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Benzothiazoles (BTHs) and benzotriazoles (BTRs) are widely used in various consumer products. However, their occurrence and fate in wastewater treatment plants (WWTPs) in the United States remain poorly understood. In this study, wastewater and sludge samples were collected from two WWTPs from the Albany area of New York State (WWTPA and WWTPB) and the concentrations of three BTH derivatives (BTH, 2-OH-BTH, and 2-Me-S-BTH) and five BTR derivatives (1-OH-BTR, XTR, 4-OH-BTR, TTR, and BTR) were determined. The geometric mean (GM) concentrations of Σ(BTHs) and Σ(BTRs) in influent were in the range of 7550-8690 and 4590-6240 ng/L, whereas those in effluent were 6650-7150 and 4620-6800 ng/L, respectively. In the influent of two WWTPs, BTH, BTR, and TTR were identified as the major chemicals at respective GM concentrations of 8440, 4200, and 1280 ng/L in WWTPA, and 7300, 1180, and 2090 ng/L in WWTPB. The removal efficiencies of BTHs and BTRs following activated sludge treatment were < 80 %, and Σ(BTRs) showed a negative removal in both WWTPs. The respective mass loadings of Σ(BTHs) and Σ(BTRs) were 7240 and 5200 mg/d/1000 individuals in WWTPA, and 3530 and 2140 mg/d/1000 individuals in WWTPB. The environmental emissions of Σ(BTHs) and Σ(BTRs) from WWTP discharges were estimated at 3110-6030 and 2160-5700 mg/d/1000 individuals, respectively. Overall, BTHs and BTRs are not efficiently removed in WWTP processes. This study provides baseline information regarding the loading, fate, and discharge of BTHs and BTRs from WWTPs in the USA.
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Over 10,000 metric-ton broiler livers are produced annually in Taiwan. Concerning unpleasant odor and healthy issue, broiler livers are not attractive to consumers. Although the patented chicken-liver hydrolysates (CLHs) through pepsin digestion possess several biofunctionalities, there is no study on hepatoprotection of CLH-based formula capsule (GBHP01) against binge drinking (Whiskey, 50% Alc./Vol.). GBHP01 led to an accelerated blood-alcohol clearance in rats, as evidenced by lowering blood-alcohol increment within 0 to 4 h, increasing blood-alcohol decrement within 4 to 8 h, and smaller blood alcohol concentration areas under the curve (BAC AUC) in the 8-h period (p < 0.05). The ameliorative effects of GBHP01 against binge drinking in rats over 6 wk were attributed to accelerated alcohol metabolism by further increasing alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities while downregulating cytochrome P450 2E1 (CYP2E1) protein expression, elevating antioxidant capacity, decreasing zonula occludens-1 (ZO-1) protein decrement and serum endotoxin, and reducing inflammation related protein levels, that is, toll-like receptor 4 (TLR4) and mitogen-activated protein kinase (MAPK), and proinflammatory cytokines. The development of CLH supplements could not only enhance the added value of broiler livers through nutraceutical development but also offer a strategy to maximize the utilization of poultry processing residues, as shown in this study.
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Consumo Excessivo de Bebidas Alcoólicas , Galinhas , Fígado , Animais , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Ratos , Hidrolisados de Proteína/química , Hidrolisados de Proteína/administração & dosagemRESUMO
Severe alopecia areata (AA) is a nonscarring hair loss for immune disorder and SALT score ≥ 50%. The guidelines for managing patients with severe AA suggest treatments: systemic steroids, JAK inhibitors, and contact immunotherapy. However, there is a lack of evidence indicating the superiority of one treatment over another. Therefore, this study aimed to identify the most effective treatment for severe AA through network meta-analysis. Following the PRISMA guidelines, we conducted a network meta-analysis. The literature search was retrieved across four databases. The Cochrane 5.1 risk of bias assessment tool and ROBINS-I tool assessed quality of the included studies. Subsequently, efficacy and safety comparisons among the three treatments were conducted using Stata 14.0 on account of the frequency method. The SUCRA rank indicated that oral dexamethasone (95.9%) > diphenylcyclopropenone(DPCP) (74.5%) > oral ritlecitinib (62.6%) > oral baricitinib (46.9%) > squaric acid dibutyl ester(SADBE) (20.1%) > placebo (0.0%) from high to low in the aspect of improving efficacy. As for safety, placebo(88.4%) > oral ritlecitinib (86.5%) > oral baricitinib (62.1%) > SADBE (37.0%) > oral dexamethasone(22.3%) > DPCP(3.8%) in the aspect of decreasing adverse events. Oral dexamethasone and DPCP showed superior efficacy compared to oral ritlecitinib and oral baricitinib. However, in terms of safety, oral ritlecitinib was preferable. Some adverse events associated with oral dexamethasone and DPCP were intolerable to patients, whereas those related to oral ritlecitinib and oral baricitinib were more manageable. Overall, ritlecitinib and baricitinib remain promising drugs in the future treatment of severe AA.
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Alopecia em Áreas , Inibidores de Janus Quinases , Metanálise em Rede , Humanos , Alopecia em Áreas/tratamento farmacológico , Alopecia em Áreas/imunologia , Inibidores de Janus Quinases/efeitos adversos , Inibidores de Janus Quinases/uso terapêutico , Inibidores de Janus Quinases/administração & dosagem , Resultado do Tratamento , Administração Oral , Purinas/administração & dosagem , Purinas/efeitos adversos , Azetidinas/administração & dosagem , Azetidinas/efeitos adversos , Azetidinas/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Dexametasona/uso terapêutico , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Sulfonamidas/uso terapêutico , Imunoterapia/métodos , Imunoterapia/efeitos adversos , Ciclopropanos/administração & dosagem , Ciclopropanos/efeitos adversos , Ciclopropanos/uso terapêutico , Índice de Gravidade de Doença , PirazóisRESUMO
The thiophene- and pyrrole-fused heterocyclic compounds have garnered significant interest for their distinctive electron-rich characteristics and notable optoelectronic properties. However, the construction of high-performance systems within this class is of great challenge. Herein, we develop a series of novel dithieno[3,2-b:2',3'-d] pyrrole (DTP) and tetrathieno[3,2-b:2',3'-d] pyrrole (TTP) bridged arylamine compounds (DTP-C4, DTP-C12, DTP-C4-Fc, TTP-C4-OMe, TTP-C4, and TTP-C12) with varying carbon chain lengths. The pertinent experimental results reveal that this series of compounds undergo completely reversible multistep redox processes. Notably, TTP-bridged compounds TTP-C4 and TTP-C12 exhibit impressive multistep near-infrared (NIR) absorption alterations with notable color changes and electroluminescent behaviors, which are mainly attributed to the charge transfer transitions from terminal arylamine units to central bridges, as supported by theoretical calculations. Additionally, compound DTP-C4 demonstrates the ability to visually identify gram-positive and gram-negative bacteria. Therefore, this work suggests the promising electroresponsive nature of compounds TTP-C4 and TTP-C12, positioning them as excellent materials for various applications. It also provides a facile approach to constructing high-performance multifunctional luminescent materials, particularly those with strong and long-wavelength NIR absorption capabilities.
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Aminas , Oxirredução , Pirróis , Tiofenos , Pirróis/química , Tiofenos/química , Aminas/química , Espectroscopia de Luz Próxima ao Infravermelho/métodos , BactériasRESUMO
Since its emergence, SARS-CoV-2 has been continuously evolving, hampering the effectiveness of current vaccines against COVID-19. mAbs can be used to treat patients at risk of severe COVID-19. Thus, the development of broadly protective mAbs and an understanding of the underlying protective mechanisms are of great importance. Here, we isolated mAbs from donors with breakthrough infection with Omicron subvariants using a single-B cell screening platform. We identified a mAb, O5C2, which possesses broad-spectrum neutralization and antibody-dependent cell-mediated cytotoxic activities against SARS-CoV-2 variants, including EG.5.1. Single-particle analysis by cryo-electron microscopy revealed that O5C2 targeted an unusually large epitope within the receptor-binding domain of spike protein that overlapped with the angiotensin-converting enzyme 2 binding interface. Furthermore, O5C2 effectively protected against BA.5 Omicron infection in vivo by mediating changes in transcriptomes enriched in genes involved in apoptosis and interferon responses. Our findings provide insights into the development of pan-protective mAbs against SARS-CoV-2.
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Anticorpos Antivirais , COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , SARS-CoV-2/imunologia , Humanos , COVID-19/imunologia , COVID-19/virologia , Anticorpos Antivirais/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/química , Animais , Camundongos , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/imunologia , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Microscopia Crioeletrônica , Epitopos/imunologia , Anticorpos Amplamente Neutralizantes/imunologia , Citotoxicidade Celular Dependente de Anticorpos/imunologia , FemininoRESUMO
Background: Delayed wound healing in skin injuries has become a significant problem in clinics, seriously affecting and even threatening life and health. Recently, research interest has increased in developing wound dressings containing bioactive compounds capable of improving outcomes for complex healing needs. Methods: In this study, Puerarin-loaded nanoparticles (Pue-NPs) were prepared using the cell-penetrating peptide-poly (lactic-co-glycolic acid) (CPP-PLGA) as a drug carrier by the emulsified solvent evaporation method. Then, they were added into poly (acrylic acid) to obtain a self-assembled nanocomposite hydrogels (SANHs) drug delivery system using the co-polymerization method. The particle size, zeta potential, and micromorphology of Pue-NPs were measured; the appearance, mechanical properties, adhesive strength, and biological activity of SANHs were performed. Finally, the potential of SANHs for wound healing was further evaluated in streptozotocin-induced diabetic mice. Results: Pue-NPs were regularly spherical, with an average particle size of 134.57 ± 1.42 nm and a zeta potential of 2.14 ± 0.78 mV. SANHs was colorless and transparent with a honeycomb-like porous structure and had an excellent swelling ratio (917%), water vapor transmission rate (3077 g·m-2·day-1), mechanical properties (Young's modulus of 18 kPa, elongation at break of 307%), and adhesive strength (15.5 kPa). SANHs exhibited sustained release of Pue over 48h, with a cumulative release of 55.60 ± 6.01%. In vitro tests revealed that the SANHs presented a 92.22% antibacterial rate against Escherichia coli after 4h, and a 61.91% scavenging rate of 1.1-diphenyl-2-trinitrophenylhydrazine (DPPH) radical. In vivo experiments showed that SANHs accelerated wound repair by reducing the inflammatory response at the wound site, promoting angiogenesis, and facilitating epidermal regeneration and collagen deposition. Conclusion: In conclusion, we successfully prepared SANHs. Our results show that SANHs have excellent performance and improves wound healing in diabetic mice model, indicating that it can be used to develop an effective strategy for the treatment of diabetic wounds.
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Diabetes Mellitus Experimental , Nanopartículas , Camundongos , Animais , Hidrogéis/química , Diabetes Mellitus Experimental/tratamento farmacológico , Cicatrização , Nanopartículas/química , Antibacterianos/farmacologia , Polímeros/farmacologia , Peptídeos/farmacologiaRESUMO
[This corrects the article DOI: 10.1371/journal.pntd.0001636.].
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OBJECTIVE: To investigate the toxic effect of chlorambucil combined with ibrutinib on mantle cell lymphoma (MCL) cell line Jeko-1 and its related mechanism. METHODS: The MCL cell line Jeko-1 was incubated with different concentrations of chlorambucil or ibrutinib or the combination of the two drugs, respectively. CCK-8 assay was used to detect the proliferation of the cells, and Western blot was used to measure the protein expression levels of BCL-2, caspase-3, PI3K, AKT and P-AKT. RESULTS: After Jeko-1 cells were treated with chlorambucil (3.125, 6.25, 12.5, 25, 50 µmol/L) and ibrutinib (3.125, 6.25, 12.5, 25, 50 µmol /L) alone for 24, 48, 72h respectively, the cell proliferation was inhibited in a time- and dose-dependent manner. Moreover, the two drugs were applied in combination at low doses (single drug inhibition rate<50%), and the results showed that the combination of two drugs had a more significant inhibitory effect (all P < 0.05). Compared with the control group, the apoptosis rate of the single drug group of chlorambucil (3.125, 6.25, 12.5, 25, 50 µmol/L) and ibutinib (3.125, 6.25, 12.5, 25, 50 µmol/L) was increased in a dose-dependent manner. The combination of the two drugs at low concentrations (3.125, 6.25, 12.5 µmol/L) could significantly increase the apoptosis rate compared with the corresponding concentration of single drug groups (all P < 0.05). Compared with control group, the protein expression levels of caspase-3 in Jeko-1 cells were upregulated, while the protein expression levels of BCL-2, PI3K, and p-AKT/AKT were downregulated after treatment with chlorambucil or ibrutinib alone. The combination of the two drugs could produce a synergistic effect on the expressions of the above-mentioned proteins, and the differences between the combination group and the single drug groups were statistically significant (all P < 0.05). CONCLUSION: Chlorambucil and ibrutinib can promote the apoptosis of MCL cell line Jeko-1, and combined application of the two drugs shows a synergistic effect, the mechanism may be associated with the AKT-related signaling pathways.
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Adenina/análogos & derivados , Linfoma de Célula do Manto , Piperidinas , Humanos , Adulto , Linfoma de Célula do Manto/tratamento farmacológico , Clorambucila/farmacologia , Clorambucila/uso terapêutico , Caspase 3/metabolismo , Proteínas Proto-Oncogênicas c-akt , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fosfatidilinositol 3-QuinasesRESUMO
Lonicerae japonicae (L. japonicae) flos is a medical and food homology herb. This study investigated the phenolic acid and flavonoid contents in L. japonicae flos water extract solution (LJWES) and the preventive effects of LJWES against liver fibrogenesis via FL83B cells and rats. LJWES contains many polyphenols, such as chlorogenic acid, morin, and epicatechin. LJWES increased cell viability and decreased cytotoxicity in thioacetamide (TAA)-treated FL83B cells (75 mM) (p < .05). LJWES decreased (p < .05) gene expressions of Tnf-α, Tnfr1, Bax, and cytochrome c but upregulated Bcl-2 and Bcl-xl in TAA-treated cells; meanwhile, increased protein levels of P53, cleaved caspase 3, and cleaved caspase 9 in TAA treated cells were downregulated (p < .05) by LJWES supplementation. In vivo, results indicated that TAA treatment increased serum liver damage indices (alanine aminotransferase [ALT] and alkaline phosphatase [ALP]) and cytokines (interleukin-6 and transforming growth factor-ß1) levels and impaired liver antioxidant capacities (increased thiobarbituric acid reactive substance value but decreased catalase/glutathione peroxidase activities) in rats (p < .05) while LJWES supplementation amended (p < .05) them. Liver fibrosis scores, collagen deposition, and alpha-smooth muscle actin deposition in TAA-treated rats were also decreased by LJWES supplementation (p < .05). To sum up, LJWES could be a potential hepatoprotective agent against liver fibrogenesis by enhancing antioxidant ability, downregulating inflammation in livers, and reducing apoptosis in hepatocytes.
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Medicamentos de Ervas Chinesas , Ratos , Animais , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Fígado , Hepatócitos , FlavonoidesRESUMO
Tons of broiler livers are produced yearly in Taiwan but always considered waste. Our team has successfully patented and characterized a chicken-liver hydrolysate (CLH) with several biofunctions. Chronic alcohol consumption causes hepatosteatosis or even hepatitis, cirrhosis, and cancers. This study was to investigate the hepatoprotection of CLH-based supplement (GBHP01™) against chronic alcohol consumption. Results showed that GBHP01™ could reduce (p < .05) enlarged liver size, lipid accumulation/steatosis scores, and higher serum AST, ALT, γ-GT, triglyceride, and cholesterol levels induced by an alcoholic liquid diet. GBHP01™ reduced liver inflammation and apoptosis in alcoholic liquid-diet-fed mice via decreasing TBARS, interleukin-6, interleukin-1ß, and tumor necrosis factor-α levels, increasing reduced GSH/TEAC levels and activities of SOD, CAT and GPx, as well as downregulating CYP2E1, BAX/BCL2, Cleaved CASPASE-9/Total CASPASE-9 and Active CASPASE-3/Pro-CASPASE-3 (p < .05). Furthermore, GBHP01™ elevated hepatic alcohol metabolism (ADH and ALDH activities) (p < .05). In conclusion, this study prove the hepatoprotection of GBHP01™ against alcohol consumption.
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Antioxidantes , Fígado Gorduroso , Animais , Camundongos , Antioxidantes/metabolismo , Galinhas/metabolismo , Caspase 9/metabolismo , Fígado/metabolismo , Anti-Inflamatórios/farmacologia , Estresse OxidativoRESUMO
BACKGROUND: In the field of head and neck microvascular reconstruction, no previous study has compared arterial and venous grafting as methods of anterolateral thigh (ALT) pedicle lengthening. Therefore, we conducted this comparative study to compare the outcomes between the two pedicle lengthening techniques. METHODS: We performed comparative effectiveness research by conducting a retrospective chart review from January 2012 to December 2021 to identify patients who underwent head and neck reconstruction with non-descending branch ALT perforator flaps using either the in situ pedicle lengthening (ISPL) technique or the vein graft (VG) technique. A total of 26 patients were analyzed, including 14 who underwent ISPL, and 12 who underwent VG. The collected data, including patient demographics, surgical indications, history of prior free flap, prior neck dissection, radiation therapy, chemotherapy, graft length, and flap outcomes, were analyzed. The flap outcomes were categorized as total flap loss, partial flap loss, flap compromise that required operating room visits, or minor issues, including infection or dehiscence. The flap characteristics and postoperative outcomes were compared between the two groups. RESULTS: The VG group had two flap losses, whereas the ISPL group had none. Although the failure rate was higher in the VG group than that in the ISPL group, the difference was not statistically significant (0% vs. 16.7%, p = 0.203). Additionally, there were no significant differences in flap take-back (14.3% vs. 16.7%, p = 1) and minor complications between the two groups (35.7% vs. 33.3%, p = 1). CONCLUSIONS: If pedicle lengthening with vessel graft is inevitable in head and neck reconstruction, arterial graft may provide a reliable outcome and may be considered an effective alternative when compared to vein grafts.
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Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço , Procedimentos de Cirurgia Plástica , Humanos , Estudos Retrospectivos , Neoplasias de Cabeça e Pescoço/cirurgia , Pescoço/cirurgia , Retalhos de Tecido Biológico/irrigação sanguínea , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Coxa da Perna/cirurgiaRESUMO
Andrographolide (AND) is a bioactive component of the herb Andrographis paniculata and a well-known anti-inflammatory agent. Atherosclerosis is a chronic inflammatory disease of the vasculature, and oxidized LDL (oxLDL) is thought to contribute heavily to atherosclerosis-associated inflammation. The aim of this study was to investigate whether AND mitigates oxLDL-mediated foam cell formation and diet-induced atherosclerosis (in mice fed a high-fat, high-cholesterol, high-cholic acid [HFCCD] diet) and the underlying mechanisms involved. AND attenuated LPS/oxLDL-mediated foam cell formation, IL-1[Formula: see text] mRNA and protein (p37) expression, NLR family pyrin domain containing 3 (NLRP3) mRNA and protein expression, caspase-1 (p20) protein expression, and IL-1[Formula: see text] release in BMDMs. Treatment with oxLDL significantly induced protein and mRNA expression of CD36, lectin-like oxLDL receptor-1 (LOX-1), and scavenger receptor type A (SR-A), whereas pretreatment with AND significantly inhibited protein and mRNA expression of SR-A only. Treatment with oxLDL significantly induced ROS generation and Dil-oxLDL uptake; however, pretreatment with AND alleviated oxLDL-induced ROS generation and Dil-oxLDL uptake. HFCCD feeding significantly increased aortic lipid accumulation, ICAM-1 expression, and IL-1[Formula: see text] mRNA expression, as well as blood levels of glutamic pyruvic transaminase (GPT), total cholesterol, and LDL-C. AND co-administration mitigated aortic lipid accumulation, the protein expression of ICAM-1, mRNA expression of IL-1[Formula: see text] and ICAM-1, and blood levels of GPT. These results suggest that the working mechanisms by which AND mitigates atherosclerosis involve the inhibition of foam cell formation and NLRP3 inflammasome-dependent vascular inflammation as evidenced by decreased SR-A expression and IL-1[Formula: see text] release, respectively.
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Aterosclerose , Inflamassomos , Animais , Camundongos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Macrófagos/metabolismo , Lipoproteínas LDL , Células Espumosas/metabolismo , Receptores Depuradores , Inflamação/metabolismo , Colesterol/metabolismo , Aterosclerose/tratamento farmacológico , Aterosclerose/etiologia , Aterosclerose/metabolismo , RNA Mensageiro/metabolismo , Interleucina-1/metabolismoRESUMO
Theories of innovation emphasize the role of social networks and teams as facilitators of breakthrough discoveries1-4. Around the world, scientists and inventors are more plentiful and interconnected today than ever before4. However, although there are more people making discoveries, and more ideas that can be reconfigured in new ways, research suggests that new ideas are getting harder to find5,6-contradicting recombinant growth theory7,8. Here we shed light on this apparent puzzle. Analysing 20 million research articles and 4 million patent applications from across the globe over the past half-century, we begin by documenting the rise of remote collaboration across cities, underlining the growing interconnectedness of scientists and inventors globally. We further show that across all fields, periods and team sizes, researchers in these remote teams are consistently less likely to make breakthrough discoveries relative to their on-site counterparts. Creating a dataset that allows us to explore the division of labour in knowledge production within teams and across space, we find that among distributed team members, collaboration centres on late-stage, technical tasks involving more codified knowledge. Yet they are less likely to join forces in conceptual tasks-such as conceiving new ideas and designing research-when knowledge is tacit9. We conclude that despite striking improvements in digital technology in recent years, remote teams are less likely to integrate the knowledge of their members to produce new, disruptive ideas.
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Difusão de Inovações , Cooperação Internacional , Invenções , Inventores , Patentes como Assunto , Pesquisadores , Relatório de Pesquisa , Conjuntos de Dados como Assunto , Processos Grupais , Conhecimento , Patentes como Assunto/estatística & dados numéricos , Pesquisadores/organização & administração , Pesquisadores/psicologia , Pesquisadores/tendências , Relatório de Pesquisa/tendências , Rede Social , Invenções/classificação , Invenções/estatística & dados numéricos , Inventores/organização & administração , Inventores/psicologia , Comportamento CooperativoRESUMO
Drought stress impedes viticultural plant growth and development by modifying various metabolic pathways. However, the regulatory network response underlying drought stress is not yet clear. In this study, the leaves and roots of "Shine Muscat" ("SM," Vitis labruscana × Vitis vinifera) and "Thompson Seedless" ("TS," V. vinifera L. cv.) were subjected to drought stress to study the regulatory network used by drought stress. Morphophysiological results showed that the malondialdehyde content after 28 days of drought stress increased more significantly in "TS" than "SM." Furthermore, the multiomics analysis studies showed that a total of 3036-6714 differentially expressed genes and 379-385 differentially abundant metabolites were identified in "SM" and "TS" grapevine cultivars under drought stress. Furthermore, the retained intron was the major form of differential alternative splicing event under drought stress. The photosynthesis pathway, antioxidant system, plant hormone signal transduction, and osmotic adjustment were the primary response systems in the two grapevine cultivars under drought stress. We have identified GRIK1, RFS2, and LKR/SDH as the hub genes in the coexpression network of drought stress. In addition, the difference in the accumulation of pheophorbide-a reveals different drought resistance mechanisms in the two grapevine cultivars. Our study explained the difference in drought response between cultivars and tissues and identified drought stress-responsive genes, which provides reference data for further understanding the regulatory network of drought tolerance in grapevine.
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Antioxidantes , Vitis , Antioxidantes/metabolismo , Secas , Reguladores de Crescimento de Plantas/metabolismo , Fotossíntese , Folhas de Planta/metabolismo , Vitis/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
BACKGROUND: Human angiotensin-converting enzyme 2 (hACE2) is the receptor mediating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. hACE2 expression is low in the lungs and is upregulated after SARS-CoV-2 infection. How such a hACE2-limited pulmonary environment supports efficient virus transmission and how dynamic hACE2 expression affects SARS-CoV-2 infection are unclear. METHODS: We generated stable cell lines with different expression levels of hACE2 to evaluate how the hACE2 expression level can affect SARS-CoV-2 transmission. RESULTS: We demonstrated that the hACE2 expression level controls the mode of SARS-CoV-2 transmission. The hACE2-limited cells have an advantage for SARS-CoV-2 shedding, which leads to cell-free transmission. By contrast, enhanced hACE2 expression facilitates the SARS-CoV-2 cell-to-cell transmission. Furthermore, this cell-to-cell transmission is likely facilitated by hACE2-containing vesicles, which accommodate numerous SARS-CoV-2 virions and transport them to neighboring cells through intercellular extensions. CONCLUSIONS: This hACE2-mediated switch between cell-free and cell-to-cell transmission routes provides SARS-CoV-2 with advantages for either viral spread or evasion of humoral immunity, thereby contributing to the COVID-19 pandemic and pathogenesis.
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COVID-19 , SARS-CoV-2 , Animais , Humanos , Camundongos , Enzima de Conversão de Angiotensina 2/genética , COVID-19/transmissão , Camundongos Transgênicos , Pandemias , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Glicoproteína da Espícula de Coronavírus/genéticaRESUMO
Fucoidans are a class of long chain sulfated polysaccharides and have multiple biological functions. Herein, four natural fucoidans extracted from Fucus vesiculosus, F. serratus, Laminaria japonica and Undaria pinnatifida, were tested for their HCoV-OC43 inhibition and found to demonstrate EC50 values ranging from 0.15 to 0.61 µg/mL. That from U. pinnatifida exhibited the most potent anti-HCoV-OC43 activity with an EC50 value of 0.15 ± 0.02 µg/mL, a potency largely independent of its sulfate content. Comparison of the gene expression profiles of fucoidan-treated and untreated cells infected with HCoV-OC43 revealed that fucoidan treatment effectively diminished HCoV-OC43 gene expressions associated with induced chemokines, cytokines and viral activities. Further studies using a highly fucoidan-resistant HCoV-OC43 determined that fucoidan inhibited HCoV-OC43 infection via interfering with viral entry and led to the identification of the specific site on the N-terminal region of spike protein, that located adjacent to the host cell receptor binding domain, targeted by the virus. Furthermore, in a SARS-CoV-2 pseudovirus neutralization assay, fucoidan also blocked SARS-CoV-2 entry. In vitro and in vivo, fucoidan decreased SARS-CoV-2 viral loads and inhibited viral infection in Calu-3 or Vero E6 cells and SARS-CoV-2 infected hamsters, respectively. Fucoidan was also found to inhibit furin activity, and reported furin inhibitors were found to inhibit viral infection by wild type HCoV-OC43 or SARS-CoV-2. Accordingly, we conclude that fucoidans inhibit coronaviral infection by targeting viral spike protein and host cell furin to interfere with viral entry.
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COVID-19 , Coronavirus Humano OC43 , Animais , Cricetinae , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Furina/metabolismoRESUMO
BACKGROUND: In autologous tissue breast reconstruction, recipient vessels are important for artery perfusion and venous drainage to ensure free flap survival. There are insufficient clinical outcomes to select efficient recipient vessels in bi-pedicled deep inferior epigastric perforator (DIEP) flap reconstruction. METHODS: We presented a retrospective observational series of 108 patients regarding the diameter, anastomosis time, and re-anastomosis rate in internal mammary (IM), circumflex scapular (CS), thoracodorsal (TD), thoracoacromial (TA), lateral thoracic (LT), and internal mammary perforator (IMP) vessels of bi-pedicled DIEP flaps for breast reconstruction after mastectomy. The outcomes were the vessel re-anastomosis rate, flap failure rate, vessel anastomosis time, and complications. Data were gleaned from the chi-square test, Fisher's test, and analysis of variance using Scheffe's test as a post hoc analysis. The level of significance was p < 0.05. RESULTS: There were no significant differences in the diameters of the artery, first vein, and second vein across the recipient vessels (p > 0.05). However, the anastomosis time was longer in IM and TA than in CS, TD, and LT (p < 0.001). Also, there were no significant differences for re-anastomosis, flap necrosis, and fat necrosis among different recipient vessels (p > 0.05). CONCLUSIONS: Because of the altered mastectomy incisions, this study provides complete anatomical vascular properties and suggests that altering recipient vessel selection for bi-pedicled DIEP flaps can shorten anastomosis time and better conceal scars.
Assuntos
Neoplasias da Mama , Mamoplastia , Artéria Torácica Interna , Retalho Perfurante , Feminino , Humanos , Neoplasias da Mama/cirurgia , Neoplasias da Mama/complicações , Artérias Epigástricas/cirurgia , Mamoplastia/efeitos adversos , Artéria Torácica Interna/cirurgia , Mastectomia/efeitos adversos , Retalho Perfurante/irrigação sanguínea , Complicações Pós-Operatórias/etiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Cognitive-behavioral therapy (CBT) and biofeedback therapy are commonly regarded as effective treatment modalities for panic disorder. The aim of this study was to establish a Taiwanese version of an integrated cognitive-behavioral and biofeedback therapy (ICB) and examine its effects on panic disorder using psychological and physiological indicators. METHODS: Thirty patients with panic disorder were enrolled in this study. They were randomly assigned to either the ICB group (n = 15) or the treatment as usual (TAU) group (n = 15). The intervention consisted of six sessions, conducted once a week. Psychological indicators were measured at baseline (prior to intervention), week 3, and week 6, while physiological indicators were measured at baseline and week 6. The psychological indicators included five scales, with the Panic Disorder Severity Scale (PDSS) being the primary measure. The physiological indicators included respiratory sinus arrhythmia (RSA) and skin conductance, which respectively represent parasympathetic and sympathetic activity. RESULTS: Considering all participants, PDSS scores significantly decreased over time, but the difference between the ICB and TAU groups did not reach statistical significance. Among the physiological indicators, resting-state RSA and RSA under relaxation showed significant between-group differences over time, with the ICB group demonstrating a more pronounced improvement in RSA. CONCLUSION: In the context of existing pharmacological treatments, the benefits of ICB for panic disorder may not be observable through psychological indicators. However, it can lead to enhancement of parasympathetic activity as evidenced by the physiological indicators.