Men are particularly sensitive to penis size,especially those with a deformed or injured penis.This can lead to a strong desire for penis enlargement surgery.Given the ethical sensitivities of the penis,penile implant...Men are particularly sensitive to penis size,especially those with a deformed or injured penis.This can lead to a strong desire for penis enlargement surgery.Given the ethical sensitivities of the penis,penile implants need to be developed with both efficacy and safety.In this study,a polyvinyl alcohol(PVA)patch for penile enlargement prepared via cyclic freeze‒thaw cycles and alkaline treatment.The PVA hydrogels treated with 5 M NaOH had the best mechanical properties and stability.A negative Poisson’s ratio structure is incorporated into the design of the enlargement patch,which allows it to conform well to the deformation of the penis.In rabbit models,the enlarged patches can effectively enlarge the penis without degradation or fibrosis while maintaining long-term stability in vivo.This innovation not only provides a safe option for patients in need of penile enlargement but also promises to make a broader contribution to the field of dynamic tissue repair.展开更多
Renal unilateral ischemia-reperfusion injury(UIRI)constitutes a significant global health challenge,with poor recovery leading to chronic kidney disease and subsequent renal fibrosis.Extracellular vesicles(EVs)present...Renal unilateral ischemia-reperfusion injury(UIRI)constitutes a significant global health challenge,with poor recovery leading to chronic kidney disease and subsequent renal fibrosis.Extracellular vesicles(EVs)present substantial potential benefits for renal diseases.However,the limited yield and efficacy of EVs produced through traditional methodologies(2D-EVs)severely restrict their widespread application.Moreover,the efficient and effective strategies for using EVs in UIRI treatment and their mechanisms remain largely unexplored.In this study,we propose an innovative approach by integrating bioprinted mesenchymal stem cell microfiber extracellular vesicles production technology(3D-EVs)with a tail vein injection method,introducing a novel treatment strategy for UIRI.Our comparison of the biological functions of 2D-EVs and 3D-EVs,both in vitro and in vivo,reveals that 3D-EVs significantly outperform 2D-EVs.Specifically,in vitro,3D-EVs demonstrate a superior capacity to enhance the proliferation and migration of NRK-52E cells and mitigate hypoxia/reoxygenation(H/R)-induced injuries by reducing epithelial-mesenchymal transformation,extracellular matrix deposition,and ferroptosis.In vivo,3D-EVs exhibit enhanced therapeutic effects,as evidenced by improved renal function and decreased collagen deposition in UIRI mouse kidneys.We further elucidate the mechanism by which 3D-EVs derived from KLF15 ameliorate UIRI-induced tubular epithelial cells(TECs)ferroptosis through the modulation of SLC7A11 and GPX4 expression.Our findings suggest that bioprinted mesenchymal stem cells microfiberderived EVs significantly ameliorate renal UIRI,opening new avenues for effective and efficient EV-based therapies in UIRI treatment.展开更多
The authors regret that two images in Fig.3A were originally misplaced by a careless mistake.The corrected versions of these images are provided below.These corrections do not alter any findings and conclusions report...The authors regret that two images in Fig.3A were originally misplaced by a careless mistake.The corrected versions of these images are provided below.These corrections do not alter any findings and conclusions reported in this article.No additional text corrections are needed in the article.The authors would like to apologise for any inconvenience caused.展开更多
Many hydrogen-bonded cross-linked hydrogels possess unique properties,but their limited processability hinders their potential applications.By incorporating a hydrogen bond dissociator(HBD)into these hydrogels,we deve...Many hydrogen-bonded cross-linked hydrogels possess unique properties,but their limited processability hinders their potential applications.By incorporating a hydrogen bond dissociator(HBD)into these hydrogels,we developed injectable 3D printing inks termed diffusion-induced phase separation(DIPS)3D printing inks.Upon extrusion into water and subsequent diffusion of HBD,these ink cure rapidly.The DIPS-printed scaffold retained most of the original hydrogel properties due to the regeneration of hydrogen bonds.Additionally,the reversible nature of hydrogen bonds provides DIPS 3D-printed scaffolds with exceptional recycling and reprinting capabilities,resulting in a reduction in the waste of valuable raw ink materials or additives.Postprocessing introduces new crosslinking methods that modulate the mechanical properties and degradation characteristics of DIPS scaffolds over a broad range.Based on its suitable mechanical properties and bioactivity,we successfully repaired and functionally reconstructed a complex defect in penile erectile tissue using the DIPS scaffold in a rabbit model.In summary,this approach is relevant for various hydrogen-bonded cross-linked hydrogels that offer mild printing conditions and enable the incorporation of bioactive agents.They can be used as scaffolds for dynamic tissue reconstruction,wearable devices,or soft robots.展开更多
Copy number variations(CNVs), which can affect the role of long non-coding RNAs(lncRNAs), are important genetic changes seen in some malignant tumors. We analyzed lncRNAs with CNV to explore the relationship between l...Copy number variations(CNVs), which can affect the role of long non-coding RNAs(lncRNAs), are important genetic changes seen in some malignant tumors. We analyzed lncRNAs with CNV to explore the relationship between lncRNAs and prognosis in bladder cancer(BLCA). Messenger RNA(mRNA) expression levels, DNA methylation, and DNA copy number data of 408 BLCA patients were subjected to integrative bioinformatics analysis. Cluster analysis was performed to obtain different subtypes and differently expressed lncRNAs and coding genes. Weighted gene co-expression network analysis(WGCNA) was performed to identify the co-expression gene and lncRNA modules. CNV-associated lncRNA data and their influence on cancer prognosis were assessed with Kaplan-Meier survival curve. Multi-omics integration analysis revealed five prognostic lncRNAs with CNV, namely NR2 F1-AS1, LINC01138, THUMPD3-AS1, LOC101928489, and TMEM147-AS1, and a risk-score signature related to overall survival in BLCA was identified. Moreover, validated results in another independent Gene Expression Omnibus(GEO) dataset, GSE31684, were consistent with these results. Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis revealed that the mitogen-activated protein kinase(MAPK) signaling pathway, focal adhesion pathway, and Janus kinase-signal transducers and activators of transcription(JAK-STAT) signaling pathway were enriched in a high-risk score pattern, suggesting that imbalance in these pathways is closely related to tumor development. We revealed the prognosis-related lncRNAs by analyzing the expression profiles of lncRNAs and CNVs, which can be used as prognostic biomarkers for BLCA.展开更多
The aim of this paper is to investigate the clin-ical features and transformation of elderly male patients with normal blood glucose levels at fasting and 2 hours after glucose intake but with hyperglycemia(>11.1 m...The aim of this paper is to investigate the clin-ical features and transformation of elderly male patients with normal blood glucose levels at fasting and 2 hours after glucose intake but with hyperglycemia(>11.1 mmol/L)1 hour after oral glucose tolerance test(OGTT-1h HG).Seven years of follow-up visits were per-formed on 189 elderly male outpatients with OGTT-1h HG and data was recorded on their body mass index(BMI),blood pressure,serum cholesterol and triglyceride test results and on their glucose tolerance changes every 1–2 years after taking OGTT;their possible causes were analysed.Follow-up visits revealed that 19 patients with OGTT-1h HG were diagnosed with diabetes(10.1%),78 patients with impaired glucose tolerance(IGT,41.3%),2 patients transformed to normal glucose tolerance(NGT,1.1%)and the remaining 90 patients(47.6%)remained unchanged.Synchronized comparison with IGT patients showed that the ratio of OGTT-1h HG patients turning to diabetes was lower than that of IGT patients(21.1%,x2513.05,P,0.01),and the ratio of OGTT-1h HG patients transforming to NGT was slightly higher(0.4%,x252.46,P.0.05).The prevalence of complications of hypertension,coronary heart disease,cerebral vascular diseases and dyslipidemia in patients with OGTT-1h HG were higher than those with NGT(P,0.05)and were similar to that of IGT patients.As a special phenotype of OGTT and as part of an abnormal glucose tolerance con-formation,patients with OGTT-1h HG warrant special attention,since about half of them were found to have developed diabetes or IGT,and their risk of suffering from vascular diseases were also increased.展开更多
基金the financial support from the National Key Research and Development Program of China(2021YFB3800800)the National Natural Science Foundation of China(U22A20157,32401141)+2 种基金the Guangdong Basic and Applied Basic Research Foundation(2022B1515130010,2023A1515110794,2024B1515040030)the Postdoctoral Fellowship Program of CPSF under Grant Number GZC20231080the China Postdoctoral Science Foundation(2024M751311).
文摘Men are particularly sensitive to penis size,especially those with a deformed or injured penis.This can lead to a strong desire for penis enlargement surgery.Given the ethical sensitivities of the penis,penile implants need to be developed with both efficacy and safety.In this study,a polyvinyl alcohol(PVA)patch for penile enlargement prepared via cyclic freeze‒thaw cycles and alkaline treatment.The PVA hydrogels treated with 5 M NaOH had the best mechanical properties and stability.A negative Poisson’s ratio structure is incorporated into the design of the enlargement patch,which allows it to conform well to the deformation of the penis.In rabbit models,the enlarged patches can effectively enlarge the penis without degradation or fibrosis while maintaining long-term stability in vivo.This innovation not only provides a safe option for patients in need of penile enlargement but also promises to make a broader contribution to the field of dynamic tissue repair.
基金supported by the Natural Science Foundation of China(Grant No.52075285)the Natural Science Foundation of Guang Dong Province(2019A1515010386,2024A1515010266).
文摘Renal unilateral ischemia-reperfusion injury(UIRI)constitutes a significant global health challenge,with poor recovery leading to chronic kidney disease and subsequent renal fibrosis.Extracellular vesicles(EVs)present substantial potential benefits for renal diseases.However,the limited yield and efficacy of EVs produced through traditional methodologies(2D-EVs)severely restrict their widespread application.Moreover,the efficient and effective strategies for using EVs in UIRI treatment and their mechanisms remain largely unexplored.In this study,we propose an innovative approach by integrating bioprinted mesenchymal stem cell microfiber extracellular vesicles production technology(3D-EVs)with a tail vein injection method,introducing a novel treatment strategy for UIRI.Our comparison of the biological functions of 2D-EVs and 3D-EVs,both in vitro and in vivo,reveals that 3D-EVs significantly outperform 2D-EVs.Specifically,in vitro,3D-EVs demonstrate a superior capacity to enhance the proliferation and migration of NRK-52E cells and mitigate hypoxia/reoxygenation(H/R)-induced injuries by reducing epithelial-mesenchymal transformation,extracellular matrix deposition,and ferroptosis.In vivo,3D-EVs exhibit enhanced therapeutic effects,as evidenced by improved renal function and decreased collagen deposition in UIRI mouse kidneys.We further elucidate the mechanism by which 3D-EVs derived from KLF15 ameliorate UIRI-induced tubular epithelial cells(TECs)ferroptosis through the modulation of SLC7A11 and GPX4 expression.Our findings suggest that bioprinted mesenchymal stem cells microfiberderived EVs significantly ameliorate renal UIRI,opening new avenues for effective and efficient EV-based therapies in UIRI treatment.
文摘The authors regret that two images in Fig.3A were originally misplaced by a careless mistake.The corrected versions of these images are provided below.These corrections do not alter any findings and conclusions reported in this article.No additional text corrections are needed in the article.The authors would like to apologise for any inconvenience caused.
基金National Funded Postdoctoral Researcher Program,Grant/Award Number:GZC20231080National Key Research and Development Program of China,Grant/Award Number:2021YFB3800800+1 种基金Guangdong Basic and Applied Basic Research Foundation,Grant/Award Numbers:2022B1515130010,2023A1515110794National Natural Science Foundation of China,Grant/Award Number:U22A20157。
文摘Many hydrogen-bonded cross-linked hydrogels possess unique properties,but their limited processability hinders their potential applications.By incorporating a hydrogen bond dissociator(HBD)into these hydrogels,we developed injectable 3D printing inks termed diffusion-induced phase separation(DIPS)3D printing inks.Upon extrusion into water and subsequent diffusion of HBD,these ink cure rapidly.The DIPS-printed scaffold retained most of the original hydrogel properties due to the regeneration of hydrogen bonds.Additionally,the reversible nature of hydrogen bonds provides DIPS 3D-printed scaffolds with exceptional recycling and reprinting capabilities,resulting in a reduction in the waste of valuable raw ink materials or additives.Postprocessing introduces new crosslinking methods that modulate the mechanical properties and degradation characteristics of DIPS scaffolds over a broad range.Based on its suitable mechanical properties and bioactivity,we successfully repaired and functionally reconstructed a complex defect in penile erectile tissue using the DIPS scaffold in a rabbit model.In summary,this approach is relevant for various hydrogen-bonded cross-linked hydrogels that offer mild printing conditions and enable the incorporation of bioactive agents.They can be used as scaffolds for dynamic tissue reconstruction,wearable devices,or soft robots.
基金supported by the Natural Science Foundation of Guangdong Province (No. 2017A030313898)the Guangzhou Science and Technology Plan Projects (No. 201707010113), China。
文摘Copy number variations(CNVs), which can affect the role of long non-coding RNAs(lncRNAs), are important genetic changes seen in some malignant tumors. We analyzed lncRNAs with CNV to explore the relationship between lncRNAs and prognosis in bladder cancer(BLCA). Messenger RNA(mRNA) expression levels, DNA methylation, and DNA copy number data of 408 BLCA patients were subjected to integrative bioinformatics analysis. Cluster analysis was performed to obtain different subtypes and differently expressed lncRNAs and coding genes. Weighted gene co-expression network analysis(WGCNA) was performed to identify the co-expression gene and lncRNA modules. CNV-associated lncRNA data and their influence on cancer prognosis were assessed with Kaplan-Meier survival curve. Multi-omics integration analysis revealed five prognostic lncRNAs with CNV, namely NR2 F1-AS1, LINC01138, THUMPD3-AS1, LOC101928489, and TMEM147-AS1, and a risk-score signature related to overall survival in BLCA was identified. Moreover, validated results in another independent Gene Expression Omnibus(GEO) dataset, GSE31684, were consistent with these results. Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis revealed that the mitogen-activated protein kinase(MAPK) signaling pathway, focal adhesion pathway, and Janus kinase-signal transducers and activators of transcription(JAK-STAT) signaling pathway were enriched in a high-risk score pattern, suggesting that imbalance in these pathways is closely related to tumor development. We revealed the prognosis-related lncRNAs by analyzing the expression profiles of lncRNAs and CNVs, which can be used as prognostic biomarkers for BLCA.
文摘The aim of this paper is to investigate the clin-ical features and transformation of elderly male patients with normal blood glucose levels at fasting and 2 hours after glucose intake but with hyperglycemia(>11.1 mmol/L)1 hour after oral glucose tolerance test(OGTT-1h HG).Seven years of follow-up visits were per-formed on 189 elderly male outpatients with OGTT-1h HG and data was recorded on their body mass index(BMI),blood pressure,serum cholesterol and triglyceride test results and on their glucose tolerance changes every 1–2 years after taking OGTT;their possible causes were analysed.Follow-up visits revealed that 19 patients with OGTT-1h HG were diagnosed with diabetes(10.1%),78 patients with impaired glucose tolerance(IGT,41.3%),2 patients transformed to normal glucose tolerance(NGT,1.1%)and the remaining 90 patients(47.6%)remained unchanged.Synchronized comparison with IGT patients showed that the ratio of OGTT-1h HG patients turning to diabetes was lower than that of IGT patients(21.1%,x2513.05,P,0.01),and the ratio of OGTT-1h HG patients transforming to NGT was slightly higher(0.4%,x252.46,P.0.05).The prevalence of complications of hypertension,coronary heart disease,cerebral vascular diseases and dyslipidemia in patients with OGTT-1h HG were higher than those with NGT(P,0.05)and were similar to that of IGT patients.As a special phenotype of OGTT and as part of an abnormal glucose tolerance con-formation,patients with OGTT-1h HG warrant special attention,since about half of them were found to have developed diabetes or IGT,and their risk of suffering from vascular diseases were also increased.