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1.
BMC Public Health ; 21(1): 1821, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627194

RESUMO

BACKGROUND: Objectively measured differences in physical activity (PA) and sleep have been documented among people with osteoarthritis (OA) and rheumatoid arthritis (RA) compared to non-arthritic controls. However, it is not clear whether OA and RA subgroups also differ on these indexes or the extent to which distinct arthritis subgroups versus controls can be accurately identified on the basis of objective PA and sleep indexes compared to self-report responses on questionnaires. This study addressed these gaps. METHODS: This case-control study comprised Chinese adults with OA (N = 40) or RA (N = 40) diagnoses based on physician assessments as well as a control group of adults without chronic pain (N = 40). All participants wore a Sensewear Armband (SWA) for consecutive 7 days and completed the International Physical Activity Questionnaire Short Form-Chinese as well as Pittsburgh Sleep Diary to obtain objective and subjective PA and sleep data, respectively. RESULTS: There were no differences between the three groups on any self-report indexes of PA or sleep. Conversely, OA and RA subgroups displayed significantly lower PA levels and more sleep problems than controls did on a majority of SWA indexes, though arthritis subgroups were not differentiated from one another on these measures. Logistic regression analyses indicated four non-multicollinear SWA indexes (i.e., steps, active energy expenditure, vigorous activity, time awake after sleep onset) correctly identified the subgroup membership of 75.0-82.5% of participants with RA or OA while classification accuracy results were attenuated for controls. CONCLUSIONS: Where possible, objective measures should be used to assess PA and sleep of adults with OA and RA while particular self-report PA questionnaires should be used sparingly.

2.
Adv Mater ; : e2105707, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34623716

RESUMO

Embedding catalysts inside of plastics affords accelerated chemical modification with programmable latency and pathways. Nanoscopically embedded enzymes can lead to near-complete degradation of polyesters via chain-end mediated processive depolymerization. The overall degradation rate and pathways have a strong dependence on the morphology of semicrystalline polyesters. Yet, most studies to date focus on pristine polymers instead of mixtures that contain additives and other components despite their nearly universal use in plastic production. Here, additives are introduced to purposely change the morphology of polycaprolactone (PCL) by increasing the bending and twisting of crystalline lamellae. These morphological changes immobilize chain ends preferentially at the crystalline/amorphous interfaces and limit chain-end accessibility by the embedded processive enzyme. This chain-end redistribution reduces the polymer-to-monomer conversion from >95% to less than 50%, causing formation of highly crystalline plastic pieces, including microplastics. By synergizing both random chain scission and processive depolymerization, it is feasible to navigate morphological changes in polymer/additive blends and to achieve near-complete depolymerization. The random scission enzymes in the amorphous domains create new chain ends that are subsequently bound and depolymerized by processive enzymes. Present studies further highlight the importance to consider how the host polymer's morphologies affect the reactions catalyzed by embedded catalytic species.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34623807

RESUMO

Herein, a portable lab-in-a-syringe device integrated with a smartphone sensing platform was designed for rapid, visual quantitative determination of organophosphorus pesticides (OPs) via colorimetric and fluorescent signals. The device was chiefly made up of a conjugate pad labeled with cetyltrimethylammonium bromide-coated gold nanoparticles (CTAB-Au NPs) and a sensing pad modified by ratiometric probes (red-emission quantum dots@SiO2 nanoparticles@green-emission quantum dots, rQDs@SiO2@gQDs probe), which was assembled through a disposable syringe and reusable plastic filter. In the detection system, thiocholine (Tch), the hydrolysis product of thioacetylcholine (ATch) by acetylcholinesterase (AchE), could trigger the aggregation of CTAB-Au NPs, resulting in a significant color change from red to purple. Then, CTAB-Au NPs flowed vertically upward and bound to the rQDs@SiO2@gQDs probe on the sensing pad, reducing the fluorescence resonance energy transfer effect between CTAB-Au NPs and gQDs. Meanwhile, rQDs embedded in SiO2 NPs remained stable as internal reference fluorescence, achieving a color transition from red to green. Thus, based on the inhibition of AChE activity by OPs, a colorimetric and fluorescent dual-mode platform was constructed for on-site detection of OPs. Using glyphosate as a model, with the support of a color recognizer application (APP) on a smartphone, the ratio of red and green channel values could be utilized for accurate OP quantitative analysis ranging from 0 to 10 µM with a detection limit of 2.81 nM (recoveries, 90.8-122.4%; CV, 1.2-3.4%). Overall, the portable lab-in-a-syringe device based on a smartphone sensing platform integrated sample monitoring and result analysis in the field, implying great potential for on-site detection of OPs.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34639570

RESUMO

There has long been a gender bias in medicine. This qualitative study aims to identify the experience of sexism among frontline female nurses and further explore their expectations and possible strategies to get rid of gender bias. This is a descriptive phenomenological study of 23 female nurses with 11 ± 3.98 years of experience who spent 36 ± 6.50 days at the frontline during the initial COVID-19 outbreak. We employed Colaizzi's phenomenological analysis method to understand the subjective experiences, revealing the following themes: (a) materialization of gender identity; (b) incoordinate relationships; (c) future voice of female nurses. The gender bias experienced by female frontline nurses further challenges their emotional identity and self-identity. Therefore, it is important to require extensive consciousness-raising and policy support to defend female nurses' rights.

5.
Int J Biol Macromol ; 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34610351

RESUMO

The purpose of this study was to prepare spiky titanium dioxide nanoparticles-loaded Plantaginis Semen polysaccharide (SN-TiO2-PSP), and the structural characterization and immune response of infectious laryngotracheitis (ILT) vaccine in Hetian chickens were investigated. The structural characterization of SN-TiO2-PSP was analyzed by FT-IR, TEM, and TGA analysis. And the immune organs indexes, lymphocytes proliferation, specific antibody levels, and ratios of CD4+ and CD8+ T lymphocytes were studied. Structural characterization results showed that SN-TiO2-PSP has a typical polysaccharide absorption peak and good stability. The SN-TiO2-PSP's shape was similar to sea urchin, and its zeta potential and particle size were 27.56 mV and 976.11 nm, respectively. In vivo results showed that SN-TiO2-PSP could enhance the proliferation of peripheral lymphocytes, specific antibody levels, CD4+ and CD8+ T lymphocytes ratios, IL-4 and INF-γ levels in Hetian chickens vaccinated with ILT vaccine on D7, D14, D21, and D28. In addition, SN-TiO2-PSP not only enhanced the indexes of immune organs but also promoted the development of immune organs. Therefore, SN-TiO2-PSP has immune adjuvant activity and may become a new potential immune adjuvant.

6.
J Voice ; 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34526225

RESUMO

OBJECTIVE: The aim of this study was to assess the reliability and validity of the Mandarin (simplified) Chinese version of the Voice Fatigue Handicap Questionnaire (MC-VFHQ). METHODS: A total of 358 participants were included from June 2020 to April 2021: 243 patients with voice disorders (patient group) and 115 vocally healthy individuals (control group). The internal consistency, test-retest reliability, content validity, clinical, sensitivity and specificity were analyzed, and the cutoff point was determined. RESULTS: The internal consistency of the MC-VFHQ was high, and the internal consistency assessed with Cronbach α coefficients for the subscale scores ranged from 0.821 to 0.983; the values for the total score were 0.952 and 0.943 in the patient and control group, respectively. Test-retest reliability was high for the total score (intraclass correlation coefficient (ICC) = 0.924) and the subscales (ICCs = 0.969, 0.939, 0.922). The patient group had significantly higher total score, subscale scores, and item scores than the control group (P < 0.001). The cutoff point for screening between the two groups was 63.5, with a sensitivity of 84.8% and a specificity of 84.30%. CONCLUSIONS: The MC-VFHQ is a valid and reliable tool for identifying individuals with probable vocal fatigue. It has good reliability, validity, sensitivity, and specificity in the Mandarin Chinese-speaking population.

7.
PLoS Comput Biol ; 17(9): e1009279, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34529652

RESUMO

Replicability, the ability to replicate scientific findings, is a prerequisite for scientific discovery and clinical utility. Troublingly, we are in the midst of a replicability crisis. A key to replicability is that multiple measurements of the same item (e.g., experimental sample or clinical participant) under fixed experimental constraints are relatively similar to one another. Thus, statistics that quantify the relative contributions of accidental deviations-such as measurement error-as compared to systematic deviations-such as individual differences-are critical. We demonstrate that existing replicability statistics, such as intra-class correlation coefficient and fingerprinting, fail to adequately differentiate between accidental and systematic deviations in very simple settings. We therefore propose a novel statistic, discriminability, which quantifies the degree to which an individual's samples are relatively similar to one another, without restricting the data to be univariate, Gaussian, or even Euclidean. Using this statistic, we introduce the possibility of optimizing experimental design via increasing discriminability and prove that optimizing discriminability improves performance bounds in subsequent inference tasks. In extensive simulated and real datasets (focusing on brain imaging and demonstrating on genomics), only optimizing data discriminability improves performance on all subsequent inference tasks for each dataset. We therefore suggest that designing experiments and analyses to optimize discriminability may be a crucial step in solving the replicability crisis, and more generally, mitigating accidental measurement error.

8.
Reprod Toxicol ; 105: 91-100, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34478853

RESUMO

Pulmonary arterial hypertension is a progressive disorder characterized by remodeling and increased small pulmonary arteries resistance. Endothelin-1 (ET-1) was related to PAH and ET-1 receptors were up-regulated selectively in the lung when exposed to toxic factor hypoxia. However, the role of ET-1 signaling in the pathogenesis of prenatal hypoxia-induced pulmonary abnormalities remains to be elucidated. Pregnant rats were divided into prenatal hypoxia (10.5 % O2 from gestational day 4-21) and control group. Their three-month-old offspring male rats were tested for vascular functions and molecular analysis, DNA methylation was assessed for cellular hypoxia. Functional testing showed that ET-1-mediated vasoconstriction was enhanced, and the expressions of endothelin A receptor/B receptor (ETAR/ETBR), inositol 1,4,5-trisphosphate receptor, type 1, and the sensitivity of calcium channels were increased in the small pulmonary arteries following prenatal hypoxia. q-PCR and DHE staining showed that the expressions of NADPH oxidase 1/4 (Nox1/4) were up-regulated, along with the increased production of superoxide anion. Furthermore, superoxide anion promoted ET-1-mediated pulmonary artery contraction. In the pulmonary artery smooth muscle cell experiments, q-PCR, Western Blot, CCK8 and DHE staining showed that the expressions of ETBR, Nox1/4, and superoxide anion were increased by hypoxia, along with promoted cell proliferation. 2,2,6,6-Tetramethyl-1-piperidinyloxy reversed hypoxia-induced cell proliferation. ETBR antagonist BQ788 inhibited hypoxia-increased expressions of Nox1/4, superoxide anion production, and proliferation of cells. Moreover, methylation analysis indicated that hypoxia decreased the methylation levels of the ETBR promoter in the pulmonary artery smooth muscle cells. The results indicated that prenatal toxic factor hypoxia resulted in abnormal ETBR activation, which enhanced ET-1-mediated vasoconstriction of pulmonary arteries and pulmonary artery smooth muscle cell proliferation through ETBR/Nox1/4-derived ROS pathway.

9.
Ecotoxicol Environ Saf ; 225: 112754, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34488145

RESUMO

Aflatoxin B1 (AFB1) is an unavoidable contaminant in animal feed and agricultural products. AFB1 has been found to impair the liver and kidney function of sheep. However, few data are available, which explain the toxic damage of AFB1 exposure on meat quality. In the study, male Dorper RAMS sheep (6-month-old) were orally administrated with AFB1 at the dose of 1 mg/kg body weight once. The body temperature, serum biochemistry, meat quality-related parameters, oxidation indicators in meat and serum, the mRNA expression of pro-inflammatory cytokines and anti-inflammatory, and microbiota composition of feces were measured 24 h after AFB1 exposure. The results showed that the body temperature was slightly increased, the mental state of mutton sheep was suppressed, and biochemical indicators were significantly changed after AFB1 exposure. AFB1 impaired mutton quality reflected by the structure of muscle fibers was changed, and increased muscle drip loss and lightness (L*), and decreased muscle redness (a*). Moreover, we found that AFB1 caused changes in the oxidative stress indicators T-SOD, T-AOC, MDA, GSH level, and GSH/GSSG ratio, and inflammation damage of mutton reflected by increasing pro-inflammatory TNF-α and reducing anti-inflammatory IL-10 mRNA levels, disrupts the secretion of inflammatory factors, and changed the composition of gut microbiota reflected by significantly increased Firmicutes/Bacteroidetes ratio and decreased the abundances of Butyrivibrio, which are related to the quality of the mutton. In summary, gut microbiota participates in AFB1 to damage mutton quality, which may be co-mediated by oxidative stress, inflammation, and gut microbiota.


Assuntos
Aflatoxina B1 , Microbioma Gastrointestinal , Aflatoxina B1/toxicidade , Animais , Inflamação/induzido quimicamente , Masculino , Carne , Estresse Oxidativo , Ovinos
10.
Mol Biol Evol ; 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34534352

RESUMO

Hydrothermal vents and hydrocarbon seeps in the deep ocean are rare oases fuelled by chemosynthesis. Biological communities inhabiting these ecosystems are often distributed in widely separated habitats, raising intriguing questions on how these organisms achieve connectivity and whether habitat types facilitate intraspecific divergence. The deep-sea patellogastropod limpet Bathyacmaea nipponica that colonises both vents and seeps across ∼2,400 km in the Northwest Pacific is a feasible model to answer these questions. We analysed 123 individuals from four vents and three seeps using a comprehensive method incorporating population genomics and physical ocean modelling. Genome survey sequencing and genotyping-by-sequencing resulted in 9,838 single-nucleotide polymorphisms (SNPs) for population genomic analyses. Genetic divergence and demographic analyses revealed four habitat-linked (i.e., three seep and one vent) genetic groups, with the vent genetic group established via the opportunistic invasion of a few limpet larvae from a nearby seep genetic group. TreeMix analysis uncovered three historical seep-to-vent migration events. ADMIXTURE and divMigrate analyses elucidated weak contemporary gene flow from a seep genetic group to the vent genetic group. Physical ocean modelling underlined the potential roles of seafloor topography and ocean currents in shaping the genetic connectivity, contemporary migration, and local hybridisation of these deep-sea limpets. Our study highlighted the power of integrating genomic and oceanographic approaches in deciphering the demography and diversification of deep-sea organisms. Given the increasing anthropogenic activities (e.g., mining and gas hydrate extraction) affecting the deep ocean, our results have implications for the conservation of deep-sea biodiversity and establishment of marine protected areas.

11.
Contrast Media Mol Imaging ; 2021: 8343002, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34526873

RESUMO

The study aimed to explore the application value of MRI images based on the optimized self-adaptive edge detection algorithm in the diagnosis of placenta previa and in the prediction of postpartum hemorrhage. Specifically, a self-adaptive edge detection algorithm was constructed based on optimized edge operators, with the nearest scale parameters analyzed. It was then used to process the MRI images of 36 patients with placenta previa. MRI images of different types of placenta previa were analyzed. The results found that the placenta of the complete placenta previa was attached to the lower wall of the uterus and covered the internal cervix in U shape, and the placenta adhered to the anterior and lower wall of the uterus, with widespread placenta accreta noted. With the results of cesarean section as the standard, it was observed that 2 cases of complete placenta previa were diagnosed as partial placenta previa. The diagnostic accuracy rate was 94.44%, which was not notably different from the results of cesarean section (p > 0.05). The postpartum hemorrhage rate and hysterectomy rate of complete placenta previa were higher than partial placenta previa and marginal placenta previa, and the difference was notable (p < 0.05), but no notable differences were noted in placenta adhesion, placenta accreta, neonatal death, and neonatal asphyxia between the three types of placenta previa (p > 0.05). The incidence of thinned myometrium, placenta penetrating the cervix, placenta accreta, and uneven placental signal in patients with postpartum hemorrhage was higher versus those without postpartum hemorrhage, and the difference was notable (p < 0.05). In a word, MRI images based on the self-adaptive edge detection algorithm can clearly show the status of placenta previa and exhibit better diagnosis effects and a higher accuracy rate. The thinned myometrium, the placenta penetrating the cervix, placenta accreta, and uneven placental signal may be the related risk factors for postpartum hemorrhage in patients with placenta previa.

12.
Ann Palliat Med ; 10(8): 8701-8708, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34488359

RESUMO

BACKGROUND: There is a lack of data on drug-related problems (DRPs) occurring in nephrology department in China. The objective of this study was to identify and categorize the types and causes of DRPs and to assess their severity. DRPs were examined by clinical pharmacists and the results of their interventions were rated. METHODS: Clinical pharmacists reviewed all medication orders for patients and documented clinical pharmacy services within a nine-month study period. The Pharmaceutical Care Network Europe (PCNE) classification (Version 9.00) was used to identify DRPs. Our Primary outcomes measured the number, causes, types, potential hazards of DRPs and the types and success rate of intervention. RESULTS: Admission medication reconciliation data of 113 patients with chronic kidney disease (CKD) were collected and all of the medications were reviewed retrospectively. Exclude 26 patients who did not occurred DRPs, 87 patients (77%) identified 101 DRPs. The average DRP number per patient was 1.16. The most common type of problem was "treatment effectiveness P1" (84.16%; 85/101). The most common causes were "drug selection C1" (36.00%; 45/125), "dose selection C3" (29.60%; 37/125), and "patient related C7" (26.40%; 33/125). Clinical pharmacists totally proposed 249 interventions, of which 190 (76.31%) were fully accepted and implemented. CONCLUSIONS: DRPs are common among CKD patients in the nephrology department. Hence the necessity for pharmaceutical care to be improved to ensure the ongoing safety of patients.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Nefrologia , Preparações Farmacêuticas , Humanos , Farmacêuticos , Estudos Retrospectivos , Centros de Atenção Terciária
13.
Adv Mater ; : e2101368, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34561914

RESUMO

With the increasing demand for wearable electronics (such as smartwatch equipment, wearable health monitoring systems, and human-robot interface units), flexible energy storage systems with eco-friendly, low-cost, multifunctional characteristics, and high electrochemical performances are imperative to be constructed. Nanocellulose with sustainable natural abundance, superb properties, and unique structures has emerged as a promising nanomaterial, which shows significant potential for fabricating functional energy storage systems. This review is intended to provide novel perspectives on the combination of nanocellulose with other electrochemical materials to design and fabricate nanocellulose-based flexible composites for advanced energy storage devices. First, the unique structural characteristics and properties of nanocellulose are briefly introduced. Second, the structure-property-application relationships of these composites are addressed to optimize their performances from the perspective of processing technologies and micro/nano-interface structure. Next, the recent specific applications of nanocellulose-based composites, ranging from flexible lithium-ion batteries and electrochemical supercapacitors to emerging electrochemical energy storage devices, such as lithium-sulfur batteries, sodium-ion batteries, and zinc-ion batteries, are comprehensively discussed. Finally, the current challenges and future developments in nanocellulose-based composites for the next generation of flexible energy storage systems are proposed.

14.
Curr Neuropharmacol ; 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34561983

RESUMO

Chronic pain, as a common distressing neurological disorder, about 30% of the global population suffers from it. In addition to being highly prevalent, chronic pain causes heavy economic and social burden. Although substantial progress has been achieved to dissect the underlying mechanism of chronic pain in the past few decades, the incidence and treatment of this neurological illness is yet not properly managed in clinical practice. While nerve injury-, chemotherapy- or inflammation-induced functional regulation of gene expression in the dorsal root ganglion and spinal cord are extensively reported to be involved in the pathogenic process of chronic pain, the specific mechanism of these altered transcriptional profile still remains unclear. Recent studies have shown that epigenetic mechanisms, including DNA/RNA methylation, histone modification and circular RNAs regulation, are involved in the occurrence and development of chronic pain. In this review, we provide a description of research on the role of epigenetic mechanism in chronic pain, summarize the latest clinical and preclinical advance in this field, and propose the potential directions for further research to elucidate the molecular mechanism underlying the pathogenesis of chronic pain.

15.
Org Lett ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34581592

RESUMO

A new and green route to skeletally diverse oxo-heterocyclic architectures such as pyrano[3,4-c]chromen-2-ones and pyrano[3,4-c]quinolin-2-ones is reported via an unprecedented photocatalytic Kharasch-type cyclization/1,5-(SN″)-substitution/elimination/6π-electrocyclization/double nucleophilic substitution cascade starting from easily available heteroatom-linked 1,7-diynes and low-cost CBrCl3. During this reaction process, the full scission of carbon-halogen bonds of BrCCl3 was realized to directly build two new rings, including a lactone scaffold, using H2O as the oxygen source of the ester group.

16.
Chemistry ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34549465

RESUMO

Surface cracks could improve the optical and photoelectronic properties of crystalline materials as they increase specific surface area, but the controlled self-assembly of fullerene (C60 ) molecules into micro-/nanostructures with surface cracks is still challenging. Herein, we report the morphology engineering of novel C60 microstructures bearing surface cracks for the first time, selecting phenetole and propan-1-ol (NPA) as good and poor solvents, respectively. Our systematic investigations reveal that phenetole molecules initially participate in the formation of the ends of the C60 microstructures, and then NPA molecules are involved in the gradual growth of the sidewalls of the microstructures. Therefore, the surface cracks of C60 microstructures can be finely regulated by adjusting the addition of NPA and the crystallization time. Interestingly, the cracked C60 microstructures show superior photoluminescence properties relative to the smooth microstructures due to the increased specific surface area. In addition, C60 microstructures with wide cracks show preferential recognition of silica particles over C60 particles owing to electrostatic interactions between the negatively charged C60 microstructures and the positively charged silica microparticles. These C60 crystals with surface cracks have potential applications from optoelectronics to biology.

17.
Oral Dis ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479400

RESUMO

BACKGROUND: Oral squamous cell carcinoma (OSCC), a main type of squamous cell cancer, is associated with considerable morbidity and mortality. Recent reports suggested methyltransferase-like 3 (METTL3)-mediated N6-methyladenosine (m6A) modification to be an essential regulator in the fate determination of stem cells. However, the functional significance of METTL3 in OSCC remains largely unknown. METHODS: METTL3 expression was examined in OSCC patient samples, followed by correlation analysis against clinical tumor features. Functional assays, such as assessment of surface marker expression, colony forming, BrdU incorporation, tumor xenograft assay, and m6A dot blot, were conducted to study the impact of METTL3 knockdown (KD) in OSCC cells. RESULTS: High METTL3 expression was positively correlated with more severe clinical features of OSCC tumors. METTL3 KD caused impairment of stem-like capacities in OSCC cells, such as tumorigenicity in vivo and colony-forming ability in vitro. Furthermore, METTL3-KD and cycloleucine, a methylation inhibitor, decreased m6A levels and down-regulated p38 expression in OSCC cells. On the contrary, the impaired cell proliferation capacity of OSCC cells after METTL3-KD was restored by exogenous expression of p38. CONCLUSION: Our findings identified m6A methyltransferase METTL3 as a key element in the regulation of tumorigenesis in OSCC.

18.
Food Funct ; 12(18): 8635-8646, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34346464

RESUMO

Ulcerative colitis (UC) is a chronic lifetime disorder with a high incidence worldwide. A functional food-based method to prevent UC would be a good option for disease control. G. lemaneiformis oligosaccharides (GLOs) should have potent benefits for the gastrointestinal tract, based on in vitro fermentation assessed in our previous study. This study evaluated the therapeutic potential of GLOs in UC, as well as their possible mechanisms of action. The administration of GLOs was able to reduce the severity of dextran sulphate sodium-induced colitis by protecting mice from weight loss, reductions in colon length, inflammatory infiltration, and colon damage. Gut microbiota composition analysis showed that at the phylum level, GLOs could restore the composition of Bacteroidetes and decrease the level of Firmicutes. Consistently, it increased the contents of beneficial microbial metabolites and short-chain fatty acids in the mouse colitis model. In conclusion, GLOs could comprise a promising functional food strategy to alleviate UC symptoms.

19.
Nucleic Acids Res ; 49(16): 9194-9210, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34365510

RESUMO

Eukaryotic cells express a wide variety of endogenous small regulatory RNAs that function in the nucleus. We previously found that erroneous rRNAs induce the generation of antisense ribosomal siRNAs (risiRNAs) which silence the expression of rRNAs via the nuclear RNAi defective (Nrde) pathway. To further understand the biological roles and mechanisms of this class of small regulatory RNAs, we conducted forward genetic screening to identify factors involved in risiRNA generation in Caenorhabditis elegans. We found that risiRNAs accumulated in the RNA exosome mutants. risiRNAs directed the association of NRDE proteins with pre-rRNAs and the silencing of pre-rRNAs. In the presence of risiRNAs, NRDE-2 accumulated in the nucleolus and colocalized with RNA polymerase I. risiRNAs inhibited the transcription elongation of RNA polymerase I by decreasing RNAP I occupancy downstream of the RNAi-targeted site. Meanwhile, exosomes mislocalized from the nucleolus to nucleoplasm in suppressor of siRNA (susi) mutants, in which erroneous rRNAs accumulated. These results established a novel model of rRNA surveillance by combining ribonuclease-mediated RNA degradation with small RNA-directed nucleolar RNAi system.

20.
Bioorg Chem ; 115: 105257, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34426156

RESUMO

Honokiol is a bioactive biphenolic component derived from Magnoliae officinalis Cortex (known as "Hou Po" in Chinese), a traditional Chinese herbal medicine. A series of novel 1,3,4-thiadiazole/oxadiazole-linked honokiol derivatives were synthesized and tested for anticancer activity against seven human cancer cell lines in this study. Among all derivatives, 8a had the most potent cytotoxic effect on all tested cancer cells, with IC50 values ranging from 1.62 ± 0.19 to 4.61 ± 0.51 µM, which were 10.38-34.36 folds more potent than the parental honokiol (IC50 values of 30.96 ± 1.81-55.67 ± 0.31 µM). On A549, HCT116, and MDA-MB-231 cell lines, 8a demonstrated 5.69-fold, 5.65-fold, and 4.83-fold greater cytotoxicity than cisplatin, respectively. Compound 8a also had higher selectivity (SI values of 8.41-49.38) towards seven cancer cell lines over the normal cell lines than cisplatin (SI values of 1.24-2.52). The analysis of structure-activity relationships (SARs) revealed that honokiol derivatives bearing 1,3,4-thiadiazoles (8a-j) possessed stronger anticancer activity than those containing 1,3,4-oxadiazoles. Further mechanistic investigation indicated that 8a induced cytotoxic autophagy in cancer cells in a time- and dose-independent manner via suppressing the PI3K/Akt/mTOR pathway. Molecular docking suggested that 8a could bind to the PI3Kα active sites. Additionally, 8a inhibited the migration and invasion of A549 and MDA-MB-231 cancer cells.

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