PHGDH/SYK: a hub integrating anti-fungal immunity and serine metabolism.

Immune cells modify their metabolic pathways in response to fungal infections. Nevertheless, the biochemical underpinnings need to be better understood. This study reports that fungal infection drives a switch from glycolysis to the serine synthesis pathway (SSP) and one-carbon metabolism by inducing the interaction of spleen tyrosine kinase (SYK) and phosphoglycerate dehydrogenase (PHGDH). As a result, PHGDH promotes SYK phosphorylation, leading to the recruitment of SYK to C-type lectin receptors (CLRs). The CLR/SYK complex initiates signaling cascades that lead to transcription factor activation and pro-inflammatory cytokine production. SYK activates SSP and one-carbon metabolism by inducing PHGDH activity. Then, one-carbon metabolism supports S-adenosylmethionine and histone H3 lysine 36 trimethylation to drive the production of pro-inflammatory cytokines and chemokines. These findings reveal the crosstalk between amino acid metabolism, epigenetic modification, and CLR signaling during fungal infection.

Enhancing drought resistance in Pinus tabuliformis seedlings through root symbiotic fungi inoculation.

Background: Drought constitutes a major abiotic stress factor adversely affecting plant growth and productivity. Plant-microbe symbiotic associations have evolved regulatory mechanisms to adapt to environmental stress conditions. However, the interactive effects of different fungi on host growth and stress tolerance under drought conditions remain unclear. Objective: This study explored the effects of varying polyethylene glycol (PEG-6000) concentrations (0%, 15%, 25%, and 35%) on the growth and physiological responses of two ectomycorrhizal fungi (Suillus granulatus (Sg) and Pisolithus tinctorius (Pt)) and two dark septate endophytes (Pleotrichocladium opacum (Po) and Pseudopyrenochaeta sp. (Ps)) isolated from the root system of Pinus tabuliformis. Specifically, the study aimed to evaluate six inoculation treatments, including no inoculation (CK), single inoculations with Sg, Pt, Po, Ps, and a mixed inoculation (Sg: Pt : Po: Ps = 1:1:1:1), on the growth and physiological characteristics of P. tabuliformis seedlings under different water regimes: well-watered at 70% ± 5%, light drought at 50% ± 5%, and severe drought at 30% ± 5% of the maximum field water holding capacity. Results: All four fungi exhibited the capacity to cope with drought stress by enhancing antioxidant activities and regulating osmotic balance. Upon successful root colonization, they increased plant height, shoot biomass, root biomass, total biomass, and mycorrhizal growth response in P. tabuliformis seedlings. Under drought stress conditions, fungal inoculation improved seedling drought resistance by increasing superoxide dismutase and catalase activities, free proline and soluble protein contents, and promoting nitrogen and phosphorus uptake. Notably, mixed inoculation treatments significantly enhanced antioxidant capacity, osmotic adjustment, and nutrient acquisition abilities, leading to superior growth promotion effects under drought stress compared to single inoculation treatments. Conclusion: All four fungi tolerated PEG-induced drought stress, with increased antioxidant enzyme activities and osmotic adjustment substances and they promoted the growth and enhanced drought resistance of P. tabuliformis seedlings.

GmBSK1-GmGSK1-GmBES1.5 regulatory module controls heat tolerance in soybean.

INTRODUCTION: Heat stress poses a severe threat to the growth and production of soybean (Glycine max). Brassinosteroids (BRs) actively participate in plant responses to abiotic stresses, however, the role of BR signaling pathway genes in response to heat stress in soybean remains poorly understood. OBJECTIVES: In this study, we investigate the regulatory mechanisms of GmBSK1 and GmBES1.5 in response to heat stress and the physiological characteristics and yield performance under heat stress conditions. METHODS: Transgenic technology and CRISPR/Cas9 technology were used to generated GmBSK1-OE, GmBES1.5-OE and gmbsk1 transgenic soybean plants, and transcriptome analysis, LUC activity assay and EMSA assay were carried out to elucidate the potential molecular mechanism underlying GmBSK1-GmBES1.5-mediated heat stress tolerance in soybean. RESULTS: CRISPR/Cas9-generated gmbsk1 knockout mutants exhibited increased sensitivity to heat stress due to a reduction in their ability to scavenge reactive oxygen species (ROS). The expression of GmBES1.5 was up-regulated in GmBSK1-OE plants under heat stress conditions, and it directly binds to the E-box motif present in the promoters of abiotic stress-related genes, thereby enhancing heat stress tolerance in soybean plants. Furthermore, we identified an interaction between GmGSK1 and GmBES1.5, while GmGSK1 inhibits the transcriptional activity of GmBES1.5. Interestingly, the interaction between GmBSK1 and GmGSK1 promotes the localization of GmGSK1 to the plasma membrane and releases the transcriptional activity of GmBES1.5. CONCLUSION: Our findings suggest that both GmBSK1 and GmBES1.5 play crucial roles in conferring heat stress tolerance, highlighting a potential strategy for breeding heat-tolerant soybean crops involving the regulatory module consisting of GmBSK1-GmGSK1-GmBES1.5.

Case report: Individualized 3D-printed uncemented distal fibular prosthesis preserving the lateral malleolus for repair of distal fibular defects.

Background: Involvement of the distal fibula by alveolar soft-part sarcoma is rare. Extensive resection or amputation may be needed; however, distal fibula resection can disrupt foot and ankle biomechanics, leading to ankle joint instability. Reports on joint preservation for maintaining optimal ankle joint function are scarce. Computer-aided design and individualized three-dimensional (3D)-printed uncemented implants represent an evolving solution for reconstructing the distal fibula. Case presentation: A 34-year-old woman was diagnosed with alveolar soft-part sarcoma in the right lower leg involving the cortical bone of the fibula. After anlotinib treatment, the tumor size decreased, and the tumor response rate was a partial response (PR); however, the patient continued to experience adverse reactions. With multiple disciplinary team discussions, surgical resection was deemed appropriate. Due to the extensive defect and ankle joint instability after resection, a custom-made 3D-printed prosthesis was designed and fabricated to reconstruct the defect, preserving the lateral malleolus. During the follow-up, the patient achieved favorable ankle function, and no prosthesis-related complications were observed. Conclusion: 3D-printed personalized uncemented implants constitute a novel approach and method for addressing the reconstruction issues of the distal fibula and ankle joint. Through the personalized design of 3D-printed prostheses, the lateral malleolus can be preserved, ensuring the normal anatomical structure of the ankle joint. They achieve a well-integrated interface between the prosthesis and bone, ensuring satisfactory postoperative function. Additionally, they offer valuable insights for reconstructing distal bone defects near joints in the extremities. However, confirming these findings requires extensive cohort studies.

A droplet digital PCR assay to detect Chinese rice-field eels rhabdovirus.

Chinese rice-field eels rhabdovirus (CrERV) causes haemorrhagic disease in Chinese rice-field eels (Monopterus albus), leading to significant mortality and economic losses. Sensitive detection of CrERV nucleic acids is essential to control the spread of this pathogen and to treat infected individuals. Herein, we developed an efficient and sensitive droplet digital PCR (ddPCR) method to rapidly detect and quantify CrERV. The ddPCR assay optimal conditions were an annealing temperature of 53°C, and primer and probe concentrations of 0.5 and 0.25 µM, respectively. The assay had a diagnostic sensitivity of 0.23 copies/µL, and was highly specific, showing no cross reactivity with other viruses (infectious haematopoietic necrosis virus, grass carp reovirus, spring viremia of carp virus, largemouth bass ranavirus, carp edema virus, Chinese giant salamander iridovirus, and white spot syndrome virus). Real-time quantitative PCR testing of 30 Chinese rice-field eels samples detected CrERV in 7 samples (23.3%), whereas ddPCR detected CrERV in 12 samples (40%), demonstrating its higher sensitivity. Thus, ddPCR represents an advanced method to absolutely quantify CrERV in infected fish with low virus concentrations, providing a valuable tool to manage the spread and impact of CrERV.

Differentiating calcifications from cerebral microbleeds using quantitative susceptibility mapping.

OBJECTIVES: To differentiate cerebral microbleeds (CMBs) and calcifications using quantitative susceptibility mapping (QSM). METHODS: CMBs were visualized and located using QSM from susceptibility-weighted imaging data collected on a 3-T MR scanner. Calcifications of the pineal gland and the choroid plexus were localized first using CT. All calcifications and CMBs were assessed using QSM to evaluate their magnetic susceptibility. The distribution of the magnetic susceptibility for the CMBs was determined and the CT attenuation was correlated with the mean magnetic susceptibility for the calcifications. RESULTS: A total of 232 hypointense foci were selected from the QSM data: 121 were CMBs and 111 were calcifications. The mean magnetic susceptibility was -214 ± 112 ppb for the calcifications and 392 ± 204 ppb for the CMBs. The minimum value of magnetic susceptibility was 75 ppb for all the CMBs and the maximum value was -52 ppb for all the calcifications. The calcifications were clearly differentiable from the CMBs from the sign alone (p < 0.001). The magnetic susceptibility for the CMBs was 299 ± 133 ppb in the lobar subcortical white matter and 499 ± 220 ppb for deep CMBs in the basal ganglia, thalamus, and brainstem. There was a significant difference in the susceptibility between these two regions (p < 0.001). CONCLUSION: The sign of the magnetic susceptibility was sufficient to differentiate calcifications and CMBs. The concentration of calcium or iron can be determined from the susceptibility value itself. The deep CMBs had higher susceptibility on average than lobar bleeds. CLINICAL RELEVANCE STATEMENT: This study's ability to differentiate between CMBs and calcifications using QSM could enhance diagnostic accuracy, guiding more precise treatment decisions for stroke or tumor patients. KEY POINTS: The sign of magnetic susceptibility is sufficient to differentiate calcifications and CMBs. QSM can successfully differentiate calcifications from microbleeds. The concentration of calcium or iron can be determined from the susceptibility value itself.

Spatial Transcriptomics Reveals the Transcriptomic Signatures in a Mouse Model of Pediatric Metabolic Dysfunction-Associated Steatohepatitis.

Metabolic dysfunction-associated steatohepatitis (MASH) is considered the progressive form of metabolic dysfunction-associated steatotic liver disease, which is the leading cause of chronic liver disease in children. However, the pathogenesis of pediatric MASH remains poorly understood because of the lack of animal models. In this study, we developed a mouse model of pediatric MASH and characterized the hepatic transcriptomic profile using spatial transcriptomics technology. C57BL/6J mice were fed a Western diet (WD) along with weekly injections of carbon tetrachloride (CCl4) from the age of 3 to 8 weeks. After 5 weeks of feeding, WD + CCl4-treated mice showed significant liver injury without the development of insulin resistance. Histologically, WD + CCl4 induced key features of type 2 MASH, the most common type observed in children, characterized by liver steatosis, portal inflammation, and portal fibrosis. Through spatial transcriptomics analysis of liver tissues, we identified that cluster 0 in the mouse from the WD + CCl4 group was enriched in pathways associated with lipid metabolism. Further investigation revealed that cytochrome p450 2E1 was the top marker gene of cluster 0, and its expression was increased in the periportal area of mice from the WD + CCl4 group. These findings suggest that our mouse model of pediatric MASH mirrors the histologic features of human MASH, and the up-regulation of cytochrome p450 2E1 may be linked to the disease pathogenesis.

Bioinspired triple-layered membranes for periodontal guided bone regeneration applications.

Barrier membranes have been used for the treatment of alveolar bone loss caused by periodontal diseases or trauma. However, an optimal barrier membrane must satisfy multiple requirements simultaneously, which are challenging to combine into a single material. We herein report the design of a bioinspired membrane consisting of three functional layers. The primary layer is composed of clay nanosheets and chitin, which form a nacre-inspired laminated structure. A calcium phosphate mineral layer is deposited on the inner surface of the nacre-inspired layer, while a poly(lactic acid) layer is coated on the outer surface. The composite membrane integrates good mechanical strength and deformability because of the nacre-inspired structure, facilitating operations during the implant surgery. The mineral layer induces the osteogenic differentiation of bone marrow mesenchymal stem cells and increases the stiffness of the membrane, which is an important factor for the regeneration process. The poly(lactic acid) layer can prevent unwanted mineralization on the outer surface of the membrane in oral environments. Cell experiments reveal that the membrane exhibits good biocompatibility and anti-infiltration capability toward connective tissue/epithelium cells. Furthermore, in vitro analyses show that the membrane does not degrade too fast, allowing enough time for bone regeneration. In vivo experiments prove that the membrane can effectively induce better bone regeneration and higher trabecular bone density in alveolar bone defects. This study demonstrates the potential of this bioinspired triple-layered membrane with hierarchical structures as a promising barrier material for periodontal guided tissue regeneration.

The application of lung immune prognostic index in predicting the prognosis of 302 STS patients.

Background: Soft tissue sarcoma (STS) are heterogeneous and rare tumors, and few studies have explored predicting the prognosis of patients with STS. The Lung Immune Prognostic Index (LIPI), calculated based on baseline serum lactate dehydrogenase (LDH) and the derived neutrophils/(leukocytes minus neutrophils) ratio (dNLR), was considered effective in predicting the prognosis of patients with pulmonary cancer and other malignancies. However, the efficacy of the LIPI in predicting the prognosis of patients with STS remains unclear. Methods: This study retrospectively reviewed patients with STS admitted to our center from January 2016 to January 2021. Their hematological and clinical characteristics were collected and analyzed to construct the LIPI specific to STS. The correlations between various predictive factors and overall survival (OS) were examined using Kaplan-Meier and Cox regression analyses. Independent risk factors for OS were identified using univariate and multivariate analyses. Finally, a LIPI nomogram model for STS was established. Results: This study enrolled 302 patients with STS, of which 87 (28.9%), 162 (53.6%), and 53 (17.5%) were classified into three LIPI-based categories: good, moderate, and poor, respectively (P < 0.0001). The time-dependent operator curve showed that the LIPI had better prognostic predictive ability than other hematological and clinical characteristics. Univariate and multivariate analyses identified the Fédération Nationale des Centres de Lutte Contre le Cancer grade (FNCLCC/G), tumor size, and LIPI as independent risk factors. Finally, a nomogram was constructed by integrating the significant prognostic factors. Its C-index was 0.72, and the calibration curve indicated that it could accurately predict the three- and five-year OS of patients with STS. The decision and clinical impact curves also indicated that implementing this LIPI-nomogram could significantly benefit patients with STS. Conclusion: This study explored the efficacy of the LIPI in predicting the prognosis of 302 patients with STS, classifying them into three categories to evaluate the prognosis. It also reconstructed a LIPI-based nomogram to assist clinicians in predicting the three- and five-year OS of patients with STS, potentially enabling timely intervention and customized management.

Krüppel-like transcription factor 14 alleviates alveolar epithelial cell senescence by inhibiting endoplasmic reticulum stress in pulmonaryfibrosis.

Pulmonary fibrosis (PF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia, occurring primarily in older adults with poor prognosis. Alveolar epithelial cell (AEC) senescence is the critical pathological mechanism of PF. However, the molecular mechanisms regulating AEC senescence in PF are incompletely understood. Herein, we provided evidence to support the function of Krüppel-like factor 14 (KLF14), a novel Krüppel-like transcription factor, in the regulation of AEC senescence during PF. We confirmed that the expression of KLF14 was up-regulated in PF patients and mice treated with bleomycin (BLM). KLF14 knockdown resulted in more pronounced structural disruption of the lung tissue and swelling of the alveolar septum, which led to significantly increased mortality in BLM-induced PF mice. Mechanistically, RNA-seq analysis indicated that KLF14 decreased the senescence of AECs by inhibiting endoplasmic reticulum (ER) stress. Furthermore, the pharmacological activation of KLF14 conferred protection against PF in mice. In conclusion, our findings reveal a protective role for KLF14 in preventing AECs from senescence and shed light on the development of KLF14-targeted therapeutics for PF.

High expression of ABL2 promotes gastric cancer cells migration, invasion and proliferation via the TGF-ß and YAP signaling pathways.

Background: The Abelson-Related Gene (ABL2) is expressed in various malignancies. However, its role in gastric cancer (GC) regarding tumor proliferation, metastasis, and invasion remains unclear. Methods: ABL2 expression in clinical specimens was assessed using quantitative real-time fluorescence PCR (qRT-PCR). Western blotting and immunofluorescence assay determined protein levels. Additionally, Transwell migration and invasion, cell counting kit-8 (CCK-8) and colony-formation assays analyzed the effect of ABL2 on GC cells. Protein levels related to GC cells were assessed through Western blotting. The effects of si-ABL2 combined with GA-017 that activated YAP on cell migration, invasion and proliferation were investigated. Results: ABL2 expression was upregulated in human GC tissues compared to paracancer tissues, and it was positively related to tumor node metastasis classification (TNM) stage. Furthermore, high ABL2 levels promoted the proliferation, metastasis, and invasion capacity in GC cells. Elevated ABL2 expression enhanced the expression of MMP2, MMP9, and PCNA while decreasing TIMP1 and TIMP2 expression. It also increased the p-SMAD2/3 expression and YAP expression, decreased the expression of p-YAP in GC cells. Furthermore, GA-017 increased ABL2 expression in MGC-803 cells and counteracted the effects of si-ABL2 on cell migration, invasion and proliferation. Conclusion: These findings indicated that heightened ABL2 expression could activate TGF-ß/SMAD2/3 and YAP signaling pathway, promoting epithelial mesenchymal transformation (EMT), and enhancing multiplication, metastasis, and invasion in GC cells.

Impact of risk factors on intervened and non-intervened coronary lesions.

INTRODUCTION: In-stent restenosis (ISR) and aggravated non-intervened coronary lesions (ANL) are two pivotal aspects of disease progression in patients with coronary artery disease (CAD). Established risk factors for both include hyperlipidemia, hypertension, diabetes, chronic kidney disease, and smoking. However, there is limited research on the comparative risk factors for the progression of these two aspects of progression. The aim of this study was to analyze and compare the different impacts of identical risk factors on ISR and ANL. METHODS: This study enrolled a total of 510 patients with multiple coronary artery lesions who underwent repeated coronary angiography (CAG). All patients had previously undergone percutaneous coronary intervention (PCI) and presented non-intervened coronary lesions in addition to the previously intervened vessels. RESULTS: After data analysis, it was determined that HbA1c (OR 1.229, 95% CI 1.022-1.477, P=0.028) and UA (OR 1.003, 95% CI 1.000-1.005, P=0.024) were identified as independent risk factors for ISR. Furthermore, HbA1c (OR 1.215, 95% CI 1.010-1.460, P=0.039), Scr (OR 1.007, 95% CI 1.003-1.017, P=0.009), and ApoB (OR 1.017, 95% CI 1.006-1.029, P=0.004) were identified as independent risk factors for ANL. The distribution of multiple blood lipid levels differed between the ANL only group and the ISR only group. Non-HDL-C (2.17 mmol/L vs. 2.44 mmol/L, P=0.007) and ApoB (63.5 mg/dL vs. 71.0 mg/dL, P=0.011) exhibited significantly higher values in the ANL only group compared to the ISR only group. CONCLUSIONS: Blood glucose levels and chronic kidney disease were identified as independent risk factors for both ISR and ANL, while elevated lipid levels were only significantly associated with ANL. In patients with non-intervened coronary lesions following PCI, it is crucial to assess the concentration of non-HDL-C and ApoB as they serve as significant risk factors.

Neutrophil extracellular traps trigger alveolar epithelial cell necroptosis through the cGAS-STING pathway during acute lung injury in mice.

Extensive loss of alveolar epithelial cells (AECs) undergoing necroptosis is a crucial mechanism of acute lung injury (ALI), but its triggering mechanism needs to be thoroughly investigated. Neutrophil extracellular traps (NETs) play a significant role in ALI. However, the effect of NETs on AECs' death has not been clarified. Our study found that intratracheal instillation of NETs disrupted lung tissue structure, suggesting that NETs could induce ALI in mice. Moreover, we observed that NETs could trigger necroptosis of AECs in vivo and in vitro. The phosphorylation levels of RIPK3 and MLKL were increased in MLE12 cells after NETs treatment (P < 0.05). Mechanistically, NETs taken up by AECs through endocytosis activated the cGAS-STING pathway and triggered AECs necroptosis. The expression of cGAS, STING, TBK1 and IRF3 were increased in MLE12 cells treated with NETs (P < 0.05). Furthermore, the cGAS inhibitor RU.521 inhibited NETs-triggered AECs necroptosis and alleviated the pulmonary damage induced by NETs in mice. In conclusion, our study demonstrates that NETs taken up by AECs via endocytosis can activate the cGAS-STING pathway and trigger AECs necroptosis to promote ALI in mice. Our findings indicate that targeting the NETs/cGAS-STING/necroptosis pathway in AECs is an effective strategy for treating ALI.

The causal effects of inflammatory and autoimmune skin diseases on thyroid diseases: evidence from Mendelian randomization study.

Background: To clarify the controversy between inflammatory or autoimmune skin diseases and thyroid diseases, we performed two-sample Mendelian randomization (MR) analyses. Participants: Genetic data on factors associated with atopic dermatitis (AD, n=40,835), seborrheic dermatitis (SD, n=339,277), acne (n=363,927), rosacea (n=299,421), urticaria (n=374,758), psoriasis (n=373,338), psoriasis vulgaris (n=369,830), systemic lupus erythematosus (SLE, n=14,267), vitiligo (n=353,348), alopecia areata (AA, n=361,822), pemphigus (n=375,929), bullous pemphigoid (BP, n=376,274), systemic sclerosis (SSc, n=376,864), localized scleroderma (LS, n=353,449), hypothyroidism (n=314,995 or n=337,159), and hyperthyroidism (n=281,683 or n=337,159) were derived from genome-wide association summary statistics of European ancestry. Main measures: The inverse variance weighted method was employed to obtain the causal estimates of inflammatory or autoimmune skin diseases on the risk of thyroid diseases, complemented by MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO). Key results: AD, SLE, SD, and psoriasis vulgaris were associated with an increased risk of hypothyroidism, whereas BP was associated with a lower risk of hypothyroidism (all with p < 0.05). The multivariable MR analyses showed that AD (OR = 1.053; 95%CI: 1.015-1.092; p = 0.006), SLE (OR = 1.093; 95%CI: 1.059-1.127; p < 0.001), and SD (OR = 1.006; 95%CI: 1.002-1.010; p = 0.006) independently and predominately contributed to the genetic causal effect on hypothyroidism after adjusting for smoking. The results showed no causal effects of inflammatory or autoimmune skin diseases on hyperthyroidism. Conclusion: The findings showed a causal effect of AD, SLE, SD on hypothyroidism, but further investigations should be conducted to explore the pathogenic mechanisms underlying these relationships.

Biochemical profiling of the protein encoded by grass carp reovirus genotype II.

In this study, we obtained the whole genome sequence of GCRV-DY197 and investigated the localization, post-translational modifications, and host interactions of the 11 viral proteins encoded by GCRV-DY197 in grass carp ovary (GCO) cells. The whole genome sequence is 24,704 kb and contains 11 segments (S1-S11). Subcellular localization showed that the VP1, VP2, VP3, VP5, VP56, and VP35 proteins were localized in both cytoplasm and nucleus, whereas the NS79, VP4, VP41, VP6, and NS38 proteins were localized in the cytoplasm. The NS79 and NS38 proteins were phosphorylated, and the ubiquitination modification sites were identified in VP41 and NS38. An interaction network containing 9 viral proteins and 140 host proteins was also constructed. These results offer a theoretical basis for an in-depth understanding of the biochemical characteristics and pathogenic mechanism of GCRV-II.

A Biobased Vitrimer: Self-Healing, Shape Memory, and Recyclability Induced by Dynamic Covalent Bond Exchange.

Plant oil-based vitrimer is an innovative and sustainable polymer with wide-ranging potential applications in the field of advanced materials. However, its restricted application is caused by the poor mechanical properties and the need for catalysts during preparation. Using renewable cardanol as the raw material, epoxy cardanol glycidyl ether (ECGE) with an end epoxide group was obtained by the clicking reaction and epoxidation reaction. After the application of citric acid (CA), ECGE was successfully cured, resulting in the production of fully biobased ECGE-CA vitrimers. This material does not require a catalyst, possesses self-healing properties, and exhibits high mechanical strength. On account of the introduction of hydroxyl groups in citric acid, plenty of hydrogen bonds are formed, allowing the topological network rearrangement of the material in the absence of a catalyst. Recyclable adhesives and repairable materials, vitrimer polymers have good shape memory, self-healing, and recyclability since of their dynamic ester and hydroxyl bonds.

OsRAV1 Regulates Seed Vigor and Salt Tolerance During Germination in Rice.

Seed vigor is a complex trait encompassing seed germination, seedling emergence, growth, seed longevity, and stress tolerance, all are crucial for direct seeding in rice. Here, we report that the AP2/ERF transcription factor OsRAV1 (RELATED TO ABI3 AND VP1) positively regulates seed germination, vigor, and salt tolerance. Additionally, OsRAV1 was differently expressed in embryo and endosperm, with the OsRAV1 localized in the nucleus. Transcriptomic analysis revealed that OsRAV1 modulates seed vigor through plant hormone signal transduction and phenylpropanoid biosynthesis during germination. Haplotype analysis showed that rice varieties carrying Hap3 displayed enhanced salt tolerance during seed germination. These findings suggest that OsRAV1 is a potential target in breeding rice varieties with high seed vigor suitable for direct seeding cultivation.

Restoration of ARA metabolic disorders in vascular smooth muscle cells alleviates intimal hyperplasia.

Intimal hyperplasia (IH) is an innegligible issue for patients undergoing interventional therapy. The proliferation and migration of vascular smooth muscle cells (VSMCs) induced by platelet-derived growth factor-BB (PDGF-BB) are critical events in the development of IH. While the exact mechanism and effective target for IH needs further investigation. Metabolic disorders of arachidonic acid (ARA) are involved in the occurrence and progression of various diseases. In this study, we found that the expressions of soluble epoxide hydrolase (sEH) and cyclooxygenase-2 (COX-2) were significantly increased in the VSMCs during balloon injury-induced IH. Then, we employed a COX-2/sEH dual inhibitor PTUPB to increase the concentration of epoxyeicosatrienoic acids (EETs) while prevent the release of pro-inflammatory prostaglandins. Results showed that PTUPB treatment significantly reduced neointimal thickening induced by balloon injury in rats in vivo and inhibited PDGF-BB-induced proliferation and migration of VSMCs in vitro. Our results showed that PTUPB may reverse the phenotypic transition of VSMCs by inhibiting Pttg1 expression. In conclusion, we found that the dysfunction of ARA metabolism in VSMCs contributes to IH, and the COX-2/sEH dual inhibitor PTUPB attenuates IH progression by reversing the phenotypic switch in VSMC through the Sirt1/Pttg1 pathway.

[Expression and Function of circ_0073585 in Acute Myeloid Leukemia].

OBJECTIVE: To investigate the expression level, clinical significance and function of circular RNAs (circRNAs) circ_0073585 in the bone marrow of patients with acute myeloid leukemia (AML). METHODS: The expression levels of circ_0073585 in bone marrow samples of 106 newly diagnosed AML patients and 38 controls were detected by real-time quantitative PCR (RQ-PCR). The differences were compared between the two groups and their clinical significance was analyzed. The diagnostic value of circ_0073585 expression for AML was evaluated by receiver operating characteristic curve(ROC). THP-1 cells with lentivirus overexpressing circ_0073585 vector and empty vector were divided into two groups: circ_0073585-THP-1 and NC-THP-1 group. CCK-8 assay and flow cytometry were used to study the effects of circ_0073585 on THP-1 cell proliferation, survival, apoptosis and drug sensitivity. RESULTS: Compared with the controls, the expression level of circ_0073585 in the bone marrow of AML patients was significantly reduced (P < 0.001). There was a statistically significant difference between the high and low expression groups of circ_0073585 in the white blood cell count, platelet count (P < 0.01) and chromosome risk (P < 0.05). Compared with NC-THP-1 cells, the proliferation and viability of circ_0073585-THP-1 cells were weakened (P < 0.01), the apoptosis rate was increased (P < 0.01), and the sensitivity to homoharringtonine (P < 0.05) and daunorubicin hydrochloride (P < 0.001) was increased. CONCLUSION: The expression level of circ_0073585 is decreased in AML patients. Overexpression of circ_0073585 can inhibit the proliferation and viability of leukemic cells, promote apoptosis, and increase sensitivity of leukemia cells to chemotherapy drugs.

Predictive nomogram for hearing deficits after microvascular decompression treatment.

We explored the impact of brainstem auditory evoked potentials monitoring, as well as anatomical characteristics, in relation to their influence on hearing deficits. A total of 851 patients diagnosed with idiopathic hemifacial spasm underwent microvascular decompression treatment were recruited in our study. A nomogram was developed based on the regression analysis. Nomogram performance was evaluated through receiver operating characteristic (ROC), decision curve analyses and calibration curve. The rate of positive wave V change was also higher in the hearing deficit group (71.8% vs no hearing deficit group, p < 0.001). Furthermore, greater retraction depth (0.78 ± 0.25 cm vs 0.55 ± 0.12 cm, p < 0.001), duration (74.43 ± 15.74 min vs 55.71 ± 7.01 min, p < 0.001) and retraction distance (4.38 ± 0.38 cm vs 4.17 ± 0.24 cm, p = 0.001) were evident in the hearing deficit patients. Multivariate logistic regression showed that positive wave V change (OR 5.43), greater retraction depth (OR 55.57) and longer retraction duration (OR 1.14) emerged as significant independent predictors of postoperative hearing deficit. The external validation cohort exhibited a favorable discrimination with an AUC of 0.88. The calibration curves further confirmed the reliability of the predicted outcome in relation to the observed outcome in the external validation cohort (p = 0.89). The decision curves demonstrated that the nomogram outperformed the All or None scheme when the threshold probability ranged from > 2% to < 60% in the external validation cohort. We constructed a nomogram, including wave V, retraction depth, and retraction duration, which can effectively predict the occurrence of hearing deficits and has good clinical applicability.