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1.
J Hazard Mater ; 421: 126830, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34396975

RESUMO

Numerous studies have investigated neurobehavioral toxicity of microplastics, but no studies have illustrated mechanism via brain-gut axis. Here, juvenile discus fish (Symphysodon aequifasciatus) were exposed for 96 h to microfibers (900 µm, fiber, MFs) or nanoplastics (~88 nm, bead, NPs) with three concentrations (0, 20 and 200 µg/L). Accumulation in fish gut was independent of plastics type and concentration. MFs reduced growth performance while NPs weakened swimming and predatory performance of post-exposed discus. For brain cholinesterase activity, acetylcholinesterase was activated by NPs while NPs/MFs exposure inhibited butyrylcholinesterase. Concentrations of neurotransmitters (acetylcholine, dopamine and γ-aminobutyric acid) increased in brain but decreased in gut after NPs or MFs exposure. For gut microbiota, increased richness under MFs exposure was observed. At phylum level, Proteobacteria proportion was lower in NPs but higher in MFs. Abundance of Clostridia and Fusobacteriia (Bacillus), potentially secreting neurotransmitters, increased in NPs but decreased in MFs. Brain transcriptomics revealed seven upregulated and four downregulated genes concerning neural-activities. Pathways of neuroactive ligand-receptor interaction and serotonergic synapse were enriched in both MFs and NPs, but dopaminergic synapse pathway was enriched only in MFs. These results established a novel mechanism by which microplastics might cause behavioral toxicities via brain-gut-microbiota axis.


Assuntos
Microbioma Gastrointestinal , Plásticos , Acetilcolinesterase , Animais , Encéfalo , Butirilcolinesterase , Microplásticos
2.
Environ Res ; 203: 111821, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34370988

RESUMO

Frequent ozone and fine particulate matter (PM2.5) pollution have been occurring in the Guanzhong Plain in China. To effectively control the tropospheric ozone and PM2.5 pollution, this study performed measurements of 102 VOCs species from Sep.19-25 (autumn) and Nov.27-Dec. 8, 2017 (winter) at Weinan in the central Guanzhong Plain. The total volatile organic compounds (TVOCs) concentrations were 95.8 ± 30.6 ppbv in autumn and 74.4 ± 37.1 ppbv in winter. Alkanes were the most abundant group in both of autumn and winter, accounting for 33.5% and 39.6% of TVOCs concentrations, respectively. The levels of aromatics and oxygenated VOCs were higher in autumn than in winter, mainly due to changes in industrial activities and combustion strength. Photochemical reactivities and ozone formation potentials (OFPs) of VOCs were calculated by applying the OH radical loss rate (LOH) and maximum incremental reactivity (MIR) method, respectively. Results showed that Alkenes and aromatics were the key VOCs in term ozone formation in Weinan, which together contributed 59.6% ̶ 65.3% to the total LOH and OFP. Secondary organic aerosol formation potentials (SOAFP) of the measured VOCs were investigated by employing the fractional aerosol coefficient (FAC) method. Aromatics contributed 94.9% and 96.2% to the total SOAFP in autumn and winter, respectively. The regional transport effects on VOCs and ozone formation were investigated by using trajectory analysis and potential source contribution function (PSCF). Results showed that regional anthropogenic sources from industrial cities (Tongchuan, Xi'an city) and biogenic sources from Qinling Mountain influenced VOCs levels and OFP at Weinan. Future studies need to emphasize on meteorological factors and sources that impact on VOCs concentrations in Weinan.

3.
Front Psychiatry ; 12: 755159, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721118

RESUMO

To explore the relationship between negative affect, mind-wandering, rumination and obsessive-compulsive symptoms, 100 patients with obsessive-compulsive disorder and 100 healthy controls were assessed using the Obsessive-Compulsive Inventory, the Beck Anxiety Inventory, the Beck Depression Inventory, the Mind Wandering Scale and the Ruminative Response Scale. The results show that (i) patients diagnosed with obsessive-compulsive disorder displayed higher obsessive-compulsive symptoms, negative affect, mind-wandering and rumination compared with healthy controls; (ii) negative affect, mind-wandering and rumination were positively correlated with the severity of obsessive-compulsive symptoms; (iii) mind-wandering predicted the severity of obsessive-compulsive symptoms (both directly and indirectly); (iv) rumination and negative affect mediated the relationship between mind-wandering and obsessive-compulsive symptoms. The results preliminarily reveal the relationship between mind-wandering and psychopathological obsessive-compulsive symptoms, providing a reference for exploring novel psychological treatments for obsessive-compulsive disorder.

4.
J Neurotrauma ; 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34726508

RESUMO

Excessive activation of voltage-gated sodium channel Nav1.3 has been recently reported in secondary traumatic brain injury (TBI). However, the molecular mechanisms underlying regulating voltage-gated sodium channel (Nav1.3) has not been well understood. The present study used a TBI rat model induced by a fluid percussion device and performed a circRNA microarray (n=3) to profile the altered circRNAs in the hippocampus after TBI. After PCR validation, certain circRNA was selected to investigate the function and mechanism in regulating Nav1.3 in the TBI rat model by intracerebroventricular (ICV) injection with lentivirus. The neurological outcome was evaluated by Morris water maze (MWM) test, modified Neurological Severity Score (mNSS), brain water content measurement, hematoxylin, and eosin (H&E) staining. The related molecular mechanisms were explored with PCR, western blotting, luciferase reporter, chromatin immunoprecipitation (ChIP), and electrophoretic mobility shift assay (EMSA). A total of 347 circRNAs were observed to be differentially expressed (FC ≥1.2 and p < 0.05) after TBI, including 234 up-regulated and 113 down-regulated circRNAs. Among 10 validated circRNAs, we selected circRNA_009194 with the maximized up-regulated fold change (n=5, FC=4.45, p<0.001) for the in vivo functional experiments. Down-regulation of circRNA_009194 resulted in a 27.5% reduced mNSS in rat brain (n=6, p<0.01) after TBI and regulated the expression levels of miR-145-3p, Sp1, and Nav1.3, which was reversed by sh-miR-145-3p or Sp1/Nav1.3 overexpression (n=5, p<0.05). Mechanistically, circRNA_009194 might act as a sponge for miR-145-3p to regulate Sp1-mediated Nav1.3. This study demonstrated that circRNA_009194 knockdown could improve neurological outcomes in TBI in vivo by inhibiting Nav1.3, directly or indirectly (Graphical Summary).

5.
Bioengineered ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34784837

RESUMO

Umbilical cord mesenchymal stem cells (UCMSCs) are regarded as an ideal source for clinical use. Increasing evidence has suggested that microRNAs (miRNAs) work as a crucial regulator in the development of plentiful diseases, including intrauterine adhesions (IUA). Herein, we investigated the specific impacts of UCMSCs overexpressing miR-455-5p in IUA. UCMSCs were cocultured with endometrial stromal cells (ESCs). Thirty-two female mice were divided into four different treated groups: sham, model, model + UCMSC-miR-NC and model + UCMSC-miR-455-5p. Mice in model groups were induced by uterine curettage. MiR-455-5p overexpressed UCMSCs facilitated the proliferation and cell cycle progression of ESCs according to 5-ethynyl-2'-deoxyuridine assay and flow cytometry analysis. Hematoxylin-eosin and Masson staining revealed that miR-455-5p upregulation in UCMSCs increased the number of endometrial glands and suppressed endometrial fibrosis in murine uterine tissues. Western blotting displayed that miR-455-5p overexpressed UCMSCs promoted the activation of Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling in ESCs and murine uterine tissues. Mechanistically, miR-455-5p targeted 3' untranslated region of suppressor of cytokine signaling 3 (SOCS3), which was confirmed by luciferase reporter assay. Reverse transcription quantitative polymerase chain reaction demonstrated that miR-455-5p was lowly expressed and SOCS3 was highly expressed in murine uterine tissues of IUA model. Moreover, Pearson correlation analysis showed that their expression was inversely correlated. Rescue assays suggested that inhibiting JAK/STAT3 signaling reversed effects of miR-455-5p on the behaviors of ESCs. The results indicated that miR-455-5p overexpression in UCMSCs helps to attenuate endometrial injury and repair damaged endometrium by activating SOCS3-mediated JAK/STAT3 signaling.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34807567

RESUMO

Metal-organic frameworks (MOFs) with a high surface area and excellent stability are potential candidates for uranium (U) adsorption. Amidoxime (AO) is the most widely used functional group to extract U, which is usually introduced into MOFs by two-step post-synthetic methods (PSMs). Herein, MOF UiO-66-NH-(AO) was obtained by a one-step PSM with amidoximation from UiO-66-NH-(CN), which was synthesized by a new organic ligand of 2-cyano-terephthalic acid and whose morphology was octahedron and could be well controlled with the new ligand. The one-step PSM can greatly maintain the octahedron of the MOFs. What is more, UiO-66-NH-(AO) showed good adsorption performance for U, the adsorption equilibrium was obtained within 1500 min, and the adsorption capacity of U was calculated to be 134.1 mg/g according to the Langmuir model. It also had excellent selectivity for U in the presence of high concentrations of vanadium (V), ferrum (Fe), magnesium (Mg), calcium (Ca), and zirconium (Zr). The adsorption capacity of U in natural seawater was determined to be 5.2 mg/g within 8 days. The recyclability of UiO-66-NH-(AO) in simulated seawater was demonstrated for at least four adsorption/desorption cycles. The binding mechanism was investigated by the extended X-ray absorption fine structure spectroscopy, revealing that U binding occurs in a fashion η2 motif. This study provides a reliable idea for the modification of MOFs and the potential for MOF-based materials to extract U from seawater.

7.
J Cancer ; 12(23): 7223-7236, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34729123

RESUMO

Background: At present, there is no clinical prediction model for ovarian carcinosarcoma (OCS) that is based on a large sample of real data. This study aimed to construct nomograms using data extracted from the Surveillance, Epidemiology, and End Results (SEER) database that can be used to predict the overall survival (OS) and cancer-specific survival (CSS) of patients with OCS and further guide the choice of clinical treatment. Methods: We selected 2753 cases of OCS from the SEER database from 1998 to 2016. Patients were randomly divided in a 7:3 ratio into a training cohort (n = 1929) and a validation cohort (n = 824). Cox analysis was used to select prognostic factors for OS and CSS, and nomograms were then established. The performance of nomogram models was assessed using the concordance index, the area under the receiver operating characteristic curve, calibration curves, and by decision curve analysis. Data from 21 OCS patients at Shengjing Hospital from 2001 to 2021 were collected for external verification. Kaplan-Meier curves were plotted to compare survival outcomes between subgroups. Results: Nomograms based on independent prognostic factors showed good predictive power and clinical practicality. Internal and external validation indicated that the nomograms performed better than staging and grading systems. Significant differences were observed in the survival curves of different risk subgroups. Conclusions: The developed nomograms will enable individualized evaluation of the OS and CSS, thus guiding the treatment of patients with OCS.

8.
Asian J Androl ; 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34747721

RESUMO

This paper presents a meta-analysis regarding the detection rate (DR) of fluorine-18 (18F)-labeled prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) in the management of patients with prostate cancer (PCa). Relevant studies regarding 18F-PSMA PET/CT in the management of PCa published until June 1, 2021, were electronically searched in online databases including EMBASE, PubMed, and Web of Science. The primary outcome was the DR of 18F-PSMA PET/CT in managing PCa patients, while the secondary outcome was the DR of 18F-PSMA PET/CT according to Gleason scores and serum prostate-specific antigen (PSA) level. The pooled DR was calculated on a per-patient basis, with pooled odd ratios and 95% confidence intervals (CIs). In total, 17 observational studies evaluating 1019 patients with PCa met the inclusion criteria. The DR of 18F-PSMA PET/CT was 0.83 (95% CI: 0.78-0.88), in the random-effects model. Subsequently, the analysis of DR of 18F-PSMA PET/CT in PCa patients using Gleason score (≤7 vs ≥8), showed a significant difference in PCa patients. Based on the above results, the higher Gleason score of PCa patients, the higher DR of 18F-PSMA PET/CT. The DR of 18F-PSMA PET/CT in PCa was 0.57 for PSA <0.5 ng ml-1; 0.75 for PSA ≥0.5 ng ml-1 and <1.0 ng ml-1; 0.93 for PSA ≥1.0 ng ml-1 and <2.0 ng ml-1; and 0.95 for PSA ≥2.0 ng ml-1. Therefore, the significant diagnostic value was found in terms of the DR of 18F-PSMA PET/CT in managing PCa patients and was associated with Gleason score and serum PSA level.

9.
Proc Natl Acad Sci U S A ; 118(46)2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34750273

RESUMO

What determines the rate at which a multicellular organism matures is a fundamental question in biology. In plants, the decline of miR156 with age serves as an intrinsic, evolutionarily conserved timer for the juvenile-to-adult phase transition. However, the way in which age regulates miR156 abundance is poorly understood. Here, we show that the rate of decline in miR156 is correlated with developmental age rather than chronological age. Mechanistically, we found that cell division in the apical meristem is a trigger for miR156 decline. The transcriptional activity of MIR156 genes is gradually attenuated by the deposition of the repressive histone mark H3K27me3 along with cell division. Our findings thus provide a plausible explanation of why the maturation program of a multicellular organism is unidirectional and irreversible under normal growth conditions and suggest that cell quiescence is the fountain of youth in plants.

10.
Int J Mol Sci ; 22(21)2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34769365

RESUMO

Loach (Misgurnus anguillicaudatus) is well known to perform air-breathing through the posterior intestine and skin. However, we find here for the first time a unique central vascular structure in the loach barbel, with a blood-gas diffusion distance as short as that of the posterior intestine. Under acute hypoxia, the distance of loach barbels became significantly shorter. Moreover, barbel removal significantly decreased air-breathing frequency of the loach. These findings imply that the barbel is another air-breathing organ of the loach. For further investigation of loach barbel air-breathing, a transcriptome analysis of barbels with air exposure treatment was performed. A total of 2546 differentially expressed genes (DEGs) between the T-XU (air exposure) and C-XU (control) group were identified, and 13 key DEGs related to barbel air-breathing were screened out. On this foundation, sequence, expression, and location analysis results indicated an important positive role of fibronectin 1b (fn1b) in loach barbel air-breathing. We further generated an fn1b-depletion loach (MT for short) using the CRISPR/Cas9 technique. It was indicated that depletion of fn1b could weaker barbel air-breathing ability. In conclusion, due to nonlethal and regenerative characteristics, the loach barbel, a newly discovered and fn1b-related fish air-breathing organ, can be a good model for fish air-breathing research.

11.
J Affect Disord ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34801604

RESUMO

BACKGROUND: Obsessive-compulsive disorder (OCD) is a disabling condition for which approximately 40% of patients do not respond to first-line treatment. Transcranial direct current stimulation (tDCS) is a safe and accessible technique that modulates cortical excitability and inhibition, but evidence of its efficacy for OCD is insufficient. OBJECTIVE: To investigate the efficacy of tDCS for OCD and alterations of cortical excitability and inhibition after treatment measured by concurrent transcranial magnetic stimulation-electroencephalography (TMS-EEG). METHODS: Twenty-four OCD patients underwent 10 20-min sessions of 1.5mA high-definition tDCS with a cathode placed over the right orbitofrontal cortex (OFC) and anode electrodes set around the cathodal electrode. TMS-EEG was performed before and after tDCS treatment. OCD symptom severitys was assessed using Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and the Beck Depression Inventory-Ⅱ (BDI-Ⅱ), and Beck Anxiety Inventory (BAI) were used to assess the severity of depression and anxiety symptoms. Twenty-seven healthy controls were recruited with TMS-EEG recorded. RESULTS: Following tDCS, the Y-BOCS, BDI-Ⅱ, and BAI scores decreased significantly (all p = 0.000). TMS-evoked N100 amplitude, thought to be related to GABAB receptor function, was significantly reduced after tDCS (Z = -2.143, p = 0.032) which was higher in OCD patients than in healthy controls at baseline (Z = -2.151, p = 0.031). LIMITATIONS: Pharmacotherapy during tDCS treatment may influence the effect of tDCS and EEG. CONCLUSIONS: Cathodal high-definition tDCS applied over the OFC could improve OCD, depression, and anxiety symptoms along with alleviation of GABAB receptor function.

12.
J Psychiatry Neurosci ; 46(6): E628-E638, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34785511

RESUMO

BACKGROUND: Cognitive behavioural therapy (CBT) is considered an effective first-line treatment for obsessive-compulsive disorder (OCD). However, the neural basis of CBT for OCD has not yet been elucidated. The role of the amygdala in OCD and its functional coupling with the cerebral cortex have received increasing attention, and may provide new understanding of the neural basis of CBT for OCD. METHODS: We acquired baseline resting-state functional MRI (fMRI) scans from 45 unmedicated patients with OCD and 40 healthy controls; we then acquired another wave of resting-state fMRI scans from the patients with OCD after 12 weeks of CBT. We performed seed-based resting-state functional connectivity analyses of the amygdala subregions to examine changes in patients with OCD as a result of CBT. RESULTS: Compared to healthy controls, patients with OCD showed significantly increased resting-state functional connectivity at baseline between the left basolateral amygdala and the right middle frontal gyrus, and between the superficial amygdala and the right cuneus. In patients with OCD who responded to CBT, we found decreased resting-state functional connectivity after CBT between the amygdala subregions and the visual association cortices and increased resting-state functional connectivity between the amygdala subregions and the right inferior parietal lobe. Furthermore, these changes in resting-state functional connectivity were positively associated with changes in scores on the compulsion or obsession subscales of the Yale-Brown Obsessive-Compulsive Scale. LIMITATIONS: Because of the lack of a second scan for healthy controls after 12 weeks, our results may have been confounded by other variables. CONCLUSION: Our findings yield insights into the pathophysiology of OCD; they also reveal the potential neural changes elicited by CBT, and thus have implications for guiding effective treatment strategies with CBT for OCD.

13.
J Hazard Mater ; : 127751, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34799162

RESUMO

As detriments in aquatic environments, microplastics (MPs) have been commonly studied on organisms, but tissue-scale effects of MPs were poorly understood. Discus fish (Symphysodon aequifasciatus), herewith, were exposed to polystyrene MPs (0/20/200 µg/L) for 28 d. We found that MPs significantly inhibited growth performance. MPs were observed in skin, gill and intestine after 14/28-d exposure. MPs bioaccumulation was independent of exposure time, but increased with MPs concentrations. Microbial community diversity of fish gill, but not skin and intestine, in MPs treatments was significantly increased. Bacterial community of MP-treated skin and gill were obviously separated from control. Skin dominant phyla changed from Actinobacteriota to Proteobacteria and Firmicutes. Proteobacteria gradually occupied dominance in gill after exposure. Furthermore, MPs-induced skin oxidative stress was demonstrated by the activation of superoxide dismutase and catalase. Skin malondialdehyde also increased and showed significant correlations with four bacterial phyla, e.g., Proteobacteria. Gill Na+/K+-ATPase activity decreased, strongly correlating to microbial community changes caused by MPs. Intestinal digestive enzymes activity (pepsin, lipase and α-amylase) reduced, revealing correlation with bacterial community especially Fibrobacterota. These results suggest a tissue-specific effect of MPs to microbial community and biomarkers in aquatic organism.

14.
J Neurosci Res ; 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34766648

RESUMO

Thalamus and thalamocortical connectivity are crucial for consciousness; however, their microstructural changes in patients with a disorder of consciousness (DOC) have not yet been thoroughly characterized. In the present study, we applied the novel fixel-based analysis to comprehensively investigate the thalamus-related microstructural abnormalities in 10 patients with DOC using 7-T diffusion-weighted imaging data. We found that compared to healthy controls, patients with DOC showed reduced fiber density (FD) and fiber density and cross-section (FDC) in the mediodorsal, anterior, and ventral anterior thalamic nuclei, while fiber-bundle cross-section (FC) was not significantly altered in the thalamus. Impaired thalamocortical connectivity in the DOC cohort was mainly connected to the middle frontal gyrus, anterior cingulate gyrus, fusiform gyrus, and sensorimotor cortices, including the precentral gyrus and postcentral gyrus, with predominant microstructural abnormalities in FD and FDC. Correlation analysis showed that FC of the right mediodorsal thalamus was negatively correlated with the level of consciousness. Our results suggest that microstructural abnormalities of thalamus and thalamocortical connectivity in DOC were mainly attributed to axonal injury. In particular, the microstructural integrity of the thalamus is a vital factor in consciousness generation.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34797400

RESUMO

The combined cross-linked enzyme aggregates (combi-CLEAs) containing galactitol dehydrogenase (Gdh) and NADH oxidase (Nox) were prepared for L-tagatose synthesis. To prevent the excess consumption of cofactor, Nox in the combi-CLEAs was used to in situ regenerate NAD+. In the immobilization process, ammonia sulfate and glutaraldehyde were used as the precipitant and cross-linking reagent, respectively. The preparation conditions were optimized as follows: 60% ammonium sulfate, 1:1 (molar ratio) of Gdh to Nox, 20:1 (molar ratio) of protein to glutaraldehyde, and 6 h of cross-linking time at 35 °C. Under these conditions, the activity of the combi-CLEAs was 210 U g-1. The combi-CLEAs exhibited higher thermostability and preserved 51.5% of the original activity after eight cycles of reuses at 45 °C. The combi-CLEAs were utilized for the preparation of L-tagatose without by-products. Therefore, the combi-CLEAs have the industrial potential for the bioconversion of galactitol to L-tagatose.

16.
Ann Palliat Med ; 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34775772

RESUMO

BACKGROUND: Evidence suggests that poor mental health (MH) is a risk factor for the health of older adults. Dietary diversity is considered to be related to healthy aging. However, the relationship between diet and MH is still unclear. Therefore, the purpose of this study was to investigate the relationship between dietary diversity score (DDS) and anxiety and depression among centenarians and their offspring and spouses. METHODS: Evidence suggests that poor mental health (MH) is a risk factor for the health of older adults. Dietary diversity is considered to be related to healthy aging. However, the relationship between diet and MH is still unclear. Therefore, the purpose of this study was to investigate the relationship between dietary diversity score (DDS) and anxiety and depression among centenarians and their offspring and spouses. RESULTS: Among the 288 older adults, 12.8% reported symptoms of depression, and 8.7% reported anxiety. People with a lower dietary diversity had higher rates of anxiety and depression. After controlling for age, place of residence, economic status, alcohol drinking, and physical activity, a lower DDS was found to be a risk factor for depressive symptoms [odds ratio (OR): 2.237; 95% confidence interval (CI): 1.009-4.959; P=0.048]. DDS was negatively correlated with depression score in older adults (r=-0.224; P<0.001), especially offspring and their spouses (r=-0.275; P<0.001). However, no significant relationship was observed between DDS and anxiety. In addition, eating legumes (OR: 0.415; 95% CI: 0.188-0.920; P=0.030) and nuts (OR: 0.255; 95% CI: 0.116-0.561; P=0.001) at least once a week can act as protective factors for depression. Eating nuts (OR: 0.405; 95% CI: 0.168-0.978; P=0.044) and meat (OR: 0.396, 95% CI: 0.161-0.975; P=0.044) at least once a week can act as protective factors for anxiety. CONCLUSIONS: These results suggest an association between low dietary diversity and a higher incidence of mental disorders. Further, the possibility of reverse causality cannot be ruled out. It is necessary to conduct further prospective studies.

17.
Adv Ther ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34739698

RESUMO

INTRODUCTION: Ovarian cancer has a high mortality rate due to difficulties in early detection and chemotherapy resistance. Human epididymal protein 4 (HE4) has been adopted as a novel serum biomarker for early ovarian cancer diagnosis, and the presence of Lewis y antigen modifications on HE4 in ovarian cancer cell lines has been detected in previous studies. The aim of this study was to analyze the expression of HE4 and Lewis y antigen in human ovarian cancer in order to find a correlation between them, as well as with the clinical pathological parameters of patients with ovarian cancer. METHODS: Immunohistochemistry was used to detect the respective expression of these compounds in two patient groups (chemotherapy-resistant and chemotherapy-sensitive) containing a total of 95 patients. Then, a bioinformatic approach was adopted and online large sample databases (TCGA, CCLE, and GTEx; Metascape, Cytoscape) were used to explore the potential mechanisms of action of these compounds. RESULTS: The results of this study demonstrate that high HE4 and Lewis y expression could be used as markers for chemotherapy resistance and poor prognosis in patients with ovarian cancer. These two expression events were widely correlated in various cancer tissues and are thought to act by activating the p38 mitogen-activated protein kinases (MAPK) pathway and inducing Vascular Endothelial Growth Factor A (VEGFA), Prostaglandin-Endoperoxide Synthase 2 (PTGS2), Early Growth Response 1 (EGR1), and Hypoxia-Inducible Factor 1-Alpha (HIFI1A), thereby promoting malignant biological behavior and resistance in ovarian cancer. CONCLUSIONS: These findings not only reveal the possible mechanism by which HE4 and Lewis y antigen affect ovarian cancer but also identify a four-gene signature that could be very useful in ovarian cancer detection and/or the development of new targeted therapies.

18.
Front Microbiol ; 12: 751863, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745056

RESUMO

Streptococcus dysgalactiae subsp. dysgalactiae (SDSD) is one of the most prevalent pathogens causing bovine mastitis worldwide. However, there is a lack of comprehensive information regarding genetic diversity, complete profiles of virulence factors (VFs), and antimicrobial resistance (AMR) genes for SDSD associated with bovine mastitis in China. In this study, a total of 674 milk samples, including samples from 509 clinical and 165 subclinical mastitis cases, were collected from 17 herds in 7 provinces in China from November 2016 to June 2019. All SDSD isolates were included in phylogenetic analysis based on 16S rRNA and multi-locus sequence typing (MLST). In addition, whole genome sequencing was performed on 12 representative SDSD isolates to screen for VFs and AMR genes and to define pan-, core and accessory genomes. The prevalence of SDSD from mastitis milk samples was 7.57% (51/674). According to phylogenetic analysis based on 16S rRNA, 51 SDSD isolates were divided into 4 clusters, whereas based on MLST, 51 SDSD isolates were identified as 11 sequence types, including 6 registered STs and 5 novel STs (ST521, ST523, ST526, ST527, ST529) that belonged to 2 distinct clonal complexes (CCs) and 4 singletons. Based on WGS information, 108 VFs genes in 12 isolates were determined in 11 categories. In addition, 23 AMR genes were identified in 11 categories. Pan-, core and accessory genomes were composed of 2,663, 1,633 and 699 genes, respectively. These results provided a comprehensive profiles of SDSD virulence and resistance genes as well as phylogenetic relationships among mastitis associated SDSD in North China.

19.
Chaos ; 31(9): 093137, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34598453

RESUMO

We discuss the formation of secondary synchronized clusters, that is, small clusters of synchronized oscillators besides the main cluster, in second-order oscillator networks and the role of inertia in this process. Such secondary synchronized clusters give rise to non-stationary states such as oscillatory and standing wave states. After describing the formation of such clusters through numerical simulations, we use a time-periodic mean field ansatz to obtain a qualitative understanding of the formation of non-stationary states. Finally, the effect of inertia in the formation of secondary synchronized clusters is analyzed through a minimal model. The analysis shows that the effect of the main synchronized cluster on the other oscillators is weakened by inertias, thus leading to secondary synchronized clusters during the transition to synchronization.

20.
Front Oncol ; 11: 740732, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34604085

RESUMO

Objective: To build and assess a pre-treatment dual-energy CT-based clinical-radiomics nomogram for the individualized prediction of clinical response to systemic chemotherapy in advanced gastric cancer (AGC). Methods: A total of 69 pathologically confirmed AGC patients who underwent dual-energy CT before systemic chemotherapy were enrolled from two centers in this retrospective study. Treatment response was determined with follow-up CT according to the RECIST standard. Quantitative radiomics metrics of the primary lesion were extracted from three sets of monochromatic images (40, 70, and 100 keV) at venous phase. Univariate analysis and least absolute shrinkage and selection operator (LASSO) were used to select the most relevant radiomics features. Multivariable logistic regression was performed to establish a clinical model, three monochromatic radiomics models, and a combined multi-energy model. ROC analysis and DeLong test were used to evaluate and compare the predictive performance among models. A clinical-radiomics nomogram was developed; moreover, its discrimination, calibration, and clinical usefulness were assessed. Result: Among the included patients, 24 responded to the systemic chemotherapy. Clinical stage and the iodine concentration (IC) of the tumor were significant clinical predictors of chemotherapy response (all p < 0.05). The multi-energy radiomics model showed a higher predictive capability (AUC = 0.914) than two monochromatic radiomics models and the clinical model (AUC: 40 keV = 0.747, 70 keV = 0.793, clinical = 0.775); however, the predictive accuracy of the 100-keV model (AUC: 0.881) was not statistically different (p = 0.221). The clinical-radiomics nomogram integrating the multi-energy radiomics signature with IC value and clinical stage showed good calibration and discrimination with an AUC of 0.934. Decision curve analysis proved the clinical usefulness of the nomogram and multi-energy radiomics model. Conclusion: The pre-treatment DECT-based clinical-radiomics nomogram showed good performance in predicting clinical response to systemic chemotherapy in AGC, which may contribute to clinical decision-making and improving patient survival.

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