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Abstract Lung squamous cell carcinoma (LUSC) is associated with high mortality and has few therapeutic options. Chemotherapy remains the main treatment for LUSC patients, but multi-drug resistance has become the dominant challenge in the failure of chemotherapy in various cancers. Therefore, the effective therapeutic strategy for LUSC patients is an urgent unmet need. Here, we found vasohibin-2 (VASH2) was a prognostic biomarker for LUSC patients, and VASH2 promoted the malignant biological behaviors of LUSC cells and chemoresistance by increasing the detyrosination of α-tubulin. The high level of detyrosinated-tubulin was negatively associated with patient prognosis. Blocking the tubulin carboxypeptidase (TCP) activity of VASH2 inhibited the xenograft tumor growth and improved the treatment efficacy of paclitaxel in vivo. Results revealed that VASH2-induced increase in tubulin detyrosination boosted the binding of kinesin family member 3C (KIF3C) to microtubules and enhanced KIF3C-dependent endosomal recycling of EGFR, leading to the prolonged activation of PI3K/Akt/mTOR signaling. This study demonstrated that VASH2 was not only a prognostic biomarker but also a promising therapeutic target in LUSC, which offers a novel insight that combination of chemotherapy and EpoY, a TCP inhibitor, may be a promising treatment strategy for LUSC patients.

Abstract PA1895-1897 is a quorum sensing (QS) operon regulated by the anti-activator LuxR homologue QscR in Pseudomonas aeruginosa. We aimed to investigate its impact on bacterial metabolism, and whether it contributes to the delayed QS activation. We performed liquid chromatograph-mass spectrometer-based metabolomics using wildtype PAO1, PA1895-1897-knockout mutant, and mutant with pJN105.PA1895-1897 overexpression vector. The impact of metabolites on QS signaling molecule (3OC12-HSL and C4-HSL) concentrations, pyocyanin production, and QS gene (lasR, lasI, rhlR, and rhlI) expression was examined. Metabolomics analysis found that fatty acid biosynthesis had the highest fold enrichment among all metabolic pathways in PA1895-1897-overexpressed mutants. Among these enriched fatty acids, palmitoleic acid and acetic acid were the predominantly abundant ones that significantly affected by PA1895-1897 operon. When different doses of exogenous palmitoleic acid or acetic acid were added to the cultures of PA1895-1897 knockout mutants, their levels of 3OC12-HSL, C4-HSL, and pyocyanin were decreased in a dose-dependent manner. High doses of palmitoleic acid and acetic acid suppressed the mRNA expression of lasR, rhlR, and rhlI. Inhibition of fatty acid biosynthesis increased the production of 3OC12-HSL, C4-HSL, and pyocyanin in PA1895-1897-overexpressed cultures. Our data suggest that fatty acid synthesis is promoted by PA1895-1897 operon, and contributes the delayed expression of QS phenotypes, furthering the understanding about the regulation of bacterial QS activation.

Abstract Background Circular RNAs (circRNAs) can influence a variety of biological functions and act as a significant role in the progression and recurrence of glioblastoma (GBM). However, few coding circRNAs have been discovered in cancer, and their role in GBM is still unknown. The aim of this study was to identify coding circRNAs and explore their potential roles in the progression and recurrence of GBM. Methods CircSPECC1 was screened via circRNAs microarray of primary and recurrent GBM samples. To ascertain the characteristics and coding ability of circSPECC1, we conducted a number of experiments. Afterward, through in vivo and in vitro experiments, we investigated the biological functions of circSPECC1 and its encoded novel protein (SPECC1-415aa) in GBM, as well as their effects on TMZ sensitivity. Results By analyzing primary and recurrent GBM samples via circRNAs microarray, circSPECC1 was found to be a downregulated circRNA with coding potential in recurrent GBM compared with primary GBM. CircSPECC1 suppressed the proliferation, migration, invasion, and colony formation abilities of GBM cells by encoding a new protein known as SPECC1-415aa. CircSPECC1 restored TMZ sensitivity in TMZ-resistant GBM cells by encoding the new protein SPECC1-415aa. The m6A reader protein IGF2BP1 can bind to circSPECC1 to promote its expression and stability. Mechanistically, SPECC1-415aa can bind to ANXA2 and competitively inhibit the binding of ANXA2 to EGFR, thus resulting in the inhibition of the phosphorylation of EGFR (Tyr845) and its downstream pathway protein AKT (Ser473). In vivo experiments showed that the overexpression of circSPECC1 could combine with TMZ to treat TMZ-resistant GBM, thereby restoring the sensitivity of TMZ-resistant GBM to TMZ. Conclusions CircSPECC1 was downregulated in recurrent GBM compared with primary GBM. The m6A reader protein IGF2BP1 could promote the expression and stability of circSPECC1. The sequence of SPECC1-415aa, which is encoded by circSPECC1, can inhibit the binding of ANXA2 to EGFR by competitively binding to ANXA2 and inhibiting the phosphorylation of EGFR and AKT, thereby restoring the sensitivity of TMZ-resistant GBM cells to TMZ.

After the underground coal gasification is completed, a hyperbolic shaped coal pillar is formed between the two cavities to support the overlying rock and ensure the safety and stability of the gasification area. The work aimed to study the bearing mechanical characteristics of hyperbolic shaped coal pillar. Based on the acoustic emission (AE) monitoring system and the XTDIC 3D full-field strain measure system, 6 sets of “hyperbolic” coal samples with different lateral arch heights (h=0, 3 mm, 7 mm, 10 mm, 13 mm, 17 mm) were tested for uniaxial compression. The influence of h on peak load, deformation damage, and AE characteristics of coal samples were analyzed to reveal the bearing failure mechanism. The results are as follows. ① The “hyperbolic” coal sample can be divided into rectangular structure (main load-bearing body) and lateral arch structure, and its load-bearing failure mechanism is related to the force form and lateral arch structure. As h increases, the bearing capacity of the coal sample decreases. Compared with h=0 mm coal samples, the peak load was reduced by 7.66, 13.56, 26.83, 35.28, and 62.75%. ② The overall force form of coal samples changed from pressure-based to pressure-bending with increased h. Stress concentration occurs in the middle region of the coal sample, forming a weak area. The corresponding horizontal displacement field migrates towards the middle and finally at the edge of the middle. The vertical displacement field changed from a horizontal strip to an inclined strip, and ultimately concentrated at the upper end of the lateral arch structure of the coal sample. ③ Under axial load, the lateral arch structure of the coal sample exerts an equivalent force on the middle area of its rectangular structure, and is affected by the heterogeneity of the coal sample, which exacerbates the damage degree of the weak area in the middle. The effect increases with the increase of h, the coal sample undergoes shear failure when the load does not exceed its tensile strength. The failure mode of the coal samples shifted from tensile-shear mixed failure to shear failure, and all typical coal samples have experienced varying degrees of peeling and local ejection failure. ④ The evolution of the cumulative count-time curve of coal AE can be divided into three types. When h is 0 mm and 3 mm, it can be divided into four stages: “upward convex” growth, relatively rapid growth, rapid growth, and “sudden” growth, and its evolutionary characteristics are consistent with conventional rock samples. When h is 7 mm and 10 mm, it can be divided into three stages: relatively rapid growth, rapid growth, and “sudden” growth. When h is 13 mm and 17 mm, it can be divided into two stages: rapid growth and “sudden” growth. The post-peak stage shows a “sudden” growth pattern, while the inconsistent growth pattern in the pre-peak stage is caused by the stable expansion of coal sample cracks and continuous damage in the central region.

This study aims to quantitatively assess the adjustment effects of various visual guiding schemes on the abrupt change of vehicle trajectory. A driving simulation experiment was conducted using five simulated scenes: (1) baseline (actual situation), (2) pavement (road studs), (3) low position (flexible guideposts), (4) high position (warning alignment signs and retroreflective arches) and (5) multilayer (combination of all devices). Raw data, including vehicle positions, steering wheel angles and lateral offset, were collected. Based on these data, the gradual change degree of vehicle trajectory (G) and average steering wheel angle (SWAav) were computed to quantitatively evaluate the extent of vehicle trajectory deviation and the stability of steering wheel operations respectively. These two evaluation indicators were then translated into trajectory gradualness (TG) and operation stability (OS), respectively, to assess the adjustment effects of different visual guiding schemes. The study results demonstrate that road studs perform a certain degree of enhancement on operation stability (OS). Flexible guideposts exhibit the best effects on operation stability (OS). Additionally, the combination of warning alignment signs and retroreflective arches demonstrate the best regulation of trajectory gradualness (TG). Multilayer visual guiding system achieves the optimal trajectory gradualness (TG) and operation stability (OS).

Abstract Antiferromagnets are promising for nano-scale oscillator in a wide frequency range from gigahertz up to terahertz. Experimentally realizing antiferromagnetic moment oscillation via spin-orbit torque, however, remains elusive. Here, we demonstrate that the optical spin-orbit torque induced by circularly polarized laser can be used to drive free decaying oscillations with a frequency of 2 THz in metallic antiferromagnetic Mn2Au thin films. Due to the local inversion symmetry breaking of Mn2Au, ultrafast a.c. current is generated via spin-to-charge conversion, which can be detected through free-space terahertz emission. Both antiferromagnetic moments switching experiments and dynamics analyses unravel the antiferromagnetic moments, driven by optical spin-orbit torque, deviate from its equilibrium position, and oscillate back in 5 ps once optical spin-orbit torque is removed. Besides the fundamental significance, our finding opens a new route towards low-dissipation and controllable antiferromagnet-based spin-torque oscillators.

Abstract Glioblastoma (GBM) represents a primary malignant brain tumor. Temozolomide resistance is a major hurdle in GBM treatment. Proteins encoded by circular RNAs (circRNAs) can modulate the sensitivity of multiple tumor chemotherapies. However, the impact of circRNA-encoded proteins on GBM sensitivity to temozolomide remains unknown. Herein, we discover a circRNA (circCOPA) through the circRNA microarray profile in GBM samples, which can encode a novel 99 amino acid protein (COPA-99aa) through its internal ribosome entry site. Functionally, circCOPA overexpression in GBM cells inhibits cell proliferation, migration, and invasion in vitro and growth in vivo. Rather than itself, circCOPA mainly functions as a suppressive effector by encoding COPA-99aa. Moreover, we reveal that circCOPA is downregulated in GBM tissues and high expression of circCOPA is related to a better prognosis in GBM patients. Mechanistically, a heteromer of SFPQ and NONO is required for double-strand DNA break repair. COPA-99aa disrupts the dimerization of NONO and SFPQ by separately binding with the NONO and SFPQ proteins, thus resulting in the inhibition of proliferation or invasion and the increase of temozolomide-induced DNA damage in GBM cells. Collectively, our data suggest that circCOPA mainly contributes to inhibiting the GBM malignant phenotype through its encoded COPA-99aa and that COPA-99aa increases temozolomide-induced DNA damage by interfering with the dimerization of NONO and SFPQ. Restoring circCOPA or COPA-99aa may increase the sensitivity of patients to temozolomide.

In order to meet the power source requirements of C-band linear accelerators for industrial applications, a C-band high power klystron operating at a frequency of 5 712 MHz was developed. For this klystron, the development objective of the output power is no less than 3.5 MW and the efficiency is no less than 35%. During the entire design process, the output power was optimized to over 4 MW and the power efficiency over 40% to compensate for the disadvantage effects caused by manufacturing and testing errors in the development processes. Firstly, the electron optics system with a Pierce gun and a combination of five forward and one reverse focusing coils was designed. The Pierce gun with a perveance of 2 μP was adopted and the beam voltage and current were chosen as 120 kV and 83.3 A. By iteratively calculating the structure of the electron gun with EGUN code and optimizing the magnetic field between the electron gun and the beam-wave interaction section, the final electron beam pass rate reaches 100% and the fluctuation of the beam envelop is only 4.8%. Secondly, the efficiency optimization and PIC simulation of the beam-wave interaction section were carried out using the one dimensional AJDISK code, 1.5 dimensional KlyC code and three dimensional CST code. The scheme of six resonant cavities was ultimately determined and the basic cavity parameters were optimized based on the principles of stagger tuning. The simulation results of different codes all indicate that the efficiency can reach above 46.5%, and the output power can all reach above 4.650 MW. And the influence of frequency errors and output external quality factor on efficiency was also analyzed to guide the manufacturing process. After that, the mechanical structure of cavities was designed and all cavities were manufactured with oxygen free copper. The cold test and tuning of all cavities were carried out and the frequency error is mostly within the range of ±5 MHz, which basically does not affect the output power. Finally, the electron gun, the beam-wave interaction section and the collector were welded together. And the high power test was conducted immediately after the first high power C-band klystron protype was completed. When the electron gun operates at the voltage of 115 kV and current of 79.6 A, the klystron peak output power reaches 3.52 MW, the gain reaches 45.5 dB and the efficiency reaches about 38.5%. The high power test results show that this C-band high power klystron achieves the expected development goals.

When the CO2 in a supercritical state (SCCO2) is released from deep coal seams, it reacts with minerals in coal, changing the porosity of coal, which in turn affects the effect of CO2 sequestration in coal seams and the effect of increasing methane production. In order to discover the influence characteristics of SCCO2-H2O-coal rock interaction on the porosity in coal, the experiments on the supercritical CO2 reforming coal under different water content conditions were carried out with coking coal as the research object. Based on the results of mineral composition and porosity measurements, the differences between the main minerals and the changes in pore cleavage at various scales in coal were compared, and the action mechanism of the SCCO2 fluid on the pore cleavage properties under various water content states was explored. The results show that: ① After the SCCO2 treatment, the surface of the coal body is rough and loose, some fissures are penetrated as a result of mineral dissolution, and the connectivity of micro fissure is improved. ② The SCCO2 fluid has a “pore-expanding”effect on coal, which is manifested by a decrease of the content of micro- and small pores, and an increase of the proportion of medium- and large pores, i.e., the conversion of micro- and small-sized pores to large pores, as well as the improvement of pore connectivity. Furthermore, it is discovered that the fractal dimension of the adsorption pores of the coal samples increases slightly in size and roughness, while the fractal dimension of the seepage pores decreases significantly, and the complexity and non-homogeneity are reduced. ③ The SCCO2 fluid has the best solubility on the carbonate minerals in coal, followed by clay minerals, and with the increase of water content, the proportion of carbonate minerals in the extracted coal first increases and then decreases. The SCCO2 fluid makes the carbonate minerals in the coal samples of the dry basal state and saturated water state dissolve significantly, which effectively improves the pore structure, and the effect on the coal samples of the saturated water state is better. After the air-dry basal coal samples were subjected to the SCCO2, the newly formed dolomite minerals gathered in the pore throats to cause the plugging effect, reducing the original large pore size, which is the main cause of the differential changes in the pore space of coals with different water content states.

Air staged combustion reduces NOx emissions, but increases the H2S concentration in primary combustion zone. The excessive H2S concentration near the furnace wall is an important factor that aggravates the high-temperature corrosion of the water-cooled wall. With large-scale renewable power integrated into the grid, the demand for flexible peak-shaving operation of traditional thermal power units has increased. The H2S concentration distribution near the furnace wall under different boiler loads deserves attention. Hence, the influence of different operating parameters of tangentially coal-fired boiler on H2S concentration distribution near the furnace wall was investigated by orthogonal test. A supercritical 600 MW tangentially coal-fired boiler was selected to establish a numerical model. The L16(45) orthogonal numerical conditions was designed to cover four boiler loads, including 100% BMCR, 75% THA, 50% THA and 35% BMCR. A user-defined SOx generation model was employed to calculate the H2S concentration distribution inside the furnace. The release of fuel sulfur and mutual transformation of sulfur components were considered. At the same time, the model included a multiple surface reaction model for describing the heterogeneous reaction between coke and O2/CO2/H2O, and the ratio of the gasification rate to the consumption rate for char particle was calculated. The results show that the high H2S concentration areas are mainly located below the bottom burner that on operation and between the top burner and SOFA nozzle. The main reason for the high H2S concentration in the latter area is that the tangential circle of flue gas increases gradually along the furnace height. The orthogonal analysis indicates that the average H2S concentration in the key area of the furnace wall under 35% BMCR load is 364 μL/L, which is significantly lower than that under the other loads. In addition, the impact of operating parameters on the H2S concentration in key areas follows the order of boiler load > primary air rate > excess air coefficient of main combustion zone > imaginary tangent circle diameter > vertical swing angle of burner.

Abstract Objective The aim of our study is to find a better way to identify a group of papillary thyroid carcinoma (PTC) with more aggressive behaviors and to provide a prediction model for lymph node metastasis to assist in clinic practice. Methods Targeted sequencing of DNA/RNA was used to detect genetic alterations. Gene expression level was measured by quantitative real-time PCR, western blotting or immunohistochemistry. CCK8, transwell assay and flow cytometry were used to investigate the effects of concomitant gene alterations in PTC. LASSO-logistics regression algorithm was used to construct a nomogram model integrating radiomic features, mutated genes and clinical characteristics. Results 172 high-risk variants and 7 fusion types were detected. The mutation frequencies in BRAF, TERT, RET, ATM and GGT1 were significantly higher in cancer tissues than benign nodules. Gene fusions were detected in 16 samples (2 at the DNA level and 14 at the RNA level). ATM mutation (ATM MUT) was frequently accompanied by BRAF MUT, TERT MUT or gene fusions. ATM MUT alone or ATM co-mutations were significantly positively correlated with lymph node metastasis. Accordingly, ATM knock-down PTC cells bearing BRAF V600E, KRAS G12R or CCDC6-RET had higher proliferative ability and more aggressive potency than cells without ATM knock-down in vitro. Furthermore, combining gene alterations and clinical features significantly improved the predictive efficacy for lymph node metastasis of radiomic features, from 71.5 to 87.0%. Conclusions Targeted sequencing of comprehensive genetic alterations in PTC has high prognostic value. These alterations, in combination with clinical and radiomic features, may aid in predicting invasive PTC with higher accuracy.

Background: We compared heart rate variability (HRV) indices between people living with HIV (PLWH) and HIV-negative individuals to ascertain the independent association between HIV infection and reduced HRV, and further investigated whether distinct clinical laboratory profiles exist between PLWH with and without reduced HRV. Methods: This cross-sectional analysis included 304 PLWH and 147 HIV-negative individuals with comparable age and sex. Thirty-two routine clinical laboratory indices (including hematology and biochemistry) closest to the survey were extracted from the Electronic Medical Record System. HRV indices were divided into two categories: low (lowest quartile, Q1) and moderate-to-high (combined, Q2‒Q4). Results: The time domain indices, ln(SDNN), ln(RMSSD), and ln(PNN50), as well as the frequency domain indices, ln(HF), ln(LF), and ln(VLF), were all significantly reduced in PLWH versus HIV-negative individuals (all p

IntroductionThis cross-sectional study examined the mechanisms underlying adolescent math achievement by investigating the relationship between parents’ rearing styles (including different dimensions of rearing style) and adolescent self-control, math anxiety, and math achievement based on the ecological systems theory.MethodA total of 584 junior high school students (M age = 12.52) completed the Parenting Style Questionnaire, Self-control Scale, and Math Anxiety Rating Scale and provided their math test scores.ResultsThe rearing styles of both fathers and mothers directly predicted adolescents’ math achievement. Maternal rearing style indirectly predicted adolescents’ math achievement through their self-control and math anxiety; however, the indirect effect of paternal rearing style on adolescents’ math achievement was not significant. After distinguishing the three dimensions of rearing styles, we found that paternal emotional warmth can increase adolescents’ self-control, while maternal emotional warmth can reduce adolescents’ self-control. Further, paternal overprotectiveness can directly and positively predict adolescents’ math achievement, while maternal rejection and overprotectiveness can positively predict adolescents’ math achievement. None of the three dimensions of rearing styles can predict math achievement through adolescents’ self-control; however, they can predict math achievement indirectly through adolescents’ math anxiety and the chain-mediation of adolescents’ self-control and math anxiety.DiscussionOur results suggest both commonalities and differences in how paternal and maternal rearing styles, along with their three dimensions (emotional warmth, rejection, overprotection), predict adolescent math achievement. These findings highlight the importance of paternal and maternal rearing styles on adolescents’ math achievement and underscore the need to examine them separately to better understand their impact.

IntroductionRecently, a novel type of metabolic-regulated cell demise titled disulfidptosis has been discovered. Studies have demonstrated its importance in immune responses against cancer and its impact on the proliferation of cancer cells. Nonetheless, the precise mechanism and roles of disulfidptosis are not fully understood, particularly regarding the prognosis for individuals with uterine corpus endometrial carcinoma (UCEC).MethodsIn this research, a distinctive disulfidptosis pattern was developed in UCEC, and by utilizing Non-negative Matrix Factorization (NMF) on 23 disulfidptosis related genes within the TCGA database, 3 distinct subgroups were distinguished. To collect data, we acquired gene expression profiles, somatic mutation information, copy number variation data, and corresponding clinical data from the TCGA and GEO database, specifically from UCEC patients. Cell line experiments and immunohistochemical (IHC) staining were conducted to validate the role of the LRPPRC in proliferation, migration and invasion.ResultsThe genetic features and immune microenvironment of these subgroups were examined. It is worth mentioning that these subgroups offer important insights into comprehending the tumor microenvironment (TME) and the response of patients to immunotherapy and chemotherapy. Moreover, a disulfidptosis model was developed and validated, demonstrating a high level of accuracy in predicting the prognosis and outcomes of immunotherapy in UCEC patients. Additionally, a novel biomarker, LRPPRC, was identified, which can server as a promising predictor for forecasting prognosis in UCEC patients, with validation through tissue microarray staining and cell line experiments.DiscussionThis study has designed a classification system and a disulfidptosis model for UCEC, in addition to identifying a new biomarker, LRPPRC, for UCEC. These advancements serve as reliable and positive indicators for predicting outcomes and the efficacy of immunotherapy for each UCEC patient.

This research aimed to determine the effect of dietary guar gum inclusion in high-lipid diets on the liver health of common carp (Cyprinus carpio). Four high-fat diets (10 % crude lipid) containing 0 % (HF), 0.3 % (HFG0.3), 1 % (HFG1), and 3 % (HFG3) of guar gum and a normal-lipid diet (5 % crude lipid; Control) were formulated. The tested diets were evenly and randomly distributed to fifteen tanks, with each tank containing thirty fish (4.53 ± 0.05 g). Fish were fed until apparent satiation for eight weeks. Compared to HF, diets HFG0.3, HFG1, and HFG3 significantly improved feed efficiency, with the HFG0.3 diet enhancing weight gain rate and specific growth rate. The results indicated that HF induced gut dysbiosis, hepatic lipid accumulation, oxidative stress, inflammation, and disturbance in hepatic lipid and cholesterol metabolism. Compared to the HF diet, diets HFG0.3, HFG1, and HFG3 substantially decreased hepatic lipid accumulation and malonaldehyde content, increased catalase activity and the expression of AMP-activated protein kinase (AMPKα2), peroxisomal proliferator-activated receptor alpha (PPARα), cholesterol 7alpha-hydroxylase, and decreased the expression of interleukin-1β (IL-1β). Moreover, the HFG0.3 and HFG1 diets dramatically increased nuclear factor erythroid 2-related factor 2 and liver X receptor expression and decreased protein carbonyl contents and expression of IL-8, nuclear factor kappa B (NF-κB p65), and tumor necrosis factor α. Furthermore, the HFG1 diet significantly increased carnitine palmitoyltransferase 1 and peroxisomal proliferator-activated receptor gamma coactivator 1 expression and reduced expression levels of fibroblast growth factor 19, farnesoid X receptor, and sterol regulatory element-binding protein type 1. The linear discriminant analysis effect size (LEfSe) analysis showed that HFG 0.3 and HFG1 substantially increased the enrichment of beneficial microbiota (e.g., lactic acid bacteria, Cetobacterium, and Fusobacterial) and decreased the enrichment of harmful microbiota (e.g., Proteobacteria, Acinetobacter, and Pseudomonas) compared to HF. These results suggested that guar gum can mitigate high-fat diet-induced liver damage in fish.

BackgroundIn this retrospective study, we aimed to identify key risk factors and establish an interpretable model for HCC with a diameter ≥ 5 cm using Lasso regression for effective risk stratification and clinical decision-making.MethodsIn this study, 843 patients with advanced hepatocellular carcinoma (HCC) and tumor diameter ≥ 5 cm were included. Using Lasso regression to screen multiple characteristic variables, cox proportional hazard regression and random survival forest models (RSF) were established. By comparing the area under the curve (AUC), the optimal model was selected. The model was visualized, and the order of interpretable importance was determined. Finally, risk stratification was established to identify patients at high risk.ResultLasso regression identified 8 factors as characteristic risk factors. Subsequent analysis revealed that the lasso-cox model had AUC values of 0.773, 0.758, and 0.799, while the lasso-RSF model had AUC values of 0.734, 0.695, and 0.741, respectively. Based on these results, the lasso-cox model was chosen as the superior model. Interpretability assessments using SHAP values indicated that the most significant characteristic risk factors, in descending order of importance, were tumor number, BCLC stage, alkaline phosphatase (ALP), ascites, albumin (ALB), and aspartate aminotransferase (AST). Additionally, through risk score stratification and subgroup analysis, it was observed that the median OS of the low-risk group was significantly better than that of the middle- and high-risk groups.ConclusionWe have developed an interpretable predictive model for middle and late HCC with tumor diameter ≥ 5 cm using lasso-cox regression analysis. This model demonstrates excellent prediction performance and can be utilized for risk stratification.

BackgroundDespite increasing awareness, silica dust–induced silicosis still contributes to the huge disease burden in China. Worryingly, recent silica dust exposure levels and silicosis risk in Chinese noncoal mines remain unclear. ObjectiveWe aimed to determine recent silica dust exposure levels and assess the risk of silicosis in Chinese noncoal mines. MethodsBetween May and December 2020, we conducted a retrospective cohort study on 3 noncoal mines and 1 public hospital to establish, using multivariable Cox regression analyses, prediction formulas of the silicosis cumulative hazard ratio (H) and incidence (I) and a cross-sectional study on 155 noncoal mines in 10 Chinese provinces to determine the prevalence of silica dust exposure (PDE), free silica content, and total dust and respirable dust concentrations. The qualitative risk of silicosis was assessed using the International Mining and Metals Commission’s risk-rating table and the occupational hazard risk index; the quantitative risk was assessed using prediction formulas. ResultsKaplan-Meier survival analysis revealed significant differences in the silicosis probability between silica dust–exposed male and female miners (log-rank test χ21=7.52, P=.01). A total of 126 noncoal mines, with 29,835 miners and 4623 dust samples, were included; 13,037 (43.7%) miners were exposed to silica dust, of which 12,952 (99.3%) were male. The median PDE, free silica content, total dust concentration, and respirable dust concentration were 61.6%, 27.6%, 1.30 mg/m3, and 0.58 mg/m3, respectively, indicating that miners in nonmetal, nonferrous metal, small, and open-pit mines suffer high-level exposure to silica dust. Comprehensive qualitative risk assessment showed noncoal miners had a medium risk of silicosis, and the risks caused by total silica dust and respirable silica dust exposure were high and medium, respectively. When predicting H and I over the next 10, 20, and 30 years, we assumed that the miner gender was male. Under exposure to current total silica dust concentrations, median I10, I20, and I30 would be 6.8%, 25.1%, and 49.9%, respectively. Under exposure to current respirable silica dust concentrations, median I10, I20, and I30 would be 6.8%, 27.7%, and 57.4%, respectively. These findings showed that miners in nonmetal, nonferrous metal, small, and open-pit mines have a higher I and higher qualitative silicosis risk. ConclusionsChinese noncoal miners, especially those in nonmetal, nonferrous metal, small, and open-pit mines, still suffer high-level exposure to silica dust and a medium-level risk of silicosis. Data of both total silica dust and respirable silica dust are vital for occupational health risk assessment in order to devise effective control measures to reduce noncoal mine silica dust levels, improve miners’ working environment, and reduce the risk of silicosis.

Microorganisms are closely related to human health, and changes in the microbiome can lead to the occurrence of diseases. With advances in sequencing technology and research, it has been discovered that intratumoral microbiota exists in various cancer tissues and differs in various cancers. Microorganism can colonize tumor tissues through intestine of damaged mucosal barrier, proximity to normal tissues and bloodstream circulation. Increasing evidence suggests that intratumoral microbiota promotes tumor progression by increasing genomic instability, affecting host immune systems, promoting tumor migration, and regulating tumor signaling pathways. This review article summarizes the latest progress in intratumoral microbiome research, including the development history of intratumoral microbiota, their composition and sources within tumors, their distribution in various cancer tissues, as well as their role in cancer development. Furthermore, the application of intratumoral microbiota in clinical settings is emphasized and we innovatively summarize the clinical trials involving microbial applications for cancer diagnosis and treatment across different countries.

Benzene is a common environmental pollutant and significant health hazard. Low-dose benzene exposure is common in most industrial settings, and some workers exhibit hematotoxicity characterized by impaired hematopoietic function. Consequently, understanding the early hematopoietic damage and biomarkers associated with low-dose benzene exposure is of critical importance for health risk assessment. Using data from a 5-year prospective cohort study on benzene exposure and the National Center for Biotechnology Information's Gene Expression Omnibus database, we detected significant downregulation of the ubiquitin-conjugating enzyme UBE2L3 (E2) in benzene-exposed subjects compared to control subjects. Liquid chromatography tandem mass spectrometry and co-immunoprecipitation experiments illustrated the binding interaction between UBE2L3 and the ubiquitin-protein ligase ZNF598 (E3). We applied deep learning algorithms to predict candidate interacting proteins and then conducted validation via co-immunoprecipitation experiments, which showed that ZNF598 engages in binding with the autophagy protein LAMP-2. Subsequent overexpression and knockdown of UBE2L3 coupled with immunofluorescence experiments and transmission electron microscopy revealed that UBE2L3 disrupts the ubiquitination-degradation of LAMP-2 by ZNF598, reduces GPX4 expression levels, and activates an autophagy-dependent ferroptosis pathway. It also leads to increased lipid peroxidation, thereby promoting ferroptosis and contributing to the hematotoxicity induced by benzene. In summary, our results suggest that UBE2L3 may be involved in early hematopoietic damage by modulating the autophagy-dependent ferroptosis signaling pathway in benzene-induced hematotoxicity.

Diamond-Blackfan anemia syndrome (DBAS) is an inherited bone marrow failure disorder that typically presents in infancy as hypoplastic anemia and developmental abnormalities in approximately 50% of cases. DBAS is caused by haploinsufficiency in one of 24 ribosomal protein genes, with RPS19 mutations accounting for 25% of cases. We generated iPSC lines from two patients with different heterozygous RPS19 mutations (c.191T > C and c.184C > T) and isogenic lines in which the mutations were corrected by Cas9-mediated homology directed repair.

Abstract A large number of economic forests, especially apple orchards (AOs) in the Loess Plateau region of China, have been planted to develop the local economy and increase the income of farmers. The two main constraints preventing AOs on the Loess Plateau from developing sustainably and producing a high and steady yield are soil moisture content (SMC) and soil organic carbon (SOC). Nevertheless, little is currently known about the contributions of roots to these changes in the soil profile and the temporal modes of the SMC-SOC coupled effects. In our research, we analyzed the dynamic changes in SMC and SOC in AOs of various years in northern Shaanxi Province, as well as the coupled relationship between the two, and attempted to describe the function of roots in these changes. Research have shown: (1) As the age of the AOs increased, the SMC continued to decline throughout the 0–500 cm profile, especially at depths of 100–500 cm. SMC depletion mainly occurred in AOs aged 20 years (30.02%/year) and 30 years (31.18%/year). (2) Compared with abandoned land (AL), all the AOs except for the 6-year-old AO showed a carbon sequestration effect, and the carbon sequestration effect increased with age. The carbon sequestration rate of the 12-year-old AO was the highest and then decreased with age. Both surface and deeper soils showed better carbon sequestration, with a large amount of SOC being sequestered in deeper soil layers (> 100 cm). (3) The coupled effects of SMC and SOC varied with age and depth. The SMC in the deeper layers was significantly negatively correlated with SOC. Root dry weight density (RDWD) was significantly negatively correlated with SMC and significantly positively correlated with SOC. Path analysis suggested that SMC directly affects SOC at different soil depths, and regulates SOC by affecting RDWD, but these effects are significantly different at different depths. Therefore, we propose that management of AO should focus on the moisture deficit and carbon sequestration capabilities of deeper soils to ensure the sustainability of water use in AOs and the stability of agricultural carbon sequestration on the Loess Plateau.

Abstract Néel spin-orbit torque allows a charge current pulse to efficiently manipulate the Néel vector in antiferromagnets, which offers a unique opportunity for ultrahigh density information storage with high speed. However, the reciprocal process of Néel spin-orbit torque, the generation of ultrafast charge current in antiferromagnets has not been demonstrated. Here, we show the experimental observation of charge current generation in antiferromagnetic metallic Mn2Au thin films using ultrafast optical excitation. The ultrafast laser pulse excites antiferromagnetic magnons, resulting in instantaneous non-equilibrium spin polarization at the antiferromagnetic spin sublattices with broken spatial symmetry. Then the charge current is generated directly via spin-orbit fields at the two sublattices, which is termed as the reciprocal phenomenon of Néel spin-orbit torque, and the associated THz emission can be detected at room temperature. Besides the fundamental significance on the Onsager reciprocity, the observed magnonic charge current generation in antiferromagnet would advance the development of antiferromagnetic THz emitter.

ABSTRACTCandida albicans is a common fungal pathogen that can cause life-threatening infections. MIR1 is considered to be a mitochondrial phosphate carrier of C. albicans, while its role in virulence has not been fully elucidated. In this study, we found that mir1Δ/Δ mutant exhibited severe virulence defect in both nematode and murine models. Further mechanism studies revealed that the mir1Δ/Δ mutant grew more slowly than the wild-type strain and showed severe filamentation defects on the hypha-inducing agar media, including YPD + serum, Lee, Spider + glucose, SLAD, SLD, and YPS. Furthermore, the loss of MIR1 resulted in unfermentable carbon utilisation defect, ATP decrease, and reactive oxygen species (ROS) accumulation in C. albicans. Antioxidant proanthocyanidins, vitamin E, and N-acetyl cysteine (NAC) could reduce intracellular ROS levels and partially rescue the filamentation defects of the mir1Δ/Δ mutant. Accordingly, hypha-specific genes, as well as CEK1 and RIM101 were down-regulated in the mir1Δ/Δ mutant, and this down-regulation could be partially rescued by the addition of the antioxidant NAC. Collectively, MIR1 plays an important role in C. albicans mitochondrial function, filamentation and virulence, and would be a promising antifungal target.

In this study, a quantitative model was developed using near-infrared spectroscopy to analyze protein content in dried purple alfalfa, employing preprocessing methods (SG, SNV, MSC, FD) and variable selection algorithms (CARS, IRIV) to optimize spectra. Models using ELM, PLSR, SVM, and LSTM were tested; the MSC-CARS-PLSR-SVM model achieved the highest accuracy, with a calibration determination coefficient (R²) of 0.9982 and root mean square error (RMSE) of 0.1088, and a prediction R² of 0.9645 with RMSE of 0.5230, offering a precise and reliable method for protein content prediction.

Abstract Objectives Silicosis people are at high risk of developing pulmonary tuberculosis. Whether silica exposure increases the likelihood of latent tuberculosis infection (LTBI) was not well understood, and potential factors involved in LTBI risk among silicosis people were not evaluated before. Thus, LTBI among silicosis people and potential risk factors for LTBI among silicosis people were evaluated in this study. Methods A cross-sectional study was undertaken for 130 miner workers with silicosis. The QFT-GIT was performed for LTBI detection. Results The LTBI was high to 31.6% (36/114) for silicosis participants, and 13.1% (13/99) had a history of tuberculosis. Drinking was associated with LTBI risk (OR = 6.92, 95%CI, 1.47–32.66, P = 0.015). Meanwhile, tunneling work was associated with an increased risk of LTBI compared with other mining occupations (OR = 3.91,95%CI,1.20–12.70, P = 0.024). Conclusions The LTBI rate of silicosis participants was high and more than 10% had a history of tuberculosis. Drinking alcohol and tunneling were independent risk factors for LTBI in silicosis participants.

Abstract Aging is a global challenge, marked in the lungs by function decline and structural disorders, which affects the health of the elderly population. To explore anti-aging strategies, we develop a dynamic atlas covering 45 cell types in human lungs, spanning from embryonic development to aging. We aim to apply the discoveries of lung’s development to address aging-related issues. We observe that both epithelial and immune cells undergo a process of acquisition and loss of essential function as they transition from development to aging. During aging, we identify cellular phenotypic alternations that result in reduced pulmonary compliance and compromised immune homeostasis. Furthermore, we find a distinctive expression pattern of the ferritin light chain (FTL) gene, which increases during development but decreases in various types of lung cells during the aging process.

Turbine blisk is one of the typical components of gas turbine engines. The fatigue life of turbine blisk directly affects the reliability and safety of both turbine blisk and aeroengine whole-body. To monitor the performance degradation of an aeroengine, an efficient deep learning-based modeling method called convolutional-deep neural network (C-DNN) method is proposed by absorbing the advantages of both convolutional neural network (CNN) and deep neural network (DNN), to perform the probabilistic low cycle fatigue (LCF) life prediction of turbine blisk regarding uncertain influencing parameters. In the C-DNN method, the CNN method is used to extract the useful features of LCF life data by adopting two convolutional layers, to ensure the precision of C-DNN modeling. The two close-connected layers in DNN are employed for the regression modeling of aeroengine turbine blisk LCF life, to keep the accuracy of LCF life prediction. Through the probabilistic analysis of turbine blisk and the comparison of methods (ANN, CNN, DNN and C-DNN), it is revealed that the proposed C-DNN method is an effective mean for turbine blisk LCF life prediction and major factors affecting the LCF life were gained, and the method holds high efficiency and accuracy in regression modeling and simulations. This study provides a promising LCF life prediction method for complex structures, which contribute to monitor health status for aeroengines operation.

Abstract Mobile edge computing (MEC) is a novel computing paradigm that pushes computation and storage resources to the edge of the network. The interconnection of edge servers forms small-scale data centers, enabling MEC to provide low-latency network services for mobile users. Nowadays, Remote Direct Memory Access (RDMA) has been widely deployed in such data centers to reduce CPU overhead and network latency. Plenty of congestion control mechanisms have been proposed for RDMA data centers, aiming to provide low-latency data delivery and high throughput network services. However, our fine-grained experimental analysis reveals that existing congestion control mechanisms still have performance limitations due to inappropriate congestion notifications and the long congestion feedback cycle. In this paper, we propose Mercury, which is an accurate and fast congestion feedback mechanism. Mercury comprises two key components: (1) the state-driven congestion detection and (2) the window-based congestion notification. Specifically, the state-driven congestion detection monitors the queue length and the number of packets received at the switch egress port when the PFC is triggered. It determines the states of egress ports and identifies flows that really contribute to congestion. Then, window-based congestion notification calculates the window sizes for congested flows and rapidly returns Congestion Notification Packets (CNPs) with the window information to the sender. It facilitates the rate adjustment of congested flows. Mercury is compatible with existing RDMA CC mechanisms and can be easily implemented in switches. We employ real-world data sets and conduct both micro-benchmark and large-scale simulations to evaluate the performance of Mercury. The results indicate that, thanks to the accurate and fast congestion feedback, Mercury achieves a reduction in the 99th tail flow completion time by up to 45.1%, 41.8%, 38.7%, 30.9%, and 37.9% compared with Timely, DCQCN, DCQCN+TCD, PACC, and HPCC, respectively.

To study the feasibility of using municipal sewage as a reserve water source for oilfield reinjection, the water sample treated by the municipal sewage treatment plant and the produced water of the Chang 2 reservoir were taken as the research objects. Through the analysis of water quality and compatibility, the optimal ratio of reinjection water samples was determined. At the same time, the clay swelling experiment and reservoir damage experiment were carried out. The experimental results show that the salinity of municipal sewage is low, and the content of scale ions is low. When the ratio of produced water to municipal sewage is 7:3, the scale formation amount can reach 42.5 mg.L-1, and when the scale inhibitor is added, the scale formation amount can be reduced to 10.4 mg.L-1. The mixed water sample will not cause clay expansion. Meanwhile, Chang 2 reservoir is moderately weak water sensitive and weak acid sensitive. The oil content, suspended solids content, and median particle size of the mixed water sample during reinjection should be controlled at 5 mg.L-1, 5 mg.L-1, and 5 μm to ensure that the reinjected water sample does not cause damage to the reservoir.

Per- and polyfluorinated substances (PFASs) contaminates the arable soil through multiple paths, and poses a threat to both farmland ecosystems and human health. In this study, the potential sources and distribution characteristics of 12 legacy PFASs in the soil and rivers for irrigation purposes were investigated in farmland systems, and the risks posed by PFASs to earthworm and aquatic organisms were also assessed. Based on field investigations in Yangtze River Basin, we found long-chain perfluoroalkyl carboxylic acids (PFCAs) were the major contaminants in arable soil and rivers for irrigation purposes, with PFOA (Perfluorooctanoic acid) being the most dominant monomer. Concentration levels of PFASs in arable soil were strongly related to land use types, the average concentration of PFASs (341.18 ± 600.19 ng/g) in the paddy fields was 100-fold higher than that of dry fields (3.79 ± 4.11 ng/g). Source apportionment revealed that PFASs detected in paddy fields were mainly associated with industrial effluents, domestic sewage, and irrigation water. In rivers for irrigation purposes, higher PFASs contamination were primarily distributed in industrial areas, such as plastic processing, paper, textile and electronics factories. The PFASs in the irrigation river water posed a low-medium risk to daphnia and fish, while the PFASs (PFOA and perfluorododecanoic acid (PFDoDA)) in soil posed a medium-high risk to earthworms. These results provided insights that sewage irrigation caused serious pollution of PFASs in the agricultural environment, should be paid more attention.