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Abstract Calcium (Ca) is an essential mineral nutrient and plays a crucial signaling role in all living organisms. Increasing Ca content in staple foods such as rice is vital for improving Ca nutrition of humans. Here we map a quantitative trait locus that controls Ca concentration in rice grains and identify the causal gene as GCSC1 (Grain Ca and Sr Concentrations 1), which encodes a chloroplast vesicle localized homo-oligomeric protein. GCSC1 exhibits Ca2+ transport activity in heterologous assays in yeast and Xenopus laevis oocytes and is involved in the efflux of Ca2+ from the chloroplast to the cytosol. Knockout of GCSC1 results in increased chloroplast Ca concentration, lower stomatal conductance in leaves and enhanced Ca allocation to grains. Natural variation in grain Ca concentration is attributed to the variable expression of GCSC1 resulting from its promoter sequence variation. Our study identifies a chloroplast localized heavy metal-associated domain containing protein that regulates chloroplast Ca2+ efflux and provides a way to biofortify Ca in rice to benefit human nutrition.

Abstract Chronic obstructive pulmonary disease (COPD) is an irreversible and progressive chronic inflammatory lung disease which affects millions of people worldwide. Activated fibroblasts are observed to accumulate in lung of COPD patients and promote COPD progression through aberrant extracellular matrix (ECM) deposition. In this study, we identified that miR-1307-5p expression was significantly increased in lung fibroblasts derived from COPD patients. Mechanistically, we found that upregulation of miR-1307-5p promoted TGF-β induced lung fibroblast activation and transdifferentiation. We also identified FBXL16 as a direct target for miR-1307-5p mediated myofibroblast activation in COPD. Knockdown of FBXL16 by siRNA prominently increased the expression of myofibroblast markers in MRC-5 fibroblasts after TGF-β administration. Ectopic expression of FBXL16 in MRC-5 counteracted miR-1307-5p agomir-induced fibroblast transdifferentiation. Furthermore, We found that miR-1307-5p promoted pulmonary fibroblast transdifferentiation through FBXL16 regulated HIF1α degradation. In general, our findings indicate that miR-1307-5p is important for COPD pathogenesis, and may serve as a potential target for COPD treatment.

AIM: To evaluate the application of an intelligent diagnostic model for pterygium. METHODS: For intelligent diagnosis of pterygium, the attention mechanisms—SENet, ECANet, CBAM, and Self-Attention—were fused with the lightweight MobileNetV2 model structure to construct a tri-classification model. The study used 1220 images of three types of anterior ocular segments of the pterygium provided by the Eye Hospital of Nanjing Medical University. Conventional classification models—VGG16, ResNet50, MobileNetV2, and EfficientNetB7—were trained on the same dataset for comparison. To evaluate model performance in terms of accuracy, Kappa value, test time, sensitivity, specificity, the area under curve (AUC), and visual heat map, 470 test images of the anterior segment of the pterygium were used. RESULTS: The accuracy of the MobileNetV2+Self-Attention model with 281 MB in model size was 92.77%, and the Kappa value of the model was 88.92%. The testing time using the model was 9ms/image in the server and 138ms/image in the local computer. The sensitivity, specificity, and AUC for the diagnosis of pterygium using normal anterior segment images were 99.47%, 100%, and 100%, respectively; using anterior segment images in the observation period were 88.30%, 95.32%, and 96.70%, respectively; and using the anterior segment images in the surgery period were 88.18%, 94.44%, and 97.30%, respectively. CONCLUSION: The developed model is lightweight and can be used not only for detection but also for assessing the severity of pterygium.

Abstract Over the past decades, the immune responses have been suspected of participating in the mechanisms for epilepsy. To assess the immune related pathway in temporal lobe epilepsy (TLE), we explored the altered immune pathways in TLE patients with and without hippocampal sclerosis (HS). We analyzed RNA-seq data from 3 TLE-HS and 3 TLE-nonHS patients, including identification of differentially expressed RNA, function pathway enrichment, the protein–protein interaction network and construction of ceRNA regulatory network. We illustrated the immune related landscape of molecules and pathways on human TLE-HS. Also, we identified several differential immune related genes like HSP90AA1 and SOD1 in TLE-HS patients. Further ceRNA regulatory network analysis found SOX2-OT connected to miR-671-5p and upregulated the target gene SPP1 in TLE-HS patients. Also, we identified both SOX2-OT and SPP1 were significantly upregulated in five different databases including TLE-HS patients and animal models. Our findings established the first immune related genes and possible regulatory pathways in TLE-HS patients and animal models, which provided a novel insight into disease pathogenesis in both patients and animal models. The immune related SOX2-OT/miR-671-5p/SPP1 axis may be the potential therapeutic target for TLE-HS.

Silica aerogel composites have promising applications in high-temperature heat storage insulation. However, the impact of high temperatures and moisture on their insulation performance remains unclear. To reveal the influences of high temperature and moisture absorption property on the heat transfer of silica aerogel composites, an experimental and numerical study was conducted to explore the micromorphology, thermophysical parameters, moisture absorption characteristics, and temperature response. The service temperature limit of the silica aerogel composite has been clarified. Measurements have conducted for the thermal conductivity, specific heat capacity, thermal diffusivity, specific surface area, density, porosity, and pore size distribution of the heated silica aerogel composite (at temperatures of 600, 800, 1,000, 1,100 and 1,200 °C). The moisture absorption characteristic curve at 20 °C has been obtained. Thermal testing of silica aerogel composites under varying heating temperatures and moisture content has been completed. Additionally, a numerical method has been developed to calculate the temperature curve of moist silica aerogel composites. The insulation performance of silica aerogel composite with varying moisture contents depends on the game between thermal conductivity and latent heat. Compared with the negative effect of the moisture content on insulation performance, the positive influence of moisture evaporation and heat absorption is dominant in situations involving temperatures higher than the phase transition temperature.

We delve into the critical role of the gut microbiota and its metabolites in the pathogenesis and progression of hepatobiliary and pancreatic (HBP) cancers, illuminating an urgent need for breakthroughs in diagnostic and therapeutic strategies. Given the high mortality rates associated with HBP cancers, which are attributed to aggressive recurrence, metastasis, and poor responses to chemotherapy, exploring microbiome research presents a promising frontier. This research highlights how microbial metabolites, including secondary bile acids, short-chain fatty acids, and lipopolysaccharides, crucially influence cancer cell behaviors such as proliferation, apoptosis, and immune evasion, significantly contributing to the oncogenesis and progression of HBP cancers. By integrating the latest findings, we discuss the association of microbial alterations with HBP cancers, key metabolites, and their implications, and how metabolomics and microbiomics can enhance diagnostic precision. Furthermore, the paper explores strategies for targeted therapies through microbiome metabolomics, including the direct therapeutic effects of microbiome metabolites and potential synergistic effects on conventional therapies. We also recognize that the field of microbial metabolites for the diagnosis and treatment of tumors still has a lot of problems to be solved. The aim of this study is to pioneer microbial metabolite research and provide a reference for HBP cancer diagnosis, treatment, and prognosis.

Abstract Purpose To investigate whether the mixed approach is a safe and advantageous way to operate laparoscopic right hemicolectomy. Methods A retrospective study was performed on 316 patients who underwent laparoscopic right hemicolectomy in our center. They were assigned to the middle approach group (n = 158) and the mixed approach group (n = 158) according to the surgical approaches. The baseline data like gender、age and body mass index as well as the intraoperative and postoperative conditions including operation time, blood loss, postoperative hospital stay and complications were analyzed. Results There were no significant differences in age, sex, BMI, ASA grade and tumor characteristics between the two groups. Compared with the middle approach group, the mixed approach group was significantly lower in terms of operation time (217.61 min vs 154.31 min, p

Abstract Structural annotation of small molecules in tandem mass spectrometry has always been a central challenge in mass spectrometry analysis, especially using a miniaturized mass spectrometer for on-site testing. Here, we propose the Transformer enabled Fragment Tree (TeFT) method, which combines various types of fragmentation tree models and a deep learning Transformer module. It is aimed to generate the specific structure of molecules de novo solely from mass spectrometry spectra. The evaluation results on different open-source databases indicated that the proposed model achieved remarkable results in that the majority of molecular structures of compounds in the test can be successfully recognized. Also, the TeFT has been validated on a miniaturized mass spectrometer with low-resolution spectra for 16 flavonoid alcohols, achieving complete structure prediction for 8 substances. Finally, TeFT confirmed the structure of the compound contained in a Chinese medicine substance called the Anweiyang capsule. These results indicate that the TeFT method is suitable for annotating fragmentation peaks with clear fragmentation rules, particularly when applied to on-site mass spectrometry with lower mass resolution.

Objective: This study aimed to analyse the association between lipoprotein-associated phospholipase A2 (Lp-PLA2) and 25-hydroxy-vitamin D (25[OH]D) and early diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM) and evaluate the potential roles of these two biomarkers in the clinical diagnosis of DKD. Methods: A total of 422 inpatients with T2DM were retrospectively enrolled between January 2018 and March 2022 at the First Affiliated Hospital of Nanjing Medical University. The baseline clinical parameters of each patient were determined, and their demographic characteristics were extracted from the hospital information system. The patients were separated into groups according to serum Lp-PLA2 and 25(OH)D levels and binary logistic regression analysis was used to determine independent predictors of early DKD incidence. Results: Levels of Lp-PLA2 significantly increased and those of 25(OH)D significantly decreased with DKD progression (both P

IntroductionMembers of the plant-specific B3 transcription factor superfamily play crucial roles in various plant growth and developmental processes. Despite numerous valuable studies on B3 genes in other species, little is known about the B3 superfamily in pearl millet.Methods and resultsHere, through comparative genomic analysis, we identified 70 B3 proteins in pearl millet and categorized them into four subfamilies based on phylogenetic affiliations: ARF, RAV, LAV, and REM. We also mapped the chromosomal locations of these proteins and analyzed their gene structures, conserved motifs, and gene duplication events, providing new insights into their potential functional interactions. Using transcriptomic sequencing and real-time quantitative PCR, we determined that most PgB3 genes exhibit upregulated expression under drought and high-temperature stresses, indicating their involvement in stress response regulation. To delve deeper into the abiotic stress roles of the B3 family, we focused on a specific gene within the RAV subfamily, PgRAV-04, cloning it and overexpressing it in tobacco. PgRAV-04 overexpression led to increased drought sensitivity in the transgenic plants due to decreased proline levels and peroxidase activity.DiscussionThis study not only adds to the existing body of knowledge on the B3 family’s characteristics but also advances our functional understanding of the PgB3 genes in pearl millet, reinforcing the significance of these factors in stress adaptation mechanisms.

Patients with severe carbapenem-resistant Acinetobacter baumannii (CRAB) infections currently face significant treatment challenges. When patients display signs of infection and the clinical suspicion of CRAB infections is high, appropriate treatment should be immediately provided. However, current treatment plans and clinical data for CRAB are limited. Inherent and acquired resistance mechanisms, as well as host factors, significantly restrict options for empirical medication. Moreover, inappropriate drug coverage can have detrimental effects on patients. Most existing studies have limitations, such as a restricted sample size, and are predominantly observational or non-randomized, which report significant variability in patient infection severity and comorbidities. Therefore, a gold-standard therapy remains lacking. Current and future treatment options of infections due to CRAB were described in this review. The dose and considerable side effects restrict treatment options for polymyxins, and high doses of ampicillin-sulbactam or tigecycline appear to be the best option at the time of initial treatment. Moreover, new drugs such as durlobactam and cefiderocol have substantial therapeutic capabilities and may be effective salvage treatments. Bacteriophages and antimicrobial peptides may serve as alternative treatment options in the near future. The advantages of a combination antimicrobial regimen appear to predominate those of a single regimen. Despite its significant nephrotoxicity, colistin is considered a primary treatment and is often used in combination with antimicrobials, such as tigecycline, ampicillin-sulbactam, meropenem, or fosfomycin. The Infectious Diseases Society of America (IDSA) has deemed high-dose ampicillin-sulbactam, which is typically combined with high-dose tigecycline, polymyxin, and other antibacterial agents, the best option for treating serious CRAB infections. A rational combination of drug use and the exploration of new therapeutic drugs can alleviate or prevent the effects of CRAB infections, shorten hospital stays, and reduce patient mortality.

Programmed death-1 (PD-1) acts as a T cell checkpoint and is important in controlling T cell exhaustion. Blocking the intercommunication across PD-1 and PD-L1 is promising for advanced lung cancer treatment. However, the response rate requires being strengthened. This study aimed to determine whether the combination treatment of Qingfei mixture (QFM) and PD-1 inhibitor could improve the sensitivity of monoclonal antibody by regulating STAT1/IDO1-mediated tryptophan (Trp)-kynurenine (Kyn) pathway. The in vivo imaging system, immunofluorescence, hematoxylin-eosin staining, TUNEL, flow cytometry, HPLC, and ELISA were used to estimate the anti-tumor effects in LLC-luc tumor-bearing C57BL/6 mice treated with QFM, PD-1 inhibitor, 2-NP (enhancer of STAT1 transcription), and FICZ (AhR agonist) alone or in combination. IFN-γ-mediated A549 and LLC cells were treated with QFM-containing serum and fludarabine (FLU, STAT1 inhibitor), and cell viability, apoptosis, and Kyn content were then evaluated using CCK-8 assays, flow cytometry, and HPLC assays, respectively. Additionally, the expressions of STAT1, IDO1, AhR, NFATc1, TRIP12, PD-1, and PD-L1 were measured in vivo and in vitro. We found QFM increased the anti-cancer actions of PD-1 inhibitors by increasing the CD8+IFNγ+ T cells infiltration and decreasing the ratio of Kyn/Trp. Besides, QFM-containing serum suppressed the proliferation and promoted apoptosis in A549 and LLC cells, meanwhile, FLU boosted the effects of QFM-containing serum. Moreover, the suppression of tumor growth in the combination therapy was attenuated in the mice receiving 2-NP or FICZ. The occurrence of the above results was accompanied by a decrease in STAT1, IDO1, AhR, PD-1, and PD-L1 expressions. Collectively, the findings suggested that QFM may increase the influences of PD-1 inhibitors at least partially by blocking the STAT1/IDO1-mediated tryptophan-kynurenine pathway in lung cancer.