Curcumin inhibits PAT-induced renal ferroptosis via the p62/Keap1/Nrf2 signalling pathway.

Patulin (PAT), the most common mycotoxin, is widespread in foods and beverages which poses a serious food safety issue to human health. Our previous research confirmed that exposure to PAT can lead to acute kidney injury (AKI). Curcumin is the most abundant active ingredient in turmeric rhizome with various biological activities. The aim of this study is to investigate whether curcumin can prevent the renal injury caused by PAT, and to explore potential mechanisms. In vivo, supplementation with curcumin attenuated PAT-induced ferroptosis. Mechanically, curcumin inhibited autophagy, led to the accumulation of p62 and its interaction with Keap1, promoted the nuclear translocation of nuclear factor E2 related factor 2 (Nrf2), and increased the expression of antioxidant stress factors in the process of ferroptosis. These results have also been confirmed in HKC cell experiments. Furthermore, knockdown of Nrf2 in HKC cells abrogated the protective effect of curcumin on ferroptosis. In conclusion, we confirmed that curcumin mitigated PAT-induced AKI by inhibiting ferroptosis via activation of the p62/Keap1/Nrf2 pathway. This study provides new potential targets and ideas for the prevention and treatment of PAT.

The Protective Effects of Curcumin against Renal Toxicity.

Curcumin is a naturally polyphenolic compound used for hepatoprotective, thrombosuppressive, neuroprotective, cardioprotective, antineoplastic, antiproliferative, hypoglycemic, and antiarthritic effects. Kidney disease is a major public health problem associated with severe clinical complications worldwide. The protective effects of curcumin against nephrotoxicity have been evaluated in several experimental models. In this review, we discussed how curcumin exerts its protective effect against renal toxicity and also illustrated the mechanisms of action such as anti-inflammatory, antioxidant, regulating cell death, and anti-fibrotic. This provides new perspectives and directions for the clinical guidance and molecular mechanisms for the treatment of renal diseases by curcumin.

Combination of a human articular cartilage-derived extracellular matrix scaffold and microfracture techniques for cartilage regeneration: A proof of concept in a sheep model.

Background: The utilization of decellularized extracellular matrix has gained considerable attention across numerous areas in regenerative research. Of particular interest is the human articular cartilage-derived extracellular matrix (hACECM), which presents as a promising facilitator for cartilage regeneration. Concurrently, the microfracture (MF) â€‹technique, a well-established marrow stimulation method, has proven efficacious in the repair of cartilage defects. However, as of the current literature review, no investigations have explored the potential of a combined application of hACECM and the microfracture technique in the repair of cartilage defects within a sheep model. Hypothesis: The combination of hACECM scaffold and microfracture will result in improved repair of full-thickness femoral condyle articular cartilage defects compared to the use of either technique alone. Study design: Controlled laboratory study. Methods: Full-thickness femoral condyle articular cartilage defect (diameter, 7.0 â€‹mm; debrided down to the subchondral bone plate) were created in the weight-bearing area of the femoral medial and lateral condyles (n â€‹= â€‹24). All of defected sheep were randomly divided into four groups: control, microfracture, hACECM scaffold, and hACECM scaffold â€‹+ â€‹microfracture. After 3, 6 and 12 months, the chondral repair was assessed for standardized (semi-) quantitative macroscopic, imaging, histological, immunohistochemical, mechanics, and biochemical analyses in each group. Result: At 3, 6 and 12 months after implantation, the gross view and pathological staining of regenerative tissues were better in the hACECM scaffold and hACECM scaffold â€‹+ â€‹microfracture groups than in the microfracture and control groups; Micro-CT result showed that the parameters about the calcified layer of cartilage and subchondral bone were better in the hACECM scaffold and hACECM scaffold â€‹+ â€‹microfracture groups than the others, and excessive subchondral bone proliferation in the microfracture group. The results demonstrate that human cartilage extracellular matrix scaffold alone is an efficient, safe and simple way to repair cartilage defects. Conclusion: hACECM scaffolds combined with/without microfracture facilitate chondral defect repair. The translational potential of this article: Preclinical large animal models represent an important adjunct and surrogate for studies on articular cartilage repair, while the sheep stifle joint reflects many key features of the human knee and are therefore optimal experimental model for future clinical application in human. In this study, we developed a human articular cartilage-derived extracellular matrix scaffold and to verify the viability of its use in sheep animal models. Clinical studies are warranted to further quantify the effects of hACECM scaffolds in similar settings.

Association of air pollution and risk of chronic kidney disease: A systematic review and meta-analysis.

Although epidemiological studies have evaluated the association between ambient air pollution and chronic kidney disease (CKD), the results remain mixed. To clarify the nature of the association, we conducted a comprehensive systematic review and meta-analysis to assess the global relationship between air pollution and CKD. The Web of Science, PubMed, Embase and Cochrane Library databases systematically were searched for studies published up to July 2023 and included 32 studies that met specific criteria. The random effects model was used to derive overall risk estimates for each pollutant. The meta-analysis estimated odds ratio (ORs) of risk for CKD were 1.42 (95% confidence interval [CI]: 1.31-1.54) for each 10 µg/m3 increase in PM2.5 ; 1.20 (95% CI: 1.14-1.26) for each 10 µg/m3 increase in PM10 ; 1.07 (95% CI: 1.05-1.09) for each 10 µg/m3 increase in NO2 ; 1.03 (95% CI: 1.02-1.03) for each 10 µg/m3 increase in NOX ; 1.07 (95% CI: 1.01-1.12) for each 1 ppb increase in SO2 ; 1.03 (95% CI: 1.00-1.05) for each 0.1 ppm increase in CO. Subgroup analysis showed that this effect varied by gender ratio, age, study design, exposure assessment method, and income level. Furthermore, PM2.5 , PM10 , and NO2 had negative effects on CKD even within the World Health Organization-recommended acceptable concentrations. Our results further confirmed the adverse effect of air pollution on the risk of CKD. These findings can contribute to enhance the awareness of the importance of reducing air pollution among public health officials and policymakers.

Sleep Duration and Insomnia with Comorbid Depression and Anxiety Symptoms in Chinese Adults: A Cross-Sectional Study.

Purpose: Depression and anxiety are two highly prevalent mental disorders that commonly coexist. However, little is known about the association between sleep and comorbid depressive and anxiety symptoms (CDAS). Therefore, this study aims to explore the relationship between sleep duration, insomnia and CDAS. Methods: This is a cross-sectional study of 22,004 community adults who participated in the China Multi-Ethnic Cohort (CMEC) study. Chinese version of Patient Health Questionnaire-2 and Generalized Anxiety Disorder-2 were used to screen CDAS in community adults. A positive score on each scale was considered indicative of CDAS. All participants received face-to-face interviews, medical examinations, and biochemical examinations to assess sleep duration and insomnia and collect covariates. The self-reported sleep duration was divided into three groups: <7 hr, 7-9 hr and >9 hr groups. Logistic regression was used to analyze the association between sleep duration, insomnia and CDAS. A restricted cubic spline (RCS) was used to explore the dose-response relationship between sleep duration and CDAS. Stratified analysis based on gender and age was conducted. Results: Overall, 2.8% (95% CI 2.6%~3.0%) of participants reported having CDAS. After adjusting the potential covariates, sleep duration <7 hr (OR=1.635, 95% CI=1.335~2.004) was significantly associated with CDAS, compared with sleep 7-9 hr. After RCS analysis, there was a nonlinear relationship between sleep duration and CDAS. The increase in the number of types of insomnia, the greater the likelihood of CDAS (p for trend<0.05). In sensitivity analysis, it was found that the results were consistent with those of the main analysis. After stratification by gender and age, the association between sleep duration and CDAS was only observed in female and young and middle-aged adults, not in men and older adults. Conclusion: Both insufficient sleep duration and insomnia are associated with a higher prevalence of CDAS in Chinese adults.

Association between leisure sedentary behaviour and uterine fibroids in non-menopausal women: a population-based study.

OBJECTIVE: Sedentary behaviour is associated with a variety of adverse health outcomes, including obesity, oestrogen metabolism and chronic inflammation, all of which are related to the pathogenesis of uterine fibroids (UFs). This study aimed to explore the relationship between leisure sedentary time (LST) and UFs. DESIGN: Cross-sectional. SETTING: We conducted a cross-sectional analysis of data from patients from the Yunnan region in the China Multi-Ethnic Cohort Study. PARTICIPANTS: A total of 6623 non-menopausal women aged 30-55 years old were recruited. Menstrual status was self-reported. Participants who lacked a unique national identity card, suffered from serious mental illness, did not have a clear diagnosis of UFs, or provided incomplete information were excluded. PRIMARY AND SECONDARY OUTCOME: UFs were diagnosed by abdominal B-ultrasound. Leisure sedentary behaviour was assessed by using a face-to-face questionnaire interview. Logistic regression and restricted cubic spline were employed to explore the relationship between LST and UFs. RESULTS: A total of 562 participants had UFs, with a prevalence rate of 8.5% (7.8%, 9.2%). Multivariate adjusted logistic regression analysis showed that the risk of UFs in women with LST≥6 hour/day was 2.008 times that in women with LST<2 hour/day (95% CI 1.230 to 3.279). The restricted cubic spline results showed that there was a linear dose‒response relationship between LST and UFs (p for non-linearity>0.05). According to the results of the stratified analysis for menstrual status and body mass index (BMI), there was a correlation between LST and the prevalence of UFs only in women with a BMI<24 kg/m2 or perimenopause. CONCLUSION: LST was independently associated with the prevalence of UFs, and a linear dose‒response relationship was observed. Our study provides evidence on the factors influencing UFs, and further research is needed to propose feasible measures for UFs prevention.

Mitochondrial dysfunction and endoplasmic reticulum stress induced by activation of PPARα leaded testicular to apoptosis in SD rats explored to di-(2-ethylhexyl) phthalate (DEHP).

Di-2-ethylhexyl phthalate (DEHP), as a common endocrine disrupting chemicals, can induce toxicity to reproductive system. However, the mechanism remains to be explored. In our study, DEHP exposure induced testicular injury in rats. The high throughput transcriptional sequencing was performed to identify differentially expressed genes (DEGs) between the treatment and control groups. KEGG analysis revealed that DEGs were enriched in apoptosis, PPARα, and ER stress pathway. DEHP up-regulated the expression of PPARα, Bax, Bim, caspase-4. GRP78, PERK, p-PERK, eIF2α, p-eIF2α, ATF4 and CHOP. This view has also been confirmed in TM3 and TM4 cells. In vitro, after pre-treatment with GW6471 (an inhibitor of PPARα) or GSK (an inhibitor of PERK), the apoptosis was inhibited and mitochondrial dysfunction was improved. Moreover, the improvement of mitochondrial dysfunction decreased the expression of PERK pathway by using SS-31(a protective agent for mitochondrial function). Interestingly, ER stress promoted the accumulation of ROS by ERO1L (the downstream of CHOP during ER stress), and the ROS further aggravated the ER stress, thus forming a feedback loop during the apoptosis. In this process, a vicious cycle consisting of PERK, eIF2α, ATF4, CHOP, ERO1L, ROS was involved. Taken together, our results suggested that mitochondrial dysfunction and ER stress-ROS feedback loop caused by PPARα activation played a crucial role in DEHP-induced apoptosis. This work provides insight into the mechanism of DEHP-induced reproductive toxicity.

Advancing drug delivery to articular cartilage: From single to multiple strategies.

Articular cartilage (AC) injuries often lead to cartilage degeneration and may ultimately result in osteoarthritis (OA) due to the limited self-repair ability. To date, numerous intra-articular delivery systems carrying various therapeutic agents have been developed to improve therapeutic localization and retention, optimize controlled drug release profiles and target different pathological processes. Due to the complex and multifactorial characteristics of cartilage injury pathology and heterogeneity of the cartilage structure deposited within a dense matrix, delivery systems loaded with a single therapeutic agent are hindered from reaching multiple targets in a spatiotemporal matched manner and thus fail to mimic the natural processes of biosynthesis, compromising the goal of full cartilage regeneration. Emerging evidence highlights the importance of sequential delivery strategies targeting multiple pathological processes. In this review, we first summarize the current status and progress achieved in single-drug delivery strategies for the treatment of AC diseases. Subsequently, we focus mainly on advances in multiple drug delivery applications, including sequential release formulations targeting various pathological processes, synergistic targeting of the same pathological process, the spatial distribution in multiple tissues, and heterogeneous regeneration. We hope that this review will inspire the rational design of intra-articular drug delivery systems (DDSs) in the future.

Asymptomatic hyperuricemia associated with increased risk of nephrolithiasis: a cross-sectional study.

BACKGROUND: Existing evidence shows that there is an independent correlation between nephrolithiasis and gout, and hyperuricemia is the most important risk factor for gout. However, hyperuricemia was often used as an accompanying symptom of gout to explore its association with nephrolithiasis, there were few studies to explore whether hyperuricemia itself or serum uric acid (SUA) is related to the risk of nephrolithiasis. Evidence on the relationship between hyperuricemia and nephrolithiasis is still insufficient. METHODS: A total of 22,303 participants aged 30 to 79 years who participated in the China Multi-Ethnic Cohort (CMEC) study in Yunnan Province from May 2018 to September 2019 were included in the study. All participants received standardized face-to-face interviews, medical examinations, and biochemical examinations. Logistic regression was used to estimate the association between hyperuricemia and nephrolithiasis, and a restricted cubic spline (RCS) model was used to explore the dose-response relationship between SUA and the risk of nephrolithiasis. RESULTS: 14.5% of all participants were diagnosed with hyperuricemia, and 12.1% were diagnosed with nephrolithiasis. After adjusting for all potential confounders, the OR (95%CI) for nephrolithiasis in participants with hyperuricemia compared with participants without hyperuricemia was 1.464 (1.312,1.633), p < 0.001. Restricted cubic spline regression analysis showed that the risk of nephrolithiasis increased with the increase of SUA, and when the level of SUA is higher than 356 µmol/L in males and higher than 265 µmol/L in females, there is a dose-response relationship between the increase of SUA and the risk of nephrolithiasis in both males and females (p for nonlinearity = 0.1668, p for nonlinearity = 0.0667). CONCLUSION: Asymptomatic hyperuricemia is associated with an increased risk of developing nephrolithiasis. Before reaching the diagnostic criteria for hyperuricemia, the risk of nephrolithiasis rises with the increase in SUA. This suggests that controlling SUA levels may be significant for the prevention of nephrolithiasis.

Visualization and bibliometric analysis of 3D printing in cartilage regeneration.

The self-repair ability of cartilage defects is limited, and 3D printing technology provides hope for the repair and regeneration of cartilage defects. Although 3D printing technology and cartilage repair and regeneration have been studied for decades, there are still few articles specifically describing the relationship between 3D printing and cartilage defect repair and regeneration, and a bibliometric analysis has not been completed. To supplement, sort out and summarize the content in related fields, we analyzed the research status of 3D printing technology and cartilage repair and regeneration from 2002 to 2022. According to the set search strategy, the Web of Science Core Collection was used as the data source, and the literature search was completed on December 6, 2022. CiteSpace V and VOSviewer were used as bibliometric tools to complete the analysis of the research focus and direction of the published literature. Based on the analysis results, we focus on the occurrence and development of this field of combined medical and engineering research. Moreover, the current advantages and limitations of this field as well as future development prospects are discussed in depth. It will help to shape researchers' understanding of 3D printing and cartilage repair and regeneration, inspire researchers' research ideas, guide research directions, and promote related research results to clinical application.

Mechanism of testicular injury induced by Di-ethylhexyl phthalate and its protective agents.

Di-ethylhexyl phthalate (DEHP) is used as an important plasticizer in a wide range of products such as paints, food packaging, medical devices and children's toys. In recent years, there has been increasing interest in the toxic effects of DEHP on the male reproductive organs, the testicles. Here, we reviewed the basic pathways of testicular damage caused by DEHP. The mechanism involves oxidative stress, ferroptosis, interfering with hypothalamic-pituitary-gonadal axis (HPGA) and testosterone level. We summarized the protective agents that have been shown to be effective in repairing this type of testicular damage in recent years. This provides a new perspective and direction for future research into the health effects and molecular mechanisms of DEHP.

Engineering exosomes by three-dimensional porous scaffold culture of human umbilical cord mesenchymal stem cells promote osteochondral repair.

Improving the poor microenvironment in the joint cavity has potential for treating cartilage injury, and mesenchymal stem cell (MSC)-derived exosomes (MSC-Exos), which can modulate cellular behavior, are becoming a new cell-free therapy for cartilage repair. Here, we used acellular cartilage extracellular matrix (ACECM) to prepare 3D scaffolds and 2D substrates by low-temperature deposition modeling (LDM) and tape casting. We aimed to investigate whether MSC-Exos cultured on scaffolds of different dimensions could improve the poor joint cavity microenvironment caused by cartilage injury and to explore the related mechanisms. In vitro experiments showed that exosomes derived from MSCs cultured on three-dimensional (3D) scaffolds (3D-Exos) had increased efficiency. In short-term animal experiments, compared with exosomes derived from MSCs cultured in a two-dimensional (2D) environment (2D-Exos), 3D-Exos had a stronger ability to regulate the joint cavity microenvironment. Long-term animal studies confirmed the therapeutic efficacy of 3D-Exos over 2D-Exos. Thus, 3D-Exos were applied in the rat knee osteochondral defect model after adsorption in the micropores of the scaffold and combined with subsequent articular cavity injections, and they showed a stronger cartilage repair ability. These findings provide a new strategy for repairing articular cartilage damage. Furthermore, miRNA sequencing indicated that the function of 3D-Exos may be associated with high expression of miRNAs. Thus, our study provides valuable insights for the design of 3D-Exos to promote cartilage regeneration.

Triethanolamine-assisted synthesis of NiFe layered double hydroxide ultrathin nanosheets for efficient oxygen evolution reaction.

Water electrolysis is a promising technique for producing high-quality hydrogen, the application of which is impeded by the sluggish oxygen evolution reaction (OER) process. In this study, ultrathin nickel-iron layered double hydroxide (NiFe LDH) nanosheets were successfully synthesized through a facile hydrothermal reaction with the assistance of triethanolamine (TEA). Morphological and structural characterizations revealed that the presence of TEA modified the morphology of NiFe LDH, facilitated the synthesis of high-purity NiFe LDH, improved the crystallinity of NiFe LDH and resulted in a slight decrease in specific surface area. X-ray photoelectron spectroscopy (XPS) analysis demonstrated the modulation of the electronic structure engendered by the addition of TEA, with nickel and iron appearing in high valence state in the resulting NiFe LDH nanosheets. The as-prepared NiFe LDH nanosheets possessed outstanding OER activity with fast kinetics, exhibiting a low overpotential of 261 mV to achieve a current density of 10 mA cm-2 and a small Tafel slope of 32.5 mV dec-1 in 1 M KOH. The excellent OER performance and rapid OER kinetics are mainly attributed to the high-valence Ni and Fe rather than the modification in the morphology and microstructure.

Mediating role of social capital on the association between negative life events and quality of life among adults in China: A population-based study.

Objective: To evaluate whether social capital played a mediating role in the relationship between negative life events (NLE) and quality of life (QoL) among adults in China after proposed a conceptual model based on stress buffering theory. Methods: A cross-sectional study was conducted based on baseline survey from the Chinese Multi-ethnic Cohort (CMEC) in Yunnan province. A total of 22,866 adults were recruited by multistage stratified cluster sampling. A structured questionnaire was used to collect the general demographic characteristics and the occurrence of NLE. A self-developed brief social capital scale was utilized to assess the social capital and the EQ-5D-5L scale was used to measure the QoL. The relationships among NLE, social capital and QoL were analyzed using multiple linear regression analyses. Structural equation models were used to evaluate whether social capital had a mediating effect on the relationship between NLE and QoL. The standardize coefficient (ß) and it's 95% confidence intervals (CI) were calculated in this process. Results: The mean age of participants was 52.70 years old. The mean of EQ-5D index value was 0.92 (SD = 0.12) and the mean of EQ-VAS score was 71.77 (SD = 13.80). NLE not only directly affected EQ-5D index value [ß = -0.127, 95% CI (-0.144, -0.110)] but also indirectly negatively affected EQ-5D index value through social capital [ß = -0.019, 95% CI (-0.023, -0.015)]. Social capital had a direct positive effect on EQ-5D index value [ß = 0.114, 95% CI (0.097, 0.133)]. A similar pattern was identified for the association between NLE and EQ-VAS score. The direct effect of NLE on EQ-VAS score was negatively significant [ß = -0.132, 95% CI (-0.146, -0.118)]. Moreover, the indirect effect through social capital was also negatively significant [ß = -0.022, 95% CI (-0.026, -0.019)]. There was a positive direct effect of social capital on EQ-VAS score [ß = 0.135, 95% CI (0.117, 0.151)]. Conclusion: Social capital played an important mediating role in the relationship between NLE and QoL, and it alleviated the negative effects of NLE on the QoL of the community residents in China. Providing reliable social capital for community residents experiencing NLE could effectively improve their quality of life.

Integrated bioactive scaffold with aptamer-targeted stem cell recruitment and growth factor-induced pro-differentiation effects for anisotropic meniscal regeneration.

Reconstruction of the knee meniscus remains a significant clinical challenge owing to its complex anisotropic tissue organization, complex functions, and limited healing capacity in the inner region. The development of in situ tissue-engineered meniscal scaffolds, which provide biochemical signaling to direct endogenous stem/progenitor cell (ESPC) behavior, has the potential to revolutionize meniscal tissue engineering. In this study, a fiber-reinforced porous scaffold was developed based on aptamer Apt19S-mediated mesenchymal stem cell (MSC)-specific recruitment and dual growth factor (GF)-enhanced meniscal differentiation. The aptamer, which can specifically recognize and recruit MSCs, was first chemically conjugated to the decellularized meniscus extracellular matrix (MECM) and then mixed with gelatin methacrylate (GelMA) to form a photocrosslinkable hydrogel. Second, connective tissue growth factor (CTGF)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and transforming growth factor-ß3 (TGF-ß3)-loaded PLGA microparticles (MPs) were mixed with aptamer-conjugated MECM to simulate anisotropic meniscal regeneration. These three bioactive molecules were delivered sequentially. Apt19S, which exhibited high binding affinity to synovium-derived MSCs (SMSCs), was quickly released to facilitate the mobilization of ESPCs. CTGF incorporated within PLGA NPs was released rapidly, inducing profibrogenic differentiation, while sustained release of TGF-ß3 in PLGA MPs remodeled the fibrous matrix into fibrocartilaginous matrix. The in vitro results showed that the sequential release of Apt19S/GFs promoted cell migration, proliferation, and fibrocartilaginous differentiation. The in vivo results demonstrated that the sequential release system of Apt/GF-scaffolds increased neomeniscal formation in rabbit critical-sized meniscectomies. Thus, the novel delivery system shows potential for guiding meniscal regeneration in situ.

Microenvironmentally optimized 3D-printed TGFß-functionalized scaffolds facilitate endogenous cartilage regeneration in sheep.

Clinically, microfracture is the most commonly applied surgical technique for cartilage defects. However, an increasing number of studies have shown that the clinical improvement remains questionable, and the reason remains unclear. Notably, recent discoveries revealed that signals from regenerated niches play a critical role in determining mesenchymal stem cell fate specification and differentiation. We speculate that a microenvironmentally optimized scaffold that directs mesenchymal stem cell fate will be a good therapeutic strategy for cartilage repair. Therefore, we first explored the deficiency of microfractures in cartilage repair. The microfracture not only induced inflammatory cell aggregation in blood clots but also consisted of loose granulation tissue with increased levels of proteins related to fibrogenesis. We then fabricated a functional cartilage scaffold using two strong bioactive cues, transforming growth factor-ß3 and decellularized cartilage extracellular matrix, to modulate the cell fate of mesenchymal stem cells. Additionally, poly(ε-caprolactone) was also coprinted with extracellular matrix-based bioinks to provide early mechanical support. The in vitro studies showed that microenvironmentally optimized scaffolds exert powerful effects on modulating the mesenchymal stem cell fate, such as promoting cell migration, proliferation and chondrogenesis. Importantly, this strategy achieved superior regeneration in sheep via scaffolds with biomechanics (restored well-organized collagen orientation) and antiapoptotic properties (cell death-related genes were also downregulated). In summary, this study provides evidence that microenvironmentally optimized scaffolds improve cartilage regeneration in situ by regulating the microenvironment and support further translation in human cartilage repair. STATEMENT OF SIGNIFICANCE: Although microfracture (MF)-based treatment for chondral defects has been commonly used, critical gaps exist in understanding the biochemistry of MF-induced repaired tissue. More importantly, the clinically unsatisfactory effects of MF treatment have prompted researchers to focus on tissue engineering scaffolds that may have sufficient therapeutic efficacy. In this manuscript, a 3D printing ink containing cartilage tissue-specific extracellular matrix (ECM), methacrylate gelatin (GelMA), and transforming growth factor-ß3 (TGF-ß3)-embedded polylactic-coglycolic acid (PLGA) microspheres was coprinted with poly(ε-caprolactone) (PCL) to fabricate tissue engineering scaffolds for chondral defect repair. The sustained release of TGF-ß3 from scaffolds successfully directed endogenous stem/progenitor cell migration and differentiation. This microenvironmentally optimized scaffold produced improved tissue repair outcomes in the sheep animal model, explicitly guiding more organized neotissue formation and therefore recapitulating the anisotropic structure of native articular cartilage. We hypothesized that the cell-free scaffolds might improve the clinical applicability and become a new therapeutic option for chondral defect repair.

Depressive Symptoms and ADL/IADL Disabilities Among Older Adults from Low-Income Families in Dalian, Liaoning.

Purpose: This study aimed to assess the prevalence of depressive symptoms and ADL/IADL disabilities and explore their correlation and associated factors for depressive symptoms among community-dwelling older adults from low-income families in Dalian, Liaoning Province, China. Methods: This cross-sectional study included 522 participants aged 60 years and older from low-income families in Dalian. The 30-Item Geriatric Depression Scale was employed to measure depressive symptoms. The Katz ADL Scale and IADL Scale were used to evaluate the performance of activities necessary for independent life. SPSS 22.0 was employed to analyze the data. Logistic regression was used to estimate the relationship between depressive symptoms and ADL/IADL disabilities in five models. Results: The prevalence of depressive symptoms among older people from low-income families in Dalian was 57.3%. A total of 19.0% had difficulties performing ADLs, and 40.2% had difficulties performing IADLs. Logistic regression analysis revealed that ADL/IADL disabilities were associated with depressive symptoms even after controlling for people's sociodemographic characteristics, welfare, health conditions and informal care. The following factors were associated with depressive symptoms: education, self-reported health, number of chronic diseases, and emotional support from families. Conclusion: Given that older people from low-income families in Dalian have a notable prevalence rate of depressive symptoms, and ADL/IADL disabilities were independently associated with these symptoms, it is crucial to give priority to this particular group in geriatric health services due to economic and health disparities.

Patulin Induces Acute Kidney Injury in Mice through Autophagy-Ferroptosis Pathway.

Patulin (PAT) is a common mycotoxin, widely found in cereals, seafood, nuts, and especially in fruits and their products. Exposure to this mycotoxin has been reported to induce kidney injury. However, the possible mechanism remains unclear. In our study, short-term high-dose intake of PAT caused acute kidney injury (AKI) in mice. We performed high-throughput transcriptional sequencing to identify differentially expressed genes (DEGs) between the treatment and control groups. The ferroptosis signaling pathway had the highest enrichment, suggesting ferroptosis is involved in PAT-induced AKI. Further, the existence of ferroptosis and autophagy was confirmed by observing the changes of mitochondria morphology and the formation of autophagosomes by electron microscopy. And the expression of solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), p62, nuclear receptor coactivator 4 (NCOA4), and ferritin heavy chain 1 (FTH1) were downregulated, whereas acyl-CoA synthase long-chain family member 4 (ACSL4), transferrin (TF), LC3, and ferritin light chain (FTL) expression were upregulated in PAT-exposed mice. These results suggested autophagy-dependent ferroptosis occurred in the animal model. This view has also been confirmed in the human renal tubular epithelial cell (HKC) experiments. Autophagy inhibitor 3-methyladenine (3MA) attenuated PAT-induced ferroptosis and the iron contents in HKC cells. Simultaneous autophagy-dependent ferroptosis can be inhibited by ferroptosis inhibitors ferrostatin-1 (Fer-1) and desferrioxamine (DFO). In general, this study provides a new perspective for exploring the new mechanism of acute kidney injury caused by PAT.

Oxidation Mechanism of Core-Shell Structured Al@PVDF Powders Synthesized by Solvent/Non-Solvent Method.

Micron-sized aluminum (Al) powders are extensively added to energy-containing materials to enhance the overall reactivity of the materials. However, low oxidation efficiency and energy release limit the practical application of Al powders. Polyvinylidene fluoride (PVDF), the most common fluoropolymer, can easily react with Al to form aluminum fluoride (AlF3), thus promoting the oxidation of Al powders. In this paper, core-shell structured Al@PVDF powders were synthesized by solvent/non-solvent method. Thermal analysis results show that the weight and exothermic enthalpy of Al@PVDF powders are 166.10% and 11,976 J/g, which are superior to pure Al powders (140.06%, 6560 J/g). A detailed description of the oxidation mechanisms involved is provided. Furthermore, constant volume pressure results indicate that Al@PVDF powders have outstanding pressure output ability in the environment of 3 MPa oxygen. The study provides a valuable reference for the application of Al powders in energetic materials.

DEHP induces ferroptosis in testes via p38α-lipid ROS circulation and destroys the BTB integrity.

Exposure to Di (2-ethylhexyl) phthalate (DEHP) has been associated with toxic effects of the reproductive system. However, the exact mechanism remains to be elucidated. In this study we explored the testicular toxicity induced by DEHP, and the probable molecular mechanism in the process. In vivo, the results demonstrated that DEHP affected testosterone levels and blood-testosterone barrier (BTB) integrity and caused ferroptosis. We further demonstrated that DEHP up-regulated the expression of p38α, p-p38α, p53, p-p53, SAT1, ALOX15. This view has also been confirmed in TM4 cells. After pre-treatment with fer-1 or si-MAPK14, the expression of either p53, p-p53, SAT1 and ALOX15 up-regulated by MEHP was inhibited in vitro. Interestingly, p38α can prevent the accumulation of lipid ROS, and the production of lipid ROS in turn promoted the expression of p38α, thus forming a feedback loop during the ferroptosis. In this process, a vicious cycle consisting of p38α, p53, SAT1, ALOX15, lipid ROS was involved. This study provides new mechanistic insights into DEHP-induced toxicity of the reproductive system.