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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.
Many waterflooding oil fields, injecting water into an oil-bearing reservoir for pressure maintenance, are in their middle to late stages of development. To explore the geological conditions and improve oilfield recovery of the most important well group of the Hu 136 block, located on the border areas of three provinces (Henan, Shandong, and Hebei), Zhongyuan Oilfield, Sinopec, central China, a 14C cross-well tracer monitoring technology was developed and applied in monitoring the development status and recognize the heterogeneity of oil reservoirs. The tracer response in the production well was tracked, and the water drive speed, swept volume of the injection fluid were obtained. Finally, the reservoir heterogeneity characteristics, such as the dilution coefficient, porosity, permeability, and average pore-throat radius, were fitted according to the mathematical model of the heterogeneous multi-layer inter-well theory. The 14C-AMS technique developed in this work is expected to be a potential analytical method for evaluating underground reservoir characteristics and providing crucial scientific guidance for the mid to late oil field recovery process.
Brachiopods suffered high levels of extinction during the Permian–Triassic crisis, and their diversity failed to return to Permian levels. In the aftermath of the Permian-Triassic mass extinction, brachiopods were extremely rare worldwide, especially in the southern hemisphere. Here, we report a new Early Triassic brachiopod fauna from the Selong section in southern Tibet, China. A new genus and three new species have been identified: Selongthyris plana Wang and Chen n. gen. n. sp., Piarorhynchella selongensis Wang and Chen n. sp., and Schwagerispira cheni Wang and Chen n. sp., which are typical. The ontogenies and internal structures of these three new species are described in detail. This brachiopod fauna corresponds to the Neospathodus pakistanensis and Neospathodus waageni conodont biozones and Kashmirites and Anasibirites ammonoid biozones, indicating a late Dienerian to late Smithian age. The post-extinction recovery of brachiopods in the Himalayas may have begun by the early Smithian of the Early Triassic. In addition, these species did not persist into the Spathian substage, suggesting that the newly evolved brachiopods in the southern Tethys were severely affected by the late Smithian extinction event.
With the increase of crewed space missions and the rise of space microbiology, the research of microbes grown under microgravity environment has been attracting more attention. The research scope in space microbiology has been extended beyond pathogens directly related to spaceflight. Y. pestis, the causative agent of plague, is also of interest to researchers. After being cultivated for 40 consecutive passages in either simulated microgravity (SMG) or normal gravity (NG) conditions, the Y. pestis strain 201 cultures were analysed regarding their phenotypic features. By using crystal violet staining assays, increased biofilm amount was detected in Y. pestis grown under SMG condition. Besides that, the damage degrees of Hela cell caused by SMG-grown Y. pestis were found diminished in comparison to those under NG condition. Consistent with this observation, the death course was delayed in mice infected with SMG-grown Y. pestis, suggesting that microgravity condition can contribute the attenuated virulence. RNA-seq-based transcriptomics analysis showed that a total of 218 genes were differentially regulated, of which 91 upregulated and 127 downregulated. We found that dozens of virulence-associated genes were downregulated, which partially explained the reduced virulence of Y. pestis under SMG condition. Our study demonstrated that long-term exposure to SMG influences the pathogenesis and biofilm formation ability of Y. pestis, which provides a novel avenue to study the mechanism of physiology and virulence of this pathogen. Microgravity enhanced the ability of biofilm formation and reduced the virulence and cytotoxicity of Y. pestis. Many virulence-associated genes of Y. pestis were differentially regulated in response to the stimulated microgravity. However, there is no molecular evidence to explain the enhanced biofilm formation ability, which requires further research. Taken together, the phenotype changes of Y. pestis under SMG conditions can provide us a new research direction of its potential pathogenesis.
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.
Aims
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.
Method
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.
Results
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.
Conclusions
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.
Contrasting the well-described effects of early intervention (EI) services for youth-onset psychosis, the potential benefits of the intervention for adult-onset psychosis are uncertain. This paper aims to examine the effectiveness of EI on functioning and symptomatic improvement in adult-onset psychosis, and the optimal duration of the intervention.
Methods
360 psychosis patients aged 26–55 years were randomized to receive either standard care (SC, n = 120), or case management for two (2-year EI, n = 120) or 4 years (4-year EI, n = 120) in a 4-year rater-masked, parallel-group, superiority, randomized controlled trial of treatment effectiveness (Clinicaltrials.gov: NCT00919620). Primary (i.e. social and occupational functioning) and secondary outcomes (i.e. positive and negative symptoms, and quality of life) were assessed at baseline, 6-month, and yearly for 4 years.
Results
Compared with SC, patients with 4-year EI had better Role Functioning Scale (RFS) immediate [interaction estimate = 0.008, 95% confidence interval (CI) = 0.001–0.014, p = 0.02] and extended social network (interaction estimate = 0.011, 95% CI = 0.004–0.018, p = 0.003) scores. Specifically, these improvements were observed in the first 2 years. Compared with the 2-year EI group, the 4-year EI group had better RFS total (p = 0.01), immediate (p = 0.01), and extended social network (p = 0.05) scores at the fourth year. Meanwhile, the 4-year (p = 0.02) and 2-year EI (p = 0.004) group had less severe symptoms than the SC group at the first year.
Conclusions
Specialized EI treatment for psychosis patients aged 26–55 should be provided for at least the initial 2 years of illness. Further treatment up to 4 years confers little benefits in this age range over the course of the study.
Bullfrog is one of the most important economic aquatic animals in China that is widely cultured in southern China and is a key breed recommended as an industry of poverty alleviation in China. During recent years, a fatal bacterial disease has often been found in cultured bullfrogs. The clinical manifestations of the diseased bullfrogs were severe intestinal inflammation and an anal prolapse. A bacterial pathogen was isolated from the diseased bullfrog intestines. The bacterium was identified as Vibrio cholerae using morphological, biochemical and 16S rRNA phylogenetic analysis. In this study, V. cholerae was isolated and identified in diseased bullfrogs for the first time, providing a basis for the diagnosis and control of the disease. Therefore, attention should be paid to the modes of transmission of V. cholerae from bullfrog and formulate reasonable safety measures.
We investigated the propagation of turbulent fronts in pipe flow at high Reynolds numbers by direct numerical simulation. We used a technique combining a moving frame of reference and an artificial damping to isolate the fronts in short periodic pipes, which enabled us to explore the bulk Reynolds number up to $Re=10^5$ with affordable computation power. We measured the propagation speed of the downstream front and observed that a fit of $1.971-(Re/1925)^{-0.825}$ (in unit of bulk speed) captures this speed above $Re\simeq 5000$ very well. The speed increases monotonically as $Re$ increases, in stark contrast to the decreasing trend above $Re\simeq 10\,000$ reported by Wygnanski & Champagne (J. Fluid Mech., vol. 59, 1973, pp. 281–335). The speed of the upstream front overall agrees with the former studies and $0.024+(Re/1936)^{-0.528}$ fits our data well, and those from the literature. Based on our analysis of the front dynamics, we proposed that both front speeds would keep their respective monotonic trends as the Reynolds number increases further. We show that, at high Reynolds numbers, the local transition at the upstream front tip is via high-azimuthal-wavenumber structures in the high-shear region near the pipe wall, whereas at the downstream front tip is via low-azimuthal-wavenumber structures in the low-shear region near the pipe centre. This difference is possibly responsible for the asymmetric speed scalings between the upstream and downstream fronts.
Previous studies have demonstrated structural and functional changes of the hippocampus in patients with major depressive disorder (MDD). However, no studies have analyzed the dynamic functional connectivity (dFC) of hippocampal subregions in melancholic MDD. We aimed to reveal the patterns for dFC variability in hippocampus subregions – including the bilateral rostral and caudal areas and its associations with cognitive impairment in melancholic MDD.
Methods
Forty-two treatment-naive MDD patients with melancholic features and 55 demographically matched healthy controls were included. The sliding-window analysis was used to evaluate whole-brain dFC for each hippocampal subregions seed. We assessed between-group differences in the dFC variability values of each hippocampal subregion in the whole brain and cognitive performance on the MATRICS Consensus Cognitive Battery (MCCB). Finally, association analysis was conducted to investigate their relationships.
Results
Patients with melancholic MDD showed decreased dFC variability between the left rostral hippocampus and left anterior lobe of cerebellum compared with healthy controls (voxel p < 0.005, cluster p < 0.0125, GRF corrected), and poorer cognitive scores in working memory, verbal learning, visual learning, and social cognition (all p < 0.05). Association analysis showed that working memory was positively correlated with the dFC variability values of the left rostral hippocampus-left anterior lobe of the cerebellum (r = 0.338, p = 0.029) in melancholic MDD.
Conclusions
These findings confirmed the distinct dynamic functional pathway of hippocampal subregions in patients with melancholic MDD, and suggested that the dysfunction of hippocampus-cerebellum connectivity may be underlying the neural substrate of working memory impairment in melancholic MDD.
Insulin-like growth factor 1 receptor (IGF1R) is a cell surface receptor, belonging to the tyrosine kinase receptor superfamily. IGF1R plays a role not only in normal cell development but also in malignant transformation, which has become a candidate therapeutic target for the treatment of human cancer. This study aimed to explore insertions and deletions (indels) in IGF1R gene and investigate their association with growth traits in four Chinese cattle breeds (Xianan cattle, Jinnan cattle, Qinchuan cattle and Nanyang cattle). The current paper identified a 28-bp indel by polymerase chain reaction within IGF1R gene. The analysis showed that there was a significant correlation between the locus and the hucklebone width of Nanyang cattle in four periods, in which it was highly correlated at 6, 12 and 18 months. At the age of 6 months, it was also significantly correlated with body height, body weight and body length. Association analysis showed that the locus in Jinnan cattle was extremely significantly correlated with body slanting length and body weight, and significantly correlated with chest circumference. There was no significant correlation between this locus and growth traits of Xianan cattle and Qinchuan cattle. The detected indel in the IGF1R gene was significantly associated with growth traits in Jinnan and Nanyang cattle, and could be used as a molecular marker for growth trait selection.
The Middle Miocene Climatic Optimum is known for abrupt events during the global cooling trend of the past 20 Ma. Its identification in the Tibetan Plateau can help explain the cause of the critical Middle Miocene climate transition in Central Asia. In this study, fine-grained mixed sediments widely distributed in the Miocene Qaidam Lake in the northern Tibetan Plateau were used as a sensitive indicator for palaeoclimate. Their geochemical characteristics were investigated, together with an analysis of 2600 m long successive gamma-ray logging data from the whole JS2 drillcore, to understand the mid-Miocene climate transition in the Tibetan Plateau. By comparing the gamma-ray curve of the mixed sediments with global temperature, the Middle Miocene Climatic Optimum event can be easily identified. Further, the detailed petrological features and geochemical data of lacustrine fine-grained mixed sediments from a 400 m drillcore show oxidizing, high-sedimentation rate and brackish-saline water conditions in a semi-arid climate during the Middle Miocene period, demonstrating a dryer climate in the Qaidam Basin than in the monsoon-sensitive regions in Central Asia. These fine-grained mixed sediments have recorded climate drying before 15.3 Ma that represents a climatic transition within the Middle Miocene Climatic Optimum; increasing carbonate-rich mixed sediments, decreasing algal limestone layers and decreasing lacustrine organic matter are indicators of this transition. Regional tectonic events include the retreat of the Paratethys from Central Asia at ∼15 Ma and the synchronous tectonic reorganization of the Altyn-Tagh fault system and the northeastern Tibetan Plateau. We find that global climate change is the primary factor affecting the overall characteristics and changes of the Neogene climate in the Qaidam Basin, including the occurrence of the Middle Miocene Climatic Optimum and the cooling and drying tendency, while the regional events are a secondary factor.
The satellite attitude control system (SACS) is a complicated system. In order to reflect the relationship among different components in SACS and analyse the impact of component faults on system performance, a complete simulation platform of the SACS based on Simulink is built in this paper. With the embedding of the specific reaction flywheel, gyroscope and earth sensor model, and the design of the controller based on the quaternion feedback, the simulation platform can not only simulate the real SACS at the component level, but it can also realise the injection of component faults for analysing the system performance. Simulations are conducted to verify the performance of the simulation platform. Simulation results show that this simulation platform has the ability to accurately reflect the control performance of the SACS, and the output accuracy of the component model is high. The research results reveal that this simulation platform can provide model support for verifying the algorithm of fault diagnosis, prediction and tolerant control of the SACS. This simulation platform is easy to use and can be expanded and improved.
To explore the characteristics of the mitochondrial genome (mitogenome) of the squeaking silkmoths Rhodinia, a genus of wild silkmoths in the family Saturniidae of Lepidoptera, and reveal phylogenetic relationships, the mitogenome of Rhodinia fugax Butler was determined. This wild silkmoth spins a green cocoon that has potential significance in sericulture, and exhibits a unique feature that its larvae can squeak loudly when touched. The mitogenome of R. fugax is a circular molecule of 15,334 bp long and comprises 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and an A + T-rich region, consistent with previous observations of Saturniidae species. The 370-bp A + T-rich region of R. fugax contains no tandem repeat elements and harbors several features common to the Bombycidea insects, but microsatellite AT repeat sequence preceded by the ATTTA motif is not present. Mitogenome-based phylogenetic analysis shows that R. fugax belongs to Attacini, instead of Saturniini. This study presents the first mitogenome for Rhodinia genus.
In recent years, the controlling nutritional status (CONUT) score has increasingly became an effective indicator associated with tumor prognosis. This study was conducted to synthesise data on the prognostic value of CONUT score on patients with upper tract urothelial carcinoma (UTUC) or renal cell carcinoma (RCC) undergoing nephrectomy. We designed and performed a systematic analysis of studies that verified the correlation between preoperative CONUT score and prognosis for UTUC and RCC using PubMed, Web of Science and Embase. The conclusion was clarified by pooled hazard ratios (HR) and 95% confidence intervals (95% CI). Subgroup analysis were further conducted in accordance with different primary tumor. Six studies involving 3529 patients were included in this evidence synthesis, which revealed that the CONUT score had a potential role to predict the survival of UTUC and RCC patients accepting surgery. Pooled analysis showed that the overall survival (OS, HR 2·32, p < 0·0001), cancer-specific survival (CSS, HR 2·68, p < 0·0001) and disease-free survival (DFS, HR 1·62, p < 0·00001) were inferior in the high CONUT score group when compared with low score group. Subgroup analysis revealed that this result was in line with UTUC (OS: HR 1·86, p = 0·02; CSS: HR 2·24, p = 0·01; DFS: HR 1·54, p < 0·00001) and RCC (OS: HR 3·05, p < 0·00001; CSS: HR 3·47, p < 0·00001; DFS: HR 2·21, p = 0·0005) patients respectively. Consequently, the CONUT score is a valuable preoperative index to predict the survival of patients with UTUC or RCC undergoing nephrectomy.
The present study evaluated whether fat mass assessment using the triceps skinfold (TSF) thickness provides additional prognostic value to the Global Leadership Initiative on Malnutrition (GLIM) framework in patients with lung cancer (LC). We performed an observational cohort study including 2672 LC patients in China. Comprehensive demographic, disease and nutritional characteristics were collected. Malnutrition was retrospectively defined using the GLIM criteria, and optimal stratification was used to determine the best thresholds for the TSF. The associations of malnutrition and TSF categories with survival were estimated independently and jointly by calculating multivariable-adjusted hazard ratios (HR). Malnutrition was identified in 808 (30·2 %) patients, and the best TSF thresholds were 9·5 mm in men and 12 mm in women. Accordingly, 496 (18·6 %) patients were identified as having a low TSF. Patients with concurrent malnutrition and a low TSF had a 54 % (HR = 1·54, 95 % CI = 1·25, 1·88) greater death hazard compared with well-nourished individuals, which was also greater compared with malnourished patients with a normal TSF (HR = 1·23, 95 % CI = 1·06, 1·43) or malnourished patients without TSF assessment (HR = 1·31, 95 % CI = 1·14, 1·50). These associations were concentrated among those patients with adequate muscle mass (as indicated by the calf circumference). Additional fat mass assessment using the TSF enhances the prognostic value of the GLIM criteria. Using the population-derived thresholds for the TSF may provide significant prognostic value when used in combination with the GLIM criteria to guide strategies to optimise the long-term outcomes in patients with LC.
The objective was to investigate associations between life-course adiposity and sex hormone concentrations: trajectory of adiposity from age 5 to 40 (premenopausal)/60 (postmenopausal women and men) in relation to levels of oestrone (E1), oestradiol (E2), sex hormone-binding globulins (SHBG), testosterone in 4801 premenopausal and 6019 postmenopausal women in the Nurses’ Health Study (NHS) and NHS II, and 2431 men in the Health Professionals Follow-up Study. We used group-based trajectory models to identify groups within each cohort based on recalled somatotypes and reported BMI. Multivariate linear regression models were used to compare sex hormone concentration across different trajectory groups. The mean age at blood draw was 64·1 ± 8·1 years for men, 59·4 ± 6·0 for postmenopausal and 44·1 ± 4·6 for premenopausal women. In men, compared with the medium-stable group, lean-marked increase and medium increase groups had lower levels of SHBG (percentage difference: −17 and −9 %) and testosterone (−15 and −13 %). In postmenopausal women, compared with the medium-stable group, lean-marked increase and medium increase groups had higher levels of E1 (21 and 34 %) and E2 (45 and 68 %) but lower level of SHBG (–29 and −35 %). In premenopausal women, compared with the lean-moderate increase group, medium-stable/increase and heavy-stable/increase groups had lower levels of SHBG (–6 and −28 %). Attained adulthood adiposity and middle-life weight gain were associated with lower SHBG and testosterone in men, higher E1 and E2 and lower SHBG in postmenopausal women, and lower SHBG in premenopausal women. The study indicates the importance of maintaining a healthy body weight throughout life course for homoeostasis of sex hormones.
This study aimed to investigate the environmental contamination of nucleic acid at 2019 novel coronavirus (2019-nCOV) vaccination site and to evaluate the effect of improvement to the vaccination process. Nucleic acid samples were collected from the surface of the objects in 2019-nCOV vaccination point A (used between 15 November 2020 and 25 December 2020) and point B (used after 27 December 2020) in a comprehensive tertiary hospital. Samples were collected from point A before improvement to the vaccination process, and from point B (B1 and B2) after improvement to the vaccination process. The real-time fluorescence polymerase chain reaction method was used for detection. The positive rate of vaccination room was 47.06% (24/51) at point A. No positive result was found in point B1 both at working hours (0/27) and after terminal disinfection (0/27). In point B2, the positive results were found in vaccine's outer packaging and staff gloves at working hours, with a positive rate of 7.41% (2/27). The positive rate was 0 (0/27) after terminal disinfection in point B2. The nucleic acid contamination in the vaccination room of 2019-nCOV vaccine nucleic acid sampling point is serious, which can be avoided through the improvement and intervention (such as personal protection, vaccination operation and disinfection methods).