Unearthing the Potential Therapeutic Effects of Oxyresveratrol Based on Intrinsic Links between Pharmacological Effects: Implications for the Gut-Liver-Brain Axis.

Oxyresveratrol is a stilbene compound with a simple chemical structure and various therapeutic potentials. This study summarized and analyzed the multiple pharmacological effects and mechanisms of oxyresveratrol, identifying its prominent performance in neuroprotection, hepatoprotection, and anti-inflammatory activities in the intestines. By integrating the pharmacological effects of oxyresveratrol with insights from the network pharmacology and molecular docking of its interactions with targets linked to gut-liver-brain axis disorders, it has been shown that oxyresveratrol may hold promise for the treatment of gut-liver-brain axis-related disorders. The synergistic effect between various mechanisms has inspired further research and the development of oxyresveratrol's application value.

Effects of feeding patterns on production performance, lipo-nutritional quality and gut microbiota of Sunit sheep.

This study aimed to investigate the impact of feeding patterns on the production performance, lipo-nutritional quality, and gut microbiota of Sunit sheep. A total of 24 sheep were assigned to two groups: confinement feeding (CF) and pasture feeding (PF) groups. After 90 days, the CF group exhibited significantly increased average daily gain, carcass weight, backfat thickness, and intramuscular fat content of the sheep, whereas the PF group showed significantly increased pH24h and decreased L∗ value and cooking loss of the longissimus lumborum (LL) muscle (P < 0.05). In the PF group, the contents of linoleic, α-linolenic, and docosahexaenoic acids were considerably higher and the n-6/n-3 polyunsaturated fatty acid ratio was significantly lower (P < 0.05). Furthermore, the triglyceride, cholesterol, and nonesterified fatty acid levels in the serum of the CF group significantly increased, whereas the enzyme contents of fatty acid synthase (FASN) and hormone-sensitive lipase (HSL) in the LL muscle of the PF group were markedly elevated (P < 0.05). The PF group also showed altered expression of lipid metabolism-related genes, including upregulated FASN, HSL, fatty acid binding protein 4 (FABP4), and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) (P < 0.05). Meanwhile, differences were observed in the abundance of key bacteria and microbiota functions between the groups. Correlation analysis revealed that production performance and lipid metabolism may be related to the differential effects of bacteria. In conclusion, the transition in the feeding patterns of Sunit sheep caused changes in the gut microbial community and lipid metabolism level in the muscle as well as differences in fat deposition and meat quality.

The Asymmetric Total Synthesis of the Female-Produced Sex Pheromone of the Tea Tussock Moth.

The tea tussock moth is a pest that damages tea leaves, affecting the quality and yield of tea and causing huge economic losses. The efficient asymmetric total synthesis of the sex pheromone of the tea tussock moth was achieved using commercially available starting materials with a 25% overall yield in 11 steps. Moreover, the chiral moiety was introduced by Evans' template and the key C-C bond construction was accomplished through Julia-Kocienski olefination coupling. The synthetic sex pheromone of the tea tussock moth will facilitate the subsequent assessment and implementation of pheromones as environmentally friendly tools for pest management.

Inborn errors of immunity and its clinical significance in children with lymphoma in China: a single-center study

Abstract Objective: To investigate the incidence, clinical and genetic characteristics of pediatric lymphoma patients of China with inborn errors of immunity (IEI)-related gene mutations, which have not been fully studied. Method: From Jan. 2020 to Mar. 2023, IEI-related genetic mutations were retrospectively explored in 108 children with lymphomas admitted to Beijing Children's Hospital by NGS. Genetic rule and clinical characteristics as well as treatment outcomes were compared between patients with or without IEI-related gene mutations. Results: A total of 17 patients (15.7 %) harbored IEI-associated mutations, including 4 cases with X-linked lymphoproliferative syndrome (XLP), 3 cases had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), 2 cases with Activated p110 syndrome (APDS). Patients with IEI all had alteration of immunocompetence with decreased levels of immunoglobulin and lymphocyte subsets. Recurrent infection existed in 41.2 % of patients. The 18-month event-free survival (EFS) and the overall response rate (ORR) of patients with IEI are significantly lower than those without IEI (33.86% vs. 73.26 %, p = 0.011; 52.94% vs. 87.91 %, p = 0.002, respectively). In addition, patients with IEI had a higher progression disease (PD) rate of 23.5 % than those without IEI of 4.4% (p = 0.006). Conclusion: The present study demonstrated that IEI-associated lymphomas were much more common than originally appreciated in pediatric lymphomas, and those were insensitive to treatment and more likely to progress or relapse. The genomic analysis and a thorough review of the medical history of IEI can be used to distinguish them from pediatric lymphomas without IEI, which are beneficial for the early diagnosis and direct intervention.

Intermittent Fasting Targets Osteocyte Neuropeptide Y to Relieve Osteoarthritis.

Osteoarthritis is a highly prevalent progressive joint disease that still requires an optimal therapeutic approach. Intermittent fasting is an attractive dieting strategy for improving health. Here this study shows that intermittent fasting potently relieves medial meniscus (DMM)- or natural aging-induced osteoarthritic phenotypes. Osteocytes, the most abundant bone cells, secrete excess neuropeptide Y (NPY) during osteoarthritis, and this alteration can be altered by intermittent fasting. Both NPY and the NPY-abundant culture medium of osteocytes (OCY-CM) from osteoarthritic mice possess pro-inflammatory, pro-osteoclastic, and pro-neurite outgrowth effects, while OCY-CM from the intermittent fasting-treated osteoarthritic mice fails to induce significant stimulatory effects on inflammation, osteoclast formation, and neurite outgrowth. Depletion of osteocyte NPY significantly attenuates DMM-induced osteoarthritis and abolishes the benefits of intermittent fasting on osteoarthritis. This study suggests that osteocyte NPY is a key contributing factor in the pathogenesis of osteoarthritis and intermittent fasting represents a promising nonpharmacological antiosteoarthritis method by targeting osteocyte NPY.

Analyzing the correlation between low proportion of hobnail features in papillary thyroid carcinoma and clinical aggressiveness risk.

PURPOSE: Hobnail features may enhance the clinical aggressiveness of papillary thyroid carcinoma (PTC). However, whether a low proportion (<30%) of these features contributes to increased PTC aggressiveness remains unclear. This study investigated whether PTC cases with a low proportion hobnail features (<30%) exhibit clinical invasiveness and pathological features of aggressiveness. METHODS: Pathological specimens from patients with postoperatively diagnosed PTC were retrospectively analyzed. Among them, 29 PTC cases with a low proportion of hobnail features (<30%) were compared with 173 consecutive classical PTC (cPTC) cases. Data regarding age at presentation, sex, tumor size, number of tumors, and histological characteristics were obtained by reviewing electronic medical records. Postoperative information was obtained during follow-up visits and telephone interviews. RESULTS: Twenty-nine patients with PTC with a low proportion of hobnail features (<30%) were identified, exhibiting a median age of 34 years. At a median follow-up of 31 (IQR, 23-37) months, two patients had recurrent disease in the PTC with a low proportion of hobnail features (<30%) group, whereas there was no recurrence in the cPTC group. No distant metastasis and postoperative mortality were observed in either group. Compared with the cPTC group, patients with PTC and a low proportion of hobnail features exhibited larger tumor volumes and higher susceptibility to capsular invasion and lymph node metastasis. Tumor size and hobnail features emerged as independent risk factors for lymph node metastasis. CONCLUSION: PTC with a low proportion hobnail features (<30%) and larger tumor volumes are associated with the occurrence of lymph node metastasis. A low proportion of hobnail features (<30%) in PTC may heighten invasiveness, elevating the risk of recurrence.

Neutrophil percentage-to-albumin ratio is a potential marker of intravenous immunoglobulin resistance in Kawasaki disease.

Intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD) was associated with coronary artery lesions. Neutrophil percentage-to-albumin ratio (NPAR) is an index of mortality in several inflammatory diseases. This study focused on the association of NPAR with IVIG- resistance in KD. Clinical and laboratory data of 438 children with KD before IVIG treatment were retrospectively analyzed. Notably, high NPAR was associated with older age, high WBC, NP, ALT, total bilirubin and CRP, as well as with high the incidence of IVIG-resistance, and with low hemoglobin (Hb), PLT, ALB and sodium levels. NPAR (OR: 2.366, 95% CI: 1.46-3.897, p = 0.001) and Hb (OR: 0.967, 95% CI: 0.944-0.989, p = 0.004) were independent risk factors for IVIG-resistance. NPAR showed linear relation with IVIG-resistance (p for nonlinear = 0.711) and the nonlinear correlation was found between IVIG-resistance and Hb (p for nonlinear = 0.002). The predictive performance of NPAR was superior to Beijing model (z = 2.193, p = 0.028), and not inferior to Chongqing model (z = 0.983, p = 0.326) and the combination of NPAR and Hb (z = 1.912, p = 0.056). These findings revealed that NPAR is a reliable predictor of IVIG-resistance.

Tuning Octahedron Sites of CoV2O4 via Cationic Competition for Efficient Oxygen Evolution Reaction.

Doping transition metal oxide spinels with metal ions represents a significant strategy for optimizing the electronic structure of electrocatalysts. Herein, a bimetallic Fe and Ru doping strategy to fine-tune the crystal structure of CoV2O4 spinel for highly enhanced oxygen evolution reaction (OER) is presented performance. The incorporation of Fe and Ru is observed at octahedral sites within the CoV2O4 structure, effectively modulating the electronic configuration of Co. Density functional theory calculations have confirmed that Fe acts as a novel reactive site, replacing V. Additionally, the synergistic effect of Fe, Co, and Ru effectively optimizes the Gibbs free energy of the intermediate species, reduces the reaction energy barrier, and accelerates the kinetics toward OER. As expected, the best-performing CoVFe0.5Ru0.5O4 displays a low overpotential of 240 mV (@10 mA cm-2) and a remarkably low Tafel slope of 38.9 mV dec-1, surpassing that of commercial RuO2. Moreover, it demonstrates outstanding long-term durability lasting for 72 h. This study provides valuable insights for the design of highly active polymetallic spinel electrocatalysts for energy conversion applications.

Altering electronic structure of nickel foam supported CoNi-based oxide through Al ions modulation for efficient oxygen evolution reaction.

Developing highly active and durable non-precious metal-based electrocatalysts for the oxygen evolution reaction (OER) is crucial in achieving efficient energy conversion. Herein, we reported a CoNiAl0.5O/NF nanofilament that exhibits higher OER activity than previously reported IrO2-based catalysts in alkaline solution. The as-synthesized CoNiAl0.5O/NF catalyst demonstrates a low overpotential of 230 mV at a current density of 100 mA cm-2, indicating its high catalytic efficiency. Furthermore, the catalyst exhibits a Tafel slope of 26 mV dec-1, suggesting favorable reaction kinetics. The CoNiAl0.5O/NF catalyst exhibits impressive stability, ensuring its potential for practical applications. Detailed characterizations reveal that the enhanced activity of CoNiAl0.5O/NF can be attributed to the electronic modulation achieved through Al3+ incorporation, which promotes the emergence of higher-valence Ni metal, facilitating nanofilament formation and improving mass transport and charge transfer processes. The synergistic effect between nanofilaments and porous nickel foam (NF) substrate significantly enhances the electrical conductivity of this catalyst material. This study highlights the significance of electronic structures for improving the activity of cost-effective and non-precious metal-based electrocatalysts for the OER.

Conservation tillage facilitates the accumulation of soil organic carbon fractions by affecting the microbial community in an eolian sandy soil.

Conservation tillage (CT) is an important agronomic measure that facilitates soil organic carbon (SOC) accumulation by reducing soil disturbance and plant residue mulching, thus increasing crop yields, improving soil fertility and achieving C neutrality. However, our understanding of the microbial mechanism underlying SOC fraction accumulation under different tillage practices is still lacking. Here, a 6-year in situ field experiment was carried out to explore the effects of CT and traditional tillage (CK) practices on SOC fractions in an eolian sandy soil. Compared with CK, CT increased the particulate OC (POC) content in the 0-30 cm soil layer and the mineral-associated OC (MAOC) content in the 0-20 cm soil layer. Moreover, tillage type and soil depth had significant influences on the bacterial, fungal and protistan community compositions and structures. The co-occurrence network was divided into 4 ecological modules, and module 1 exhibited significant correlations with the POC and MOC contents. After determining their topological roles, we identified the keystone taxa in the network. The results indicated that the most common bacterial taxa may result in SOC loss due to low C use efficiency, while specific fungal (Cephalotrichum) and protistan (Cercozoa) species could facilitate SOC fraction accumulation by promoting macroaggregate formation and predation. Therefore, the increase in keystone fungi and protists, as well as the reduction in bacteria, drove module 1 community function, which in turn promoted SOC sequestration under CT. These results strengthen our understanding of microbial functions in the accrual of SOC fractions, which contributes to the development of conservation agriculture on the Northeast China Plain.

Effect of Glycolipids Application Combined with Nitrogen Fertilizer Reduction on Maize Nitrogen Use Efficiency and Yield.

Microbial-driven N turnover is important in regulating N fertilizer use efficiency through the secretion of metabolites like glycolipids. Currently, our understanding of the potential of glycolipids to partially reduce N fertilizer use and the effects of glycolipids on crop yield and N use efficiency is still limited. Here, a three-year in situ field experiment was conducted with seven treatments: no fertilization (CK); chemical N, phosphorus and potassium (NPK); NPK plus glycolipids (N+PKT); and PK plus glycolipids with 10% (0.9 N+PKT), 20% (0.8 N+PKT), 30% (0.7 N+PKT), and 100% (PKT) N reduction. Compared with NPK, glycolipids with 0-20% N reduction did not significantly reduce maize yields, and also increased N uptake by 6.26-11.07%, but no significant changes in grain or straw N uptake. The N resorption efficiency under 0.9 N+PKT was significantly greater than that under NPK, while the apparent utilization rates of N fertilizer and partial factor productivity of N under 0.9 N+PKT were significantly greater than those under NPK. Although 0.9 N+PKT led to additional labor and input costs, compared with NPK, it had a greater net economic benefit. Our study demonstrates the potential for using glycolipids in agroecosystem management and provides theoretical support for optimizing fertilization strategies.

A novel method for precise implantation of tracheal Y-shaped stent.

The tracheal Y-shaped stent is mainly used for the treatment of critical patients with airway stenosis or esophagotracheal fistula near carina. A novel method for precise implantation of Y-shaped tracheal stents was developed using double-lumen endotracheal intubation and flexible bronchoscopy. This approach aims to address the limitations associated with X-ray or rigid bronchoscopy guidance, such as operational difficulties and the risk of inaccurate stent placement leading to implantation failure or suffocation. With this new technique, 13 tracheal Y-shaped stents were successfully implanted. This method shows promise in reducing the complexity of stent implantation and facilitating timely treatment for patients in need. Additionally, it has the potential to update current operating standards and guidelines for this procedure.

Lightweight semantic segmentation network for tumor cell nuclei and skin lesion.

In the field of medical image segmentation, achieving fast and accurate semantic segmentation of tumor cell nuclei and skin lesions is of significant importance. However, the considerable variations in skin lesion forms and cell types pose challenges to attaining high network accuracy and robustness. Additionally, as network depth increases, the growing parameter size and computational complexity make practical implementation difficult. To address these issues, this paper proposes MD-UNet, a fast cell nucleus segmentation network that integrates Tokenized Multi-Layer Perceptron modules, attention mechanisms, and Inception structures. Firstly, tokenized MLP modules are employed to label and project convolutional features, reducing computational complexity. Secondly, the paper introduces Depthwise Attention blocks and Multi-layer Feature Extraction modules. The Depthwise Attention blocks eliminate irrelevant and noisy responses from coarse-scale extracted information, serving as alternatives to skip connections in the UNet architecture. The Multi-layer Feature Extraction modules capture a wider range of high-level and low-level semantic features during decoding and facilitate feature fusion. The proposed MD-UNet approach is evaluated on two datasets: the International Skin Imaging Collaboration (ISIC2018) dataset and the PanNuke dataset. The experimental results demonstrate that MD-UNet achieves the best performance on both datasets.

Inborn errors of immunity and its clinical significance in children with lymphoma in China: a single-center study.

OBJECTIVE: To investigate the incidence, clinical and genetic characteristics of pediatric lymphoma patients of China with inborn errors of immunity (IEI)-related gene mutations, which have not been fully studied. METHOD: From Jan. 2020 to Mar. 2023, IEI-related genetic mutations were retrospectively explored in 108 children with lymphomas admitted to Beijing Children's Hospital by NGS. Genetic rule and clinical characteristics as well as treatment outcomes were compared between patients with or without IEI-related gene mutations. RESULTS: A total of 17 patients (15.7 %) harbored IEI-associated mutations, including 4 cases with X-linked lymphoproliferative syndrome (XLP), 3 cases had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), 2 cases with Activated p110 syndrome (APDS). Patients with IEI all had alteration of immunocompetence with decreased levels of immunoglobulin and lymphocyte subsets. Recurrent infection existed in 41.2 % of patients. The 18-month event-free survival (EFS) and the overall response rate (ORR) of patients with IEI are significantly lower than those without IEI (33.86% vs. 73.26 %, p = 0.011; 52.94% vs. 87.91 %, p = 0.002, respectively). In addition, patients with IEI had a higher progression disease (PD) rate of 23.5 % than those without IEI of 4.4 % (p = 0.006). CONCLUSION: The present study demonstrated that IEI-associated lymphomas were much more common than originally appreciated in pediatric lymphomas, and those were insensitive to treatment and more likely to progress or relapse. The genomic analysis and a thorough review of the medical history of IEI can be used to distinguish them from pediatric lymphomas without IEI, which are beneficial for the early diagnosis and direct intervention.

Ruxolitinib induces apoptosis and pyroptosis of anaplastic thyroid cancer via the transcriptional inhibition of DRP1-mediated mitochondrial fission.

Anaplastic thyroid carcinoma (ATC) has a 100% disease-specific mortality rate. The JAK1/2-STAT3 pathway presents a promising target for treating hematologic and solid tumors. However, it is unknown whether the JAK1/2-STAT3 pathway is activated in ATC, and the anti-cancer effects and the mechanism of action of its inhibitor, ruxolitinib (Ruxo, a clinical JAK1/2 inhibitor), remain elusive. Our data indicated that the JAK1/2-STAT3 signaling pathway is significantly upregulated in ATC tumor tissues than in normal thyroid and papillary thyroid cancer tissues. Apoptosis and GSDME-pyroptosis were observed in ATC cells following the in vitro and in vivo administration of Ruxo. Mechanistically, Ruxo suppresses the phosphorylation of STAT3, resulting in the repression of DRP1 transactivation and causing mitochondrial fission deficiency. This deficiency is essential for activating caspase 9/3-dependent apoptosis and GSDME-mediated pyroptosis within ATC cells. In conclusion, our findings indicate DRP1 is directly regulated and transactivated by STAT3; this exhibits a novel and crucial aspect of JAK1/2-STAT3 on the regulation of mitochondrial dynamics. In ATC, the transcriptional inhibition of DRP1 by Ruxo hampered mitochondrial division and triggered apoptosis and GSDME-pyroptosis through caspase 9/3-dependent mechanisms. These results provide compelling evidence for the potential therapeutic effectiveness of Ruxo in treating ATC.