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1.
Crit Rev Oncol Hematol ; 197: 104348, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38588967

RESUMO

Prostate cancer (PCa) is a common health threat to men worldwide, and castration-resistant PCa (CRPC) is the leading cause of PCa-related deaths. Extracellular vesicles (EVs) are lipid bilayer compartments secreted by living cells that are important mediators of intercellular communication. EVs regulate the biological processes of recipient cells by transmitting heterogeneous cargoes, contributing to CRPC occurrence, progression, and drug resistance. These EVs originate not only from malignant cells, but also from various cell types within the tumor microenvironment. EVs are widely dispersed throughout diverse biological fluids and are attractive biomarkers derived from noninvasive liquid biopsy techniques. EV quantities and cargoes have been tested as potential biomarkers for CRPC diagnosis, progression, drug resistance, and prognosis; however, technical barriers to their clinical application continue to exist. Furthermore, exogenous EVs may provide tools for new therapies for CRPC. This review summarizes the current evidence on the role of EVs in CRPC.

2.
J Rehabil Med ; 56: jrm21372, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38659375

RESUMO

OBJECTIVE: To investigate the community integration of patients following stroke and determine the predictors of their level of community integration at 1-year follow-up. DESIGN: A multicenter, longitudinal, and observational study. SUBJECTS: Sixty-five inpatients (41 men) with a mean age of 56.9 (standard deviation = 17.0) years, who had their first stroke at least 1 month prior to this study were recruited from 4 rehabilitation inpatient wards in China. METHODS: In the initial assessment, the participants were evaluated using the Community Integration Questionnaire, the Fugl-Meyer Assessment, the Berg Balance Scale, the Modified Barthel Index, the Mini Mental State Examination, and the Modified Ashworth Scale. In the follow-up assessments, which were conducted via telephone no less than 1 year after discharge, the participants were evaluated using the Community Integration Questionnaire and also assessed for other disease-related conditions. RESULTS: The participants' scores on the Community Integration Questionnaire in the follow-up assessment were significantly greater than those at the initial assessment (p < 0.05). In addition, the participants' Community Integration Questionnaire scores in the follow-up assessment were significantly correlated with their ages, numbers of years of education, and Modified Barthel Index, Berg Balance Scale, Mini Mental State Examination scores in the initial assessment (p < 0.05), and marginally significantly correlated with their scores on Fugl-Meyer Assessment in the initial assessment (p = 0.058). The participants' ages, numbers of years of education, and Modified Barthel Index, Berg Balance Scale, Mini Mental State Examination, Fugl-Meyer Assessment of the lower extremity, and Fugl-Meyer Assessment scores in the initial assessment were predictive of their Community Integration Questionnaire scores at follow-up, with coefficients of determination ranging from 0.254 to 0.056 (p < 0.05). CONCLUSIONS: The level of community integration of the participants was generally low, but it was greater at 1-year follow-up than it was initially. Balance function and daily living ability may be key predictors of community integration of patients following stroke.


Assuntos
Integração Comunitária , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Reabilitação do Acidente Vascular Cerebral/métodos , Estudos Longitudinais , Idoso , Acidente Vascular Cerebral/fisiopatologia , Inquéritos e Questionários , Adulto , China , Avaliação da Deficiência , Equilíbrio Postural/fisiologia
3.
Environ Sci Technol ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38653213

RESUMO

The interaction effects between the main components (proteins (P), carbohydrates (C), and lipids (L)) of protein-rich biomass during microwave-assisted pyrolysis were investigated in depth with an exploration of individual pyrolysis and copyrolysis (PC, PL, and CL) of model compounds. The average heating rate of P was higher than those of C and L, and the interactions in all copyrolysis groups reduced the max instant heating rate. The synergistic extent (S) of PC and PL for bio-oil yield was 16.78 and 18.24%, respectively, indicating that the interactions promoted the production of bio-oil. Besides, all of the copyrolysis groups exhibited a synergistic effect on biochar production (S = 19.43-28.24%), while inhibiting the gas generation, with S ranging from -20.17 to -6.09%. Regarding the gaseous products, apart from H2, P, C, and L primarily generated CO2, CO, and CH4, respectively. Regarding bio-oil composition, the interactions occurring within PC, PL, and CL exhibited a significantly synergistic effect (S = 47.81-412.96%) on the formation of N-heterocyclics/amides, amides/nitriles, and acids/esters, respectively. Finally, the favorable applicability of the proposed interaction effects was verified with microalgae. This study offers valuable insights for understanding the microwave-assisted pyrolysis of protein-rich biomass, laying the groundwork for further research and process optimization.

4.
Histol Histopathol ; : 18738, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38591191

RESUMO

Chondroitin polymerizing factor (CHPF) has been reported to play a pivotal role in the progression of multiple cancers, however, the relationship between CHPF and colorectal cancer (CRC) progression has not been fully understood. The current study revealed that CHPF expression was upregulated in patients with CRC and correlated with an unfavorable prognosis. Also, CHPF knockdown effectively suppressed the viability and mobility of CRC cells and the growth of xenograft tumors. Additionally, SMAD9 was identified as a downstream target of CHPF. SMAD9 knockdown successfully abrogated the promotion of CHPF overexpression in CRC progression, indicating that CHPF regulated the development of CRC through SMAD9. Mechanistically, SMAD9 is ubiquitinated by ASB2, and the regulatory effect of CHPF on SMAD9 activity was exerted via its mediation of ASB2. Collectively, CHPF functioned as a promising prognostic biomarker and tumor-promoter of CRC by regulating the ASB2-mediated ubiquitination of SMAD9.

5.
Wei Sheng Yan Jiu ; 53(1): 30-41, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38443170

RESUMO

OBJECTIVE: To analyze the relationship between food intake and chronic diseases of Jinuo Minority residents living in Yunnan Province. METHODS: A total of 392 Jinuo Minority residents 20-80-year-old among 304 families(male 135, female 257; aged 20-49 years old 140, aged 50-59 years old 136, aged 60-80 years old 116)in Jinghong District in Yunnan Province were selected with stratified multistage cluster sampling method. To apply the method of food frequency questionnaire and questionnaire survey obtain the condition of dietary structure and overweight or obesity, diabetes and dyslipidemia among Jinuo Minority in the past 12 months. Non-conditional Logistic regression analysis was utilized to analyze the correlation between food intake and chronic diseases. RESULTS: In 2020, the prevalence of overweight/obesity, hypertension, diabetes and dyslipidemias among Jinuo adults in Jinghong District were 38.8%(n=152), 19.1%(n=75), 3.6%(n=14)and 26.3%(n=103). Jinuo residents aged 20 and above who have consumed noodle and instant noodle(OR=1.677, 95%CI 1.028-2.736), fermented soybean curd(OR=3.056, 95%CI 1.853-5.038), grass carp(OR=2.245, 95%CI 1.270-3.971), ethnic food/peanut(OR=1.975, 95%CI 1.162-3.355) were more likely to experience overweight/obesity compared to those who did not consume them. On the other hand, individuals who consumed snacks/bread(OR=0.322, 95%CI 0.190-0.545) were less likely to develop overweight/obesity compared to those who did not consume them. Jinuo residents aged 20 and above who have consumed other cereals and cereals products, such as buckwheat(OR=7.029, 95%CI 1.494-33.070), were more likely to develop diabetes than those who did not consume them. And those who have eaten cabbage vegetables(such as cauliflower/cabbage)(OR=0.155, 95%CI 0.034-0.708), and kernel fruits(such as apple/pear)(OR=0.227, 95% CI 0.069-0.743) were less likely to develop diabetes than those who did not consume them. Adults who consumed cooked meat and other livestock and poultry, such as donkey/horse meat(OR=9.676, 95% CI 1.418-66.027), were more likely to cause dyslipidemias compared to did not consume them. Conversely, individuals who consumed root vegetables(such as radish/lotus root)(OR=0.405, 95%CI 0.204-0.803), cooked pork from animal foods(OR=0.482, 95%CI 0.263-0.885), snacks/snack bread(OR=0.590, 95%CI 0.357-0.974) and plum blossom(OR=0.173, 95%CI 0.038-0.793) were less likely to develop dyslipidemia than those who did not consume them. CONCLUSION: In Jinghong District, the overweight/obesity of Jinuo adults aged 20-80 was positively correlated to the consumption of noodles and instant noodles, fermented bean curd, grass carp, and ethnic food/peanut. And there was a negative correlation with the consumption of snacks/bread. Regarding diabetes, a positive correlation was observed with the consumption of other grains and products, while negative correlations were found with the consumption of cabbage vegetables and kernel fruits. For dyslipidemias, there was a positive correlation with the consumption of cooked meat and other livestock and poultry, and negative correlations were identified with the consumption of root vegetables, cooked pork from animal foods, snacks/snack bread, and prunes.


Assuntos
Diabetes Mellitus , Dislipidemias , Adulto , Animais , Feminino , Masculino , Humanos , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Sobrepeso/epidemiologia , China/epidemiologia , Verduras , Obesidade/epidemiologia , Arachis , Doença Crônica
6.
Antonie Van Leeuwenhoek ; 117(1): 48, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429402

RESUMO

A gram-stain-positive, aerobic, rod-shaped bacterial strain capable of producing siderophores, named YIM B08730T, was isolated from a soil sample collected from Wumeng Mountain National Nature Reserve, Zhaotong City, Yunnan Province. Growth occurred at 10-45 °C (optimum, 35-40 â„ƒ), pH 7.0-9.0 (optimum, 7.0) and in the presence of 0-5 % (w/v) NaCl (optimum, 0-1 %, w/v). A comparative analysis of the 16S rRNA gene sequence (1558 bp) of strain YIM B08730T showed the highest similarity to Solibacillus isronensis JCM 13838T (96.2 %), followed by Solibacillus silvestris DSM 12223T (96.0 %) and Solibacillus kalamii ISSFR-015T (95.4 %). The main polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylserine and one unidentified lipid. The main respiratory quinone of strain YIM B08730T was menaquinone 7 (MK-7). The major fatty acids were iso-C15:0 and C16:1ω7c alcohol. The digital DNA-DNA hybridization and average nucleotide identity values between strain YIM B08730T and the reference strain S. isronensis JCM 13838T were 24.8 % and 81.2 %, respectively. The G + C content of the genomic DNA was 37.1 mol%. The genome of the novel strain contained genes associated with the production of siderophores, and it also revealed other functional gene clusters involved in plant growth promotion and soil bioremediation. Based on these phenotypic, chemotaxonomic and phylogenetic analyses, strain YIM B08730T is considered to be a novel species of the genus Solibacillus, for which the name Solibacillus ferritrahens sp. nov. is proposed. The type strain is YIM B08730T (= NBRC 116268T = CGMCC 1.60169T).


Assuntos
Bactérias , Fosfolipídeos , Fosfolipídeos/análise , Filogenia , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , China , Bactérias/genética , Solo
7.
Dalton Trans ; 53(14): 6168-6172, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38488062

RESUMO

Cucurbit[6]uril (Q[6]) could serve as a selective absorbent for the toxic anion Cr2O72-, which was demonstrated by the results of UV-vis, ICP, XPS, SEM, and EDS experiments. Single-crystal X-ray diffraction analysis revealed that capture capacity could be attributed to the outer-surface interactions of cucurbit[n]uril between Cr2O72- and the outer surface of Q[6].

8.
Chem Commun (Camb) ; 60(28): 3830-3833, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38497214

RESUMO

The heavy-atom effect usually quenches fluorescence, but scarcely enhances it. Herein, fluorescence turn-on sensors without or with a bromine atom for F- detection are presented, achieving fast response time within 1 min, and the LODs of 1.9 × 10-7 and 8.5 × 10-8 M, reflecting that halogen atom introduction is beneficial for F- detection ability improvement. The sensing mechanism of -OH unit deprotonation is confirmed based on the results of a 1 : 2 stoichiometric ratio, 1H NMR titration and TD-DFT calculation. The water environment F- detection and spiked recovery experiments demonstrate their potential for real sample detection.

9.
Bioorg Med Chem Lett ; 103: 129709, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38494040

RESUMO

A class of unique hydrazyl hydroxycoumarins (HHs) as novel structural scaffold was developed to combat dreadful bacterial infections. Some HHs could effectively suppress bacterial growth at low concentrations, especially, pyridyl HH 7 exhibited a good inhibition against Pseudomonas aeruginosa 27853 with a low MIC value of 0.5 µg/mL, which was 8-fold more active than norfloxacin. Furthermore, pyridyl HH 7 with low hemolytic activity and low cytotoxicity towards NCM460 cells showed much lower trend to induce the drug-resistant development than norfloxacin. Preliminarily mechanism exploration indicated that pyridyl HH 7 could eradicate the integrity of bacterial membrane, result in the leakage of intracellular proteins, and interact with bacterial DNA gyrase via non-covalent binding, and ADME analysis manifested that compound 7 gave good pharmacokinetic properties. These results suggested that the newly developed hydrazyl hydroxycoumarins as potential multitargeting antibacterial agents should be worthy of further investigation for combating bacterial infection.


Assuntos
Norfloxacino , Pseudomonas aeruginosa , Norfloxacino/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , DNA Girase , Testes de Sensibilidade Microbiana
10.
Cancer Imaging ; 24(1): 45, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38549132

RESUMO

BACKGROUND/PURPOSE: Risk factors for re-bleeding and death after acute variceal bleeding (AVB) in cirrhotic HCC patients are not fully understood.We aimed to (1) explore how the combination of high-risk esophageal varices, HCC status, and portal vein tumor thrombus (i.e., HCC Portal Hypertension Imaging Score [HCCPHTIS]) helps predict increased risk of variceal re-bleeding and mortality; (2) assess predictability and reproducibility of the identified variceal re-bleeding rules. METHODS: This prospective study included 195 HCC patients with first-time AVB and liver cirrhosis, and conducted multivariable Cox regression analysis and Kaplan-Meier analysis. Receiver operating characteristic curve analysis was calculated to find the optimal sensitivity, specificity, and cutoff values of the variables. The reproducibility of the results obtained was verified in a different but related group of patients. RESULTS: 56 patients (28.7%) had re-bleeding within 6 weeks; HCCPHTIS was an independent risk factor for variceal re-bleeding after AVB (Odd ratio, 2.330; 95% confidence interval: 1.728-3.142, p < 0.001). The positive predictive value of HCCPHTIS cut off value > 3 was 66.2%, sensitivity 83.9%, and specificity 82.3%. HCCPHTIS area under the curve was higher than Child-Pugh score (89% vs. 75%, p < 0.001). 74(37.9%) death occurred within 6 weeks; HCCPHTIS > 4 was associated with increased risk of death within 6 weeks after AVB (p < 0.001). CONCLUSION: HCCPHTIS > 3 is a strong predictor of variceal re-bleeding within the first 6 weeks. However, patients with HCCPHTIS > 4 were at increased risk of death within 6 weeks.


Assuntos
Carcinoma Hepatocelular , Varizes Esofágicas e Gástricas , Hipertensão Portal , Neoplasias Hepáticas , Humanos , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/complicações , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/complicações , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/diagnóstico por imagem , Estudos Prospectivos , Reprodutibilidade dos Testes , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico por imagem , Hipertensão Portal/complicações , Hipertensão Portal/diagnóstico por imagem , Cirrose Hepática/complicações , Tomografia Computadorizada por Raios X/efeitos adversos
11.
Psychooncology ; 33(3): e6319, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38497821

RESUMO

OBJECTIVES: Unmet supportive care needs are associated with psychological symptoms such as depression and anxiety. However, so far, few studies have explored the protective psychological factors of unmet needs. Therefore, this study intends to explore the protective effect of self-compassion on unmet needs of Chinese cancer patients and to examine the predictive role of self-compassion on these needs during treatment. METHODS: A longitudinal study was performed at Shaanxi Provincial Cancer Hospital in Xi'an, China. A total of 153 heterogeneous cancer patients were assessed after the first diagnosis (T1), at the beginning (T2) and end (T3) of medical treatment. Hierarchical linear regression analyses were used to examine the research questions. RESULTS: Cross-sectional regression analyses showed that self-compassion at T1 was significantly related to psychological needs at T1. Negative self-compassion at T1 was significantly related to total unmet needs, psychological needs, health system, and information and sexual needs. Longitudinal regression analyses showed that self-compassion at T1 significantly predicted total unmet needs; health system and information (HSI) needs at T2, psychological needs at T3, and negative self-compassion at T1 significantly predicted total unmet needs, HSI needs, physical needs, and patient care needs at T2 when controlling for unmet needs at T1. Positive self-compassion was not a predictor of unmet needs. CONCLUSIONS: Self-compassion can be a protective factor of unmet needs in cancer patients. Future intervention studies should focus on improving the overall level of self-compassion and reducing the level of negative self-compassion in cancer patients to reduce patients' unmet needs.


Assuntos
Neoplasias , Autocompaixão , Humanos , Estudos Transversais , Estudos Longitudinais , Ansiedade , Neoplasias/terapia
12.
J Hazard Mater ; 468: 133797, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38377906

RESUMO

Heavy metals raise a global concern and can be easily retained by ubiquitous iron (oxyhydr)oxides in natural and engineered systems. The complex interaction between iron (oxyhydr)oxides and heavy metals results in various mineral-metal binding configurations, such as outer-sphere complexes and edge-sharing inner-sphere complexes, which determine the accumulation and release of heavy metals in the environment. However, traditional experimental approaches are time-consuming and inadequate to elucidate the complex binding relationships and configurations between iron (oxyhydr)oxides and heavy metals. Herein, a workflow that integrates the binding configuration data of 11 heavy metals on 7 iron (oxyhydr)oxides and then trains machine learning models to predict unknown binding configurations was proposed. The well-trained multi-grained cascade forest models exhibited high accuracy (> 90%) and predictive performance (R2 ∼ 0.75). The underlying effects of mineral properties, metal ion species, and environmental conditions on mineral-metal binding configurations were fully interpreted with data mining. Moreover, the metal release rate was further successfully predicted based on mineral-metal binding configurations. This work provides a method to accurately and quickly predict the binding configuration of heavy metals on iron (oxyhydr)oxides, which would provide guidance for estimating the potential release behavior of heavy metals and remediating heavy metal pollution in natural and engineered environments.

13.
Org Biomol Chem ; 22(10): 2021-2026, 2024 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-38372990

RESUMO

cis-Zeatin (cZ), a cytokinin often overlooked compared to trans-zeatin (tZ), can now be controlled in live cells and plants through a new biocompatible reaction. Using flavin photosensitizers, cZ can be isomerized to tZ or degraded, depending on the presence of a reducing reagent. This breakthrough offers a novel approach for regulating plant growth through chemical molecules.


Assuntos
Mononucleotídeo de Flavina , Zeatina , Zeatina/química , Zeatina/metabolismo , Mononucleotídeo de Flavina/metabolismo , Isomerismo , Citocininas
14.
Bioact Mater ; 35: 362-381, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38379697

RESUMO

Cell implantation offers an appealing avenue for heart repair after myocardial infarction (MI). Nevertheless, the implanted cells are subjected to the aberrant myocardial niche, which inhibits cell survival and maturation, posing significant challenges to the ultimate therapeutic outcome. The functional cardiac patches (CPs) have been proved to construct an elastic conductive, antioxidative, and angiogenic microenvironment for rectifying the aberrant microenvironment of the infarcted myocardium. More importantly, inducing implanted cardiomyocytes (CMs) adapted to the anisotropic arrangement of myocardial tissue by bioengineered structural cues within CPs are more conducive to MI repair. Herein, a functional Cig/(TA-Cu) CP served as biomimetic cardiac niche was fabricated based on structural anisotropic cigarette filter by modifying with tannic acid (TA)-chelated Cu2+ (TA-Cu complex) via a green method. This CP possessed microstructural anisotropy, electrical conductivity and mechanical properties similar to natural myocardium, which could promote elongation, orientation, maturation, and functionalization of CMs. Besides, the Cig/(TA-Cu) CP could efficiently scavenge reactive oxygen species, reduce CM apoptosis, ultimately facilitating myocardial electrical integration, promoting vascular regeneration and improving cardiac function. Together, our study introduces a functional CP that integrates multimodal cues to create a biomimetic cardiac niche and provides an effective strategy for cardiac repair.

15.
Nutr Metab (Lond) ; 21(1): 2, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166933

RESUMO

BACKGROUND: Type 1 diabetes is believed to be an autoimmune condition, characterized by destruction of insulin-producing cells, due to the detrimental inflammation in pancreas. Growing evidences have indicated the important role of type I interferon in the development of type 1 diabetes. METHODS: Trex1-deficient rats were generated by using CRISPR-Cas9. The fasting blood glucose level of rat was measured by a Roche Accuchek blood glucose monitor. The levels of insulin, islet autoantibodies, and interferon-ß were measured using enzyme-linked immunosorbent assay. The inflammatory genes were detected by quantitative PCR and RNA-seq. Hematein-eosin staining was used to detect the pathological changes in pancreas, eye and kidney. The pathological features of kidney were also detected by Masson trichrome and periodic acid-Schiff staining. The distribution of islet cells, immune cells or ssDNA in pancreas was analyzed by immunofluorescent staining. RESULTS: In this study, we established a Trex1-deletion Sprague Dawley rat model, and unexpectedly, we found that the Trex1-/- rats spontaneously develop type 1 diabetes. Similar to human diabetes, the hyperglycemia in rats is accompanied by diabetic complications such as diabetic nephropathy and cataract. Mechanistical investigation revealed the accumulation of ssDNA and the excessive production of proinflammatory cytokines, including IFN-ß, in Trex1 null pancreas. These are likely contributing to the inflammation in pancreas and eventually leading to the decline of pancreatic ß cells. CONCLUSIONS: Our study links the DNA-induced chronic inflammation to the pathogenesis of type 1 diabetes, and also provides an animal model for type 1 diabetes studies.

16.
Lancet Infect Dis ; 24(2): 129-139, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38006892

RESUMO

BACKGROUND: Spread of SARS-CoV-2 led to a global pandemic, and there remains unmet medical needs in the treatment of Omicron infections. VV116, an oral antiviral agent that has potent activity against SARS-CoV-2, was compared with a placebo in this phase 3 study to investigate its efficacy and safety in patients with mild-to-moderate COVID-19. METHODS: This multicentre, double-blind, phase 3, randomised controlled study enrolled adults in hospitals for infectious diseases and tertiary general hospitals in China. Eligible patients were randomly assigned in a 1:1 ratio using permuted block randomisation to receive oral VV116 (0·6 g every 12 h on day 1 and 0·3 g every 12 h on days 2-5) or oral placebo (on the same schedule as VV116) for 5 days. Randomisation stratification factors included SARS-CoV-2 vaccination status and the presence of high-risk factors for progression to severe COVID-19. Inclusion criteria were a positive SARS-CoV-2 test, an initial onset of COVID-19 symptoms 3 days or less before the first study dose, and a score of 2 or more for any target COVID-19-related symptoms in the 24 h before the first dose. Patients who had severe or critical COVID-19 or who had taken any antiviral drugs were excluded from the study. The primary endpoint was the time to clinical symptom resolution for 2 consecutive days. Efficacy analyses were performed on a modified intention-to-treat population, comprising all patients who received at least one dose of VV116 or placebo, tested positive for SARS-CoV-2 nucleic acid, and did not test positive for influenza virus before the first dose. Safety analyses were done on all participants who received at least one dose of VV116 or placebo. This study was registered with ClinicalTrials.gov, NCT05582629, and has been completed. FINDINGS: A total of 1369 patients were randomly assigned to treatment groups and 1347 received either VV116 (n=674) or placebo (n=673). At the interim analysis, VV116 was superior to placebo in reducing the time to sustained clinical symptom resolution among 1229 patients (hazard ratio [HR] 1·21, 95% CI 1·04-1·40; p=0·0023). At the final analysis, a substantial reduction in time to sustained clinical symptom resolution was observed for VV116 compared with placebo among 1296 patients (HR 1·17, 95% CI 1·04-1·33; p=0·0009), consistent with the interim analysis. The incidence of adverse events was similar between groups (242 [35·9%] of 674 patients vs 283 [42·1%] of 673 patients). INTERPRETATION: Among patients with mild-to-moderate COVID-19, VV116 significantly reduced the time to sustained clinical symptom resolution compared with placebo, with no observed safety concerns. FUNDING: Shanghai Vinnerna Biosciences, Shanghai Science and Technology Commission, and the National Key Research and Development Program of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Assuntos
Adenosina , COVID-19 , Adulto , Humanos , SARS-CoV-2 , Vacinas contra COVID-19 , China/epidemiologia , Método Duplo-Cego , Adenosina/análogos & derivados
17.
Huan Jing Ke Xue ; 44(12): 6811-6822, 2023 Dec 08.
Artigo em Chinês | MEDLINE | ID: mdl-38098406

RESUMO

NaHCO3-activated buckwheat biochar was studied, and an optimal biochar of 0.25N-BC [m(NaHCO3):m(buckwheat bark)=0.25:1]was selected. SEM, BET, XRD, Raman, FTIR, and XPS methods were applied to analyze the effects of NaHCO3 on the physicochemical properties of buckwheat biochar. The adsorption properties and mechanism of NaHCO3-activated buckwheat biochar for iopamidol(IPM), a nonionic iodol X-ray contrast agent, were also investigated. The results showed that compared with buckwheat skin biochar(BC), NaHCO3-activated biochar had higher structural defects(surface area and pore volume increased, respectively, from 480.40 m2·g-1 and 0.29 cm3·g-1 to 572.83 m2·g-1 and 0.40 cm3·g-1, with ID/IG being 1.22 times that of BC), the carbon and oxygen functional groups on the BC surface changed significantly, and the polarity increased [(N+O)/C from 0.15 to 0.24]. The maximum adsorption capacity of 0.25N-BC for IPM was 74.94 mg·g-1, which was 9.51 times that of BC(7.88 mg·g-1). The pseudo-second-order adsorption kinetics and Langmuir and Freundlich isotherm models could well fit the adsorption of 0.25N-BC for IPM. The adsorption processes were mainly chemical, monolayer, and heterogeneous multilayer adsorption. Pore filling, hydrogen bonding, π-π, and n-π interactions were the main mechanisms of 0.25N-BC adsorption for IPM. Comparing the activated buckwheat biochar by different bases [KOH, Na2CO3, NaHCO3, KHCO3, and Ca(HCO3)2], 0.25N-BC exhibited high adsorption capability and short equilibrium time and could effectively remove the IPM residue in the actual water(secondary sedimentation tank effluent and lake). The removal rate of IPM remained at 74.91% after three adsorption-desorption cycles. The results showed that NaHCO3-activated buckwheat biochar was a green, effective, and sustainable adsorbent for the removal of iodine-containing organic matter.


Assuntos
Fagopyrum , Poluentes Químicos da Água , Iopamidol , Adsorção , Poluentes Químicos da Água/análise , Carvão Vegetal/química , Cinética
18.
Huan Jing Ke Xue ; 44(12): 6700-6709, 2023 Dec 08.
Artigo em Chinês | MEDLINE | ID: mdl-38098396

RESUMO

Organophosphate esters(OPEs), as a substitute for brominated flame retardants, are widely used in production and life, and their environmental pollution and toxic effects have attracted widespread attention. In this study, the concentrations and distribution characteristics of OPEs in seven major drainage basins of China were sorted out. The average daily dose of OPEs in Chinese adults, adolescents, and children was calculated to assess the health risks, and the reliability of the results was evaluated using Monte Carlo simulation. The toxic effect concentrations of 12 OPEs on aquatic organisms were investigated, and the species sensitivity distribution(SSD) curve was constructed to assess the ecological risk. The results showed that the 5th percentile concentration of ΣOPEs in the seven drainage basins was 52.61 ng·L-1 under the low exposure scenario. The median concentration of ΣOPEs in the seven basins was 499.74 ng·L-1, with trichloroethyl phosphate(TCEP), triethyl phosphate(TEP), and triethyl phosphate(1,3-dichloro-2-propyl) esters(TDCP) as the main contaminants. Under the high exposure scenario, the 95th percentile concentration of ΣOPEs in the seven basins was 1904.4 ng·L-1, 3.8 times that of the intermediate exposure scenario, and the Yangtze River Basin had the highest ΣOPEs concentration under the high exposure scenario. The health risk assessment showed that the non-carcinogenic risk of OPEs exposure through drinking water was within acceptable limits for different populations. Trimethyl phosphate(TMP), triisobutyl phosphate(TiBP), and TCEP were the main contributors to cancer risk. The results of ecological risk assessment showed that TCEP had medium ecological risk at the high exposure level, tributyl phosphate(TnBP) had medium ecological risk under the intermediate exposure scenario, and there was higher ecological risk under the high exposure scenario. Triphenyl phosphate(TPhP) had a risk quotient greater than 1 under the low, intermediate, and high exposure scenarios, and there was a high ecological risk, which requires special attention.


Assuntos
Monitoramento Ambiental , Retardadores de Chama , Criança , Humanos , Adolescente , Monitoramento Ambiental/métodos , Rios , Reprodutibilidade dos Testes , Organofosfatos , Poluição Ambiental , Medição de Risco , China , Ésteres , Fosfatos , Retardadores de Chama/análise
19.
Gen Physiol Biophys ; 42(6): 507-519, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37994427

RESUMO

We investigated the effect of mRNA-VEGF@ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles on the repair of human brain microvascular endothelial cell (HBMECs) injury and its related mechanisms. mRNA-VEGF@USPIO nanoparticles were designed, prepared, and characterized using NTA and UV spectrophotometry. Cell viability was determined using the CCK-8. Cells in the control, TNF-α, and mRNA-VEGF@USPIO groups were sequenced and the differentially expressed genes (DEGs) were identified. Finally, a functional analysis of the DEGs was performed. Both NTA and spectrophotometry results indicated that mRNA-VEGF@USPIO was successfully constructed. TNF-α significantly reduced cell viability and promoted apoptosis compared with the control group (p < 0.05), whereas mRNA-VEGF@USPIO nanoparticles reversed the changes caused by TNF-α. Via sequencing, 9063 DEGs were identified between the control and TNF-α groups, 9125 DEGs were identified between the control and mRNA-VEGF@USPIO groups, and 211 DEGs were identified between the TNF-α and mRNA-VEGF@USPIO groups. Additionally, 71 overlapping DEGs were identified in the three groups using Venn diagrams. These overlapping DEGs were mainly enriched in cytokine-cytokine receptor interactions and the TNF signaling pathway, NF-κB signaling pathway, and NOD-like receptor signaling pathway. This study shows that mRNA-VEGF@USPIO nanoparticles can repair HBMECs injury.


Assuntos
Nanopartículas de Magnetita , Fator A de Crescimento do Endotélio Vascular , Humanos , Fator A de Crescimento do Endotélio Vascular/genética , Fator de Necrose Tumoral alfa/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Dextranos/metabolismo , Células Endoteliais , Encéfalo/metabolismo , Imageamento por Ressonância Magnética
20.
Inorg Chem ; 62(46): 19142-19152, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37945528

RESUMO

Studies on the syntheses, photophysical properties, and applications of cis-bis(2-phenylpyridine) platinum(II) complex (Pt(ppy)2) family are of great importance, but very limited progress has been achieved to date. Herein, a one-pot method was established for the syntheses of Pt(ppy)2-type complexes Pt-ppy and Pt-tBu. These two compounds were nonemissive in dilute solutions. However, they produced intense red and deep-red phosphorescence in the aggregation and film states, with lifetimes and quantum yields up to 1.92 µs and 70%, respectively, exhibiting unique aggregation-induced emission (AIE) characteristics. According to the experimental and theoretical studies, molecular configuration transformation (MCT) in the excited state may occur because of the d-d transition from the Pt center, causing nonradiative transitions in the solution. Nevertheless, the MCT would be largely restricted by the intermolecular interactions or rigid matrix, thereby enabling efficient phosphorescence in the aggregation state and in the PMMA films. Consequently, the AIE characteristics of Pt-ppy and Pt-tBu probably result from the restriction of molecular configuration transformation (RMCT). Due to the π-π and/or weak Pt-Pt interactions and the concentration-dependent emission characteristics, they emit deep-red and NIR emissions generated by excimer and/or MMLCT emitting species. Inspired by their AIE features, electroluminescence and cell imaging applications are explored. To the best of our knowledge, this is the first comprehensive study on the synthesis optimization, photophysical properties, AIE characteristics, and applications of the Pt(ppy)2-type complexes, which may rebloom the research studies on this type of Pt(II) complex family and provide valuable insights on the development of phosphorescent AIE metal-organic complexes.

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