A novel fast robust optimization algorithm for intensity-modulated proton therapy with minimum monitor unit constraint.

BACKGROUND: Intensity-modulated proton therapy (IMPT) optimizes spot intensities and position, providing better conformability. However, the successful application of IMPT is dependent upon addressing the challenges posed by range and setup uncertainties. In order to address the uncertainties in IMPT, robust optimization is essential. PURPOSE: This study aims to develop a novel fast algorithm for robust optimization of IMPT with minimum monitor unit (MU) constraint. METHODS AND MATERIALS: The study formulates a robust optimization problem and proposes a novel, fast algorithm based on the alternating direction method of multipliers (ADMM) framework. This algorithm enables distributed computation and parallel processing. Ten clinical cases were used as test scenarios to evaluate the performance of the proposed approach. The robust optimization method (RBO-NEW) was compared with plans that only consider nominal optimization using CTV (NMO-CTV) without handling uncertainties and PTV (NMO-PTV) to handle the uncertainties, as well as with conventional robust-optimized plans (RBO-CONV). Dosimetric metrics, including D95, homogeneity index, and Dmean, were used to evaluate the dose distribution quality. The area under the root-mean-square dose (RMSD)-volume histogram curves (AUC) and dose-volume histogram (DVH) bands were used to evaluate the robustness of the treatment plan. Optimization time cost was also assessed to measure computational efficiency. RESULTS: The results demonstrated that the RBO plans exhibited better plan quality and robustness than the NMO plans, with RBO-NEW showing superior computational efficiency and plan quality compared to RBO-CONV. Specifically, statistical analysis results indicated that RBO-NEW was able to reduce the computational time from 389.70 ± 207.40 $389.70\pm 207.40$ to 228.60 ± 123.67 $228.60\pm 123.67$ s ( p < 0.01 $p<0.01$ ) and reduce the mean organ-at-risk (OAR) dose from 9.38 ± 12.80 $9.38\pm 12.80$ % of the prescription dose to 9.07 ± 12.39 $9.07\pm 12.39$ % of the prescription dose ( p < 0.05 $p<0.05$ ) compared to RBO-CONV. CONCLUSION: This study introduces a novel fast robust optimization algorithm for IMPT treatment planning with minimum MU constraint. Such an algorithm is not only able to enhance the plan's robustness and computational efficiency without compromising OAR sparing but also able to improve treatment plan quality and reliability.

Advanced biomedical and electronic dual-function skin patch created through microfluidic-regulated 3D bioprinting.

Artificial skin involves multidisciplinary efforts, including materials science, biology, medicine, and tissue engineering. Recent studies have aimed at creating skins that are multifunctional, intelligent, and capable of regenerating tissue. In this work, we present a specialized 3D printing ink composed of polyurethane and bioactive glass (PU-BG) and prepare dual-function skin patch by microfluidic-regulated 3D bioprinting (MRBP) technique. The MRBP endows the skin patch with a highly controlled microstructure and superior strength. Besides, an asymmetric tri-layer is further constructed, which promotes cell attachment and growth through a dual transport mechanism based on hydrogen bonds and gradient structure from hydrophilic to superhydrophilic. More importantly, by combining the features of biomedical skin with electronic skin (e-skin), we achieved a biomedical and electronic dual-function skin patch. In vivo experiments have shown that this skin patch can enhance hemostasis, resist bacterial growth, stimulate the regeneration of blood vessels, and accelerate the healing process. Meanwhile, it also mimics the sensory functions of natural skin to realize signal detection, where the sensitivity reached up to 5.87 kPa-1, as well as cyclic stability (over 500 cycles), a wide detection range of 0-150 kPa, high pressure resolution of 0.1 % under the pressure of 100 kPa. This work offers a versatile and effective method for creating dual-function skin patches and provide new insights into wound healing and tissue repair, which have significant implications for clinical applications.

Patient-reported outcomes for the phase 3 FURLONG study of furmonertinib versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small cell lung cancer.

Background: Furmonertinib showed superior efficacy compared with gefitinib as first-line therapy in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) in the FURLONG study. Here we present prespecified secondary endpoints of patient-reported outcomes (PRO). Methods: In this multicentre, double-blind, double-dummy, randomised phase 3 study, patients were 1:1 randomly assigned to receive furmonertinib 80 mg once daily or gefitinib 250 mg once daily. PROs assessed by the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 and Quality-of-Life Questionnaire Lung Cancer 13 were analysed using a mixed model for repeated measures and time-to-event analyses. A difference in score of 10 points or more was deemed clinically relevant. Findings: Three hundred and fifty-seven patients (furmonertinib group, n = 178; gefitinib group, n = 179) received at least one dose of the study drug, all of whom completed at least one PRO assessment. Statistically significant difference of overall score changes from baseline favoured furmonertinib in physical functioning (between-group difference 2.14 [95% CI 0.25-4.04], p = 0.027), nausea/vomiting (-1.56 [95% CI -2.62 to -0.49], p = 0.004), appetite loss (-2.24 [95% CI -4.26 to -0.23], p = 0.029), diarrhoea (-3.36 [95% CI -5.19 to -1.54], p < 0.001), alopecia (-2.62 [95% CI -4.54 to -0.71], p = 0.007), and pain in other parts (-4.55 [95% CI -7.37 to -1.74], p = 0.002), but not reached clinical relevance. Time to deterioration in physical functioning (hazard ratio 0.63 [95% CI 0.42-0.94], p = 0.021), cognitive functioning (0.73 [95% CI 0.54-0.98], p = 0.034), nausea/vomiting (0.64 [95% CI 0.41-0.99], p = 0.042), appetite loss (0.63 [95% CI 0.43-0.92], p = 0.016), diarrhoea (0.63 [95% CI 0.46-0.85], p = 0.002), dyspnoea (0.72 [95% CI 0.53-0.98], p = 0.034), cough (0.67 [95% CI 0.44-1.00], p = 0.049), dysphagia (0.54 [95% CI 0.35-0.83], p = 0.004), and alopecia (0.62 [95% CI 0.42-0.90], p = 0.012) was longer with furmonertinib versus gefitinib. Interpretation: In patients with locally advanced or metastatic EGFR mutation-positive NSCLC, furmonertinib showed improved scores and delayed deterioration in several functioning and symptoms compared to gefitinib. Funding: Shanghai Allist Pharmaceutical Technology Co., Ltd and the National Science and Technology Major Project for Key New Drug Development (2017ZX09304015).

C-reactive protein-albumin-lymphocyte index as a feasible nutrition-immunity-inflammation marker of the outcome of all-cause and cardiovascular mortality in elderly.

BACKGROUND & AIMS: The imbalance of nutrition-immunity-inflammation status might be associated with the mortality risk in the elderly. This study aimed to assess the relationship between the C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index and all-cause and cardiovascular disease (CVD) mortality in the elderly. METHODS: The data from records of older adults (≥ 60 years) were derived from 1999 to 2010 and 2015-2018 National Health and Nutrition Examination Survey. Weighted Cox proportional hazard regression was used to analyze the relationship between CALLY and all-cause mortality and CVD mortality in three different models, and the linear trend was analyzed. A restricted cubic spline model was used to evaluate the nonlinear dose-response relationship and determine the critical threshold of CALLY to divide the population into two groups. Kaplan-Meier analysis and log-rank test were used to evaluate the cumulative survival rates of different groups. Subgroup analyses and sensitivity analyses were performed to ensure robustness. RESULTS: Compared to the first quartile of natural log-transformation (ln) CALLY, the highest quartile of ln CALLY was negatively correlated with the risk of all-cause mortality (HR = 0.67, 95% CI: 0.56-0.79. P < 0.05) and CVD mortality (HR = 0.65, 95% CI: 0.47-0.89. P < 0.05) in model 3. Ln CALLY was linear dose-response correlated with mortality. We determined that the critical threshold for ln CALLY in elderly was 1.00. Elderly with higher ln CALLY (≥ 1.00) had significantly increased survival rates (P < 0.05). CONCLUSION: CALLY showed a significant negative linear association with the risk of all-cause mortality and CVD mortality, and higher CALLY was beneficial to the survival outcomes of the elderly.

Effect of combined electrolyzed reduced water and slightly acidic electrolyzed water spraying on the control of Salmonella, eggshell quality, and shelf life of eggs during storage.

Slightly acidic electrolyzed water (SAEW) is a safe and effective disinfectant, but its sterilizing efficiency is compromised by organic matter on the egg surface. Electrolyzed reduced water (ERW) is a harmless cleaner with a decontamination effect on a variety of surfaces and can be used to remove organic matter. This study assesses the effectiveness of a combination of ERW and SAEW in eliminating Salmonella and manure mixture from egg surfaces, as well as its impact on egg quality during storage. The results show that ERW (74.14%) was more effective than deionized water (DW, 64.69%) and SAEW (70.20%) (P < 0.05) in removing manure from egg surfaces. The damage to the cuticle of eggshell treated with ERW for 28 s was similar to that of DW (P > 0.05) and less than that of SAEW (P < 0.05). Spraying ERW for 10 s followed by SAEW for 18 s (ERW + SAEW) completely removed Salmonella from the egg surface, with no bacteria detected in the residual wash solution. Additionally, ERW + SAEW demonstrated superior preservation of egg quality during storage at 25℃ than the control and ERW single treatment (P < 0.05). Moreover, ERW + SAEW resulted in less weight loss compared to SAEW single treatment (P < 0.05). In conclusion, the sequential use of ERW and SAEW appears to be a promising approach for sterilizing eggs. It not only removes organic matter and Salmonella from the egg surface but also improves the preservation quality of the egg at 25 ℃.

The architecture of silk-secreting organs during the final larval stage of silkworms revealed by single-nucleus and spatial transcriptomics.

Natural silks are renewable proteins with impressive mechanical properties and biocompatibility that are useful in various fields. However, the cellular and spatial organization of silk-secreting organs remains unclear. Here, we combined single-nucleus and spatially resolved transcriptomics to systematically map the cellular and spatial composition of the silk glands (SGs) of mulberry silkworms late in larval development. This approach allowed us to profile SG cell types and cell state dynamics and identify regulatory networks and cell-cell communication related to efficient silk protein synthesis; key markers were validated via transgenic approaches. Notably, we demonstrated the indispensable role of the ecdysone receptor (ultraspiracle) in regulating endoreplication in SG cells. Our atlas presents the results of spatiotemporal analysis of silk-secreting organ architecture late in larval development; this atlas provides a valuable reference for elucidating the mechanism of efficient silk protein synthesis and developing sustainable products made from natural silk.

Quantum gate control of polar molecules with machine learning.

We propose a scheme for achieving basic quantum gates using ultracold polar molecules in pendular states. The qubits are encoded in the YbF molecules trapped in an electric field with a certain gradient and coupled by the dipole-dipole interaction. The time-dependent control sequences consisting of multiple pulses are considered to interact with the pendular qubits. To achieve high-fidelity quantum gates, we map the control problem for the coupled molecular system into a Markov decision process and deal with it using the techniques of deep reinforcement learning (DRL). By training the agents over multiple episodes, the optimal control pulse sequences for the two-qubit gates of NOT, controlled NOT, and Hadamard are discovered with high fidelities. Moreover, the population dynamics of YbF molecules driven by the discovered gate sequences are analyzed in detail. Furthermore, by combining the optimal gate sequences, we successfully simulate the quantum circuit for entanglement. Our findings could offer new insights into efficiently controlling molecular systems for practical molecule-based quantum computing using DRL.

Exploring the therapeutic potential of garlic in alcoholic liver disease: a network pharmacology and experimental validation study.

OBJECTIVE: Employing network pharmacology and molecular docking, the study predicts the active compounds in garlic and elucidates their mechanism in inhibiting the development of alcoholic liver disease (ALD). ALD is a global chronic liver disease with potential for hepatocellular carcinoma progression. METHODS: The main active ingredients and targets of garlic were identified through screening the TCMSP, TCM-ID, and ETCM databases. ALD disease targets were sourced from DisGeNET, GeneCards, and DiGSeE databases, and intervention targets for garlic were determined through intersections. Protein interaction networks were constructed using the STRING platform, and GO and KEGG pathway enrichment analyses were performed with R software. The garlic component-disease-target network was established using Cytoscape software. Validation of active ingredients against core targets was conducted through molecular docking simulations using AutoDock Vina software. Expression validation of core targets was carried out using human sequencing data of ALD obtained from the GEO database. RESULTS: Integration of garlic drug targets with ALD disease targets identified 83 target genes. Validation through an alcohol-induced ALD mouse model supported certain network pharmacology findings, suggesting that garlic may impede disease progression by mitigating the inflammatory response and promoting ethanol metabolism. CONCLUSION: This study provides insights into the potential therapeutic mechanisms of garlic in inhibiting ALD development. The identified active ingredients offer promising avenues for further investigation and development of treatments for ALD, emphasizing the importance of botanical remedies in liver disease management.

Exploring the cobia (Rachycentron canadum) genome: unveiling putative male heterogametic regions and identification of sex-specific markers.

BACKGROUND: Cobia (Rachycentron canadum) is the only member of the Rachycentridae family and exhibits considerable sexual dimorphism in growth rate. Sex determination in teleosts has been a long-standing basic biological question, and the molecular mechanisms of sex determination/differentiation in cobia are completely unknown. RESULTS: Here, we reported 2 high-quality, chromosome-level annotated male and female cobia genomes with assembly sizes of 586.51 Mb (contig/scaffold N50: 86.0 kb/24.3 Mb) and 583.88 Mb (79.9 kb/22.5 Mb), respectively. Synteny inference among perciform genomes revealed that cobia and the remora Echeneis naucrates were sister groups. Further, whole-genome resequencing of 31 males and 60 females, genome-wide association study, and sequencing depth analysis identified 3 short male-specific regions within a 10.7-kb continuous genomic region on male chromosome 18, which hinted at an undifferentiated sex chromosome system with a putative XX/XY mode of sex determination in cobia. Importantly, the only 2 genes within/between the male-specific regions, epoxide hydrolase 1 (ephx1, renamed cephx1y) and transcription factor 24 (tcf24, renamed ctcf24y), showed testis-specific/biased gene expression, whereas their counterparts cephx1x and ctf24x, located in female chromosome 18, were similarly expressed in both sexes. In addition, male-specific PCR targeting the cephx1y gene revealed that this genomic feature is conserved in cobia populations from Panama, Brazil, Australia, and Japan. CONCLUSION: The first comprehensive genomic survey presented here is a valuable resource for future studies on cobia population structure and dynamics, conservation, and evolutionary history. Furthermore, it establishes evidence of putative male heterogametic regions with 2 genes playing a potential role in the sex determination of the species, and it provides further support for the rapid evolution of sex-determining mechanisms in teleost fish.

Proton-Induced Reversible Spin-State Switching in Octanuclear FeIII Spin-Crossover Metal-Organic Cages.

Responsive spin-crossover (SCO) metal-organic cages (MOCs) are emerging dynamic platforms with potential for advanced applications in magnetic sensing and molecular switching. Among these, FeIII-based MOCs are particularly noteworthy for their air stability, yet they remain largely unexplored. Herein, we report the synthesis of two novel FeIII MOCs using a bis-bidentate ligand approach, which exhibit SCO activity above room temperature. These represent the first SCO-active FeIII cages and feature an atypical {FeN6}-type coordination sphere, uncommon for FeIII SCO compounds. Our study reveals that these MOCs are sensitive to acid/base variations, enabling reversible magnetic switching in solution. The presence of multiple active proton sites within these SCO-MOCs facilitates multisite, multilevel proton-induced spin-state modulation. This behavior is observed at room temperature through 1H NMR spectroscopy, capturing the subtle proton-induced spin-state transitions triggered by pH changes. Further insights from extended X-ray absorption fine structure (EXAFS) and theoretical analyses indicate that these magnetic alterations primarily result from the protonation and deprotonation processes at the NH active sites on the ligands. These processes induce changes in the secondary coordination sphere, thereby modulating the magnetic properties of the cages. The capability of these FeIII MOCs to integrate magnetic responses with environmental stimuli underscores their potential as finely tunable magnetic sensors and highlights their versatility as molecular switches. This work paves the way for the development of SCO-active materials with tailored properties for applications in sensing and molecular switching.

Modification of Microstructure and Mechanical Properties of Extruded AZ91-0.4Ce Magnesium Alloy through Addition of Ca.

The effect of the addition of alkali earth element Ca on the microstructure and mechanical properties of extruded AZ91-0.4Ce-xCa (x = 0, 0.4, 0.8, 1.2 wt.%) alloys was studied by using scanning electron microscopy, transmission electron microscopy, and tensile tests. The results showed that the addition of Ca could significantly refine the second phase and grain size of the extruded AZ91-0.4Ce alloy. The refinement effect was most obvious when 0.8 wt.% of Ca was added, and the recrystallized grain size was 4.75 µm after extrusion. The addition of Ca resulted in the formation of a spherical Al2Ca phase, which effectively suppressed the precipitation of the ß-Mg17Al12 phase, promoted dynamic recrystallization and grain refinement, impeded dislocation motion, and exerted a positive influence on the mechanical properties of the alloy. The yield strength (YS), ultimate tensile strength (UTS), and elongation (EL) of the AZ91-0.4Ce-0.8Ca alloy were 238.7 MPa, 338.3 MPa, and 10.8%, respectively.

Dynamic change of neutrophil-to-lymphocyte ratio and its predictive value of prognosis in acute ischemic stroke.

OBJECTIVE: The present research aimed to explore the dynamic change of the neutrophil-to-lymphocyte ratio (NLR) and its relationship with functional outcome following an acute ischemic stroke (AIS), whether receiving intravenous thrombolysis (IVT) or not. METHODS: We retrospectively analyzed data that were prospectively acquired from patients with AIS treated with IVT or not. For patients receiving IVT, the NLR was based on a blood test performed prior to IVT (d0) and at different time points after disease onset (d1, d3, d7). In addition, in the non-IVT group, the NLR was obtained at different time points after disease onset (d1, d3, d7). Follow-ups were performed 3 months after onset via telephone. In addition, a good outcome was defined as a modified Rankin scale (mRS) ≤1; a poor outcome means 2 ≤ mRS ≤ 6. RESULTS: A total of 204 AIS patients were included in this study. The NLR presented a dynamic change as it increased to its peak at day 1 and gradually declined to its baseline at day 7, no matter whether patients were receiving IVT or not. Patients with poor outcomes have a higher NLR at various time points. The results of multivariate logistic regression analysis demonstrated that the National Institutes of Health Stroke Scale (NIHSS), NLR d1, NLR d3, and NLR d7 were independently associated with functional outcomes. The area under the receiver operating characteristic curve of NLR in predicting outcomes was as follows: NLR d3 demonstrated robust predictive power within the IVT therapy cohort, whereas NLR d7 was predictive in the non-IVT cohort. However, the most potent predictor emerged as the combination of NIHSS and NLR. CONCLUSION: NLR has the potential to predicate diagnosis for AIS, especially when combined with the NIHSS score.

Shrimp shapes a resistance trait against vibriosis by memorizing the colonization resistance of intestinal microbiota.

Vibriosis is one of the most serious diseases that commonly occurs in aquatic animals, thus, shaping a steady inherited resistance trait in organisms has received the highest priority in aquaculture. Whereas, the mechanisms underlying the development of such a resistance trait are mostly elusive. In this study, we constructed vibriosis-resistant and susceptible families of the Pacific white shrimp Litopenaeus vannamei after four generations of artificial selection. Microbiome sequencing indicated that shrimp can successfully develop a colonization resistance trait against Vibrio infections. This trait was characterized by a microbial community structure with specific enrichment of a single probiotic species (namely Shewanella algae), and notably, its formation was inheritable and might be memorized by host epigenetic remodeling. Regardless of the infection status, a group of genes was specifically activated in the resistant family through disruption of complete methylation. Specifically, hypo-methylation and hyper-expression of genes related to lactate dehydrogenase (LDH) and iron homeostasis might provide rich sources of specific carbon (lactate) and ions for the colonization of S. algae, which directly results in the reduction of Vibrio load in shrimp. Lactate feeding increased the survival of shrimp, while knockdown of LDH gene decreased the survival when shrimp was infected by Vibrio pathogens. In addition, treatment of shrimp with the methyltransferase inhibitor 5-azacytidine resulted in upregulations of LDH and some protein processing genes, significant enrichment of S. algae, and simultaneous reduction of Vibrio in shrimp. Our results suggest that the colonization resistance can be memorized as epigenetic information by the host, which has played a pivotal role in vibriosis resistance. The findings of this study will aid in disease control and the selection of superior lines of shrimp with high disease resistance.

SIRT1 promotes chemoradiotherapy resistance in esophageal squamous cell carcinoma.

Introduction Identifying accurate biomarkers for predicting response to chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC) is a critical challenge. The protein SIRT1, recognized for its implications in longevity, has been associated with tumor promotion in ESCC. However, data regarding its correlation with CRT sensitivity remains unreported. Therefore, in this study, we aimed to investigate the relationship between SIRT1 expression and CRT sensitivity and concurrently assess the effect of SIRT1 knockdown on CRT sensitivity in ESCC. Methods This study included 73 patients who underwent radical esophagectomy after CRT. SIRT1 expression in pre-treatment endoscopic biopsies was assessed through immunostaining, followed by a comparative analysis of CRT effects on surgical specimens. Small interfering RNA was used to attenuate SIRT1 expression in TE5 and TE10 cells, which were then subjected to cisplatin treatment at varying doses and concentrations and irradiation with X-rays, respectively. Results High SIRT1 tissue expression was significantly associated with CRT resistance. Multivariate analysis identified high SIRT1 expression as an independent biomarker for poor CRT response. In TE-5 and TE-10 cells, SIRT1 knockdown significantly decreased cell viability and increased sensitivity to cisplatin and radiation treatment compared to that of the negative control. Conclusion Our study results demonstrate the potential of SIRT1 as a predictive biomarker for CRT response in ESCC, highlighting the heightened sensitivity to CRT upon the transcriptional inactivation of SIRT1. Targeting SIRT1 emerges as a promising strategy for enhancing the efficacy of CRT for ESCC.

A High-Performance Pixel-Level Fully Pipelined Hardware Accelerator for Neural Networks.

The design of convolutional neural network (CNN) hardware accelerators based on a single computing engine (CE) architecture or multi-CE architecture has received widespread attention in recent years. Although this kind of hardware accelerator has advantages in hardware platform deployment flexibility and development cycle, it is still limited in resource utilization and data throughput. When processing large feature maps, the speed can usually only reach 10 frames/s, which does not meet the requirements of application scenarios, such as autonomous driving and radar detection. To solve the above problems, this article proposes a full pipeline hardware accelerator design based on pixel. By pixel-by-pixel strategy, the concept of the layer is downplayed, and the generation method of each pixel of the output feature map (Ofmap) can be optimized. To pipeline the entire computing system, we expand each layer of the neural network into hardware, eliminating the buffers between layers and maximizing the effect of complete connectivity across the entire network. This approach has yielded excellent performance. Besides that, as the pixel data stream is a fundamental paradigm in image processing, our fully pipelined hardware accelerator is universal for various CNNs (MobileNetV1, MobileNetV2 and FashionNet) in computer vision. As an example, the accelerator for MobileNetV1 achieves a speed of 4205.50 frames/s and a throughput of 4787.15 GOP/s at 211 MHz, with an output latency of 0.60 ms per image. This extremely shorts processing time and opens the door for AI's application in high-speed scenarios.

Identification of State Markers in Anorexia Nervosa: Replication and Extension of Inflammation-Associated Biomarkers Using Multiplex Profiling.

Background: Proteomics offers potential for detecting and monitoring anorexia nervosa (AN) and its variant, atypical AN (atyp-AN). However, research has been limited by small protein panels, a focus on adult AN, and lack of replication. Methods: In this study, we performed Olink multiplex profiling of 92 inflammation-related proteins in females with AN/atyp-AN (n = 64), all of whom were ≤90% of expected body weight, and age-matched healthy control individuals (n = 44). Results: Five proteins differed significantly between the primary AN/atyp-AN group and the healthy control group (lower levels: HGF, IL-18R1, TRANCE; higher levels: CCL23, LIF-R). The expression levels of 3 proteins (lower IL-18R1, TRANCE; higher LIF-R) were uniquely disrupted in participants with AN in our primary model. No unique expression levels emerged for atyp-AN. In the total sample, 12 proteins (ADA, CD5, CD6, CXCL1, FGF-21, HGF, IL-12B, IL18, IL-18R1, SIRT2, TNFSF14, TRANCE) were positively correlated with body mass index and 5 proteins (CCL11, FGF-19, IL8, LIF-R, OPG) were negatively correlated with body mass index in our primary models. Conclusions: Our results replicate the results of a previous study that demonstrated a dysregulated inflammatory status in AN and extend those results to atyp-AN. Of the 17 proteins correlated with body mass index, 11 were replicated from a previous study that used similar methods, highlighting the promise of inflammatory protein expression levels as biomarkers of AN disease monitoring. Our findings underscore the complexity of AN and atyp-AN by highlighting the inability of the identified proteins to differentiate between these 2 subtypes, thereby emphasizing the heterogeneous nature of these disorders.

We examined 73 inflammation proteins in adolescent girls with anorexia nervosa (AN) and atypical AN and compared them with age-matched healthy control girls. Significant differences were found, driven by 5 key proteins (lower: HGF, IL-18R1, TRANCE; higher: CCL23, LIF-R). Three proteins (TRANCE, LIF-R, IL-18R1) uniquely distinguished low-weight participants with AN from control participants. Our study reveals distinct inflammation patterns in AN and atypical AN and sheds light on potential state-specific factors that underlie these disorders.

Significant influence of land use types and anthropogenic activities on the distribution of microplastics in soil: A case from a typical mining-agricultural city.

Microplastics pollution in soil has become a prominent issue in the field of ecological environment. However, relevant data on the microplastics pollution characteristics in mining industry-agricultural soil ecosystems is still limited. In this study, an extensive investigation on the characteristics of microplastics pollution in typical mining-agricultural city soil was conducted, revealing abundances, features, and influencing factors of microplastics in five land use types including facility farmland (FF), traditional farmland (TF), residential land (RL), industrial land (IL), and grassland (GL). The results showed that the distribution of microplastics abundances exhibits a nonuniform pattern, and the highest microplastics abundance was found in FF (3738 ± 2097 items·kg-1) compared with the other four land use types of this study area. Moreover, the key polymers identified were polypropylene (PP) and polyethylene (PE) with a smaller size (<0.01 mm) accounting for the majority at ,45 %, primary colors of microplastics were transparent with the dominant shapes being fibers and fragments. Additionally, principal component analysis and cluster analysis characterized microplastics features across various land use patterns, revealing that agricultural plastic waste, irrigation, and fertilization may be the main the primary sources of agricultural microplastics, while domestic sewage, household waste (include construction waste), and mining transportation activities are the potential urban sources. Correlation analysis indicates a positive relationship between TN, TP, SOC, and the abundances of microplastics (P < 0.05), and a negative relationship between pH and microplastic abundances. Furthermore, Cd, Cu, and As exhibit a significant positive correlation with microplastic characteristics (P < 0.05). Notably, the distribution trends of Cd content and microplastic abundance are similar. Overall, comprehensive analysis of environmental dynamics on microplastics in agricultural soil in coal industrial cities is crucial for developing effective measures to prevent and control microplastic pollution.

Inverse Isotope Kinetic Effect of the Charge Transfer Reactions of Ar+ with H2O and D2O.

Hydrogen isotopic effect, as the key to revealing the origin of Earth's water, arises from the H/D mass difference and quantum dynamics at the transition state of reaction. The ion-molecule charge-exchange reaction between water (H2O/D2O) and argon ion (Ar+) proceeds spontaneously and promptly, where there is no transition-state or intermediate complex. In this energetically resonant process, we find an inverse kinetic isotope effect (KIE) leading to the higher charge transfer rate for D2O, by the velocity map imaging measurements of H2O+/D2O+ products. Using the average dipole orientation capture model, we estimate the orientation angles of C2v axis of H2O/D2O relative to the Ar+ approaching direction and attribute to the difference of stereodynamics. According to the long-distance Landau-Zener charge transfer model, this inverse KIE could be also attributed to the density-of-state difference of molecular bending motion between H2O+ and D2O+ around the resonant charge transfer.

Central nervous system efficacy of aumolertinib versus gefitinib in patients with untreated, EGFR-mutated, advanced non-small cell lung cancer: data from a randomized phase III trial (AENEAS).

BACKGROUND: The initial randomized, double-blinded, actively controlled, phase III ANEAS study (NCT03849768) demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first-line therapy in epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC). Metastatic disease in the central nervous system (CNS) remains a challenge in the management of NSCLC. This study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS study. METHODS: Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double-blinded fashion. Patients with asymptomatic, stable CNS metastases were included. Follow-up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months, then every 12 weeks. CNS response was assessed by a neuroradiological blinded, independent central review (neuroradiological-BICR). The primary endpoint for this subgroup analysis was CNS progression-free survival (PFS). RESULTS: Of the 429 patients enrolled and randomized in the ANEAS study, 106 patients were found to have CNS metastases (CNS Full Analysis Set, cFAS) at baseline by neuroradiological-BICR, and 60 of them had CNS target lesions (CNS Evaluable for Response, cEFR). Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS (29.0 vs. 8.3 months; hazard ratio [HR] = 0.31; 95% confidence interval [CI], 0.17-0.56; P < 0.001) and cEFR (29.0 vs. 8.3 months; HR = 0.26; 95% CI, 0.11-0.57; P < 0.001). The confirmed CNS overall response rate in cEFR was 85.7% and 75.0% in patients treated with aumolertinib and gefitinib, respectively. Competing risk analysis showed that the estimated probability of CNS progression without prior non-CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNS metastases at baseline. No new safety findings were observed. CONCLUSIONS: These results indicate a potential advantage of aumolertinib over gefitinib in terms of CNS PFS and the risk of CNS progression in patients with EGFR-mutated advanced NSCLC with baseline CNS metastases. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03849768.

Effects of combined treatment with hydrogen-rich electrolyzed water and tea polyphenols on oxidative stress, intestinal injury and intestinal flora disruption in heat-stressed mice.

Heat stress (HS) can cause damage to the organism, especially the intestinal tract. In this paper, we investigated the effects of the combined action of tea polyphenols (TP) and hydrogen-rich electrolyzed water (HRW) on HS in mice. The combination of HRW feeding and TP of intraperitoneal injection was screened by in vitro antioxidant activity assay. The results revealed that the combined treatment was more helpful in alleviating the effects of HS on the behavior, growth performance, oxidative damage, and intestinal tract of mice compared with the respective treatments of TP and HRW (P < 0.05). Additionally, the combined treatment could repair HS-induced intestinal dysbiosis in mice, augmenting the number and abundance of bacteria, increasing the number of beneficial genera (Lachnospiraceae_NK4A136_group and Lactobacillus), and decreasing the number of harmful genera (Desulfovibrio and Enterorhabdus), and the effect was significantly better than that of individual treatment (P < 0.05). In conclusion, the combined treatment of TP and HRW effectively mitigates the adverse effects of HS on mouse behavior, growth performance, oxidative damage, and intestinal dysbiosis, surpassing the efficacy of individual treatments with TP or HRW alone.