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Background & Aims: Currently, there is limited knowledge on the clinical profile of drug-induced liver injury (DILI) in Chinese children. We aimed to assess the clinical characteristics, suspected drugs, and outcomes associated with pediatric DILI in China. Methods: This nationwide, multicenter, retrospective study, conducted between 2012 and 2014, analyzed 25,927 cases of suspected DILI at 308 medical centers using the inpatient medical register system. Utilizing the Roussel Uclaf causality assessment method score, only patients with scores ≥6 or diagnosed with DILI by three experts after scoring

BackgroundTo investigate whether the novel mutation of PKHD1 could cause polycystic kidney disease by affecting splicing with a recessive inheritance pattern.MethodsA nonconsanguineous Chinese couple with two recurrent pregnancies showed fetal enlarged echogenic polycystic kidney and oligoamnios were recruited. Pedigree WES, minigene splicing assay experiment and following bioinformatics analysis were performed to verify the effects, and inheritance pattern of diseasing-causing mutations.ResultsWES revealed that both fetuses were identified as carrying the same novel mutation c.3592_3628 + 45del, p.? and c.11207 T>C, p.(Ile3736Thr) in the PKHD1 gene (NM_138694.4), which inherited from the father and mother respectively. Both bioinformatic method prediction and minigene splicing assay experience results supported the mutation c.3592_3628 + 45del, p.? affects the splicing of the PKHD1 transcript, resulting in exon 31 skipping. Another missense mutation c.11207 T>C, p.(Ile3736Thr) has a low frequency in populations and is predicted to be deleterious by bioinformatic methods.ConclusionThese findings provide a direct clinical and functional evidence that the truncating mutations of the PKHD1 gene could lead to more severe phenotypes, and cause ARPKD as a homozygous or compound heterozygous pattern. Our study broadens the variant spectrum of the PKHD1 gene and provides a basis for genetic counseling and diagnosis of ARPKD.

Recent research has reevaluated the traditional view of cancer's linear progression and recurrence by introducing cellular reprogramming a process in which cancer cells can their state under certain conditions. This change is driven by a combination of genetic and epigenetic factors, with pivotal roles played by key genes, and pathways, notably Wnt and Notch. The complexity of cancer's behavior is further influenced by factors such as the epithelial-mesenchymal transition (EMT) and therapy-induced stress, both of which are significant contributors to cancer recurrence. In this context bibliometric analysis emerges as a crucial tool for evaluating the impacts and trends within scientific literature. Our study utilized bibliometrics to analysis the role of cellular reprogramming oncology over the past two decades, highlighting its potential to improve cancer treatment outcomes. In conducting this analysis, we searched for literature search on cellular reprogramming (CR) in the Web of Science database, covering the years 2002–2022. We employed visualization tools like Citespace, VOSviewer, and Bibliometrix to analyze the collected data resulting in a dataset of 3102 articles. The United States and China emerged as leading contributors to this field, with the University of Texas MD Anderson Cancer Center being the most prolific institution. Menendez was the most influential scholar in this research domain. Cancers was the journal with the most publications on this subject. The most local-cited document was the article titled “Hallmarks of Cancer: The Next Generation”. A comprehensive analysis has been conducted based on keywords and cited references. In recent years, the research emphasis has shifted to “extracellular vesicles,” “cancer therapy,” and “cellular plasticity”. Therefore, this analysis uses bibliometrics to chart cutting-edge progress in cancer's cellular reprogramming, aiding experts to quickly understand and innovate in this crucial area.

The zinc/iron-regulated transporter-like proteins (ZIP) family acts as an important transporter for divalent metal cations such as Zn, Fe, Mn, Cu, and even Cd. However, their condition is unclear in Tartary buckwheat (Fagopyrum tataricum). Here, 13 ZIP proteins were identified and were predicted to be mostly plasma membrane-localized. The transient expressions of FtZIP2 and FtZIP6 in tobacco confirmed the prediction. Multiple sequence alignment analysis of FtZIP proteins revealed that most of them had 8 putative transmembrane (TM) domains and a variable region rich in histidine residues between TM3 and TM4, indicating the reliable affinity to metal ions. Gene expression analysis by qRT-PCR showed that FtZIP genes were markedly different in different organs, such as roots, stems, leaves, flowers, fruits and seeds. However, in seedlings, the relative expression of FtZIP10 was notably induced under the CdCl2 treatment, while excessive Zn2+, Fe2+, Mn2+ and Cd2+ increased the transcript of FtZIP5 or FtZIP13, in comparison to normal conditions. Complementation of yeast mutants with the FtZIP family genes demonstrate that FtZIP7/10/12 transport Zn, FtZIP5/6/7/9/10/11 transport Fe, FtZIP12 transports Mn and FtZIP2/3/4/7 transport Cd. Our data suggest that FtZIP proteins have conserved functions of transportation of metal ions but with distinct spatial expression levels.

Identifying spatial heterogeneity in ecosystem services and understanding the spatial and temporal correlations between ecosystem service exploration and human activity intensity are vital for achieving regional harmony between human activities and the environment, ultimately fostering sustainable development. Previous studies primarily concentrated on the impact of human activities on ecosystem services while overlooking the intricate spatiotemporal dynamics and nonlinear relationships. In this study, which leveraged multi-source data, we found increasing trends in Human Footprint Index (HFI), most pronounced in the central region of Shaanxi Province. From 2000 to 2020, Shaanxi Province consistently exhibited an ecosystem service distribution pattern characterized by a 'high in the central-south and low in the northwest' trend. Habitat Quality (HQ) consistently maintained high values, signifying favorable habitat conditions, while Food Production (FP) remained relatively stable. Carbon Sequestration (CS) and Soil Conservation (SC) displayed diverse temporal patterns, whereas Water Yield (WY) showed noticeable fluctuations.This analysis revealed a negative correlation between HFI indicators and Total Ecosystem Services (TES). Constraint lines delineated hump-shaped relationships between TES and human activity intensity across various geomorphic areas. Notably, the differences between regions were significant, and threshold dynamics were identified. HFI negatively correlated with TES, moderate HFI growth improved services, yet exceeding ecological thresholds caused decline. Overall,this study informs necessary ecosystem management in Shaanxi, highlighting the need for balanced policies and predictive models that ensure sustainable development without crossing critical ecological thresholds. Future work should concentrate on developing predictive models that incorporate environmental, technological, and socio-economic variables, to better anticipate and mitigate the ecological impacts of human activities.

In order to study the influence of fissures on the burst tendency of coal, the test and numerical simulation of the burst tendency of coal with different burst angles were carried out. The evolution law of the burst tendency index of coal under the influence of burst angle was analyzed, and the mechanism of energy storage and release of coal under the influence of fissure angle was revealed. The results show that compared with the specimens without prefabricated cracks, the uniaxial compressive strength of the specimens with 0° cracks is reduced by 48.4%, the dynamic failure time is increased by 279.4%, the burst energy index is reduced by 54%, and the burst energy velocity index is reduced by 87.9%. After that, with the increase of prefabricated crack angle, the uniaxial compressive strength of coal increases gradually, the dynamic failure time decreases gradually, the burst energy index increases gradually, and the burst energy velocity index increases gradually. That is to say, the larger the crack angle contained in the coal body, the stronger the burst tendency of the coal body, but it is still lower than that of the complete coal body. With the increase of prefabricated crack angle, the proportion of prepeak elastic energy of coal body increases, the less energy dissipation in the whole loading process of coal body, and the faster energy release rate during failure. The research results can provide some theoretical support for the prevention and control of rock burst disaster.

The interaction between urbanization and ecosystem services (ESs) is a hot topic in the modern human-earth system science. Currently, most studies only focus on the effects of urbanization on ESs supply, few studies have accurately quantified the ESs demand and explored the spatial–temporal coupling interactions between urbanization and ESs supply–demand balance. To address these gaps, this study used process-based modeling to estimate the absolute number of ESs demand. Ecosystem supply–demand ratio (ESDR) is employed to measure the ESs balance. Finally, pearson correlation analysis, coupling coordination degree model, and bivariate local Moran’s I method were used to explore the interactive relationship between urbanization and ESs balance in the Loess Plateau (LP). Results indicated that the LP experienced rapid urbanization with characteristics of faster economic urbanization than land and population urbanization from 2000 to 2018. Negative correlations between construction land proportion and ESDR enhanced over time. Although the coupling coordination degree between urbanization and ESDR increased, most counties were mild incoordination and basic coordination. The spatial interaction of urbanization and ESDR was divided into four types: co-promotion type, ecological lag type, urbanization lag type, and co-loss type. This study can contribute to providing a scientific reference and practical guidance for coordinating ecological protection and high-quality development in underdeveloped areas.

Reanalysis datasets provide a reliable reanalysis of climate input data for hydrological models in regions characterized by limited weather station coverage. In this paper, the accuracy of precipitation, the maximum and minimum temperatures of four reanalysis datasets, the China Meteorological Assimilation Driving Datasets for the SWAT model (CMADS), time-expanded climate forecast system reanalysis (CFSR+), the European Centre for Medium-Range Weather Forecast Reanalysis (ERA). and the China Meteorological Forcing Dataset (CMFD), were evaluated by using data from 28 ground-based observations (OBs) in the Source of the Yangtze and Yellow Rivers (SYYR) region and were used as input data for the SWAT model for runoff simulation and performance evaluation, respectively. And, finally, the CMADS was optimized using Integrated Calibrated Multi-Satellite Retrievals for Global Precipitation Measurement (AIMERG) data. The results show that CMFD is the most representative reanalysis data for precipitation characteristics in the SYYR region among the four reanalysis datasets evaluated in this paper, followed by ERA5 and CFSR, while CMADS performs satisfactorily for temperature simulations in this region, but underestimates precipitation. And we contend that the accuracy of runoff simulations is notably contingent upon the precision of daily precipitation within the reanalysis dataset. The runoff simulations in this region do not effectively capture the extreme runoff characteristics of the Yellow River and Yangtze River sources. The refinement of CMADS through the integration of AIMERG satellite precipitation data emerges as a potent strategy for enhancing the precision of runoff simulations. This research can provide a reference for selecting meteorological data products and optimization methods for hydrological process simulation in areas with few meteorological stations.

Karst lands provide a poor substrate to support plant growth, as they are low in nutrients and water content. Common buckwheat (Fagopyrum esculentum) is becoming a popular crop for its gluten-free grains and their high levels of phenolic compounds, but buckwheat yields are affected by high water requirements during grain filling. Here, we describe a wild population of drought-tolerant Fagopyrum leptopodum and its potential for enhancing drought tolerance in cultivated buckwheat. We determined that the expression of a gene encoding a Basic leucine zipper (bZIP) transcription factor, FlbZIP12, from F. leptopodum is induced by abiotic stresses, including treatment with the phytohormone abscisic acid, salt, and polyethylene glycol. In addition, we show that overexpressing FlbZIP12 in Tartary buckwheat (Fagopyrum tataricum) root hairs promoted drought tolerance by increasing the activities of the enzymes superoxide dismutase and catalase, decreasing malondialdehyde content, and upregulating the expression of stress-related genes. Notably, FlbZIP12 overexpression induced the expression of key genes involved in flavonoid biosynthesis. We also determined that FlbZIP12 interacts with protein kinases from the FlSnRK2 family in vitro and in vivo. Taken together, our results provide a theoretical basis for improving drought tolerance in buckwheat via modulating the expression of FlbZIP12 and flavonoid contents.

Identifying the spatial heterogeneity characteristics of ecosystem services (ESs) and their influencing mechanisms is crucial for regional ecological management and sustainable development. This study quantified net primary production (NPP), water yield (WY), soil conservation (SC), sand fixation (SF), habitat quality (HQ) and total ecosystem service (TES) on the Qinghai Tibet Plateau (QTP), and then analyzed the spatial–temporal characteristics of ESs. The geographical detector model (GDM), geographically weighted regression (GWR) model, and constraint lines were used to explore the effects of influencing factors on ESs. The results showed that (1) NPP, WY, SC, HQ and TES showed an increasing trend from 2000 to 2018, while SF showed a decreasing trend. NPP, WY, SC and TES showed a spatial distribution pattern of “high values in the southeast and low values in the northwest”, while the high values of SF were located in the northern QTP and the high values of HQ were located in the southern QTP. (2) NDVI was the key factor influencing NPP, SC, HQ and TES, and precipitation dominated WY, and SF was mainly influenced by Largest patch index (LPI). (3) In most of the study areas, the natural factors (precipitation, temperature, DEM, slope and NDVI) had positive effects on NPP, SC and TES and both positive and negative effects on WY, SF and HQ. The human factors (Resident, Road and LPI) had positive effects on HQ and both positive and negative effects on other ESs. There were mainly non-monotonic constraint effects of influencing factors on ESs. Overall, natural factors had a much stronger influence on ESs than human factors, and the interactions among factors were much stronger than their independent effects. The results of this study can provide a basis for ecological protection on the QTP.

Study region: The source regions of the Yellow River and Yangtze River in the central-eastern part of the Tibetan Plateau. Study focus: Hydrological model is an important tool in the simulation of watershed hydrology. However, as more and more basic geographic data becomes publicly available and shared globally, researchers are developing a 'symptom' of difficulty in choosing data, so a systematic comparative analysis for model input data selection is necessary. We tested the effects of different types, sources, and resolutions of input data on the model output results based on the SWAT model, and focused on the mechanism of the role of different input data in the model and how to select an appropriate input data for similar studies. New hydrological insights for the region: The results show that: the meteorological data is crucial in the model's runoff simulation, and ground meteorological observation station data outperforms reanalysis data such as CFSR. Optimizing CFSR significantly improves the model's performance. The DEM resolution minimally impacts runoff simulation, as the difference in results is primarily due to the topographic characteristics of the watershed. DEM selection should consider TWI complexity and its compatibility with the watershed network. The selection of LULC data has little effect on the simulation, and the best input data combination is OBS + 90 m DEM + CNLULC. These findings assist input data selection for similar watersheds using the SWAT model.

To enhance the precision of detecting defects on steel plate surfaces and diminish the incidences of false detection and leakage, the ESI-YOLOv8 algorithm is introduced. This algorithm introduces a novel EP module and integrates the large separation convolutional attention module and the spatial pyramid pooling module to propose the SPPF-LSKA module. Additionally, the original CIOU loss function is replaced with the INNER-CIOU loss function. The EP module minimizes redundant computations and model parameters to optimize efficiency and simultaneously increases the multi-scale fusion mechanism to expand the sensory field. The SPPF-LSKA module reduces computational complexity, accelerates model operation speed, and improves detection accuracy. Additionally, the INNER-CIOU loss function can improve detection speed and model accuracy by controlling the scale size of the auxiliary border.The results of the experiment indicate that, following the improvements made, the algorithm’s detection accuracy has increased to 78%, which is 3.7% higher than the original YOLOv8. Furthermore, the model parameters were reduced, and the verification was conducted using the CoCo dataset, resulting in an average accuracy of 77.8%. In conclusion, the algorithm has demonstrated its ability to perform steel plate surface defect detection with efficiency and accuracy.

As the scale and complexity of software for industrial equipment increases, the risk of defects being introduced into the software also increases. Over-the-air (OTA) technology eliminates software defects by regularly updating and maintaining the software equipment. However, downloading an upgraded file is time-consuming. The differential compression algorithm can rapidly complete OTA software upgrades. To solve the low-efficiency problem of suffix array sorting in the BsDiff algorithm, a fusion algorithm based on the suffix array induced sorting and BsDiff methods was proposed to reduce the time consumption in the OTA upgrade process. The execution of the difference algorithm in the cloud was simulated using bench experiments. Subsequently, the function and performance of the proposed algorithm were experimentally evaluated. The results showed that the optimized algorithm could save more than 35% of the time compared to the original algorithm, which improved the OTA upgrade efficiency to a certain extent.

Abstract This paper presents a fuzzy fixed‐time learning path tracking control strategy for autonomous vehicles with saturated input and uncertainties. First, Takagi‐Sugeno (T‐S) model is designed to realize an accurate description of the nonlinear path tracking systems. The T‐S model is the weighted sum of a series of linear dynamics models. The weighting coefficients are described by fuzzy membership functions. Then, with the consideration of the saturated input, a fixed‐time learning control is proposed. It contains a learning law to estimate the uncertainties of the system on‐line. The fixed‐time convergence and the robustness properties are analyzed through Lyapunov stability theory. Finally, the effectiveness of the proposed control method has been verified through the CarSim/Simulink co‐simulations under different driving conditions. The results demonstrate that the developed controller significantly improves the performance of path tracking and follows the desired path well even in the case of parameter uncertainties and external disturbances.

Abstract. For the detection of steatosis, quantitative ultrasound imaging techniques have achieved great progress in past years. Magnetic resonance imaging proton density fat fraction is currently the most accurate test to detect hepatic steatosis. Some blood biomarkers correlate with non-alcoholic steatohepatitis, but the accuracy is modest. Regarding liver fibrosis, liver stiffness measurement by transient elastography (TE) has high accuracy and is widely used across the world. Magnetic resonance elastography is marginally better than TE but is limited by its cost and availability. Several blood biomarkers of fibrosis have been used in clinical trials and hold promise for selecting patients for treatment and monitoring treatment response. This article reviews new developments in the non-invasive assessment of non-alcoholic fatty liver disease (NAFLD). Accumulating evidence suggests that various non-invasive tests can be used to diagnose NAFLD, assess its severity, and predict the prognosis. Further studies are needed to determine the role of the tests as monitoring tools. We cannot overemphasize the importance of context in selecting appropriate tests.

Background/Aims We aimed to determine the association between blood urea level and incident cirrhosis, hepatic decompensation, and hepatocellular carcinoma in chronic liver disease (CLD) patients. Methods The association between blood urea level and liver fibrosis/liver-related events were evaluated on continuous scale with restricted cubic spline curves based on generalized additive model or Cox proportional hazards models. Then, the above associations were evaluated by urea level within intervals. Results Among 4,282 patients who had undergone liver stiffness measurement (LSM) by transient elastography, baseline urea level had a U-shaped association with LSM and hepatic decompensation development after a median follow-up of 5.5 years. Compared to patients with urea of 3.6–9.9 mmol/L, those with urea ≤3.5 mmol/L (adjusted hazard ratio [aHR], 4.15; 95% confidence interval [CI], 1.68–10.24) and ≥10 mmol/L (aHR, 5.22; 95% CI, 1.86–14.67) had higher risk of hepatic decompensation. Patients with urea ≤3.5 mmol/L also had higher risk of incident cirrhosis (aHR, 3.24; 95% CI, 1.50–6.98). The association between low urea level and incident cirrhosis and hepatic decompensation was consistently observed in subgroups by age, gender, albumin level, and comorbidities. The U-shaped relationship between urea level and LSM was validated in another population screening study (n=917). Likewise, urea ≤3.5 mmol/L was associated with a higher risk of incident cirrhosis in a territory-wide cohort of 12,476 patients with nonalcoholic fatty liver disease at a median follow-up of 9.9 years (aHR, 1.27; 95% CI, 1.03–1.57). Conclusions We identified a U-shaped relationship between the urea level and liver fibrosis/incident cirrhosis/hepatic decompensation in patients with CLD.

Background: Trimethylamine-N-oxide (TMAO) is an intestinal metabolic toxin, which is produced by gut flora via metabolizing high-choline foods. TMAO is known to increase the risk of atherosclerosis and cardiovascular events in chronic kidney disease (CKD) patients. Objectives: The objective of this study was to explore the role and mechanism of TMAO aggravating kidney injury. Method: We used the five-sixths nephrectomy (5/6 Nx)-induced CKD rats to investigate whether TMAO could aggravate kidney damage and its possible mechanisms. Six weeks after the operation, the two groups of 5/6 Nx rats were subjected to intraperitoneal injection with 2.5% glucose peritoneal dialysis fluid (2.5% PDF) and 2.5% PDF plus TMAO 20 mg/kg/day. Results: In this study, we provided evidence showing TMAO significantly aggravated renal failure as well as inflammatory cell infiltration and in five-sixths nephrectomy-induced CKD rats. We found that TMAO could upregulate inflammatory factors including MCP-1, TNF-α, IL-6, IL-1β, and IL-18 by activating p38 phosphorylation and upregulation of human antigen R. TMAO could aggravate oxidative stress by upregulating NOX4 and downregulating SOD. The result also confirmed that TMAO promoted NLRP3 inflammasome formation as well as cleaved caspase-1 and IL-1β activation in the kidney tissue. Conclusions: Taken together, the present study validates TMAO as a pro-inflammatory factor that causes renal inflammatory injury and renal function impairment. Inhibition of TMAO synthesis or promoting its clearance may be a potential therapeutic approach of CKD in the future.

Slope-gully system is an important watershed component of the Loess Plateau and the main source of erosion and sediment yield in small watersheds. Its forest and grass measures are of great significance to vegetation restoration and reconstruction and water and soil conservation. In the experiment, the effects of different slope vegetation patterns (upper slope, middle slope, lower slope, bare slope) on hydrodynamic characteristics and sediment yield of slope-gully system were studied by field flushing test under the condition of 75 % vegetation coverage and 12 L/min discharge. The results showed that: (1) Vegetation distribution in the lower part of the slope had the most obvious effect on reducing runoff shear force while vegetation distribution in the middle of the slope had the most obvious effect on reducing runoff power of the slope-gully system. (2) The water storage benefits of vegetation distributed on upper slope, middle slope, lower slope was 88 %, 87 %, and 81 %, and the benefits of sediment reduction was 96 %, 98 %, and 97 % (compared with bare slope). (3) The sediment reduction effect of the slope-gully system under different slope vegetation patterns is better than the water storage effect. On the whole, the effect of soil and water conservation was best when the vegetation was placed in the middle and lower of the slope. The results of this study provide a scientific basis for optimizing vegetation allocation in the Loess Plateau and promote the effective development of soil and water conservation.

Ecological risk assessment (ERA) is an important element in territorial spatial planning, and the integration of ecosystem services into ERA is a current hot topic. In this study, taking the Tibetan Plateau as an example, a two-dimensional matrix is constructed based on the probability of risk occurrence and the possible loss caused by the risk for ecological risk assessment, with topographic sensitivity, ecological resilience, landscape vulnerability, and ecological sensitivity as probability representations, and the degradation of key ecosystem services as loss representations to improve the traditional ERA model. The results show that: (1) the probability shows a distribution pattern of high in the northwest and low in the southeast, with high-probability dominating, accounting for about 55.94%; the loss shows a distribution of low in the north and high in the south, with 30.54% of the region experiencing increased losses. (2) The ecological risk level is dominated by middle-high and high, the sum of the two accounts for 55.44%, while low and middle-low risk areas account for only 10.47%. Based on the proportion of high-risk in 45 cities, the risk control priority areas are identified: Naqu, Ali and Rikaze. (3) The Moran's I for probability, loss, and risk were 0.878, 0.615, and 0.567, respectively, indicating that all three showed significant positive spatial autocorrelation. The negative correlation between probability and loss indicates that there is spatial heterogeneity between them.

The benefit of colonoscopy and/or polypectomy for colorectal cancer (CRC) prevention in patients with nonalcoholic fatty liver disease (NAFLD) remains unclear. We aimed to estimate the incidence rate of CRC in patients with NAFLD who had and had not undergone colonoscopy. We conducted a retrospective territory‐wide cohort study for patients aged over 40 years with NAFLD identified with the International Classification of Diseases, Ninth Revision, Clinical Modification codes between January 1, 2000, and December 31, 2014. Patients were followed until CRC diagnosis, death, or December 31, 2017. We estimated CRC incidence and standardized incidence ratio (SIR) using the general population of Hong Kong as reference. We included 8,351 patients with NAFLD in the final analysis (median age, 56.2 years; interquartile ratio [IQR], 49.2‐65.3 years; 45.4% male; median follow‐up, 7.4 years; IQR, 5.4‐9.6 years). Compared with the general population, patients with NAFLD who had not undergone colonoscopy had a higher incidence of CRC (SIR, 2.20; 95% confidence interval [CI], 1.64‐2.88; P 2.67) had a significantly higher risk of CRC after adjusting for demographic and metabolic factors. Conclusion: Patients with NAFLD who had undergone colonoscopy had a lower incidence of CRC than the general population, especially among those aged ≥50 years or with DM. A high FIB‐4 index was associated with a higher risk of CRC.

Abstract Porcine circovirus type 3 (PCV3), which was first detected in the United States of America in 2015, is a potential threat to the swine industry. However, the prevalence of PCV3 in Shanxi Province, China, is unclear. In this research, the prevalence and genetic diversity of PCV3 were investigated in above area. Lung tissue samples (n = 491) from 19 pig slaughterhouses across 11 cities throughout Shanxi Province were analyzed for PCV3 infection by PCR in 2019. The results showed that PCV3 positive rates in slaughterhouses and individuals were 100% (19/19) and 86.76% (426/491), respectively. PCV2 and PCV3 double-positive rates in slaughterhouses and individuals were 100% (19/19) and 59.27% (291/491), respectively. PCR positive samples were further sequenced and 8 PCV3 isolates were identified. The nucleotide homology of these isolates with other PCV3 isolates in NCBI database was 97.45–99.90%. A phylogenetic analysis, based on the complete genomic sequence and ORF2, divided these PCV3 strains into 2 major groups. Based on A24/V and R27/K amino acid mutations of capsid protein, the 8 identified PCV3 strains were separated to 2 clades. This was the first detailed investigation into the epidemiology of PCV3 in Shanxi Province. Our findings enabled us to assess the possibility of widespread transmission from this region. Thus, current findings establish a basis for further studies of genetic variations in PCV3 strains circulating in China.

The calcium/calcineurin signaling pathway plays a key role in the development and virulence of plant pathogenic fungi, but the regulation of this signaling pathway is still not clear. In this study, we identified a calcineurin regulator MoRCN1 in the plant pathogenic fungus Magnaporthe oryzae and found it is important for virulence by regulating the calcineurin pathway. MoRCN1 deletion mutants were severely decreased in colony growth and conidia formation. More importantly, the deletion of MoRCN1 led to a significant reduction in virulence due to defects in appressorium formation and invasive growth. The ΔMorcn1 mutants were more sensitive to different stresses and induced host ROS accumulation, suggesting a role of MoRCN1 in stress adaptation. We found that MoRCN1 directly interacted with the calcineurin catalytic subunit MoCNA and affected its protein stability, which was therefore important for regulating the calcineurin pathway. Transcriptome analysis showed that MoRCN1 significantly activated 491 genes and suppressed 337 genes in response to calcium ion, partially overlapped with the MoCRZ1-bound genes. Gene Ontology and KEGG pathway analyses indicated that MoRCN1-regulated genes were enriched in stress adaptation, lipid metabolism, and secondary metabolite biosynthesis, reflecting a function of MoRCN1 in host cell adaptation. Altogether, these results suggest MoRCN1 functions as a regulator of the calcium/calcineurin signaling pathway for fungal development and infection of host cells.

BackgroundPorcine circovirus disease is currently the greatest threat to pig farming. Four main porcine circovirus genotypes are circulating worldwide.ObjectiveThe study aimed to assess the prevalence of porcine circovirus genotypes in the central part of Shanxi province.MethodsWe investigated the prevalence of porcine circovirus type 2 (PCV2), porcine circovirus type 3 (PCV3), and porcine circovirus type 4 (PCV4). Porcine circoviruses were analyzed by polymerase chain reaction (PCR) in the lung tissues of 180 pigs from 7 slaughterhouses in central Shanxi, China.ResultsThe prevalence of PCV2, PCV3, and PCV4 were 56.8, 80, and 9.4%, respectively, and the negative rate was 10% for all three pathogens. The co-infection with PCV2 + PCV3, PCV2 + PCV4, PCV3 + PCV4, and PCV2 + PCV3 + PCV4 were 47.2, 7.4, 7.4, and 5.6%, respectively. Among PCV4-positive samples, the positive rate of PCV4 + PCV2 was 52.9% (9/17), whereas that of PCV4 + PCV3 was 100% (17/17). On the other hand, PCV2 and PCV3 were detected in 57.1% (93/163) and in 78.5% (128/163) of PCV4-negative samples, respectively. Phylogenetic analysis demonstrated that PCV2, PCV3, and PCV4 were not in the same clade and were distant from each other.ConclusionThe high positive rates of PCV3, PCV2 + PCV3, and PCV3 + PCV4 suggest that PCV3 may play a decisive role in PCV2 and PCV4 infections. Therefore, further control of PCV3 is needed to reduce the spread of the virus.

The RNA polymerase II degradation factor Degradation Factor 1 (Def1) is important for DNA damage repair and plays various roles in eukaryotes; however, the biological role in plant pathogenic fungi is still unknown. In this study, we investigated the role of Def1 during the development and infection of the rice blast fungus Magnaporthe oryzae. The deletion mutant of Def1 displayed slower mycelial growth, less conidial production, and abnormal conidial morphology. The appressoria of Δdef1 was impaired in the penetration into host cells, mainly due to blocking in the utilization of conidial storages, such as glycogen and lipid droplets. The invasive growth of the Δdef1 mutant was also retarded and accompanied with the accumulation of reactive oxygen species (ROS) inside the host cells. Furthermore, compared with the wild type, Δdef1 was more sensitive to multiple stresses, such as oxidative stress, high osmotic pressure, and alkaline/acidic pH. Interestingly, we found that Def1 was modified by O-GlcNAcylation at Ser232, which was required for the stability of Def1 and its function in pathogenicity. Taken together, the O-GlcNAc modified Def1 is required for hyphae growth, conidiation, pathogenicity, and stress response in M. oryzae. This study reveals a novel regulatory mechanism of O-GlcNAc-mediated Def1 in plant pathogenic fungi.

BackgroundUnlike chemical drugs with a single or a few kinds of active compounds, traditional Chinese medicines (TCMs)uses herbal formulas composed of numerous kinds of chemical constituents. Therefore, TCM clinical trials require unique and stricter standards for collecting, preserving, and transporting fecal samples than those used for chemical drugs. Unfortunately, there are no special standards for processing fecal samples in TCM clinical trials.MethodsWe invited interdisciplinary experts within TCM clinical trials and gut microbiome research to help formulate this standard. After more than a year’s in-depth discussion and amendments, we achieved a standard via expert interviews, literature research, questionnaire surveys, and public opinion solicitation. This standard has been reviewed and approved by the Standards Office of China of the Association of Chinese medicine.ResultsWe established a sample information processing method prior to TCM clinical sample collection, which is adapted to the unique features of TCM. The method formulates detailed processing requirements for TCM information in addition to the factors that may disturb the gut microbiome. We also constructed a set of methods for collecting, preserving, and transporting fecal samples that meet the characteristics of TCM. These methods formulate detailed operating specifications on the collection approaches, storage conditions, transportation requirements, and management of fecal samples.ConclusionsThis standard guides the information processing prior to sample collection and the standard operating procedures for the collection, preservation, and transportation of fecal samples in TCM clinical trials, which also can be used as a reference by clinicians and researchers in modern medicines.

Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide. Although it has become one of the leading causes of cirrhosis and hepatocellular carcinoma in the Western world, the proportion of NAFLD patients developing these complications is rather small. Therefore, current guidelines recommend non-invasive tests for the initial assessment of NAFLD. Among the available non-invasive tests, transient elastography by FibroScan® (Echosens, Paris, France) is commonly used by hepatologists in Europe and Asia, and the machine has been introduced to the United States in 2013 with rapid adoption. Transient elastography measures liver stiffness and the controlled attenuation parameter simultaneously and can serve as a one-stop examination for both liver steatosis and fibrosis. Liver stiffness measurement also correlates with clinical outcomes and can be used to select patients for varices screening. Although obesity is a common reason for measurement failures, the development of the XL probe allows successful measurements in the majority of obese patients. This article reviews the performance and limitations of transient elastography in NAFLD and highlights its clinical applications. We also discuss the reliability criteria for transient elastography examination and factors associated with false-positive liver stiffness measurements.

Increasing studies have demonstrated that microRNAs (miRNAs) are associated with the metastasis of gallbladder carcinoma (GBC). Recently, miR-324-5p has been reported to be a tumour-suppressive miRNA in many types of malignant cancer. However, the biological function and molecular mechanism of miR-324-5p in GBC still remain largely unknown. Here, we found that miR-324-5p expression was notably down-regulated in both GBC tissues and cells compared with that in normal controls. Downregulated miR-324-5p expression was negatively associated with the status of local invasion and lymph node metastasis and predicted a poor prognosis in GBC patients. Further functional assays revealed that restoration of miR-324-5p significantly suppressed GBC cell migration, invasion and epithelial-mesenchymal transition (EMT) in vitro and impeded the metastasis of GBC cells in vivo. Moreover, RNA immunoprecipitation (RIP) and dual-luciferase reporter assay confirmed that the transforming growth factor beta 2 (TGFB2) was a direct target gene of miR-324-5p in GBC cells. Mechanically, small interfering RNA (siRNA)-mediated knockdown of TGFB2 partially phenocopied the inhibitory effects of miR-324-5p overexpression on GBC cell metastatic phenotypes. In summary, our findings demonstrated that miR-324-5p targets TGFB2 expression to inhibit GBC cell metastatic behaviors, and implying miR-324-5p as a potential biomarker for diagnostic and therapeutic strategies in GBC.

Denoising is a permanent topic and there are various denoisers proposed in the fault diagnosis of industrial systems. However, it is still ambiguous to evaluate their performance quantitatively in terms of mean square error (MSE) and further achieve their maximum gains, because it is always infeasible to obtain the MSE metric without real feature signals in the engineering practices. Therefore, leveraging Stein Unbiased Risk Estimator (SURE) theory, a bi-level nested sparse optimization framework (BiNSOF) is proposed to jointly optimize a parameterized sparse denoiser as well as its regularization parameter, further obtaining the near-optimal fault features with a minimum MSE. The inner level of BiNSOF utilizes a $\ell _{1}$ regularized sparse denoiser to describe the intrinsic sparse structure of feature information, which can be effectively addressed by popular primal-dual splitting schemes. The core of the outer optimization level is a SURE-based unbiased estimator for MSE, and the minimum MSE search problem is transformed into a quadratic optimization problem which could be fast solved by classic golden section search schemes. The proposed BiNOSP can perfectly approximate the oracle MSE without any real feature information, and further provides a reliable way to obtain the optimal hyper-parameter sets for the maximum performance gains of the sparse denoiser. The computational complexity of the advocated approach is also investigated. Moreover, its feasibility and performances are profoundly evaluated by a set of comprehensive numerical studies. Lastly, two bearing fault detection cases confirm the applicability and superiority of the proposed framework.

There is an extremely complex interactive coupling relationship between social development and ecological protection, and how to achieve the coordinated development of the two is a hot topic in sustainable development research. This paper constructs a comprehensive evaluation index system of Social-Ecological System(SES) on the Qinghai-Tibet Plateau, and then multi-scale analysis of the coupling coordination status and temporal-spatial evolution characteristics of the SES from 2003 to 2018 based on the coupling coordination degree model(CCDM), scissors difference, etc.The results show that: (1) the comprehensive evaluation index of social system shows an increasing trend, with a growth rate of 16.46% and a spatial distribution pattern of high in the northeast and low in the southwest; the ecosystem comprehensive evaluation index fluctuates down, with a decline rate of 32.80% and a spatial distribution pattern of low in the northwest and high in the southeast. (2) There are differences in the types of coordination among different scales: the Qinghai-Tibet Plateau as a whole is mild disorders; on the provincial scale, the lowest coupling coordination degree is mild disorders in Tibet, followed by primary coordination in Sichuan and Qinghai, and Gansu, Yunnan, and Xinjiang are the highest, all of which are moderate coordination; on the county scale, the proportion of severe disorders, moderate disorders and primary coordination decreased by 7.03%, 2.63% and 7.20% respectively, while mild disorders and moderate coordination increased by 11.28% and 5.59% respectively. (3) The scissors difference rising in volatility, and the difference between the evolutionary trends of the two subsystems has increased. (4) The dynamic coupling degree is distributed in the interval of [45°, 90°], indicating that the SES of the Qinghai-Tibet Plateau is in a stage of common development, but the conflicts between the two are beginning to emerge. An in-depth analysis of the internal interaction process and the coupling coordination status of the SES can provide a theoretical basis and policy reference for sustainable development of the Qinghai-Tibet Plateau.

Cardiovascular remodeling occurs in cardiomyocytes, collagen meshes, and vascular beds in the progress of cardiac insufficiency caused by a variety of cardiac diseases such as chronic ischemic heart disease, chronic overload heart disease, myocarditis, and myocardial infarction. The morphological changes that occur as a result of remodeling are the critical pathological basis for the occurrence and development of serious diseases and also determine morbidity and mortality. Therefore, the inhibition of remodeling is an important approach to prevent and treat heart failure and other related diseases. The endoplasmic reticulum (ER) and mitochondria are tightly linked by ER-mitochondria contacts (ERMCs). ERMCs play a vital role in different signaling pathways and provide a satisfactory structural platform for the ER and mitochondria to interact and maintain the normal function of cells, mainly by involving various cellular life processes such as lipid metabolism, calcium homeostasis, mitochondrial function, ER stress, and autophagy. Studies have shown that abnormal ERMCs may promote the occurrence and development of remodeling and participate in the formation of a variety of cardiovascular remodeling-associated diseases. This review focuses on the structure and function of the ERMCs, and the potential mechanism of ERMCs involved in cardiovascular remodeling, indicating that ERMCs may be a potential target for new therapeutic strategies against cardiovascular remodeling-induced diseases.

Abstract Background and Aims Metformin is an oral anti‐hyperglycemic recommended by the American Diabetes Association (ADA) as a preferred initial pharmacologic agent for type 2 diabetes. Metabolic acidosis is a rare yet severe side effect of it. We examined the association of metformin use and dosage on the risk of metabolic acidosis in diabetic patients with different degrees of chronic hepatitis B (CHB)‐related cirrhosis and chronic kidney disease (CKD). Methods Metabolic acidosis was defined by blood pH ≤7.35, together with lactate >5 mmol/L or arterial bicarbonate ≤18 mmol/L or venous bicarbonate ≤21 mmol/L, and/or diagnosis codes. Child‐Pugh class and CKD stage were included in the model as time‐dependent covariates. Age, gender, comorbidities, and use of relevant medications were adjusted as covariates. Maximum daily dose of metformin was classified into ≤1000 mg and >1000 mg. Results We identified 4431 diabetic patients with CHB‐related cirrhosis between 2000 and 2017 from a territory‐wide database in Hong Kong. The risk of metabolic acidosis increased with Child‐Pugh class B and C cirrhosis regardless of CKD stage (adjusted subdistribution hazard ratio [aSHR] ranged from 3.50 to 86.16). Metformin use was associated with a higher risk in patients with Child‐Pugh class B or C cirrhosis and stage 3A CKD or above (aSHR ranged from 1.55 to 2.46). In stage 4/5 CKD, a daily dose of metformin ≤1000 mg was still associated with a higher risk of metabolic acidosis regardless of the severity of cirrhosis (aSHR ranged from 2.45 to 3.92). Conclusion In conclusion, patients with Child‐Pugh class B cirrhosis or above were at a higher risk of metabolic acidosis. Metformin further increased the risk in patients with Child‐Pugh class B cirrhosis or above and stage 3A CKD or above. Dose adjustment in stage 4/5 CKD did not reduce the risk of metabolic acidosis.

Based on the biological characteristics of tulip, the low driving voltage and fast response of ionic polymer metal composite (IPMC), we analyzed the fabrication, morphology and performance of the platinum IPMC (Pt-IPMC) and selected the right IPMC for driving bionic tulip. The preparation and performance of IPMC was analyzed first in this paper such as blocking force, output displacement and bending angle of IPMC under the different directed current voltage (DC). The optimal IPMC sample size and driving voltage were selected based on tulip blooming angles and the strain energy density of IPMC, which completed the blooming process of bionic tulip. The feasibility of IPMC used in driving bionic field was fully proved in this paper, which laid a foundation for the application of IPMC in driving biomimetic biological robots.

Sapphire is one of the most widely used electronic substrate materials in the industry. The manufacturing process of sapphire and such hard and brittle materials is extremely time and energy consuming because of their superior material properties in physical and chemical behaviors. In this study, the ultraviolet-curable resin is introduced into the fabrication of the diamond abrasive lapping plate as a bonding agent. A practical manufacturing process is established in the laboratory to develop an ultraviolet-curable resin bond fixed abrasive lapping plate for the precision machining of sapphire substrates, the machining performance of which is examined through a series of comparative experiments among the conventional fixed-abrasive lapping, the slurry-based lapping and this originally developed plate involved lapping. The surface topography and surface roughness of the machined sapphire workpieces are measured to evaluate the surface quality, and the weight loss of the workpieces in each machining process is recorded to estimate the respective machining efficiency. The promising results achieved from the ultraviolet-curable resin plate lapping process, in terms of a relatively higher material removal rate and better surface quality, indicate that the occurrence of a corporate action integrating both the advantages of the fixed abrasive grains and loose abrasive grains. A summarized hypothesis is drawn to describe the dynamically balanced state of the hybrid precision abrasive machining process, in which the 2-body abrasion and 3-body abrasion material removal mechanism participate simultaneously and interconvert to each other continuously.

Redox modification, a post-translational modification, has been demonstrated to be significant for many physiological pathways and biological processes in both eukaryotes and prokaryotes. However, little is known about the global profile of protein redox modification in fungi. To explore the roles of redox modification in the plant pathogenic fungi, a global thiol proteome survey was performed in the model fungal pathogen Magnaporthe oryzae. A total of 3713 redox modification sites from 1899 proteins were identified through a mix sample containing mycelia with or without oxidative stress, conidia, appressoria, and invasive hyphae of M. oryzae. The identified thiol-modified proteins were performed with protein domain, subcellular localization, functional classification, metabolic pathways, and protein–protein interaction network analyses, indicating that redox modification is associated with a wide range of biological and cellular functions. These results suggested that redox modification plays important roles in fungal growth, conidium formation, appressorium formation, as well as invasive growth. Interestingly, a large number of pathogenesis-related proteins were redox modification targets, suggesting the significant roles of redox modification in pathogenicity of M. oryzae. This work provides a global insight into the redox proteome of the pathogenic fungi, which built a groundwork and valuable resource for future studies of redox modification in fungi.

A safe and effective approach is needed to prevent and reduce the incidence of diabetes worldwide. The hypoglycemic efficacy of salicylic acid (salsalate, SAL), which has anti-inflammatory properties, has been empirically demonstrated in studies conducted at the Joslin Diabetes Center and elsewhere. Here, we investigated the potential role of SAL in preventing the onset of diabetes in Zucker diabetic fatty (ZDF) rats and attempted to elucidate its underlying mechanisms. ZDF and Zucker lean (ZL) rats were administered a high-fat diet with or without SAL intervention, and their relative rates of diabetes were compared. Our results showed that all rats in the placebo group developed diabetes, whereas only 10% of the SAL-treated rats presented with impaired glucose tolerance (IGT). None of the latter progressed to diabetes. Relative to the untreated rats, SAL lowered plasma glucagon and insulin while improving insulin sensitivity and β-cell function. SAL may protect against hyperglycemia by increasing the microbial diversity, ameliorating gut dysbiosis, restoring intestinal epithelial cell connections, inhibiting endotoxin influx into the blood, and attenuating inflammation. Together, these findings suggest that SAL may be a candidate prophylactic therapy against diabetes. The protective role of SAL may be attributed to its ability to reduce intestinal inflammation and improve gut dysbiosis.

Spontaneous unilateral cryptorchid boars have one testis in the abdomen or inguinal canal, causing its temperature to be at or near the body temperature, which impairs spermatogenesis, although the histomorphometry and molecular mechanisms underlying this process remain unclear. The aim of the present study was to determine the histomorphometry, proliferation, apoptosis, and autophagy alterations in spermatogonia and Sertoli cells in unilateral cryptorchid, scrotal (contrascrotal), and preweaning piglet (preweaning) testes. Histomorphometrical analysis of cryptorchid testes showed that the seminiferous tubules contained only Sertoli cells and a few spermatogonia, but did not contain post-meiotic germ cells. The number of spermatogonia markedly decreased, and the number of Sertoli cells did not change remarkably in cryptorchid testes. TUNEL assay results showed that apoptosis signals were predominantly observed in spermatogonia. In cryptorchid and contrascrotal testes, proliferating cell nuclear antigen (PCNA) and LC3 were located in spermatogonia. The number of PCNA-positive, TUNEL-positive, and LC3-positive germ cells was low, and the protein and mRNA levels of PCNA and LC3 were significantly decreased in cryptorchid testes. Taken together, the number of Sertoli cells did not change remarkably, whereas the number of germ cells decreased in the cryptorchid testes, compared with that in the contrascrotal testes. Insufficient proliferation, excessive apoptosis, and autophagy were involved in the regulation of the decrease in spermatogonia in cryptorchid boar testes.

Extensive ecosystem restoration is increasingly seen as an essential practice to mitigate climate change and protect the ecological environment. However, the indirect impact of surface vegetation improvement on the regional climate, such as the climate effect of sand-dust events reduction, has never been evaluated. Here, we estimated the feedback of temperature and precipitation on the change of sand-dust events, arising from the vegetation growth with ecological restoration, using a simple theoretical framework with a series of scenario simulations based on a regional climate model (RegCM). The results showed that revegetation reduced dust emissions, with a contribution rate of approximately 40.15%. With the combined influence of ecological restoration and climate change, the cooling effect of sand-dust events strengthened with the increase in the intensity of sand-dust events, which is mainly caused by the strong absorption of shortwave radiation by the atmosphere. The response of precipitation was uncertain because of tropospheric circulation feedback and shortwave radiation absorption. Our results also indicate that changes in sand-dust events caused by vegetation restoration play important roles in shaping the future climate near the arid and semi-arid regions of northern China. The climatic effects of sand-dust events should be included in assessing ecological restoration impacts to promote sustainable development and enhance our understanding of climate change.

Background: Element-tagged immunoassay coupled with inductively coupled plasma mass spectrometry (ICP-MS) detection has the potential to revolutionize immunoassay analysis for multiplex detection. However, a further study referring to the standard evaluation and clinical sample verification is needed to ensure its reliability for simultaneous analysis in clinical laboratories. Methods: Carcinoembryonic antigen (CEA) and α-fetoprotein (AFP) were chosen for the duplex immunoassay. The performance of the assay was evaluated according to guidelines from the Clinical and Laboratory Standards Institute (CLSI). Moreover, reference intervals (RIs) of CEA and AFP were established. At last, 329 clinical samples were analyzed by the proposed method and results were compared with those obtained with electrochemiluminescent immunoassay (ECLIA) method. Results: The measurement range of the assay was 2–940 ng/mL for CEA and 1.5–1000 ng/mL for AFP, with a detection limit of 0.94 ng/mL and 0.34 ng/mL, respectively. The inter-assay and intra-assay imprecision were all less than 6.58% and 10.62%, respectively. The RI of CEA and AFP was 0–3.84 ng/mL and 0–9.94 ng/mL, respectively. Regarding to clinical sample detection, no significant difference was observed between the proposed duplex assay and the ECLIA method. Conclusions: The ICP-MS-based duplex immunoassay was successfully developed and the analytical performance fully proved clinical applicability. Well, this could be different with other analytes.

Laser desorption ionization mass spectrometry (LDI-MS) is a primary tool for biological analysis. Its success relies on the use of chemical matrices that facilitate soft desorption and ionization of the biomolecules, which, however, also limits its application for metabolomics study due to the chemical interference by the matrix compounds. The requirement for sample pretreatment is also undesirable for direct sampling analysis or tissue imaging. In this study, antireflection (AR) metal surfaces were investigated as sample substrates for matrix-free LDI-MS. They were prepared through ultrafast laser processing, with high light-to-heat energy conversion efficiency. The morphology and micro/nanostructures on the metal surfaces could be adjusted and optimized by tuning the laser fabrication process. The super-high UV absorption at 97% enabled highly efficient thermal desorption and ionization of analytes. The analytical performance for the matrix-free LDI was explored by analyzing a variety of biological compounds, including carbohydrates, drugs, metabolites, and amino acids. Its applicability for direct analysis of complex biological samples was also demonstrated by direct analysis of metabolites in yeast cells.

Ultraviolet-curable resin was introduced as a bonding agent into the fabrication process of precision abrasive machining tools in this study, aiming to deliver a rapid, flexible, economical, and environment-friendly additive manufacturing process to replace the hot press and sintering process with thermal-curable resin. A laboratory manufacturing process was established to develop an ultraviolet-curable resin bond diamond lapping plate, the machining performance of which on the ceramic workpiece was examined through a series of comparative experiments with slurry-based iron plate lapping. The machined surface roughness and weight loss of the workpieces were periodically recorded to evaluate the surface finish quality and the material removal rate. The promising results in terms of a 12% improvement in surface roughness and 25% reduction in material removal rate were obtained from the ultraviolet-curable resin plate-involved lapping process. A summarized hypothesis was drawn to describe the dynamically-balanced state of the hybrid precision abrasive machining process integrated both the two-body and three-body abrasion mode.

Chiral separations of five β-adrenergic antagonists (propranolol, esmolol, atenolol, metoprolol, and bisoprolol) were studied by capillary electrophoresis using six cyclodextrins (CDs) as the chiral selectors. Carboxymethylated-β-cyclodextrin (CM-β-CD) exhibited a higher enantioselectivity power compared to the other tested CDs. The influences of the concentration of CM-β-CD, buffer pH, buffer concentration, temperature, and applied voltage were investigated. The good chiral separation of five β-adrenergic antagonists was achieved using 50 mM Tris buffer at pH 4.0 containing 8 mM CM-β-CD with an applied voltage of 24 kV at 20 °C. In order to understand possible chiral recognition mechanisms of these racemates with CM-β-CD, host-guest binding procedures of CM-β-CD and these racemates were studied using the molecular docking software Autodock. The binding free energy was calculated using the Autodock semi-empirical binding free energy function. The results showed that the phenyl or naphthyl ring inserted in the hydrophobic cavity of CM-β-CD and the side chain was found to point out of the cyclodextrin rim. Hydrogen bonding between CM-β-CD and these racemates played an important role in the process of enantionseparation and a model of the hydrogen bonding interaction positions was constructed. The difference in hydrogen bonding formed with the –OH next to the chiral center of the analytes may help to increase chiral discrimination and gave rise to a bigger separation factor. In addition, the longer side chain in the hydrophobic phenyl ring of the enantiomer was not beneficial for enantioseparation and the chiral selectivity factor was found to correspond to the difference in binding free energy.

To confirm the relationship between Circ_0003855 and EC, we purchased the Human esophageal carcinoma cell line Eca109 and normal human esophageal epithelial cells HEEC, and the expression levels of Circ_0003855, miR-622, and FLOT1 were detected. The results show that Circ_0003855 and FLOT1 were highly expressed in Eca109 cells, while miR-622 was lowly expressed (p < 0.05). Subsequently, Circ_0003855 small interfering RNA (si-Circ_0003855) and its negative control (si-NC) were used to detect changes in cellular biological behaviors. We found that the activity of Eca109 cells was reduced after interfering with the expression of Circ_0003855, and miR-622 expression was elevated, while FLOT1 was decreased (p < 0.05). Additionally, si-Circ_0003855 and miR-622 inhibitor sequence (miR-622-inhibition) were co-transfected into cells with miR-622-inhibition alone, and untreated Eca109 cells were used as a control to detect the expression of FLOT1. Co-transfection of si-Circ_0003855 and miR-622-inhibition showed no significant difference in FLOT1 expression compared to the control cells (p > 0.05). Synthesizing the results of these experiments above, we believe that interfering with the expression of Circ_0003855 can inhibit the activity of EC cells, and its mechanism is related to miR-622 and FLOT1. [ABSTRACT FROM AUTHOR]

Background & Aims: We aimed to determine the trends in risk factor control and treatment among patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) in 2000-2020. Methods: We conducted a territory-wide cohort study of adult patients with NAFLD and T2D diagnosed between 1 January 2000 and 31 July 2021 in Hong Kong. T2D was defined by use of any anti-diabetic agents, laboratory tests and/or diagnosis codes. Results: This study included 16,084 patients with NAFLD and T2D (mean age, 54.8 ± 12.0 years; 7124 male [44.3%]). The percentage of patients achieving individualised haemoglobin A1c (HbA1c) targets increased from 44.5% (95% confidence interval [CI], 42.9-46.1) to 64.8% (95% CI, 64.1-65.5), and percentage of patients achieving individualised low-density lipoprotein-cholesterol (LDL-C) targets increased from 23.3% (95% CI, 21.9-24.7) to 54.3% (95% CI, 53.5-55.1) from 2000-2005 to 2016-2020, whereas percentage of patients achieving blood pressure control (<140/90 mm Hg) remained static at 53.1-57.2%. Combination therapy for diabetes increased, especially among those with poor glycaemic control, but there was no increase in combination therapy for hypertension. Fewer cirrhotic patients achieved blood pressure control and individualised LDL-C targets, but they were more likely to achieve individualised HbA1c targets than non-cirrhotics. Metformin and statins were underused in cirrhotic patients. Younger patients (18-44 years) were less likely to achieve individualised HbA1c targets than middle-aged (45-64 years) and older ones (=65 years). Conclusions: From 2000 to 2020, glycaemic and lipid control improved significantly, whereas blood pressure control remained static among patients with NAFLD and T2D. [ABSTRACT FROM AUTHOR]

This paper puts forward the robust control problem of rail vehicle virtual coupling platoon that is subject to nonlinear and time-varying uncertainties. The uncertainties are caused by external disturbances and parameter variations. To this end, this paper designs a robust controller based on the Udwadia-Kalaba (UK) equation. First, we introduce the concept of virtual coupling and establish the longitudinal dynamics model of the rail vehicle. In order to ensure the control objective of the virtual coupling process, the spatial constraint on position and bidirectional inequality constraints for the spacing error between the marshalling trains are established. After changing the bounded state into the unbounded state through the state transformation, the UK approach can be used. Then, the constraint-following robust controller design is based on the UK approach and Lyapunov stability theory. The controller can render the unbounded state eventual uniform boundedness and uniformultimate boundedness, which also satisfies the spatial constraint and the bidirectional restriction for the spacing error. Moreover, an optimized design scheme for the tunable parameter of this controller is proposed, which minimizes the control cost and comprehensive index of system performance. Finally, numerical simulations are given to illustrate the effectiveness of the proposed methods. [ABSTRACT FROM AUTHOR]