From materials to structures: A holistic examination of achieving linearity in flexible pressure sensors.

As a pivotal category in the realm of wearable electronics, flexible pressure sensors have become a focal point due to their diverse applications such as human-machine interfaces and health monitoring. To cater for these applications, novel material design and fabrication strategies have been devised as to enhance the device performance by manipulating mechanical and electrical properties. This work primarily reviews the development of flexible pressure sensors during recent years with a focus on sensitive materials and related applications. First, an overview of the fundamental working mechanisms for various sensors was elucidated. Then, the influence of distinct surface microstructures or internal microstructures on the linearity of flexible sensors was explored. Following this, we delve into diverse applications of linear flexible pressure sensors, spanning from robotics, safety, electronic skin, to health monitoring. Finally, the existing constraints and future research prospects are outlined to pave the way for the further development of high-performance flexible pressure sensors. .

Traditional Chinese Medicine treatment for postoperative axial symptoms of cervical spondylotic myelopathy: a systematic review.

BACKGROUND: Axial symptoms (AS) represent one of the primary complications after cervical spondylotic myelopathy (CSM) surgery. Traditional Chinese Medicine (TCM), as a complementary and alternative therapy, is widely used in the treatment of postoperative AS in CSM. However, it lacks standardised treatment protocols, uniform therapeutic criteria, assessment methods and a sufficiently in-depth understanding of its mechanisms of action. These shortcomings impact the credibility of TCM treatment in clinical practice. METHODS AND ANALYSIS: We will conduct comprehensive searches, both manual and electronic, on literature published up to 31 July 2024, and database searches will commence after the publication of this agreement, with an estimated commencement date of 1 October 2024 and the end date of 31 March 2025, without language restrictions. Key databases such as MEDLINE, PubMed, Embase, Web of Science, Cochrane Library, WHO International Clinical Trial Registration Platform, China National Knowledge Network, China Biomedical Literature Database, China Scientific Journal Database and Wanfang Database will be explored. In addition, we will include resources such as library journals and conference abstracts. After identifying and screening all randomised controlled trials focused on TCM for postoperative AS of CSM, the two investigators will conduct a meta-analysis of the included studies. The results will be summarised as the risk ratio for binary data and the standardised or weighted average difference for continuous data. ETHICS AND DISSEMINATION: Ethical approval is not required since this review does not involve individual patient data. The review's findings will provide clinicians with evidence on using TCM treatment for AS post-CSM surgery, disseminated through peer-reviewed publications or conferences. PROSPERO REGISTRATION NUMBER: CRD42024505160.

Mutation of tomato xyloglucan transglucosylase/hydrolase5 increases fruit firmness and contributes to prolonged shelf life.

Fruit ripening in tomato is a highly coordinated developmental process accompanied with fruit softening, which is closely associated with cell wall degradation and remodeling. Xyloglucan endotransglucosylase/hydrolases (XTHs) are known to play an essential role in cell wall xyloglucan metabolism. Tomato XTH5 exhibits xyloglucan endotransglucosylase (XET) activity in vitro, but the understanding of its biological role in fruit ripening remains unclear. In this study, we revealed that SlXTH5 is highly expressed in mature fruits. Knockout mutant plants of SlXTH5 were generated by CRISPR/Cas9 gene editing strategy in tomato cultivar Micro-Tom. The mutant fruits showed accelerated transition from unripe to ripe process and earlier ethylene accumulation compared to wild type fruits. Although the mutation of SlXTH5 did not affect the size, weight and number of fruits, it indeed increased fruit firmness and extended shelf life, which is probably attributed to the increased cell layer and cell wall thickness of pericarp tissue. Pathogen infection experiment showed the enhanced resistance of mutant fruits to Botrytis cinerea. These results revealed the role of SlXTH5 in fruit ripening process, and provide new insight into how cell wall metabolism and remodeling regulate fruit softening and shelf life.

Single-nucleus sequencing unveils heterogeneity in renal cell carcinomas microenvironment: Insights into pathogenic origins and treatment-responsive cellular subgroups.

BACKGROUND: Different individuals with renal cell carcinoma (RCC) exhibit substantial heterogeneity in histomorphology, genetic alterations in the proteome, immune cell infiltration patterns, and clinical behavior. OBJECTIVES: This study aims to use single-nucleus sequencing on ten samples (four normal, three clear cell renal cell carcinoma (ccRCC), and three chromophobe renal cell carcinoma (chRCC)) to uncover pathogenic origins and prognostic characteristics in patients with RCC. METHODS: By using two algorithms, inferCNV and k-means, the study explores malignant cells and compares them with the normal group to reveal their origins. Furthermore, we explore the pathogenic factors at the gene level through Summary-data-based Mendelian Randomization and co-localization methods. Based on the relevant malignant markers, a total of 212 machine-learning combinations were compared to develop a prognostic signature with high precision and stability. Finally, the study correlates with clinical data to investigate which cell subtypes may impact patients' prognosis. RESULTS & CONCLUSION: Two main origin tumor cells were identified: Proximal tubule cell B and Intercalated cell type A, which were highly differentiated in epithelial cells, and three gene loci were determined as potential pathogenic genes. The best malignant signature among the 212 prognostic models demonstrated high predictive power in ccRCC: (AUC: 0.920 (1-year), 0.920 (3-year) and 0.930 (5-year) in the training dataset; 0.756 (1-year), 0.828 (3-year), and 0.832 (5-year) in the testing dataset. In addition, we confirmed that LYVE1+ tissue-resident macrophage and TOX+ CD8 significantly impact the prognosis of ccRCC patients, while monocytes play a crucial role in the prognosis of chRCC patients.

Protocol for systematic review and meta-analysis on the efficacy and safety of acupuncture for residual low back pain after percutaneous kyphoplasty in patients with osteoporotic vertebral compression fracture.

INTRODUCTION: Osteoporotic vertebral compression fracture (OVCF) is a common complication in elderly patients with osteoporosis. Despite undergoing percutaneous kyphoplasty (PKP) treatment, a significant percentage of OVCF patients (1.8% to 31.9%) continue to experience residual low back pain. While acupuncture has shown promise in relieving this pain, there is currently no systematic review on its efficacy specifically for residual low back pain after PKP in OVCF patients. This project aims to evaluate the effectiveness and safety of acupuncture as a treatment for this condition. METHODS AND ANALYSIS: A comprehensive search will be conducted, including manual and electronic searches of literature published. Various databases such as MEDLINE, PubMed, EMBASE, Web of Science, Cochrane Library, International Clinical Trial Registration Platform, China National Knowledge Network, China Biomedical Literature Database, China Scientific Journal Database and Wan-fang Database will be explored. Additional sources like bibliographies and meeting minutes will also be searched. All randomised controlled clinical trials related to acupuncture for treating residual low back pain after PKP in OVCF patients will be included. Two researchers will independently perform study selection, data extraction and quality assessment. The primary outcome measure will be pain relief assessed using a visual analogue scale (VAS) or other validated scales. Secondary outcomes include effectiveness, Oswestry dysfunction index (ODI), quality of life questionnaire (QUALEFFO-41), follow-up relapse rate and adverse events. If feasible, a meta-analysis using RevMan V.5.3 software will be conducted. Otherwise, descriptive or subgroup analyses will be performed. Database searches will commence after the publication of this agreement, with an estimated commencement date of 1 August 2024. ETHICS AND DISSEMINATION: Ethical approval is not required since this review does not involve individual patient data. The findings will be disseminated through peer-reviewed journals or relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42023478838.

Roles of Akirin1 in early prediction and treatment of graft kidney ischemia‒reperfusion injury.

Ferroptosis is a predominant contributor to graft kidney ischemia‒reperfusion injury (IRI), resulting in delayed graft function (DGF). However, much less is known about the early predicting biomarkers and therapeutic targets of DGF, especially aiming at ferroptosis. Here, we propose a precise predicting model for DGF, relying on the Akirin1 level in extracellular vesicles (EVs) derived from recipient urine 48 h after kidney transplant. In addition, we decipher a new molecular mechanism whereby Akirin1 induces ferroptosis by strengthening TP53-mediated suppression of SLC7A11 during the graft kidney IRI process, that is, Akirin1 activates the EGR1/TP53 axis and inhibits MDM2-mediated TP53 ubiquitination, accordingly upregulating TP53 in two ways. Meanwhile, we present the first evidence that miR-136-5p enriched in EVs secreted by human umbilical cord mesenchymal stem cells (UM-EVs) confers robust protection against ferroptosis and graft kidney IRI by targeted inhibition of Akirin1 but knockout of miR-136-5p in UM sharply mitigates the protection of UM-EVs. The functional and mechanistic regulation of Akirin1 is further corroborated in an allograft kidney transplant model in wild-type and Akirin1-knockout mice. In summary, these findings suggest that Akirin1, which prominently induces ferroptosis, is a pivotal biomarker and target for early diagnosis and treatment of graft kidney IRI and DGF after kidney transplant.

The MEF2A/SNHG16/miR-425-5p/NOTCH2 axis induces gemcitabine resistance by inhibiting ferroptosis in the starving bladder tumor microenvironment.

Gemcitabine resistance is one of the leading causes of bladder cancer (BCa) recurrence and progression. The dysregulation of ferroptosis is involved in this process; however, the underlying mechanisms remain unclear. In the current study, we found a prominent increase in long non-coding RNA (lncRNA) small nucleolar RNA host gene 16 (SNHG16) in tumor samples, which was related to advanced tumor grade and poor prognosis. SNHG16 is overexpressed in the starving tumor microenvironment (STME) and induces gemcitabine resistance by inhibiting ferroptosis in BCa. SNHG16 knockdown promotes ferroptosis and increases chemosensitivity to gemcitabine. Mechanistically, the transcription factor MEF2A was markedly upregulated in the STME, facilitating SNHG16 expression. SNHG16 acts as a competing endogenous RNA that sponges miR-425-5p and promotes NOTCH2 expression. SNHG16/miR-425-5p/NOTCH2 is demonstrated, for the first time, to suppress ferroptosis by inducing SLC7A11 and GPX4 expression in vitro and in vivo. Upregulation of miR-425-5p reverses NOTCH2-mediated inhibition of ferroptosis, thereby mitigating gemcitabine resistance. In conclusion, these findings reveal that the STME-activated MEF2A/SNHG16/miR-425-5p/NOTCH2 axis induces gemcitabine resistance by inhibiting ferroptosis and implicate SNHG16 as a potential therapeutic target for chemoresistance.

A Model to Predict Prognosis of Renal Cell Clear Cell Carcinoma Based on 3 Angiogenesis-related Long Non-coding RNAs.

Background: Tumor angiogenesis is closely related to the progression of clear cell renal cell carcinoma (ccRCC). Long non-coding RNAs (lncRNAs) regulating angiogenesis could be potential biomarkers for predicting ccRCC prognosis. With this study, we aimed to construct a prognostic model based on lncRNAs and explore its underlying mechanisms. Methods: RNA data and clinical information were obtained from The Cancer Genome Atlas (TCGA) database. Angiogenesis-related genes (ARGs) were extracted from the Molecular Signatures database. Pearson correlation and LASSO and COX regression analyses were performed to identify survival-related AR-lncRNAs (sAR-lncRNAs) and construct a prognostic model. The predictive power of the prognostic model was verified according to Kaplan‒Meier curve, receiver operating characteristic (ROC) curve and nomogram analyses. The correlation between the prognostic model and clinicopathological characteristics was assessed via univariate and multivariate analyses. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was subsequently performed to elucidate the mechanisms of the sAR-lncRNAs. In vitro qPCR, immunohistochemistry, migration and invasion assays were conducted to confirm the angiogenic function of sAR-lncRNAs. Results: Three sAR-lncRNAs were used to construct a prognostic model. The model was moderately accurate in predicting 1- , 3- and 5-year ccRCC prognosis, and the risk score according to this model was closely related to clinicopathological characteristics such as T grade and T stage. A nomogram was constructed to precisely estimate the overall survival of ccRCC patients. KEGG enrichment analysis indicated that the MAPK and Notch pathways were highly enriched in high-risk patients. Additionally, we found that the expression of the lncRNAs AC005324.4 and AC104964.4 in the prognostic model was lower in ccRCC cell lines and cancer tissues than in the HK-2 cell line and paracancerous tissues, while the expression of the lncRNA AC087482.1 showed the opposite trend. In a coculture model, knockdown of lncRNA AC005324.4 and lncRNA AC104964.4 significantly promoted the migration and invasion of human umbilical vein endothelial cells (HUVECs), but siR-AC087482.1 transfection alleviated these effects. Conclusions: We constructed a prognostic model based on 3 sAR-lncRNAs and validated its value in clinicopathological characteristics and prognostic prediction of ccRCC patients, providing a new perspective for ccRCC treatment decision making.

AAT resistance-related AC007405.2 and AL354989.1 as novel diagnostic and prognostic markers in prostate cancer.

OBJECTIVE: Prostate cancer (PCa) is the second disease threatening men's health, and anti-androgen therapy (AAT) is a primary approach for treating this condition. Increasing evidence suggests that long non-coding RNAs (lncRNAs) play crucial roles in the development of PCa and the process of AAT resistance. The objective of this study is to utilize bioinformatics methods to excavate lncRNAs association with AAT resistance and investigate their biological functions. METHODS: AAT resistance-related risk score model (ARR-RSM) was established by multivariate Cox analysis. Paired clinical tissue samples of 36 PCa patients and 42 blood samples from patients with PSA over 4 ng/ml were collected to verify the ARR-RSM. In vitro, RT-qPCR, CCK-8 and clone formation assays were displayed to verify the expression and function of AL354989.1 and AC007405.2. RESULTS: Pearson correlation analysis identified 996 lncRNAs were associated with AAT resistance (ARR-LncRs). ARR-RSM was established using multivariate Cox regression analysis, and PCa patients were divided into high-risk and low-risk groups. High-risk patients showed increased expression of AL354989.1 and AC007405.2 had poorer prognoses. The high-risk score correlated with advanced T-stage and N-stage. The AUC of ARR-RSM outperformed tPSA in diagnosing PCa. Silencing of AC007405.2 and AL354989.1 inhibited PCa cells proliferation and AAT resistance. CONCLUSIONS: In this study, we have discovered the clinical significance of AC007405.2 and AL354989.1 in predicting the prognosis and diagnosing PCa patients. Furthermore, we have confirmed their correlation with various clinical features. These findings provide potential targets for PCa treatment and a novel diagnostic and predictive indicator for precise PCa diagnosis.

Luminol-conjugated cyclodextrin biological nanoparticles for the treatment of severe burn-induced intestinal barrier disruption.

Background: The breakdown of intestinal barrier integrity occurs after severe burn injury and is responsible for the subsequent reactions of inflammation and oxidative stress. A new protective strategy for the intestinal barrier is urgently needed due to the limitations of the traditional methods. Recently, the application of nanoparticles has become one of the promising therapies for many inflammation-related diseases or oxidative damage. Herein, we developed a new anti-inflammatory and antioxidant nanoparticle named luminol-conjugated cyclodextrin (LCD) and aimed to evaluate its protective effects in severe burn-induced intestinal injury. Methods: First, LCD nanoparticles, engineered with covalent conjugation between luminol and ß-cyclodextrin (ß-CD), were synthesized and examined. Then a mouse burn model was successfully established before the mouse body weight, intestinal histopathological manifestation, permeability, tight junction (TJ) expression and pro-inflammatory cytokines were determined in different groups. The proliferation, apoptosis, migration and reactive oxygen species (ROS) of intestinal epithelial cells (IECs) were assessed. Intraepithelial lymphocytes (IELs) were isolated and cultured for analysis by flow cytometry. Results: LCD nanoparticle treatment significantly relieved the symptoms of burn-induced intestinal injury in the mouse model, including body weight loss and intestinal permeability abnormalities. Moreover, LCD nanoparticles remarkably recovered the mechanical barrier of the intestine after severe burn, renewed TJ structures, promoted IEC proliferation and migration, and inhibited IEC apoptosis. Mechanistically, LCD nanoparticles dramatically alleviated pro-inflammation factors (tumor necrosis factor-α, IL-17A) and ROS accumulation, which could be highly involved in intestinal barrier disruption. Furthermore, an increase in IL-17A and the proportion of IL-17A+Vγ4+ γδ T subtype cells was also observed in vitro in LPS-treated Vγ4+ γδ T cells, but the use of LCD nanoparticles suppressed this increase. Conclusions: Taken together, these findings demonstrate that LCD nanoparticles have the protective ability to ameliorate intestinal barrier disruption and provide a therapeutic intervention for burn-induced intestinal injury.

MiR-15b-3p weakens bicalutamide sensitivity in prostate cancer via targeting KLF2 to suppress ferroptosis.

Bicalutamide (BIC) resistance impedes the treatment of prostate cancer (PCa) and seems to involve ferroptosis; however, the underlying mechanism remains unclear. Our study aimed to explore how miR-15b-3p modulates ferroptosis in response to BIC resistance and determine whether the miRNA is suitable for early screening of PCa. Here, we found that PCa tissues had significantly higher miR-15b-3p expression than adjacent normal tissues. Analysis of blood samples in patients who underwent prostate-specific antigen (PSA) screening revealed that miR-15b-3p was a more accurate diagnostic than PSA (miR-15b-3p area under the curve [AUC] = 0.941, PSA AUC = 0.815). In vitro experiments then demonstrated that miR-15b-3p expression was markedly higher in LNCaP, PC-3, and DU145 cells than in RWPE-1 cells. Treatment with BIC decreased miR-15b-3p expression and progressive ferroptosis. Mechanistically, we identified KLF2 as the downstream target of miR-15b-3p. Overexpressing KLF2 facilitated ferroptosis via augmenting MDA and iron concentrations, in turn inhibiting the SLC7A11/GPX4 axis and decreasing GSH concentration. Through modulating ferroptosis, miR-15b-3p mimic and inhibitor weakened and enhanced BIC sensitivity, respectively. Furthermore, BIC treatment limited xenograft tumor volume in vivo, whereas agomir-15b-3p promoted tumor growth, indicating that miR-15b-3p attenuated the tumor-suppressive effects of BIC. Taken together, our results suggested that miR-15b-3p is crucial to BIC resistance, specifically via targeting KLF2 and thereby suppressing ferroptosis. High miR-15b-3p expression in early PCa screening should reflect a higher probability of cancer. In conclusion, miR-15b-3p has strong potential as a screening and diagnostic biomarker with reliable prospects for clinical application. Furthermore, because patients with high miR-15b-3p and low KLF2 expression have a greater risk of BIC resistance and malignant progression, targeting the miRNA and its downstream protein may be a new treatment strategy.

Extracellular vesicles secreted from mesenchymal stem cells ameliorate renal ischemia reperfusion injury by delivering miR-100-5p targeting FKBP5/AKT axis.

The incidence of acute kidney injury (AKI) due to ischemia-reperfusion (IR) injury is increasing. There is no effective treatment for AKI, and because of this clinical challenge, AKI often progresses to chronic kidney disease, which is closely associated with poor patient outcomes and high mortality rates. Small extracellular vesicles from human umbilical cord mesenchymal stem cells (hUCMSC-sEVs) play increasingly vital roles in protecting tissue function from the effects of various harmful stimuli owing to their specific biological features. In this study, we found that miR-100-5p was enriched in hUCMSC-sEVs, and miR-100-5p targeted FKBP5 and inhibited HK-2 cell apoptosis by activating the AKT pathway. HK-2 cells that were exposed to IR injury were cocultured with hUCMSC-sEVs, leading to an increase in miR-100-5p levels, a decrease in FKBP5 levels, and an increase in AKT phosphorylation at Ser 473 (AKT-473 phosphorylation). Notably, these effects were significantly reversed by transfecting hUCMSCs with an miR-100-5p inhibitor. Moreover, miR-100-5p targeted FKBP5, as confirmed by a dual luciferase reporter assay. In vivo, intravenous infusion of hUCMSC-sEVs into mice suffering from IR injury resulted in significant apoptosis inhibition, functional maintenance and renal histological protection, which in turn decreased FKBP5 expression levels. Overall, this study revealed an effect of hUCMSC-sEVs on inhibiting apoptosis; hUCMSC-sEVs reduced renal IR injury by delivering miR-100-5p to HK-2 cells, targeting FKBP5 and thereby promoting AKT-473 phosphorylation to activate the AKT pathway. This study provides novel insights into the role of hUCMSC-sEVs in the treatment of AKI.

Identifying endoplasmic reticulum stress-related genes as new diagnostic and prognostic biomarkers in clear cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is one of the most common cancers worldwide, and its incidence is increasing every year. Endoplasmic reticulum stress (ERS) caused by protein misfolding has broad and profound effects on the progression and metastasis of various cancers. Accumulating evidence suggests that ERS is closely related to the occurrence and progression of ccRCC. This study aimed to identify ERS-related genes for evaluating the prognosis of ccRCC. Methods: Transcriptomic expression profiles were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), and clinical data were downloaded from the TCGA. First, the differentially expressed genes (DEGs) were analyzed using the limma package, and the DEGs related to ERS (ERS-DEGs) were identified from the GeneCards database. Second, a function and pathway enrichment analysis and a Gene Set Enrichment Analysis (GSEA) were performed. Third, a protein-protein interaction (PPI) network was constructed to identify the hub genes, and a gene-micro RNA (miRNA) network and gene-transcription factor (TF) network were established using the hub genes. Finally, a least absolute shrinkage and selection operator (LASSO) regression analysis was conducted to establish a diagnostic model, and a Cox analysis was used to analyze the correlations between the expression of the characteristic genes and the clinical characteristics. Results: We identified 11 signature genes and established a diagnostic model. Further, the Cox analysis results revealed a correlation between the expression levels of the signature genes and the clinical characteristics. Ultimately, five signature genes (i.e., TNFSF13B, APOL1, COL5A3, and CDH5) were found to be associated with a poor prognosis. Conclusions: This study suggests that TNFSF13B, APOL1, COL5A3, and CDH5 may have potential as prognostic biomarkers in ccRCC and may provide new evidence to support targeted therapy in ccRCC.

Immune characteristics of dedifferentiated retroperitoneal liposarcomas and the reliability of regional samples in evaluating their tumor immune microenvironments.

BACKGROUND: Tumor immunotherapy is a new treatment breakthrough for retroperitoneal liposarcoma (RPLS), which is highly invasive and has few effective treatment options other than tumor resection. However, the heterogeneity of the tumor immune microenvironment (TIME) leads to missed clinical diagnosis and inappropriate treatment. Therefore, it is crucial to evaluate whether the TIME of a certain part of the tumor reliably represents the whole tumor, particularly for very large tumors, such as RPLS. METHODS: We conducted a prospective study to evaluate the TIME in different regions of dedifferentiated RPLS (DDRPLS) by detecting the expressions of markers such as CD4+, CD8+, Foxp3+, CD20+, CD68+, LAMP3+, PD-1+ tumor-infiltrating lymphocytes (TILs), and PD-L1 in tumors and corresponding paratumor tissues via immunohistochemistry and RNA sequencing. RESULTS: In DDRPLS, very few TILs were observed. Differentially expressed genes were significantly enriched in cell part and cell functions, as well as the metabolic pathway and PI3K-Akt signaling pathway. In addition, for most tumors (70-80%), the TIME was similar in different tumor regions. CONCLUSIONS: For most tumors (70-80%), the TIME in any region of the tumor reliably represents the whole tumor. DDRPLS may regulate cell functions by modulating the metabolic and PI3K-Akt signaling pathways to promote its malignant behavior.

Copy number variation of the restorer Rf4 underlies human selection of three-line hybrid rice breeding.

Cytoplasmic male sterility (CMS) lines are important for breeding hybrid crops, and utilization of CMS lines requires strong fertility restorer (Rf) genes. Rf4, a major Rf for Wild-Abortive CMS (CMS-WA), has been cloned in rice. However, the Rf4 evolution and formation of CMS-WA/Rf system remain elusive. Here, we show that the Rf4 locus emerges earlier than the CMS-WA gene WA352 in wild rice, and 69 haplotypes of the Rf4 locus are generated in the Oryza genus through the copy number and sequence variations. Eight of these haplotypes of the Rf4 locus are enriched in modern rice cultivars during natural and human selections, whereas non-functional rf4i is preferentially selected for breeding current CMS-WA lines. We further verify that varieties carrying two-copy Rf4 haplotype have stronger fertility restoration ability and are widely used in three-line hybrid rice breeding. Our findings increase our understanding of CMS/Rf systems and will likely benefit crop breeding.

[Risk modeling based on HER-2 related genes for bladder cancer survival prognosis assessment].

OBJECTIVE: To investigate the correlation between the human epidermal growth factor receptor-2-related genes (HRGs) and survival prognosis of bladder cancer and to construct a predictive model for survival prognosis of bladder cancer patients based on HRGs. METHODS: HRGs in bladder cancer were found by downloading bladder tumor tissue mRNA sequencing data and clinical data from the cancer genome atlas (TCGA), downloading HER-2 related genes from the molecular signatures database (MsigDB), and crossing the two databases. Further identifying HRGs associated with bladder cancer survival (P < 0.05) by using single and multi-factor Cox regression analysis and constructing HRGs risk score model (HRSM), the bladder cancer patients were categorized into high-risk and low-risk groups accor-ding to the median risk score. Survival analysis of the patients in high- and low-risk groups was conducted using R language and correlation of HRGs with clinical characteristics. A multi-factor Cox regression analysis was used to verify the independent factors affecting the prognosis of the patients with bladder cancer. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) of HRSM was calculated, and a nomogram was constructed for survival prediction of the bladder cancer patients. Analysis of HRSM and patient immune cell infiltration correlation was made using the TIMER database. RESULTS: A total of 13 HRGs associated with patient survival were identified in this study. Five genes (BTC, CDC37, EGF, PTPRR and EREG) were selected for HRSM by multi-factor Cox regression analysis. The 5-year survival rate of the bladder cancer patients in the high-risk group was significantly lower than that of the patients in the low-risk group. High expression of PTPRR was found to be significantly and negatively correlated with tumor grade and stage by clinical correlation analysis, while EREG was found to be the opposite; Increased expression of EGF was associated with high grade, however, the high expression ofCDC37showed the opposite result. And no significant correlation was found between BTC expression and clinical features. Correlation analysis of HRSM with immune cells revealed a positive correlation between risk score and infiltration of dendritic cells, CD8+T cells, CD4+T cells, neutrophils and macrophages. CONCLUSION: HRGs have an important role in the prognosis of bladder cancer patients and may serve as new predictive biomarkers and potential targets for treatment.

Nitrogen addition stimulates N2O emissions via changes in denitrification community composition in a subtropical nitrogen-rich forest.

Microbially driven nitrification and denitrification play important roles in regulating soil N availability and N2O emissions. However, how the composition of nitrifying and denitrifying prokaryotic communities respond to long-term N additions and regulate soil N2O emissions in subtropical forests remains unclear. Seven years of field experiment which included three N treatments (+0, +50, +150 kg N ha-1 yr-1; CK, LN, HN) was conducted in a subtropical forest. Soil available nutrients, N2O emissions, net N mineralization, denitrification potential and enzyme activities, and the composition and diversity of nitrifying and denitrifying communities were measured. Soil N2O emissions from the LN and HN treatments increased by 42.37% and 243.32%, respectively, as compared to the CK. Nitrogen addition significantly inhibited nitrification (N mineralization) and significantly increased denitrification potentials and enzymes. Nitrification and denitrification abundances (except nirK) were significantly lower in the HN, than CK treatment and were not significantly correlated with N2O emissions. Nitrogen addition significantly increased nirK abundance while maintaining the positive effects of denitrification and N2O emissions to N deposition, challenging the conventional wisdom that long-term N addition reduces N2O emissions by inhibiting microbial growth. Structural equation modeling showed that the composition, diversity, and abundance of nirS- and nirK-type denitrifying prokaryotic communities had direct effects on N2O emissions. Mechanistic investigations have revealed that denitrifier keystone taxa transitioned from N2O-reducing (complete denitrification) to N2O-producing (incomplete denitrification) with increasing N addition, increasing structural complexity and diversity of the denitrifier co-occurrence network. These results significantly advance current understanding of the relationship between denitrifying community composition and N2O emissions, and highlight the importance of incorporating denitrifying community dynamics and soil environmental factors together in models to accurately predict key ecosystem processes under global change.

Small extracellular vesicles delivering lncRNA WAC-AS1 aggravate renal allograft ischemia‒reperfusion injury by inducing ferroptosis propagation.

Ferroptosis is a predominant contributor to renal ischemia reperfusion injury (IRI) after kidney transplant, evoking delayed graft function and poorer long-term outcomes. The wide propagation of ferroptosis among cell populations in a wave-like manner, developing the "wave of ferroptosis" causes a larger area of tubular necrosis and accordingly aggravates renal allograft IRI. In this study, we decipher a whole new metabolic mechanism underlying ferroptosis and propose a novel spreading pathway of the "wave of ferroptosis" in the renal tissue microenvironment, in which renal IRI cell-secreted small extracellular vesicles (IRI-sEVs) delivering lncRNA WAC-AS1 reprogram glucose metabolism in adjacent renal tubular epithelial cell populations by inducing GFPT1 expression and increasing hexosamine biosynthesis pathway (HBP) flux, and consequently enhances O-GlcNAcylation. Additionally, BACH2 O-GlcNAcylation at threonine 389 in renal tubular epithelial cells prominently inhibits its degradation by ubiquitination and promotes importin α5-mediated nuclear translocation. We present the first evidence that intranuclear BACH2 suppresses SLC7A11 and GPX4 transcription by binding to their proximal promoters and decreases cellular anti-peroxidation capability, accordingly facilitating ferroptosis. Inhibition of sEV biogenesis and secretion by GW4869 and knockout of lncRNA WAC-AS1 in IRI-sEVs both unequivocally diminished the "wave of ferroptosis" propagation and protected against renal allograft IRI. The functional and mechanistic regulation of IRI-sEVs was further corroborated in an allograft kidney transplant model and an in situ renal IRI model. In summary, these findings suggest that inhibiting sEV-mediated lncRNA WAC-AS1 secretion and targeting HBP metabolism-induced BACH2 O-GlcNAcylation in renal tubular epithelial cells may serve as new strategies for protecting against graft IRI after kidney transplant.

The conscious processing of emotion in depression disorder: a meta-analysis of neuroimaging studies.

Background: Depression is generally accompanied by a disturbed conscious processing of emotion, which manifests as a negative bias to facial/voice emotion information and a decreased accuracy in emotion recognition tasks. Several studies have proved that abnormal brain activation was responsible for the deficit function of conscious emotion recognition in depression. However, the altered brain activation related to the conscious processing of emotion in depression was incongruent among studies. Therefore, we conducted an activation likelihood estimation (ALE) analysis to better understand the underlying neurophysiological mechanism of conscious processing of emotion in depression. Method: Electronic databases were searched using the search terms "depression," "emotion recognition," and "neuroimaging" from inceptions to April 10th, 2023. We retrieved trials which explored the neuro-responses of depressive patients to explicit emotion recognition tasks. Two investigators independently performed literature selection, data extraction, and risk of bias assessment. The spatial consistency of brain activation in conscious facial expressions recognition was calculated using ALE. The robustness of the results was examined by Jackknife sensitivity analysis. Results: We retrieved 11,365 articles in total, 28 of which were included. In the overall analysis, we found increased activity in the middle temporal gyrus, superior temporal gyrus, parahippocampal gyrus, and cuneus, and decreased activity in the superior temporal gyrus, inferior parietal lobule, insula, and superior frontal gyrus. In response to positive stimuli, depressive patients showed hyperactivity in the medial frontal gyrus, middle temporal gyrus, and insula (uncorrected p < 0.001). When receiving negative stimuli, a higher activation was found in the precentral gyrus, middle frontal gyrus, precuneus, and superior temporal gyrus (uncorrected p < 0.001). Conclusion: Among depressive patients, a broad spectrum of brain areas was involved in a deficit of conscious emotion processing. The activation of brain regions was different in response to positive or negative stimuli. Due to potential clinical heterogeneity, the findings should be treated with caution. Systematic review registration: https://inplasy.com/inplasy-2022-11-0057/, identifier: 2022110057.