The OsNAC41-RoLe1-OsAGAP module promotes root development and drought tolerance in upland rice.

Drought is a major environmental stress limiting crop yields worldwide. Upland rice (Oryza sativa) has evolved complex genetic mechanisms to adjust to drought stress. However, few genetic variants have been identified that mediate drought resistance in upland rice, and little is known about the evolution of this trait during domestication. Here, using a genome-wide association study in rice, we identified ROOT LENGTH 1 (RoLe1) controlling root length and drought resistance. We demonstrate that a G-to-T polymorphism in the RoLe1 promoter increases binding of the transcription factor OsNAC41 to activate its transcription. We also show that RoLe1 interacts with and interferes with the function of OsAGAP, an ARF-GTPase activating protein involved in auxin-dependent root development, to modulate root development. Furthermore, RoLe1 enhanced crop yield by increasing the seed setting rate under moderate drought conditions. Genomic evolution analysis showed that a newly arisen favorable allelic variant, proRoLe1-526T, originated from Region I (Midwest Asia) and was retained in upland rice during domestication. Our findings propose a OsNAC41-RoLe1-OsAGAP module, providing promising genetic targets for molecular breeding of drought-resistant varieties in rice.

Inflammatory burden index: associations between osteoarthritis and all-cause mortality among individuals with osteoarthritis.

BACKGROUND: The newly described inflammatory burden index (IBI) reflects a patient's inflammatory burden. This study aimed to estimate the association between IBI, osteoarthritis (OA), and all-cause mortality in patients with OA. METHODS: We extracted the data of adults from the National Health and Nutrition Examination Survey database between 1999 and 2018. After using appropriate survey weights to correct for sample bias, we conducted multivariate logistic regression analyses to explore the association between IBI and OA across three models: in the unadjusted model, partially adjusted model (adjusting age, sex, race, education level, marital status, PIR, BMI, smoking status, drinking status, stroke, CVD, DM, and hypertension) and fully adjusted model (which included additional variables: HBA1C, ALT, AST, BUN, TC, and HDL). And the odds ratios (OR) and 95% confidence intervals (CI) were calculated. Similarly, using comparable survey weights and covariates adjustments, we employed Cox proportional hazards regression analysis to investigate the association between IBI and all-cause mortality in the other 3 models. The Cox proportional hazards regression models were fitted to calculate the hazard ratios (HR) and 95% CI of the association between IBI and all-cause mortality. A restricted cubic spline (RCS) was used to explore the nonlinear relationships between association effects. Subgroup analysis was performed to validate the reliability of their effects. RESULTS: In total, 22,343 eligible participants were included. Multiple logistic regression models revealed that participants with the highest IBI had 2.54 times (95%CI, 2.23, 2.90)) higher risk of OA than those with the lowest IBI in Model 1, whereas the OR was 1.21 (95%CI, 1.03, 1.42) in Model 2 and 1.23 (95%CI,1.05, 1.45) in Model 3. Multiple Cox regression models showed participants with the highest IBI had 186% (95%CI, 1.50, 2.31) times risk of developing all-cause death than those with the lowest IBI in Model 1. This trend remained stable in Models 2 (HR,1.54; 95%CI,1.22, 1.95) and 3 (HR, 1.41; 95%CI, 1.10, 1.80). The RCS revealed a significant positive association between IBI and OA risk. With respect to the association between IBI and all-cause mortality, a slight decrease in mortality was observed from the lowest quartile to the second quartile of IBI, and the mortality risk increased with increasing IBI. Subgroup analyses showed that age, cardiovascular disease, and hypertension were pivotal in the association of IBI with all-cause mortality, whereas the association of IBI with OA remained stable after stratification by other factors such as sex, race, education level, marital, smoking, and drinking status, hypertension, and most serological indices. CONCLUSIONS: This study provides evidence of a positive association between IBI, OA, and all-cause mortality. IBI may be a promising signature for assessing the inflammatory burden in patients with OA, which, in turn, is conducive to precise references for high-risk population recognition, anti-inflammatory guidance, and reducing mortality intervention.

A Novel Microbial Compound Inhibitor and Its Efficacy in Preventing and Controlling Mine Fire Risks: A Case Study on Low-Rank Coal Spontaneous Combustion.

To guarantee the safety and sustainability of coal mining by effectively mitigating the substantial risk associated with coal spontaneous combustion, this study proposes a multifaceted prevention strategy aligned with green environmental principles. A compound flame retardant with a physicochemical control mechanism was prepared using indigenous microorganisms to mineralize residual coal after mining, utilizing Bacillus pasteurelli as a substitute material for inorganic salts. Under laboratory conditions simulating coal self-combustion, biobased flame retardants were employed to investigate the physical and chemical transformations of heat and mass evolution from ambient temperature to combustion in two representative low-rank coals. By quantitatively comparing alterations in microbiome-based groups among raw lignite, bioretarded lignite, and two control samples, the inhibitory mechanism of biobased materials on the oxygen reaction pathway was elucidated. The findings substantiated that biobased modification can consolidate the methyl and methylene groups present in aliphatic hydrocarbon side chains, which are prone to instigating low-temperature oxidation reactions. Additionally, the preventive performance of biobased flame retardants was assessed through temperature-programmed experiments, which involved estimating the critical self-heating temperature, oxygen consumption, and gas production rates of compared coal samples. The results demonstrated significant enhancements in the resistance to spontaneous combustion following bioretarded modification. Notably, the identification grade of long flame coal shifted from easy to moderate susceptibility to spontaneous combustion. Furthermore, biobased flame retardants exhibited remarkable flame retardancy rates of approximately 80% for lignite, thereby validating their efficacy as more environmentally friendly and technologically advanced substitute materials for inhibiting spontaneous combustion in low-rank coals.

Sub-bundle based analysis reveals the role of human optic radiation in visual working memory.

White matter (WM) functional activity has been reliably detected through functional magnetic resonance imaging (fMRI). Previous studies have primarily examined WM bundles as unified entities, thereby obscuring the functional heterogeneity inherent within these bundles. Here, for the first time, we investigate the function of sub-bundles of a prototypical visual WM tract-the optic radiation (OR). We use the 7T retinotopy dataset from the Human Connectome Project (HCP) to reconstruct OR and further subdivide the OR into sub-bundles based on the fiber's termination in the primary visual cortex (V1). The population receptive field (pRF) model is then applied to evaluate the retinotopic properties of these sub-bundles, and the consistency of the pRF properties of sub-bundles with those of V1 subfields is evaluated. Furthermore, we utilize the HCP working memory dataset to evaluate the activations of the foveal and peripheral OR sub-bundles, along with LGN and V1 subfields, during 0-back and 2-back tasks. We then evaluate differences in 2bk-0bk contrast between foveal and peripheral sub-bundles (or subfields), and further examine potential relationships between 2bk-0bk contrast and 2-back task d-prime. The results show that the pRF properties of OR sub-bundles exhibit standard retinotopic properties and are typically similar to the properties of V1 subfields. Notably, activations during the 2-back task consistently surpass those under the 0-back task across foveal and peripheral OR sub-bundles, as well as LGN and V1 subfields. The foveal V1 displays significantly higher 2bk-0bk contrast than peripheral V1. The 2-back task d-prime shows strong correlations with 2bk-0bk contrast for foveal and peripheral OR fibers. These findings demonstrate that the blood oxygen level-dependent (BOLD) signals of OR sub-bundles encode high-fidelity visual information, underscoring the feasibility of assessing WM functional activity at the sub-bundle level. Additionally, the study highlights the role of OR in the top-down processes of visual working memory beyond the bottom-up processes for visual information transmission. Conclusively, this study innovatively proposes a novel paradigm for analyzing WM fiber tracts at the individual sub-bundle level and expands understanding of OR function.

Charge-Delocalized Triptycene-Based Ionic Porous Organic Polymers as Quasi-Solid-State Electrolytes for Lithium Metal Batteries.

Ideal solid electrolytes for lithium (Li) metal batteries should conduct Li+ rapidly with low activation energy, exhibit a high Li+ transference number, form a stable interface with the Li anode, and be electrochemically stable. However, the lack of solid electrolytes that meet all of these criteria has remained a considerable bottleneck in the advancement of lithium metal batteries. In this study, we present a design strategy combining all of those requirements in a balanced manner to realize quasi-solid-state electrolyte-enabled Li metal batteries (LMBs). We prepared Li+-coordinated triptycene-based ionic porous organic polymers (Li+@iPOPs). The Li+@iPOPs with imidazolates and phenoxides exhibited a high conductivity of 4.38 mS cm-1 at room temperature, a low activation energy of 0.627 eV, a high Li+ transference number of 0.95, a stable electrochemical window of up to 4.4 V, excellent compatibility with Li metal electrodes, and high stability during Li deposition/stripping cycles. The high performance is attributed to charge delocalization in the backbone, mimicking the concept of lithium bis(trifluoromethanesulfonyl)imide (LiTFSI), which facilitates the diffusion of coordinated Li+ through the porous space of the triptycene-based iPOPs. In addition, Li metal batteries assembled using Li+@Trp-Im-O-POPs as quasi-solid-state electrolytes and a LiFePO4 cathode showed an initial capacity of 114 mAh g-1 and 86.7% retention up to 200 cycles.

Missing-Linker Defect Functionalized Metal-Organic Frameworks Accelerating Zinc Ion Conduction for Ultrastable All-Solid-State Zinc Metal Batteries.

Solid-state polymer electrolytes (SPEs) are promising for high-performance zinc metal batteries (ZMBs), but they encounter critical challenges of low ionic conductivity, limited Zn2+ transference number (tZn2+), and an unstable electrolyte-electrode interface. Here, we present an effective approach involving a missing-linker metallic organic framework (MOF)-catalyzed poly(ethylene glycol) diacrylate (PEGDA)/polyacrylamide (PAM) copolymer SPE for single Zn2+ conduction and seamless electrolyte-electrode contact. The single-Zn2+ conduction is facilitated by the anchoring of the OTF- anions onto the unsaturated metal sites of missing-linker MOF, while the PEGDA and PAM chains in competitive coordination with Zn2+ ions promote rapid Zn ion transport. Our all-solid-state electrolyte simultaneously achieves a superior ionic conductivity of 1.52 mS cm-1 and a high tZn2+ of 0.83 at room temperature, alongside uniform Zn metal deposition (1000 cycles in symmetric cells) and high Zn plating/striping efficiencies (>99% after 600 cycles in asymmetric cells). Applications of our SPE in Zn//VO2 full cells are further demonstrated with a long lifespan of 2000 cycles and an extremely low-capacity degradation rate of 0.012% per cycle. This work provides an effective strategy for using a missing-linker MOF to catalyze competitively coordinating copolymers for accelerating Zn2+ ion conduction, assisting the future design of all-solid-state ZMBs.

Machine-Learning Models Reliably Predict Clinical Outcomes in Medial Patellofemoral Ligament Reconstruction.

PURPOSE: To develop a machine-learning model to predict clinical outcomes after medial patellofemoral ligament reconstruction (MPFLR) and identify the important predictive indicators. METHODS: This study included patients who underwent MPFLR from January 2018 to December 2022. The exclusion criteria were as follows: (1) concurrent bony procedures, (2) history of other knee surgeries, and (3) follow-up period of less than 12 months. Forty-two predictive models were constructed for 7 clinical outcomes (failure to achieve minimum clinically important difference of clinical scores, return to preinjury sports, pivoting sports, and recurrent instability) using 6 machine-learning algorithms (random forest, logistic regression, support vector machine, decision tree, implemented multilayer perceptron, and K-nearest neighbor). The performance of the model was evaluated using metrics such as the area under the receiver operating characteristic curve, accuracy, specificity, and sensitivity. In addition, SHapley Additive exPlanation summary plot was employed to identify the important predictive factors of the best-performing model. RESULTS: A total of 218 patients met criteria. For the best-performing models in predicting failure to achieve the minimum clinically important difference for Lysholm, International Knee Documentation Committee, Kujala, and Tegner scores, the area under the receiver operating characteristic curves and accuracies were 0.884 (good) and 87.3%, 0.859 (good) and 86.2%, 0.969 (excellent) and 97.0%, and 0.760 (fair) and 76.8%, respectively; 0.952 (excellent) and 95.2% for return to preinjury sports; 0.756 (fair) and 75.4% for return to pivoting sports; and 0.943 (excellent) and 94.9% for recurrent instability. Low preoperative Tegner score, shorter time to surgery, and absence of severe trochlear dysplasia were significant predictors for return to preinjury sports, whereas the absence of severe trochlear dysplasia and patellar alta were significant predictors for return to pivoting sports. Older age, female sex, and low preoperative Lysholm score were highly predictive of recurrent instability. CONCLUSIONS: The predictive models developed using machine-learning algorithms can reliably forecast the clinical outcomes of MPFLR, particularly demonstrating excellent performance in predicting recurrent instability. LEVEL OF EVIDENCE: Level III, case-control study.

MRGazer: decoding eye gaze points from functional magnetic resonance imaging in individual space.

Objective. Eye-tracking research has proven valuable in understanding numerous cognitive functions. Recently, Freyet alprovided an exciting deep learning method for learning eye movements from functional magnetic resonance imaging (fMRI) data. It employed the multi-step co-registration of fMRI into the group template to obtain eyeball signal, and thus required additional templates and was time consuming. To resolve this issue, in this paper, we propose a framework named MRGazer for predicting eye gaze points from fMRI in individual space.Approach. The MRGazer consists of an eyeball extraction module and a residual network-based eye gaze prediction module. Compared to the previous method, the proposed framework skips the fMRI co-registration step, simplifies the processing protocol, and achieves end-to-end eye gaze regression.Main results. The proposed method achieved superior performance in eye fixation regression (Euclidean error, EE = 2.04°) than the co-registration-based method (EE = 2.89°), and delivered objective results within a shorter time (∼0.02 s volume-1) than prior method (∼0.3 s volume-1).Significance. The MRGazer is an efficient, simple, and accurate deep learning framework for predicting eye movement from fMRI data, and can be employed during fMRI scans in psychological and cognitive research. The code is available athttps://github.com/ustc-bmec/MRGazer.

A novel selenium analog of HDACi-based twin drug induces apoptosis and cell cycle arrest via CDC25A to improve prostate cancer therapy.

Cancer therapy has moved from single agents to more mechanism-based targeted approaches. In recent years, the combination of HDAC inhibitors and other anticancer chemicals has produced exciting progress in cancer treatment. Herein, we developed a novel prodrug via the ligation of dichloroacetate to selenium-containing potent HDAC inhibitors. The effect and mechanism of this compound in the treatment of prostate cancer were also studied. Methods: The concerned prodrug SeSA-DCA was designed and synthesized under mild conditions. This compound's preclinical studies, including the pharmacokinetics, cell toxicity, and anti-tumor effect on prostate cancer cell lines, were thoroughly investigated, and its possible synergistic mechanism was also explored and discussed. Results: SeSA-DCA showed good stability in physiological conditions and could be rapidly decomposed into DCA and selenium analog of SAHA (SeSAHA) in the tumor microenvironment. CCK-8 experiments identified that SeSA-DCA could effectively inhibit the proliferation of a variety of tumor cell lines, especially in prostate cancer. In further studies, we found that SeSA-DCA could also inhibit the metastasis of prostate cancer cell lines and promote cell apoptosis. At the animal level, oral administration of SeSA-DCA led to significant tumor regression without obvious toxicity. Moreover, as a bimolecular coupling compound, SeSA-DCA exhibited vastly superior efficacy than the mixture with equimolar SeSAHA and DCA both in vitro and in vivo. Our findings provide an important theoretical basis for clinical prostate cancer treatment. Conclusions: Our in vivo and in vitro results showed that SeSA-DCA is a highly effective anti-tumor compound for PCa. It can effectively induce cell cycle arrest and growth suppression and inhibit the migration and metastasis of PCa cell lines compared with monotherapy. SeSA-DCA's ability to decrease the growth of xenografts is a little better than that of docetaxel without any apparent signs of toxicity. Our findings provide an important theoretical basis for clinical prostate cancer treatment.

Novel antibody-antibiotic conjugate using KRM-1657 as payload eliminates intracellular MRSA in vitro and in vivo.

Staphylococcus aureus is considered to be an extracellular pathogen. However, survival of S.aureus within host cells may cause long-term colonization and clinical failure. Current treatments have poor efficacy in clearing intracellular bacteria. Antibody-antibiotic conjugates (AACs) is a novel strategy for eliminating intracellular bacteria. Herein, we use KRM-1657 as payload of AAC for the first time, and we conjugate it with anti S. aureus antibody via a dipeptide linker (Valine-Alanine) to obtain a novel AAC (ASAK-22). The ASAK-22 exhibits good in vitro pharmacokinetic properties and inhibitory activity against intracellular MRSA, with 100 µg/mL of ASAK-22 capable of eliminating intracellular MRSA to the detection limit. Furthermore, the in vivo results demonstrate that a single administration of ASAK-22 significantly reduces the bacterial burden in the bacteremia model, which is superior to the vancomycin treatment.

Abnormalities in subcortical function and their treatment response in Wilson's disease.

Extensive neuroimaging abnormalities in subcortical regions build the pathophysiological basis of Wilson's disease (WD). Yet, subcortical topographic organization fails to articulate, leaving a huge gap in understanding the neural mechanism of WD. Thus, how functional abnormalities of WD subcortical regions influence complex clinical symptoms and response to treatment remain unknown. Using resting-state functional MRI data from 232 participants (including 130 WD patients and 102 healthy controls), we applied a connectivity-based parcellation technique to develop a subcortical atlas for WD. The atlas was further used to investigate abnormalities in subcortical function (ASF) by exploring intrasubcortical functional connectivity (FC) and topographic organization of cortico-subcortical FC. We further used support vector machine (SVM) to integrate these functional abnormalities into the ASF score, which serves as a biomarker for characterizing individual subcortical dysfunction for WD. Finally, the baseline ASF score and one-year treatment data of the follow-up WD patients were used to assess treatment response. A group set of subcortical parcellations was evaluated, in which 26 bilateral regions well recapitulated the anatomical nuclei of the subcortical areas of WD. The results of cortico-subcortical FC and intrasubcortical FC reveal that dysfunction of the somatomotor networks-lenticular nucleus-thalamic pathways is involved in complex symptoms of WD. The ASF score was able to characterize disease progression and was significantly associated with treatment response of WD. Our findings provide a comprehensive elaboration of functional abnormalities of WD subcortical regions and reveal their association with clinical presentations, improving our understanding of the functional neural underpinnings in WD. Furthermore, abnormalities in subcortical function could serve as a potential biomarker for understanding the disease progression and evaluating treatment response of WD.

A ß-Carboline Derivate PAD4 Inhibitor Reshapes Neutrophil Phenotype and Improves the Tumor Immune Microenvironment against Triple-Negative Breast Cancer.

Triple-negative breast cancer is a highly aggressive and heterogeneous breast cancer subtype characterized by early metastasis, poor prognosis, and high recurrence. Targeting histone citrullination-mediated chromatin dysregulation to induce epigenetic alterations shows great promise in TNBC therapy. We report the synthesis, optimization, and evaluation of a novel series of ß-carboline-derived peptidyl arginine deiminase 4 inhibitors that exhibited potent inhibition of TNBC cell proliferation. The most outstanding PAD4 inhibitor, compound 28, hindered the PAD4-H3cit-NET signaling pathway and inhibited the growth of solid tumors and pulmonary metastatic nodules in the 4T1 in situ mouse model. Furthermore, 28 improved the tumor immune microenvironment by reshaping neutrophil phenotype, upregulating the proportions of dendritic cells and M1 macrophages, and reducing the amount of myeloid-derived suppressor cells. In conclusion, our work offered 28 as an efficacious PAD4 inhibitor that exerts a combination of conventional chemotherapy and immune-boosting effects, which represents a potential therapy strategy for TNBC.

Zero-valent iron (ZVI) facilitated in-situ selenium (Se) immobilization and its recovery by magnetic separation: Mechanisms and implications for microbial ecology.

Selenium (Se(VI)) is environmentally toxic. One of the most popular reducing agents for Se(VI) remediation is zero-valent iron (ZVI). However, most ZVI studies were carried out in water matrices, and the recovery of reduced Se has not been investigated. A water-sediment system constructed using natural sediment was employed here to study in-situ Se remediation and recovery. A combined effect of ZVI and unacclimated microorganisms from natural sediment was found in Se(VI) removal in the water phase with a removal efficiency of 92.7 ± 1.1% within 7 d when 10 mg L-1 Se(VI) was present. Soluble Se(VI) was removed from the water and precipitated to the sediment phase (74.8 ± 0.1%), which was enhanced by the addition of ZVI (83.3 ± 0.3%). The recovery proportion of the immobilized Se was 34.2 ± 0.1% and 92.5 ± 0.2% through wet and dry magnetic separation with 1 g L-1 ZVI added, respectively. The 16 s rRNA sequencing revealed the variations in the microbial communities in response to ZVI and Se, which the magnetic separation could potentially mitigate in the long term. This study provides a novel technique to achieve in-situ Se remediation and recovery by combining ZVI reduction and magnetic separation.

Comparison of Different Ultrasonic Screening Methods and Analysis of High Risk Factors for Fetal Cardiac Malformation in Second Trimester of Pregnancy.

Current study aims to compare the application of two-dimensional (2D) color doppler ultrasound (CDU) and four-dimensional (4D) ultrasound spatiotemporal image correlation (STIC) in fetal congenital heart disease in the second trimester of pregnancy and to analyze the high risk factors of the disease. From August 2019 to July 2021, 135 second-trimester patients with highly suspected congenital heart malformations were selected who underwent prenatal screening at South Taihu Hospital Affiliated to Huzhou University. 2D-CDU, 4D STIC, and postnatal examination were completed in all patients. 2D-CDU, 4D STIC and 2D-CDU combined with 4D STIC were used to detect fetal cardiac malformations and classify cardiac malformations. The sensitivity, specificity, positive predictive value, negative predictive value and coincidence rate of 2D-CDU, 4D STIC and 2D-CDU combined with 4D STIC were compared. The results of 2D-CDU, 4D STIC and 2D-CDU combined with 4D STIC screening were analyzed for consistency using the results of postpartum diagnosis as the gold standard. Moreover, effects of maternal gestational factors on fetal cardiac malformations by univariate and multivariate analysis. 2D-CDU combined with 4D STIC showed significantly higher section display number than 2D-CDU or 4D STIC in the view of ductal arch, aortic arch, and aortic short-axis. A total of 45 cases of fetal congenital heart malformation were detected in 135 patients in the second trimester, 40, 38 or 42 cases were detected by 2D-CDU, 4D STIC or 2D-CDU combined with 4D STIC, respectively. The sensitivity, specificity, positive predictive value, negative predictive value and coincidence rate of 2D-CDU combined with 4D ultrasound in congenital heart malformation screening were higher than those of 2D-CDU or 4D STIC. Kappa agreement analysis showed that the diagnostic results of 4D STIC and 2D-CDU combined with 4D ultrasound in fetuses with suspected congenital heart malformation were in excellent agreement (κ > 0.75), while 2D-CDU was in good agreement with postpartum diagnosis (κ < 0.75). Univariate and multivariate regression analysis revealed that maternal age ≥ 35, drinking during pregnancy, and history of adverse pregnancy and childbirth were all independent risk factors for fetal cardiac malformations, while folic acid supplementation was an independent protective factor for fetal cardiac malformations. 2D-CDU combined with 4D echocardiography may be superior to single 2D-CDU or 4D STIC in the screening of fetal congenital heart malformation in the second trimester. In order to reduce the incidence of fetal heart anomalies, we should strengthen the screening of pregnancy anomalies in high-risk pregnant women and control the risk factors.

A novel histone deacetylase inhibitor Se-SAHA attenuates isoproterenol-induced heart failure via antioxidative stress and autophagy inhibition.

Heart failure is associated with histone deacetylase (HDAC) regulation of gene expression, the inhibition of which is thought to be beneficial for heart failure therapy. Here, we explored the cardioprotective effects and underlying mechanism of a novel selenium-containing HDAC inhibitor, Se-SAHA, on isoproterenol (ISO)-induced heart failure. We found that pretreatment with Se-SAHA attenuated ISO-induced cardiac hypertrophy and fibrosis in neonatal rat ventricular myocytes (NRVMs). Se-SAHA significantly attenuated the generation of ISO-induced reactive oxygen species (ROS) and restored the expression levels of superoxide dismutase 2 (SOD2) and heme oxygenase-1 (HO-1) in vitro. Furthermore, Se-SAHA pretreatment prevented the accumulation of autophagosomes. Se-SAHA reversed the high expression of HDAC1 and HDAC6 induced by ISO incubation. However, after the addition of the HDAC agonist, the effect of Se-SAHA on blocking autophagy was inhibited. Using ISO-induced mouse models, cardiac ventricular contractile dysfunction, hypertrophy, and fibrosis was reduced treated by Se-SAHA. In addition, Se-SAHA inhibited HDAC1 and HDAC6 overexpression in ISO-treated mice. Se-SAHA treatment significantly increased the activity of SOD2 and improved the ability to eliminate free radicals. Se-SAHA hindered the excessive levels of the microtubule-associated protein 1 light chain 3 (LC3)-II and Beclin-1 in heart failure mice. Collectively, our results indicate that Se-SAHA exerts cardio-protection against ISO-induced heart failure via antioxidative stress and autophagy inhibition.

A comparative study of the hypolipidemic effects and mechanisms of action of Laminaria japonica- and Ascophyllum nodosum-derived fucoidans in apolipoprotein E-deficient mice.

The structural characteristics of fucoidans exhibit species and regional diversity. Previous studies have demonstrated that Laminaria japonica- and Ascophyllum nodosum-derived fucoidans have type I and type II fucosyl chains, respectively. These chemical differences may contribute to distinct hypolipidemic effects and mechanisms of action. Chemical analysis demonstrated that the percentage contents of sulfate, glucuronic acid, and galactose were higher in L. japonica-derived fucoidans than those of A. nodosum-derived fucoidans. In hyperlipidemic apolipoprotein E-deficient mice, both A. nodosum- and L. japonica-derived fucoidans significantly decreased the plasma and hepatic levels of total cholesterol and triglyceride, leading to the reduction of atherosclerotic plaques. Western blotting experiments demonstrated that these fucoidans significantly enhanced the expression and levels of scavenger receptor B type 1, cholesterol 7 alpha-hydroxylase A1, and peroxisome proliferator-activated receptor (PPAR)-α, contributing to circulating lipoprotein clearance and fatty acid degradation, respectively. Differentially, L. japonica-derived fucoidan significantly increased the LXR/ATP-binding cassette G8 signaling pathway in the small intestine, as revealed by real-time quantitative PCR, which may lead to further cholesterol and other lipid excretion. Collectively, these data are useful for understanding the hypolipidemic mechanisms of action of seaweed-derived fucoidans, and their potential application for the prevention and/or treatment of atherosclerotic cardiovascular diseases.

Application of gel based on medical image inspection in total closure resection of oral cancer patients.

Oral cancer is a common malignant tumor, and total closed resection is a common treatment. However, it has always been a challenge to determine the exact extent of excision during surgery. The application of medical image examination in surgery can provide important reference information, but the current methods still have some limitations. This study explored the application of gels based on medical image examination in the total closed resection of oral cancer patients to improve the accuracy of resection range and surgical treatment effect. The study collected medical image data of patients with oral cancer for image enhancement and determination of resection boundaries. By comparing the results of the experimental group and the control group, the application effect of gel in operation was evaluated. Through the application of medical image inspection technology, the determination of surgical resection boundary is more accurate, and the positive incisal margin of patients is effectively avoided. Gel technology improves the success rate and efficacy of surgery, and this method helps to improve the accuracy of surgery and the certainty of the scope of resection, which is of great significance for improving the surgical treatment effect and the survival rate of patients.

Diagnostic Performance of 18 F-FDG Positron Emission Tomography/Computed Tomography and Blood Test Parameters for Pulmonary Inflammatory Pseudotumor.

PURPOSE: Pulmonary inflammatory pseudotumor (PIP) is an inflammatory proliferative tumor-like lesion that frequently exhibits hypermetabolism on 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography imaging (PET/CT) and is readily misdiagnosed as a malignant tumor. The purpose of this study was to identify PIP by combining PET/computed tomography metabolic and blood test characteristics with machine learning. PATIENTS AND METHODS: We recruited 27 patients with PIP and 28 patients with lung cancer (LC). The PET metabolic and blood test parameters were collected, and the differences between the groups were evaluated. In addition, we combined the support vector machine (SVM) classifier with the indicators that differed between the groups to classify PIP and LC. RESULTS: For PET metabolic parameters, our findings showed that, as compared with the LC group, maximal standardized uptake value ( P < 0.001, t = -4.780), Mean standardized uptake value SUV mean , P < 0.001, t = -4.946), and SD40% ( P < 0.001, t = -4.893) were considerably reduced in the PIP group, whereas CV40% ( P = 0.004, t = 3.012) was significantly greater. For blood test parameters, the total white blood cell count ( P < 0.001, t = 6.457) and absolute neutrophil count ( P < 0.001, t = 6.992) were substantially higher in the PIP group than in the LC group. Furthermore, the performance of SVM trained solely on PET metabolic parameters (mean area under the curve [AUC] = 0.84) was comparable to that of SVM trained solely on blood test parameters (mean AUC = 0.86). Surprisingly, utilizing the combined parameters increased SVM performance significantly (mean AUC = 0.98). CONCLUSION: PET metabolic and blood test parameters differed significantly between the PIP and LC groups, and the SVM paradigm using these significantly different features has the potential to be used to classify PIP and LC, which has important clinical implications.

Structure-Activity Relationship of PAD4 Inhibitors and Their Role in Tumor Immunotherapy.

Protein arginine deiminase 4 (PAD4) plays an important role in cancer progression by participating in gene regulation, protein modification, and neutrophil extracellular trap (NET) formation. Many reversible and irreversible PAD4 inhibitors have been reported recently. In this review, we summarize the structure-activity relationships of newly investigated PAD4 inhibitors to bring researchers up to speed by guiding and describing new scaffolds as optimization and development leads for new effective, safe, and selective cancer treatments. In addition, some recent reports have shown evidence that PAD4 inhibitors are expected to trigger antitumor immune responses, regulate immune cells and related immune factors, enhance the effects of immune checkpoint inhibitors, and enhance their antitumor efficacy. Therefore, PAD4 inhibitors may potentially change tumor immunotherapy and provide an excellent direction for the development and clinical application of immunotherapy strategies for related diseases.

Abnormal occipital and frontal activity during voluntary convergence in intermittent exotropia: A task-fMRI study.

Intermittent exotropia (IXT) is characterized by intermittently outward deviation of the eye and involved with vergence dysfunction. This study aimed to investigate the brain areas related to voluntary convergence and cortical activation changes between IXT patients and normal subjects. A total of 21 subjects, including 11 IXT patients and 10 age- and sex-matched normal subjects, were recruited for this study. A voluntary convergence task was employed, with changes in brain function measured by functional magnetic resonance imaging (fMRI). Correlations between cortical activation and clinical measurements were conducted by Pearson's correlation analysis. fMRI results showed that during voluntary convergence, the medial frontal gyrus (MFG) and bilateral occipital cortex were activated in the normal group, whereas only activation of the occipital cortex in IXT patients. Compared with the normal, IXT patients showed hypo-activation of both the MFG and cuneus during the task. The activation of MFG was negatively correlated to the duration of IXT. This study demonstrates that both MFG and occipital cortex may participate in voluntary convergence in normal subjects, while IXT patients have an aberrant cortical function of the MFG and cuneus, and the duration of IXT likely influences the severity of MFG. These findings may provide valuable insights for understanding the relationship between convergence and IXT.