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Taxanes are a widely used class of anticancer agents that play a vital role in the treatment of a variety of cancers. However, toxicity remains a major concern of using taxane drugs as some toxicities are highly prevalent, they can not only adversely affect patient prognosis but also compromise the overall treatment plan. Among all kinds of factors that associated with taxane toxicity, taxane exposure has been extensively studied, with different pharmacokinetic (PK) parameters being used as toxicity predictors. Compared to other widely used predictors such as the area under the drug plasma concentration curve versus time (AUC) and time above threshold plasma drug concentration, maximum plasma concentration (Cmax) is easier to collect and shows promise for use in clinical practice. In this article, we review the previous research on using Cmax to predict taxane treatment outcomes. While Cmax and toxicity have been extensively studied, research on the relationship between Cmax and efficacy is lacking. Most of the articles find a positive relationship between Cmax and toxicity but several articles have contradictory findings. Future clinical trials are needed to validate the relationship between Cmax and treatment outcome and determine whether Cmax can serve as a useful surrogate endpoint of taxane treatment efficacy. [ABSTRACT FROM AUTHOR]

Aims: This study aims to investigate the effect of aerobic exercise training on BKCa channel in diabetic vascular smooth muscle and explore the underlying mechanism. Methods: Control m/m mice and diabetic db/db mice were randomly assigned to sedentary groups (W and D) and exercise training groups (WE and DE). Mice in exercise groups underwent training sessions lasting for 12 weeks, with a speed of 12 m/min for 60 min, five times per week. The thoracic aorta was extracted isolated and examined for measurement of vascular structure, global levels of reactive oxygen species (ROS), vasodilation, and protein expression. Rat thoracic aorta vascular smooth muscle cells (USMCs) were cultured, and siRNA transfection was conducted to detect whether AMPK contributed to the regulation. ROS level and protein expression were measured. Results: Compared with control mice, diabetic mice had a larger vascular medium thickness, impaired BKCa-mediated vasodilation, a higher level of ROS, and a lower expression of BKCa α, BKCa β1, Nrf2, p-Nrf2, p-Nrf2/Nrf2, HO-1, and p-AMPK/AMPK. Exercise training increased the expression of BKCa α, Nrf2, p-Nrf2, p-Nrf2/Nrf2, HO-1, and p-AMPK/AMPK. AMPK deletion led to lower ROS levels and expression of BKCa α, β1, Nrf2, and HO-1 in USMCs cultured in high glucose conditions. Conclusions: BKCa channel protein expression reduction in VSMCs contributes to vasodilation and vascular remodeling dysfunction in diabetes mellitus. Aerobic exercise can promote the expression of BKCa channel and improve BKCa-mediated vascular dysfunction in diabetic VSMCs through AMPK/Nrf2/HO-1 signaling pathway. [ABSTRACT FROM AUTHOR]

Important properties of biochar as an effective soil amendment are its high water-holding capacity (WHC) and inhibition of water evaporation. However, the mechanism and the importance of biochar properties in controlling its own WHC and bound water evaporation remain little known. In this study, wheat straw and pine sawdust biochars were pyrolyzed in N2-flow, CO2-flow, and air-limitation environments at 300–750 ℃, and a series of the produced biochars' properties were characterized to explore the dominant controlling factors of their WHC and bound water evaporation. The results have shown that with the increasing contents of hydrogen, nitrogen, and oxygen as well as such ratios as H/C, and (O + N)/C, WHC of the biochars was also increasing while the evaporation of biochar-bound water was decreasing. With an increase in the other studied factors, such as carbon content, pH, and specific surface area (SSA), WHC of the biochars was decreasing, and the evaporation of biochar-bound water was increasing. That was connected with the fact that biochar-nitrogen was mainly in pyridinic and pyrrolic forms, while oxygen was in the form of C = O and C–O bonds. These forms of nitrogen and oxygen could be the receptors of hydrogen bonds to link to H2O molecules. Aliphatic hydrogen with a weak positive charge could be a donor of hydrogen bonds to link to H2O molecules. However, high carbon content, as well as high SSA, indicated more exposed aromatic carbon (hydrophobic sites) that could suppress the binding of H2O molecules. Additionally, high pH indicated that H2O molecules were dominated by OH–, which generated strong electrostatic repulsion with the negatively charged nitrogen- and oxygen-containing groups of biochar. It was also shown that the nitrogen-containing groups played a more important role (importance – 0.31) in WHC of the biochar than other parameters, including carbon, oxygen, hydrogen, ash contents, pH, SSA (importance from 0.02 to 0.09). Nitrogen, oxygen, and carbon contents had the most important influence on the evaporation of biochar-bound water in all studied factors. Furthermore, wheat straw biochar produced at low pyrolysis temperatures in N2 atmosphere (with high nitrogen and oxygen contents) had the highest WHC and the lowest evaporation of biochar-bound water. Consequently, it can be suggested that biochar rich in nitrogen can be an effective water retention agent and can improve agricultural soil moisture. Highlights: Nitrogen-containing groups (pyridinic and pyrrolic nitrogen) played a crucial role in the improvement of biochar water-holding capacity. Nitrogen- and oxygen-containing groups inhibited the evaporation of biochar-bound water. Biochar rich in nitrogen and oxygen may be an effective water retention agent to maintain soil moisture. [ABSTRACT FROM AUTHOR]

Non‐small cell lung cancer (NSCLC) is an aggressive and devastating cancer due to its metastasis induced by increased invasion. Lentinan is a polysaccharide exerting antitumor roles in multiple cancers, including lung cancer. However, the influence of lentinan on cell invasion in NSCLC remains unclear. Cell invasion was detected by transwell analysis. Matrix metallopeptidase 9 (MMP9) levels were measured through immunofluorescence staining. The markers arginase‐1 (Arg‐1), CD206 and interleukin (IL)‐10 (IL‐10) of M2 macrophages, Wnt3a, and β‐catenin levels were measured by western blot or enzyme linked immunosorbent assay. Lentinan did not affect cell viability and proliferation in NSCLC cells. Lentinan suppressed cell invasion and reduced the expression and secretion of MMP9. Lentinan attenuated also M2 polarization of tumor‐associated macrophages. Moreover, lentinan mitigated the M2 macrophage conditioned medium‐mediated cell invasion and MMP9 alterations in NSCLC cells. Lentinan inhibited the activation of the Wnt/β‐catenin signaling in NSCLC cells. The activated Wnt/β‐catenin pathway reversed the suppressive effects of lentinan on cell invasion and MMP9 level in NSCLC cells. In conclusion, lentinan reduces cell invasion in NSCLC cells by inhibiting the M2 polarization of tumor‐associated macrophages and the Wnt/β‐catenin signaling. [ABSTRACT FROM AUTHOR]

In order to broaden the muffler frequency band in the low-frequency range of the exhaust muffler and to achieve the purpose of broadband noise reduction, in this paper, a model of an annular connecting pipe muffler is proposed using the finite element method (FEM) to simulate the nonreflection boundary condition and to solve the transmission loss (TL). In addition, the experimental value is obtained by the spatial five-point measurement method and compared with the simulated value, and the validity and reliability of the solution model are verified. Compared with a simple expansion muffler, the average TL of the annular connecting pipe muffler is increased by 11.86 dB, and the maximum TL is increased by 18.31 dB, effectively widening the muffler frequency area, and the overall performance is effectively improved. Finally, the influence of structural factors is analyzed, including the width (W) of the annular connecting pipe, the length (L) of the annular connecting pipe, and the length ratio (m) of the front and rear chambers on the TL and on the width of the anechoic frequency band. The results reveal that the width and length of the annular connecting pipe and front-to-back cavity length ratio are the most significant factors to influence the TL, muffler frequency band, and elimination or reduction of the passing frequency, respectively. [ABSTRACT FROM AUTHOR]

Wind-induced vibration has become increasingly prominent for long-span bridges. Flutter instability, as a type of divergent vibration, is a key component in the wind resistance investigation of long-span bridges. Based on the principle of instantaneous power balance (IPB) of the flutter critical state of bridge girders, an algorithm for predicting the flutter critical wind speed of long-span bridges was proposed by utilizing a nonlinear optimization strategy. For the bending–torsional coupling two-dimensional (2-D) motion system, the contribution of the wind-induced self-excited and structural elastic forces of the 2-D bridge section to the energy of the system was revealed to be dependent on some key parameters, such as reduced frequency, wind speed, amplitude ratio, and phase lag between vertical and torsional motions. Therefore, according to the principle of IPB during the critical flutter state, the prediction of flutter onset wind velocity can be transformed into an extreme value optimization problem of the IPB objective function. The feasibility and accuracy of the IPB algorithm were verified by comparing them with those obtained from segmental model wind tunnel tests and previous 2-D flutter prediction algorithms. Compared with the traditional methods characterized by force balance, the proposed method clearly and quantitatively presents the contribution relationship among multiple self-excited aerodynamic components on the flat plate and bridge section while flutter occurs; the method first evaluates the flutter critical state as an alternative algorithm from an energy perspective. [ABSTRACT FROM AUTHOR]

Objective: To explore the parameters influencing intraoperative calculi excretion (ICE) during flexible ureteroscopy lithotripsy (fURL) using in vitro simulation experiments. Methods: 3D-printed human kidney models were used to simulate the elimination of gravel during fURL. The factors influencing the ICE during fURL were analyzed by comparing the effects of different degrees of hydronephrosis (mild, moderate, and severe), surgical positions (supine and lateral position), ratios of endoscope-sheath diameter (RESD) (0.625, 0.725, and 0.825), gravel sizes (0.50–1.00 mm, 0.25–0.50 mm, and 0.10–0.25 mm), and ureteral access sheaths (UASs) (traditional UAS and negative-pressure UAS) on ICE. Results: The impacts of various UAS, RESD, degree of hydronephrosis, surgical positions, and gravel sizes on ICE were all significant (p < 0.05). We found no evidence of multicollinearity for all the independent variables, and the linear regression equation fitted as ICE (g / min) = 0.102 + 0.083 ∗ UAS grade - 0.050 ∗ RESD grade - 0.048 ∗ hydronephrosis grade + 0.065 ∗ position grade - 0.027 ∗ gravel size grade (R2 = 0.569). Conclusion: Employing negative-pressure UAS, smaller RESD, milder hydronephrosis, lateral position, and smaller gravel size contribute to improved ICE during fURL. Among them, the adoption of negative-pressure UAS had the most substantial effects. [ABSTRACT FROM AUTHOR]

Trap–mediated non–radiative loss is a major efficiency and stability obstale for solution–processed perovskite solar cells (PSCs). To address this issue, defect passivation using organic molecules has been identified as an effective strategy due to the ionic nature of the perovskite lattice. Herein, Ostwald ripening by using formamidine iodine (FAI) is reported to inhibit the carrier trap induced recombination via promoting secondary grain growth at perovskite surface. Based on secondary grain growth with FAI treatment, the graded passivation was presented caused by FA+ and I- from FAI. Moreover, the findings from time resolved photoluminescence and space charge–limited current technology indicate enhancements in the crystal quality. Consequently, this approach yielded a remarkable power conversion efficiency (PCE) of 20.62% for the FAI modified MAPbI 3 photovoltaics, with significantly improved open–circuit voltage ratio of 3.10%, short–circuit density ratio of 6.11%, fill factor ratio of 9.46% and PCE ratio of 19.06%. Moreover, the device show the excellent stability. This study introduces simple and reproducible procedures for fabricating PSCs, which can be readily extended to diverse optoelectronic device applications. • We use formamidine iodine (FAI) to induce secondary grain growth via Ostwald ripening. • The graded passivation was presented caused by FA and I from FAI. • The crystal quality is facilely modulated by FAI, which is also effective for other perovskite optoelectronic devices. [ABSTRACT FROM AUTHOR]

• Fatty acid structure affected the 3D printability of corn starch–fatty acid (CS-FA) complex gels. • The formation of CS-FA complexes inhibited the "extrusion swelling" of CS gels. • CS-FA complexes changed the microstructure of corn starch gel. • Rheological and printing properties of CS-FA gel highly depend on FA structure. • Complex gels with 12-carbon fatty acid had the highest printing accuracy. The effect of corn starch-fatty (CS-FA) complexes from varying carbon chain length and degree of unsaturation on the rheological and 3D printing properties of corn CS–FA complex gels. The CS-FA complexes with longer carbon chain lengths and lower saturation enhanced the ability of gels to bind water, promoting the formation of intermolecular hydrogen bonds. The CS-FA complexes inhibit retrogradation and increase the amount of bound water, thereby reducing the structural integrity and transforming the original skeleton structure into a flake-like structure. These changes in gel structure led to lower flow stress and storage modulus for CS-FA gels containing FAs with shorter carbon chain lengths and lower saturation, resulting in reduced "extrusion swelling" of the material and facilitating its extrusion. The decreased "extrusion swelling" of gel improved print line width and printing performance. The CS-FA complex gel-printed product with a 12-carbon chain FA has the greatest printing accuracy, thanks to its moderate G', flow stress, and viscosity. This study provides important information for the CS-FA complexes for the preparation of starch-based 3D printing materials. [ABSTRACT FROM AUTHOR]

Iron slag, a byproduct of the wet zinc refining process, contains a substantial amount of valuable metals such as iron and zinc, making it highly valuable for comprehensive recovery and reuse. However, before recovery, the iron slag requires dehydration pretreatment. The water content in iron slag remains relatively high and difficult to remove even after pressure filtration, leading to extended drying times, reduced drying efficiency, and increased energy consumption. This study explores a novel ultrasonic pretreatment process for iron slag. Using the response surface methodology, we investigated the effects of ultrasonic power, ultrasonic time, liquid-to-solid ratio, and their interactions on the water content, capillary suction time (CST), and filtration resistance of the slag. Regression equations were established to predict the relationships between the water content, CST, filtration resistance, and the various factors. The optimal process parameters were determined as an ultrasonic power of 60 W, ultrasonic time of 22 s, and a liquid-to-solid ratio of 4:1. Under these conditions, the dehydration performance of the iron slag was optimal. The measured values closely matched the predicted values, demonstrating the reliability of the model and the feasibility of the optimized process. Our study of the mechanism of ultrasonic action on iron slag found that under the influence of ultrasonic waves, the particle size of the slag significantly decreased, and the particle morphology changed. Compared to conventional drying, the drying rate of the iron slag after ultrasonic pretreatment was accelerated, and the drying time was reduced. [ABSTRACT FROM AUTHOR]

The study examined the impact of phase morphological transformations within the corn starch/gelatin system, induced by varying gelatin content, on its rheological properties and 3D printing performance. Gelatin addition inhibited the gelatinization and retrogradation of starch, which leaded to the transformation of continuous phase structure. The transition process from starch continuous phase to gelatin continuous phase promoted a thinner wall structure of the gel and loosed its dense network, resulting in reduced flow stress (τ f) and storage modulus (G′). These changes improved the extrusion and "extrusion swelling" of gel ink materials, which made the print size of printed product closer to the set model. The formation of a gelatin continuous phase in the gel was helpful in increasing τ f and G′, resulting in enhanced support capacity of the printed product. This study presented meaningful information for the application of 3D printing to starch-gelatin complex foods. [ABSTRACT FROM AUTHOR]

White matter hyperintensities (WMHs) are associated with higher anxiety or depression (A/D) incidence. We investigated associations of WMHs with A/D, cerebrovascular reactivity (CVR), and functional connectivity (FC) to identify potential pathomechanisms. Participants with WMH (n = 239) and normal controls (NCs, n = 327) were assessed for A/D using the Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD). The CVR and FC maps were constructed from resting-state functional MRI. Two-way analysis of covariance with fixed factors A/D and WMH was performed to identify regional CVR abnormalities. Seed-based FC analyses were then conducted on regions with WMH × A/D interaction effects on CVR. Logistic regression models were constructed to examine the utility of these measurements for identifying WMH-related A/D. Participants with WMH related A/D exhibited significantly greater CVR in left insula and lower CVR in right superior frontal gyrus (SFG.R), and HAMA scores were negatively correlated with CVR in SFG.R (r = −0.156, P = 0.016). Insula–SFG.R negative FC was significantly weaker in WMH patients with suspected or definite A/D. A model including CVR plus FC changes identified WMH-associated A/D with highest sensitivity and specificity. In contrast, NCs with A/D exhibited greater CVR in prefrontal cortex and stronger FC within the default mode network (DMN) and between the DMN and executive control network. This cross-sectional study requires validation by longitudinal and laboratory studies. Impaired CVR in SFG.R and weaker negative FC between prefrontal cortex and insula may contribute to WMH-related A/D, providing potential diagnostic imaging markers and therapeutic targets. • Impaired CVR in right superior frontal gyrus can aggravate WMH related anxiety or depression. • Negative hyper-connectivity of prefrontal-insula existed in WMH with anxiety or depression. • Altered CVR and FC were both potential imaging markers of WMH-related anxiety or depression. • The CVR and FC were increased as compensation in control subjects with anxiety or depression. [ABSTRACT FROM AUTHOR]

We aimed to improve the detection accuracy of laser methane sensors in expansive temperature application environments. In this paper, a large-scale dataset of the measured concentration of the sensor at different temperatures is established, and a temperature compensation model based on the ISSA-BP neural network is proposed. On the data side, a large-scale dataset of 15,810 sets of laser methane sensors with different temperatures and concentrations was established, and an Improved Isolation Forest algorithm was used to clean the large-scale data and remove the outliers in the dataset. On the modeling framework, a temperature compensation model based on the ISSA-BP neural network is proposed. The quasi-reflective learning, chameleon swarm algorithm, Lévy flight, and artificial rabbits optimization are utilized to improve the initialization of the sparrow population, explorer position, anti-predator position, and position of individual sparrows in each generation, respectively, to improve the global optimization seeking ability of the standard sparrow search algorithm. The ISSA-BP temperature compensation model far outperforms the four models, SVM, RF, BP, and PSO-BP, in model evaluation metrics such as MAE, MAPE, RMSE, and R-square for both the training and test sets. The results show that the algorithm in this paper can significantly improve the detection accuracy of the laser methane sensor under the wide temperature application environment. [ABSTRACT FROM AUTHOR]

Ovarian tissue cryopreservation is considered to be the only means to preserve fertility for prepubertal girls and women whose cancer treatment cannot be postponed. However, ovarian tissues are inevitably damaged by oxidative stress during cryopreservation, which threatens follicle survival and development, and thus affects female fertility. Therefore, reducing tissue oxidative stress injury is one of the major challenges to achieving efficient cryopreservation of ovarian tissues, especially for whole ovaries. Here, we proposed a new method to improve the antioxidant capacity of whole ovaries during cryopreservation, static magnetic field assisted thawing. The results demonstrated that the antioxidant capacity of the ovarian tissue was significantly improved by static magnetic field treatment. In addition, ovarian tissue allograft transplantation was carried out, which successfully achieved vascular regeneration and maintained follicular development. The findings of this study not only provide a new reference for the preservation of female fertility, but also is a major step forward in the cryopreservation of tissues and organs. It will have good application prospects in the field of assisted reproduction and cryo‐biomedicine. [ABSTRACT FROM AUTHOR]

Vaccination has been proven effective against infection with enterovirus A71 (EV-A71) in clinical trials, but vaccine effectiveness in real-world situations remains incompletely understood. Furthermore, it is not clear whether previous vaccination will result in symptom attenuation among post-vaccinated cases. Based on long-term data extracted from the only designed referral hospital for infectious diseases, we used a test-negative case-control design and multivariate logistic regression models to analyze the effectiveness of EV-A71 vaccine against hand, foot and mouth disease (HFMD). And then, generalized linear regression models were used to evaluate the associations between prior vaccination and disease profiles. We selected 4883 inpatients for vaccine efficacy estimations and 2188 inpatients for disease profile comparisons. Vaccine effectiveness against EV-A71-induced HFMD for complete vaccination was 63.4 % and 51.7 % for partial vaccination. The vaccine effectiveness was higher among cases received the first dose within 12 months. No protection was observed against coxsackievirus (CV) A6-, CV-A10- or CV-A16-associated HFMD among children regardless of vaccination status. Completely vaccinated cases had shorter hospital stay and disease course compared to unvaccinated cases (P < 0.05). These findings reiterate the need to continue the development of a multivalent vaccine or combined vaccines, and have implications for introducing optimized vaccination strategies. [ABSTRACT FROM AUTHOR]

Monocyte-derived tumor-associated macrophages (Mo-TAMs) intensively infiltrate diffuse gliomas with remarkable heterogeneity. Using single-cell transcriptomics, we chart a spatially resolved transcriptional landscape of Mo-TAMs across 51 patients with isocitrate dehydrogenase (IDH)-wild-type glioblastomas or IDH-mutant gliomas. We characterize a Mo-TAM subset that is localized to the peri-necrotic niche and skewed by hypoxic niche cues to acquire a hypoxia response signature. Hypoxia-TAM destabilizes endothelial adherens junctions by activating adrenomedullin paracrine signaling, thereby stimulating a hyperpermeable neovasculature that hampers drug delivery in glioblastoma xenografts. Accordingly, genetic ablation or pharmacological blockade of adrenomedullin produced by Hypoxia-TAM restores vascular integrity, improves intratumoral concentration of the anti-tumor agent dabrafenib, and achieves combinatorial therapeutic benefits. Increased proportion of Hypoxia-TAM or adrenomedullin expression is predictive of tumor vessel hyperpermeability and a worse prognosis of glioblastoma. Our findings highlight Mo-TAM diversity and spatial niche-steered Mo-TAM reprogramming in diffuse gliomas and indicate potential therapeutics targeting Hypoxia-TAM to normalize tumor vasculature. [Display omitted] • Single-cell omics reveals functional and spatial diversity of Mo-TAMs in glioblastomas • Tumor cues and hypoxia concertedly induce Hypoxia-TAM signature via activating p50 • ADM secreted by Hypoxia-TAM stimulates a destabilized tumor vasculature • ADM blockade improves vessel integrity, drug delivery, and anti-tumor efficacy Pronounced necrosis in glioblastomas is accompanied by abundant destabilized microvessels. Wang et al. show that the niche cues from the peri-necrotic regions polarize macrophages toward a hypoxic state, which in turn augments vascular hyperpermeability. Targeting adrenomedullin produced by hypoxic macrophages normalizes tumor neovasculature and improves anti-tumor drug delivery and efficacy. [ABSTRACT FROM AUTHOR]

Background: The relationship between parental age at pregnancy and offspring development in low- and middle-income countries remains unclear. We aimed to examine the associations of parental age at pregnancy with adolescent development in rural China. Methods: We conducted a prospective birth cohort study of offspring born to pregnant women who participated in an antenatal micronutrient supplementation trial in rural Western China. Adolescent cognitive development and emotional and behavioural problems were assessed by using the Wechsler Intelligence Scale for Children-IV and the Youth Self-Report-2001, respectively. After accounting for the possible nonlinear relationships, we examined the linear associations between parental age (in years) at pregnancy and scores of adolescent cognitive development and emotional and behavioural problems by performing generalized estimating equations. Results: Among 1897 adolescents followed from birth to early adolescence, 59.5% were male with a mean age of 11.8 (standard deviation (SD): 0.8) years. The mean ages of mothers and fathers at pregnancy were 24.6 (SD: 4.4) and 27.9 (SD: 4.1) years old, respectively. All the P values of the nonlinear terms between parental age and adolescent development in all domains were greater than 0.05. Each one-year increase in maternal age at pregnancy was associated with a 0.29-point (95% confidence interval (CI) 0.06, 0.52) increase in the full-scale intelligence quotient in early adolescence. After parental age was categorized into quartiles, the total behavioural problem scores of adolescents with fathers with an age in the fourth quartile (Q4) were 6.71 (95% CI 0.86, 12.57) points higher than those of adolescents with fathers with an age in the first quartile (Q1), with a linear trend P value of 0.01. Similarly, higher scores (worse behavioural problems) were observed for internalizing behavioural problems and other emotional and behavioural symptoms related to anxiety, withdrawal, social problems, thought problems and aggressive behaviour. Conclusions: At conception, older maternal age was independently linked to better adolescent cognitive development, whereas advanced paternal age was independently associated with a greater risk of adolescent emotional and behavioral problems. These findings suggest that public health policies targeting an optimal parental age at pregnancy should be developed in the context of offspring developmental consequences. [ABSTRACT FROM AUTHOR]

To evaluate the predictive performance of multiparameter and histogram features derived from amide proton transfer-weighted imaging (APTWI), intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) for histopathological types of breast tumors. Region of interest (ROI) was delineated by outlining the largest slice of the tumor on the false-color images of the DKI, IVIM and APTWI parameters, and extracted the histogram features. Receiver operating characteristic (ROC) curve was used to evaluate the performance of parameters in predicting benign and malignant breast lesions, molecular prognostic biomarkers, lymph node status, and subtypes of breast lesions. The Spearman correlation coefficient was used to determine the correlations between each parameter and clinical-pathological factors. All 52 breast lesions were enrolled in this prospective study, including 8 benign lesions and 44 breast cancers. To diagnose malignant and benign breast lesions, the value of APT (min) performed best, with the AUC reaching 0.983. According to the different imaging methods, the APTWI performed best. To predict the positive status of ER, PR, Ki67, the value of D app (uniformity) , D app (uniformity) , f (entropy) performed best, with the AUC values reaching 0.743, 0.770, 0.848, respectively. For the identification of Luminal B, HER2-enriched, and TNBC breast cancers, K app (max) , f (kurtosis) , and D app (uniformity) performed best, with AUC values reaching 0.679, 0.826, 0.771, respectively. This study found the APTWI, IVIM and DKI parameters could diagnose breast cancer. The histogram features of DKI and IVIM, based on tumor heterogeneity, may help to predict breast cancer subtypes. [ABSTRACT FROM AUTHOR]

Exposure of dark-grown etiolated seedlings to light triggers the transition from skotomorphogenesis/etiolation to photomorphogenesis/de-etiolation. In the life cycle of plants, de-etiolation is essential for seedling development and plant survival. The mobilization of soluble sugars (glucose [Glc], sucrose, and fructose) derived from stored carbohydrates and lipids to target organs, including cotyledons, hypocotyls, and radicles, underpins de-etiolation. Therefore, dynamic carbohydrate biochemistry is a key feature of this phase transition. However, the molecular mechanisms coordinating carbohydrate status with the cellular machinery orchestrating de-etiolation remain largely opaque. Here, we show that the Glc sensor HEXOKINASE 1 (HXK1) interacts with GROWTH REGULATOR FACTOR5 (GRF5), a transcriptional activator and key plant growth regulator, in Arabidopsis (Arabidopsis thaliana). Subsequently, GRF5 directly binds to the promoter of phytochrome A (phyA), encoding a far-red light (FR) sensor/cotyledon greening inhibitor. We demonstrate that the status of Glc within dark-grown etiolated cotyledons determines the de-etiolation of seedlings when exposed to light irradiation by the HXK1–GRF5–phyA molecular module. Thus, following seed germination, accumulating Glc within dark-grown etiolated cotyledons stimulates a HXK1-dependent increase of GRF5 and an associated decrease of phyA, triggering the perception, amplification, and relay of HXK1-dependent Glc signaling, thereby facilitating the de-etiolation of seedlings following light irradiation. Our findings, therefore, establish how cotyledon carbohydrate signaling under subterranean darkness is sensed, amplified, and relayed, determining the phase transition from skotomorphogenesis to photomorphogenesis on exposure to light irradiation. This study reveals how sugar signaling under subterranean darkness is sensed, amplified, and relayed to determine skototophotomorphogenesis upon exposure to light irradiation. [ABSTRACT FROM AUTHOR]

Purpose: To maintain safe intrarenal pelvic pressure (IPP), the combination of flexible ureteroscope (fURS) and traditional ureteral access sheath (T-UAS) should maintain a basic rule that is the ratio of endoscope-sheath diameter (RESD) ≤ 0.75. However, the negative-pressure ureteral access sheath (NP-UAS) may break the rule of negative pressure suction. This study aimed to examine the effect of NP-UAS on IPP and flow rate (FR) with varying RESD. Methods: In a 3D-printed renal model, flexible ureteroscopy lithotripsy (fURL) was replicated. Six sizes of fURS paired with 12Fr T-UAS and NP-UAS resulted in six distinct RESDs of 0.63, 0.78, 0.87, 0.89, 0.90, and 0.91. While the irrigation pressure (IRP) was set between 100 and 800 cmH2O and the sucking pressure (SP) was set between 0 and 800 cmH2O, the IPP and FR were measured in each RESD. Results: NP-UASs can reduce the IPP and increase the FR at the same RESD compared to T-UASs. The IPP decreased with increasing SP with NP-UAS. When RESD ≤ 0.78, T-UAS and NP-UAS can maintain IPP < 40 cmH2O in most circumstances. When RESD = 0.87, it is challenging for T-UAS to sustain IPP < 40 cmH2O; however, NP-UAS can do so. When RESD ≥ 0.89, it is difficult to maintain an IPP < 40 cmH2O even with NP-UAS. Conclusion: NP-UAS can decrease IPP and increase FR compared with T-UAS. To maintain a safe IPP, it is recommended that RESD < 0.85 when utilizing NP-UAS. [ABSTRACT FROM AUTHOR]

Formation and extinction of thermal stratifications impact the reservoir ecosystems and have been closely influenced by meteorological and hydrological factors. However, quantifying the relative importance of these crucial environmental factors and mechanisms in reservoir regions characterized by various depths remain comparatively uninvestigated. Tianbao Reservoir is a typical monomictic warm and drinking water source reservoir in Southwest China. This study supplemented field observations with a three-dimensional numerical simulation model to quantitatively analyze mixing and turnover events. Air temperature and wind were two important meteorological factors resulting in hydrodynamics during stratification and mixing processes. Air temperature led to variations in stratification strength and wind-induced fluctuations of thermocline depth. A 10% rise in air temperature increased stratification strength by 18%, and a 3 m/s rise in wind speed induced the deepening of the thermocline by 2.09 m. Two hydrodynamics involved penetrative convection caused by temperature plummets and wind-induced mixing during winter turnover events were identified. Penetrative convection was the main driving force, and wind shear mixed the upper 21% of the mixed layer, which was contributed by convection. Response of water temperature to air temperature in shallow regions was faster (58 d), and the mixing depth caused by the wind was smaller than that in deep regions. Research on physical processes during stratification and mixing processes can provide support for further study on water quality deterioration distributions. • Increase of water temperature to climate change in Tianbao Reservoir was relatively lower than global average. • Convection caused by temperature plummets was the driving force of winter turnover which was more important than wind. • Asynchronous turnover events caused greater potential threats to water quality in tropical monomictic reservoirs. [ABSTRACT FROM AUTHOR]

• HWH486 was a novel irreversible inhibitor of Bruton's tyrosine kinase (BTK). • HWH486 was well tolerated and safe in healthy individuals. • This study will confirm the efficacy of HWH486 in autoimmune diseases. HWH486 inhibits Bruton's tyrosine kinase and therefore shows promise as a treatment against rheumatoid arthritis and chronic spontaneous urticaria. This phase I trial assessed tolerability, safety, pharmacokinetics and pharmacodynamics of a single oral dose of HWH486 capsules in healthy adults. A single-center, randomized, double-blind, placebo-controlled, dose-escalation study from 10 to 800 mg was conducted in 96 healthy Chinese adults, of whom 80 received HWH486 and 16 received placebo. A total of 96 subjects were enrolled, and all completed the study. In the HWH486 group, mean T max ranged from 1.03 to 2.00 h, and mean T 1/2 ranged from 0.85 to 8.67 h across the dose range from 10 to 800 mg. Mean C max increased linearly with dose, while mean AUC 0-t increased non-linearly. Occupancy of Bruton's tyrosine kinase peaked within 0.50–4.00 h after administration across the dose groups, and the delay until peak occupancy decreased with increasing dose. Twenty-five subjects (31.25 %) in the HWH486 group experienced 35 treatment-emergent adverse events, while four subjects (25.00 %) in the placebo group experienced eight such events. HWH486 is well tolerated and safe in healthy adults, in whom it can strongly bind Bruton's tyrosine kinase. These findings justify clinical studies of HWH486 efficacy against autoimmune diseases. [ABSTRACT FROM AUTHOR]

Branched-chain amino acid transferase 1 (BCAT1) is highly expressed in multiple cancers and is associated with poor prognosis, particularly in glioblastoma (GBM). However, the post-translational modification (PTM) mechanism of BCAT1 is unknown. Here, we investigated the cross-talk mechanisms between phosphorylation and ubiquitination modifications in regulating BCAT1 activity and stability. We found that BCAT1 is phosphorylated by branched chain ketoacid dehydrogenase kinase (BCKDK) at S5, S9, and T312, which increases its catalytic and antioxidant activity and stability. STUB1 (STIP1 homology U-box-containing protein 1), the first we found and reported E3 ubiquitin ligase of BCAT1, can also be phosphorylated by BCKDK at the S19 site, which disrupts the interaction with BCAT1 and inhibits its degradation. In addition, we demonstrate through in vivo and in vitro experiments that BCAT1 phosphorylation inhibiting its ubiquitination at multiple sites is associated with GBM proliferation and that inhibition of the BCKDK-BCAT1 axis enhances the sensitivity to temozolomide (TMZ). Overall, we identified novel mechanisms for the regulation of BCAT1 modification and elucidated the importance of the BCKDK-STUB1-BCAT1 axis in GBM progression. [Display omitted] • BCAT1 is phosphorylated by BCKDK at S5, S19, and T312 to enhance its activity and stability. • STUB1 is a novel E3 ubiquitin ligase of BCAT1. • BCKDK-mediated phosphorylation of STUB1 at S19 inhibits the interaction with BCAT1. • The BCKDK-STUB1-BCAT1 signaling axis promotes GBM progression. [ABSTRACT FROM AUTHOR]

The accessory proteins of coronaviruses play a crucial role in facilitating virus-host interactions and modulating host immune responses. Previous study demonstrated that the NS7a protein of porcine deltacoronavirus (PDCoV) partially hindered the host immune response by impeding the induction of IFN-α/β. However, the potential additional functions of NS7a protein in evading innate immunity have yet to be elucidated. This study aimed to investigate the mechanism of PDCoV NS7a protein regulating the JAK/STAT signaling pathway. We presented evidence that NS7a effectively inhibited ISRE promoter activity and ISGs transcription. NS7a hindered STAT1 phosphorylation, interacted with STAT2 and IRF9, and further impeded the formation and nuclear accumulation of ISGF3. Furthermore, comparative analysis of NS7a across different PDCoV strains revealed that the mutation of Leu4 to Pro4 led to an increase in the molecular weights of NS7a and disrupted its inhibition on the JAK/STAT signaling pathway. This finding implied that NS7a with key amino acids may be an indicator of virulence for PDCoV strains. Taken together, this study revealed a novel role of NS7a in antagonizing the IFN-I signaling pathway. [ABSTRACT FROM AUTHOR]

• •OH could be rapidly generated from Fe2+/EDTA system (O 2 atmosphere). • Fe2+-EDTA activate O 2 to induce H 2 O 2 in-situ via direct 2-electron transformation. • EDTA tune the production pathways of radical or intermediate in Fenton system. • The dual effect of •OH and O 2 •− was revealed in Fe3+/EDTA/H 2 O 2 system. The Fenton system was a generation system of reactive oxygen species via the chain reactions, which employed H 2 O 2 and O 2 as radical precursors and Fe2+/Fe3+ as electron-donor/acceptor for triggering or terminating the generation of radicals. Recent work mainly emphasized the Fe2+- activated H 2 O 2 and the application of in-situ generated •OH, while neglecting other side-reactions. In this work, EDTA (Ethylene diamine tetraacetic acid) was employed as a chelating agent of iron ions, which simultaneously changed the redox property of coordinated iron. The Fe2+-EDTA complexes in the presence of dissolved oxygen enabled the two-electron transfer from Fe2+ to O 2 and the in-situ production of H 2 O 2 , which further activate H 2 O 2 for yielding •OH. Meanwhile, coordinated Fe3+ exhibited non-negligible reactivity toward H 2 O 2 , which was higher than that of free Fe3+ in the traditional Fenton system. The complexation of EDTA with Fe3+ could enhance the Fe2+ generation reaction by the H 2 O 2 , accompanied by the O 2 •− formation. The enhancement of O 2 •− formation and Fe2+-EDTA regeneration induced the subsequent H 2 O 2 activation by Fe2+-EDTA, thus accelerating the Fe3+-EDTA/Fe2+-EDTA cycle for simultaneously producing O 2 •− and •OH. To sum up, the EDTA-chelated Fenton system extended the applicable pH range to circumneutral/alkaline level and tuned the redox property of coordinated iron for diversifying the •OH production routes. The research reinterpreted the chain reactions in the Fenton system, revealing another way to enhance the radical production or other property of the Fenton/Fenton-like system. [Display omitted] [ABSTRACT FROM AUTHOR]