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Steel containment vessels for nuclear power plants can experience gas leakage due to minute defects such as cracks, corrosion, and aging, leading to gas leakage. A gas leakage model for microchannels is established to elucidate the mechanism underlying gas leakage within microchannels caused by these defects, specifically addressing the issue of unidirectional gas flow. Computational Fluid Dynamics (CFD) and the UK R6 method are employed to calculate the gas leakage rate within microchannels. Furthermore, the characteristics of gas flow within microchannels are explored, including the factors affecting the gas leakage rate. Validation of the calculation results is verified experimentally. The results indicate that the gas mass flow rate exhibits a linear decrease with decreasing internal pressure and a non-linear decline as temperature increases. Additionally, the gas mass flow rate demonstrates a negative correlation with the microchannel length but a positive association to its hydraulic diameter. The primary influencing factors on gas leakage rates are hierarchically ranked as follows: pressure difference, microchannel cross-sectional area, temperature, microchannel length, and microchannel hydraulic diameter.

This paper introduces a base isolation system-tuned mass damper inerter (BIS-TMDI) hybrid system to the AP1000 nuclear power plant (NPP), which reduces seismic damage potential of the NPP structure. The effects of fluid-structure interaction (FSI) caused by the passive containment cooling system water storage tank (PCCWST) on NPP's seismic performance are investigated. The FSI of water tank theoretical model is considered based on the Housner's model, and a series of time history analyses are performed to prove the rationality of the proposed model. Three single-objective optimization strategies are employed to minimize the relative displacement variance and absolute acceleration variance of the upper structure, as well as the filtered energy index (FEI). Furthermore, a multi-objective optimization strategy considering all these three indexes is proposed to obtain optimal parameters of vibration control. The influence of vibration control strategies on the relative deformation and acceleration of the upper structure is explored with various water level ratios. The analytical results indicate that the proposed BIS-TMDI strategy has significantly reduced the NPP structure's seismic response. The effectiveness of the vibration control strategy is influenced by the water level ratio, emphasizing the significance of designing an appropriate water level ratio to reduce NPP structure's seismic response.

Abstract Rock typing plays a crucial role in describing the heterogeneity of the reservoir. Most of the conventional rock typing methods are implemented to classify the target reservoir into various rock types based on various petrophysical properties (e.g., porosity and permeability), but fail to provide more critical information that significantly affects the final performance of the reservoir characterization including: (1) the porosity and permeability contribution of each rock type and (2) the geological genesis of each rock type. Along with the universal application of various imaging devices, the image-based microscale rock typing (IMRT) can be directly conducted based on the observed pore structures which fundamentally determine the rock types. The IMRT belongs to the computer vision field which can be divided into pattern recognition-related rock typing (PRRT) and texture segmentation-related rock typing (TSRT). The PRRT is mainly used to identify the category (e.g., lithofacies, reservoir zone, or Dunham textures) of a given rock sample. The TSRT aims to classify a single image into several areas where each area denotes a relatively homogeneous porous structure. In this paper, the popular IMRT methods and their applications are reviewed thoroughly. Many successful applications proved that IMRT is an effective way to quantitatively estimate the porosity and permeability contributions of each rock type in a heterogeneous rock sample with the help of numerical flow simulation. Besides, the IMRT results also can be used to reveal the geological genesis of each rock type when its texture is determined by a special geological process.

BackgroundAs the world population recovers from the COVID-19 infection, a series of acute sequelae emerge including new incident diabetes. However, the association between COVID-19 infection and new incident diabetes is not fully understood. We purpose to determine the risk of new incident diabetes after COVID-19 infection.MethodsPubMed, Embase, and Cochrane Library were used as databases to search for cohort studies published from database inception to February 4, 2024. Two reviewers independently conducted the study screening, data extraction, and risk of bias assessment. A random-effects model was adopted to pool the hazard ratio (HR) with corresponding 95% confidence intervals (CI). Subgroup analysis was conducted to explore the potential influencing factors.ResultsA total of 20 cohort studies with over 60 million individuals were included. The pooling analysis illustrates the association between COVID-19 infection and an increased risk of new incident diabetes (HR = 1.46; 95% CI: 1.38-1.55). In subgroup analysis, the risk of type 1 diabetes was HR=1.44 (95% CI: 1.13-1.82), and type 2 diabetes was HR=1.47 (95% CI: 1.36-1.59). A slightly higher risk of diabetes was found in males (HR=1.37; 95% CI: 1.30-1.45) than in females (HR=1.29; 95% CI: 1.22-1.365). The risk of incident diabetes is associated with hospitalization: non-hospitalized patients have an HR of 1.16 (95% CI: 1.07-1.26), normal hospitalized patients have an HR of 2.15 (95% CI: 1.33-3.49), and patients receiving intensive care have the highest HR of 2.88 (95% CI: 1.73-4.79).ConclusionsCOVID-19 infection is associated with an elevated risk of new incident diabetes. Patients ever infected with COVID-19 should be recognized as a high-risk population with diabetes.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42024522050.

Abstract Reservoir characterization, essential for understanding subsurface heterogeneity, often faces challenges due to scale-dependent variations. This study addresses this issue by utilizing hydraulic flow unit (HFU) zonation to group rocks with similar petrophysical and flow characteristics. Flow Zone Indicator (FZI), a crucial measure derived from pore throat size, permeability, and porosity, serves as a key parameter, but its determination is time-consuming and expensive. The objective is to employ supervised and unsupervised machine learning to predict FZI and classify the reservoir into distinct HFUs. Unsupervised learning using K-means clustering and supervised algorithms including Random Forest (RF), Extreme Gradient Boosting (XGB), Support Vector Machines (SVM), and Artificial Neural Networks (ANN) were employed. FZI values from RCAL data formed the basis for model training and testing, then the developed models were used to predict FZI in unsampled locations. A methodical approach involves 3 k-fold cross-validation and hyper-parameter tuning, utilizing the random search cross-validation technique over 50 iterations was applied to optimize each model. The four applied algorithms indicate high performance with coefficients determination (R2) of 0.89 and 0.91 in training and testing datasets, respectively. RF showed the heist performance with training and testing R2 values of 0.957 and 0.908, respectively. Elbow analysis guided the successful clustering of 212 data points into 10 HFUs using k-means clustering and Gaussian mixture techniques. The high-quality reservoir zone was successfully unlocked using the unsupervised technique. It has been discovered that the areas between 2370–2380 feet and 2463–2466 feet are predicted to be high-quality reservoir potential areas, with average FZI values of 500 and 800, consecutively. The application of machine learning in reservoir characterization is deemed highly valuable, offering rapid, cost-effective, and precise results, revolutionizing decision-making in field development compared to conventional methods.

Plasma membrane intrinsic proteins (PIPs) are conserved plant aquaporins that transport small molecules across the plasma membrane to trigger instant stress responses and maintain cellular homeostasis under biotic and abiotic stress. To elucidate their roles in plant immunity to pathogen attack, we characterized the expression patterns, subcellular localizations, and H2O2-transport ability of 11 OsPIPs in rice (Oryza sativa), and identified OsPIP2;6 as necessary for rice disease resistance. OsPIP2;6 resides on the plasma membrane and facilitates cytoplasmic import of the immune signaling molecule H2O2. Knockout of OsPIP2;6 increases rice susceptibility to Magnaporthe oryzae, indicating a positive function in plant immunity. OsPIP2;6 interacts with OsPIP2;2, which has been reported to increase rice resistance to pathogens via H2O2 transport. Our findings suggest that OsPIP2;6 cooperates with OsPIP2;2 as a defense signal transporter complex during plant–pathogen interaction.

Phase unwrapping (PU) is a critical processing step for obtaining information on land surface deformation from interferometric synthetic aperture radar (InSAR) images. Traditional PU methods take the phase continuity assumption as the precondition. However, in actual applications, there are many factors that can cause phase discontinuities, resulting in large errors in the PU results. With the fast development of deep learning, the data-driven deep learning methods for PU may help address this issue. Therefore, this study proposes a coherence-guided InSAR PU method with cycle-consistent adversarial networks. In this method, PU was considered a pixel-level regression problem from the interferogram to the unwrapped phase; cycle-consistent adversarial networks as one-step PU model were imported with the interferogram as the input and the unwrapped phase as the output. Except for adversarial loss and cycle consistency loss, based on the PU theory and the coherence of SAR images, the $\mathcal {L}_{1}$ loss with the weight of the coherence coefficient was added to guide the training process of networks. In addition to the traditional mean square error index, the root mean square value of the phase loop closure was introduced to evaluate the quality of the generated unwrapped phase. The results show that the proposed method can not only achieve the accuracy of the traditional PU method in the region with good coherence but also obtain better unwrapping results in the region with poor coherence, where the traditional PU method is restricted. It is also superior to the existing PU method with a conditional adversarial network.

Abstract Multiferroic materials offer a promising avenue for manipulating digital information by leveraging the cross-coupling between ferroelectric and ferromagnetic orders. Despite the ferroelectricity has been uncovered by ion displacement or interlayer-sliding, one-unit-cell of multiferroic materials design and wafer-scale synthesis have yet to be realized. Here we develope an interface modulated strategy to grow 1-inch one-unit-cell of non-layered chromium sulfide with unidirectional orientation on industry-compatible c-plane sapphire. The interfacial interaction between chromium sulfide and substrate induces the intralayer-sliding of self-intercalated chromium atoms and breaks the space reversal symmetry. As a result, robust room-temperature ferroelectricity (retaining more than one month) emerges in one-unit-cell of chromium sulfide with ultrahigh remanent polarization. Besides, long-range ferromagnetic order is discovered with the Curie temperature approaching 200 K, almost two times higher than that of bulk counterpart. In parallel, the magnetoelectric coupling is certified and which makes 1-inch one-unit-cell of chromium sulfide the largest and thinnest multiferroics.

As a common foodborne pathogen, infection with L. monocytogenes poses a significant threat to human life and health. The objective of this study was to employ comparative genomics to unveil the biodiversity and evolutionary characteristics of L. monocytogenes strains from different regions, screening for potential target genes and mining novel target genes, thus providing significant reference value for the specific molecular detection and therapeutic targets of L. monocytogenes strains. Pan-genomic analysis revealed that L. monocytogenes from different regions have open genomes, providing a solid genetic basis for adaptation to different environments. These strains contain numerous virulence genes that contribute to their high pathogenicity. They also exhibit relatively high resistance to phosphonic acid, glycopeptide, lincosamide, and peptide antibiotics. The results of mobile genetic elements indicate that, despite being located in different geographical locations, there is a certain degree of similarity in bacterial genome evolution and adaptation to specific environmental pressures. The potential target genes identified through pan-genomics are primarily associated with the fundamental life activities and infection invasion of L. monocytogenes, including known targets such as inlB, which can be utilized for molecular detection and therapeutic purposes. After screening a large number of potential target genes, we further screened them using hub gene selection methods to mining novel target genes. The present study employed eight different hub gene screening methods, ultimately identifying ten highly connected hub genes (bglF_1, davD, menE_1, tilS, dapX, iolC, gshAB, cysG, trpA, and hisC), which play crucial roles in the pathogenesis of L. monocytogenes. The results of pan-genomic analysis showed that L. monocytogenes from different regions exhibit high similarity in bacterial genome evolution. The PCR results demonstrated the excellent specificity of the bglF_1 and davD genes for L. monocytogenes. Therefore, the bglF_1 and davD genes hold promise as specific molecular detection and therapeutic targets for L. monocytogenes strains from different regions.

Abstract Microbial production of monoterpenoid indole alkaloids (MIAs) provides a sustainable and eco‐friendly means to obtain compounds with high pharmaceutical values. However, efficient biosynthesis of MIAs in heterologous microorganisms is hindered due to low supply of key precursors such as geraniol and its derivative 8‐hydroxygeraniol catalyzed by geraniol 8‐hydroxylase (G8H). In this study, we developed a facile evolution platform to screen strains with improved yield of geraniol by using the SCRaMbLE system embedded in the Sc2.0 synthetic yeast and confirmed the causal role of relevant genomic targets. Through genome mining, we identified several G8H enzymes that perform much better than the commonly used CrG8H for 8‐hydroxygeraniol production in vivo. We further showed that the N‐terminus of these G8H enzymes plays an important role in cellular activity by swapping experiments. Finally, the combination of the engineered chassis, optimized biosynthesis pathway, and utilization of G8H led to the final strain with more than 30‐fold improvement in producing 8‐hydroxygeraniol compared with the starting strain. Overall, this study will provide insights into the construction and optimization of yeast cells for efficient biosynthesis of 8‐hydroxygeraniol and its derivatives.

Deep learning has increasingly been used to identify minerals. However, deep learning can only be used to identify minerals within the distribution of the training set, while any mineral outside the spectrum of the training set is inevitably categorized erroneously within a predetermined class from the training set. To solve this problem, this study introduces the approach that combines a One-Class Support Vector Machine (OCSVM) with the ResNet architecture for out-of-distribution mineral detection. Initially, ResNet undergoes training using a training set comprising well-defined minerals. Subsequently, the first two layers obtained from the trained ResNet are employed to extract the discriminative features of the mineral under consideration. These extracted mineral features then become the input for OCSVM. When OCSVM discerns the mineral in the training set’s distribution, it triggers the subsequent layers within the trained ResNet, facilitating the accurate classification of the mineral into one of the predefined categories encompassing the known minerals. In the event that OCSVM identifies a mineral outside of the training set’s distribution, it is categorized as an unclassified or ‘unknown’ mineral. Empirical results substantiate the method’s capability to identify out-of-distribution minerals while concurrently maintaining a commendably high accuracy rate for the classification of the 36 in-distribution minerals.

Abstract Effective treatment for metastasis, a leading cause of cancer‐associated death, is still lacking. To seed on a distal organ, disseminated cancer cells (DCCs) must adapt to the local tissue microenvironment. However, it remains elusive how DCCs respond the pro‐metastatic niche signals. Here, systemic motif‐enrichment identified myocyte enhancer factor 2D (MEF2D) as a critical sensor of niche signals to regulate DCCs adhesion and colonization, leading to intrahepatic metastasis and recurrence of liver cancer. In this context, MEF2D transactivates Itgb1 (coding β1‐integrin) and Itgb4 (coding β4‐integrin) to execute temporally unique functions, where ITGB1 recognizes extracellular matrix for early seeding, and ITGB4 acts as a novel sensor of neutrophil extracellular traps‐DNA (NETs‐DNA) for subsequent chemotaxis and colonization. In turn, an integrin‐FAK circuit promotes a phosphorylation‐dependent USP14‐orchastrated deubiquitination switch to stabilize MEF2D via circumventing degradation by the E3‐ubiquitin‐ligase MDM2. Clinically, the USP14(pS432)‐MEF2D‐ITGB1/4 feedback loop is often hyper‐active and indicative of inferior outcomes in human malignancies, while its blockade abrogated intrahepatic metastasis of DCCs. Together, DCCs exploit a deubiquitination‐dependent switch on MEF2D to integrate niche signals in the liver mesenchyme, thereby amplifying the pro‐metastatic integrin‐FAK signaling. Disruption of this feedback loop is clinically applicable with fast‐track potential to block microenvironmental cues driving metastasis.

The emergence of SARS-CoV-2 recombinants is of particular concern as they can result in a sudden increase in immune evasion due to antigenic shift. Recent recombinants XBB and XBB.1.5 have higher transmissibility than previous recombinants such as “Deltacron.” We hypothesized that immunity to a SARS-CoV-2 recombinant depends on prior exposure to its parental strains. To test this hypothesis, we examined whether Delta or Omicron (BA.1 or BA.2) immunity conferred through infection, vaccination, or breakthrough infection could neutralize Deltacron and XBB/XBB.1.5 recombinants. We found that Delta, BA.1, or BA.2 breakthrough infections provided better immune protection against Deltacron and its parental strains than did the vaccine booster. None of the sera were effective at neutralizing the XBB lineage or its parent BA.2.75.2, except for the sera from the BA.2 breakthrough group. These results support our hypothesis. In turn, our findings underscore the importance of multivalent vaccines that correspond to the antigenic profile of circulating variants of concern and of variant-specific diagnostics that may guide public health and individual decisions in response to emerging SARS-CoV-2 recombinants.

AbstractBackground Hypertension has become increasingly prevalent in Chinese children and adolescents in recent decades, which affects growth and development of children, leads to cognitive decline and multiple target organ damage. Here, we assessed the impact of different body mass index (BMI) trajectories on the occurrence of hypertension in children and adolescents using a cohort study in Northeast China.Materials and methods Children and adolescents aged 5–18 years was extracted for physical examination in Fuxin City, Liaoning Province, China during the 2009–2015 period. A latent category growth mixed model (LCGMM) was used to classify BMI changes and analyze the effect of different BMI trajectories on the risk of occurrence of hypertension in these participants within 5 years.Results All participates were divided into five BMI trajectories by LCGMM method: slow increasing group (n = 2616, 30.8%), overweight and obesity (OW/OB) group (n = 1141, 13.4%), normal decreasing group (n = 232, 2.7%), stable normal group (n = 4383, 51.6%), and fast-increasing group (n = 120, 1.4%). Compared with the stable normal group, the slow increasing group [adjusted odds ratio (AOR): 1.610, 95% confidence interval (CI): 1.304–1.989], the OW/OB group (AOR: 3.172, 95% CI: 2.500–4.023) and the fast-increasing group (AOR: 2.708, 95% CI: 1.445–5.074) all increased the risk of developing hypertension in children and adolescents.Conclusion The potential of developing hypertension varies among groups of children aged 5–18 with different BMI trajectories. Children and adolescents in the normal BMI range (the slow growth group) still need to be aware of the change in BMI trajectory to stop or slow down the progression of BP abnormalities.

This study was conducted to examine the effects of two types microencapsulated Origanum oils (MOO) (HMOO: hot spray microencapsulated Origanum oils; CMOO: cold spray microencapsulated Origanum oils) supplemented at different levels (0, 100, 200, and 300 mg/kg) on growth performance, antioxidant ability, nonspecific immune responses, gut bacterial communities, gut histology, and disease resistance of juvenile largemouth black bass (mean body weight = 9.72 g). The growth performance were significantly improved in both HMOO and CMOO groups (P 0.05). A significant interaction between the microencapsulation techniques and dosages was observed in some parameters (e.g., CAT, SOD, GSH-PX, MDA, LYZ, AKP, and ACP) of serum, liver, and intestine, which were influenced by MOO dosage. The α diversity index (observed_species, Chao1, and ACE) of intestinal bacteria and the relative abundance of certain bacterial taxa (Fusobacteriota, Proteobacteria, Cetobacterium, Plesiomonas, and Romboutsia) were significantly affected by different MOO supplemental levels (P 0.05). Villus height and disease resistance increased in the HMOO groups with different MOO dosages (P 0.05). HMOO had more positive effects on villus height and disease resistance than CMOO. In conclusion, the effects of MOO on black bass were more dependent on the supplemental dosage than the microencapsulation techniques.

A study was conducted to evaluate the effects of dietary lentinan (LNT) on growth performance, nonspecific immunity and disease resistance to Aeromonas hydrophila in largemouth bass (Micropterus salmoides). Largemouth bass (initial weight: 10.31 ± 0.25 g) were divided into the CK, L1, L2, L3, L4 and L5 groups in triplicate and fed with diets containing LNT at 0%, 0.05%, 0.1%, 0.2%, 0.3% and 0.4% for eight weeks. Results showed that FBW, WGR, SGR and FE were significantly increased in the L3, L4 and L5 groups compared to the CK group. VSI, HSI, crude protein, crude fat and crude ash were similar among different treatment groups. Trypsin and lipase activities of intestinal tract were elevated in the L4 and L5 groups. The length of intestinal microvilli was increased in all experimental groups (P

This paper investigates the terrain-following problem for an autonomous underwater vehicle (AUV) from control perspectives with full consideration of terrain characteristics. By equipping the AUV with three simple single-beam echo sounders, a set of precise along-track bottom slopes are obtained in a real-time manner, and the occurrence of the lost bottom lock phenomenon caused by a single sonar altimeter is eliminated. A slope-based data processing method is developed, which enables an AUV to characterize seafloor features with complementary sensing modalities to generate proper adaptive height-modified values. In order to keep a fixed height when maneuvering over rugged terrains, a back-stepping depth control is implemented by adjusting horizontal rudder angle, and Lyapunov theory is adopted to analyze the asymptotic stability of the resulting terrain-following control system. At last, simulation results indicate the feasibility and effectiveness of the proposed methodology with a discussion of various sensor configurations.

In view of the defects in the previous detection of cuaminosulfate, which only focused on the analysis of copper ions, there is currently no analysis method available to determine the actual state of cuaminosulfate as chelated or bound. In order to investigate the dissipation and terminal residues in soil and watermelon of cuaminosulfate for food safety and environmental risk, a highly effective technique was developed to detect cuaminosulfate residues in watermelon and soil, and field experiments were conducted in China. After single-factor experiments, residual cuaminosulfate in samples was extracted by pure water, purified using a liquid–liquid approach combined with a dispersive solid-phase extraction, and detected by liquid chromatography tandem mass spectrometry (LC-MS/MS). The Box–Behnken design (BBD) study was used to find the optimal solutions for the time of liquid–liquid purification, the amount of extraction solvent, and the amounts of cleanup sorbents for the analytical method. The average recovery of the method was in the range of 80.0% to 101.1%, the average relative standard deviation (RSD) was 5.3–9.9%, and the detection limit was lower than 0.05 mg/kg. The BBD study not only improved the extraction rate of the method, but also saved time and was operated easily. The final residues of cuaminosulfate in watermelon at different sampling intervals were all lower than 0.05 mg/kg under field conditions. The cuaminosulfate in soils dissipated following exponential kinetics, with half-life values in the range of 9.39 to 12.58 days, which varied by different locations. Based on the validated method, food safety residues and soil residues can be determined rapidly and accurately.

To resolve photons hungry for weak diffraction samples by the crystallographic method, a double-multilayer monochromator (DMM) was employed on an undulator beamline (BL17UM) at the Shanghai Synchrotron Radiation Facility (SSRF) to provide a focused sub-micron beam with high brightness for macromolecular crystallography experiments. High-quality crystallographic datasets from model protein crystal samples were collected and processed by an existing crystallographic program for structure solution and refinement. The data quality was compared with datasets from a normal silicon crystal monochromator to evaluate the bandwidth of the DMM effect on these crystallographic data. This experiment demonstrates that multilayer optics on an undulator beamline may play a valuable role in satisfying the demands of structure-related research, which requires novel methods.

BackgroundOver the last few decades, although the age-standardized mortality rate (ASMR) of injury has shown a significant declining trend in China, this pattern has dramatically reversed recently. ObjectiveWe aimed to elucidate the geographical, demographic, and temporal trends of cause-specific injuries, the reversal phenomenon of these trends, and the fluctuations of injury burden from 2005 to 2019 in China. MethodsA longitudinal observational study was performed using the raw data of injury deaths in the National Cause-of-Death surveillance data provided by the disease surveillance points system in 2005-2019. The cause-specific injuries were divided into disparate subgroups by sex, age, urban/rural region, and eastern/central/western areas of China. The burden of injury was assessed using potential years of life lost (PYLL), average years of life lost (AYLL), and PYLL rate (PYLLR). Temporal trends of mortality rates and burden were evaluated using best-fitting joinpoint models. ResultsInjury deaths accounted for 7.51% (1,156,504/15,403,835) of all-cause deaths in China in 2005-2019. The crude mortality rate of all-cause injury was 47.74 per 100,000 persons. The top 3 injury types (traffic accident, falls, and suicide) accounted for 70.57% (816,145/1,156,504) of all injury-related deaths. The ASMR of all-cause injury decreased (P=.003), while the crude mortality rate remained unchanged (P=.52) during 2005-2019. A significant reverse trend in ASMR of all-cause injury was observed in urban older adults since 2013, mainly due to the inverted trend in injuries from falls. A reverse trend in ASMR of suicide was observed among individuals aged 10-24 years, with notable increases by 35.18% (annual percentage change 15.4%, 95% CI 4.1%-28.0%) in men since 2017. The AYLL and PYLLR of all-cause injury among older adults showed consistent ascending trends from 2005 to 2019 (average annual percentage change [AAPC] 6.1%, 95% CI 5.4%-6.9%, 129.04% increase for AYLL; AAPC 5.4%, 95% CI 2.4%-8.4%, 105.52% increase for PYLLR). The AYLL due to suicide for individuals aged 10-24 years showed a considerable upswing tendency (AAPC 0.5%, 95% CI 0.4%-0.7%, 8.02% increase). ConclusionsAlthough the ASMR of all-cause injury decreased in China from 2005 to 2019, the trend in suicide among adolescents and young adults and falls among older adults has been on the rise in recent years. Interventions should be encouraged to mitigate the cause-specific burdens of injury death.

How to efficiently and quickly train large-scale AI models has become a hot topic in recent deep learning. Mixed-precision training is an effective technique to speed up training and reduce memory usage. At present, the automatic mixed-precision training method mainly uses half-precision (FP16) for the matrix operations of forward and backward propagation of the entire model and accumulates the FP32 weight copies to avoid rounding errors. However, this method is not optimized for each layer individually, leading to poor convergence in large-scale model training because different layers have different data patterns. Therefore, this paper proposes a layered mixed-precision training method, which can flexibly adjust training precisions according to the contribution of each layer to the training effect. Applying the layered mixed-precision method, the ResNet model achieves a 1.9× speedup compared to the baseline and a lower percentage of accuracy loss. In addition, this paper combines the layered mixed-precision method with distributed training strategies. Combining data parallel training, the model achieves a 3.74× speedup by using four Tesla V100 GPUs. The applicability of the layered mixed-precision method in model parallel training has been verified. Combining optimized pipeline parallel training, the model achieves a 3.26× speedup by using three Tesla V100 GPUs.

The nonuniform emissivity of material surface will adversely affect the detection results of the thermal imaging technology. Aiming at the influence of uneven emissivity on the dynamic detection mode of eddy current thermography, a suppression method based on edge detection is proposed in this paper. Since the traditional threshold selection methods are not ideal, a local adaptive threshold selection (LATS) method is applied in this study. This method can automatically obtain the optimal threshold for edge detection to suppress the influence of uneven emissivity. Roberts, Sobel, Prewitt, and Canny operators are tested by using LATS. The results show that Roberts, Sobel, and Prewitt operators can achieve the suppression effect, but the effect of Sobel and Prewitt are similar and better than Roberts.

2D multiferroic materials have garnered broad interests due to their magnetoelectric properties and multifunctional applications. Here, the authors discover a multiferroic feature in physical vapor deposition synthesized 2D metallic p-doped SnSe.

ObjectivesWe aimed to elucidate trends in the crude mortality rate (CMR), age-standardized mortality rate (ASMR), and burden of mental disorders (MD) in China.MethodsA longitudinal observational study was performed using the data of MD deaths in the National Disease Surveillance System (DSPs) during 2009–2019. The mortality rates were normalized using the Segis global population. Trends in the mortality of MDs stratified by age, gender, region, and residency, respectively. The burden of MD was evaluated using age-standardized person years of life loss per 100,000 people (SPYLLs) and average years of life lost (AYLL).ResultA total of 18,178 MD deaths occurred during 2009–2019, accounting for 0.13% of total deaths, and 68.3% of MD deaths occurred in rural areas. The CMR of MD in China was 0.75/100,00 persons (ASMR: 0.62/100,000 persons). The ASMR of all MDs decreased mainly due to the decrease in ASMR in rural residents. Schizophrenia and alcohol use disorder (AUD) were the leading causes of death in MD patients. The ASMR of schizophrenia and AUD was higher in rural residents than in urban residents. The ASMR of MD was highest in the 40–64 age group. As the leading causes of MD burden, the SPYLL and AYLL of schizophrenia were 7.76 person-years and 22.30 years, respectively.ConclusionAlthough the ASMR of all MDs decreased during 2009–2019, schizophrenia and AUD were still the most important causes of death for MDs. Targeted efforts focusing on men, rural residents, and the 40–64 years old population should be strengthened to decrease MD-related premature deaths.

The Ras GTPase-activating protein SH3 domain-binding protein (G3BP) belongs to the highly conserved family of RNA-binding proteins, which has been well-investigated in humans and animals. However, limited study of plant G3BP has been reported, and the precise biological function of the G3BP family has not been elucidated yet. In this study, the Arabidopsis G3BP family, comprising seven members, was comparatively analyzed. Transcriptome analysis showed that most G3BP genes are ubiquitously expressed in various tissues/organs. Transient expression analysis revealed that all G3BPs were presented in the cytoplasm, among which G3BP6 was additionally found in the nucleus. Further study revealed a conserved NLS motif required for the nuclear localization of G3BP6. Additionally, phenotypic analysis revealed that loss-of-function g3bp6 presented late-flowering phenotypes. RNA-sequencing analysis and qRT-PCR assays demonstrated that the expressions of abundant floral genes were significantly altered in g3bp6 plants. We also discovered that overexpression of G3BP6 in the nucleus, rather than in the cytoplasm, propelled bolting. Furthermore, we revealed that the scaffold protein Receptor for Activated C Kinase 1 (RACK1) interacted with and modulated the nuclear localization of G3BP6. Altogether, this study sheds new light on G3BP6 and its specific role in regulating the flowering transition in Arabidopsis.

Abstract Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that results from widespread immune complex deposition and secondary tissue injury. Hydroxychloroquine (HCQ) has been used clinically to treat SLE, while its exact mechanism has still remained elusive. Some studies have shown that myeloid-derived suppressor cells (MDSCs) play a vital role in the regulation of SLE. In this study, we aimed to explore the effects of HCQ on the apoptosis of MDSCs in lupus mice and its possible molecular regulatory mechanism. Methods We constructed the imiquimod (IMQ)-induced lupus model in mice. The proportion and apoptosis of MDSCs were measured by flow cytometry. CD81-overexpressed adeno-associated virus was intraperitoneally injected into the lupus mice. We also transfected the CD81 siRNA into bone marrow-derived MDSCs, and employed qRT-PCR and Western blotting to quantify the level of CD81. Results The results showed that HCQ ameliorated IMQ-induced lupus symptoms, and simultaneously inhibited the expansion of MDSCs. In particular, HCQ induced the apoptosis of MDSCs, and also up-regulated the expression level of CD81 in MDSCs, which might indicate the relationship between the expression level of CD81 and the apoptosis of MDSCs. CD81 was further confirmed to participate in the apoptosis of MDSCs and lupus disease progression by overexpressing CD81 in vivo. Molecular docking experiment further proved the targeting effect of HCQ on CD81. And then we interfered CD81 in bone marrow derived MDSCs in vitro, and it was revealed that HCQ rescued the decreased expression level of CD81 and relieved the immune imbalance of Th17/Treg cells. Conclusion In summary, HCQ promoted the apoptosis of MDSCs by up-regulating the expression level of CD81 in MDSCs, and ultimately alleviated lupus symptoms. Our results may assist scholars to develop further effective therapies for SLE.

Ablemma Roewer, 1963 is a species-rich genus of the family Tetrablemmidae O. Pickard-Cambridge, 1873, currently comprising 28 known species. This genus is mainly distributed in Southeast Asia. Currently, only one species, A. prominens Tong & Li, 2008 is known to occur in China.The species Ablemma shimojanai (Komatsu, 1968), presently only known from the Ryuku Islands in Japan, is reported from China for the first time on the basis of material collected in Guangdong Province. A morphological description and detailed images are provided.

Abstract Background Different methods of acetabular reconstruction with total hip arthroplasty (THA) for Crowe II and III of adult developmental dysplasia of the hip (DDH) acetabular bone defect have been implemented clinically. However, the biomechanical effect of different augmented materials for acetabular reconstruction in THA on shell stability has never been discussed. Methods In the present study, autologous bone graft (BG)and metal (Ti6Al4V) augment (MA) were simulated with several acetabular bone defect models of DDH in THA. The contact pressure and micromotion between the shell and host bone were measured for evaluating the shell stability using a finite element method. Results The peak contact stress between shell and host bone was higher in the MA situation (12.45 vs 8.71 MPa). And the load transfer path was different, for BG models, the high local contact stresses were found at the junction of bone graft and host bone while for MA models the concentrated contact stresses were at the surface of MA. The peak relative micromotion between shell and host bone was higher in the MA situation (12.61 vs 11.13 µm). However, the peak micromotion decreased in the contact interface of MA and cup compared to the BG models. Conclusions The higher micromotion was found in MA models, however, enough for bone ingrowth, and direct stronger fixation was achieved in the MA-cup interface. Thus, we recommended the MA can be used as an option, even for Crowe III, however, the decision should be made from clinical follow-up results.

Abstract Diffuse lower-grade gliomas (LGG) represent the highly heterogeneous and infiltrative neoplasms in the central nervous system (CNS). Replication factor C 2 (RFC2) is a subunit of the RFC complex that modulates DNA replication and repair. However, the prognosis value of RFC2 and its association with the immune signature of tumor microenvironment (TME) in LGG remains unknown. Based on Oncomine, TCGA, GTEx, TIMER, GEPIA, and HPA databases, we evaluated RFC2 expression levels and its clinical prognostic value in LGG and other cancers. Then we analyzed the correlations between RFC2 expression and tumor mutation burden (TMB), tumor microsatellite instability (MSI), and mismatch repair (MMR) genes across cancers. And CIBERSORT and ESTIMATE algorithms were conducted to estimate the association of RFC2 with immune cell infiltration of LGG. Additionally, we performed the functional enrichment analyses of RFC2 in LGG. Then functional experiments were employed to further validate the oncogenic role of RFC2 in LGG. Our results showed that RFC2 was widely highly expressed in most types of cancer. And its expression was closely related to the clinicopathological features and prognosis in LGG and other cancer types. RFC2 levels were also correlated with TMB and MSI across various cancers. Furthermore, RFC2 was positively associated with the infiltration levels of immune cells and immune checkpoint genes in LGG. Additionally, in vitro experiments revealed that RFC2 played an oncogenic role in LGG progression. In conclusion, our findings revealed that RFC2 could serve as a reliable biomarker to predict the prognosis and immune signature for LGG.

The Weather Research and Forecasting (WRF) model is a mesoscale numerical weather prediction system, which is widely used in major high-performance server platforms. This study focuses on the performance evaluation and optimization of WRF on Huawei’s self-developed kunpeng 920 processor platform, aiming to improve the operational efficiency of WRF. The results of the study show that the scalability of WRF on kunpeng 920 processor is well performed; the performance of WRF on kunpeng 920 processor is improved by 32.6% after invoking the Fast Math Library and Domain Decomposition Core Tile Division optimization. In terms of IO, the main optimizations are parallel IO and asynchronous IO. Eventually, the single output time of WRF is reduced from 37.28 s in serial IO mode to 0.14 s in asynchronous IO mode, and the overall running time is reduced from 1078.80 s to 807.94 s.

Geoscience, as an interdisciplinary field, is dedicated to revealing the operational mechanisms and evolutionary patterns of the Earth system [...]

The mortality rate from COVID-19 appears to be higher in solid organ transplant (SOT) recipients when compared with other populations. Vaccination is a key strategy to prevent the COVID-19 pandemic. However, it is unclear how readily SOT recipients will get vaccinated against COVID-19. We conducted an internet-based survey to investigate the vaccination willingness among Chinese SOT recipients and further explore possible influencing factors. Eight hundred and thirteen respondents participated in the survey. Overall, 46 (5.7%) recipients were vaccinated against COVID-19, while 767 (94.3%) were not. Among those not vaccinated, 175 (22.8%) intended to be vaccinated, while 592 (77.2%) were categorized as vaccine-hesitant. The most common reason for vaccination hesitancy is fear of preexisting comorbidities, followed by fear of side effects and doctors’ negative advice. Factors associated with vaccination willingness were as follows: with liver transplantation, the main source of information on COVID-19 vaccines was from medical doctors, scientists, and scientific journals, with at least college-level education, positive intention toward influenza vaccination during the current season, perceived importance of vaccination for SOT recipients, and having been vaccinated against influenza during the last season. Our survey indicated the necessity for SOT recipients to receive more comprehensive and accessible health education about vaccination and emphasized the critical role of transplantation physicians in promoting vaccine acceptance among SOT recipients. We hope that our survey results will help governments to better target communication in the ongoing COVID-19 vaccination campaign.

IntroductionRepeated hepatic arterial delivery of therapeutic agents to the liver by percutaneously implanted port-catheter systems has been widely used to treat unresectable liver cancer. This approach is applied to assess the therapeutic efficacy of repeated low-density lipoprotein-docosahexaenoic acid (LDL-DHA) nanoparticle treatments in a rat model of hepatocellular carcinoma.MethodsN1S1 hepatoma bearing rats underwent placement of a percutaneously implanted hepatic artery port-catheter system and were allocated to untreated, control LDL-triolein (LDL-TO) or LDL-DHA nanoparticle infusions groups. Treatments were performed every three days over a nine day study period. MRI was performed at baseline and throughout the study. At the end of the study tissue samples were collected for analyses.Results and DiscussionImplantation of the port catheters was successful in all rats. MRI showed that repeated infusions of LDL-DHA nanoparticles significantly impaired the growth of the rat hepatomas eventually leading to tumor regression. The tumors in the LDL-TO treated group showed delayed growth, while the untreated tumors grew steadily throughout the study. Histopathology and MRI support these findings demonstrating extensive tumor necrosis in LDL-DHA treated groups while the control groups displayed minor necrosis. Molecular and biochemical analyses also revealed that LDL-DHA treated tumors had increased levels of nuclear factor-kappa B and lipid peroxidation and depletion of glutathione peroxidase 4 relative to the control groups. Evidence of both ferroptosis and apoptosis tumor cell death was observed following LDL-DHA treatments. In conclusion repeated transarterial infusions of LDL-DHA nanoparticles provides sustained repression of tumor growth in a rat hepatoma model.

BackgroundPostoperative cognitive dysfunction (POCD) is a debilitating neurological complication in surgical patients. Current research has focused mainly on microglial activation, but less is known about the resultant neuronal synaptic changes. Recent studies have suggested that Sirtuin-1 (SIRT1) plays a critical role in several different neurological disorders via its involvement in microglial activation. In this study, we evaluate the effects of SIRT1 activation in a POCD mouse model.Materials and methodsExploratory laparotomy was performed in mice aged 12–14 months under sevoflurane anesthesia to establish our animal POCD model. Transcriptional changes in the hippocampus after anesthesia and surgery were evaluated by RNA sequencing. SIRT1 expression was verified by Western Blot. Mice were treated with SIRT1 agonist SRT1720 or vehicle after surgery. Changes in microglia morphology, microglial phagocytosis, presence of dystrophic neurites, and dendritic spine density were evaluated. Cognitive performance was evaluated using the Y maze and Morris water maze (MWM).ResultsSirtuin-1 expression levels were downregulated in POCD. Exposure to anesthesia and surgery lead to alteration in microglia morphology, increased synaptic engulfment, dendritic spine loss, and cognitive deficits. These effects were alleviated by SRT1720 administration.ConclusionThis study suggests an important neuroprotective role for SIRT1 in POCD pathogenesis. Increasing SIRT1 function represents a promising therapeutic strategy for prevention and treatment of POCD.

Background: Flurochloridone (FLC), a selective herbicide used on a global scale, has been reported to have male reproductive toxicity whose evidence is limited, but its mechanism remains unclear. The present study was conducted to systematically explore the male reproductive toxicity of FLC, including sperm quality, spermatogenesis, toxicity targets, and potential mechanisms. Methods: Male C57BL/6 mice aged 6–7 weeks received gavage administration of FLC (365/730 mg/kg/day) for 28 consecutive days. Then, the tissue and sperm of mice were collected for analysis. We measured the gonadosomatic index and analyzed sperm concentration, motility, malformation rate, and mitochondrial membrane potential (MMP). Spermatocyte immunofluorescence staining was performed to analyze meiosis. We also performed pathological staining on the testis and epididymis tissue and TUNEL staining, immunohistochemical analysis, and ultrastructural observation on the testicular tissue. Results: Results showed that FLC caused testicular weight reduction, dysfunction, and architectural damage in mice, but no significant adverse effect was found in the epididymis. The exposure interfered with spermatogonial proliferation and meiosis, affecting sperm concentration, motility, kinematic parameters, morphology, and MMP, decreasing sperm quality. Furthermore, mitochondrial damage and apoptosis of testicular Sertoli cells were observed in mice treated with FLC. Conclusion: We found that FLC has significant adverse effects on spermatogonial proliferation and meiosis. Meanwhile, apoptosis and mitochondrial damage may be the potential mechanism of Sertoli cell damage. Our study demonstrated that FLC could induce testicular Sertoli cell damage, leading to abnormal spermatogenesis, which decreased sperm quality. The data provided references for the toxicity risk and research methods of FLC application in the environment.

Abstract Glioma is the most frequent primary malignancy in the brain; temozolomide (TMZ) is the first-line chemotherapeutic agent used to combat this tumor. We showed here that astrocyte elevated gene-1 (AEG-1) was overexpressed in glioma tissues and associated with a worse subtype and a poor prognosis. CCK-8 proliferation assays and clone formation experiments presented that AEG-1 knockdown sensitizes glioma cells to TMZ. The γH2AX foci formation assays indicated that AEG-1 silencing promotes TMZ-induced DNA damage in glioma cells. Glioma-associated microglia/macrophages (GAMs), the largest subpopulation infiltrating glioma, play important roles in the tumor microenvironment. Bioinformatics analyses and functional studies demonstrated that AEG-1 silencing decreased M2-polarization of HMC3 microglia and the secretion of tumor supportive cytokines IL-6 and TGF-β1. The expression of AEG-1 was positively associated with M2 markers in glioma tissues varified by IHC staining. Based on the results of Affymetrix microarray and GSEA analyses, Western blot and Co-Immunoprecipitation assays were conducted to show that AEG-1 activates Wnt/β-catenin signaling by directly interacting with GSK-3β. The co-localization of AEG-1 and GSK-3β in the cytoplasm of glioma cells was detected through immunofluorescence staining. This study raises the possibility that targeting AEG-1 might improve the efficiency of chemotherapy and reduce immunosuppressive M2 GAMs in glioma.

Abstract Background Intertrochanteric curved varus osteotomy (CVO) has been widely used to remove the necrotic bone away from the weight-bearing portion in the treatment of osteonecrosis of the femoral head (ONFH). However, whether all types of necrosis will benefit from CVO, in terms of the stress level, the effect of different center-edge (CE) angles of acetabulum on stress distribution of necrosis after CVO, and the relationship between the intact ratio and the stress of necrosis, has never been addressed. The purpose of the study was to evaluate the influence of CVO on the stress reduction in necrotic bone using a finite element analysis (FEA) with different CE angles. Methods CVO finite element models of the hip joint were simulated with a lesion of 60°. The osteotomy angles were divided into four configurations (15°, 20°, 25°, and 30°), and three types (A, B, and C1) of lesions were established based on the Japanese Investigation Committee (JIC) classification. In addition, two CE angles (18° and 33°) of acetabulum were considered. The maximum and mean von Mises stress were analyzed in terms of the necrotic bone by a physiological loading condition. Moreover, the correlation of the intact ratio measured in 3D and the stress distribution after CVO was analyzed. Results Stress reduction was obtained after CVO. For type B, the CVO angle was 20° (0.61 MPa), and for type C1, the CVO angle was 30° (0.77 MPa), if the mean stress level was close to type A (0.61 MPa), as a standard. The maximum and mean von Mises stress were higher in the CE angle of 18°models, respectively. The intact ratio measured in 3D had a good negative correlation with stress after CVO and had more influence on stress distribution in comparison to other geometric parameters. Conclusions For making decisions about the biomechanics of CVO, a CVO angle of > 20° was recommended for type B and > 30° was safe for type C1. The risk of progressive collapse was increased in the insufficient situation of the weight-bearing portion after CVO. The intact ratio could provide information about clinical outcomes and stress distribution after CVO.

Background: The involvement of glycolysis in the regulation of the tumor immune microenvironment has become a novel research field. In this study, the specific functions and clinical significance of glycolysis-related genes (GRGs) and immune-related genes (IRGs) were systematically characterized in lung squamous cell carcinoma (LUSC).Methods: We evaluated the prognostic value, interactions, somatic mutations, and copy-number variations of GRGs and IRGs in LUSC from a dataset of The Cancer Genome Atlas (TCGA). An integrated glycolysis–immune score (GIS) model was generated by random forest algorithm and stepwise Cox regression analysis. The predictive power of the GIS was examined by survival analysis, receiver operating characteristics, univariate and multivariate analyses, and subgroup analysis. The correlations between GIS and biological functions, glycolysis, immune activity, immune cell infiltration, and genomic changes were analyzed, and the potential of GIS to guide clinical treatment decisions was evaluated.Results: A total of 54 prognostic GRGs and IRGs were identified, and a strong correlation was noted among them. However, most of them had somatic mutations and a high incidence of CNV. The GIS model that contained two GRGs (PYGB and MDH1) and three IRGs (TSLP, SERPIND1, and GDF2) was generated and a high GIS indicated poor survival. Moreover, we found that low GIS was associated with immune pathway activation, M1 macrophage infiltration, and higher immune scores. Finally, patients with low GIS were more sensitive to chemotherapy and immunotherapy.Conclusion: An integrated model based on glycolysis and immune genes can distinguish the biological functions and immune infiltration patterns of individual tumors, quantitatively estimate the prognosis of patients with LUSC, and guide chemotherapy and immunotherapy decisions.

BackgroundHypercalcemia induced by multiple myeloma (MM) affects the biological functions of excitable and non-excitable cells. However, red blood cells (RBCs) regulatory effect on calcium in hypercalcemia is still not fully understood.MethodsA total of 113 patients with MM osteolytic lesions were studied retrospectively. Flow cytometry and atomic absorption spectroscopy were used to detect calcium content. Immunofluorescence and Western blotting were used to investigate protein expression. GEO and miRNA databases were used to screen miRNAs. Exosomal miR-4261 migration was investigated by Transwell assay. Dual-luciferase assays confirmed the targeting relationship between miR-4261 and ATP2B4. An RBC oxidative stress model was constructed, and Omega-Agatoxin IVA was used to study the role of plasma membrane Ca2+-ATPase 4 (PMCA4) in RBCs.ResultsThe results showed that MM RBCs had calcium overload, and serum calcium levels increased as the number of RBCs decreased. The expression of PMCA4 in MM RBCs was significantly lower than in normal RBCs. The exosomal miR-4261 produced by MM cells could be transferred to RBCs to downregulate the expression of ATP2B4.ConclusionsStudies have confirmed that RBCs experience calcium overload in MM with osteolytic lesions, which is related to the downregulation of ATP2B4 by MM exosomal miR-4261.

Currently, braking control systems used in regional railways are open-loop systems, such as metro and tramways. Given that the performance of braking can be influenced by issues such as wheel sliding or the properties of the friction components present in brake systems, our study puts forward a novel closed-loop mechanism to autonomously stabilize braking performance. It is able to keep train deceleration close to the target values required by the braking control unit (BCU), especially in terms of the electrical–pneumatic braking transform process. This method fully considers the friction efficiency characteristics of brake pads and encompasses running tests using rolling stock. The test results show that the technique is able to stabilize the actual deceleration at a closer rate to the target deceleration than before and avoid wheel sliding protection (WSP) action, especially during low-speed periods.

Background: Maternal exposure to ambient fine particulate matters (PM2.5) is associated with low birth weight (LBW) in offspring, but the underlying biological mechanisms are not yet fully understood. As the bridge that connects mother and fetus, the placenta plays a crucial role in fetal development by providing the fetus with nutrients and oxygen. However, whether PM2.5 exposure would impact the placental development and the related mechanisms are unclear. Results: In the present study, female C57Bl/6j mice were exposed to filtered air (FA) or concentrated ambient PM2.5 (CAP) during pregestational and gestational periods, and the fetal development and placental structure were investigated. Our results showed that maternal exposure to CAP induced fetal growth restriction (FGR) and LBW. The placenta from CAP-exposed mice exhibited abnormal development including significant decrease of surface area, smaller junctional zone and impaired spiral artery remodeling. Meanwhile, CAP exposure altered trophoblast lineage differentiation and disrupted the balance between angiogenic and angiostatic factors in placenta. In addition, the inflammatory cytokines levels in lung, placenta and serum were significantly increased after ambient PM2.5 exposure. Conclusion: Our findings indicate that maternal exposure to PM2.5 disrupts normal structure and spiral artery remodeling of placenta and further induces FGR and LBW. This effect may be caused by the placental inflammation response subsequent to the pulmonary and systemic inflammation induced by ambient PM2.5 exposure.

In this study, the effect of choline chloride on intestinal microbiota and its association with the liver lipid accumulation were tested in zebrafish (Danio rerio) as a model. We performed a trial for six weeks on zebrafish dietary with high-lipid diets containing different choline chloride levels (0%, 0.2%, 0.4% and 0.6%; labelled as C0, C2, C4 and C6 treatment, respectively). The liver samples were collected for oil red O (ORO) staining at the 2nd, 4th and 6th week. The liver fatty infiltration were formed at the 2nd week and reached maximum proportion in C0 treatment at the 6th week, while the lowest proportion was present in C6 treatment. High-throughput sequencing was performed to characterise intestinal microbiota of fish fed C0 and C6 choline chloride. In comparison with C0 treatment, the relative abundances of Sphingomonas, Phyllobacterium and Bacteroides were increased in C6 treatment. Bacterial genes predicted that the flora of fish in C6 treatment was mainly concentrated in lipid metabolism, amino acid metabolism, xenobiotics biodegradation and metabolism. Thereafter, the gut microbiota of C0 or C6 treatment was transferred to germ-free (GF) 3 dpf (days post fertilisation) zebrafish and fed with high-lipid diet without choline. ORO revealed that the intestinal microbiota was contributed to reduce the liver lipid accumulation of fish accepted bacteria of C6 treatment (GFTC6). Transcriptome analysis showed that differentially expressed genes were mainly involved in dephosphorylation, lipid transport, lipid localisation and lipoprotein metabolic process in GFTC6 treatment. Our findings suggested a probable association between composition changes of intestinal microflora and liver fat accumulation in fish dietary with choline chloride.

The study focuses on the strategic decisions including on the location and capacity of stations and the fleet size for designing the one-way station-based carsharing systems. Under demand uncertainty, we introduce a two-stage risk-averse stochastic model to maximize the mean return and minimize the risk, where the conditional value-at-risk (CVaR) is specified as the risk measure. To solve the problem efficiently, a branch-and-cut algorithm and a scenario decomposition algorithm are developed. We conduct computational experiments based on historical use data and generate efficient frontiers so that the system operator can make a trade-off between return and risk. We then utilize an evaluation method to analyze the necessity of introducing risk. Finally, the efficiency of the proposed algorithms is elaborated through comparative experiments. Both branch-and-cut algorithm and scenario decomposition algorithm can tackle the small- and medium-scale problems well. For large-scale problems that cannot be solved by using an optimization solver or the branch-and-cut algorithm, scenario decomposition method can provide favorable solutions within a reasonable time.

As high performance computing technology continues to develop rapidly, graphics processing units (GPUs) are more widely used for daily computing tasks. However, some applications, such as weather forecasting, require large-scale computation. Thus, due to the computationally intensive characteristics of the rapid radiative transfer model for general circulation models (RRTMG) in the Earth system model, this study uses GPU-related technology to accelerate computation of the model. First, two kinds of algorithms using GPU technology to accelerate the RRTMG shortwave radiation scheme (RRTMG_SW) are proposed. Then, an optimization method for data transmission between host and device is proposed. Finally, after using CUDA Fortran and CUDA C to implement these algorithms, two GPU versions of RRTMG_SW, namely CF-RRTMG_SW (CUDA Fortran version) and CC-RRTMG_SW (CUDA C version), were developed. The experimental results demonstrate that the proposed acceleration algorithms are effective. Without I/O transfer, running CC-RRTMG_SW on a NVIDIA GeForce Titan V GPU achieved a $38.88\times $ speedup when compared to a single Intel Xeon E5-2680 CPU core.

Intrahepatic cholangiocarcinoma (ICC) is a highly lethal hepatobiliary neoplasm, which originates from the bile ducts proximal to the second-order division. ICC can be anatomically divided into two subtypes: the large duct type (mucin-production ICC, muc-ICC) and the small duct type (mixed-ICC) origins from hepatic progenitor cells (HPCs). The immunoreactivity of S100P and neural cell adhesion molecule (NCAM) are useful biomarkers to distinguish the two subtypes. In this study, we report a difficult-to-diagnose case of metastatic retroperitoneal tumor of occult hepatolithiasis-associated ICC. Besides, this case was both positive for S100P and NCAM, considered as a rare muc-ICC with the HPCs features. Tumor whole exome sequencing detection results by Genetron (China) revealed that there were 41 gene mutations in this patient. The SMAD4-p.His530ThrfsTer47 and KRAS-p.Gly12Val mutation might promote the occurrence and distant metastasis of the tumor.

Introduction: Evidence demonstrates that N6-methyladenosine (m6A) modification plays an increasingly important role in the development of tumors. The aim of this study is to explore the expression of m6A-related regulators in lung adenocarcinoma, identify the effect of altered key factors modified by m6A on the prognosis of patients with lung adenocarcinoma. Methods: A comprehensive analysis of m6A-related gene expressions in patients with lung adenocarcinoma based on The Cancer Genome Atlas database (TCGA) and the CBioPortal database. A prognostic risk score was established based on a linear combination of 4 key gene expression levels using the regression coefficients of the multivariate Cox regression models. Immunohistochemical staining analysis was performed to validate the relationship between the protein expression level of m6A regulators and the prognosis of patients retrospectively. The possible mechanism and prospective therapeutic targets of these key m6A molecules were explored by the M6A2Target database and the CMAP database. Results: Mutation pattern analysis revealed that 32% of 656 patients had genetic alterations. Four genes (writer: methyltransferase like 3 [METTL3] and three readers: insulin like growth factor 2 mRNA binding protein 2 [IGF2BP2], heterogeneous nuclear ribonucleoprotein C [HNRNPC], and heterogeneous nuclear ribonucleoprotein A2/B1 [HNRNPA2B1]) were selected to construct a survival risk prediction model and the results of immunohistochemical staining showed that the expression of these four m6A genes was significantly different between lung adenocarcinoma tissues and normal lung tissues ( p

The highly prevalent cognitive impairment in hemodialysis patients is associated with all-cause mortality; however, the role of different cognitive domain impairments in this association is still not clarified. Our objective was to determine the association between cognitive domain impairment and all-cause mortality in elderly adult patients undergoing hemodialysis. We conducted a prospective cohort study including patients from 11 hemodialysis centers in Beijing. Baseline data were collected, and a series of neuropsychological batteries covering 5 domains of cognitive function were included for the assessment of cognitive function. According to the fifth version of the Diagnostic and Statistical Manual of Mental Disorders criteria (DSM-V), the patients were classified as normal, mild, and major cognitive impairment for global and domain cognitive function, then followed up for 1 year. Kaplan–Meier survival analysis was used to compare the difference in the cumulative survival rate in different cognitive domains. A multivariate Cox proportional hazards regression analysis was used to determine the association between global or domain cognitive impairment and all-cause mortality. A total of 613 patients were enrolled, the mean age was 63.82 ± 7.14 years old, and 42.1% were women. After 49.53 ± 8.42 weeks of follow-up, 69 deaths occurred. Kaplan–Meier plots demonstrated a significant association of cognitive impairment in memory, executive function, attention, and language domains with all-cause death. Multivariate Cox regression analysis showed that mild and major impairment of global cognition (HR = 2.89 (95% CI, 1.01–8.34), p = 0.049 and HR = 4.35 (95% CI, 1.55–12.16), p = 0.005, respectively), executive cognitive domain (HR = 2.51 (95% CI, 1.20–5.24), p = 0.014; HR = 3.91 (95% CI, 1.70–9.03), p = 0.001, respectively), and memory cognitive domain (HR = 2.13 (95% CI, 1.07–4.24), p = 0.031; HR = 3.67 (95% CI, 1.71–7.92), p = 0.001, respectively) were associated with all-cause mortality. Combined impairment of 3, 4, and 5 cognitive domains was associated with all-cause mortality [HR = 5.75 (95% CI, 1.88–17.57), p = 0.002; HR = 12.42 (95% CI, 3.69–41.80), p < 0.001; HR = 13.48 (95% CI, 3.38–53.73), p < 0.001, respectively]. We demonstrate an association between the executive and memory cognitive domain impairment and all-cause mortality in hemodialysis patients. Our data suggest that the impairments in these cognitive domains might help in the early identification of hemodialysis patients at risk of death.

Background: Ambient fine particles (PM2.5) are known to cause various reproductive and developmental diseases. However, the potential mechanisms of PM2.5 exposure induced female reproductive damage remain unclear. Methods: Four weeks old female C57BL/6 J mice were exposed to filtered air (FA, n = 10) or concentrated ambient PM2.5 (CAP, n = 10) using a versatile aerosol concentration enrichment system. After 9 weeks of the exposure, mice were sacrificed under sevoflurane anesthesia and tissue samples were collected. Immunohistochemical analysis, enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, and RNA-sequencing were performed to analyze the effects of PM2.5 exposure on follicle development and elucidate its potential mechanisms. Results: Chronic PM2.5 exposure resulted in follicular dysplasia. Compared to the FA-exposed group, follicular atresia in the CAP-exposed mice were significantly increased. Further studies confirmed that CAP induced apoptosis in granulosa cells, accompanied by a distortion of hormone homeostasis. In addition, RNA-sequencing data demonstrated that CAP exposure induced the alteration of ovarian gene expressions and was associated with inflammatory response. Conclusions: Chronic exposure to CAP can induce follicular atresia, which was associated with hormone modulation and inflammation.

The new regionalism distinguishes itself from the old one that it has emerged from, amid new circumstances and is catalyzed by new impetus. Its appearance shows that the free-market economy is being challenged and that the market mechanism of resource allocation has again been taken over by political game. The United States and some major Western powers are attempting to secure their hegemony by minimizing spillover of critical technology and industry within controllable regions which would accelerate technological growth by creating effective market space. The battle over technology and industry is becoming the mainstream paradigm of major-country competition, which is being intensified by nation states’ concern over industrial security, techno-nationalism, and major-power politics — three main drivers of the new regionalism. While supporting globalization unswervingly, China has inevitably been affected by this widespread protectionism and is also embarking on the path of regional development. New regionalism could also provide another perspective to investigate the post-pandemic role of the Belt and Road Initiative and “dual circulation” strategy of China in order to consider the prospects of globalization.

Abstract Background The timing of when to initiate dialysis for progressive chronic kidney disease (CKD) patients has not been well established. There has been a strong trend for early dialysis initiation for these patients over the past decades. However, the perceived survival advantage of early dialysis has been questioned by a series of recent observational studies. The only randomized controlled trial (RCT) research on this issue found the all-cause mortality, comorbidities, and quality of life showed no difference between early and late dialysis starters. To better understand optimal timing for dialysis initiation, our research will evaluate the efficacy and safety of deferred dialysis initiation in a large Chinese population. Methods The trial adopts a multicenter, cluster randomized, single-blind (outcomes assessor), and endpoint-driven design. Eligible participants are 18–80 years old, in stable CKD stages 4–5 (eGFR > 7 ml/min /1.73 m2), and with good heart function (NYHA grade I or II). Participants will be randomized into a routine or deferred dialysis group. The reference eGFR at initiating dialysis for asymptomatic patients is 7 ml/min /1.73 m2 (routine dialysis group) and 5 ml/min/1.73 m2 or less (deferred dialysis group) in each group. The primary endpoint will be the difference of all-cause mortality and acute nonfatal cerebro-cardiovascular events between the two groups. The secondary outcomes include hospitalization rate and other safety indices. The primary and secondary outcomes will be analyzed by appropriate statistical methods. Discussion This study protocol represents a large, cluster randomized study evaluating deferred and routine dialysis intervention for an advanced CKD population. The reference eGFR to initiate dialysis for both treatment groups is targeted at less than 7 ml/min/1.73m2. With this design, we aim to eliminate lead-time and survivor bias and avoid selection bias and confounding factors. We acknowledge that the study has limitations. Even so, given the low-targeted eGFR values of both arms, this study still has potential economic, health, and scientific implications. This research is unique in that such a low targeted eGFR value has never been studied in a clinical trial. Trial registration The trial has been approved by ClinicalTrials.gov (Trial registration ID NCT02423655). The date of registration was April 22, 2015.