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N-acetylcysteine (NAC) possesses a strong capability to ameliorate high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in mice, but the underlying mechanism is still unknown. Our study aimed to clarify the involvement of long non-coding RNA (lncRNA) in the beneficial effects of NAC on HFD-induced NAFLD. C57BL/6J mice were fed a normal-fat diet (10 % fat), a HFD (45 % fat) or a HFD plus NAC (2 g/l). After 14-week of intervention, NAC rescued the deleterious alterations induced by HFD, including the changes in body and liver weights, hepatic TAG, plasma alanine aminotransferase, plasma aspartate transaminase and liver histomorphology (haematoxylin and eosin and Oil red O staining). Through whole-transcriptome sequencing, 52 167 (50 758 known and 1409 novel) hepatic lncRNA were detected. Our cross-comparison data revealed the expression of 175 lncRNA was changed by HFD but reversed by NAC. Five of those lncRNA, lncRNA-NONMMUT148902·1 (NO_902·1), lncRNA-XR_001781798·1 (XR_798·1), lncRNA-NONMMUT141720·1 (NO_720·1), lncRNA-XR_869907·1 (XR_907·1), and lncRNA-ENSMUST00000132181 (EN_181), were selected based on an absolute log2 fold change value of greater than 4, P-value < 0·01 and P-adjusted value < 0·01. Further qRT-PCR analysis showed the levels of lncRNA-NO_902·1, lncRNA-XR_798·1, and lncRNA-EN_181 were decreased by HFD but restored by NAC, consistent with the RNA sequencing. Finally, we constructed a ceRNA network containing lncRNA-EN_181, 3 miRNA, and 13 mRNA, which was associated with the NAC-ameliorated NAFLD. Overall, lncRNA-EN_181 might be a potential target in NAC-ameliorated NAFLD. This finding enhanced our understanding of the biological mechanisms underlying the beneficial role of NAC.
Fibronectin type III domain-containing protein 5 (FNDC5) is a transmembrane protein and the precursor of irisin, which serves as a systemic exerkine/myokine with multiple origins. Since its discovery in 2012, this hormone-like polypeptide has rapidly evolved to a component significantly involved in a gamut of metabolic dysregulations and various liver diseases. After a decade of extensive investigation on FNDC5/irisin, we are still surrounded by lots of open questions regarding its diagnostic and therapeutic values. In this review, we first concentrated on the structure–function relationship of FNDC5/irisin. Next, we comprehensively summarised the current knowledge and research findings regarding pathogenic roles/therapeutic applications of FNDC5/irisin in the context of non-alcoholic fatty liver disease, fibrosis, liver injury due to multiple detrimental insults, hepatic malignancy and intrahepatic cholestasis of pregnancy. Moreover, the prominent molecules involved in the underlying mechanisms and signalling pathways were highlighted. As a result, emerging evidence reveals FNDC5/irisin may act as a proxy for diagnosing liver disease pathology, a sensitive biomarker for assessing damage severity, a predisposing factor for surveilling illness progression and a treatment option with protective/preventive impact, all of which are highly dependent on disease grading and contextually pathological features.
Due to the lack of research between the inner layers in the structure of colonic mucous and the metabolism of fatty acid in the constipation model, we aim to determine the changes in the mucous phenotype of the colonic glycocalyx and the microbial community structure following treatment with Rhubarb extract in our research. The constipation and treatment models are generated using adult male C57BL/6N mice. We perform light microscopy and transmission electron microscopy (TEM) to detect a Muc2-rich inner mucus layer attached to mice colon under different conditions. In addition, 16S rDNA sequencing is performed to examine the intestinal flora. According to TEM images, we demonstrate that Rhubarb can promote mucin secretion and find direct evidence of dendritic structure-linked mucus structures with its assembly into a lamellar network in a pore size distribution in the isolated colon section. Moreover, the diversity of intestinal flora has noticeable changes in constipated mice. The present study characterizes a dendritic structure and persistent cross-links have significant changes accompanied by the alteration of intestinal flora in feces in models of constipation and pretreatment with Rhubarb extract.
Dietary l-carnitine (LC) is a nutritional factor that reduces liver lipid content. However, whether dietary LC can improve lipid metabolism via simultaneous activation of mitochondrial fatty acid (FA) β-oxidation and suppression of endoplasmic reticulum (ER) stress is still unknown. Large yellow croaker were fed with a high-fat diet (HFD) supplemented with dietary LC at 0, 1·2 or 2·4 ‰ for 10 weeks. The results indicated that a HFD supplemented with LC reduced the liver total lipid and TAG content and improved serum lipid profiles. LC supplementation administered to this fish increased the liver antioxidant capacity by decreasing serum and liver malondialdehyde levels and enhancing the liver antioxidant capacity, which then relieved the liver damage. Dietary LC increased the ATP dynamic process and mitochondrial number, decreased mitochondrial DNA damage and enhanced the protein expression of mitochondrial β-oxidation, biogenesis and mitophagy. Furthermore, dietary LC supplementation increased the expression of genes and proteins related to peroxisomal β-oxidation and biogenesis. Interestingly, feeding fish with LC-enriched diets decreased the protein levels indicative of ER stress, such as glucose-regulated protein 78, p-eukaryotic translational initiation factor 2a and activating transcription factor 6. Dietary LC supplementation downregulated mRNA expression relative to FA synthesis, reduced liver lipid and relieved liver damage through regulating β-oxidation and biogenesis of mitochondria and peroxisomes, as well as the ER stress pathway in fish fed with HFD. The present study provides the first evidence that dietary LC can improve lipid metabolism via simultaneously promoting FA β-oxidation capability and suppressing the ER stress pathway in fish.
A fast numerical method for unsteady aerodynamic calculation of 3D wing is established, which is suitable for the preliminary design. Based on the lifting-line method, the aerodynamic data of the 2D aerofoil obtained by the unsteady CFD simulation is used as the model input to solve the aerodynamic force of the 3D wing. Compared with the traditional steady lifting-line method, the augmented method adopts the unsteady Kutta-Jouowski (K-J) theorem to calculate the circulation and improve the accuracy of the method through the circulation correction. The pitching motion of 3D wing at different aspect ratio and reduction frequencies are studied. The results show that the aerodynamic forces obtained by the augmented lifting-line method have good agreement with the 3D unsteady CFD calculations. Compared with 3D CFD calculation, the calculation efficiency of the improved method is increased by more than 12 times. The improved method has extensive applicability and can be used to estimate the unsteady aerodynamic forces of 3D single or multiple wing configurations.
Demodex infestation and density changes remain one of the main challenges in some clinical settings. Tumour necrosis factor-α (TNF-α) inhibitors have been recommended as a first-line treatment for ankylosing spondylitis (AS). However, there have been no studies investigating the impact of TNF-α inhibitor adalimumab on changes in the Demodex density in patients with AS. The aim of this study was to investigate Demodex density changes before and after adalimumab treatment and analyse the relationship between the Demodex density and clinical characteristics in AS. It was found that the Demodex density was positively correlated with age and C-reactive protein levels and the number of Demodex mites could increase after adalimumab treatment in AS.
Current studies on inhibitory effects of n-3 PUFA on pro-inflammatory cytokines have inconsistent results. Thus, a meta-analysis of randomised controlled trials was conducted to identify the effects of n-3 PUFA administration on circulating IL-6 and TNF in patients with cancer. Studies that examined the effects of n-3 PUFA administration on circulating IL-6 and TNF in patients with cancer were identified by searching PubMed and EMBASE from January 1975 to February 2021. Differences in n-3 PUFA administration and control conditions were determined by calculating standardised mean differences (SMD) with 95 % CI. Twenty studies involving 971 patients met the inclusion criteria. The overall SMD were 0·485 (95 % CI 0·087, 0·883) for IL-6 and 0·712 (95 % CI 0·461, 0·962) for TNF between n-3 PUFA administration and control conditions. Sources of heterogeneity were not found through subgroup and meta-regression analyses. Publication bias was observed in TNF with a slight contribution to the effect size. n-3 PUFA can reduce circulating IL-6 and TNF levels in patients with cancer. Results supported the recommendation of n-3 PUFA as adjuvant therapy for patients with cancer, possibly excluding head and neck cancer, owing to their anti-inflammatory properties.
This article contributes to the growing body of research on social assistance (SA) dynamics by analyzing patterns of SA receipt in China, a middle-income country with a large informal employment sector. Using national low-income household survey data and event history analysis, this study explored the mechanisms underlying exit from Dibao (formally known as Minimum Living Security) and changes in exit probability over time. We found that in the context of an informal economy, the ‘explicit’ change of individual characteristics and employment structure decisively affects receipt duration on the micro and macroeconomic levels, respectively. On the policy level, affected by the informal employment structure, employment services tend to be of low quality and fail to promote Dibao exit effectively. Although the specific Dibao payment strategy, which is used to address the difficulty in means tests, largely curbs the risks of declining working motivation, it considerably increases the possibility of prolonged Dibao use. With this systemic influence of informal employment, a unique pattern of SA receipt characterized by the combination of long-term use and a nondecreasing hazard rate has developed in China.
Residents of long-term care facilities face significantly greater risk of contracting or dying from coronavirus disease 2019 (COVID-19). However, little is known about COVID-19 in assisted living communities (ALCs) and the potential determinants of its spread. We examined the association between COVID-19 cases in ALCs and the proportion of Medicare-Medicaid (dual) eligible minority residents, neighborhood area deprivation, and state COVID-19 policy stringency.
We conducted longitudinal analyses employing data on confirmed COVID-19 cases in ALCs in 5 states. We sought to determine the weekly cumulative number of COVID-19 cases in ALCs. Covariates were ALC characteristics, area deprivation index, and state COVID-19 policy stringency. Multivariate 2-part models were used to determine the associations between independent variables and the likelihood of an outbreak and the overall count of cases.
In our study sample, 201 ALCs (7.04%) reported 1 or more COVID-19 cases as of August 17, 2020. A higher percentage of minority residents was associated with an increased likelihood of an ALC reporting at least 1 COVID-19 case (odds ratio [OR], 1.06; P = .032). Conditional on having at least 1 case, ALCs in states with stricter social distancing policies had lower case counts (incidence rate ratio [IRR], 0.98; P < .001). Greater neighborhood deprivation was associated with higher case count (IRR, 1.36; P = .049).
ALCs with higher proportions of dual-eligible minority residents were more likely to have COVID-19 outbreaks within their communities. ALCs located in more socioeconomically deprived neighborhoods, and in states with less stringent state social distancing policies, tended to have more COVID-19 cases.
Aldehyde oxidases (AOXs) are a group of metabolic enzymes that play critical roles in the degradation of xenobiotics and chemicals. However, the physiological function of this enzyme in insects remains poorly understood. In this study, three TcAOX genes (TcAOX1, TcAOX2, TcAOX3) were identified and characterized from Tribolium castaneum genome. Spatiotemporal expression profiling showed that TcAOX1 expression was most highly expressed at the early pupal stage and was predominantly expressed in the antennae of adults, indicating that TcAOX1 was involved in the degradation of chemical signals; TcAOX2 expression was most highly expressed at the late pupal stage and was mainly expressed in the fat body, epidermis of larvae and adults, respectively; and TcAOX3 expression was in all stages and was primarily expressed in the head of adults. Moreover, the transcripts of TcAOX2 and TcAOX3 were significantly induced after exposure to plant oil, and RNA interference (RNAi) targeting of each of them enhanced the susceptibility of beetles to this plant toxicant, suggesting that these two genes are associated with plant toxicant detoxification. Intriguingly, knockdown of the TcAOX1 led to reductions in female egg-laying but unchanged the hatchability and the development of genital organs, suggesting that this gene may mediate fecundity by effecting the inactivation of chemical signals in T. castaneum. Overall, these results shed new light on the function of AOX genes in insects, and could facilitate the development of research on pest control management.
Previous analyses of grey and white matter volumes have reported that schizophrenia is associated with structural changes. Deep learning is a data-driven approach that can capture highly compact hierarchical non-linear relationships among high-dimensional features, and therefore can facilitate the development of clinical tools for making a more accurate and earlier diagnosis of schizophrenia.
To identify consistent grey matter abnormalities in patients with schizophrenia, 662 people with schizophrenia and 613 healthy controls were recruited from eight centres across China, and the data from these independent sites were used to validate deep-learning classifiers.
We used a prospective image-based meta-analysis of whole-brain voxel-based morphometry. We also automatically differentiated patients with schizophrenia from healthy controls using combined grey matter, white matter and cerebrospinal fluid volumetric features, incorporated a deep neural network approach on an individual basis, and tested the generalisability of the classification models using independent validation sites.
We found that statistically reliable schizophrenia-related grey matter abnormalities primarily occurred in regions that included the superior temporal gyrus extending to the temporal pole, insular cortex, orbital and middle frontal cortices, middle cingulum and thalamus. Evaluated using leave-one-site-out cross-validation, the performance of the classification of schizophrenia achieved by our findings from eight independent research sites were: accuracy, 77.19–85.74%; sensitivity, 75.31–89.29% and area under the receiver operating characteristic curve, 0.797–0.909.
These results suggest that, by using deep-learning techniques, multidimensional neuroanatomical changes in schizophrenia are capable of robustly discriminating patients with schizophrenia from healthy controls, findings which could facilitate clinical diagnosis and treatment in schizophrenia.
To study the effectiveness of unilateral cochlear implantation, binaural-bimodal hearing devices, and bilateral cochlear implantation in children with inner-ear malformation.
This study comprised 261 patients who were allocated to inner-ear malformation or control groups. Twenty-four months after surgery, aided sound-field thresholds were tested, and the Meaningful Auditory Integration Scale, Infant-Toddler Meaningful Auditory Integration Scale, Meaningful Use of Speech Scale, Categories of Auditory Performance scale and Speech Intelligibility Rating test were completed.
Aided sound-field thresholds were significantly better for bilateral cochlear implantation patients than for unilateral cochlear implantation or binaural-bimodal hearing device patients. There was no significant difference in Meaningful Auditory Integration Scale, Infant-Toddler Meaningful Auditory Integration Scale, or Categories of Auditory Performance scores among the three groups. The binaural-bimodal hearing device patients outperformed unilateral cochlear implantation patients on both Meaningful Use of Speech Scale and Speech Intelligibility Rating scores. No statistical difference was observed between the two subgroups.
Children who received bilateral cochlear implants have the best auditory awareness in a quiet environment. Children with binaural-bimodal hearing devices have better voice control and verbal skills than unilateral cochlear implantation patients, and people are more likely to understand them. Children with inner-ear malformations benefit from cochlear implantation.
We investigated the drug resistance of Mycobacterium tuberculosis isolates from patients with tuberculosis (TB) and HIV, and those diagnosed with only TB in Sichuan, China. TB isolates were obtained from January 2018 to December 2020 and subjected to drug susceptibility testing (DST) to 11 anti-TB drugs and to GeneXpert MTB/RIF testing. The overall proportion of drug-resistant TB (DR-TB) isolates was 32.1% (n = 10 946). HIV testing was not universally available for outpatient TB cases, only 29.5% (3227/10 946) cases had HIV testing results. The observed proportion of multidrug-resistant TB (MDR-TB) isolates was almost double than that of the national level, with approximately 1.5% and 0.1% of the isolates being extensively drug resistant and universally drug resistant, respectively. The proportions of resistant isolates were generally higher in 2018 and 2019 than in 2020. Furthermore, the sensitivities of GeneXpert during 2018–2020 demonstrated a downward trend (80.9, 95% confidence intervals (CI) 76.8–85.0; 80.2, 95% CI 76.4–84.1 and 75.4, 95% CI 70.7–80.2, respectively). Approximately 69.0% (7557/10 946) of the TB cases with DST results were subjected to GeneXpert detection. Overall, the DR-TB status and the use of GeneXpert in Sichuan have improved, but DR-TB challenges remain. HIV testing for all TB cases is recommended.
Due to less light scattering and a better signal-to-noise ratio in deep imaging, two-photon fluorescence microscopy (TPFM) has been widely used in biomedical photonics since its advent. However, optical aberrations degrade the performance of TPFM in terms of the signal intensity and the imaging depth and therefore restrict its application. Here, we introduce adaptive optics based on the genetic algorithm to detect the distorted wavefront of the excitation laser beam and then perform aberration correction to optimize the performance of TPFM. By using a spatial light modulator as the wavefront controller, the correction phase is obtained through a signal feedback loop and a process of natural selection. The experimental results show that the signal intensity and imaging depth of TPFM are improved after aberration correction. Finally, the method was applied to two-photon fluorescence lifetime imaging, which helps to improve the signal-to-noise ratio and the accuracy of lifetime analysis. Furthermore, the method can also be implemented in other experiments, such as three-photon microscopy, light-sheet microscopy, and super-resolution microscopy.
To compare the prevalence of overweight or obesity (ow/ob) with WHO BMI cut-off points, International Obesity Task Force (IOTF) cut-off points and Chinese BMI criteria and examine its potential factors among preschool children in Hunan Province.
A cross-sectional survey including anthropometric measurements and questionnaires about children’s information, caregivers’ socio-demographic characteristics and maternal characteristics. χ2 tests and univariate and multivariate binary logistic regression were performed to evaluate the possible factors of ow/ob.
Hunan, China, from September to October 2019.
In total, 7664 children 2 to 6 years of age.
According to Chinese BMI criteria, about 1 in 7–8 children aged 2–6 years had ow/ob in Hunan, China. The overall estimated prevalence of ow/ob among 2- to 6-year-old children was significantly higher when based on the Chinese BMI criteria compared with the WHO BMI cut-off points and IOTF cut-off points. According to Chinese BMI criteria, ow/ob was associated with residing in urban areas, older age, male sex, eating snacking food more frequently, macrosomia delivery, caesarean birth, heavier maternal prepregnancy weight and pre-delivery weight.
The prevalence of ow/ob in preschool children in Hunan Province remains high. More ow/ob children could be screened out according to Chinese BMI cut-offs compared with WHO and IOTF BMI criteria. In the future, targeted intervention studies with matched controls will be needed to assess the long-term effects of intervention measures to provide more information for childhood obesity prevention and treatment.
The efficiency of establishing pig pluripotent embryonic stem cell clones from blastocysts is still low. The transcription factor Nanog plays an important role in maintaining the pluripotency of mouse and human embryonic stem cells. Adequate activation of Nanog has been reported to increase the efficiency of establishing mouse embryonic stem cells from 3.5 day embryos. In mouse, Nanog starts to be strongly expressed as early as the morula stage, whereas in porcine NANOG starts to be strongly expressed by the late blastocyst stage. Therefore, here we investigated both the effect of expressing NANOG on porcine embryos early from the morula stage and the efficiency of porcine pluripotent embryonic stem cell clone formation. Compared with intact porcine embryos, NANOG overexpression induced a lower blastocyst rate, and did not show any advantages for embryo development and pluripotent embryonic stem cell line formation. These results indicated that, although NANOG is important pluripotent factor, NANOG overexpression is unnecessary for the initial formation of porcine pluripotent embryonic stem cell clones in vitro.
High-Mg andesites (HMAs) are crucial for the reconstruction of plate tectonics, continental margin formation and lithospheric evolution. In this study, we present new fossil age, whole-rock geochemical and Sr–Nd isotope data on the newly discovered Dundunshan Group HMAs in the Dundunshan area of the Beishan orogen (central-southern Central Asian Orogenic Belt). The Dundunshan HMA samples are characterized by high MgO (6.47–7.02 wt%) contents and high Mg# values (67.27–68.77), with SiO2 (58.57–62.13 wt%), Al2O3 (14.49–16.07 wt%) and CaO (5.05–6.24 wt%) resembling typical HMAs. The Dundunshan HMA samples are calc-alkaline and strongly enriched in light rare earth elements (LREEs) and large-ion lithophile elements (LILEs), with slightly negative Eu anomaly and high-field-strength element (HFSE) depletions. Their (87Sr/86Sr)i ratios (0.7041–0.7057) and ϵNd(t) (3.73–5.59) indicate that the Dundunshan HMAs were mainly formed by the interactions between subducted oceanic sediment-derived melts and mantle peridotites. Fossil evidence and published radiometric age data constrain the formation of the Dundunshan HMAs to early Late Devonian time. Sedimentological features of the Middle Devonian Sangejing Formation and regional tectonic correlation suggest that the Hongliuhe–Niujuanzi–Xichangjing Ocean in the Dundunshan area was likely closed during late Middle Devonian time, and that the Dundunshan HMAs were formed in a post-collision extensional setting.
Considering the polishing requirements for high-precision aspherical optical mirrors, a hybrid polishing robot composed of a serial–parallel manipulator and a dual rotor grinding system is proposed. Firstly, based on the kinematics of serial components, the equivalent load model for the parallel manipulator is established. Then, the elastodynamic model of kinematic branched-chains of the parallel manipulator is established by using the spatial beam element, and the rigid–flexible coupling dynamic model of the polishing robot is obtained with Kineto-elasto dynamics theory. Further, considering the dynamic properties of the joint clearance, the rigid–flexible coupling dynamic model with the joint clearance for the polishing robot is established. Finally, the equivalent load distribution of the parallel manipulator is analyzed, and the effect of the branched-chain elasticity and joint clearance on the motion error of the polishing robot is studied. This article provides a theoretical basis for improving the motion accuracy and dynamic performance of the hybrid polishing robot.