Exosomes Induce Crosstalk Between Multiple Types of Cells and Cardiac Fibroblasts: Therapeutic Potential for Remodeling After Myocardial Infarction.

Recanalization therapy can significantly improve the prognosis of patients with acute myocardial infarction (AMI). However, infarction or reperfusion-induced cardiomyocyte death, immune cell infiltration, fibroblast proliferation, and scarring formation lead to cardiac remodeling and gradually progress to heart failure or arrhythmia, resulting in a high mortality rate. Due to the inability of cardiomyocytes to regenerate, the healing of infarcted myocardium mainly relies on the formation of scars. Cardiac fibroblasts, as the main effector cells involved in repair and scar formation, play a crucial role in maintaining the structural integrity of the heart after MI. Recent studies have revealed that exosome-mediated intercellular communication plays a huge role in myocardial repair and signaling transduction after myocardial infarction (MI). Exosomes can regulate the biological behavior of fibroblasts by activating or inhibiting the intracellular signaling pathways through their contents, which are derived from cardiomyocytes, immune cells, endothelial cells, mesenchymal cells, and others. Understanding the interactions between fibroblasts and other cell types during cardiac remodeling will be the key to breakthrough therapies. This review examines the role of exosomes from different sources in the repair process after MI injury, especially the impacts on fibroblasts during myocardial remodeling, and explores the use of exosomes in the treatment of myocardial remodeling after MI.

Delayed fragmentation of weakly bound Kr2.

We report the experimental observation of the delayed fragmentation of the weakly bound dimer Kr2+ produced through the single ionization of Kr2 by a femtosecond laser field. The observed time delay between ionization and fragmentation, which reflects the survival time of the resulting Kr2+, is measured on the microsecond timescale. A detailed analysis of the kinetic energy releases of the ejected fragments and photoelectrons suggests that this delayed fragmentation arises from the radiative decay of the long-lived Kr2+, transitioning from the bound state II(1/2u) to the repulsive state I(1/2g).

Precursor-Directed Biosynthesis of Panepoxydone Derivatives with Nitric Oxide Production Inhibitory Activity.

Panepoxydone is a natural NF-кB inhibitor isolated from basidiomycetes belonging to the genus Panus and Lentinus. It is biosynthesized from prenylhydroquinone through successive hydroxylation, epoxidation, and reduction reactions. In this study, we establish an efficient precursor-directed biosynthesis strategy for the structural expansion of panepoxydone based on its biosynthetic pathway. Supplementation of the panepoxydone-producing strain, Panus rudis, with various prenylhydroquinone analogues enabled the production of fourteen previously undescribed panepoxydone derivatives, panepoxyquinoid A-N (2-14). The obtained panepoxydone derivatives together with their parental molecules were evaluated for their inhibitory activity on LPS-induced NO production in RAW 264.7 cells. Compounds 1, 5-6, 10-11, and 14-15 displayed significant suppressive effects on LPS-induced NO production with IC50 values ranging from 4.3 to 30.1 µM.

Pear twig biochar combined with nitrogen fertilizer regulates morpho-physiological growth, copper uptake and tuber quality of potato (Solanum tuberosum L.) grown in polluted soil.

Application of pear twig derived biochar and nitrogen fertilizer is strategic for addressing the challenges posed by copper pollution in soils. Their combined use aims to improve plant health and promote sustainable agricultural practices, which leads to better potato growth and quality. Therefore, this study was carried out to investigate the effects of different levels of pear twig biochar (B0:0, B1:3, B2:5, B3:7% w/w) combined with nitrogen fertilizer (N0:0, N1:150, N2:200, N3:250, N4:300 mg kg-1) on morpho-physiological growth and copper uptake of potato cultivated in Cu polluted soil. Results showed that combined approach of pear twig biochar and nitrogen significantly influenced morpho-physiology, antioxidant enzyme activity, mineral content and tuber quality of potato. B2N3 significantly increased the plant height and chlorophyll in plants as compared to B0N0 (control). Malondialdehyde and proline contents were highest in control; however, maximum reductions in MDA and proline contents were recorded at B2N4 (70.32% and 92.12% at budding stage, respectively) and at B2N3 (82.44% and 91.93% at flowering stage, respectively). Likewise, B2N3 showed maximum reduction in activities of peroxidase (7343.47 and 11077.27 U g-1), catalase (1184.98 and 165.64 U g-1) and superoxide dismutase (14.84 and 19.94 U g-1) at budding and flowering stages, respectively. However, lowest contents of soil available Cu (2.03 ± 0.5 µg g-1) and tuber flesh Cu (4.44 ± 0.3 µg g-1) were recorded at B2N3 as compared to control. Interestingly, 7% biochar at all levels of nitrogen exhibited a significant decrease in soil available Cu and tuber flesh Cu. Tuber quality traits were also significantly improved at B2N3 as compared to control. However, future research and field trials can help refine the best practices for integrating these elements in different agricultural systems.

The role and mechanism of vascular wall cell ion channels in vascular fibrosis remodeling.

Fibrosis is usually the final pathological state of many chronic inflammatory diseases and may lead to organ malfunction. Excessive deposition of extracellular matrix (ECM) molecules is a characteristic of most fibrotic tissues. The blood vessel wall contains three layers of membrane structure, including the intima, which is composed of endothelial cells; the media, which is composed of smooth muscle cells; and the adventitia, which is formed by the interaction of connective tissue and fibroblasts. The occurrence and progression of vascular remodeling are closely associated with cardiovascular diseases, and vascular remodeling can alter the original structure and function of the blood vessel. Dysregulation of the composition of the extracellular matrix in blood vessels leads to the continuous advancement of vascular stiffening and fibrosis. Vascular fibrosis reaction leads to excessive deposition of the extracellular matrix in the vascular adventitia, reduces vessel compliance, and ultimately alters key aspects of vascular biomechanics. The pathogenesis of fibrosis in the vasculature and strategies for its reversal have become interesting and important challenges. Ion channels are widely expressed in the cardiovascular system; they regulate blood pressure, maintain cardiovascular function homeostasis, and play important roles in ion transport, cell differentiation, proliferation. In blood vessels, different types of ion channels in fibroblasts, smooth muscle cells and endothelial cells may be relevant mediators of the development of fibrosis in organs or tissues. This review discusses the known roles of ion channels in vascular fibrosis remodeling and discusses potential therapeutic targets for regulating remodeling and repair after vascular injury.

Prediction of Unexplained Recurrent Miscarriages Using Thromboelastography.

Objective: This study investigates the thromboelastography (TEG) changes in patients with unexplained recurrent spontaneous abortion (URSA) to identify effective diagnostic markers for URSA. Methods: We retrospectively analyzed 160 URSA patients from the Gynecology Department of the First People's Hospital of Lianyungang (June 2017 - June 2020) and compared them with 190 healthy, fertile women without adverse pregnancy histories (control group). TEG parameters were assessed using logistic regression, applying stepwise selection for model optimization. Model performance was evaluated using Receiver Operating Characteristic (ROC) curves, determining sensitivity and specificity. The Youden index identified optimal cut points for predictive probabilities. Results: Significant differences were observed between the URSA and control groups in coagulation reaction time (R), clot formation time (K), clot formation rate (Angle-α), and maximum clot strength (MA) (P<0.05). Multivariable logistic regression identified R, Angle-α, and MA as independent URSA risk factors. The model demonstrated excellent discrimination (AUC: 0.940; 95% CI: 0.918-0.962). The optimal cut point of predictive probability (Youden index) was P=0.355, yielding a sensitivity of 0.925 and specificity of 0.795. Conclusion: URSA patients exhibit a hypercoagulable state even when not pregnant. More research is needed to validate our findings and explore the potential clinical implications of anticoagulants in treating URSA.

Eliminating the effect of pH: Dual-matrix modulation adsorbent enables efficient lithium extraction from concentrated seawater.

Lithium ion sieve adsorbents frequently extract liquid lithium resources due to their adsorption effect and cost advantages. However, the adsorption effect is significantly influenced by the ambient pH. The pH effects on the adsorption process can be categorized into two main areas: the competition adsorption of impurity ions and the difference in surface zeta potential. A dual-matrix modulation adsorbent was prepared, comprising a carrier matrix modified with zwitterionic quaternary ammonium bases and an adsorption matrix modified with carboxylation. The zwitterionic quaternary ammonium base groups were employed to mitigate the competitive adsorption of impurity ions by acid-base neutralization. Furthermore, the negative charge of carboxyl groups was employed to diminish the discrepancy in surface zeta potential. The adsorption effect of the ion sieve adsorbent under natural conditions appeared to be significantly enhanced by the dual-matrix modulation, with the saturated adsorption capacity (28 mg/g) and adsorption selectivity (α(Li+/Mg2+)=24.23) being 6.3 and 7.8 times higher than that of the manganese-based adsorbent (HMO) under the same conditions, respectively. Moreover, the adsorption effect was found to be consistent with HMO under alkaline conditions. The results demonstrate that by optimizing the adsorption conditions of the adsorbent, the detrimental impact of pH on the adsorption process of lithium ion sieves can be eliminated.

Method development, multi-residue determination, and dietary exposure risk assessment of plant growth regulators in homologous materials of medicine and food.

Residues of plant growth regulators (PGRs) in homologous materials of medicine and food threaten public health. This study aimed to develop a rapid, sensitive, and high-throughput method for simultaneously determining 16 PGR residues in homologous materials of medicine and food. Furthermore, the established method was applied to actual samples to assess the potential exposure risk of multi-PGR residues. A modified high-throughput quick, easy, cheap, effective, rugged, and safe (QuEChERS) method coupled with ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed and validated. The extraction solvent, type of extraction method, and subsequent purification techniques were investigated to achieve a better analysis of the target. Risk assessment was based on chronic dietary risk assessment. Ultrasonic extraction with 1% formic acid-acetonitrile was employed, and MgSO4 + NaAc was selected as the clean-up sorbent. The 16 PGRs showed a good linear relationship in the range of 1 ~ 200 µg/L (r ≥ 0.9960), with detection limits ranging from 0.3 to approximately 3 µg/kg. The recovery rate ranged from 65 to 109%, with RSD from 0.01 to 10% (n = 6). The total detection rate of 16 PGRs in the samples was 87%. The risk assessment indicated that the multi-residues of PGRs in homologous materials of medicine and food would not pose a potential risk to human health. This work provides a valuable reference for the monitoring of multiple PGRs. It has also improved our understanding of the possible exposure risk of PGR residues in homologous materials of medicine and food.

Clinical effects of different types of flaps selected according to local conditions in the treatment of diabetic foot defects.

BACKGROUND: The repair of diabetic foot defects (DFD) is a major challenge in clinical practice. The purpose of this study was to investigate the difference in clinical efficacy of different flap techniques in repairing DFD wounds, and to compare the difference in clinical efficacy of anterolateral thigh perforator flap (ALTP) in repairing DFD and non-DFD. METHODS: This study is a retrospective clinical study of different types of flap reconstruction in patients with DFD admitted to our hospital from January 2010 to December 2021. A total of 40 patients with DFD and 43 patients with non-DFD were included in this study. Detailed preoperative basic information, intraoperative details, postoperative complications and long-term follow-up results were collected. RESULT: The comorbidities, wound infection and wound duration of DFD group were more serious than those of non-DFD group. In addition, the incidence of complications was higher in DFD group, the wound healing time was longer, the aesthetic evaluation, the functional recovery rate of ankle joint and the sensory recovery effect of flaps were worse. CONCLUSION: In this study, it is concluded that different flap techniques can obtain better clinical efficacy in repairing DFD wounds. Compared with non-DFD wounds, the postoperative risk of DFD wounds using free ALTP flaps is higher, but the risk can be reduced by reasonable preoperative vascular examination. Free flap can deal with various irregular wounds and provide more options for clinical repair. LEVEL OF EVIDENCE: III, Case-control study.

METS-IR as an important predictor of neurological impairment severity in patients with severe cerebral infarction: a multicenter study based on the Chinese population.

Background: Insulin resistance (IR) is linked to an increased risk of neurological impairment following a stroke and may contribute to poor neurological prognosis in affected patients. The metabolic score for the insulin resistance index, shortened as the METS-IR, generally serves as a surrogate index for IR. However, its association with the severity of neurological impairment in patients with severe cerebral infarction (CI) in neurological intensive care units (ICU) has not been fully established. Methods: Patients with a diagnosis of CI, admitted to the neurological ICUs of Yangzhou University's Affiliated Hospital and Xuzhou Medical University's Affiliated Hospital, were included in the study. A multivariate logistic regression model and restricted cubic splines (RCS) were employed to explore the relationship between the METS-IR index and the severity of neurological impairment in these patients. The predictive capabilities of the METS-IR index and the triglyceride-glucose (TyG) index for outcome measures were compared through the ROC curve. Furthermore, a decision curve analysis was executed, and the integrated discrimination improvement (IDI) index was computed to evaluate the enhancements in predictive performance and clinical utility of various scoring systems with the inclusion of the METS-IR index. Subgroup analysis was conducted regarding age, BMI, and smoking status. Results: The study ultimately included 504 participants. Adjusted logistic regression and RCS results showed that as the METS-IR index increases, the risk of neurological impairment in patients with severe CI consistently grows (P for overall = 0.0146, P-nonlinear: 0.0689). The METS-IR index's predictive capability for neurological impairment (AUC = 0.669) was superior to that of the TyG index (AUC = 0.519). Conclusion: From the study results, the METS-IR index can serve as an important predictor for neurological impairment in ICU patients with severe CI. It can aid in the identification and early intervention of neurological impairment in these patients.

CRISPR-Cas13-mediated RNA editing in the silkworm Bombyx mori.

The CRISPR-Cas13 system, an RNA-guided editing tool, has emerged as a highly efficient and stable RNA editing technique. Although the CRISPR-Cas13 system has been developed in several insect species, its application in lepidopterans has not yet been reported. In the present study, we evaluated the RNA cleavage activity of the CRISPR-Cas13 system in the silkworm ( Bombyx mori), a model lepidopteran insect, both ex vivo and in vivo. We established two stable silkworm BmE cell lines expressing PspCas13b and CasRx, respectively. Further analysis demonstrated that both PspCas13b and CasRx effectively down-regulated the transcription of exogenously-introduced target and endogenous genes in these cell lines. In addition, we generated two transgenic silkworm strains, one expressing CasRx and the other expressing RNA-guided CRISPR RNA targeting Sex combs reduced ( Scr). Further crossing experiments showed that CasRx induced a down-regulation of Scr transcription in silkworms, which impaired systemic growth of larvae. Overall, this study demonstrated that the CRISPR-Cas13 RNA editing system works efficiently in the silkworm, providing a potential alternative approach for RNA manipulation in lepidopteran insects.

A predictive model and rapid multi-dynamic algorithm developed based on tumor-stroma percentage in gastric cancer: a retrospective, observational study.

Background: Tumor-stroma percentage (TSP) is a prognostic risk factor in numerous solid tumors. Despite this, the prognostic significance of TSP in gastric cancer (GC) remains underexplored. Through the development of a personalized predictive model and a semi-automatic identification system, our study aimed to fully unlock the predictive potential of TSP in GC. Methods: We screened GC patients from Shanghai General Hospital (SGH) between 2012 and 2019 to develop and validate a nomogram. Univariate and multivariate Cox proportional hazards regression analyses were employed to identify independent prognostic factors influencing the prognosis for GC patients. The nomogram was further validated externally by using a cohort from Bengbu Medical College (BMC). All patients underwent radical gastrectomy, with those diagnosed with locally advanced GC receiving adjuvant chemotherapy. The primary outcome measured was overall survival (OS). The semi-automatic identification of the TSP was achieved through a computer-aided detection (CAD) system, denoted as TSP-cad, while TSP identified by pathologists was labeled as TSP-visual. Results: A total of 813 GC patients from SGH and 59 from BMC were enrolled in our study. TSP-visual was identified as an adverse prognostic factor for OS in GC and was found to be associated with pathological Tumor Node Metastasis staging system (pTNM) stage, T stage, N stage, perineural invasion (PNI), lymphovascular invasion (LVI), TSP-visual, tumor size, and other factors. Multivariate Cox regression using the training cohort revealed that TSP-visual (hazard ratio [HR], 2.042; 95% confidential interval [CI], 1.485-2.806; P < 0.001), N stage (HR, 2.136; 95% CI, 1.343-3.397; P = 0.010), PNI (HR , 1.791; 95% CI, 1.270-2.526; P = 0.001), and LVI (HR, 1.482; 95% CI, 1.021-2.152; P = 0.039) were independent predictors. These factors were incorporated into a novel nomogram, which exhibited strong predictive accuracy for 5-year OS in the training, internal validation, and external validation cohorts (area under the curve = 0.744, 0.759, and 0.854, respectively). The decision curve analysis of the nomogram and concordance indexes across the three cohorts outperformed the traditional pTNM (P < 0.05). Additionally, TSP-cad assessment using a rapid multi-dynamic algorithm demonstrated good agreement with TSP-visual. Conclusions: The novel nomogram based on TSP could effectively identify individuals at risk of a poor prognosis among patients with GC. TSP-cad is anticipated to enhance the evaluation process of TSP.

Microfluidic-SERS sensing system based on dual signal amplification and aptamer for gastric cancer detection.

Studies have found that matrix metalloproteinase-9 (MMP-9) and interleukin-6 (IL-6) play an important role in tumorigenesis. In order to detect MMP-9 and IL-6 concentrations with high sensitivity and specificity, an efficient microfluidic-SERS sensing system was prepared based on surface-enhanced Raman scattering (SERS). The aptamer recognition-release mechanism and the dual signal amplification strategy were applied in the sensing system. The sensor system was developed using two kinds of nanomaterials with excellent SERS properties, namely gold-coated iron tetroxide particles (Fe3O4@AuNPs) and gold nanocages (AuNCs). In addition, Fe3O4@AuNPs also has magnetic adsorption properties. In the sensing system, single-stranded DNA1 (ssDNA1) and aptamer were modified on Fe3O4@AuNPs. Single-stranded DNA2 (ssDNA2) and Raman tags were modified on AuNCs. When the target was present, the aptamer bound to the target and detached from the Fe3O4@AuNPs, and ssDNA2 bound to the exposed ssDNA1. At this time, the Fe3O4@AuNPs@AuNCs@SERS tag complex was formed, and the SERS signal was enhanced for the first time. Under the action of an external magnet on the microfluidic chip, the complex was magnetized and enriched. The SERS signal was enhanced for the second time. Due to the high affinity between the aptamer and the target object, the sensing system has a strong specificity. The double amplification of the SERS signal gave the system excellent sensitivity. The limit of detection (LOD) relative to MMP-9 and IL-6 were as low as 0.178 pg/mL and 0.165 pg/mL, respectively. The microfluidic-SERS sensing system has a feasible prospect in the early screening of gastric cancer.

Comparative effectiveness of upadacitinib versus dupilumab for moderate-to-severe atopic dermatitis: A retrospective cohort study.

BACKGROUND: Although efficacy and safety of Upadacitinib and Dupilumab in moderate to severe atopic dermatitis (AD) have been shown in clinical trials, real world data are still limited. The aim of this retrospective study is to indirectly compare the efficacy and safety of Upadacitinib and Dupilumab in patients with moderate to severe AD in real world practice. METHODS: A single-center retrospective cohort study was conducted. The study included patients with moderate to severe AD, who were enrolled from May 2022 to March 2024, to indirectly compare the efficacy and safety of Upadacitinib and Dupilumab over 12 weeks duration. RESULTS: Eighty-seven patients were included (46 received Upadacitinib and 41 Dupilumab). Compared with week 0, there was a significant decrease in EASI score, ADCT score and NRS score in patients of both groups in weeks 4, 8, and 12. In week 4, the reduction in EASI score, ADCT score and NRS score was significantly greater in patients of Upadacitinib group compared to those in Dupilumab group. Compared to baseline, in week 12, the decrease in IL-4, IL-13, and IL-31 level in the serum of patients in Upadacitinib group was significantly greater than that of patients in Dupilumab group. The total IgE of patients in Dupilumab group decreased significantly, while there was no significant change in patients of Upadacitinib group. Although Upadacitinib group reported more adverse events than Dupilumab group, no serious adverse events were observed. CONCLUSIONS: Both Upadacitinib and Dupilumab groups showed effective trend in patients with moderate to severe AD. Upadacitinib has better efficacy and rapid onset in the treatment of patients with moderate to severe AD.

PARP1 acetylation at K119 is essential in regulating the progression and proliferation of cervical cancer cells.

Cervical cancer, CC, is one of the malignant cancers in women worldwide. Many studies about the genesis and progression of CC have been done at genomic, transcriptional, translational, and epigenetic levels. However, much less is done at post-translational modification (PTM) level. We first used pan-PTM antibodies to compare the pan PTM levels between clinical normal cervical tissues and CC tissues; we then sent the selected samples for label-free identification of acetylation sites. Next, we employed WT or K119A mutant PARP1-EGFP-STREPII plasmid transfection in Hela cells and examined various indexes including colony formation, wound healing, ROS generation, early apoptosis, and immunofluorescence and quantification of proliferation markers (Ki67, PCNA, and p-P53). Last, we examined the levels of multiple important kinases regulating cervical cancer progression. We found that pan-acetylation was the most downregulated in clinical CC samples, whereas the acetylation of PARP1, Poly(ADP-ribose) polymerase-1, was upregulated at K119. Next, we showed that PARP1-WT overexpression significantly suppressed the proliferation and progression in CC cell line Hela, while K119A overexpression didn't show any impact. Finally, PARP1-WT overexpression significantly decreased p-ERK1/2 while didn't affect the phosphorylation levels of other important kinases such as AKT, MTOR, and RPS6. This study discovered a new type of PTM of PARP1 in CC, and showed that PARP1 acetylation at K119 is essential in regulating the proliferation and progression of CC through ERK1/2. Further studies are required to investigate how PARP1 acetylation impact its function.

Droplet Impact on the Superhydrophobic Surface with Singularities.

Reducing the contact time of an impacting droplet is highly desirable in various industrial fields including anti-icing. With the straightforward upscaling advantage, singularities on superhydrophobic surfaces can induce an annular rebound with a limited reduction in contact time. To break this limitation and further reduce contact time, this study focuses on optimizing the singularity number and arrangement. The effects of the singularity number and dimensionless spacing (l* scaled by the droplet diameter) on the dynamic and contact time characteristics of a droplet impacting the superhydrophobic surface are experimentally studied under varying Weber numbers (We). The experimental results indicate that in comparison to the single singularity, two singularities with l* < 1.0 can generate two liquid rings with four lateral liquid subunits due to the impalement at the high We region. Owing to the reduced equivalent diameter of the subunit, increasing We results in a gradually decreased contact time and accordingly breaks the limitation. However, the liquid film cannot be pierced at l* > 1.0 with a limited reduction. Considering the further reducing potential at l* < 1.0, four singularities are explored without a further reduced contact time due to the formed central liquid film. Using an additional central singularity, the central liquid film is pierced promoting its annular rebound. In consequence, five singularities significantly break the limitation in contact time, particularly a 61.7% reduction to the superhydrophobic flat surface at l* < 1.0.

Comparative analysis of transcriptome in oil biosynthesis between seeds and non-seed tissues of Symplocos paniculata fruit.

The Symplocos paniculata, a woody oil plant, has garnered attention for its oil-rich fruit, which exhibits potential for both oil production and ecological restoration endeavors, thereby presenting substantial developmental value. However, the comprehension of the distinctive oil biosynthesis and deposition strategies within the fruit's various compartments, coupled with the tissue-specific biosynthetic pathways yielding optimal fatty acid profiles, remains in its infancy. This investigation was designed to delineate the tissue specificity of oil biosynthetic disparities and to elucidate the molecular underpinnings within the fruit mesocarp and seeds of S. paniculata, employing lipidomic and transcriptomic analyses. The results revealed that oil biosynthesis within the fruit mesocarp commences approximately 40 days prior to that within the seeds, with a concomitant higher lipid content observed in the mesocarp, reaching 43% as opposed to 30% in the seeds. The fruit mesocarp was found to be enriched with palmitic acid (C16:0) and exhibited a harmonious ratio of saturated, monounsaturated, to polyunsaturated fatty acids (SFA: MUFA: PUFA=1:1:1), in stark contrast to the seed oil, which is predominantly composed of unsaturated fatty acids, accounting for 90% of its total FA content. Microstructural assessments have unveiled divergent oil deposition modalities; the fruit mesocarp oils are predominantly sequestered within oil cells (OC) and a spectrum of lipid droplets (LD), whereas the seeds predominantly harbor uniformly-sized LD. The expression patterns of pivotal genes implicated in oil biosynthesis were observed to be markedly contingent upon the tissue type and developmental stage. Notably, the light-responsive fatty acid synthase (FAS) gene demonstrated preferential transcription within the fruit mesocarp. In contrast, genes pivotal for carbon chain elongation, such as 3-ketoacyl-ACP synthase II (KASII) and fatty acyl-ACP thioesterase A (FATA), and desaturation, typified by Stearoyl-ACP desaturase (SAD) and Fatty Acid Desaturase (FAD), were noted to be more robustly transcribed within the seeds. Furthermore, isoenzyme gene families integral to the assembly of triacylglycerol (TAG), including long-chain acyl-CoA synthetases (LACSs), glycerol-3-phosphate acyltransferases (GPATs), and lysophosphatidic acid acyltransferases (LPATs), exhibited pronounced tissue specificity. This research endeavors to clarify the molecular regulatory mechanisms that oversee oil biosynthesis within both seed and non-seed tissues of oilseed-bearing plants with entire fruits. Collectively, these findings lay the groundwork and offer technical scaffolding for future targeted cultivation of woody oil plants, with the ultimate aim of augmenting fruit oil yield and refining FA compositions.

Ruxolitinib plus steroids for acute graft versus host disease: a multicenter, randomized, phase 3 trial.

Newly diagnosed patients with high-risk acute graft-versus-host disease (aGVHD) often experience poor clinical outcomes and low complete remission rates. Ruxolitinib with corticosteroids showed promising efficacy in improving response and failure free survival in our phase I study. This study (ClinicalTrials.gov: NCT04061876) sought to evaluate the safety and effectiveness of combining ruxolitinib (RUX, 5 mg/day) with corticosteroids (1 mg/kg/day methylprednisolone, RUX/steroids combined group) versus using methylprednisolone alone (2 mg/kg/day, steroids-only group). Newly diagnosed patients with intermediate- or high-risk aGVHD were included, with risk levels classified by either the Minnesota aGVHD Risk Score or biomarker assessment. Patients were randomized in a ratio of 1:1 into 2 groups: 99 patients received RUX combined with methylprednisolone, while the other 99 received methylprednisolone alone as the initial treatment. The RUX/steroids group showed a significantly higher overall response rate (ORR) on day 28 (92.9%) compared to the steroids-only group (70.7%, Odds Ratio [OR] = 5.8; 95% Confidence Interval [CI], 2.4-14.0; P < 0.001). Similarly, the ORR on day 56 was higher in the RUX/steroids group (85.9% vs. 46.5%; OR = 7.07; 95% CI, 3.36-15.75; P < 0.001). Additionally, the 18-month failure-free survival was significantly better in the RUX/steroids group (57.2%) compared to the steroids-only group (33.3%; Hazard Ratio = 0.46; 95% CI, 0.31-0.68; P < 0.001). Adverse events (AEs) frequencies were comparable between both groups, with the exception of fewer grade 4 AEs in the RUX/steroids group (26.3% vs. 50.5% P = 0.005). To our knowledge, this study is the first prospective, randomized controlled trial to demonstrate that adding ruxolitinib to the standard methylprednisolone regimen provides an effective and safe first-line treatment for newly diagnosed high-risk acute GVHD.