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Turbot (Scophthalmus maximus) is one of the most economically important fish in the northern coastal areas of China. Recently, low salinity stress is an important factor influencing the development of the turbot industry. Lately, the industry has faced challenges posed by low salinity stress, a key factor influencing turbot development. Salinity fluctuations represent a crucial environmental stressor in aquaculture, impacting osmotic pressure and inducing abnormal energy metabolism. Our preliminary research had identified that low salinity stress contributes to lipid metabolism disorders in turbot. This study aims to investigate the impact of varying lipid concentration levels on the lipid metabolism disorders induced by low salinity stress. To achieve this, feeding experiments were conducted with different lipid concentration levels under low salinity stress conditions, determining the optimal lipid requirement for turbot to cope with reduced salinity. Three salinity gradients (10, 20, and 30) were employed, with four lipid concentration gradients (8%, 12%, 16%, and 20%) for each salinity group. The results revealed that at a lipid concentration of 16%, no significant difference in the growth performance of juvenile turbot was observed between the salinities of 20 and 30. However, the growth performance under a salinity of 10 was lower than that under salinities of 20 and 30. Notably, under a salinity of 10, the growth performance of juvenile turbot increased with higher lipid concentrations, reaching its peak at 20%, surpassing values under the salinities of 20 and 30. Regarding the expression of genes related to lipid metabolism, under the salinities of 10 and 20, the expression levels of genes related to lipid synthesis, lxrα, cyp7a1, and srebp-1, showed a trend of first increasing and then decreasing with increasing lipid concentration, particularly under the salinity of 10. The expression level of the 12% lipid group was higher than that of other groups and the expression level of the 20% lipid group was significantly lower than that of other groups (P < 0.05). In addition, under a salinity of 10, the expression levels of acc and fas also showed a similar situation. They were both suppressed in the 20% lipid group, and the expression levels were higher in the 12% lipid group. The expression level of the gene apoa-IV related to lipid absorption in the 20% lipid group under a salinity of 10 was markedly higher than that in other groups under the same salinity conditions (P < 0.05) and it showed a change with salt under the condition of 20% lipid concentration. The increasing and decreasing trends were contrary to the trends in other lipid groups. The aforementioned results show that after low-salt stress affects lipid metabolism, feeds with different lipid concentrations can alleviate the adverse effects of the stress from the perspectives of lipid synthesis and lipid absorption, and this mitigation effect is more reflected at the level of lipid absorption, thereby improving growth performance under low salt stress. The results reveal the adaptability of fish to low salt from the perspective of salinity affecting lipid metabolism, enrich the concentration of fish stress physiology, and provide theoretical and technical support for the breeding of low-salt tolerant turbot varieties.

Abstract Background Septic shock is now the leading cause of mortality in intensive care units (ICUs). Refractory septic shock requires high doses of vasopressors. Some previous studies have revealed that methylene blue could improve hypotension status and help reduce the dosage of catecholamines. This study aims to investigate the clinical effect of methylene blue in septic shock and explore whether it can increase arterial pressure and reduce the usage of vasopressors. Methods This study is a multicenter, randomized, placebo-controlled trial planning to include 100 refractory septic shock patients. The protocol is to administer a bolus of 2 mg/kg methylene blue intravenously followed by a continuous infusion of 0.5 mg/kg/h for 48 h. The primary outcome is the total dose of vasopressor required in refractory septic shock in the first 48 h. Secondary outcomes include other hemodynamic parameters, oxygen metabolism indexes, tissue perfusion indexes, major organ function indexes, and certain plasma cytokines and other factors. Discussion This protocol aims to evaluate the safety and efficacy of methylene blue as adjuvant therapy for refractory septic shock. The main outcome measure will be vasopressor requirements and hemodynamic parameters. Additionally, bedside ultrasonography, blood gases, and cytokines will be assessed to evaluate perfusion, respiratory, and metabolic effects. The results are intended to provide evidence on the safety and efficacy of methylene blue in refractory septic shock, guiding clinical decision-making. Trial registration This clinical trial has been registered at ChiCTR ( https://www.chictr.org.cn/ ) on March 16, 2023. ChiCTR registration number: ChiCTR2300069430.

With the escalating prevalence of global heat waves, heat stroke has become a prominent health concern, leading to substantial liver damage. Unlike other forms of liver injury, heat stroke-induced damage is characterized by heat cytotoxicity and heightened inflammation, directly contributing to elevated mortality rates. While clinical assessments have identified elevated bilirubin levels as indicative of Kupffer cell dysfunction, their specific correlation with heat stroke liver injury remains unclear. Our hypothesis proposes the involvement of Kupffer cell ferroptosis during heat stroke, initiating IL-1β-mediated inflammation. Using single-cell RNA sequencing of murine macrophages, a distinct and highly susceptible Kupffer cell subtype, Clec4F+/CD206+, emerged, with heme oxygenase 1 (HMOX-1) playing a pivotal role. Mechanistically, heat-induced HMOX-1, regulated by early growth response factor 1, mediated ferroptosis in Kupffer cells, specifically in the Clec4F+/CD206+ subtype (KC2), activating phosphatidylinositol 4-kinase beta and promoting PI4P production. This cascade triggered NLRP3 inflammasome activation and maturation of IL-1β. These findings underscore the critical role of targeted therapy against HMOX-1 in ferroptosis within Kupffer cells, particularly in Clec4F+/CD206+ KCs. Such an approach has the potential to mitigate inflammation and alleviate acute liver injury in the context of heat stroke, offering a promising avenue for future therapeutic interventions.

Abstract Threaded fasteners are one of the most commonly used connection methods for mechanical structures. Its primary function is to generate appropriate clamping forces and fasten the connected parts. An inappropriate preload can cause loosening, fatigue fracture, and other problems. This will affect the safety and reliability of mechanical equipment. The precise control of the preload has become a critical issue in mechanical assembly processes. Over the past few decades, various tightening measures and methods have been proposed to address this issue. However, many problems continue to exist with practical applications that have not been reviewed comprehensively and systematically. First, various control methods were summarized systematically, and their advantages and disadvantages in engineering applications were analyzed. Torque control is the most widely used tightening method owing to its simple operation and low cost. Therefore, the research on the torque control method was summarized systematically from three aspects: the torque–preload correlation formula, effective friction radius, and friction characteristics during tightening. In addition, the special circumstances that may increase preload uncertainty were discussed. Finally, based on a summary of the current research status, the prospects for future research were discussed. This study would aid researchers in extensively understanding the problems in preload control.

Abstract Progressive familial intrahepatic cholestasis (PFIC) is a rare childhood manifested disease associated with impaired bile secretion with severe pruritus yellow stool, and sometimes hepatosplenomegaly. PFIC is caused by mutations in ATP8B1, ABCB11, ABCB4, TJP2, NR1H4, SLC51A, USP53, KIF12, ZFYVE19, and MYO5B genes depending on its type. ABCB11 mutations lead to PFIC2 that encodes the bile salt export pump (BSEP). Different mutations of ABCB11 have been reported in different population groups but no data available in Pakistani population being a consanguineous one. We sequenced coding exons of the ABCB11 gene along with its flanking regions in 66 unrelated Pakistani children along with parents with PFIC2 phenotype. We identified 20 variations of ABCB11: 12 in homozygous form, one compound heterozygous, and seven heterozygous. These variants include 11 missenses, two frameshifts, two nonsense mutations, and five splicing variants. Seven variants are novel candidate variants and are not detected in any of the 120 chromosomes from normal ethnically matched individuals. Insilico analysis revealed that four homozygous missense variations have high pathogenic scores. Minigene analysis of splicing variants showed exon skipping and the addition of exon. This data is a useful addition to the disease variants genomic database and would be used in the future to build a diagnostic algorithm.

Abstract Bio-inspired micro-air-vehicles (MAVs) usually operate in the atmospheric boundary layer at a low Reynolds number and complex wind conditions including large-scale turbulence, strong shear, and gusts. We develop an open jet facility (OJF) to meet the requirements of MAV flight experiments at very low speed and high turbulence intensity. Powered by a stage-driven fan, the OJF is capable of generating wind speeds covering 0.1 – 16.8 m/s, with a velocity ratio of 100:1. The contraction section of the OJF is designed using an adjoint-driven optimization method, resulting in a contraction ratio of 3:1 and a length-to-diameter ratio of 0.75. A modularized design of the jet nozzle can produce laminar or high-turbulence wind conditions. Flow field calibration results demonstrate that the OJF is capable of producing a high-quality baseline flow with steady airspeed as low as 0.1 m/s, uniform region around 80% of the cross-sectional test area, and turbulence intensity around 0.5%. Equipped with an optimized active grid (AG), the OJF can reproduce controllable, fully-developed turbulent wind conditions with the turbulence intensity up to 24%, energy spectrum satisfying the five-thirds power law, and the uniform region close to 70% of the cross-sectional area of the test section. The turbulence intensity, integral length scale, Kolmogorov length scale, and mean energy dissipation rate of the generated flow can be adjusted by varying the area of the triangular through-hole in the wings of the AG.

Abstract Scientific data are essential to advancing scientific knowledge and are increasingly valued as scholarly output. Understanding what drives dataset downloads is crucial for their effective dissemination and reuse. Our study, analysing 55,473 datasets from 69 data repositories, identifies key factors driving dataset downloads, focusing on interpretability, reliability, and accessibility. We find that while lengthy descriptive texts can deter users due to complexity and time requirements, readability boosts a dataset’s appeal. Reliability, evidenced by factors like institutional reputation and citation counts of related papers, also significantly increases a dataset’s attractiveness and usage. Additionally, our research shows that open access to datasets increases their downloads and amplifies the importance of interpretability and reliability. This indicates that easy access enhances the overall attractiveness and usage of datasets in the scholarly community. By emphasizing interpretability, reliability, and accessibility, this study offers a comprehensive framework for future research and guides data management practices toward ensuring clarity, credibility, and open access to maximize the impact of scientific datasets.

Abstract Neutrophil reverse migration (rM) is a recently identified phenomenon in which neutrophils migrate away from the inflammatory site back into the vasculature following initial infiltration, which involved in the resolution of loci inflammatory response or dissemination of inflammation. Present study was aimed to explore the mechanisms in neutrophil rM. By scRNA-seq on the white blood cells in acute lung injury model, we found rM-ed neutrophils exhibited increased gene expression of C–C motif chemokine receptor-like 2 (Ccrl2), an atypical chemokine receptor. Furthermore, an air pouch model was established to directly track rM-ed neutrophils in vivo. Air pouches were generated by 3 ml filtered sterile air injected subcutaneously for 3 days, and then LPS (2 mg/kg) was injected into the pouches to mimic the inflammatory state. For the rM-ed neutrophil tracking system, cell tracker CMFDA were injected into the air pouch to stain the inflammatory loci cells, and after 6 h, stained cells in blood were regarded as the rM-ed neutrophil. Based on this tracking system, we confirmed that rM-ed neutrophils showed increased CCRL2. We also found that the concentrations of the CCRL2 ligand chemerin in plasma was increased in the late stage. Neutralizing chemerin decreased the rM-ed neutrophil ratio in the blood. These results suggest that circulating chemerin attracts neutrophils to leave inflammatory sites by interacting with CCRL2, which might involve in the dissemination of inflammation.

Background: Brain injury often results in high mortality rates and significant sequelae following severe heatstroke (HS). Neuroinflammation aggravates HS-induced brain injury, yet the involvement of microglia in heat-induced neuroinflammation deserves further investigation. Methods: Our study investigated activation status, phenotype markers, production of pro-inflammatory cytokine and reactive oxygen species (ROS) of microglia both in vitro and in vivo under HS. Utilizing high-throughput sequencing, we identified SIRT1 as a potential modulator of microglia phenotype, and observed that SIRT1 alleviated severe heatstroke-induced brain injury following intraperitoneal administration of the SIRT1 agonist SRT-1720 and the inhibitor selisistat. Additionally, the effects of SRT-1720 and selisistat on mitochondrial dynamics and microglial phenotype transition were examined in BV2 cells in vitro. Results: Heatstroke promotes microglia activation, as evidenced by the increased production of pro-inflammatory cytokine and reactive oxygen species. High-throughput sequencing revealed elevated expression of SIRT1 in BV2 cells under HS. Upon inhibition of SIRT1 expression, there was a corresponding increase in pro-inflammatory cytokine, iNOS, and ROS expression in BV2 cells. In vivo experiments with the SIRT1 agonist SRT-1720 showed a mitigation of neuron injury under HS, as assessed by Nissl and HE staining. Activation of SIRT1 was associated with a reduction in mitochondrial injury and a decrease in the phosphorylation of mitochondrial fission protein Drp1ser616. Furthermore, the heat-induced activation of microglia was reversed by the Drp1 inhibitor, Mdivi. Conclusions: Our findings provided evidence that SIRT1 played a crucial role in inhibiting heat stress-induced microglial activation. By suppressing the phosphorylation of mitochondrial fission protein Drp1, SIRT1 contributed to the reduction of neuroinflammation and severity of heatstroke-induced brain injury.

Human activities frequently interfere with the natural environment, and environmental problems have become increasingly prominent. How to characterize the ecological compensation (EC) standard and how to quantify the coupling relationship between EC and economic development (ED) are still problems that need to be solved in research on EC mechanisms. We used 19 provincial-level administrative regions in the Yangtze River Basin (YRB) as the research area, calculated the EC standard based on the opportunity cost method, and analyzed the changes in the EC time series. The EC and ED coupling stage and coupling coordination type are determined by introducing the coupling coordination degree model in the YRB. Five scenarios, i.e., sustainability (SSP1), middle of the road (SSP2), regional rivalry (SSP3), inequality (SSP4), and fossil-fueled development (SSP5), were set on the basis of system dynamics and the shared socioeconomic pathways framework to simulate the evolutionary trends of EC and ED in the YRB. The results showed that (1) both direct and indirect opportunity costs in the YRB increased during 2010–2020. (2) In general, the EC and ED coupling coordination level was relatively low, but a good trend is expected to develop over time. (3) Different scenarios and policy-oriented development paths directly affect the change trends of EC and ED. (4) Taking SSP2 as the benchmark, the change trends of the other four scenarios were compared and analyzed. The changes in EC and GDP under SSP1 and SSP5 were consistent, and both were greater than those under the other two scenarios. SSP5 had the most significant effect on economic growth, but it also required more investment in EC. In the SSP1 scenario, R&D investment is greater, and the advancement of science and technology is more beneficial for the environment and economic development. Among the variety of scenario simulations, SSP1 is the optimal scenario for developing the economy, the environment, and science and technology.

Abstract Background Acute lung injury (ALI) is strongly associated with hospitalization and mortality in patients with sepsis. Recent evidence suggests that pyroptosis mediated by NLRP3(NOD-, LRR- and pyrin domain-containing 3) inflammasome activation plays a key role in sepsis. However, the mechanism of NLRP3 inflammasome activation in sepsis-induced lung injury remains unclear. Results in this study, we demonstrated that NLRP3 inflammasome was activated by the down-regulation of heat shock protein family A member 8 (HSPA8) in Lipopolysaccharide (LPS) and adenosine triphosphate (ATP)-treated mouse alveolar epithelial cells (AECs). Geranylgeranylacetone (GGA)-induced HSPA8 overexpression in cecum ligation and puncture (CLP) mice could significantly reduce systemic inflammatory response and mortality, effectively protect lung function, whilst HSPA8 inhibitor VER155008 aggravated this effect. The inhibition of HSPA8 was involved in sepsis induced acute lung injury by promoting pyroptosis of AECs. The down-regulation of HSPA8 activated NLRP3 inflammasome to mediate pyroptosis by promoting the degradation of E3 ubiquitin ligase S-phase kinase-associated protein 2 (SKP2). In addition, when stimulated by LPS and ATP, down-regulated SKP2 promoted pyroptosis of AECs by further attenuating ubiquitination of NLRP3. Adeno-associated virus 9-SKP2(AAV9-SKP2) could promote NLRP3 ubiquitination and degradation, alleviate lung injury and inhibit systemic inflammatory response in vivo. Conclusion in summary, our study shows there is strong statistical evidence that the suppression of HSPA8 mediates alveolar epithelial pyroptosis by promoting the degradation of E3 ubiquitin ligase SKP2 and subsequently attenuating the ubiquitination of NLRP3 to activate the NLRP3 inflammasome, which provides a new perspective and therapeutic target for the treatment of sepsis-induced lung injury.

Abstract Radiofrequency ablation (RFA) comparative efficacy of treatments using video-assisted thoracoscopic sympathectomy (VATS) in the long term remains uncertain in patients with palmar hyperhidrosis (PHH). This study aimed to compare the efficacy and safety of RFA and VATS in patients with PHH. We recruited patients aged ≥ 14 years with diagnosed PHH from 14 centres in China. The treatment options of RFA or VATS were assigned to two cohort in patients with PHH. The primary outcome was the efficacy at 1-year. A total of 807 patients were enrolled. After propensity score matching, the rate of complete remission was lower in RFA group than VATS group (95% CI 0.21–0.57; p

Loop-mediated isothermal amplification (LAMP) is a novel method for nucleic acid detection known for its isothermal properties, high efficiency, sensitivity, and specificity. LAMP employs 4 to 6 primers targeting 6 to 8 regions of the desired sequence, allowing for amplification at temperatures between 60 and 65°C and the production of up to 109 copies within a single hour. The product can be monitored by various methods such as turbidimetry, fluorometry, and colorimetry. However, it faces limitations such as the risk of non-specific amplification, challenges in primer design, unsuitability for short gene sequences, and difficulty in multiplexing. Recent advancements in polymerase and primer design have enhanced the speed and convenience of the LAMP reaction. Additionally, integrating LAMP with technologies like rolling circle amplification (RCA), recombinase polymerase amplification (RPA), and CRISPR-Cas systems has enhanced its efficiency. The combination of LAMP with various biosensors has enabled real-time analysis, broadening its application in point-of-care testing (POCT). Microfluidic technology has further facilitated the automation and miniaturization of LAMP assays, allowing for the simultaneous detection of multiple targets and preventing contamination. This review highlights advancements in LAMP, focusing on primer design, polymerase engineering, and its integration with other technologies. Continuous improvements and integration of LAMP with complementary technologies have significantly enhanced its diagnostic capabilities, making it a robust tool for rapid, sensitive, and specific nucleic acid detection with promising implications for healthcare, agriculture, and environmental monitoring.

Takifugu rubripes are warm temperate fish, suggesting that the reduced seawater temperatures in winter are likely to have a substantial impact on their survival. Considering this, there is likely to be some industrial value in breeding extremely low-temperature tolerant varieties of this fish. Here, we evaluate the expression changes in six major QTL candidate genes (tacc2, fsip1, exoc4, arhgap44a, pde10a, and unc5b) in response to reduced temperature in an effort to understand cold tolerance in T. rubripes. The expression changes of these six genes in the liver, heart, and kidney were detected using real-time quantitative PCR. This study used three groups of 8-month-old fish, all from the same family established by our research group, exposed to three different temperature gradients, where 8 ℃ and 13 ℃ acted as the minimum in the low temperature groups and 18 ℃ acted as the minimum in the control group. Our results showed that all six genes were expressed at different levels across each of these three tissues at different temperatures. The relative expression of pde10a first increased and then decreased in all three tissues, whereas the relative expression of tacc2 and exoc4 were distinctly different in the liver, kidney, and heart at 8 ℃. In this case, these transcripts first decreased and then stabilized in the liver, increased and then stabilized in the kidneys, and increased and then decreased in the heart. The relative expression of unc5b was low in the liver and heart, but high in the kidney following a second week of low-temperature growth, whereas arhgap44a expression was slightly upregulated in the liver and stable in the kidney and heart. fsip1 expression demonstrated a downward trend in the liver but seemed to first increase and then decrease in the heart and kidney. Taken together, these results demonstrate that all six of these genes are differentially expressed in different tissues of T. rubripes, with these differences exhibiting dynamic changes with respect to tissue origin and temperature. In addition, this data clearly revealed a positive correlation between cold stress and the expression of these QTL candidate genes. Thus, we can conclude that these six QTL candidate genes may play a substantial role in the low temperature adaptation of T. rubripes. This is significant because although low temperature is known to be an important factor limiting the development of the industrial utility of T. rubripes, there are still relatively few reports describing their cold stress response. This study provides a theoretical basis for the study of signaling pathways related to the low temperature tolerance response of T. rubripes and the development of low temperature tolerant varieties.

Considering that the degradation of ball screw grease involves fractal characteristics, which exhibit long-term dependency and autocorrelation, a multivariate accelerated degradation modeling and reliability assessment method based on the fractional Brownian motion process model is proposed in this paper. Firstly, a nonlinear accelerated degradation model of grease is established using fractional Brownian motion, considering the heterogeneity of samples as well as the memory effect and long-term dependence in the deterioration process, and realizing parameter estimation. Secondly, a multivariate reliability evaluation model is established by considering multivariate performance indicators in combination with the Frank copula function. Finally, the effectiveness and potential engineering application value of this method are verified through actual degradation data of the grease.

Proton magnetic resonance spectroscopy (1H-MRS) is the only non-invasive technique to quantify neurometabolic compounds in the living brain. We used 1H-MRS to evaluate the brain metabolites in a rat model of Sepsis-associated encephalopathy (SAE) established by cecal ligation and puncture (CLP). 36 male Sprague-Dawley rats were randomly divided into sham and CLP groups. Each group was further divided into three subgroups: subgroup O, subgroup M, and subgroup N. Neurological function assessments were performed on the animals in the subgroup O and subgroup N at 24 h, 48 h, and 72 h. The animals in the subgroup M were examined by magnetic resonance imaging (MRI) at 12 h after CLP. Compared with the sham group, the ratio of N-acetylaspartate (NAA) to creatine (Cr) in the hippocampus was significantly lower in the CLP group. The respective ratios of lactate (Lac), myo-inositol (mIns), glutamate and glutamine (Glx), lipid (Lip), and choline (Cho) to Cr in the CLP group were clearly higher than those in the sham group. Cytochrome c, intimately related to oxidative stress, was elevated in the CLP group. Neurofilament light (NfL) chain and glial fibrillary acidic protein (GFAP) scores in the CLP group were significantly higher than those in the sham group, while zonula occludens-1 (ZO-1) was downregulated. Compared with the sham group, the CLP group displayed higher values of oxygen extraction fraction (OEF), central venous–arterial partial pressure of carbon dioxide (P (cv-a) CO2), and central venous lactate (VLac). In contrast, jugular venous oxygen saturation (SjvO2) declined. In the present study, 1H-MRS could be used to quantitatively assess brain injury in terms of microcirculation disorder, oxidative stress, blood–brain barrier disruption, and glial cell activation through changes in metabolites within brain tissue.

Small-modulus gears, which are essential for motion transmission in precision instruments, present a measurement challenge due to their minuscule gear gaps. A high-precision measurement method under the influence of positioning errors is proposed, enabling precise evaluation of the machining quality of small-modulus gears. Firstly, a compound measurement platform for small-modulus gears is developed. Using a 3D model of the measurement system, the mathematical relationships governing motion transmission between various components are analyzed. Secondly, the formation mechanism of gear positioning error is revealed and its important influence on measurement accuracy is discussed. An optimization method for spatial coordinate transformation matrices under positioning errors of gears is proposed. Thirdly, the study focuses on small-sized gears with a modulus of 0.1 mm and a six-level accuracy. Based on the aforementioned measurement system, the tooth profile measurement points are collected in the actual workpiece coordinate system. Then, gear error parameters are extracted based on the established models for tooth profile deviation and pitch deviation. Finally, the accuracy and effectiveness of the proposed measurement method are verified by comparing the measurement results of the P26 gear measuring center.

A field determination method for small D-T neutron source yield based on the oxygen prompt gamma rays was established. A neutron-gamma transport equation of the determination device was developed. Two yield field determination devices with a thickness of 20 mm and 50 mm were made. The count rates of the oxygen prompt gamma rays were calculated using three energy spectra processing approaches, which were the characteristic peak of 6.13 MeV, the overlapping peak of 6.92 MeV and 7.12 MeV, and the total energy area. The R-square of the calibration curve is better than 94% and the maximum error of the yield test is 5.21%, demonstrating that it is feasible to measure the yield of D-T neutron source by oxygen prompt gamma rays. Additionally，the results meet the requirements for field determination of the conventional D-T neutron source yield.

Abstract Background Accurately predicting the occurrence of imminent new vertebral fractures (NVFs) in patients with osteoporotic vertebral compression fractures (OVCFs) undergoing vertebral augmentation (VA) is challenging with yet no effective approach. This study aim to examine a machine learning model based on radiomics signature and clinical factors in predicting imminent new vertebral fractures after vertebral augmentation. Methods A total of 235 eligible patients with OVCFs who underwent VA procedures were recruited from two independent institutions and categorized into three groups, including training set (n = 138), internal validation set (n = 59), and external validation set (n = 38). In the training set, radiomics features were computationally retrieved from L1 or adjacent vertebral body (T12 or L2) on T1-w MRI images, and a radiomics signature was constructed using the least absolute shrinkage and selection operator algorithm (LASSO). Predictive radiomics signature and clinical factors were fitted into two final prediction models using the random survival forest (RSF) algorithm or COX proportional hazard (CPH) analysis. Independent internal and external validation sets were used to validate the prediction models. Results The two prediction models were integrated with radiomics signature and intravertebral cleft (IVC). The RSF model with C-indices of 0.763, 0.773, and 0.731 and time-dependent AUC (2 years) of 0.855, 0.907, and 0.839 (p

Nano-silver (Ag) with ultra-small particle sizes have strong antibacterial activity because it can pass through the bacterial cell wall and enter the internal environment, causing irreversible damage to bacteria, but the disadvantages such as easy agglomeration and high toxicity alone limit its application. Therefore, In this study, by loading ∼ 3 nm ultrasmall particle sizes Ag (QDs) on the Fe3O4/Cu/CuO (FC) surface, core–shell type Fe3O4/Cu/CuO@Ag nanocomposite (FAN) was created. We used commercially available Bordeaux liquid (BM) as a control and targeted Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) to investigate the antibacterial activity of the material and its antibacterial mechanism. To examine the biocompatibility of materials with human cells and their effect on plant growth, the model plant employs mung bean as its objectives. The results showed that FAN can effectively inhibit E. coli and S. aureus for up to 99.99 % within 20 min, which is ten times greater than BM. It had a delaying effect on the adaptation period and logarithmic phase of bacterial growth, and could effectively destroy bacterial cell walls and respiratory enzymes. According to biocompatibility studies, FAN has little effect on lactation cells and can promote mung bean germination, root growth, and chlorophyll content with twice the efficiency of BM. This research opens the door to inhibition agents for bacterial control in applications.

Groundwater in southern China region contains various chemical compositions. By comparing the effects of acidic, neutral, and alkaline solutions on mechanical properties and internal structure, the changes in mechanical parameters and microstructure of chemical solution etched samples were obtained. The results show that as the pH of the solution increases from 2 to 12, the peak strength and elastic modulus of the rock samples initially increase and then decrease, while axial strain and Poisson’s ratio first decrease and then increase. The degree of deterioration of rock samples by different chemical solutions follows the order strong acid (pH ≤ 4) > strong alkali (pH ≥ 10) > weak acid (4 weak alkali (8 ≤ pH neutral (pH = 7). Alkaline and neutral solutions mainly corrode the surface of rock samples, with the wave velocity of the rock core higher than that of the surface. The wave velocities of alkaline solutions at different pH values after corrosion are essentially the same as that of pH = 7 neutral solution, ~2,850 m/s. Acidic solutions corrode both the surface and core of rock samples, with the wave velocities of the core and surface being similar. After corrosion by pH = 2 acidic solution, the wave velocity of the rock samples decreases to 2,505 m/s. With increasing acidity or alkalinity of the chemical solution, the internal pores of the rock transition from micropores to mesopores and macropores. Compared to pH = 7 neutral solution, the porosity of rock samples increases by 59.13% and 24.17% after corrosion by pH = 2 and pH = 12 solutions, respectively. Acidic and alkaline solutions exhibit distinct mechanisms: acidic solutions corrode particles and framework to form continuous fractures, whereas alkaline solutions generate new substances filling the fractures through hydration reactions. By introducing chemical damage variables and considering threshold factors, a chemical damage constitutive model is constructed to effectively describe the impact of chemical corrosion on mechanical properties. This systematic study of the chemical environment’s influence on internal structures reveals the erosion mechanisms of acidic, alkaline, and neutral saline solutions, which is crucial for the stability of underground engineering surrounding rocks and geological disaster prevention in southern China.

The red-bed soft rocks in South China have obvious creep characteristics and are prone to engineering geological disasters such as landslide and foundation settlement under the action of rainfall, groundwater, and load. In order to reveal its creep characteristics and mechanism under complex conditions, a step-loading creep test was carried out under chemical-stress-seepage coupling, and the energy evolution law of the whole creep process was analyzed based on linear energy storage and energy dissipation theory. The results also show that the acid chemical solution has the greatest influence on the triaxial strength and creep strength, and the creep damage and energy evolution of red-bed soft rock are universal. The creep damage and total strain increase with the increase of acidity, the decrease of confining pressure, and the increase of seepage pressure. The evolution law of creep damage shows the characteristics of slow-acceleration-rapid growth, and with the increase of load level, it has obvious transfer and accumulation. After entering the constant velocity creep stage, the damage rate begins to accelerate. The proportion of instantaneous strain and creep strain in the total strain increment is about 50%, and confining pressure has little influence on their respective proportions. The instantaneous strain is more sensitive to the acidity of the chemical solution, and the proportion of creep strain increases gradually with the increase of seepage pressure. The relationship between elastic energy density and total energy density is linear. The elastic energy density and dissipated energy density in the loading stage and creep stage all increase nonlinearly with loading time. The density of dissipated energy in the creep phase is lower than that in the loading phase, but the opposite is true in the higher stress phase, and the law of energy dissipation can explain the hardening damage effect in the creep process of soft rock samples. The research results provide a new perspective for us to reveal the mechanical properties and failure mechanism of red-bed soft rocks and provide an important theoretical basis for predicting and evaluating the creep instability and long-term stability of such rocks.

Translocation of 14-3-3 protein epsilon (14-3-3ε) was found to be involved in Triptolide (Tp)-induced inhibition of colorectal cancer (CRC) cell proliferation. However, the form of cell death induced by 14-3-3ε translocation and mechanisms underlying this effect remain unclear. This study employed label-free LC-MS/MS to identify 14-3-3ε-associated proteins in CRC cells treated with or without Tp. Our results confirmed that heterogeneous nuclear ribonucleoproteins C1/C2 (hnRNP C) were exported out of the nucleus by 14-3-3ε and degraded by ubiquitination. The nucleo-cytoplasmic shuttling of 14-3-3ε carrying hnRNP C mediated Tp-induced proliferation inhibition, cell cycle arrest and autophagic processes. These findings have broad implications for our understanding of 14-3-3ε function, provide an explanation for the mechanism of nucleo-cytoplasmic shuttling of hnRNP C and provide new insights into the complex regulation of autophagy.

The feed conversion rate (FCR) is a crucial economic trait in aquaculture fish, as feed costs account for the vast majority of aquaculture costs. Given the importance of this trait, there have little efforts to unravel the genomic architecture of FCR and identify key genes or genomic regions useful as selection makers. This situation may stem from the inherent swimming behavior of fish, which presents challenges in obtaining individual FCRs. In this work, we developed a specialized small cage culture system. Through this system, the Feed Conversion Ratio (FCR) of 300 individuals was successfully determined, marking the first successful determination of individual FCRs for turbot. The results revealed a range of FCR values from 35.3% to 192.6%, with an average of 126.5% ± 23.5%. On this basis, a genome-wide association study (GWAS) was conducted to identify single nucleotide polymorphisms (SNP) associated with FCR. A total of 2613,115 SNPs on 22 chromosomes were selected for GWAS analysis by Efficient Mixed-Model Association eXpedited (EMMAX) software. A linear mixed model was employed to test the association between each SNP and FCR, considering population structure and genetic relatedness among individuals. Two significant SNPs on Chr6 were identified to be correlated with FCR. According to their localization in genome, four candidate genes were identified on Chr6, including uncharacterized protein KIAA1755, Kinesin Family Member 21B (KIF21B), Discs large homolog-associated protein 4B (DLGAP4B), and Copine 5B (CPNE5B), all of which are closely located in the genome and exhibit significant functional similarities. Our results will facilitate the implementation of marker-assisted selection in breeding programs and serve as a foundation for future research in this area.

Environmental conditions regulate the growth and reproduction of fish. The increase in sea temperature during winter may have adverse effects on Takifugu rubripes. To study the mechanism of low-temperature tolerance of T. rubripes, the expression of antifreeze protein (AFP) gene, cold-induced RNA binding protein (CIRP) gene, high mobility group protein box-1 (HMGB1) gene, and Y-box binding protein (YB-1) gene in the liver, spleen, kidney, brain, heart, intestine, muscle, gonad, and skin tissues of T. rubripes obtained from different temperatures (18℃, 13℃, 8℃, and 5℃) was analyzed by quantitative real-time PCR. The results showed that the AFP gene was widely expressed in tissues, with the highest expression in the muscle (P < 0.05). With the decrease in temperature, the expression of the AFP gene in each tissue showed a significant increasing trend, reaching the highest value in the 5℃ group. The expression of the CIRP gene was the highest in the muscle (P < 0.05). With a decrease in temperature, the trend of CIRP gene expression in various tissues was different. The CIRP gene expression levels of liver, kidney, brain, heart, intestine, and skin showed a trend of initial increase, followed by a decrease, and then an increase. The expression levels in the spleen, muscle, and gonads showed an upward trend, reaching the highest value in the 5℃ group. The expression of the HMGB1 gene was the highest in muscle (P < 0.05), followed by that in the brain, liver, heart and skin. As the temperature decreased, the expression of the HMGB1 gene in all tissues except the liver increased first and then decreased, and reached the maximum value in the 8℃ group, which was significantly higher than that of the other groups (P < 0.05). The expression of the YB-1 gene was the highest in the muscle (P < 0.05), with the lowest expression level in other tissues. As the temperature decreased, the expression level of most tissues (brain, heart, intestine, kidney, liver, muscle, and spleen) increased first, then decreased, and then increased, reaching the minimum value in the 8℃ group (P < 0.05). These results show that the expression levels of the four genes are different at different temperature, reflecting the functional specificity of these four genes. Under low-temperature stress, these genes responded positively. Their expression changed to varying degrees, suggesting that the four genes may have potentially important roles in the adaptation of T. rubripes to low temperatures. In addition, by analyzing the law of gene expression, 8℃ may be the key regulatory point for T. rubripes to deal with low-temperature stress. Too low temperature may cause its regulation disorder. The results of this study can provide a relevant basis for studying the regulation mechanism of the low-temperature response of T. rubripes.

Abstract Subgrid data from earth system models are a powerful, yet underutilized, data resource for investigating the climatic impacts of land use and land cover change (LULCC). In this paper, we describe a global dataset on subgrid land surface climate variables produced by the Community Earth System Model in a fully coupled mode. The simulation was conducted at a 0.9° × 1.25° resolution under the Representative Concentration Pathway (RCP) 8.5 scenario from 2015 to 2100. Data are archived for eight subgrid tiles (urban, rural, tree, grass, shrub, bare soil, crop and lake) and include variables on the physical state, surface energy fluxes, runoff and atmospheric forcing conditions. Archival intervals are monthly, daily and hourly. Meta data on land surface parameters are also available. The data files are stored in NetCDF‐4 (Network Common Data Form, version 4) format and the meta data follow the latest Coupled Model Intercomparison Project phase 6 standards. We anticipate that this dataset will become a useful resource for characterizing local climate changes due to LULCC. This dataset can be downloaded from the Harvard Dataverse (https://doi.org/10.7910/DVN/HUXAH6).

Abstract Background To determine the diagnostic accuracy of a nanopore sequencing assay of PCR products from a M. tuberculosis complex-specific region for testing of bronchoalveolar lavage fluid (BALF) samples or sputum samples from suspected pulmonary tuberculosis (PTB) patients and compare the results to results obtained for MGIT and Xpert assays. Methods Cases with suspected PTB (n = 55) were diagnosed from January 2019 to December 2021 based on results of nanopore sequencing, MGIT culture, and Xpert MTB/RIF testing of BALF and sputum samples collected during hospitalization. Diagnostic accuracies of assays were compared. Results Ultimately, data from 29 PTB patients and 26 non-PTB cases were analyzed. PTB diagnostic sensitivities of MGIT, Xpert MTB/RIF, and nanopore sequencing assays were 48.28%, 41.38%, and 75.86%, respectively, thus demonstrating that nanopore sequencing provided greater sensitivity than was provided by MGIT culture and Xpert assays (P

In this paper, the stress–strain curves of Ti2AlNb are established based on uniaxial impact tests over wide ranges of temperature and strain rate. The Ti2AlNb exhibited the work hardening effect but did not show an obvious yield stage during a quasi-static compression test. In the SHPB test, an obvious temperature softening effect was found, the strain rate strengthening effect was detected when the strain rate was 4000–8000 s−1, and the strain rate softening effect was detected in the range of 8000–12,000 s−1. A function describing the effect of strain rate on the strain rate strengthening parameters under various temperatures was proposed to modify the basic J-C constitutive model. The relative errors between the experimental measured value and predicted values in various experimental conditions with a modified J-C model were less than 5.0%. The results verified that the modified J-C model could accurately describe the dynamic mechanical properties of Ti2AlNb at high temperatures and strain rates. The research could help to illustrate the cutting mechanism and finite element simulation of Ti2AlNb alloy.

For complex equipment, it is easy to over-evaluate the impact of failure on production by estimating the reliability level only through failure probability. To remedy this problem, this paper proposes a statistical evaluation method based on fuzzy failure data considering the multi-state characteristics of equipment failures. In this method, the new reliability-evaluation scheme is firstly presented based on the traditional statistical analysis method using the Weibull distribution function. For this scheme, the failure-grade index is defined, and a fuzzy-evaluation method is also proposed by comprehensively considering failure severity, failure maintenance, time, and cost; this is then combined with the time between failures to characterize the failure state. Based on the fuzzy failure data, an improved adaptive-failure small-sample-expansion method is proposed based on the classical bootstrap method and the deviation judgment between distributions of the original and newborn samples. Finally, a novel reliability-evaluation model, related to the failure grade and its membership degree, is established to quantify the reliability level of equipment more realistically. Example cases for three methods of the scheme (the failure-grade fuzzy-evaluation method, the sample-expansion method, and the reliability-evaluation modeling method) are presented, respectively, to validate the effectiveness and significance of the proposed reliability-evaluation technology.

This study aims to analyze the impact of uniform and eccentric load conditions on the performance of internal feedback hydrostatic thrust and journal bearing. Two distinct models are established: a three-degrees-of-freedom uniform load model and a five-degrees-of-freedom eccentric load model. The support stiffness, overturning stiffness, and flow rate for both thrust and journal bearings are calculated. Additionally, numerical analysis is conducted to examine the influence of oil film thickness, inlet pressure, and restrictor size on the operational characteristics of the bearings, revealing the interplay between an eccentric load and journal bearing speed. The validity of the theoretical algorithm is verified through finite element simulation. The research outcomes hold significant guiding implications for the design and application of internal feedback hydrostatic bearings.

The computer numerically controlled (CNC) system is the key functional component of CNC machine tool control systems, and the servo drive system is an important part of CNC systems. The complex working environment will lead to frequent failure of servo drive systems. Taking effective health management measures is the key to ensure the normal operation of CNC machine tools. In this paper, the comprehensive effect of fault prediction and fault diagnosis is considered for the first time, and a health management system for machine tool servo drive systems is proposed and applied to operation and maintenance management. According to the data collected by the system and related indicators, the technology can predict the state trend of equipment operation, identify the hidden fault characteristics in the data, and further diagnose the fault types. A health management system mainly includes fault prediction and fault diagnosis. The core of fault prediction is the gated recurrent unit (GRU). The attention mechanism is introduced into a GRU neural network, which can solve the long-term dependence problem and improve the model performance. At the same time, the Nadam optimizer is used to update the model parameters, which improves the convergence speed and generalization ability of the model and makes it suitable for solving the prediction problem of large-scale data. The core of fault diagnosis is the self-organizing mapping (SOM) neural network, which performs cluster analysis on data with different characteristics, to realize fault diagnosis. In addition, feature standardization and principal component analysis (PCA) are introduced to balance the influence of different feature scales, enhance the feature of fault data, and achieve data dimensionality reduction. Compared with the other two algorithms and their improved versions, the superiority of the health management system with high-dimensional data and the enhancement effect of fault identification are verified. The relative relationship between fault prediction and diagnosis is further revealed, and the adjustment idea of the production plan is provided for decision makers. The rationality and effectiveness of the system in practical application are verified by a series of tests of fault data sets.

Anorexia nervosa (AN) has a high mortality rate due to the widespread organ dysfunction caused by the underlying severe malnutrition. Malnutrition-induced hepatitis is common among individuals with AN especially as body mass index decreases, while acute liver failure and aplastic crisis related to coagulation disease and encephalopathy rarely occur in AN patients. The supervised increase of caloric intake can quickly improve the elevated aminotransferases caused by starvation and aplastic crisis. This current case report describes a 12-year-old adolescent girl who was admitted with a 3-month history of weight loss. Within 3 months, she had lost 10 kg of weight. The girl was diagnosed with AN, acute liver failure, severe malnutrition with emaciation, electrolyte disorder, bradycardia and aplastic crisis. She was gradually supplemented with vitamins and enteral nutrition to avoid refeeding syndrome. After treatment, her liver function and haematopoietic function returned to normal. In conclusion, acute liver failure and aplastic crisis are rare but potentially life-threatening complications of AN, which could be improved by supervised feeding and timely rehydration. AN should be considered as the potential aetiology of acute liver failure and aplastic crisis.

BackgroundThe web-based health question-and-answer (Q&A) community has become the primary and handy way for people to access health information and knowledge directly. ObjectiveThe objective of our study is to investigate how content-related, context-related, and user-related variables influence the answerability and popularity of health-related posts based on a user-dynamic, social network, and topic-dynamic semantic network, respectively. MethodsFull-scale data on health consultations were acquired from the Metafilter Q&A community. These variables were designed in terms of context, content, and contributors. Negative binomial regression models were used to examine the influence of these variables on the favorite and comment counts of a health-related post. ResultsA total of 18,099 post records were collected from a well-known Q&A community. The findings of this study include the following. Content-related variables have a strong impact on both the answerability and popularity of posts. Notably, sentiment values were positively related to favorite counts and negatively associated with comment counts. User-related variables significantly affected the answerability and popularity of posts. Specifically, participation intensity was positively related to comment count and negatively associated with favorite count. Sociability breadth only had a significant impact on comment count. Context-related variables have a more substantial influence on the popularity of posts than on their answerability. The topic diversity variable exhibits an inverse correlation with the comment count while manifesting a positive correlation with the favorite count. Nevertheless, topic intensity has a significant effect only on favorite count. ConclusionsThe research results not only reveal the factors influencing the answerability and popularity of health-related posts, which can help them obtain high-quality answers more efficiently, but also provide a theoretical basis for platform operators to enhance user engagement within health Q&A communities.

Background Currently, ferritin heavy chain (FTH1) has been increasingly found to play a crucial role in cancer as a core regulator of ferroptosis, while its role of non-ferroptosis in head and neck squamous cell carcinoma (HNSCC) is still unclear. Methods Herein, we analyzed the expression level of FTH1 in HNSCC using TCGA database, and FTH1 protein in HNSCC tissues and cell lines was determined by immunohistochemistry (IHC) and western blotting, respectively. Then, its prognostic value and relationship with clinical parameters were investigated in HNSCC patients. Additionally, the biological function of FTH1 in HNSCC was explored. Results The current study showed that FTH1 is significantly overexpressed in HNSCC tissues and related to poor prognosis and lymph node metastasis of HNSCC. FTH1 knockdown could suppress the metastasis and epithelial-mesenchymal transition (EMT) process of HNSCC. Conclusion Our findings indicate that FTH1 plays a critical role in the progression and metastasis of HNSCC and can serve as a promising prognostic factor and therapeutic target in HNSCC.

Abstract As the Earth's Third Pole and the Asian water tower, the Qinghai‐Tibet Plateau (QTP) plays a key role in global climate regulation and biodiversity maintenance. Living in harmony with nature is vital for local and global sustainable development. Current research on the conflicted or coordinated relationship between humans and nature on the QTP at a fine spatial scale remains limited. To fill the gap, we developed the human activity intensity index (HAI) and eco‐environmental quality index (EQI) at 1‐km resolution and proposed a four‐quadrant diagram approach to explore the dynamics between them. The results show a coordinated development on the QTP as the HAI and EQI both increased from 2000 to 2020, and the ratio of coordinated areas to conflicted areas was 5:1. High HAI areas were mainly in big cities such as Xining, Lhasa, Haidong, Xigaze, and along traffic lines. The significant conflicted areas were mainly outside the Lhasa metropolitan, south of the Hengduan Mountains, and along some new roads, and reduced by 8% between 2000–2010 and 2010–2020. The area of high HAI but low EQI was the smallest proportion, mainly in southern Qinghai Lake, southern Brahlung Zangbo River, Gobi oases, and western transport lines, but it implies the highest risk of ecosystem degradation. This research expands the fundamental methodology to address complex human‐natural relationships and provides implications for the sustainable development of fragile ecosystems.

Water scarcity is essentially caused by the spatiotemporal mismatch of water availability and water withdrawal. However, existing studies are still insufficient in revealing the spatiotemporal heterogeneity and rural–urban differences of global water scarcity and its influencing factors. Therefore, this study aims to fill this gap. From 1960 to 2014, both of the water-scarce population and its proportion in the total population showed a growth trend. The annual growth rate of water-scarce urban population was higher than that of water-scarce rural population, but the standard deviation of monthly water-scarce rural population was higher than that of water-scarce urban population. The proportion of water-scarce population was high and also variable across months in the middle- and low-latitude countries of the Northern Hemisphere, such as Pakistan, Mexico and Iran. Expansion of water-scarce areas had contributed to 60% of the global water-scarce population growth, while the relative contribution of population increases in the initial water-scarce catchments was about 40%. As for the expansion of water-scarce areas, the relative contributions of irrigation, domestic, and industrial water withdrawal were 35.28%, 24.28%, and 17.02%, respectively. In most high-latitude countries of the Northern Hemisphere, industrial water withdrawal was the main influencing factor. In several Southern Hemisphere countries, domestic water withdrawal was the most influential factor. In most Asian countries, the impact of irrigation water withdrawal was considerable. In addition, the impacts of water availability and irrigation water withdrawal were greatest in July, while the impacts of domestic and industrial water withdrawal were greatest in December. The relative contributions of water availability and irrigation water withdrawal were highly variable in Iran, Pakistan and India. The monthly variability in industrial water withdrawal was high in European countries. There was high variability in all influencing factors in China and some Central Asian countries. According to the variability of water scarcity and influencing factors, water-scarce countries should implement effective water resources management, based on the potential solutions such as the construction of water conservancy facilities, virtual water trade, and improving the efficiency of water use and recycling.

Introduction: Sepsis-induced apoptosis leads to lymphopenia including the decrease of CD4+ T cells thus favoring immunosuppression. Objectives: Although epidermal growth factor receptor (EGFR) inhibitors significantly improve the survival rate of septic mice, the effect of EGFR on the function and metabolism of CD4+ T cells in sepsis remained unknown. Methods: CD4+ T cells from septic mice and patients were assessed for apoptosis, activation, Warburg metabolism and glucose transporter 1 (Glut1) expression with or without the interference of EGFR activation. Results: EGFR facilitates CD4+ T cell activation and apoptosis through Glut1, which is a key enzyme that controls glycolysis in T cells. EGFR, TANK binding kinase 1 (TBK1) and Glut1 form a complex to facilitate Glut1 transportation from cytoplasm to cell surface. Both the levels of membrane expression of EGFR and Glut1 and the activation levels of CD4+ T cells were significantly higher in patients with sepsis as compared with healthy subjects. Conclusion: Our data demonstrated that through its downstream TBK1/Exo84/RalA protein system, EGFR regulates Glut1 transporting to the cell surface, which is a key step for inducing the Warburg effect and the subsequent cellular activation and apoptosis of CD4+ T lymphocytes and may eventually affect the immune functional status, causing immune cell exhaustion in sepsis.

External therapy, which has been used for millennia to treat disease, has now become the newest member of complementary and alternative therapies. A growing number of clinical studies and animal experiments have shown that external therapy exerts a positive effect on the intestinal flora. In this paper, we review the research related to external therapy on various systemic diseases and focus on changes in the intestinal flora. We found that studies on external therapy are dominated by acupuncture and tuina, primarily aimed at the treatment of digestive and neurological diseases. However, the deeper mechanism of regulation of the intestinal flora by external therapy has not yet been experimentally confirmed.

Objective Rhabdomyolysis (RM) in exertional heatstroke (EHS) often leads to multiple organ dysfunction including acute kidney injury (AKI). Studies have shown that serum creatine kinase (CK) >1000 U/L as a serological diagnostic criterion for RM does not reflect the risk of AKI or mortality.Methods This longitudinal cohort study included all patients with EHS who were admitted to intensive care unit between January 2008 and June 2019. Serum myoglobin (sMb) was studied as the serological marker of RM and compared with CK. Outcome events were AKI and 90-day mortality.Results A total of 161 patients were enrolled, of whom 52 (32.3%) had sMb ≥1000 ng/mL. Patients with sMb ≥1000 ng/mL had higher SOFA score, higher APACHE II score, lower GCS score, and higher incidence of disseminated intravascular coagulation, acute myocardial injury, acute liver injury, AKI, and 90-day mortality than patients with sMb

Abstract Background Rectal cancer is one of the most lethal of gastrointestinal malignancies. Metabonomics has gradually developed as a convenient, inexpensive and non-destructive technique for the study of cancers. Methods A total of 150 tissue samples from 25 rectal cancer patients were analyzed by liquid chromatography–mass spectrometry (LC–MS), and 6 tissue samples were collected from each patient (group 1: tumor; group 2: 0.5 cm from tumor; group 3:1 cm from tumor; group 4:2 cm from tumor; group 5:3 cm from tumor and group 6:5 cm from tumor). The differential metabolites of tumor tissues and 5 cm from the tumor (normal tissues) were first selected. The differential metabolites between tumor tissues and normal tissues were regrouped by hierarchical clustering analysis, and further selected by discriminant analysis according to the regrouping of clustering results. The potential safe margin of clinical T(cT)1,cT2 stage rectal cancer and cT3,cT4 stage rectal cancer at the metabolomic level was further identified by observing the changes in the level of differential metabolites within the samples from group 1 to group 6. Results We found 22 specific metabolites to distinguish tumor tissue and normal tissue. The most significant changes in metabolite levels were observed at 0.5 cm (cT1, cT2) and 2.0 cm (cT3, cT4) from the tumor, while the changes in the tissues afterwards showed a stable trend. Conclusions There are differential metabolites between tumor tissues and normal tissues in rectal cancer. Based on our limited sample size, the safe distal incision margin for rectal cancer surgery in metabolites may be 0.5 cm in patients with cT1 and cT2 stage rectal cancer and 2.0 cm in patients with cT3 and cT4 stage rectal cancer.

Sustainability of China’s numerous cities are threatened by both quantity- and quality-induced water scarcity, which can be measured by the water footprint from a consumption (WFcons) or production (WFprod) perspective. Although WFcons was widely assessed, the changes in WFprod of China’s cities were still unclear. A large-scale decrease in urban WFprod in China was found, with the average WFprod decreasing from 13.8 billion m3 to 10.3 billion m3 and the per capita WFprod decreasing from 1614.8 m3/person to 1184.0 m3/person (i.e., falling by more than a quarter in just six years). Such shrinkage was particularly evident in drylands, eliminating the water deficit in Xi’an and Xining. The reduction in grey WFprod caused by implementing water pollution prevention policies and other relevant measures played the most important role in the savings. In the future, the implementation of updated pollution discharge standards is projected to allow more cities to escape water deficits; however, the rapid growth of the domestic and ecological blue WFprod caused by urbanization and urban greening would destabilize this prospect. Thus, attention should be given to both water pollution prevention and domestic and ecological blue WFprod restriction to further alleviate urban water scarcity in China.

Ionic liquids (ILs) are molten organic salts consisting of organic cations and weakly coordinating organic/inorganic anions at room temperature. ILs have excellent physical and chemical properties such as high thermal stability, high combustible temperature, high miscibility with organic compounds and so on, making them good candidates for high performance lubricants and lubricant additives. The functional designability of ILs makes them novel lubrication materials that can break through the bottleneck of the active control of friction and lubrication. This paper firstly briefly introduces how to design the physical and chemical properties of the ILs required for different friction conditions by bonding specific cations with anions. Then, the lubrication mechanisms of ILs as base lubricants and additives for oils and water are focused on. The correlation between the structure of ILs and the lubrication results are established, which can guide the structural design of ILs in different applications. The response behaviors of friction characteristics under external electric fields are analyzed, which can provide a theoretical basis for the intelligent control of friction based on ILs.

The dual-drive ball screw pair serves as a crucial element within the fixed gantry machine tool with cross-rail movement. When in service, the dual-drive ball screw pair experiences variations in axial load, impacting the contact load distribution of the ball screw pair. A calculation model for determining the axial load offset of the dual-drive ball screw pair is proposed to investigate the variation in axial load. The impact of the geometric error associated with the guide rail and the position of the slide are considered. This paper presents the contact load distribution model for the dual-drive ball screw pair. This study investigates the contact load and contact angle distribution of the dual-drive ball screw pair during the machine tool in service. Additionally, based on fractal theory, the stiffness models of individual micro-convex body and contact surfaces have been established. This study provides a comprehensive analysis of the contact stiffness of the ball screw pair, considering the influence of guide rail geometric error and slide position. In addition, the three-dimensional surface morphology of ball screw pair is obtained by experiments. This paper investigates the contact stiffness distribution of dual-drive ball screw pair during service.

As increasingly extensive applications of flexible manufacturing systems (FMSs) arise, their reliability allocation has been a research hot spot. But, since FMSs are always composed of transfer and buffer devices, production machines, and complex control systems, the large number of basic elements makes the number of variables and constraints of reliability-allocation optimization increase greatly, which leads to the difficulty and inefficiency of optimization. To solve the above problem, two dimension-reduction strategies are proposed for the FMS reliability optimization with low cost and a high level of reliability as the objectives, and they are the reliability-weight double-threshold qualification strategy (RWTS) and the bi-level optimization strategy (BLOS), respectively. Based on these two strategies, an overall reliability-allocation optimization model and a bi-level reliability-allocation optimization model are established based on the FMS reliability evaluation presented in our previous work, and their algorithms based on particle swarm optimization (PSO) are presented. In terms of their contributions, for the RWTS, thresholds of reliability and the weight index of each basic element are set to dynamically reduce the number of variables in each iteration of the optimization; for the BLOS, the overall reliability-allocation optimization problem for transitioning from the FMS to basic elements can be transformed into simpler allocation optimizations from the FMS to subsystems and from subsystems to basic elements, which have fewer variables, and this can largely improve the optimization convergence performance. Through applying this to a box-parts finishing FMS, compared with the traditional optimization method, the high efficiency and the good allocation effect of the optimization based on these two strategies for improving convergence speed are verified by the simulation results. The proposed method has great significance for FMS design due to its limited cost but high-reliability requirement.

Abstract Hydrophilic polymer coatings on artificial implants generate excellent tribological properties. The friction properties of polymer coatings are affected by salt ion factors. Herein, the atomic force microscopy (AFM) was used to show that the superlubricity was achieved between poly(vinylphosphonic acid) (PVPA)-modified Ti6Al4V and polystyrene (PS) microsphere probe lubricated with monovalent salt solutions (LiCl, NaCl, KCl, and CsCl). Considering that adhesion is an important cause of friction changes, the AFM was further utilized to obtain adhesion between friction pairs in different salt solutions. The results indicated that the larger the cation radius in the lubricant, the smaller the adhesion, and the lower the friction coefficient of the PVPA coating. The electrostatic interaction between the PVPA and one-valence cations in lubricants was analyzed by the molecular dynamics (MD) simulation as it was found to be the main influencing factor of the adhesion. Combined analysis results of friction and adhesion indicated that by adjusting the size of cation radius in lubricant, the adhesion between the tribo-pairs can be changed, and eventually the magnitude of friction can be affected. This study opens up a new avenue for analyzing the friction characteristics of hydrophilic polymer coatings from the perspective of intermolecular forces.

The insufficient supply of sugar units is the key limitation for the biosynthesis of glycosylated products. The unusual sugar TDP-l-mycarose is initially attached to the C3 of the polyketide erythronolide B, resulting in 3-O-α-mycarosylerythronolide B (MEB). Here, we present the de novo biosynthesis of MEB in Escherichia coli and improve its production using multi-strategy metabolic engineering. Firstly, by blocking precursor glucose-1-phosphate competing pathways, the MEB titer of triple knockout strain QC13 was significantly enhanced to 41.2 mg/L, 9.8-fold to that produced by parental strain BAP230. Subsequently, the MEB production was further increased to 48.3 mg/L through overexpression of rfbA and rfbB. Moreover, the CRISPRi was implemented to promote the TDP-l-mycarose biosynthesis via repressing the glycolysis and TDP-l-rhamnose pathway. Our study paves the way for efficient production of erythromycins in E. coli and provides a promising platform that can be applied for biosynthesis of other glycosylated products with unusual sugars.

BackgroundBladder cancer is the ninth most common malignant tumor worldwide. As an effective evidence-based multidisciplinary protocol, the enhanced recovery after surgery (ERAS) program is practiced in many surgical disciplines. However, the function of ERAS after radical cystectomy remains controversial. This systematic review and meta-analysis aims to research the impact of ERAS on radical cystectomy.MethodsA systematic literature search on PubMed, EMBASE, SCOPUS, and the Cochrane Library databases was conducted in April 2022 to identify the studies that performed the ERAS program in radical cystectomy. Studies were selected, data extraction was performed independently by two reviewers, and quality was assessed using a random effects model to calculate the overall effect size. The odds ratio and standardized mean difference (SMD) with a 95% confidence interval (CI) served as the summary statistics for the meta-analysis. A sensitivity analysis was subsequently performed.ResultsA total of 25 studies with 4,083 patients were enrolled. The meta-analysis showed that the complications (OR = 0.76; 95% CI: 0.63–0.90), transfusion rate (OR = 0.59; 95% CI: 0.39–0.90), readmission rate (OR = 0.79; 95% CI: 0.64–0.96), length of stay (SMD = −0.79; 95% CI: −1.41 to −0.17), and time to first flatus (SMD = −1.16; 95% CI: −1.58 to −0.74) were significantly reduced in the ERAS group. However, no significance was found in 90-day mortality and urine leakage.ConclusionThe ERAS program for radical cystectomy can effectively decrease the risk of overall complications, postoperative ileus, readmission rate, transfusion rate, length of stay, and time to first flatus in patients who underwent radical cystectomy with relative safety.Systematic Review Registrationhttps://inplasy.com/, identifier INPLASY202250075.

BackgroundChildren with intractable functional constipation (IFC) who are refractory to traditional pharmacological intervention develop severe symptoms that can persist even in adulthood, resulting in a substantial deterioration in their quality of life. In order to better manage IFC patients, efficient subtyping of IFC into its three subtypes, normal transit constipation (NTC), outlet obstruction constipation (OOC), and slow transit constipation (STC), at early stages is crucial. With advancements in technology, machine learning can classify IFC early through the use of validated questionnaires and the different serum concentrations of gastrointestinal motility-related hormones.MethodA hundred and one children with IFC and 50 controls were enrolled in this study. Three supervised machine-learning methods, support vector machine, random forest, and light gradient boosting machine (LGBM), were used to classify children with IFC into the three subtypes based on their symptom severity, self-efficacy, and quality of life which were quantified using certified questionnaires and their serum concentrations of the gastrointestinal hormones evaluated with enzyme-linked immunosorbent assay. The accuracy of machine learning subtyping was evaluated with respect to radiopaque markers.ResultsOf 101 IFC patients, 37 had NTC, 49 had OOC, and 15 had STC. The variables significant for IFC subtype classification, according to SelectKBest, were stool frequency, the satisfaction domain of the Patient Assessment of Constipation Quality of Life questionnaire (PAC-QOL), the emotional self-efficacy for Functional Constipation questionnaire (SEFCQ), motilin serum concentration, and vasoactive intestinal peptide serum concentration. Among the three models, the LGBM model demonstrated an accuracy of 83.8%, a precision of 84.5%, a recall of 83.6%, a f1-score of 83.4%, and an area under the receiver operating characteristic curve (AUROC) of 0.89 in discriminating IFC subtypes.ConclusionUsing clinical characteristics measured by certified questionnaires and serum concentrations of the gastrointestinal hormones, machine learning can efficiently classify pediatric IFC into its three subtypes. Of the three models tested, the LGBM model is the most accurate model for the classification of IFC, with an accuracy of 83.8%, demonstrating that machine learning is an efficient tool for the management of IFC in children.

BackgroundChildhood functional constipation is a worldwide problem that affects the intestinal function of children and the quality of life of their families. Treatment and management of the disease need to be carried out at home by parents. Assessment of caregiving needs is an important link in planning and implementing the intervention. This study aimed to assess the caregiving needs of parents of FC infants and toddlers.MethodsThe researchers recruited convenience samples of parents from an outpatient pediatric constipation clinic of a children's medical center. Totally 211 fathers/mothers were recruited. Nursing needs were measured by a questionnaire, and associations between nursing needs and potential factors were examined using multiple regression analysis.ResultsThe vast majority of participants (88.7%) expressed the need of receiving support from professionals, and only 44 (20.85%) had obtained help from medical staff. The needs of parents mainly include information needs, health needs, psychological needs, and social needs. Of all the needs, the highest score was for information needs (3.87 ± 0.69), followed by the dimension of health needs (3.74 ± 0.82). Results showed statistically significant differences in parental education, place of residence, age of children, duration of FC, defecation frequency, difficulty of defecation, and stool traits in nursing needs (p