Sperm miR-142-3p Reprogramming Mediates Paternal Pre-Pregnancy Caffeine Exposure-Induced Non-Alcoholic Steatohepatitis in Male Offspring Rats.

Numerous studies have suggested a strong association between paternal adverse environmental exposure and increased disease susceptibility in offspring. However, the impact of paternal pre-pregnant caffeine exposure (PPCE) on offspring health remains unexplored. This study elucidates the sperm reprogramming mechanism and potential intervention targets for PPCE-induced non-alcoholic steatohepatitis (NASH) in offspring. Here, male rats are administrated caffeine (15-60 mg kg-1/d) by gavage for 8 weeks and then mated with females to produce offspring. This study finds that NASH with transgenerational inheritance occurred in PPCE adult offspring. Mechanistically, a reduction of miR-142-3p is implicated in the occurrence of NASH, characterized by hepatic lipid metabolism dysfunction and chronic inflammation through an increase in ACSL4. Conversely, overexpression of miR-142-3p mitigated these manifestations. The origin of reduced miR-142-3p levels is traced to hypermethylation in the miR-142-3p promoter region of parental sperm, induced by elevated corticosterone levels rather than by caffeine per se. Similar outcomes are confirmed in offspring conceived via in vitro fertilization using miR-142-3pKO sperm. Overall, this study provides the first evidence of transgenerational inheritance of NASH in PPCE offspring and identifies miR-142-3p as a potential therapeutic target for NASH induced by paternal environmental adversities.

Global, regional, and national burden of tracheal, bronchus, and lung cancer and its risk factors from 1990 to 2021: findings from the global burden of disease study 2021.

Background: Studies from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2021 can guide screening and prevention strategies for tracheal, bronchus, and lung (TBL) cancer. We aim to provide global, regional, and national estimates of the TBL cancer burden and its attributable risk from 1990 to 2021, including during the coronavirus disease 2019 (COVID-19) pandemic. Methods: Incidence, age-standardised incidence rate (ASIR), deaths, age-standardised mortality rate (ASMR), disability-adjusted life years (DALYs), age-standardised rate of DALYs (ASDR), and the burden due to risk factors associated with TBL cancer were analysed from 1990 to 2021. Trends in ASIR, ASMR, and ASDR of TBL cancer during the COVID-19 pandemic (2019-2021) were also determined. All statistical analyses were performed using Join-point software (version 4.9.1.0). Findings: Between 1990 and 2021, the global incidence, deaths, and DALYs of TBL cancer to varying degrees. However, the ASIR (Average Annual Percent Change [AAPC], -0.3 [-0.4 to -0.2]), ASMR (AAPC, -0.5 [-0.7 to -0.4]), and ASDR (AAPC, -0.9 [-1.0 to -0.7]) all showed a decreasing trend. However, the ASIR, ASMR, and ASDR of TBL cancer in males all showed a decreasing trend from 1990 to 2021. In contrast, the ASIR and ASMR of TBL cancer in females showed an increasing trend, while the ASDR showed a relatively stable trend. During the COVID-19 pandemic, the trends for ASIR, ASMR, and ASDR remained stable across both sexes combined, females, males, five socio-demographic index (SDI) quintiles, and the 21 GBD regions. In 2021, smoking was a major risk factor for TBL cancer DALYs, but the attributable ASDR for smoking decreased from 1990 to 2021 in both sexes combined, as well as individually for males and females. Conversely, the attributable ASDR for secondhand smoke, high fasting plasma glucose and occupational exposure factors increased primarily among females. Furthermore, the attributable ASDR for ambient particulate matter pollution, household air pollution from solid fuels, and low-fruit diets increased primarily in regions with lower SDI quintiles from 1990 to 2021. Interpretation: The burden attributable to TBL cancer has increased in some populations from 1990 to 2021, highlighting the importance of implementing targeted measures to mitigate this trend. No significant change in the burden of TBL cancer was observed during the COVID-19 pandemic; however, post-COVID-19 rates still require further observation. Funding: This study was supported by National Key Research and Development Program of China (2023YFC3503300, 2023YFC3503305), and High Level Chinese Medical Hospital Promotion Project (HLCMHPP2023085, HLCMHPP2023001, HLCMHPP2023097).

Intratumoral and Peritumoral Radiomics for Predicting the Prognosis of High-grade Serous Ovarian Cancer Patients Receiving Platinum-Based Chemotherapy.

RATIONALE AND OBJECTIVES: This study aimed to develop a deep learning (DL) prognostic model to evaluate the significance of intra- and peritumoral radiomics in predicting outcomes for high-grade serous ovarian cancer (HGSOC) patients receiving platinum-based chemotherapy. MATERIALS AND METHODS: A DL model was trained and validated on retrospectively collected unenhanced computed tomography (CT) scans from 474 patients at two institutions, which were divided into a training set (N = 362), an internal test set (N = 86), and an external test set (N = 26). The model incorporated tumor segmentation and peritumoral region analysis, using various input configurations: original tumor regions of interest (ROIs), ROI subregions, and ROIs expanded by 1 and 3 pixels. Model performance was assessed via hazard ratios (HRs) and receiver operating characteristic (ROC) curves. Patients were stratified into high- and low-risk groups on the basis of the training set's optimal cutoff value. RESULTS: Among the input configurations, the model using an ROI with a 1-pixel peritumoral expansion achieved the highest predictive accuracy. The DL model exhibited robust performance for predicting progression-free survival, with HRs of 3.41 (95% CI: 2.85, 4.08; P < 0.001) in training set, 1.14 (95% CI: 1.03, 1.26; P = 0.012) in internal test set, and 1.32 (95% CI: 1.07, 1.63; P = 0.011) in external test set. KM survival analysis revealed significant differences between the high-risk and low-risk groups (P < 0.05). CONCLUSION: The DL model effectively predicts survival outcomes in HGSOC patients receiving platinum-based chemotherapy, offering valuable insights for prognostic assessment and personalized treatment planning.

Genetic variation and recombination analysis of PRRSV-2 GP3 gene in China from 1996 to 2023.

Porcine reproductive and respiratory syndrome virus (PRRSV) has become widespread in China particularly the highly pathogenic porcine reproductive and respiratory syndromes (HP-PRRSV), NADC30, and NADC34 strains, and has posed a threat to the swine industry for over 20 years. To monitor genetic variation in PRRSV-2 GP3 strains in China, we analyzed 618 strains isolated between 1996 to 2023 and constructed phylogenetic trees. Additionally, 60 selected strains were used to analyze nucleotide and amino acid homology. PRRSV GP3 gene exhibited nucleotide identity ranging from 78.2% to 100.0% and amino acid similarity ranging from 74.9% to 99.6%. The GP3 gene in the 60 selected strains consisted of 254 amino acids, and amino acid mutations in the strains primarily occurred in B-cell epitopes, T-cell epitopes, and highly variable regions. The glycosylation sites of the strains used for amino acid sequence comparisons remained unaltered, except for the N29 site in the GD20220303-2022 strain. PRRSV-2 strains in China belong to lineages 1, 3, 5, and 8. Recombination analysis detected two recombination events, involving lineages 1 and 8. In conclusion, this study investigated multiple strains of the PRRSV-2 GP3 gene to explore the prevalence and genetic diversity of the GP3 gene in China from a gene family perspective. The results of the analyses provide a basis for clinical prevention strategies and vaccine development.

Predicting prognosis for epithelial ovarian cancer patients receiving bevacizumab treatment with CT-based deep learning.

Epithelial ovarian cancer (EOC) presents considerable difficulties in prognostication and treatment strategy development. Bevacizumab, an anti-angiogenic medication, has demonstrated potential in enhancing progression-free survival (PFS) in EOC patients. Nevertheless, the identification of individuals at elevated risk of disease progression following treatment remains a challenging task. This study was to develop and validate a deep learning (DL) model using retrospectively collected computed tomography (CT) plain scans of inoperable and recurrent EOC patients receiving bevacizumab treatment diagnosed between January 2013 and January 2024. A total of 525 patients from three different institutions were retrospectively included in the study and divided into training set (N = 400), internal test set (N = 97) and external test set (N = 28). The model's performance was evaluated using Harrell's C-index. Patients were categorized into high-risk and low-risk group based on a predetermined cutoff in the training set. Additionally, a multimodal model was evaluated, incorporating the risk score generated by the DL model and the pretreatment level of carbohydrate antigen 125 as input variables. The Net Reclassification Improvement (NRI) metric quantified the reclassification performance of our optimal model in comparison to the International Federation of Gynecology and Obstetrics (FIGO) staging model. The results indicated that DL model achieved a PFS predictive C-index of 0.73 in the internal test set and a C-index of 0.61 in the external test set, along with hazard ratios of 34.24 in the training set (95% CI: 21.7, 54.1; P < 0.001) and 8.16 in the internal test set (95% CI: 2.5, 26.8; P < 0.001). The multimodal model demonstrated a C-index of 0.76 in the internal test set and a C-index of 0.64 in the external test set. Comparative analysis against FIGO staging revealed an NRI of 0.06 (P < 0.001) for the multimodal model. The model presents opportunities for prognostic assessment, treatment strategizing, and ongoing patient monitoring.

Genetic variation and recombination analysis of the GP5 gene of the porcine reproductive and respiratory syndrome virus in Thailand.

Introduction: Porcine reproductive and respiratory syndrome (PRRS) is a significant threat to the global swine industry, and its prevalence in Thailand spans over two decades. Methods: To understand the genetic variation and recombination of the PRRS virus (PRRSV) GP5 gene in Thailand, we retrieved 726 GP5 gene sequences from the NCBI database. Phylogenetic trees were constructed using the neighbor-joining (NJ) and maximum likelihood (ML) methods, and recombination analysis was performed. Results: Homology analysis was conducted on 83 PRRSV-1 and 83 PRRSV-2 strains. Phylogenetic analysis revealed the prevalence of both PRRSV-1 and PRRSV-2 strains in Thailand, with the latter exhibiting wider distribution. PRRSV-1 strains clustered into clades A, D, and H, while PRRSV-2 strains grouped into lineages 1, 5, and sublineage 8.7, further divided into 8.7/HP and 8.7/NA sublineages. Sublineage 8.7/NA strains accounted for a significant proportion of circulating PRRSV-2 strains. Homology analysis showed nucleotide and amino acid similarities ranging from 75.4 to 100.0% and 41.3 to 100.0% for PRRSV-1, and 78.6 to 100.0% and 70.8 to 100.0% for PRRSV-2 strains. Amino acid sequence alignments revealed mutations, insertions, and deletions in PRRSV-1 GP5, and key residue mutations in PRRSV-2 GP5 associated with biological functions. Recombination analysis identified two recombination events within PRRSV-2 sublineage 8.7 strains. Discussion: These findings confirm the variability of the GP5 protein. This study enhances our understanding of PRRSV prevalence and genetic variation in Thailand, contributing valuable insights for PRRS prevention and control.

Insights into the response mechanisms of Tetradesmus obliquus to aged polylactic acid and tetracycline exposure via transcriptome analysis and physiological evaluations.

Microplastics (MPs) and antibiotics, identified as emerging pollutants, are extensively prevalent in aquatic environments and display prolonged durability. Unlike conventional plastics, biodegradable plastics are more susceptible to decomposition in the environment, resulting in the generation of microplastics and posing potential risks to the aquatic ecosystems. In this study, we assessed growth inhibition, chlorophyll a content, malondialdehyde content (MDA), and antioxidant enzyme activities. These measurements were integrated with transcriptome analysis to explore the response mechanisms of virgin and aged polylactic acid (vPLA and aPLA) and tetracycline (TC) following 14-day exposure to Tetradesmus obliquus, either individually or in combination. The findings indicated that exposure to vPLA did not significantly impact the growth of T. obliquus. Conversely, aPLA demonstrated growth-promoting effects on T. obliquus, particularly in the latter incubation stages. Moreover, a 14-day exposure significantly increased the chlorophyll a content and the activities of superoxide dismutase (SOD), catalase glutathione (CAT) and glutathione S-transferase (GST) within the algal cells. Apart from 1 mg L-1, the TC concentrations of 2.5, 5.0, and 10 mg L-1 exhibited significant toxic effects on T. obliquus, including growth inhibition, decreased chlorophyll a content, elevated activities of SOD, CAT, and GST, and increased MDA levels. Exposure to a combination of 300 mg L-1 aPLA and 5.0 mg L-1 TC, compared to solely 5 mg L-1 TC, demonstrated a notable reduction in TC toxicity to T. obliquus in the presence of aPLA. This was indicated by elevated algal cell density and chlorophyll a content, as well as a decrease in MDA content. Transcriptome analysis indicated an enrichment of differentially expressed genes (DEGs) in pathways linked to porphyrin metabolism, photosynthesis, carbon fixation, and metabolism within the aPLA + TC combined exposure. The study aid in expanding our knowledge of the potential ecological risks posed by biodegradable plastics and accompanying pollutants in aquatic environments.

Soil Organic Carbon Prediction Based on Vis-NIR Spectral Classification Data Using GWPCA-FCM Algorithm.

Soil visible and near-infrared reflectance spectroscopy is an effective tool for the rapid estimation of soil organic carbon (SOC). The development of spectroscopic technology has increased the application of spectral libraries for SOC research. However, the direct application of spectral libraries for SOC prediction remains challenging due to the high variability in soil types and soil-forming factors. This study aims to address this challenge by improving SOC prediction accuracy through spectral classification. We utilized the European Land Use and Cover Area frame Survey (LUCAS) large-scale spectral library and employed a geographically weighted principal component analysis (GWPCA) combined with a fuzzy c-means (FCM) clustering algorithm to classify the spectra. Subsequently, we used partial least squares regression (PLSR) and the Cubist model for SOC prediction. Additionally, we classified the soil data by land cover types and compared the classification prediction results with those obtained from spectral classification. The results showed that (1) the GWPCA-FCM-Cubist model yielded the best predictions, with an average accuracy of R2 = 0.83 and RPIQ = 2.95, representing improvements of 10.33% and 18.00% in R2 and RPIQ, respectively, compared to unclassified full sample modeling. (2) The accuracy of spectral classification modeling based on GWPCA-FCM was significantly superior to that of land cover type classification modeling. Specifically, there was a 7.64% and 14.22% improvement in R2 and RPIQ, respectively, under PLSR, and a 13.36% and 29.10% improvement in R2 and RPIQ, respectively, under Cubist. (3) Overall, the prediction accuracy of Cubist models was better than that of PLSR models. These findings indicate that the application of GWPCA and FCM clustering in conjunction with the Cubist modeling technique can significantly enhance the prediction accuracy of SOC from large-scale spectral libraries.

Volatile metabolomics and transcriptomics analyses provide insights into the mechanism of volatile changes during fruit development of 'Ehime 38' (Citrus reticulata) and its bud mutant.

Volatile compounds are important determinants affecting fruit flavor. Previous study has identified a bud mutant of 'Ehime 38' (Citrus reticulata) with different volatile profile. However, the volatile changes between WT and MT during fruit development and underlying mechanism remain elusive. In this study, a total of 35 volatile compounds were identified in the pulps of WT and MT at five developmental stages. Both varieties accumulated similar and the highest levels of volatiles at stage S1, and showed a downward trend as the fruit develops. However, the total volatile contents in the pulps of MT were 1.4-2.5 folds higher than those in WT at stages S2-S5, which was mainly due to the increase in the content of d-limonene. Transcriptomic and RT-qPCR analysis revealed that most genes in MEP pathway were positively correlated with the volatile contents, of which DXS1 might mainly contribute to the elevated volatiles accumulation in MT by increasing the flux into the MEP pathway. Moreover, temporal expression analysis indicated that these MEP pathway genes functioned at different developmental stages. This study provided comprehensive volatile metabolomics and transcriptomics characterizations of a citrus mutant during fruit development, which is valuable for fruit flavor improvement in citrus.

Precision Treatment of Anthracycline-Induced Cardiotoxicity: An Updated Review.

OPINION STATEMENT: Anthracycline (ANT)-induced cardiotoxicity (AIC) is a particularly prominent form of cancer therapy-related cardiovascular toxicity leading to the limitations of ANTs in clinical practice. Even though AIC has drawn particular attention, the best way to treat it is remaining unclear. Updates to AIC therapy have been made possible by recent developments in research on the underlying processes of AIC. We review the current molecular pathways leading to AIC: 1) oxidative stress (OS) including enzymatic-induced and other mechanisms; 2) topoisomerase; 3) inflammatory response; 4) cardiac progenitor cell damage; 5) epigenetic changes; 6) renin-angiotensin-aldosterone system (RAAS) dysregulation. And we systematically discuss current prevention and treatment strategies and novel pathogenesis-based therapies for AIC: 1) dose reduction and change; 2) altering drug delivery methods; 3) antioxidants, dexrezosen, statina, RAAS inhibitors, and hypoglycemic drugs; 4) miRNA, natural phytochemicals, mesenchymal stem cells, and cardiac progenitor cells. We also offer a fresh perspective on the management of AIC by outlining the current dilemmas and challenges associated with its prevention and treatment.

Unraveling urban hydro-environmental response to climate change and MCDA-based area prioritization in a data-scarce developing city.

Climate change leads to more frequent and intense heavy rainfall events, posing significant challenges for urban stormwater management, particularly in rapidly urbanizing cities of developing countries with constrained infrastructure. However, the quantitative assessment of urban stormwater, encompassing both its volume and quality, in these regions is impeded due to the scarcity of observational data and resulting limited understanding of drainage system dynamics. This study aims to elucidate the present and projected states of urban flooding, with a specific emphasis on fecal and organic contamination caused by combined sewer overflow (CSO). Leveraging a hydrological model incorporating physical and biochemical processes validated against invaluable observational data, we undertake simulations to estimate discharge, flood volume, and concentrations of suspended solids (SS), Escherichia coli (E. coli), and chemical oxygen demand (COD) within the drainage channel network of Phnom Penh City, Cambodia. Alterations in flood volumes, and pollutant concentrations and loads in overflow under two representative concentration pathways (RCPs 4.5 and 8.5) for extreme rainfall events are projected. Furthermore, we employ a multi-criteria decision analysis (MCDA) framework to evaluate flood risk, incorporating diverse indicators encompassing physical, social, and ecological dimensions. Our results demonstrate the exacerbating effects of climate change on flood volumes, expansion of flooded areas, prolonged durations of inundation, elevated vulnerability index, and heightened susceptibility to pollutant contamination under both scenarios, underscoring increased risks of flooding and fecal contamination. Spatial analysis identifies specific zones exhibiting heightened vulnerability to flooding and climate change, suggesting priority zones for investment in flood mitigation measures. These findings provide crucial insights for urban planning and stormwater management in regions with limited drainage infrastructure, offering essential guidance for decision-making in locales facing similar challenges.

The psychological side of menopause: evidence from the comorbidity network of menopausal, anxiety, and depressive symptoms.

OBJECTIVE: Numerous studies have uncovered a correlation between menopausal, anxiety, and depressive symptoms. How these symptoms interrelate and influence each other, however, remains unclear. This study aimed to identify the associations between menopausal, anxiety, and depressive symptoms using network analysis. METHODS: The participants comprised 423 women (Mage = 49.21 ± 4.01 y; range, 40-60 y) recruited from a menopause clinic at a tertiary hospital in Beijing, China. Demographic characteristics and menopausal, anxiety, and depressive symptoms were obtained through self-report questionnaires. Two networks were established: a partial correlation network and a Bayesian network. RESULTS: The menopausal symptom of nervousness exhibited a robust association with anxiety symptoms in both networks. Within the partial correlation network, the depressive symptom of tiredness emerged as a pivotal symptom, facilitating the co-occurrence of menopausal and depressive symptoms. Bayesian network analysis exhibited that the depressive symptom of a loss of interest was related to certain menopausal symptoms through depressive symptoms of tiredness and motor problems, both serving as critical links between menopausal symptoms and depression. Notably, four menopausal symptoms-arthralgia/myalgia, formication, sexual complaints, and urinary tract infection-appeared independent of other menopausal, anxiety, and depressive symptoms. CONCLUSIONS: Both psychological (eg, fatigue) and somatic (eg, hot flashes, headaches, and dizziness) menopausal symptoms demonstrate strong associations with depression. In providing optimal support for women's health during menopause, psychological interventions aimed at depression, particularly among those experiencing a loss of interest or pleasure in activities, should complement conventional therapies.

[Retracted] Puerarin improves graft bone defect through microRNA­155­3p­mediated p53/TNF­α/STAT1 signaling pathway.

Following the publication of the above paper, it has been drawn to the Editor's attention by a concerned reader that the immunohistochemical assay data shown in Fig. 4B on p. 245 were strikingly similar to data appearing in different form in another article written by different authors at different research institutes that had already been published in the journal International Journal of Biological Sciences prior to the submission of this paper to International Journal of Molecular Medicine. In view of the fact that the contentious data had already apparently been published previously, the Editor of International Journal of Molecular Medicine has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 46: 239-251, 2020; DOI: 10.3892/ijmm.2020.4595].

Homoplantaginin alleviates intervertebral disc degeneration by blocking the NF-κB/MAPK pathways via binding to TAK1.

Intervertebral disc degeneration (IVDD) is a common degenerative disease which is closely related to low back pain (LBP) and brings huge economic and social burdens. In this study, we explored the therapeutic effects of Homoplantaginin (Hom) for IVDD due to its convincing anti-inflammatory and antioxidant functions. TNF-α was used to simulate the inflammatory environment for nucleus pulposus (NP) cells in vitro. We verified that Hom could alleviate the TNF-α-induced inflammation and disturbance of ECM homeostasis through blocking the NF-κB/MAPK signaling pathways. Subsequently, we screened the binding targets of Hom and confirmed that Hom could directly bind to TAK1 and inhibit its phosphorylation to down-regulate the inflammation-related pathways. The therapeutic effects of Hom on IVDD were further validated through a needle puncture rat model in vivo. Overall, Hom was a promising small molecule for IVDD early intervention, possessing huge clinical translational value.

Investigation into Potential Allergenicity and Digestion-Resistant Linear Epitopes of Fish Skin Gelatin in Cell-Cultured Meat Scaffolds.

As a key component of cell-cultured fish, fish skin gelatin (FSG)-based cell scaffold provides support structures for cell growth, proliferation, and differentiation. However, there are potential allergenicity risks contained in FSG-based scaffolds. In this study, 3D edible scaffolds were prepared by phase separation method and showed a contact angle of less than 90°, which indicated that the scaffolds were favorable for cell adhesion. Besides, the swelling ratio was greater than 200%, implying a great potential to support cell growth. The sequence homology analysis indicated that FSG was prone to cross-reaction with collagen analogues. Additionally, a food allergic model was constructed and represented that mice gavaged with cod FSG exhibited higher levels of specific antibodies, mast cell degranulation, vascular permeability, and intestinal barrier impairment than those gavaged with pangasius and tilapias FSG. Its higher allergenicity might be attributed to a higher number of digestion-resistant linear epitopes. Moreover, the higher hydrolysis degree linked to the exposure of linear epitopes to promote the combination with IgE, which was also responsible for maintaining the higher allergenicity of cod FSG. This study clarifies allergenic risks in cell-cultured fish and further study will focus on the allergenicity reduction of FSG-based cell scaffolds.

Exploration of MPSO-Two-Stage Classification Optimization Model for Scene Images with Low Quality and Complex Semantics.

Currently, complex scene classification strategies are limited to high-definition image scene sets, and low-quality scene sets are overlooked. Although a few studies have focused on artificially noisy images or specific image sets, none have involved actual low-resolution scene images. Therefore, designing classification models around practicality is of paramount importance. To solve the above problems, this paper proposes a two-stage classification optimization algorithm model based on MPSO, thus achieving high-precision classification of low-quality scene images. Firstly, to verify the rationality of the proposed model, three groups of internationally recognized scene datasets were used to conduct comparative experiments with the proposed model and 21 existing methods. It was found that the proposed model performs better, especially in the 15-scene dataset, with 1.54% higher accuracy than the best existing method ResNet-ELM. Secondly, to prove the necessity of the pre-reconstruction stage of the proposed model, the same classification architecture was used to conduct comparative experiments between the proposed reconstruction method and six existing preprocessing methods on the seven self-built low-quality news scene frames. The results show that the proposed model has a higher improvement rate for outdoor scenes. Finally, to test the application potential of the proposed model in outdoor environments, an adaptive test experiment was conducted on the two self-built scene sets affected by lighting and weather. The results indicate that the proposed model is suitable for weather-affected scene classification, with an average accuracy improvement of 1.42%.

Mechanochemical Recycling of Flexible Polyurethane Foam Scraps for Quantitative Replacement of Polyol Using Wedge-Block-Reinforced Extruder.

Recycling flexible polyurethane foam (F-PUF) scraps is difficult due to the material's high cross-linking structure. In this work, a wedge-block-reinforced extruder with a considerable enhanced shear extrusion and stretching area between the rotating screw and the stationary wedge blocks was utilized to recycle F-PUF scraps into powder containing surface-active hydroxyl groups. The powder was then utilized for the quantitative replacement of polyol in the foaming process. Characterizations showed that the continuous shear extrusion and stretching during the extrusion process reduced the volume mean diameter (VMD) of the F-PUF powder obtained by extruding it three times at room temperature to reach 54 µm. The -OH number (OHN) of the powder prepared by extruding it three times reached 19.51 mgKOH/g due to the mechanochemical effect of the powdering method. The F-PUF containing recycled powder used to quantitively replace 10 wt.% polyol was similar in microstructure and chemical structure to the original F-PUF, with a compression set of 2%, indentation load deflection of 21.3 lbf, resilience of 43.4%, air permeability of 815.7 L/m2·s, tensile strength of 73.0 Kpa, and tear strength of 2.3 N/cm, indicating that the recycling method has potential for industrial applications.

SPARCL1 promotes chondrocytes extracellular matrix degradation and inflammation in osteoarthritis via TNF/NF-κB pathway.

Objectives: SPARCL1 is a matricellular protein that mediates the cell-matrix interactions and participates in physiological processes such as cell adhesion, differentiation and proliferation. However, its role in chondrocyte and osteoarthritis (OA) progression has not been fully characterized. We aimed to evaluate the effects of SPARCL1 on OA through in vitro and in vivo experiments. Methods: Expression of SPARCL1 was examined in 55 paired human OA samples. Effects of Sparcl1 on chondrocytes were identified in vitro. Intra-articular injection was performed in an anterior cruciate ligament transection (ACLT) mouse model. Alterations of SPARCL1-mediated signaling pathway were identified by RNA-seq analysis. qPCR and western-blot were used to demonstrate the potential signaling pathway. Results: SPARCL1 expression in the OA cartilage was increased compared with undamaged cartilage. Recombinant Sparcl1 protein induced extracellular matrix degradation in chondrocytes. Furthermore, intra-articular injection of recombinant Sparcl1 protein in ACLT mice could promote OA pathogenesis. Mechanistically, Sparcl1 activated TNF/NF-κB pathway and consequently led to increased transcription of inflammatory factors and catabolism genes of cartilage, which could be reversed by NF-κB inhibitor BAY 11-7082. Conclusion: SPARCL1 could promote extracellular matrix degradation and inflammatory response to accelerate OA progression via TNF/NF-κB pathway. The translational potential of this article: The current research could help to gain further insights into the underlying molecular mechanism in OA development, and provides a biological rationale for the use of SPARCL1 as a potential therapeutic target of OA.

Magnoflorine Ameliorates Chronic Kidney Disease in High-Fat and High-Fructose-Fed Mice by Promoting Parkin/PINK1-Dependent Mitophagy to Inhibit NLRP3/Caspase-1-Mediated Pyroptosis.

Excessive intake of fat and fructose in Western diets has been confirmed to induce renal lipotoxicity, thereby driving the progression of chronic kidney disease (CKD). This study was conducted to evaluate the efficacy of magnoflorine in a CKD mouse model subjected to high-fat and high-fructose diets. Our results demonstrated that magnoflorine treatment ameliorated abnormal renal function indices (serum creatinine, urea nitrogen, uric acid, and urine protein) in high-fat- and high-fructose-fed mice. Histologically, renal tubular cell steatosis, lipid deposition, tubular dilatation, and glomerular fibrosis were significantly reduced by the magnoflorine treatment in these mice. Mechanistically, magnoflorine promotes Parkin/PINK1-mediated mitophagy, thereby inhibiting NLRP3/Caspase-1-mediated pyroptosis. Consistent findings were observed in the palmitic acid-incubated HK-2 cell model. Notably, both silencing of Parkin and the use of a mitophagy inhibitor reversed the inhibitory effect of magnoflorine on NLRP3 inflammasome activation in vitro. Therefore, the present study provides compelling evidence that magnoflorine improves renal injury in high-fat- and high-fructose-fed mice by promoting Parkin/PINK1-dependent mitophagy to inhibit NLRP3 inflammasome activation and pyroptosis. Our findings suggest that dietary supplementation with magnoflorine and magnoflorine-rich foods (such as magnolia) might be an effective strategy for the prevention of CKD.