The Role of Oxidative Stress in Intervertebral Disc Degeneration: Mechanisms and Therapeutic Implications.

Oxidative stress is one of the main driving mechanisms of intervertebral disc degeneration(IDD). Oxidative stress has been associated with inflammation in the intervertebral disc, cellular senescence, autophagy, and epigenetics of intervertebral disc cells. It and the above pathological mechanisms are closely linked through the common hub reactive oxygen species(ROS), and promote each other in the process of disc degeneration and promote the development of the disease. This reveals the important role of oxidative stress in the process of IDD, and the importance and great potential of IDD therapy targeting oxidative stress. The efficacy of traditional therapy is unstable or cannot be maintained. In recent years, due to the rise of materials science, many bioactive functional materials have been applied in the treatment of IDD, and through the combination with traditional drugs, satisfactory efficacy has been achieved. At present, the research review of antioxidant bioactive materials in the treatment of IDD is not complete. Based on the existing studies, the mechanism of oxidative stress in IDD and the common antioxidant therapy were summarized in this paper, and the strategies based on emerging bioactive materials were reviewed.

A comprehensive analysis of patients with cerebral arteriovenous malformation with headache: assessment of risk factors and treatment effectiveness.

BACKGROUND: Due to the high mortality and disability rate of intracranial hemorrhage, headache is not the main focus of research on cerebral arteriovenous malformation (AVM), so research on headaches in AVM is still scarce, and the clinical understanding is shallow. This study aims to delineate the risk factors associated with headaches in AVM and to compare the effectiveness of various intervention treatments versus conservative treatment in alleviating headache symptoms. METHODS: This study conducted a retrospective analysis of AVMs who were treated in our institution from August 2011 to December 2021. Multivariable logistic regression analysis was employed to assess the risk factors for headaches in AVMs with unruptured, non-epileptic. Additionally, the effectiveness of different intervention treatments compared to conservative management in alleviating headaches was evaluated through propensity score matching (PSM). RESULTS: A total of 946 patients were included in the analysis of risk factors for headaches. Multivariate logistic regression analysis identified that female (OR 1.532, 95% CI 1.173-2.001, p = 0.002), supply artery dilatation (OR 1.423, 95% CI 1.082-1.872, p = 0.012), and occipital lobe (OR 1.785, 95% CI 1.307-2.439, p < 0.001) as independent risk factors for the occurrence of headaches. There were 443 AVMs with headache symptoms. After propensity score matching, the microsurgery group (OR 7.27, 95% CI 2.82-18.7 p < 0.001), stereotactic radiosurgery group(OR 9.46, 95% CI 2.26-39.6, p = 0.002), and multimodality treatment group (OR 8.34 95% CI 2.87-24.3, p < 0.001) demonstrate significant headache relief compared to the conservative group. However, there was no significant difference between the embolization group (OR 2.24 95% CI 0.88-5.69, p = 0.091) and the conservative group. CONCLUSIONS: This study identified potential risk factors for headaches in AVMs and found that microsurgery, stereotactic radiosurgery, and multimodal therapy had significant benefits in headache relief compared to conservative treatment. These findings provide important guidance for clinicians when developing treatment options that can help improve overall treatment outcomes and quality of life for patients.

Tumor immune dysfunction and exclusion subtypes in bladder cancer and pan-cancer: a novel molecular subtyping strategy and immunotherapeutic prediction model.

BACKGROUND: Molecular subtyping is expected to enable precise treatment. However, reliable subtyping strategies for clinical application remains defective and controversial. Given the significance of tumor immune dysfunction and exclusion (TIDE), we aimed to develop a novel TIDE-based subtyping strategy to guide personalized immunotherapy in the bladder cancer (BC). METHODS: Transcriptome data of BC was used to evaluate the heterogeneity and the status of TIDE patterns. Subsequently, consensus clustering was applied to classify BC patients based on TIDE marker-genes. Patients' clinicopathological, molecular features and signaling pathways of the different TIDE subtypes were well characterized. We also utilize the deconvolution algorithms to analyze the tumor microenvironment, and further explore the sensitivity and mechanisms of each subtype to immunotherapy. Furthermore, BC patient clinical information, real-world BC samples and urine samples were collected for the validation of our findings, which were used for RNA-seq analysis, H&E staining, immunohistochemistry and immunofluorescence staining, and enzyme-linked immunosorbent assay. Finally, we also explored the conservation of our novel TIDE subtypes in pan-cancers. RESULTS: We identified 69 TIDE biomarker genes and classified BC samples into three subtypes using consensus clustering. Subtype I showed the lowest TIDE status and malignancy with the best prognosis and highest sensitivity to immune checkpoint blockade (ICB) treatment, which was enriched of metabolic related signaling pathways. Subtype III represented the highest TIDE status and malignancy with the poorest prognosis and resistance to ICB treatment, resulting from its inhibitory immune microenvironment and T cell terminal exhaustion. Subtype II was in a transitional state with intermediate TIDE level, malignancy, and prognosis. We further confirmed the existence and characteristics of our novel TIDE subtypes using real-world BC samples and collected patient clinical data. This subtyping method was proved to be more efficient than previous known methods in identifying non-responders to immunotherapy. We also propose that combining our TIDE subtypes with known biomarkers can potentially improve the sensitivity and specificity of these biomarkers. Moreover, besides guiding ICB treatment, this classification approach can assist in selecting the frontline or recommended drugs. Finally, we confirmed that the TIDE subtypes are conserved across the pan-tumors. CONCLUSIONS: Our novel TIDE-based subtyping method can serve as a powerful clinical tool for BC and pan-cancer patients, and potentially guiding personalized therapy decisions for selecting potential beneficiaries and excluding resistant patients of ICB therapy.

Spontaneous delayed migration or shortening after pipeline embolization device treatment of intracranial aneurysm: incidence, management, and risk factors.

BACKGROUND: Studies reporting spontaneous delayed migration or shortening (SDMS) after treatment with the Pipeline Embolization Device (PED) are limited. This study aimed to evaluate the incidence of SDMS after PED treatment, propose management strategies, and identify the risk factors contributing to its occurrence. METHODS: We retrospectively reviewed consecutive patients with an intracranial aneurysm (IA) treated with PEDs at three institutions. SDMS was classified as type I or II based on whether the PED covered the aneurysm neck. RESULTS: The total cohort comprised 790 patients. SDMS was identified in 24 (3.04%) patients. Eighteen of the 24 patients had type I SDMS and did not require retreatment, while the remaining six patients had type II SDMS and all received retreatment. Multivariate logistic regression showed that the difference between the proximal and distal parent artery diameters (DPAD) (adjusted OR 2.977; 95% CI 1.054 to 8.405; P=0.039) and device tortuosity index (DTI) (adjusted OR 8.059; 95% CI 2.867 to 23.428; P<0.001) were independent predictors of SDMS after PED treatment, while the difference in length (DL) (adjusted OR 0.841; 95% CI 0.738 to 0.958; P=0.009) and PED plus coiling (adjusted OR 0.288; 95% CI 0.106 to 0.785; P=0.015) were protective factors. CONCLUSION: The incidence of SDMS after PED treatment of IA was 3.04%. For patients with type I SDMS with incomplete aneurysm occlusion we recommend continuous imaging follow-up while, for patients with type II SDMS, we recommend aggressive retreatment. The DPAD and DTI were independent risk predictors of SDMS after PED treatment, while the DL and PED plus coiling were protective factors.

Whole-genome resequencing of Hu sheep identifies candidate genes associated with agronomic traits.

The phenotypic diversity resulting from artificial or natural selection of sheep has made a significant contribution to human civilization. Hu sheep are a local sheep breed unique to China with high reproductive rates and rapid growth. Genome selection signatures have been widely used to investigate the genetic mechanisms underlying phenotypic variation in livestock. Here, we conduct whole-genome sequencing of 207 Hu sheep and compare them with the wild ancestors of domestic sheep (Asiatic mouflon) to investigate the genetic characteristics and selection signatures of Hu sheep. Based on six signatures of selection approaches, we detect genomic regions containing genes related to reproduction (BMPR1B, BMP2, PGFS, CYP19, CAMK4, GGT5, and GNAQ), vision (ALDH1A2, SAG, and PDE6B), nervous system (NAV1), and immune response (GPR35, SH2B2, PIK3R3, and HRAS). Association analysis with a population of 1299 Hu sheep reveal those missense mutations in the GPR35 (GPR35 g.952651 A>G; GPR35 g.952496 C>T) and NAV1 (NAV1 g.84216190 C>T; NAV1 g.84227412 G>A) genes are significantly associated (P < 0.05) with immune and growth traits in Hu sheep, respectively. This research offers unique insights into the selection characteristics of Hu sheep and facilitates further genetic improvement and molecular investigations.

Identification of the FGB gene polymorphism and analysis of its association with fat deposition traits in Hu sheep.

As a crucial economic trait, fat deposition is directly related to carcass quality and feed efficiency in sheep. The purpose of this study was to investigate the polymorphisms of the FGB gene related to fat deposition and detect the expression features of the FGB gene in different adipose tissues of sheep by using Sanger sequencing, MassARRAY® SNP technique, and quantitative real-time PCR (qRT-PCR). Results showed that in the intron region of the FGB gene, a SNP g. 3378953 A > T has been identified, and significant association was found between perirenal fat weight, perirenal fat relative weight, mesenteric fat weight, and mesenteric fat relative weight (P < 0.05). Moreover, qRT-PCR analysis showed that FGB was expressed in all three adipose tissues, and FGB gene expression level in the AA genotype was significantly lower than that in the AT or TT genotypes (P < 0.05). Therefore, the FGB gene can be used as a candidate gene to reduce fat deposition in Hu sheep breeding, and the selection of the AA genotype in Hu sheep in production practice is more conducive to improving production efficiency.

Resection or Biopsy: The Efficacy of Different Surgical Approaches for Primary Central Nervous System Lymphoma.

AIM: To analyze the efficacy of surgical resection versus brain biopsy combined with postoperative chemotherapy for primary central nervous system lymphoma (PCNSL) and to discuss a clinically standardized treatment protocol. MATERIAL AND METHODS: Patients with a pathological diagnosis of PCNSL and subsequent chemotherapy between 2016 and 2021 at Northern Jiangsu People?s Hospital were selected and divided into groups according to whether they underwent microsurgical resection or stereotactic needle biopsy. Statistical analyses were performed to compare efficacy and safety in the two groups. RESULTS: A total of 21 patients with PCNSL were identified, of whom 12 underwent resection and 9 underwent diagnostic stereotactic biopsy only. Compared with the resection group, the biopsy group had a higher proportion of deep tumors (55.6% vs. 8.3%, p=0.016), and the mean intraoperative bleeding was significantly reduced (13.33 ± 6.61 mL vs. 170.83 ± 101.04 ml, p < 0.001). In addition, the mean survival time of patients who died during the postoperative follow-up period was shorter (6.83 ± 1.60 vs. 18.56 ± 10.20 months, p=0.016), and the one-year survival rate was lower (33.3% vs. 83.3%, p=0.032). There was no significant difference between the two groups in terms of the mean progression-free survival time or new functional impairment after surgery. CONCLUSION: For PCNSL, patients who undergo surgical resection have a better outcome than those who undergo biopsy only, suggesting that when the tumor is located at a surgically resectable site, surgical resection should be actively chosen; when the tumor is located at a deep and unresectable site, brain biopsy should be chosen.

Near-infrared dual-response fluorescent probe for detection of N2H4 and intracellular viscosity changes in biological samples and various water samples.

N2H4 is a common raw material used in the production of pesticides and has good water solubility, so it may contaminate water sources and eventually enter living organisms, causing serious health problems. Viscosity is an important indicator of the cellular microenvironment and an early warning signal for many diseases. The high reactivity of hydrazine depletes glutathione (GSH) in hepatocytes, causing oxidative stress ultimately leading to significant changes in intracellular viscosity and even death. Therefore, it is particularly important to develop an effective method to detect N2H4 and viscosity in environmental and biological systems. On this basis, we developed two fluorescent probes, BDD and BHD, based on xanthene and 2-benzothiazole acetonitrile. The experimental results show that BHD and BDD have good imaging capabilities for N2H4 in cells, zebrafish and Arabidopsis. BHD and BDD also showed sensitive detection and fluorescence enhancement in the near-infrared region when the intracellular viscosity was changed. Notably, the probe BDD has also successfully imaged N2H4 in a variety of real water samples.

Fast imaging of lenticulostriate arteries by high-resolution black-blood T1-weighted imaging with variable flip angles and acceleration by compressed sensitivity encoding.

OBJECTIVE: We investigated the feasibility of using compressed sensitivity encoding (CS-SENSE) to accelerate high-resolution black-blood T1-weighted imaging with variable flip angles (T1WI-VFA) for efficient visualization and characterization of lenticulostriate arteries (LSAs) on a 3.0 T MR scanner. MATERIALS AND METHODS: Twenty-five healthy volunteers and 18 patients with the cerebrovascular disease were prospectively enrolled. Healthy volunteers underwent T1WI-VFA sequences with different acceleration factors (AFs), including conventional sensitivity encoding (SENSE) AF = 3 and CS-SENSE AF = 3, 4, 5, and 6 (SENSE3, CS3, CS4, CS5, CS6, respectively) at 3 Tesla MRI scanner. Objective evaluation (contrast ratio and number, length, and branches of LSAs) and subjective evaluation (overall image quality and LSA visualization scores) were used to assess image quality and LSA visualization. Comparisons were performed among the 5 sequences to select the best AF. All patients underwent both T1WI-VFA with the optimal AF and digital subtraction angiography (DSA) examination, and the number of LSAs observed by T1WI-VFA was compared with that by DSA. RESULTS: Pair-wise comparisons among CS3, CS4, and SENSE3 revealed no significant differences in both objective measurements and subjective evaluation (all P > 0.05). In patients, there was no significant difference in LSA counts on the same side between T1WI-VFA with CS4 and DSA (3, 3-4 and 3, 3-3, P = 0.243). CONCLUSIONS: CS3 provided better LSA visualization but a longer scan duration compared to CS4. And, CS4 strikes a good balance between LSA visualization and acquisition time, which is recommended for routine clinical use.

5-Hydroxytryptophan acts as a gap junction inhibitor to limit the spread of chemotherapy-induced cardiomyocyte injury and mitochondrial dysfunction.

Anthracycline chemotherapeutics like doxorubicin (DOX) are widely used against various cancers but are accompanied by severe cardiotoxic effects that can lead to heart failure. Through whole transcriptome sequencing and pathological tissue analysis in a murine model, our study has revealed that DOX impairs collagen expression in the early phase, causing extracellular matrix anomalies that weaken the mechanical integrity of the heart. This results in ventricular wall thinning and dilation, exacerbating cardiac dysfunction. In this work, we have identified 5-hydroxytryptophan (5-HTP) as a potent inhibitor of gap junction communication. This inhibition is key to limiting the spread of DOX-induced cardiotoxicity. Treatment with 5-HTP effectively countered the adverse effects of DOX on the heart, preserving ventricular structure and ejection fraction. Moreover, 5-HTP enhanced mitochondrial respiratory function, as shown by the O2k mitochondrial function assay, by improving mitochondrial complex activity and ATP production. Importantly, the cardioprotective benefits of 5-HTP did not interfere with DOX's ability to combat cancer. These findings shed light on the cardiotoxic mechanisms of DOX and suggest that 5-HTP could be a viable strategy to prevent heart damage during chemotherapy, offering a foundation for future clinical development. This research opens the door for 5-HTP to be considered a dual-purpose agent that can protect the heart without compromising the oncological efficacy of anthracycline chemotherapy.

Overloaded transnidal pressure gradient as the hemodynamic mechanism leading to arteriovenous malformation rupture: a quantitative analysis using intravascular pressure monitoring and color-coded digital subtraction angiography.

BACKGROUND: The hemodynamics of brain arteriovenous malformations (AVMs) may have implications for hemorrhage. This study aimed to explore the hemodynamics of ruptured AVMs by direct microcatheter intravascular pressure monitoring (MIPM) and indirect quantitative digital subtraction angiography (QDSA). METHODS: We recruited patients with AVMs at a tertiary neurosurgery center from October 2020 to March 2023. In terms of MIPM, we preoperatively super-selected a predominant feeding artery and main draining vein through angiography to measure intravascular pressure before embolization. In processing of QDSA, we adopted previously standardized procedure for quantitative hemodynamics analysis of pre-embolization digital subtraction angiography (DSA), encompassing main feeding artery, nidus, and the main draining vein. Subsequently, we investigated the correlation between AVM rupture and intravascular pressure from MIPM, as well as hemodynamic parameters derived from QDSA. Additionally, we explored the interrelationships between hemodynamic indicators in both dimensions. RESULTS: After strict screening of patients, our study included 10 AVMs (six ruptured and four unruptured). We found that higher transnidal pressure gradient (TPG) (53.00±6.36 vs 39.25±8.96 mmHg, p=0.042), higher feeding artery pressure (FAP) (72.83±5.46 vs 65.00±6.48 mmHg, p=0.031) and higher stasis index of nidus (3.54±0.73 vs 2.43±0.70, p=0.043) were significantly correlated with AVM rupture. In analysis of interrelationships between hemodynamic indicators in both dimensions, a strongly positive correlation (r=0.681, p=0.030) existed between TPG and stasis index of nidus. CONCLUSIONS: TPG and FAP from MIPM platform and nidus stasis index from QDSA platform were correlated with AVM rupture, and both were positively correlated, suggesting that higher pressure load within nidus may be the central mechanism leading to AVM rupture.

Risk factors for delayed postoperative hemorrhage in patients with brain arteriovenous malformations: an analysis of the nationwide multicenter prospective registry MATCH study.

OBJECTIVE: Reducing the incidence of delayed postoperative hemorrhage (DPH) is one of the challenges in the surgical treatment of patients with brain arteriovenous malformations (bAVMs). This study aimed to identify several risk factors for DPH after bAVM resection and evaluate the impact of these risk factors in patients with bAVMs. METHODS: The authors retrospectively reviewed consecutive patients with bAVMs who underwent microsurgical resection between August 2011 and September 2021. Patients were divided into either the DPH group or non-DPH group based on whether they experienced a postoperative intracerebral hemorrhage into the bAVM bed within 14 days after bAVM resection. Factors associated with DPH were assessed using multivariate logistic regression analyses. RESULTS: A total of 1284 consecutive patients with bAVMs were evaluated; DPH events occurred in 18 patients (1.4%). There were several differences in vascular architecture between the two cohorts. A giant nidus, a nidus involved in the eloquent area, a periventricular nidus, and a nidus accompanied by venous ectasia were more likely to be associated with DPH events. The multivariate analysis identified two independent factors associated with DPH: maximum diameter (OR 1.44 per 1-cm increase, 95% CI 1.13-1.83) and periventricular lesion (OR 4.10, 95% CI 1.33-12.59). The area under the receiver operating characteristic curve for the maximum lesion diameter and development of DPH was 0.71 (95% CI 0.58-0.84). The cutoff value for the maximum bAVM diameter was 4.15 cm. Furthermore, patients with a giant bAVM, of which the maximum diameter was ≥ 4.15 cm, had a higher DPH risk after surgery (HR 5.79, 95% CI 2.01-16.67; p < 0.01). The incidence rates of DPH for patients with periventricular lesions were higher than those for patients without periventricular lesions (HR 4.50, 95% CI 1.77-11.40; p < 0.01). CONCLUSIONS: Patients with giant bAVMs or periventricular lesions are at higher risk for DPH after surgery. Strategies such as blood pressure control, preoperative embolization, intraoperative monitoring, and careful patient selection should be considered to reduce the risk of DPH in high-risk patients.

Ecological variation in adult social play reveals a hidden cost of motherhood for wild chimpanzees.

Though common among humans, social play by adults is an uncommon occurrence in most animals, even between parents and offspring.1,2,3 The most common explanation for why adult play is so rare is that its function and benefits are largely limited to development, so that social play has little value later in life.3,4,5,6 Here, we draw from 10 years of behavioral data collected by the Kibale Chimpanzee Project to consider an alternative hypothesis: that despite its benefits, adult play in non-humans is ecologically constrained by energy shortage or time limitations. We further hypothesized that, since they may be the only available partners for their young offspring, mother chimpanzees pay greater costs of play than other adults. Our analysis of nearly 4,000 adult play bouts revealed that adult chimpanzees played both among themselves and with immature partners. Social play was infrequent when diet quality was low but increased with the proportion of high-quality fruits in the diet. This suggests that adults engage in play facultatively when they have more energy and/or time to do so. However, when diet quality was low and most adult play fell to near zero, play persisted between mothers and offspring. Increased use of play by adult chimpanzees during periods of resource abundance suggests that play retains value as a social currency beyond development but that its costs constrain its use. At the same time, when ecological conditions constrain opportunities for young to play, play by mothers fills a critical role to promote healthy offspring development.

A fluorescent probe for detecting H2O2 and delivering H2S in lysosomes and its application in maintaining the redox environments.

Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) that can be used as a marker for the occurrence of oxidative stress in the organism. Lysosomes serve as intracellular digestive sites, and when the concentration of H2O2 in them is abnormal, lysosomal function is often impaired, leading to the development of diseases. Hydrogen sulfide (H2S) acts as a gaseous signaling molecule that scavenges H2O2 from cells and tissues, thereby maintaining the redox environment of the body. However, most of the reported hydrogen peroxide fluorescent probes so far can only detect H2O2, but cannot maintain the intracellular redox environment. In this paper, an H2O2 fluorescent probe LN-HOD with lysosomal targeting properties was designed and synthesized by combining the H2O2 recognition site with a naphthylamine fluorophore via a thiocarbamate moiety. The probe has the advantages of large Stokes shift (110 nm), high sensitivity and good H2S release capability. The probe LN-HOD can be used to detect H2O2 in cells, zebrafish and plant roots. In addition, LN-HOD detects changes in the concentration of H2O2 in plant roots when Arabidopsis is stressed by cadmium ion (Cd2+). And through its ability to release H2S, it can help to remove excess H2O2 and maintain the redox environment in cells, zebrafish and plant roots. The present work provides new ideas for the detection and assisted removal of H2O2, which contributes to the in-depth study of the cellular microenvironment in organisms.

Psychometric and Circumplex Properties Evaluation of the International Personality Item Pool-Interpersonal Circumplex (IPIP-IPC) in Chinese People Living with HIV (PLWH).

Background and Purpose: With the improved life expectancy of people living with HIV (PLWH) due to widespread use of antiretroviral therapy (ART), there is a greater emphasis on enhancing long-term well-being and overall quality of life for PLWH. Understanding interpersonal personalities of PLWH can gain further insight into how to improve the overall quality of life in this population. The International Personality Item Pool-Interpersonal Circumplex (IPIP-IPC) scale has been developed to assess interpersonal personalities of individuals, and this scale has been translated into Chinese. However, the Chinese version of IPIP-IPC has not been tested among PLWH in China. In this study, we aimed to test the psychometric properties and circumplex structure of this scale. Methods: This study was based on cross-sectional, multi-center, large sample data. We employed the Chinese version of IPIP-IPC scale on 3040 PLWH from April 2022 to April 2023 in China to test its psychometric as well as circumplex properties. The structural summary method (SSM) was employed to analyze the circumplex structure of the scale. Results: The total scale exhibited a Cronbach's alpha of 0.85 and McDonald's omega of 0.91. Out of the 288 possible relationships, 275 relationships satisfy the circular properties hypothesis. The scale demonstrates good reliability and validity, meeting the requirements of psychometrics. Conclusion: Our findings demonstrate that the Chinese version of the IPIP-IPC scale is a reliable tool for evaluating interpersonal personalities in this population. These results highlight the validity and applicability of the IPIP-IPC scale specifically in the Chinese context, providing valuable insights into the intricacies of interpersonal traits among PLWH.

Relationship between sheep feces scores and gastrointestinal microorganisms and their effects on growth traits and blood indicators.

Fecal scores are crucial for assessing the digestive and gastrointestinal status of animals. The Bristol fecal scoring system is a commonly used method for the subjective evaluation of host feces, there is limited research on fecal scoring standards for fattening Hu sheep. In this study, Hu sheep were collected for rumen, rectum, and colon contents for 16S rDNA sequencing. 514 Hu sheep feces were scored based on the Bristol fecal scoring system, and production performance at each stage was measured. Finally, we developed the scoring standard of the manure of Hu sheep in the fattening period (a total of five grades). The result shows that moisture content significantly increased with higher grades (p < 0.05). We analyzed the relationship between fecal scores and production traits, blood indices, muscle nutrients, and digestive tract microorganisms. The growth traits (body weight, body height, body length, average daily gain (ADG), and average daily feed intake (ADFI) during 80-180 days), body composition traits of the F3 group, and the carcass traits were found to be significantly higher (p < 0.05) than those of the F1 and F2 groups. There was no significant difference in gastrointestinal microflora diversity among all groups (p > 0.05). Significant differences were observed in Aspartate aminotransferase, Glucose, Total bilirubin, and Red Blood Cell Count between groups (p < 0.05). The mutton moisture content in group F4 was significantly higher than in the other groups, and the protein content was also the lowest (p < 0.05). The results of the correlation analysis demonstrated that Actinobacteria, Peptostreptococcaceae, Acidaminococcales, Gammaproteobacteria, and Proteobacteria were the significant bacteria affecting fecal scores. In addition, Muribaculaceae and Oscillospiraceae were identified as the noteworthy flora affecting growth performance and immunity. This study highlights the differences in production traits and blood indicators between fecal assessment groups and the complex relationship between intestinal microbiota and fecal characteristics in Hu sheep, suggesting potential impacts on animal performance and health, which suggest strategies for improved management.

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.

METTL16 inhibits papillary thyroid cancer tumorigenicity through m6A/YTHDC2/SCD1-regulated lipid metabolism.

Papillary thyroid carcinoma (PTC) stands as the leading cancer type among endocrine malignancies, and there exists a strong correlation between thyroid cancer and obesity. However, the clinical significance and molecular mechanism of lipid metabolism in the development of PTC remain unclear. In this study, it was demonstrated that the downregulation of METTL16 enhanced lipid metabolism and promoted the malignant progression of PTC. METTL16 was expressed at lower levels in PTC tissues because of DNMT1-mediated hypermethylation of its promoter. Loss- and gain-of-function studies clarified the effects of METTL16 on PTC progression. METTL16 overexpression increased the abundance of m6A in SCD1 cells, increasing RNA decay via the m6A reader YTHDC2. The SCD1 inhibitor A939572 inhibited growth and slowed down lipid metabolism in PTC cells. These results confirm the crucial role of METTL16 in restraining PTC progression through SCD1-activated lipid metabolism in cooperation with YTHDC2. This suggests that the combination of METTL16 and anti-SCD1 blockade might constitute an effective therapy for PTC.

Structural characterization and anti-oxidative activity for a glycopeptide from Ganoderma lucidum fruiting body.

A water-soluble glycopeptide (named GL-PWQ3) with a molecular weight (Mw) of 2.40 × 104 g/mol was isolated from Ganoderma lucidum fruiting body by hot water extraction, membrane ultrafiltration, and gel column chromatography, which mainly consisted of glucose and galactose. Based on the methylation, FT-IR, 1D, and 2D NMR analysis, the polysaccharide portion of GL-PWQ3 was identified as a glucogalactan, which was comprised of unsubstituted (1,6-α-Galp, 1,6-ß-Glcp, 1,4-ß-Glcp) and monosubstituted (1,2,6-α-Galp and 1,3,6-ß-Glcp) in the backbone and possible branches that at the O-3 position of 1,3-Glcp and T-Glcp, and the O-2 position of T-Fucp, T-Manp or T-Glcp. The chain conformational study by SEC-MALLS-RI and AFM revealed that GL-PWQ3 was identified as a highly branched polysaccharide with a polydispersity index of 1.25, and might have compact sphere structures caused by stacked multiple chains. Moreover, the GL-PWQ3 shows strong anti-oxidative activity in NRK-52E cells. This study provides a theoretical basis for further elucidating the structure-functionality relationships of GL-PWQ3 and its potential application as a natural antioxidant in pharmacotherapy as well as functional food additives.