegalia/metabolismo , Cardiomegalia/tratamento farmacológico , Cardiomegalia/patologia , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Fatores de Transcrição de Choque Térmico/efeitos dos fármacos , Fatores de Transcrição de Choque Térmico/metabolismo , Hipertensão/metabolismo , Hipertensão/tratamento farmacológico , Metformina/farmacologia , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacosRESUMO
The etiology of preeclampsia (PE), a complex and multifactorial condition, remains incompletely understood. DNA methylation, which is primarily regulated by three DNA methyltransferases (DNMTs), DNMT1, DNMT3A, and DNMT3B, plays a vital role in early embryonic development and trophectoderm differentiation. Yet, how DNMTs modulate trophoblast fusion and PE development remains unclear. In this study, we found that the DNMTs expression was downregulated during trophoblast cells fusion. Downregulation of DNMTs was observed during the reconstruction of the denuded syncytiotrophoblast (STB) layer of placental explants. Additionally, overexpression of DNMTs inhibited trophoblast fusion. Conversely, treatment with the DNA methylation inhibitor 5-aza-CdR decreased the expression of DNMTs and promoted trophoblast fusion. A combined analysis of DNA methylation data and gene transcriptome data obtained from the primary cytotrophoblasts (CTBs) fusion process identified 104 potential methylation-regulated differentially expressed genes (MeDEGs) with upregulated expression due to DNA demethylation, including CD59, TNFAIP3, SDC1, and CDK6. The transcription regulation region (TRR) of TNFAIP3 showed a hypomethylation with induction of 5-aza-CdR, which facilitated CREB recruitment and thereby participated in regulating trophoblast fusion. More importantly, clinical correlation analysis of PE showed that the abnormal increase in DNMTs may be involved in the development of PE. This study identified placental DNA methylation-regulated genes that may contribute to PE, offering a novel perspective on the role of epigenetics in trophoblast fusion and its implication in PE development.
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DNA (Citosina-5-)-Metiltransferases , Metilação de DNA , Pré-Eclâmpsia , Trofoblastos , Trofoblastos/metabolismo , Feminino , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/patologia , Gravidez , Humanos , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Fusão Celular , Placenta/metabolismo , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , DNA (Citosina-5-)-Metiltransferase 1/genéticaRESUMO
Herein, we report a DNA origami plasmonic nanoantenna for the programmable surface-enhanced Raman scattering (SERS) detection of cytokine release syndrome (CRS)-associated cytokines (e.g., tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)) in cancer immunotherapy. Typically, the nanoantenna was made of self-assembled DNA origami nanotubes (diameter: â¼19 nm; length: â¼90 nm) attached to a silver nanoparticle-modified silicon wafer (AgNP/Si). Each DNA origami nanotube contains one miniature gold nanorod (AuNR) inside (e.g., length: â¼35 nm; width: â¼7 nm). Intriguingly, TNF-α and IFN-γ logically regulate the opening of the nanotubes and the dissociation of the AuNRs from the origami structure upon binding to their corresponding aptamers. On this basis, we constructed a complete set of Boolean logic gates that read cytokine molecules as inputs and return changes in Raman signals as outputs. Significantly, we demonstrated that the presented system enables the quantification of TNF-α and IFN-γ in the serum of tumor-bearing mice receiving different types of immunotherapies (e.g., PD1/PD-L1 complex inhibitors and STING agonists). The sensing results are consistent with those of the ELISA. This strategy fills a gap in the use of DNA origami for the detection of multiple cytokines in real systems.
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Técnicas Biossensoriais , Citocinas , DNA , Ouro , Imunoterapia , Nanopartículas Metálicas , Análise Espectral Raman , Animais , Camundongos , DNA/química , Citocinas/metabolismo , Citocinas/sangue , Ouro/química , Nanopartículas Metálicas/química , Humanos , Prata/química , Nanotubos/química , Neoplasias , Interferon gama/sangue , Interferon gama/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/sangueRESUMO
Chronic wounds have emerged as an increasingly critical clinical challenge over the past few decades, due to their increasing incidence and socioeconomic burdens. Platelet-derived growth factor (PDGF) plays a pivotal role in regulating processes such as fibroblast migration, proliferation, and vascular formation during the wound healing process. The delivery of PDGF offers great potential for expediting the healing of chronic wounds. However, the clinical effectiveness of PDGF in chronic wound healing is significantly hampered by its inability to maintain a stable concentration at the wound site over an extended period. In this study, a controlled PDGF delivery system based on nanocapsules is proposed. In this system, PDGF is encapsulated within a degradable polymer shell. The release rate of PDGF from these nanocapsules can be precisely adjusted by controlling the ratios of two crosslinkers with different degradation rates within the shells. As demonstrated in a diabetic wound model, improved therapeutic outcomes with PDGF nanocapsules (nPDGF) treatment are observed. This research introduces a novel PDGF delivery platform that holds promise for enhancing the effectiveness of chronic wound healing.
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Preparações de Ação Retardada , Nanocápsulas , Fator de Crescimento Derivado de Plaquetas , Cicatrização , Cicatrização/efeitos dos fármacos , Nanocápsulas/química , Fator de Crescimento Derivado de Plaquetas/administração & dosagem , Fator de Crescimento Derivado de Plaquetas/farmacologia , Fator de Crescimento Derivado de Plaquetas/metabolismo , Animais , Preparações de Ação Retardada/química , Humanos , CamundongosRESUMO
Retinal detachment (RD) refers to the separation between the neuroepithelium and the pigment epithelium layer. It is an important disease leading to irreversible vision damage worldwide, in which photoreceptor cell death plays a major role. α-Synuclein (α-syn) is reportedly involved in numerous mechanisms of neurodegenerative diseases, but the association with photoreceptor damage in RD has not been studied. In this study, elevated transcription levels of α-syn and parthanatos proteins were observed in the vitreous of patients with RD. The expression of α-syn- and parthanatos-related proteins was increased in experimental rat RD, and was involved in the mechanism of photoreceptor damage, which was related to the decreased expression of miR-7a-5p (miR-7). Interestingly, subretinal injection of miR-7 mimic in rats with RD inhibited the expression of retinal α-syn and down-regulated the parthanatos pathway, thereby protecting retinal structure and function. In addition, interference with α-syn in 661W cells decreased the expression of parthanatos death pathway in oxygen and glucose deprivation model. In conclusion, this study demonstrates the presence of parthanatos-related proteins in patients with RD and the role of the miR-7/α-syn/parthanatos pathway in photoreceptor damage in RD.
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MicroRNAs , Parthanatos , Descolamento Retiniano , Ratos , Humanos , Animais , Descolamento Retiniano/genética , Descolamento Retiniano/metabolismo , Apoptose , Células Fotorreceptoras de Vertebrados/metabolismo , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Células Fotorreceptoras/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Modelos Animais de DoençasRESUMO
Phosphorus (P) is an essential nutrient, but easily fixed in soils. Therefore, most of soil P exists in the form of inaccessible organic phosphorus (Po), particularly phytate-P. Root-associated purple acid phosphatases (PAPs) are considered to play a crucial role in phosphate (Pi) scavenging in soils. However, evidence for regulating root-associated PAPs in utilization of extracellular phytate-P remain largely unknown in plants at both transcriptional and posttranslational levels. In this study, a Pi-starvation responsive GmPAP15a was identified in soybean (Glycine max). Overexpressing GmPAP15a led to significant increases in root-associated phytase activities, as well as total P content when phytate-P was supplied as the sole P resource in soybean hairy roots. Meanwhile, mass spectrometry (MS) analysis showed GmPAP15a was glycosylated at Asn144 and Asn502 , and its glycan structures of N-linked oligosaccharide chains exhibited microheterogeneity. Moreover, two homologues of AtPHR1, GmPHR9 and GmPHR32 were found to activate GmPAP15a transcription through luciferase activity analysis. Taken together, it is strongly suggested that GmPAP15a plays a vital role in phytate-P utilization in soybean, which might be regulated at both transcriptional and glycosylation modification levels. Our results highlight the GmPHR9/GmPHR32-GmPAP15a signalling pathway might present, and control phytate-P utilization in soybean.
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Glycine max , Ácido Fítico , Glycine max/metabolismo , Glicosilação , Ácido Fítico/metabolismo , Proteínas de Plantas/metabolismo , Raízes de Plantas/metabolismo , Fósforo/metabolismo , SoloRESUMO
The regulation of legume-rhizobia symbiosis by microorganisms has obtained considerable interest in recent research, particularly in the common rhizobacteria Bacillus. However, few studies have provided detailed explanations regarding the regulatory mechanisms involved. Here, we investigated the effects of Bacillus (Bac.B) on Bradyrhizobium-soybean (Glycine max) symbiosis and elucidated the underlying ecological mechanisms. We found that two Bradyrhizobium strains (i.e. Bra.Q2 and Bra.D) isolated from nodules significantly promoted nitrogen (N) efficiency of soybean via facilitating nodule formation, thereby enhanced plant growth and yield. However, the intrusion of Bac.B caused a reverse shift in the synergistic efficiency of N2 fixation in the soybean-Bradyrhizobium symbiosis. Biofilm formation and naringenin may be importantin suppression of Bra.Q2 growth regulated by Bac.B. In addition, transcriptome and microbiome analyses revealed that Bra.Q2 and Bac.B might interact to regulateN transport and assimilation, thus influence the bacterial composition related to plant N nutrition in nodules. Also, the metabolisms of secondary metabolites and hormones associated with plant-microbe interaction and growth regulation were modulated by Bra.Q2 and Bac.B coinoculation. Collectively, we demonstrate that Bacillus negatively affects Bradyrhizobium-soybean symbiosis and modulate microbial interactions in the nodule. Our findings highlight a novel Bacillus-based regulation to improve N efficiency and sustainable agricultural development.
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Surface ligands play crucial roles in modifying the properties of metal nanoclusters and stabilizing atomically precise structures, and also serve as vital linkers for constructing cluster-based coordination polymers. In this study, we present the results of the solvothermal synthesis of eight novel copper alkynyl clusters incorporating pyridine ligands using a one-pot method. The resulting compounds underwent characterization through elemental analysis, Fourier transform infrared (FT-IR) spectroscopy, powder X-ray diffraction (PXRD), and single-crystal X-ray diffraction (SCXRD). Our observations revealed that distinct pyridine ligands with varying lengths and coordination sites exert significant influence on the structure and dimensionality of the clusters. The structural diversity of these clusters led to the formation of one-dimensional (1D), two-dimensional (2D), or dimer arrangements linked by seven pyridine bridging ligands. Remarkably, these complexes exhibited unique UV-vis absorption and photoluminescence properties, which were influenced by the specific bridging ligand and structural framework. Furthermore, density functional theory (DFT) calculations demonstrated the capability of the conjugated system in the pyridine ligand to impact the band gap of clusters. This study not only unveils the inherent structural diversity in coordination polymers based on copper alkynyl clusters but also offers valuable insights into harnessing ligand engineering for structural and property modulation.
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This study aims to explore the effects of supplementing cholesterol in plant-based feed on intestinal barriers (including physical barrier, chemical barrier, immune barrier, biological barrier) of GIFT strain tilapia (Oreochromis niloticus). Four isonitrogenous and isolipidic diets were prepared as follows: plant-based protein diet (Con group) containing corn protein powder, soybean meal, cottonseed meal, and rapeseed meal, with the addition of cholesterol at a level of 0.6 % (C0.6 % group), 1.2 % (C1.2 % group), and 1.8 % (C1.8 % group), respectively. A total of 360 fish (mean initial weight of (6.08 ± 0.12) g) were divided into 12 tanks with 30 fish per tank, each treatment was set with three tanks and the feeding period lasted 9 weeks. Histological analysis revealed that both the C0.6 % and C1.2 % groups exhibited a more organized intestinal structure, with significantly increased muscle layer thickness compared to the Con group (P < 0.05). Furthermore, in the C1.2 % group, there was a significant up-regulation of tight junction-related genes (claudin-14, occludin, zo-1) compared to the Con group (P < 0.05). 5-ethynyl-2'-deoxyuridine staining results also demonstrated a notable enhancement in intestinal cell proliferation within the C1.2 % group (P < 0.05). Regarding the intestinal chemical barrier, trypsin and lipase activities were significantly elevated in the C1.2 % group (P < 0.05), while hepcidin gene expression was considerably down-regulated in this group but up-regulated in the C1.8 % group (P < 0.05). In terms of the intestinal immune barrier, inflammation-related gene expression levels (tnf-α, il-1ß, caspase 9, ire1, perk, atf6) were markedly reduced in the C1.2 % group (P < 0.05). Regarding the intestinal biological barrier, the composition of the intestinal microbiota indicated that compared to the Con group, both the 0.6 % and 1.2 % groups showed a significant increase in Shannon index (P < 0.05). Additionally, there was a significant increase in the abundance of Firmicutes and Clostridium in the C1.2 % group (P < 0.05). In summary, supplementation of 1.2 % cholesterol in the plant-based diet exhibits the potential to enhance intestinal tight junction function and improve the composition of intestinal microbiota, thereby significantly promoting tilapia's intestinal health.
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Ração Animal , Ciclídeos , Dieta , Intestinos , Animais , Ciclídeos/imunologia , Ração Animal/análise , Dieta/veterinária , Intestinos/efeitos dos fármacos , Intestinos/imunologia , Colesterol na Dieta/administração & dosagem , Colesterol na Dieta/efeitos adversos , Doenças dos Peixes/imunologia , Suplementos Nutricionais/análise , Distribuição Aleatória , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Dieta Baseada em PlantasRESUMO
BACKGROUND: Acetyl-CoA carboxylase (ACC) catalyzes the carboxylation of acetyl-CoA to malonyl-CoA. Malonyl-CoA, which plays a key role in regulating glucose and lipid metabolism, is not only a substrate for fatty acid synthesis but also an inhibitor of the oxidation pathway. ACC exists as two isoenzymes that are encoded by two different genes. ACC1 in grass carp (Ctenopharyngodon idellus) has been cloned and sequenced. However, studies on the cloning, tissue distribution, and function of ACC2 in grass carp were still rare. METHODS AND RESULTS: The full-length cDNA of acc2 was 8537 bp with a 7146 bp open reading frame encoding 2381 amino acids. ACC2 had a calculated molecular weight of 268.209 kDa and an isoelectric point of 5.85. ACC2 of the grass carp shared the closest relationship with that of the common carp (Sinocyclocheilus grahami). The expressions of acc1 and acc2 mRNA were detected in all examined tissues. The expression level of acc1 was high in the brain and fat but absent in the midgut and hindgut. The expression level of acc2 in the kidney was significantly higher than in other tissues, followed by the heart, brain, muscle, and spleen. ACCs inhibitor significantly reduced the levels of glucose, malonyl-CoA, and triglyceride in hepatocytes. CONCLUSIONS: This study showed that the function of ACC2 was evolutionarily conserved from fish to mammals. ACCs inhibitor inhibited the biological activity of ACCs, and reduced fat accumulation in grass carp.
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Carpas , Animais , Carpas/genética , Carpas/metabolismo , Clonagem Molecular , Sequência de Bases , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Expressão Gênica , Glucose , Mamíferos/metabolismoRESUMO
BACKGROUNDS: Frequent hospitalization and the costs of hospitalization are the main burdens in China for patients with acute pancreatitis. Most admitted patients have mild disease conditions that do not require hospitalization. AIMS: Here, we compare some health and economic aspects of patients with mild acute pancreatitis who received nurse-led care at home visits against those who were hospitalized on follow-up. METHODS: Patients discharged from the hospital after treatment for mild acute pancreatitis received (NC cohort, n = 104) or did not receive (HN cohort, n = 141) regular home visits by nurses for treatment and care. Patients were rehospitalized by caregivers with or without help of nurse. RESULTS: Hospital readmission events occurred in both cohorts at a follow-up care time of 2 months. Compared with the time of discharge from the hospital, unwanted effects were higher in follow-up care in all patients (p < 0.001 for all). Patients in the NC cohort had less time to resolution of pain, less time to resumption of oral solid food intake, smaller number of patients with hospital readmissions, less average time of hospitalization, lower cost of care, and lower occurrence of unwanted effects than those of patients in the HN cohort during 2 months of follow-up care (p < 0.05 for all). CONCLUSIONS: Patients with mild acute pancreatitis who undergo treatment require nurse-led nontreatment intervention(s) for rehabilitation in follow-up. Nurse-led follow-up care at-home visits increase recovery, are beneficial and cost-effective, and decrease unwanted adverse effects in patients receiving treatment for mild acute pancreatitis. LEVEL OF EVIDENCE: IV. TECHNICAL EFFICACY: Stage 5.
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Visita Domiciliar , Pancreatite , Readmissão do Paciente , Humanos , Masculino , Feminino , Pancreatite/enfermagem , Pancreatite/terapia , Pancreatite/economia , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Readmissão do Paciente/estatística & dados numéricos , Visita Domiciliar/economia , China/epidemiologia , Doença Aguda , Índice de Gravidade de Doença , HospitalizaçãoRESUMO
BACKGROUND: Quantifying the informal caregiver burden is important for understanding the risk factors associated with caregiver overload and for evaluating the effectiveness of services provided in Long-term Care (LTC). OBJECTIVE: This study aimed to develop and validate a Caregiver Strain Index (CSI)-based score for quantifying the informal caregiver burden, while the original dataset did not fully cover evaluation items commonly included in international assessments. Subsequently, we utilized the CSI-based score to pinpoint key caregiver burden risk factors, examine the initial timing of LTC services adoption, and assess the impact of LTC services on reducing caregiver burden. METHODS: The study analyzed over 28,000 LTC cases in Southern Taiwan from August 2019 to December 2022. Through multiple regression analysis, we identified significant risk factors associated with caregiver burden and examined changes in this burden after utilizing various services. Survival analysis was employed to explore the relationship between adopting the first LTC services and varying levels of caregiver burden. RESULTS: We identified 126 significant risk factors for caregiver burden. The most critical factors included caregiving for other disabled family members or children under the age of three (ß = 0.74, p < 0.001), the employment status of the caregiver (ß = 0.30-0.53, p < 0.001), the frailty of the care recipient (ß = 0.28-0.31, p < 0.001), and the behavioral symptoms of dementia in care recipients (ß = 0.28-2.60, p < 0.05). Generally, caregivers facing higher burdens sought LTC services earlier, and providing home care services alleviated the caregiver's burden. CONCLUSION: This comprehensive study suggests policy refinements to recognize high-risk caregivers better early and provide timely support to improve the overall well-being of both informal caregivers and care recipients.
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Sobrecarga do Cuidador , Cuidadores , Assistência de Longa Duração , Humanos , Taiwan/epidemiologia , Masculino , Feminino , Sobrecarga do Cuidador/psicologia , Idoso , Cuidadores/psicologia , Assistência de Longa Duração/métodos , Pessoa de Meia-Idade , Fatores de Risco , Idoso de 80 Anos ou mais , Estresse Psicológico/psicologia , Estresse Psicológico/epidemiologia , AdultoRESUMO
OBJECTIVE: This research aimed to evaluate the impact of grading and zoning nursing management on traumatic brain injury (TBI) patients' emergency treatment outcomes. METHODS: This randomized controlled trial included 200 TBI patients. They were treated with a conventional care (control group, n = 100) and a novel grading and zoning approach (study group, n = 100), respectively. This innovative model organized care into levels based on urgency and complexity, facilitating targeted medical response and resource allocation. Key metrics compared included demographic profiles, consultation efficiency (time metrics and emergency treatment rates), physiological parameters (HR, RR, MAP, SpO2, RBS), and patient outcomes (hospital and ICU stays, complication rates, and emergency outcomes). RESULTS: The study group demonstrated significantly improved consultation efficiency, with reduced times for physician visits, examinations, emergency stays, and specialist referrals (all p < 0.001), alongside a higher emergency treatment rate (93% vs. 79%, p = 0.004), notably better physiological stability, improved HR, RR, MAP, SpO2 and RBS (p < 0.001), shorter hospital and ICU stays, fewer complications, and superior emergency outcomes. CONCLUSION: Grading and zoning nursing management substantially enhances TBI patients' emergency care efficiency and clinical outcomes, suggesting a viable model for improving emergency treatment protocols.
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Buffaloes are vital contributors to the global dairy industry. Understanding the genetic basis of milk production traits in buffalo populations is essential for breeding programs and improving productivity. In this study, we conducted whole-genome resequencing on 387 buffalo genomes from 29 diverse Asian breeds, including 132 river buffaloes, 129 swamp buffaloes, and 126 crossbred buffaloes. We identified 36,548 copy number variants (CNV) spanning 133.29 Mb of the buffalo genome, resulting in 2,100 CNV regions (CNVR), with 1,993 shared CNVR being found within the studied buffalo types. Analyzing CNVR highlighted distinct genetic differentiation between river and swamp buffalo subspecies, verified by evolutionary tree and principal component analyses. Admixture analysis grouped buffaloes into river and swamp categories, with crossbred buffaloes displaying mixed ancestry. To identify candidate genes associated with milk production traits, we employed 3 approaches. First, we used Vst-based population differentiation, revealing 11 genes within CNVR that exhibited significant divergence between different buffalo breeds, including genes linked to milk production traits. Second, expression quantitative loci analysis revealed differentially expressed CNVR-derived genes (DECG) associated with milk production traits. Notably, known milk production-related genes were among these DECG, validating their relevance. Last, a GWAS identified 3 CNVR significantly linked to peak milk yield. Our study provides comprehensive genomic insights into buffalo populations and identifies candidate genes associated with milk production traits. These findings facilitate genetic breeding programs aimed at increasing milk yield and improving quality in this economically important livestock species.
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Búfalos , Variações do Número de Cópias de DNA , Leite , Animais , Búfalos/genética , Leite/metabolismo , Feminino , Genoma , Cruzamento , Lactação/genéticaRESUMO
False data injection attacks (FDIAs) on sensor networks involve injecting deceptive or malicious data into the sensor readings that cause decision-makers to make incorrect decisions, leading to serious consequences. With the ever-increasing volume of data in large-scale sensor networks, detecting FDIAs in large-scale sensor networks becomes more challenging. In this paper, we propose a framework for the distributed detection of FDIAs in large-scale sensor networks. By extracting the spatiotemporal correlation information from sensor data, the large-scale sensors are categorized into multiple correlation groups. Within each correlation group, an autoregressive integrated moving average (ARIMA) is built to learn the temporal correlation of cross-correlation, and a consistency criterion is established to identify abnormal sensor nodes. The effectiveness of the proposed detection framework is validated based on a real dataset from the U.S. smart grid and simulated under both the simple FDIA and the stealthy FDIA strategies.
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Stylo (Stylosanthes spp.) is an important pasture legume with strong aluminum (Al) resistance. However, the molecular mechanisms underlying its Al tolerance remain fragmentary. Due to the incomplete genome sequence information of stylo, we first conducted full-length transcriptome sequencing for stylo root tips treated with and without Al and identified three Snakin/GASA genes, namely, SgSnakin1, SgSnakin2, and SgSnakin3. Through quantitative RT-PCR, we found that only SgSnakin1 was significantly upregulated by Al treatments in stylo root tips. Histochemical localization assays further verified the Al-enhanced expression of SgSnakin1 in stylo root tips. Subcellular localization in both tobacco and onion epidermis cells showed that SgSnakin1 localized to the cell wall. Overexpression of SgSnakin1 conferred Al tolerance in transgenic Arabidopsis, as reflected by higher relative root growth and cell vitality, as well as lower Al concentration in the roots of transgenic plants. Additionally, overexpression of SgSnakin1 increased the activities of SOD and POD and decreased the levels of O2·- and H2O2 in transgenic Arabidopsis in response to Al stress. These findings indicate that SgSnakin1 may function in Al resistance by enhancing the scavenging of reactive oxygen species through the regulation of antioxidant enzyme activities.
Assuntos
Alumínio , Arabidopsis , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Plantas Geneticamente Modificadas , Espécies Reativas de Oxigênio , Alumínio/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Arabidopsis/metabolismo , Arabidopsis/genética , Arabidopsis/efeitos dos fármacos , Fabaceae/metabolismo , Fabaceae/genética , Fabaceae/efeitos dos fármacos , Raízes de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/genética , Peróxido de Hidrogênio/metabolismo , Nicotiana/genética , Nicotiana/metabolismo , Nicotiana/efeitos dos fármacosRESUMO
This study aims to evaluate the effects of substituting soybean meal with fermented rapeseed meal (FRM) on growth, antioxidant capacity, and liver and intestinal health of the genetically improved farmed tilapia (GIFT, Oreochromis niloticus). A total of 450 tilapia (7.22 ± 0.15 g) were fed with five experimental diets, including a basal diet containing 40% soybean meal (CP0), which was subsequently replaced by 25% (CP25), 50% (CP50), 75% (CP75), and 100% (CP100) FRM in a recirculated aquiculture system for 9 weeks (30 fish per tank in triplicates). The results showed that the weight gain, specific growth rate, feed intake, feed efficiency, hepatosomatic index, and viscerosomatic index of fish in both CP75 and CP100 groups were significantly lower than those in CP0 group (P < 0.05). The fish in CP100 group had the lower content of muscle crude protein while the higher level of muscle crude lipid (P < 0.05). Activities of serum aspartate aminotransferase, alanine aminotransferase along with total triglyceride in CP100 group were significantly higher than those in CP0 group (P < 0.05). There were no significant differences in the contents of liver protease, amylase, and lipase among five groups (P > 0.05). The activities of liver total antioxidant capacity and superoxide dismutase exhibited the increased tendency with the increase of FRM replacement levels from 25 to 50% (P < 0.05), while then significantly decreased from 75 to 100% (P < 0.05). Histological morphology indicated that the fish in between CP75 and CP100 groups had poor liver and intestine health. Intestinal microbial diversity analysis showed that the relative abundance of Cetobacterium and Alcaligenaceae in both CP75 and CP100 groups were lower than that in other three groups. In conclusion, the maximum replacement level of soybean meal with FRM in the diet was determined to be 50% without compromising the growth performance, antioxidant status, and liver and intestinal health of tilapia under the current experimental conditions. The observed decrease in food intake and subsequent retarded growth performance in the CP75 and CP100 groups can be attributed directly to a reduction in feed palatability caused by FRM.
Assuntos
Ração Animal , Antioxidantes , Ciclídeos , Dieta , Glycine max , Intestinos , Fígado , Animais , Fígado/metabolismo , Ração Animal/análise , Antioxidantes/metabolismo , Dieta/veterinária , Ciclídeos/crescimento & desenvolvimento , Ciclídeos/metabolismo , Ciclídeos/fisiologia , Fenômenos Fisiológicos da Nutrição Animal , Fermentação , Brassica napusRESUMO
PURPOSE: To systematically evaluate the efficacy and safety of adding ketamine (K) to lidocaine (L) for intravenous regional anesthesia (IVRA). DESIGN: A systematic review and meta-analysis. METHODS: A comprehensive search of the Cochrane library, Embase, PubMed, Web of Science, and ProQuest databases, and the Google Scholar search engine was conducted from inception to March 2023. All retrieved articles were imported into Endnote X20 software and independently screened by two researchers according to predetermined inclusion and exclusion criteria. The data were analyzed using Revman 5.4 software and the assessed outcomes included the time of sensory and motor block onset, time of sensory and motor block recovery, fentanyl consumption, time of tourniquet pain onset, intraoperative and postoperative visual analog scale scores, and complications. FINDINGS: A total of 532 patients from 11 randomized controlled trials were included in the meta-analysis. The results showed that the time of sensory (P < .00001) and motor block onset (P < .00001) were shorter in the L + K group than in the L-only group. The time of sensory (P = .01) and motor block recovery (P = .006) and time of tourniquet pain onset (P < .00001) were longer in the L + K group than in the L-only group. There was a significant reduction in fentanyl consumption (P = .0002) in the L + K group compared to the L-only group. Moreover, the visual analog scale scores in the L + K group were significantly lower than the L-only group 10 minutes (P = .04), 20 minutes (P = .0004), 30 minutes (P < .00001), and 40 minutes (P < .0001) after tourniquet inflation, and 5 minutes (P < .00001), 15 minutes (P = .04), 30 minutes (P = .008), 1 hour (P = .002), 2 hours (P < .00001), and 4 hours (P < .00001) after tourniquet deflation. There was no evidence that the use of K as an adjuvant in IVRA increased adverse effects. CONCLUSIONS: The addition of K to L in IVRA shortened the onset time, prolonged the block time, and reduced intraoperative and postoperative pain without increasing complications.
RESUMO
Alloying nanoclusters (NCs) has emerged as a widely explored and versatile strategy for tailoring tunable properties, facilitating in-depth atomic-level investigations of structure-property correlations. In this study, we have successfully synthesized six atomically precise copper NCs alloyed with Group 10 metals (Pd or Pt). Notably, the Pd0 or Pt0 atom situated at the center of the distorted hexagonal antiprism Pd0/Pt0@Cu12 cage, coordinated with twelve Cu+ and two tBuC≡C- ligands. Moreover, ligand exchange strategies demonstrated the potential for Cl- and Br- to replace one or two alkynyl ligands positioned at the top or side of the NCs. The chirality exhibited by these racemic NCs is primarily attributed to the involvement of halogens and a chiral (Pd/Pt)@Cu18 skeleton. Furthermore, all the NCs exhibit near-infrared (NIR) luminescence, characterized by emission peaks at 705-755â nm, lifetimes ranging from 6.630 to 9.662â µs, and absolute photoluminescence quantum yields (PLQYs) of 1.75 %-2.52 % in their crystalline state. The experimental optical properties of these NCs are found to be in excellent agreement with the results of theoretical calculations. These alloy NCs not only offer valuable insights into the synthesis of Pd0/Pt0-Cu alloy NCs, but also bridge the gap in understanding the structure-luminescence relationships of Pd0/Pt0-Cu molecules.