Safety, immunogenicity and protective effect of sequential vaccination with inactivated and recombinant protein COVID-19 vaccine in the elderly: a prospective longitudinal study.

The safety and efficacy of COVID-19 vaccines in the elderly, a high-risk group for severe COVID-19 infection, have not been fully understood. To clarify these issues, this prospective study followed up 157 elderly and 73 young participants for 16 months and compared the safety, immunogenicity, and efficacy of two doses of the inactivated vaccine BBIBP-CorV followed by a booster dose of the recombinant protein vaccine ZF2001. The results showed that this vaccination protocol was safe and tolerable in the elderly. After administering two doses of the BBIBP-CorV, the positivity rates and titers of neutralizing and anti-RBD antibodies in the elderly were significantly lower than those in the young individuals. After the ZF2001 booster dose, the antibody-positive rates in the elderly were comparable to those in the young; however, the antibody titers remained lower. Gender, age, and underlying diseases were independently associated with vaccine immunogenicity in elderly individuals. The pseudovirus neutralization assay showed that, compared with those after receiving two doses of BBIBP-CorV priming, some participants obtained immunological protection against BA.5 and BF.7 after receiving the ZF2001 booster. Breakthrough infection symptoms last longer in the infected elderly and pre-infection antibody titers were negatively associated with the severity of post-infection symptoms. The antibody levels in the elderly increased significantly after breakthrough infection but were still lower than those in the young. Our data suggest that multiple booster vaccinations at short intervals to maintain high antibody levels may be an effective strategy for protecting the elderly against COVID-19.

An efficient method for rapid screening of triterpenoid saponins in three Glycyrrhiza species using rapid resolution liquid chromatography quadrupole time-of-flight mass spectrometry combined with mass defect filtering.

Triterpenoid saponins, a major bioactive component of liquorice, possess high hydrophilicity and often co-occur with other impurities of similar polarity. Additionally, subtle structural differences of some triterpenoid saponins bring challenges to comprehensive characterisation. In this study, triterpenoid saponins of three Glycyrrhiza species were systematically analysed using rapid resolution liquid chromatography quadrupole time-of-flight mass spectrometry (RRLC-Q-TOF-MS) coupled with mass defect filtering (MDF). Firstly, comprehensive date acquisition was achieved using RRLC-Q-TOF-MS. Secondly, a polygonal MDF method was established by summarizing known and speculated substituents and modifications based on the core structure to rapidly screen potential triterpenoid saponins. Thirdly, based on the fragmentation patterns of reference compounds, an identification strategy for characterisation of triterpenoid saponins was proposed. The strategy divided triterpenoid saponins into three distinct classes. By this strategy, 98 triterpenoid saponins including 10 potential new ones were tentatively characterised. Finally, triterpenoid saponins of three Glycyrrhiza species were further analysed using principle component analysis (PCA) and orthogonality partial least squares discriminant analysis (OPLS-DA). Among these, 18 compounds with variable importance in projections (VIP) > 1.0 and P values < 0.05 were selected to distinguish three Glycyrrhiza species. Overall, our study provided a reference for quality control and rational use of the three species.

EGCG alleviates heat-stress-induced fat deposition by targeting HSP70 through activation of AMPK-SIRT1-PGC-1α in porcine subcutaneous preadipocytes.

Obesity has emerged as a prominent global health concern, with heat stress posing a significant challenge to both human health and animal well-being. Despite a growing interest in environmental determinants of obesity, very few studies have examined the associations between heat stress-related environmental factors and adiposity. Consequently, there exists a clear need to understand the molecular mechanisms underlying the obesogenic effects of heat stress and to formulate preventive strategies. This study focused on culturing porcine subcutaneous preadipocytes at 41.5 ℃ to induce heat stress, revealing that this stressor triggered apoptosis and fat deposition. Analysis demonstrated an upregulation in the expression of HSP70, BAX, adipogenesis-related genes (PPARγ, AP2, CEBPα and FAS), the p-AMPK/AMPK ratio and SIRT1, PGC-1α in the heat stress group compared to the control group (P < 0.05). Conversely, the expression of lipid lysis-related genes (ATGL, HSL and LPL) and Bcl-2 decreased in the heat stress group compared to the control group (P < 0.05). Furthermore, subsequent activator and/or inhibitor experiments validated that heat stress modulated HSP70 and AMPK signalling pathways to enhance lipogenesis and inhibit lipolysis in porcine subcutaneous preadipocytes. Importantly, this study reveals, for the first time, that EGCG mitigates heat-stress-induced fat deposition by targeting HSP70 through the activation of AMPK-SIRT1-PGC-1α in porcine subcutaneous preadipocytes. These findings elucidate the molecular mechanisms contributing to heat stress-induced obesity and provide a foundation for the potential clinical utilisation of EGCG as a preventive measure against both heat stress and obesity.

Artificial Intelligence-Guided Gut-Microenvironment-Triggered Imaging Sensor Reveals Potential Indicators of Parkinson's Disease.

The gut-brain axis has recently emerged as a crucial link in the development and progression of Parkinson's disease (PD). Dysregulation of the gut microbiota has been implicated in the pathogenesis of this disease, sparking growing interest in the quest for non-invasive biomarkers derived from the gut for early PD diagnosis. Herein, an artificial intelligence-guided gut-microenvironment-triggered imaging sensor (Eu-MOF@Au-Aptmer) to achieve non-invasive, accurate screening for various stages of PD is presented. The sensor works by analyzing α-Syn in the gut using deep learning algorithms. By monitoring changes in α-Syn, the sensor can predict the onset of PD with high accuracy. This work has the potential to revolutionize the diagnosis and treatment of PD by allowing for early intervention and personalized treatment plans. Moreover, it exemplifies the promising prospects of integrating artificial intelligence (AI) and advanced sensors in the monitoring and prediction of a broad spectrum of diseases and health conditions.

New Methods in Digital Wood Anatomy: The Use of Pixel-Contrast Densitometry with Example of Angiosperm Shrubs in Southern Siberia.

This methodological study describes the adaptation of a new method in digital wood anatomy, pixel-contrast densitometry, for angiosperm species. The new method was tested on eight species of shrubs and small trees in Southern Siberia, whose wood structure varies from ring-porous to diffuse-porous, with different spatial organizations of vessels. A two-step transformation of wood cross-section photographs by smoothing and Otsu's classification algorithm was proposed to separate images into cell wall areas and empty spaces within (lumen) and between cells. Good synchronicity between measurements within the ring allowed us to create profiles of wood porosity (proportion of empty spaces) describing the growth ring structure and capturing inter-annual differences between rings. For longer-lived species, 14-32-year series from at least ten specimens were measured. Their analysis revealed that maximum (for all wood types), mean, and minimum porosity (for diffuse-porous wood) in the ring have common external signals, mostly independent of ring width, i.e., they can be used as ecological indicators. Further research directions include a comparison of this method with other approaches in densitometry, clarification of sample processing, and the extraction of ecologically meaningful data from wood structures.

Casein/butyrylated dextrin nanoparticles and chitosan stabilized bilayer emulsions as fat substitutes in sponge cakes.

This study aimed to evaluate the potential of the bilayer emulsions stabilized with casein/butyrylated dextrin nanoparticles and chitosan as fat substitutes in preparing low-calorie sponge cakes. Among the different cake groups, the substitution of bilayer emulsions at 60% exhibited comparable baking properties, appearance, texture characteristics and stable secondary structure to fat. The specific volume and height were increased by 36.94% and 22%, respectively, while the cake showed higher lightness (L*) in the cores and softer hardness in the crumb. In addition, the moisture content of cakes was increased while the water activity remained unchanged. These results showed that casein/butyrylated dextrin bilayer emulsion was a potential fat substitute for cake products at the ratio of 60% with the desirable characteristics.

Influence of centroid acceleration acquisition and filtering class on head injury criterion evaluation.

BACKGROUND: Although the Head Injury Criteria (HIC) has been widely applied to assess head impact injuries, it faces two outstanding problems: 1) HIC is affected strongly by the cut-off frequency when processing acceleration signals. And these cut-off frequencies are experiential and lack unified guidelines; 2) If the head was impacted on a different part, should the corresponding HIC threshold be the same? If these problems are not resolved, it could potentially lead to a critical misinterpretation of the safety assessment. METHODS: Finite element method was used to reconstruct head impacts. The head model includes tissues like skull, brainstem, cerebrospinal fluid, etc. The head model was impacted in the frontal, occipital, parietal or lateral direction with different impact velocities. Acceleration signals of the head model were extracted directly from the skull and the head centroid node. To obtain a robust HIC, the filtering class of acceleration signals were analyzed carefully. Then, the relation between rigid body HIC and the centroid node HIC were studied systematically. RESULTS: When the filtering class of rigid body acceleration and centroid node acceleration reached the cut-off frequency, the corresponding derivative of HIC tended to change smoothly. Using these cut-off frequencies, robust HICs were obtained. The rigid body HIC far exceeded that of centroid node HIC, such as 8, 9, 14 and 31 times exceeded in the frontal, occipital, parietal and lateral impact conditions, respectively. Moreover, approximate linear relations were found between the rigid body HIC and the centroid node HIC in different impact directions, respectively. From these relations, the injury thresholds of rigid body HIC of various directions were given quantitatively. CONCLUSIONS: The rational filtering class like CFC 800 and CFC 700 were given for rigid body HIC and centroid node HIC, respectively. The rigid body HIC had a significant discrepancy from the centroid node HIC. Linear relations between the rigid body HIC and centroid node HIC were found, and their slopes changed with impact directions. From these relations, we can adjust the injury thresholds reasonably if the head receives different impacts. These findings can effectively enhance the applicability of HIC.

Circulating levels of asprosin in children with obesity: a systematic review and meta-analysis.

BACKGROUND: Prior studies reported that elevated asprosin level was associated with obesity in adults and animal models. However, the relationship between asprosin level and children with obeisty remains controversial. The aim of our analysis was to systematically review available literatures linking asprosin and children with obesity for a comprehensive understanding of the relationship between circulating asprosin level and obesity in children. METHODS: Eight databases were gleaned for studies published up to January 2024. Standard mean difference with 95% confidence interval (CI) and Fisher's Z transformation was calculated to evaluate the relationship between asprosin level and children with obesity using the Review Manager 5.4 Software. Other indicators were measured via mean difference with 95% CI. RESULTS: Six observational studies were included both in systematic review and meta-analysis. The current evidence indicated that no significant difference was observed in the level of circulating asprosin between the children with and without obesity (SMD = 0.37; 95% CI:-0.22-0.95, p = 0.22). However, Fisher's Z transformation suggested the positive association of circulating asprosin levels and clinical index measuring the degree of obesity: total cholesterol (Fisher's Z: 0.11, 95% CI: 0.02-0.20, p = 0.02). CONCLUSIONS: Circulating asprosin level was not independently related to childhood obesity currently. More rigorous longitudinal researches were required to disentangle the causations. However, the positive association of asprosin levels and total cholesterol indicated that asprosin might get involved in the lipid-metabolism of childhood obesity, asprosin might be a prospective bio-index and targeted treatment of total cholesterol metabolism besides the role of glucogenic and orexigenic. TRIAL REGISTRATION: Prospero ID: CRD42023426476.

Neurogenetic underpinnings of nicotine use severity: Integrating the brain transcriptomes and GWAS variants via network approaches.

Our study focused on human brain transcriptomes and the genetic risks of cigarettes per day (CPD) to investigate the neurogenetic mechanisms of individual variation in nicotine use severity. We constructed whole-brain and intramodular region-specific coexpression networks using BrainSpan's transcriptomes, and the genomewide association studies identified risk variants of CPD, confirmed the associations between CPD and each gene set in the region-specific subnetworks using an independent dataset, and conducted bioinformatic analyses. Eight brain-region-specific coexpression subnetworks were identified in association with CPD: amygdala, hippocampus, medial prefrontal cortex (MPFC), orbitofrontal cortex (OPFC), dorsolateral prefrontal cortex, striatum, mediodorsal nucleus of the thalamus (MDTHAL), and primary motor cortex (M1C). Each gene set in the eight subnetworks was associated with CPD. We also identified three hub proteins encoded by GRIN2A in the amygdala, PMCA2 in the hippocampus, MPFC, OPFC, striatum, and MDTHAL, and SV2B in M1C. Intriguingly, the pancreatic secretion pathway appeared in all the significant protein interaction subnetworks, suggesting pleiotropic effects between cigarette smoking and pancreatic diseases. The three hub proteins and genes are implicated in stress response, drug memory, calcium homeostasis, and inhibitory control. These findings provide novel evidence of the neurogenetic underpinnings of smoking severity.

Ganoderic acids alleviate atherosclerosis by inhibiting macrophage M1 polarization via TLR4/MyD88/NF-κB signaling pathway.

BACKGROUND AND AIMS: Atherosclerosis (AS) is a chronic inflammatory disease characterized by lipid infiltration and plaque formation in blood vessel walls. Ganoderic acids (GA), a class of major bioactive compounds isolated from the Chinese traditional medicine Ganoderma lucidum, have multiple pharmacological activities. This study aimed to determine the anti-atherosclerotic effect of GA and reveal the pharmacological mechanism. METHODS: ApoE-/- mice were fed a high-cholesterol diet and treated with GA for 16 weeks to induce AS and identify the effect of GA. Network pharmacological analysis was performed to predict the anti-atherosclerotic mechanisms. An invitro cell model was used to explore the effect of GA on macrophage polarization and the possible mechanism involved in bone marrow dereived macrophages (BMDMs) and RAW264.7 cells stimulated with lipopolysaccharide or oxidized low-density lipoprotein. RESULTS: It was found that GA at 5 and 25 mg/kg/d significantly inhibited the development of AS and increased plaque stability, as evidenced by decreased plaque in the aorta, reduced necrotic core size and increased collagen/lipid ratio in lesions. GA reduced the proportion of M1 macrophages in plaques, but had no effect on M2 macrophages. In vitro experiments showed that GA (1, 5, 25 µg/mL) significantly decreased the proportion of CD86+ macrophages and the mRNA levels of IL-6, IL-1ß, and MCP-1 in macrophages. Experimental results showed that GA inhibited M1 macrophage polarization by regulating TLR4/MyD88/NF-κB signaling pathway. CONCLUSIONS: This study demonstrated that GA play an important role in plaque stability and macrophage polarization. GA exert the anti-atherosclerotic effect partly by regulating TLR4/MyD88/NF-κB signaling pathways to inhibit M1 polarization of macrophages. Our study provides theoretical basis and experimental data for the pharmacological activity and mechanisms of GA against AS.

High preseason temperature variability drives convergence of xylem phenology in the Northern Hemisphere conifers.

Wood growth is key to understanding the feedback of forest ecosystems to the ongoing climate warming. An increase in spatial synchrony (i.e., coincident changes in distant populations) of spring phenology is one of the most prominent climate responses of forest trees. However, whether temperature variability contributes to an increase in the spatial synchrony of spring phenology and its underlying mechanisms remains largely unknown. Here, we analyzed an extensive dataset of xylem phenology observations of 20 conifer species from 75 sites over the Northern Hemisphere. Along the gradient of increase in temperature variability in the 75 sites, we observed a convergence in the onset of cell enlargement roughly toward the 5th of June, with a convergence in the onset of cell wall thickening toward the summer solstice. The increase in rainfall since the 5th of June is favorable for cell division and expansion, and as the most hours of sunlight are received around the summer solstice, it allows the optimization of carbon assimilation for cell wall thickening. Hence, the convergences can be considered as the result of matching xylem phenological activities to favorable conditions in regions with high temperature variability. Yet, forest trees relying on such consistent seasonal cues for xylem growth could constrain their ability to respond to climate warming, with consequences for the potential growing season length and, ultimately, forest productivity and survival in the future.

Nonsteaming method improves the nutritional value and utilization efficiency of silkworm artificial diets.

Artificial diets for silkworms overcome the seasonal limitations of traditional rearing methods with fresh mulberry leaves. However, the current wet artificial diets, steamed at high temperatures, are not favored by silkworms, and they are cumbersome and challenging to preserve. These conditions adversely affected the development of artificial diet-based sericulture production. In this study, we disinfected dry powder diets with radiation and added distilled water without steaming before use. Then, the nutritional value of finished diets and their impact on silkworm development was assessed. Compared with steamed diets, nonsteamed diets were more attractive to silkworms. Chemical assays showed significantly more essential nutrients for silkworms, including l-ascorbic acid, vitamin B1, vitamin B2, and urease in nonsteamed diets than in steamed diets. Feeding fifth-instar silkworm larvae with nonsteamed diets significantly improved the ammonia utilization efficiency of the diet and increased the cocoon shell rate and diet/silk protein conversion efficiency by 5.9% and 13.3%, respectively. When fed with nonsteamed diets, the abundance of aerobic microorganisms in silkworm intestines increased and the abundance of pathogenic bacteria decreased. Furthermore, the vitality of the silkworm, measured by the dead worm cocoon rate, significantly improved by 16.90%. In summary, preparing sterile wet diets without high-temperature steaming effectively improved the nutritional value of the diet and enhanced silkworm growth.

Degree of methyl esterification: A key factor for the encapsulation of icaritin with pectin.

Pectin is a promising nano-carrier. The degree of methyl esterification (DM) influences the physiochemical properties of pectin. However, the effect of DM on the encapsulation capacity of pectin remains unclear. In this work, low methyl-esterified pectin (LMP) and high methyl-esterified pectin (HMP) were prepared. The molecular weight, rheological properties of these pectins with various DM levels were determined. Then icaritin/pectin micelles (IPMs) were prepared using HMP and LMP. Notably, higher loading capacities (18.75-20.12 %) were observed in HMP-IPMs compared to LMP-IPMs (15.72-16.64 %). Furthermore, LMP-IPMs demonstrated a DM-dependent reduction in particle sizes, ranging from 449 to 527 nm. In contrast, the particle sizes of HMP-IPMs varied between 342 and 566 nm, with smaller particle sizes observed in HMP-IPMs at higher DM levels. A significant positive correlation was found between DM and the formation of IPMs, including encapsulation efficiency, loading capacity, Zeta potential, and polydispersity index. Alkali de-esterification showed a weak impact on the pectin structure. Hydroxyl groups like 7-OH and 5-OH of icaritin might be involved in the formation of IPMs. The hydrogen-bond interactions between pectin and icaritin could be enhanced as DM increased.

Hepatoprotective Activity and Mechanisms of Prenylated Stilbenoids.

Dietary prenylated stilbenoids, found in various food sources, offer multiple health benefits, including liver protection. However, the underlying mechanisms of hepatoprotection remain unclear. In this study, we synthesized 13 natural prenylated stilbenoids and examined their hepatoprotective activities, with silent mating type information regulation 2 homologue-1 (SIRT1) as the primary target for screening. Among all of the prenylated stilbenoids tested, 4-C-geranyl oxyresveratrol demonstrated superior performance. It activated SIRT1 activity more effectively than resveratrol, a well-known SIRT1 activator. To further investigate the mechanism of liver protection, two in vitro models were used: the palmitic acid-induced lipid accumulation model and the H2O2-induced apoptosis model. Our findings suggested that 4-C-geranyl oxyresveratrol mitigated lipid accumulation through the SIRT1-PGC1α pathway, reduced apoptosis via the SIRT1-p53-p21 pathway, and exerted antioxidant effects through the SIRT1-Nrf2 pathway. These findings provide new insights into the chemical basis of the health benefits of prenylated stilbenoids and their potential use as functional food additives.

Anatomically Guided PET Image Reconstruction Using Conditional Weakly-Supervised Multi-Task Learning Integrating Self-Attention.

To address the lack of high-quality training labels in positron emission tomography (PET) imaging, weakly-supervised reconstruction methods that generate network-based mappings between prior images and noisy targets have been developed. However, the learned model has an intrinsic variance proportional to the average variance of the target image. To suppress noise and improve the accuracy and generalizability of the learned model, we propose a conditional weakly-supervised multi-task learning (MTL) strategy, in which an auxiliary task is introduced serving as an anatomical regularizer for the PET reconstruction main task. In the proposed MTL approach, we devise a novel multi-channel self-attention (MCSA) module that helps learn an optimal combination of shared and task-specific features by capturing both local and global channel-spatial dependencies. The proposed reconstruction method was evaluated on NEMA phantom PET datasets acquired at different positions in a PET/CT scanner and 26 clinical whole-body PET datasets. The phantom results demonstrate that our method outperforms state-of-the-art learning-free and weakly-supervised approaches obtaining the best noise/contrast tradeoff with a significant noise reduction of approximately 50.0% relative to the maximum likelihood (ML) reconstruction. The patient study results demonstrate that our method achieves the largest noise reductions of 67.3% and 35.5% in the liver and lung, respectively, as well as consistently small biases in 8 tumors with various volumes and intensities. In addition, network visualization reveals that adding the auxiliary task introduces more anatomical information into PET reconstruction than adding only the anatomical loss, and the developed MCSA can abstract features and retain PET image details.

Salvianolic acid A provides neuroprotective effects on cerebral ischemia-reperfusion injury in rats via PKA/CREB/c-Fos signaling pathway.

BACKGROUND: Cerebral ischemia-reperfusion injury (CIRI) is a phenomenon that pathological injury of ischemic brain tissue is further aggravated after the restoration of blood supply. The complex pathological mechanism of CIRI has led to the failure of multiple neuroprotective agents in clinical studies. Salvianolic acid A (SAA) is a neuroprotective extract from Salvia miltiorrhiza Bge., with significant pharmacological activities in the treatment of brain injury. However, the neuroprotective mechanisms of SAA remain unclear. PURPOSE: To explore the potential protective effect of SAA on CIRI and its mechanism, and to provide experimental basis for the research of new drugs for CIRI. STUDY DESIGN: A model of transient middle cerebral artery occlusion (tMCAO) in rats was used to simulate clinical CIRI, and the neuroprotective effect of SAA on tMCAO rats was investigated within 14 days after reperfusion. The improvement effects of SAA on cognitive impairment of tMCAO rats were investigated by behavioral tests from days 7-14. Finally, the neuroprotective mechanism of SAA was investigated on day 14. METHODS: The neuroprotective effects and mechanism of SAA were investigated by behavioral tests, HE and TUNEL staining, RNA sequence (RNA-seq) analysis and Western blot in tMCAO rats. RESULTS: The brain protective effects of SAA were achieved by alleviating cerebral infarction, cerebral edema, cerebral atrophy and nerve injury in tMCAO rats. Meanwhile, SAA could effectively improve the cognitive impairment and pathological damage of hippocampal tissue, and inhibit cell apoptosis in tMCAO rats. Besides, SAA could provide neuroprotective effects by up-regulating the expression of Bcl-2, inhibiting the activation of Caspase 3, and regulating PKA/CREB/c-Fos signaling pathway. CONCLUSION: SAA can significantly improve brain injury and cognitive impairment in CIRI rats, and this neuroprotective effect may be achieved through the anti-apoptotic effect and the regulation of PKA/CREB/c-Fos signaling pathway.

Efficacy and safety of GLP-1RAs for people with obesity: A systematic review based on RCT and Bayesian network meta-analysis.

BACKGROUND: GLP-1 receptor agonists (GLP-1RAs) reduce glucagon and glycogen secretion, inhibit appetite and slow gastric empties and have recently been approved to treat obesity. OBJECTIVE: To explore the safety and efficacy of GLP-1RAs in the treatment of obesity and clarify the optimal GLP-1RAs treatment regimen. METHODS: PubMed, Embase, Web of Science, and Cochrane Library databases were searched for English randomized controlled trials (RCTs) on GLP-1RAs in the treatment and management of obesity published before July 18, 2023. Literature screening and data extraction were performed independently by three researchers. Bayesian random effect model was used to compare the effects of interventions. Continuous variables were expressed as mean difference with 95% CI, and dichotomous variables were reported as RR with 95% CI. RESULTS: A total of 29 studies with 10,333 participants were included in the present study. The combination of cagrilintide and semaglutide (short for cagrANDsema) was an optimal strategy for weight loss and glycosylated hemoglobin (HbA1c) reduction. Compared to placebo, cagrANDsema reduced weight by - 14.13 kg (95% CI: -16.49, -11.73) and HbA1c by - 0.33% (95% CI: -0.41, -0.25). Moreover, this study indicated that orforglipron and semaglutide also had relatively good effects on weight loss. Meta-regression results indicated that higher dose levels might have better effects on weight loss. CONCLUSIONS: CagrANDsema exerts the best effect for weight loss. In terms of current dose levels, a higher dose gets better weight-loss effects without increasing the risk of adverse events.

Resveratrol improves meat quality traits by activating the lncRNAs-KEAP1-NRF2 axis in pigs.

This research aims at uncovering the effects and investigating the molecular mechanisms of dietary resveratrol (RES) supplementation on antioxidant capacity and meat quality of pigs. In this study, 20 µM RES could activate the KEAP1-NRF2 antioxidant defense pathway in response to oxidative stress in porcine skeletal muscle satellite cells was firstly found. Then, twenty-four healthy crossbred castrated boars were allocated to 4 treatments that were fed with a basal diet (control) and a basal diet supplemented with 200 mg, 400 mg or 600 mg RES per Kilogram (kg) of feed for 41 days, respectively. 400 and 600 mg/kg RES-supplemented diet can effectively improve the meat quality traits and activities of antioxidizing enzymes via the KEAP1-NRF2 signaling pathway of pigs. The molecular dynamic simulation further revealed that RES could directly binding to KEAP1 to reduce the tightness of KEAP1-NRF2 protein-protein interaction. More importantly, dietary supplementation of RES also improves antioxidant capacity through a series of KEAP1-NRF2 pathway-related lncRNAs were found by RNA sequencing (RNA-seq). Altogether, this study demonstrated that RES improves meat quality traits by effectively increasing antioxidant levels via the lncRNA-KEAP1-NRF2 axis in vivo and/or in vitro. These results provide new insights into the molecular mechanisms by which RES, as a nutritional agent, regulates antioxidant capacity and improves meat quality in pigs.

Traditional Chinese Medicine Regulation of MAPK Pathway for Treatment of Obesity： A Review / 中国实验方剂学杂志

With a global rise in morbidity rates， obesity has become a pressing public health issue. With increased adipocyte number and volume as the main characteristics， obesity is also manifested by metabolic disorders to varying degrees. At the same time， obesity is a risk factor for diabetes， hypertension， stroke， cancer， and cardiovascular diseases， imposing burdens on society and families. Influenced by lifestyle， environment， behavior， and genetics， obesity is caused by the interaction of many factors， and its pathological process is complex， involving inflammation， autophagy， and intestinal dysbiosis. The mitogen-activated protein kinase （MAPK） cascade reaction， a pivotal signaling pathway， plays a crucial role in cellular processes such as proliferation， differentiation， apoptosis， and stress responses. Both Chinese and international studies indicate that the MAPK signaling pathway can effectively regulate obesity through various pathways， including the modulation of adipocyte differentiation and apoptosis， appetite control， and inflammation improvement. Moreover， traditional Chinese medicine （TCM） has demonstrated significant efficacy in preventing and treating obesity， leveraging advantages such as multiple targets， diverse components， and minimal adverse effects. Research indicates that the MAPK signaling pathway is a primary focus of TCM regulation in this context， although a systematic review in this field is currently lacking. Therefore， this paper， by reviewing the latest Chinese and international research， provided a concise overview of the basic structure of the MAPK pathway， with a specific emphasis on recent progress in TCM interventions targeting the MAPK pathway for obesity treatment. The results indicate that regulating adipose tissue formation， differentiation， and thermogenesis， reducing inflammation and oxidative stress levels， and improving insulin sensitivity and metabolic disorders seem to be the main ways for TCM to regulate the MAPK pathway to prevent and treat obesity. However， it is necessary to find more research methods and explore potential mechanisms underlying TCM formulations based on the MAPK pathway for obesity prevention and treatment.

Tumor-associated astrocytes promote tumor progression of Sonic Hedgehog medulloblastoma by secreting lipocalin-2.

Sonic Hedgehog (SHH) subgroup of medulloblastoma (MB) accounts for about 25% of all subgroups of MB. Tumor microenvironment (TME) may play a key role in the tumor progression and therapeutic resistance. Tumor-associated astrocytes (TAAs) are reshaped to drive tumor progression through multiple paracrine signals. However, the mechanism by which TAAs modulate MB cells remains elusive. Here, we illuminated that TAAs showed a specific and dynamic pattern during SHH-MB development. Most TAAs gathered to the tumor margin during the tumor progression, rather than evenly distributed in the early-stage tumors. We further demonstrated that lipocalin-2 (LCN2) secreted by TAAs could promote the tumor growth and was correlated with the poor prognosis of MB patients. Knocking down LCN2 in TAAs in vitro impeded the proliferation and migration abilities of MB cells. In addition, we identified that TAAs accelerated the tumor growth by secreting LCN2 via STAT3 signaling pathway. Accordingly, blockade of STAT3 signaling by its inhibitor WP1066 and AAV-Lcn2 shRNA, respectively, in TAAs abrogated the effects of LCN2 on tumor progression in vitro and in vivo. In summary, we for the first time clarified that LCN2, secreted by TAAs, could promote MB tumor progression via STAT3 pathway and has potential prognostic value. Our findings unveiled a new sight in reprogramming the TME of SHH-MB and provided a potential therapeutic strategy targeting TAAs.