PpBBX32 and PpZAT5 modulate temperature-dependent and tissue-specific anthocyanin accumulation in peach fruit.

Anthocyanins are important compounds for fruit quality and nutrition. The R2R3 MYB transcription factor PpMYB10.1 is known to be critical for regulating anthocyanin accumulation in peach. However, regulatory factors upstream of PpMYB10.1 which control temperature-dependent, cultivar-contrasted and tissue-specific anthocyanin accumulation remain to be determined. In this study, differential anthocyanin accumulation in the outer flesh near the peel (OF) of peach [Prunus persica (L.) Batsch] was observed between cultivars 'Zhonghuashoutao' and 'Dongxuemi', as well as among different storage temperatures and different fruit tissues of 'Zhonghuashoutao'. By cross-comparisons of RNA-Seq data of samples with differential anthocyanin accumulation, transcription factor genes PpBBX32 and PpZAT5 were identified. These were functionally characterized as two positive regulators for anthocyanin accumulation via transient expression and genetic transformation. Various interaction assays revealed that both PpBBX32 and PpZAT5 can directly activate the PpMYB10.1 promoter and meanwhile interact at protein level as a PpZAT5-PpBBX32-PpMYB10.1 complex. Furthermore, the results of in silico analysis and exogenous application of methyl jasmonate (MeJA) indicated that MeJA favored anthocyanin accumulation, while it was also found that anthocyanin accumulation as well as PpBBX32 and PpZAT5 expression correlated significantly with endogenous JA and JA-Ile in different fruit tissues. In summary, PpBBX32 and PpZAT5 are upstream activators of PpMYB10.1, allowing JAs to take part in temperature-dependent and tissue-specific anthocyanin accumulation by modulating their expression. This work enriches the knowledge of the transcriptional regulatory mechanisms for differential anthocyanin accumulation under internal and external factors.

Primary Sjogren's Syndrome Associated with Lung Adenocarcinoma: Probing the Potential Common Pathogenic Mechanisms and Experimental Verification.

This study aimed to probe the potential common pathogenic mechanisms linking primary Sjogren's syndrome (pSS) and lung adenocarcinoma (LUAD) through bioinformatics analysis and experimental verification. The relevant genes associated with pSS and LUAD were retrieved from the Gene Expression Omnibus (GEO) database and Genecard database. Subsequently, differentially expressed genes (DEGs) associated with pSS and LUAD were screened as pSS-LUAD-DEGs. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were performed to elucidate the significant biological functions of pSS-LUAD-DEGs. Core targets were identified by constructing the protein-protein interaction (PPI) network, further assessing hub gene diagnostic accuracy through Receiver Operating Characteristic (ROC) curve analyses. In this study, NOD/Ltj mice served as pSS animal models and were stimulated with particulate matter 2.5 (PM2.5) to generate an inflammatory reaction. Quantitative real-time polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA), and western blotting were employed for relevant molecular biology experiment verification. The results revealed through KEGG and GO enrichment analyses indicate that inflammation plays a critical role in linking pSS and LUAD. IL6, CCNA2, JAK2, IL1B, ASPM, CCNB2, NUSAP1, and CEP55 were determined as key targets of pSS-LUAD. BALB/c mice and NOD/Ltj mice exhibited enhanced expression of inflammatory cytokines IL-6 and IL-1ß in lung tissues following 21 days of stimulation with PM2.5, activating the JAK2/STAT3 signaling pathway and up-regulating the expression of tumor-associated genes CCNA2, CCNB2, and CEP55, with NOD/Ltj mice exhibiting more pronounced changes than BALB/c mice. This protocol demonstrates that carcinogenesis induced by the pulmonary inflammatory microenvironment may be a key reason for the high incidence of LUAD in pSS patients. Additionally, blocking-related mechanisms may help prevent the occurrence of LUAD in pSS patients.

Evaluating T1-weighted MRI techniques for fetal gastrointestinal diagnostics: A comparative study.

PURPOSE: In clinical practice, fetal gastrointestinal magnetic resonance imaging (MRI) encounters significant challenges. T1-weighted images are particularly susceptible to the effects of fetal and maternal movements compared to other weighted images, complicating the acquisition of satisfactory results. This study aimed to compare three fast 3D-T1 weighted gradient echo (GRE) sequences-free-breathing stack-of-stars VIBE (STAR-VIBE), breath-hold VIBE (BH-VIBE), and free-breathing multi-average VIBE (MA-VIBE)-for fetal gastrointestinal MRI in fetuses with both normal and abnormal gastrointestinal tracts between 21 and 36 weeks of gestation. METHODS: This study enrolled 67 pregnant women who underwent fetal abdominal MRI at our hospital between October 2022 and October 2023, during their gestational period of 21-36 weeks. Among these participants, 22 were suspected of having fetal gastrointestinal anomalies based on ultrasound findings, while the remaining 45 were considered to have normal fetal gastrointestinal development. All subjects underwent True fast imaging with steady-state precession sequence scanning along with three T1-weighted imaging techniques on a Siemens 1.5-T Aera scanner: STAR-VIBE, BH-VIBE, and MA-VIBE. Two radiologists evaluated image quality, intestinal clarity, and lesion conspicuity using a five-point scale where higher scores indicated superior performance for each technique; they were blinded to the acquisition schemes used. Interobserver variability assessments were also conducted. RESULTS: The free-breathing MA-VIBE sequence demonstrated significantly better performance than both STAR-VIBE and BH-VIBE in terms of fetal gastrointestinal MRI quality (3.81 ± 0.40 vs. 3.35 ± 0.70 vs. 2.90 ± 0.64; p < .05). The STAR-VIBE and BH-VIBE sequences exhibited moderate consistency (kappa = 0.586 and kappa = 0.527 respectively; P < .05), whereas the MA-VIBE sequence showed higher consistency (kappa = 0.712; P < .05). CONCLUSION: The free-breathing MA-VIBE sequence provided superior visualization for assessing fetal intestinal conditions compared to other methods employed in this study. On a 1.5 T MRI device, T1-weighted images based on the free-breathing MA-VIBE sequence can effectively overcome motion artifacts and compensate for the reduced signal-to-noise ratio caused by the application of acceleration techniques, thus significantly improving the quality of T1-weighted images.

Successfully treatment of PLZF-RARα positive acute promyelocytic leukemia by Venetoclax combining with decitabine: a case report and literature review.

INTRODUCTION: Acute promyelocytic leukemia (APL) is mainly due to the chromosome translocation t(15; 17) (q22; q12), leading to the formation of PML-RARα fusion protein. However, some patients carried rare translocation involving RARα gene, and they were referred to as variant APL caused by the RAR family (RARα, RARB, and RARG) and partner genes. PLZF-RARα was a rare type of molecular genetic abnormality with unfavorable prognosis that has been reported in few cases in variant APL. Knowledge of PLZF-RARα (+) APL treatment remains limited understood. CASE REPORT: We presented a case of variant APL in a 47-year-old female, who was PLZF-RARα positive detected by reverse transcription polymerase chain reaction (RT-PCR). The patient did not respond to all-trans retinoic acid (ATRA), idarubicin, and arsenic trioxide (As2O3) combined induction chemotherapy. Then, the patient was treated with Venetoclax combining with decitabine as the salvage therapy and achieved morphological remission and PLZF/RARα gene negative. CONCLUSION: Venetoclax combining with decitabine can be used as an effective therapy in the PLZF-RARα positive APL.

Spatial resolved transcriptomics reveals distinct cross-talk between cancer cells and tumor-associated macrophages in intrahepatic cholangiocarcinoma.

BACKGROUND: Multiple studies have shown that tumor-associated macrophages (TAMs) promote cancer initiation and progression. However, the reprogramming of macrophages in the tumor microenvironment (TME) and the cross-talk between TAMs and malignant subclones in intrahepatic cholangiocarcinoma (iCCA) has not been fully characterized, especially in a spatially resolved manner. Deciphering the spatial architecture of variable tissue cellular components in iCCA could contribute to the positional context of gene expression containing information pathological changes and cellular variability. METHODS: Here, we applied spatial transcriptomics (ST) and digital spatial profiler (DSP) technologies with tumor sections from patients with iCCA. RESULTS: The results reveal that spatial inter- and intra-tumor heterogeneities feature iCCA malignancy, and tumor subclones are mainly driven by physical proximity. Tumor cells with TME components shaped the intra-sectional heterogenetic spatial architecture. Macrophages are the most infiltrated TME component in iCCA. The protein trefoil factor 3 (TFF3) secreted by the malignant subclone can induce macrophages to reprogram to a tumor-promoting state, which in turn contributes to an immune-suppressive environment and boosts tumor progression. CONCLUSIONS: In conclusion, our description of the iCCA ecosystem in a spatially resolved manner provides novel insights into the spatial features and the immune suppressive landscapes of TME for iCCA.

Evaluation and modeling of diaphragm displacement using ultrasound imaging for wearable respiratory assistive robot.

Introduction: Assessing the influence of respiratory assistive devices on the diaphragm mobility is essential for advancing patient care and improving treatment outcomes. Existing respiratory assistive robots have not yet effectively assessed their impact on diaphragm mobility. In this study, we introduce for the first time a non-invasive, real-time clinically feasible ultrasound method to evaluate the impact of soft wearable robots on diaphragm displacement. Methods: We measured and compared diaphragm displacement and lung volume in eight participants during both spontaneous and robotic-assisted respiration. Building on these measurements, we proposed a human-robot coupled two-compartment respiratory mechanics model that elucidates the underlying mechanism by which our extracorporeal wearable robots augments respiration. Specifically, the soft robot applies external compression to the abdominal wall muscles, inducing their inward movement, which consequently pushes the diaphragm upward and enhances respiratory function. Finally, we investigated the level and shape of various robotic assistive forces on diaphragm motion. Results: This robotic intervention leads to a significant increase in average diaphragm displacement by 1.95 times and in lung volume by 2.14 times compared to spontaneous respiration. Furthermore, the accuracy of the proposed respiratory mechanics model is confirmed by the experimental results, with less than 7% error in measurements of both diaphragm displacement and lung volume. Finally, the magnitude of robotic assistive forces positively correlates with diaphragm movement, while the shape of the forces shows no significant relationship with diaphragm activity. Conclusion: Our experimental findings validate the effective assistance mechanism of the proposed robot, which enhances diaphragm mobility and assists in ventilation through extracorporeal robotic intervention. This robotic system can assist with ventilation while increasing diaphragm mobility, potentially resolving the issue of diaphragm atrophy. Additionally, this work paves the way for improved robotic designs and personalized assistance, tailored to the dynamics of the diaphragm in respiratory rehabilitation.

Functional characterization of Arabidopsis hydroxynitrile lyase in response to abiotic stress and the regulation of flowering time.

BACKGROUND: Hydroxynitrile lyases (HNLs) are a class of hydrolytic enzymes from a wide range of sources, which play crucial roles in the catalysis of the reversible conversion of carbonyl compounds derived from cyanide and free cyanide in cyanogenic plant species. HNLs were also discovered in non-cyanogenic plants, such as Arabidopsis thaliana, and their roles remain unclear even during plant growth and reproduction. METHODS AND RESULTS: The pattern of expression of the HNL in A. thaliana (AtHNL) in different tissues, as well as under abiotic stresses and hormone treatments, was examined by real-time quantitative reverse transcription PCR (qRT-PCR) and an AtHNL promoter-driven histochemical ß-glucuronidase (GUS) assay. AtHNL is highly expressed in flowers and siliques, and the expression of AtHNL was dramatically affected by abiotic stresses and hormone treatments. The overexpression of AtHNL resulted in transgenic A. thaliana seedlings that were more tolerance to mannitol and salinity. Moreover, transgenic lines of A. thaliana that overexpressed this gene were less sensitive to abscisic acid (ABA). Altered expression of ABA/stress responsive genes was also observed in hnl mutant and AtHNL-overexpressing plants, suggesting AtHNL may play functional roles on regulating Arabidopsis resistance to ABA and abiotic stresses by affecting ABA/stress responsive gene expression. In addition, the overexpression of AtHNL resulted in earlier flowering, whereas the AtHNL mutant flowered later than the wild type (WT) plants. The expression of the floral stimulators CONSTANS (CO), SUPPRESSOR OF OVER EXPRESSION OF CO 1 (SOC1) and FLOWERING LOCUS T (FT) was upregulated in plants that overexpressed AtHNL when compared with the WT plants. In contrast, expression of the floral repressor FLOWERING LOCUS C (FLC) was upregulated in AtHNL mutants and downregulated in plants that overexpressed AtHNL compared to the WT plants. CONCLUSION: This study revealed that AtHNL can be induced under abiotic stresses and ABA treatment, and genetic analysis showed that AtHNL could also act as a positive regulator of abiotic stress and ABA tolerance, as well as flowering time.

Fabrication of sulfur-based functionalized activated carbon as solid phase extraction adsorbent for selective analysis of selenite in water.

Based on the important feature of sulfur with excellent selectivity toward selenite in the presence of selenate, a simple and low-cost adsorbent of solid phase extraction known as sulfur loading activated carbon (SAC-6) was successfully prepared and applied for selenite (Se(IV)) analysis in water. Microstructure and morphological characteristics of SAC-6 had been identified by XRD, TEM, BET and FT-IR. In the static adsorption experiments, Se(IV) could be separated in a wide range of pH values (pH=3-11). The retention process of Se(IV) onto SAC-6 was characterized as spontaneous exothermic reaction. An obvious change of adsorption mechanism occurred in static and dynamic adsorption processes shown that the behaviors followed monolayer and hybrid adsorption. The theoretical maximum adsorption capacity of SAC-6 calculated by Langmuir-Freundlich was 13.48 mg/g. The microcolumn filled with SAC-6 was applied to extract Se(IV) in water solution. The detection limit of Se(IV) analytical procedure was confirmed as 0.27 µg/L within a linear range of 10-1000 µg/L. A good precision with relative standard deviation of 1.34 % (100 µg/L, n = 6) was achieved. The high adaptability and accuracy of SAC-6 microcolumn was validated by analyzing natural water samples and certified reference materials. Our work successfully excavated the application value of the sulfur selectivity, and also provided a new adsorbent for Se(IV) extraction and analysis.

Comparative analysis of element and hormone content in zygotic embryos of Pinus elliottii and P. elliottii × P. caribaea.

Somatic embryogenesis is a crucial method for achieving clonal forestry in conifers. Understanding the development of zygotic embryos is essential not only for enhancing the efficiency and quality of somatic embryogenesis, but also for advancing forestry breeding programs. This study investigated dynamic changes of element and hormone contents during ZE development of Pinus elliottii and its hybrid P. elliottii × P. caribaea. Significant differences in embryo development speed among different clones were observed. Elemental analysis was conducted using inductively coupled plasma mass spectrometry (ICP-MS) and identified 68 elements, including major, minor, and beneficial elements. In both species, the contents of potassium (K), calcium (Ca), iron (Fe), boron (B) and five beneficial elements decreased during early ZE development, while phosphorus (P) and copper (Cu) increased. Significantly higher levels of K, Ca and Fe at the initial stage, and sulfur (S) and nickel (Ni) decreased at later stages were detected in P. elliottii than in the hybrid. For the other elements, except for very few significant differences at certain stages, most differences between the two species did not reach a significant level. The contents of endogenous hormones were determined and different accumulation patterns were detected in most hormones between the two species, except abscisic acid (ABA) which simultaneously decreased with developments by stage 8. Significant differences were found in indole-3-acetic acid (IAA) contents at most stages between species, while higher levels of total cytokinin (CK) at each stage were detected in the hybrid in comparison with those in P. elliottii. As a result, lower IAA to CK ratios in the hybrid than in P. elliottii. Methyl jasmonate (JA-me) and gibberellin A3 (GA3) contents showed a similar pattern and exhibited an M-shaped fluctuation in the hybrid. Furthermore, JA-me, GA3, gibberellin A4 (GA4) and brassinolide (BR) showed significantly higher levels in the hybrid than in P. elliottii. K-means clustering and correlation analyses were used to explore relationships between elements and hormones during embryo development, revealing complex interplay in both species. These data indicate different requirement in element and hormone contents for embryogenesis and suggest species-specific media composition for each step in somatic embryogenesis. The findings provide insights into their developmental processes and informing future research and applications in somatic embryogenesis and forestry breeding.

Deep longitudinal lower respiratory tract microbiome profiling reveals genome-resolved functional and evolutionary dynamics in critical illness.

The lower respiratory tract (LRT) microbiome impacts human health, especially among critically ill patients. However, comprehensive characterizations of the LRT microbiome remain challenging due to low microbial mass and host contamination. We develop a chelex100-based low-biomass microbial-enrichment method (CMEM) that enables deep metagenomic profiling of LRT samples to recover near-complete microbial genomes. We apply the method to 453 longitudinal LRT samples from 157 intensive care unit (ICU) patients in three geographically distant hospitals. We recover 120 high-quality metagenome-assembled genomes (MAGs) and associated plasmids without culturing. We detect divergent longitudinal microbiome dynamics and hospital-specific dominant opportunistic pathogens and resistomes in pneumonia patients. Diagnosed pneumonia and the ICU stay duration were associated with the abundance of specific antibiotic-resistance genes (ARGs). Moreover, CMEM can serve as a robust tool for genome-resolved analyses. MAG-based analyses reveal strain-specific resistome and virulome among opportunistic pathogen strains. Evolutionary analyses discover increased mobilome in prevailing opportunistic pathogens, highly conserved plasmids, and new recombination hotspots associated with conjugative elements and prophages. Integrative analysis with epidemiological data reveals frequent putative inter-patient strain transmissions in ICUs. In summary, we present a genome-resolved functional, transmission, and evolutionary landscape of the LRT microbiota in critically ill patients.

Highly Curative Treatment of High-Risk Acute Promyelocytic Leukemia: Induction and Consolidation with ATRA+ATO+anthracyclines and Maintenance with ATRA+RIF.

Background: The aim of the study was to evaluate the efficacy and safety of induction and consolidation with all-trans retinoic acid (ATRA) +arsenic trioxide (ATO) +anthracyclines and maintenance with ATRA +Realgar-Indigo naturalis formula (RIF) for high-risk APL. Methods: Twenty-one patients with high-risk APL treated with ATRA+ATO+ anthracyclines for induction and consolidation and ATRA+RIF for maintenance from 2012 to 2021 were analyzed. Endpoints include morphological complete remission (CR) and complete molecular remission (CMR), early death (ED) and relapse, survival and adverse events (AEs). Results: After induction treatment, all 21 patients (100%) achieved morphological CR and 14 people (66.7%) achieved CMR. Five of the 21 patients did not undergo immunological minimal residual disease (MRD) examination after induction; however, 14 of the remaining 16 patients were MRD negative (87.5%). The median time to achieve CR and CMR was 26 days (range: 16-44) and 40 days (range: 22-75), respectively. The cumulative probability of achieving CR and CMR in 45 days was 100% and 76.2% (95% CI: 56.9-91.3%), respectively. All patients achieved CMR and MRD negativity after the three courses of consolidation treatment. The median follow-up was 66 months (25-142), with no central nervous system relapse and bone marrow morphological or molecular relapse until now, and all patients survived with 100% overall survival and 100% event-free survival. Grade 4 adverse events (AEs) were observed in 3 patients (14.3%) during the induction period including arrhythmia (n = 1), pulmonary infection (n = 1) and respiratory failure (n = 1); and the most frequent grade 3 AEs were pulmonary infection, accounting for 62.0% and 28.6%, respectively, during induction and consolidation treatment, followed by neutropenia, accounting for 42.9% and 38.1%, respectively. Conclusion: For newly diagnosed high-risk APL patients, induction and consolidation with ATRA+ATO+anthracyclines and maintenance with ATRA+RIF is a highly curative treatment approach.

Artificial intelligence-based predictive model for guidance on treatment strategy selection in oral and maxillofacial surgery.

Application of deep learning (DL) and machine learning (ML) is rapidly increasing in the medical field. DL is gaining significance for medical image analysis, particularly, in oral and maxillofacial surgeries. Owing to the ability to accurately identify and categorize both diseased and normal soft- and hard-tissue structures, DL has high application potential in the diagnosis and treatment of tumors and in orthognathic surgeries. Moreover, DL and ML can be used to develop prediction models that can aid surgeons to assess prognosis by analyzing the patient's medical history, imaging data, and surgical records, develop more effective treatment strategies, select appropriate surgical modalities, and evaluate the risk of postoperative complications. Such prediction models can play a crucial role in the selection of treatment strategies for oral and maxillofacial surgeries. Their practical application can improve the utilization of medical staff, increase the treatment accuracy and efficiency, reduce surgical risks, and provide an enhanced treatment experience to patients. However, DL and ML face limitations, such as data drift, unstable model results, and vulnerable social trust. With the advancement of social concepts and technologies, the use of these models in oral and maxillofacial surgery is anticipated to become more comprehensive and extensive.

Insufficient FUNDC1-dependent mitophagy due to early environmental cadmium exposure triggers mitochondrial redox imbalance to aggravate diet-induced lipotoxicity.

Cadmium (Cd) is a toxic contaminant widely spread in natural and industrial environments. Adolescent exposure to Cd increases risk for obesity-related morbidity in young adults including type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD). Despite this recognition, the direct impact of adolescent Cd exposure on the progression of MASLD later in life, and the mechanisms underlying these effects, remain unclear. Here, adolescent rats received control diet or diets containing 2 mg Cd2+/kg feed for 4 weeks, and then HFD containing 15% lard or control diet in young adult rats was selected for 6 weeks to clarify this issue. Data firstly showed that HFD-fed rats in young adulthood due to adolescent Cd exposure exhibited more severe MASLD, evidenced by increased liver damage, disordered serum and hepatic lipid levels, and activated NLRP3 inflammasome. Hepatic transcriptome analysis revealed the potential effects of mitochondrial dysfunction in aggravated MASLD due to Cd exposure. Verification data further confirmed that mitochondrial structure and function were targeted and disrupted during this process, shown by broken mitochondrial ridges, decreased mitochondrial membrane potential, imbalanced mitochondrial dynamic, insufficient ATP concentration, and enhanced mitochondrial ROS generation. However, mitophagy is inactively involved in clearance of damaged mitochondria induced by early Cd in HFD condition due to inhibited mitophagy receptor FUNDC1. In contrast, FUNDC1-dependent mitophagy activation prevents lipotoxicity aggravated by early Cd via suppressing mitochondrial ROS generation. Collectively, our data show that insufficient FUNDC1-dependent mitophagy can drive the transition from HFD-induced MASLD to MASH, and accordingly, these findings will provide a better understanding of potential mechanism of diet-induced metabolic diseases in the context of early environmental Cd exposure.

Dietary Triple-Strain Bacillus-Based Probiotic Supplementation Improves Performance, Immune Function, Intestinal Morphology, and Microbial Community in Weaned Pigs.

Probiotics provide health benefits and are used as feed supplements as an alternative prophylactic strategy to antibiotics. However, the effects of Bacillus-based probiotics containing more than two strains when supplemented to pigs are rarely elucidated. SOLVENS (SLV) is a triple-strain Bacillus-based probiotic. In this study, we investigate the effects of SLV on performance, immunity, intestinal morphology, and microbial community in piglets. A total of 480 weaned pigs [initial body weight (BW) of 8.13 ± 0.08 kg and 28 days of age] were assigned to three treatments in a randomized complete block design: P0: basal diet (CON); P200: CON + 200 mg SLV per kg feed (6.5 × 108 CFU/kg feed); and P400: CON + 400 mg SLV per kg feed (1.3 × 109 CFU/kg feed). Each treatment had 20 replicated pens with eight pigs (four male/four female) per pen. During the 31 d feeding period (Phase 1 = wean to d 14, Phase 2 = d 15 to 31 after weaning), all pigs were housed in a temperature-controlled nursery room (23 to 25 °C). Feed and water were available ad libitum. The results showed that the pigs in the P400 group increased (p < 0.05) average daily gain (ADG) in phase 2 and tended (p = 0.10) to increase ADG overall. The pigs in the P200 and P400 groups tended (p = 0.10) to show improved feed conversion ratios overall in comparison with control pigs. The pigs in the P200 and P400 groups increased (p < 0.05) serum immunoglobulin A, immunoglobulin G, and haptoglobin on d 14, and serum C-reactive protein on d 31. The pigs in the P200 group showed an increased (p < 0.01) villus height at the jejunum, decreased (p < 0.05) crypt depth at the ileum compared with other treatments, and tended (p = 0.09) to have an increased villus-crypt ratio at the jejunum compared with control pigs. The pigs in the P200 and P400 groups showed increased (p < 0.05) goblet cells in the small intestine. Moreover, the pigs in the P400 group showed down-regulated (p < 0.05) interleukin-4 and tumor necrosis factor-α gene expressions, whereas the pigs in the P400 group showed up-regulated occludin gene expression in the ileum. These findings suggest that SLV alleviates immunological reactions, improves intestinal microbiota balance, and reduces weaning stress in piglets. Therefore, SOLVENS has the potential to improve health and performance for piglets.

Clinical efficacy and immune response of neoadjuvant camrelizumab plus chemotherapy in resectable locally advanced oesophageal squamous cell carcinoma: a phase 2 trial.

BACKGROUND: Neoadjuvant immunotherapy is under intensive investigation for esophageal squamous cell carcinoma (ESCC). This study assesses the efficacy and immune response of neoadjuvant immunochemotherapy (nICT) in ESCC. METHODS: In this phase II trial (ChiCTR2100045722), locally advanced ESCC patients receiving nICT were enrolled. The primary endpoint was the pathological complete response (pCR) rate. Multiplexed immunofluorescence, RNA-seq and TCR-seq were conducted to explore the immune response underlying nICT. RESULTS: Totally 42 patients were enrolled, achieving a 27.0% pCR rate. The 1-year, 2-year DFS and OS rates were 89.2%, 64.4% and 97.3%, 89.2%, respectively. RNA-seq analysis highlighted T-cell activation as the most significantly enriched pathway. The tumour immune microenvironment (TIME) was characterised by high CD4, CD8, Foxp3, and PD-L1 levels, associating with better pathological regression (TRS0/1). TIME was categorised into immune-infiltrating, immune-tolerant, and immune-desert types. Notably, the immune-infiltrating type and tertiary lymphoid structures correlated with improved outcomes. In the context of nICT, TIM-3 negatively influenced treatment efficacy, while elevated TIGIT/PD-1 expression post-nICT correlated positively with CD8+ T cell levels. TCR-seq identified three TCR rearrangements, underscoring the specificity of T-cell responses. CONCLUSIONS: Neoadjuvant camrelizumab plus chemotherapy is effective for locally advanced, resectable ESCC, eliciting profound immune response that closely associated with clinical outcomes.

FCSSL: fusion enhanced contrastive self-supervised learning method for parallel MRI reconstruction.

The implementation of deep learning in Magnetic Resonance Imaging (MRI) has significantly advanced the reduction of data acquisition times. However, these techniques face substantial limitations in scenarios where acquiring fully sampled datasets is unfeasible or costly. To tackle this problem, we propose a Fusion enhanced Contrastive Self-Supervised Learning (FCSSL) method for parallel MRI reconstruction, eliminating the need for fully sampled k-space training dataset and coil sensitivity maps. First, we introduce a strategy based on two pairs of re-undersampling masks within a contrastive learning framework, aimed at enhancing the representational capacity to achieve higher quality reconstruction. Subsequently, a novel adaptive fusion network, trained in a self-supervised learning manner, is designed to integrate the reconstruction results of the framework. Experimental results on knee datasets under different sampling masks demonstrate that the proposed FCSSL achieves superior reconstruction performance compared to other self-supervised learning methods. Moreover, the performance of FCSSL approaches that of the supervised methods, especially under the 2DRU and RADU masks. The proposed FCSSL, trained under the 3× 1DRU and 2DRU masks, can effectively generalize to unseen 1D and 2D undersampling masks, respectively. For target domain data that exhibit significant differences from source domain data, the proposed model, fine-tuned with just a few dozen instances of undersampled data in the target domain, achieves reconstruction performance comparable to that achieved by the model trained with the entire set of undersampled data. The novel FCSSL model offers a viable solution for reconstructing high-quality MR images without needing fully sampled datasets, thereby overcoming a major hurdle in scenarios where acquiring fully sampled MR data is difficult.

Molecular mechanisms underlying natural deficient and ultraviolet-induced accumulation of anthocyanin in the peel of 'Jinxiu' peach.

Peach varieties that differ in red coloration due to varied anthocyanin accumulation result from transcriptional regulation by PpMYB10s, a group of specific R2R3 MYBs. Here we investigated the mechanisms driving a lack of anthocyanin in yellow-skinned 'Jinxiu' peach peel, as well as accumulation induced by UV irradiance. It was found that PpMYB10.1, PpMYB10.2 and PpMYB10.3 were positive regulators of anthocyanin accumulation, but the stimulation by PpMYB10.2 was weak. Low expression of PpMYB10.1 causes natural anthocyanin deficiency in 'Jinxiu' peel. However, the promoter sequences of PpMYB10.1 were identical in 'Jinxiu' and a naturally red-coloured peach 'Hujingmilu'. Therefore, potential negative regulator(s) upstream of PpMYB10.1 were explored. A novel R2R3-MYB repressor termed PpMYB80 was identified through comparative transcriptomic analysis and then functionally confirmed via transiently overexpressing and silencing in peach fruit, as well as transformation in tobacco. PpMYB80 directly binds to the promoter of PpMYB10.1 and inhibits its expression, but does not affect PpMYB10.3. In UV-exposed 'Jinxiu' fruit, expression of PpMYB10.3 was upregulated, while PpMYB10.1 remained low and PpMYB80 enhanced, which results in accumulation of anthocyanin in peel. This study revealed a transcriptional cascade involving PpMYB activators and repressors in regulating basal and UV-induced anthocyanin accumulation in peach peel.

Operation strategy and capacity configuration of digital renewable energy power station with energy storage.

As the utilization of renewable energy sources continues to expand, energy storage systems assume a crucial role in enabling the effective integration and utilization of renewable energy. This underscores their fundamental significance in mitigating the inherent intermittency and variability associated with renewable energy sources. This study focuses on the involvement of photovoltaic (PV) plants in medium and long-term transactions. It also explores the participation of battery energy storage system (BESS) in electricity trading and frequency regulation ancillary services. The objective is to establish a strategic research model for maximizing the benefits of PV plant and the BESS in the energy arbitrage and frequency regulation markets. Sensitivity analysis was conducted to assess the impact of variations in both the rated power and maximum continuous energy storage duration of the BESS. Base on the NSGA-II algorithm and TOPSIS algorithm, an optimization model for energy storage capacity configuration is developed. The optimal capacity configuration and maximum continuous energy storage duration are determined through computational analysis, yielding values of 30.8 MW and 4.521 h, respectively. At this configuration, the daily average revenue is 2.362 × 105 yuan, the initial investment cost is 1.45 × 109 yuan, and the payback period is 4.562 years.

Depletion of NUAK2 blocks the stemness and angiogenesis and facilitates senescence of lung adenocarcinoma cells via enhancing ferroptosis.

BACKGROUND: NUAK family kinase 2 (NUAK2) has been identified as an important mediator for tumor progression in multiple malignancies. Nevertheless, its role in lung adenocarcinoma (LUAD) remains unclear. METHODS: Bioinformatic analysis was performed to assess the expression and prognosis of NUAK2 in patients with LUAD. The NUAK2 expression was measured in multiple LUAD cell lines, and the loss-of-function experiment was conducted. Cell proliferation ability was assessed using CCK-8 and colony formation assays. Spheroid formation, alkaline phosphatase (AP) staining, tube formation and SA-ß-gal staining assays were performed to examine stemness, angiogenesis and senescence. Lipid peroxidase was assessed by TBARS production and lipid ROS. Western blot was used to detect critical proteins. In addition, A549 cells were treated with ferroptosis inhibitor ferrostatin-1 (Fer-1) for a rescue assay. Finally, A549 cells were subcutaneously injected into the right flank of mice to establish LUAD-bearing mouse model, and the tumor weight and size were detected. RESULTS: NUAK2 was upregulated in patients with LUAD and LUAD cell lines. NUAK2 depletion inhibited cell viability, colonies, tumor spheres and decreased Oct4 and Nanog expression, confirming NUAK2 depletion inhibited proliferation and stemness of A549 cells. Meanwhile, NUAK2 depletion blocked angiogenesis via reducing formed tubes and VEGFR1/2 expression, and promoted senescence of A549 cells by elevating SA-ß-gal-positive cells and p16, p21 and p53 expression. Moreover, NUAK2 depletion elevated lipid ROS, TBARS production and Fe2+ level, demonstrating that NUAK2 depletion could trigger ferroptosis in A549 cells. Furthermore, the rescue experiments revealed that the impacts of NUAK2 depletion on malignant behaviors in A549 cells were partly weakened by additional Fer-1 treatment. Finally, in vivo experiments demonstrated that NUAK2 knockdown greatly inhibited tumor growth in LUAD-bearing mice. CONCLUSION: In summary, NUAK2 depletion impeded oncogenic phenotypes of A549 cells partly via triggering ferroptosis, suggesting NUAK2 as a novel target for treating LUAD.