Proteomics and SSH Analyses of ALA-Promoted Fruit Coloration and Evidence for the Involvement of a MADS-Box Gene, MdMADS1

Skin color is a key quality attribute of fruits and how to improve fruit coloration has long been a major concern. 5-Aminolevulinic acid (ALA), a natural plant growth regulator, can significantly increase anthocyanin accumulation in fruit skin and therefore effectively improve coloration of many fruits, including apple. However, the molecular mechanism how ALA stimulates anthocyanin accumulation in fruit skin remains unknown. Here, we investigated the impact of ALA on apple skin at the protein and mRNA levels. A total of 85 differentially expressed proteins in apple skins between ALA and water treatment (control) were identified by complementary gel-based and gel-freeseparation techniques. Most of these differentially expressed proteins were up-regulated by ALA. Function analysis suggested that 87.06% of the ALA-responsive proteins were associated with fruit ripening. To further screen ALA-responsive regulators, we constructed a subtracted cDNA library (tester: ALA treatment; driver: control) and obtained 104 differentially expressed unigenes, of which 38 unigenes were indicators for the fruit ripening-related gene. The differentially changed proteins and transcripts did not correspond well at an individual level, but showed similar regulated direction in function at the pathway level. Among the identified fruit ripening-related genes, the expression of MdMADS1, a developmental transcription regulator of fruit ripening, was positively correlated with expression of anthocyanin biosynthetic genes (MdCHS, MdDFR, MdLDOX and MdUFGT) in apple skin under ALA treatment. Moreover, overexpression of MdMADS1 enhanced anthocyanin content in transformed apple calli, which was further enhanced by ALA. The anthocyanin content in MdMADS1-silenced calli was less than that in the control with ALA treatment, but higher than that without ALA treatment. These results indicated that MdMADS1 is involved in ALA-induced anthocyanin accumulation. In addition, anthocyanin-related verification in apple calli suggested that the regulation of MdMADS1 on anthocyanin biosynthesis was partially independent of fruit ripening process. Taken together, our findings provide insight into the mechanism how ALA regulates anthocyanin accumulation and add new information on transcriptase regulators of fruit coloration

Resolution limits for radiation-induced acoustic imaging for in vivo radiation dosimetry

Objective.Radiation-induced acoustic (RA) computed tomographic (RACT) imaging is being thoroughly explored for radiation dosimetry. It is essential to understand how key machine parameters like beam pulse, size, and energy deposition affect image quality in RACT. We investigate the intricate interplay of these parameters and how these factors influence dose map resolution in RACT.Approach.We first conduct an analytical assessment of time-domain RA signals and their corresponding frequency spectra for certain testcases, and computationally validate these analyses. Subsequently, we simulated a series of x-ray-based RACT (XACT) experiments and compared the simulations with experimental measurements.In-silicoreconstruction studies have also been conducted to demonstrate the resolution limits imposed by the temporal pulse profiles on RACT. XACT experiments were performed using clinical machines and the reconstructions were analyzed for resolution capabilities.Main results.Our paper establishes the theory for predicting the time- and frequency-domain behavior of RA signals. We illustrate that the frequency content of RA signal is not solely dependent on the spatial energy deposition characteristics but also on the temporal features of radiation. The same spatial energy deposition through a Gaussian pulse and a rectangular pulse of equal pulsewidths results in different frequency spectra of the RA signals. RA signals corresponding to the rectangular pulse exhibit more high-frequency content than their Gaussian pulse counterparts and hence provide better resolution in the reconstructions. XACT experiments with ∼3.2 us and ∼4 us rectangular radiation pulses were performed, and the reconstruction results were found to correlate well with thein-silicoresults.Significance.Here, we discuss the inherent resolution limits for RACT-based radiation dosimetric systems. While our study is relevant to the broader community engaged in research on photoacoustics, x-ray-acoustics, and proto/ionoacoustics, it holds particular significance for medical physics researchers aiming to set up RACT for dosimetry and radiography using clinical radiation machines

Iurnal Variability of Airway Hyperresponsiveness in Asthma Patients

BackgroundThere are daytime variability in pulmonary function indexes such as peak expiratory flow (PEF) and forced expiratory volume in 1 second (FEV1) in asthma patients. Studies evaluating the effects of drug therapy on lung function and airway hyperresponsiveness (AHR) in asthma patients all required patients to perform spirometry and bronchial challenge test in the same time point of the days. However, whether there is a daily diurnal AHR variability is still not clear.ObjectiveTo explore the characteristics and diurnal variability of AHR in asthma patients.MethodsThe data of 202 patients with asthma who consulted in respiratory department of the First Affiliated Hospital of Guangzhou Medical University from January 2018 to September 2020 were included for statistical analysis. All patients completed the methacholine bronchial provocation tests, they were divided into the morning detection group (morning group) with 81 cases and the afternoon detection group (afternoon group) with 121 cases; according to the disease course, 98 cases were divided into the initial diagnosis group if the disease course was ≤6 months, and 104 cases were divided into the follow-up group if the disease course was >6 months. The initial diagnosis group and the follow-up group were divided into the initial diagnosis morning group, the initial diagnosis afternoon group, the follow-up morning group, and the follow-up afternoon group according to the detection time; according to the AHR, the patients were divided into very mild, mild, moderate and severe groups. The characteristics of AHR and the main pulmonary function indexes including FVC%pred, FEV1%pred, PEF%pred, MMEF%pred, MEF50%pred, MEF25%pred, PD20-FEV1, PD20-PEF, PD20-MMEF, PD20-MEF25%, PD20-MEF50% of these groups were analyzed and compared.ResultsThere were no significant differences of the math pulmonary function indexes and PD20 between morning and afternoon groups (P<0.05) . FEV1%pred and PD20-PEF were significantly higher in initial diagnosed group than follow-up group (P<0.05) . There was no significant difference in FVC%pred, PEF%pred, MMEF%pred, MEF50%pred, MEF25%pred, PD20-FEV1, PD20-MMEF, PD20-MEF25%, and PD20-MEF50% between the initial visit group and the follow-up visit group (P>0.05) . In follow-up group, MMEF%pred and MEF50%pred were higher in afternoon than in morning (P<0.05) . There were no differences of lung function and AHR between morning and afternoon in initial diagnosed group (P<0.05) . No obvious correlations were found between disease history and PD20. There were no significant differences of PD20-FEV1 between the morning and afternoon, initial diagnosed and follow-up (P>0.05) .ConclusionThe longer the duration of asthma, more serious impairment of lung function found in asthma, while the AHR had no significant difference between morning and afternoon

Cost-effectiveness analysis of gumarontinib versus savolitinib for the treatment of advanced or metastatic NSCLC with MET exon 14 skipping mutations in China using partitioned survival model

Background and objectivesBoth gumarontinib and savolitinib have demonstrated efficacy in treating non-small-cell lung cancer (NSCLC) with tumors harboring mesenchymal–epithelial transition factor gene exon 14 (METex14) skipping. However, the comparison of their efficacy and pharmacoeconomics profiles remains limited. This study aims to evaluate the cost-effectiveness of gumarontinib versus savolitinib for the treatment of METex14 skipping NSCLC in China.MethodsA 3-state partitioned survival model (PSM) was developed with lifetime horizon from the perspective of Chinese healthcare system. Survival inputs were based on an unanchored matching-adjusted indirect comparison using individual patient data from GLORY trial to adjust for patient characteristics in NCT02897479. Costs and outcomes were discounted at an annual rate of 5%. Sensitivity and scenario analyses were conducted to explore model uncertainty.ResultsGumarontinib gained an additional 0.10 QALYs at an incremental cost of $1,893 compared to savolitinib, resulting in the ICERs of$19,243/QALY, which is below the threshold of 3 times the GDP per capita in China ($35,007 per capita in 2022). Sensitivity and scenario analyses confirmed the robustness of the base-case results.ConclusionGumarontinib is a cost-effective option compared to savolitinib for METex14 skipping NSCLC in China

A preliminary evaluation of efficacy and safety of Wharton’s jelly mesenchymal stem cell transplantation in patients with type 2 diabetes mellitus

INTRODUCTION: Stem cell therapy has recently been introduced to treat patients with type 2 diabetes mellitus (T2DM). However, no data are available on the efficacy and safety of allogeneic Wharton’s Jelly-derived mesenchymal stem cell (WJ-MSC) transplantation in patients with T2DM. Here we performed a non-placebo controlled prospective phase I/II study to determine efficacy and safety of WJ-MSC transplantation in T2DM. METHODS: Twenty-two patients with T2DM were enrolled and received WJ-MSC transplantation through one intravenous injection and one intrapancreatic endovascular injection (catheterization). They were followed up for 12 months after transplantation. The primary endpoints were changes in the levels of glycated hemoglobin and C-peptide and the secondary endpoints included insulin dosage, fasting blood glucose (FBG), post-meal blood glucose (PBG), inflammatory markers and T lymphocyte counts. RESULTS: WJ-MSC transplantation significantly decreased the levels of glucose and glycated hemoglobin, improved C-peptide levels and beta cell function, and reduced markers of systemic inflammation and T lymphocyte counts. No major WJ-MSC transplantation-related adverse events occurred, but data suggest a temporary decrease in levels of C-peptide and beta cell function at one month after treatment, possibly related to intrapancreatic endovascular injection. CONCLUSIONS: Our data demonstrate that treatment with WJ-MSCs can improve metabolic control and beta cell function in patients with T2DM. The therapeutic mechanism may involve improvements in systemic inflammation and/or immunological regulation. TRIAL REGISTRATION: Chinese Clinical Trial Register ChiCTR-ONC-10000985. Registered 23 September 201

Berberine attenuates TNBS-induced colitis in mice by improving the intestinal microbiota

ObjectiveTo investigate the effects of berberine (BBR) as a treatment on intestinal microecological alterations and enteritis in mice produced by TNBS.MethodsThere were seven mice per group: seven in the healthy group (Ctrl), seven in the TNBS-induced enteritis group (TNBS), and seven in the berberine treatment group (BBR). The mice were weighed, slaughtered after 7 days, and subjected to high-throughput intestinal microecological analysis by Illumina, as well as haematological detection and imaging evaluation of colon pathology.ResultsThe alterations in colon length, immune cell subpopulations, inflammatory factors, and intestinal microecology of mice induced by BBR were refined using a battery of experiments and observations. According to intestinal microecological studies, BBR can increase the number of bacteria, including Lactobacillus, Verrucomicrobia, Bacteroides, and Akkermansia muciniphila.ConclusionBBR has a therapeutic effect on TNBS-induced colitis in mice, which is associated with modifications in immune cell subpopulations and intestinal microecology. It also offers a viable approach as a prospective probiotic (like Akkermansia muciniphila) to IBD therapy in clinical settings

The BMAL1/HIF2A heterodimer modulates circadian variations of myocardial injury

Acute myocardial infarction stands as a prominent cause of morbidity and mortality worldwid

Foundation models and intelligent decision-making: Progress, challenges, and perspectives

Intelligent Decision-Making (IDM) is a cornerstone of artificial intelligence (AI), designed to automate or augment decision processes. Modern IDM paradigms integrate advanced frameworks to enable intelligent agents to make effective and adaptive choices and decompose complex tasks into manageable steps, such as AI agents and high-level reinforcement learning. Recent advances in multimodal foundation-based approaches unify diverse input modalities—such as vision, language, and sensory data—into a cohesive decision-making process. Foundation Models (FMs) have become pivotal in science and industry, trans- forming decision-making and research capabilities. Their large-scale, multimodal data-processing abilities foster adaptability and interdisciplinary breakthroughs across fields such as healthcare, life sciences, and education. This survey examines IDM’s evolution, advanced paradigms with FMs, and their transformative impact on decision-making across diverse scientific and industrial domains, highlighting the challenges and opportunities in building efficient, adaptive, and ethical decision systems.<br/