Construction of Multifunctional Luminescent Lanthanide MOFs for Luminescent Sensing of Temperature, Trifluoroacetic Acid Vapor and Explosives.

Metal-organic frameworks (MOFs) with multifunctional and tunable optical properties have unique advantages in the field of sensing, and the structure and properties of MOFs are significantly influenced by the ligands. In this study, a Y-type tricarboxylic acid ligand containing amide bonds was synthesized through functional guidance, and three isomorphic and heterogeneous three-dimensional MOFs (Eu-MOF, Tb-MOF, and Gd-MOF) were obtained by solvothermal reaction. Further studies revealed that both the Tb-MOF and Eu-MOF could selectively detect picric acid (PA). The luminescence quenching of the two MOFs by PA was attributed to competing absorption and photoelectron energy transfer mechanisms. In addition, due to the energy transfer between Tb and Rhodamine B, Rhodamine B was encapsulated into Tb-MOF. The obtained material exhibited a linear relationship between the temperature parameters I544/I584 and temperature within the range of 280-400 K, the correlation coefficient (R2) reached an impressive value of 0.999, and the absolute sensitivity of the sample used for temperature sensing was 1.534% K-1. What is more, the material exhibited a good response to trifluoroacetic acid vapor, which suggests the potential of the material for temperature sensing and detection of trifluoroacetic acid vapor. The designed and investigated strategy can also serve as a reference for further research on excellent multifunctional sensors.

A Hydrophilic Mixed Lanthanide Metal-Organic Framework Monitoring H2O in D2O.

Lanthanide metal-organic framework (Ln-MOF) luminescent sensors monitoring the H2O content in D2O are still rare. We designed and built a hydrophilic mixed Ln-MOF (Eu0.4Tb0.6-MOF) monitoring the H2O content in D2O. By designing a ligand and controlling the synthesis method, we achieved a balance between the structural stability and sensing capacity. When the H2O content ranges from 0 to 100%, the photoluminescence color of Eu0.4Tb0.6-MOF can change from yellow to green, which can be observed by the naked eye. The mechanism is that the photoluminescence intensity of Eu3+ decreases faster than that of Tb3+ when the H2O content increases. The sensing mechanism was studied further by transient fluorescence spectrometry.

EP300/CBP is crucial for cAMP-PKA pathway to alleviate podocyte dedifferentiation via targeting Notch3 signaling.

Podocyte injury is the hallmark of proteinuric glomerular diseases. Notch3 is neo-activated simultaneously in damaged podocytes and podocyte's progenitor cells of FSGS, indicating a unique role of Notch3. We previously showed that activation of cAMP-PKA pathway alleviated podocyte injury possibly via inhibiting Notch3 expression. However, the mechanisms are unknown. In the present study, Notch3 signaling was significantly activated in ADR-induced podocytes in vitro and in PAN nephrosis rats and patients with idiopathic FSGS in vivo, concomitantly with podocyte dedifferentiation. In cultured podocytes, pCPT-cAMP, a selective cAMP-PKA activator, dramatically blocked ADR-induced activation of Notch3 signaling as well as inhibition of cAMP-PKA pathway, thus alleviating the decreased cell viability and podocyte dedifferentiation. Bioinformatics analysis revealed EP300/CBP, a transcriptional co-activator, as a central hub for the crosstalk between these two signaling pathways. Additionally, CREB/KLF15 in cAMP-PKA pathway competed with RBP-J the major transcriptional factor of Notch3 signaling for binding to EP300/CBP. EP300/CBP siRNA significantly inhibited these two signaling transduction pathways and disrupted the interactions between the above major transcriptional factors. These data indicate a crucial role of EP300/CBP in regulating the crosstalk between cAMP-PKA pathway and Notch3 signaling and modulating the phenotypic change of podocytes, and enrich the reno-protective mechanisms of cAMP-PKA pathway.

NAD+ Anabolism Disturbance Causes Glomerular Mesangial Cell Injury in Diabetic Nephropathy.

The homeostasis of NAD+ anabolism is indispensable for maintaining the NAD+ pool. In mammals, the mainly synthetic pathway of NAD+ is the salvage synthesis, a reaction catalyzed by nicotinamide mononucleotide adenylyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase (NMNATs) successively, converting nicotinamide (NAM) to nicotinamide mononucleotide (NMN) and NMN to NAD+, respectively. However, the relationship between NAD+ anabolism disturbance and diabetic nephropathy (DN) remains elusive. Here our study found that the disruption of NAD+ anabolism homeostasis caused an elevation in both oxidative stress and fibronectin expression, along with a decrease in Sirt1 and an increase in both NF-κB P65 expression and acetylation, culminating in extracellular matrix deposition and globular fibrosis in DN. More importantly, through constitutively overexpressing NMNAT1 or NAMPT in human mesangial cells, we revealed NAD+ levels altered inversely with NMN levels in the context of DN and, further, their changes affect Sirt1/NF-κB P65, thus playing a crucial role in the pathogenesis of DN. Accordingly, FK866, a NAMPT inhibitor, and quercetin, a Sirt1 agonist, have favorable effects on the maintenance of NAD+ homeostasis and renal function in db/db mice. Collectively, our findings suggest that NMN accumulation may provide a causal link between NAD+ anabolism disturbance and diabetic nephropathy (DN) as well as a promising therapeutic target for DN treatment.

Percutaneous endoscopic lumbar discectomy for LDH via a transforaminal approach versus an interlaminar approach: a meta-analysis.

PURPOSE: The aim of this study was to systematically compare the safety and effectiveness of percutaneous endoscopic transforaminal discectomy (PETD) versus percutaneous endoscopic interlaminar discectomy (PEID) for the treatment of lumbar disc herniation (LDH). MATERIAL AND METHODS: All studies that were performed to compare PETD with PEID to treat LDH and published until 31 August 2017 were acquired through a comprehensive search in various databases. A meta-analysis was performed using the Cochrane Collaboration's RevMan 5.3 software. RESULTS: A total of 13 trials with 974 cases consisting of 3 randomized controlled trials, 3 prospective studies and 7 retrospective studies were included. The results suggest that patients treated with PEID experienced more significant advantages with shorter operation time, less intraoperative blood loss and less intraoperative fluoroscopy times but more complications than those treated with PETD; however, the two operative approaches did not significantly differ in terms of LDH recurrence, hospital stay, Oswestry disability index (ODI) scores, visual analogue scale (VAS) scores, Japanese Orthopaedic Association (JOA) scores and MacNab criteria at the final follow-up. CONCLUSION: Based on the results of this study, although PEID may be superior to PETD in certain ways, some of its advantages have yet to be verified and the two interventions were not significantly different in terms of relief of symptoms and functional recovery. Therefore, PEID would be recommended for treating LDH especially at L5/S1 under certain conditions but a prudent attitude is necessary to choose between the two operative approaches before a large sample and high quality randomized controlled trials have been performed.

Effect of c-erbB2 overexpression on prognosis in osteosarcoma: evidence from eight studies.

C-erbB2 (HER-2/neu) plays an important role in the progression of several types of cancer by increasing tumor growth, migration, invasion, and metastasis and is associated with poor disease prognosis. Numerous studies examining the relationship between c-erbB2 expression and prognostic impact in patients with osteosarcoma have yielded inconclusive results. We therefore conducted a meta-analysis to provide a comprehensive evaluation of the prognostic role of c-erbB2 expression on 5-year survival, which compared the positive and negative expression of c-erbB2 in patients of the available studies. A detailed search was made in PubMed for relevant original articles published in English. Finally, a total of eight studies with 411 osteosarcoma patients were involved to estimate the relationship between c-erbB2 expression and 5-year overall survival. Positive expressions of c-erbB2 predicted poorer survival in osteosarcoma with the pooled RR of 1.53 (95 % CI 1.20-1.94, P = 0.0006). In conclusion, the findings from this present meta-analysis suggest that c-erbB2 overexpression is related to poor prognostic of osteosarcoma and can be a useful clinical prognostic factor for those patients.

Clinicopathological features of kidney injury in patients receiving immune checkpoint inhibitors (ICPi) combined with anti-vascular endothelial growth factor (anti-VEGF) therapy.

BACKGROUND: Immune checkpoint inhibitor (ICPi) combined with anti-vascular endothelial growth factor (VEGF) therapy has increasingly become a promising strategy in various malignancies. However, the combination might be associated with increased risk of nephrotoxicity. METHODS: We retrospectively recruited patients who suffered kidney injury and received renal biopsy after anti-VEGF/ICPi mono- or combination therapy and divided them into three groups: anti-VEGF monotherapy, ICPi monotherapy and combination therapy. Clinical and histopathological features of three groups were analysed. All patients were followed-up for 3 months after biopsy, with or without glucocorticoid treatment, and renal outcome were compared. RESULTS: A total of 46 patients were enrolled. Eighteen patients received anti-VEGF monotherapy, 12 received ICPi monotherapy and 16 received combined treatment of anti-VEGF and ICPi. Proteinuria level of anti-VEGF group, ICPi group and combination group were 4.07±3.17 g/day, 0.60±0.61 g/day and 2.05±2.50 g/day, respectively (p=0.002). The peak serum creatinine level of combination group (1.75±0.77 mg/dL) was also in between ICPi group (2.79±0.90 mg/dL) and anti-VEGF group (1.34±0.60 mg/dL) (p<0.001). Multiple histopathological patterns involving glomerulus, tubulointerstitium and vessel existed in the majority of cases in combination group (68.8%). Renal complete and partial recovery rate of combination therapy were also in between monotherapy (57.1% vs 40.0% in anti-VEGF group, 100.0% in ICPi group, respectively). CONCLUSIONS: Kidney injury in patients treated with combination therapy of ICPi and anti-VEGF shows hybrid pathological patterns and intermediate clinical features compared with monotherapy. Cohorts with larger sample and better design, as well as basic research, are needed to elucidate the mechanism of 'protection' effect of combination anti-cancer therapy to renal function.

Development of a Semi-Active Electromagnetic Vibration Absorber and Its Experimental Study.

In this work, a semiactive electromagnetic vibration absorber has been developed based on a proposed electromagnetic stiffness adjustable spring model, which presents a new solution for adjusting stiffness in the field of vibration absorber devices. Simulation study on the electromagnetic spring has been performed to determine the structural parameter of the semiactive vibration absorber. An experimental rig is also built up to investigate its practical vibration control effectiveness. Firstly, the finite element model of the test bench is used to analyze its vibration characteristics. Then, the vibration reduction effect is predicted through the simulation analysis, from which the optimal control positions are found. Finally, the experimental studies are also conducted, and the results show that this semiactive electromagnetic vibration absorber has a frequency adjustment range from 21 Hz to 25 Hz, in which considerable vibration reduction from 5 dB to 10 dB can be achieved.

Effect of yiqiyangyin recipe on heparanase and nephrin in rats with adriamycin-induced nephropathy.

OBJECTIVE: To discuss the mechanism of Yiqiyangyin recipe in rats with adriamycin (ADR)-induced nephropathy. METHODS: We randomly divided 30 Sprague-Dawley rats into 5 groups: control, model, glucocorticoid, Chinese herb, and Chinese herb plus glucocorticoid groups. The 24-h urine volume was collected on days 7, 14, 21, and 28 after ADR injection, and all rats were killed on day 28. We measured the 24-h levels of urinary protein, serum cholesterol, and serum triglycerides, and renal function of all rats by using routine biochemical methods. Pathological changes in the rat kidneys were observed under light and electron microscopes. Heparanase (HPA) mRNA expression levels were measured using real-time fluorescence-quantitative polymerase chain reaction. Urine levels of HPA in all groups were measured using enzyme-linked immunosorbent assay. The expression of nephrin was detected by immunohistochemical staining and quantitatively analyzed using Motic image analysis 3.2 software. RESULTS: The levels of urinary protein and serum triglycerides and cholesterol in rats with ADR-induced nephropathy increased on day 14. The serum albumin levels simultaneously decreased. All the changes reached the peak on day 28. Examination under the light microscope showed inflammatory cells and slight fibroplasia in the renal interstitium in the model group, but fewer inflammatory cells were observed in the intervention groups than those in the model group. Examination under the electron microscope showed extensive fusion of foot processes in ADR rats. HPA mRNA expression was higher in the model group than that in the control group. The HPA mRNA levels in the intervention groups, especially in the Chinese herb group, and Chinese herb plus glucocorticoid group were significantly lower than the level in the model group. The HPA expression levels correlated significantly with the proteinuria level. No significant difference was found in the HPA level in urine between the intervention groups and the model group, whereas the model group had a higher urinary HPA level than the control group. Nephrin mRNA expression levels in the model group were higher than those in the control group. Nephrin mRNA expression levels were significantly lower in the intervention groups than that in the model group, especially the Chinese herb plus glucocorticoid group. Compared with the control group, the model group showed increased nephrin expression in the kidney. Nephrin levels in the other groups, especially in the Chinese herb plus glucocorticoid group, were significantly lower than that in the model group. The nephrin levels in the kidney were negatively correlated with the proteinuria level. CONCLUSION: Yiqiyangyin recipe could attenuate foot process injury particularly in combination with a steroid reduce the development of proteinuria possibly by inhibition of HPA in the kidney, and regulate the expression of nephrin in rats with ADR-induced nephropathy. Our study showed that treatment with Yiqiyangyin recipe plus glucocorticoid was better than a singular intervention, and we explored the pharmacological mechanism of this combination by biochemical and molecular biological analysis to provide a basis for clinical application.

The innate immune-related genes in catfish.

Catfish is one of the most important aquaculture species in America (as well as in Asia and Africa). In recent years, the production of catfish has suffered massive financial losses due to pathogen spread and breakouts. Innate immunity plays a crucial role in increasing resistance to pathogenic organisms and has generated increasing interest in the past few years. This review summarizes the current understanding of innate immune-related genes in catfish, including pattern recognition receptors, antimicrobial peptides, complements, lectins, cytokines, transferrin and gene expression profiling using microarrays and next generation sequencing technologies. This review will benefit the understanding of innate immune system in catfish and further efforts in studying the innate immune-related genes in fish.

Mechanism of Long Noncoding RNA HOTAIR in Nucleus Pulposus Cell Autophagy and Apoptosis in Intervertebral Disc Degeneration.

OBJECTIVE: Intervertebral disc degeneration (IDD) contributes to cervical and lumbar diseases. Long noncoding RNAs (lncRNAs) are implicated in IDD. This study explored the mechanism of lncRNA HOTAIR in IDD. METHODS: Normal and degenerative nucleus pulposus (NP) cells were isolated from NP tissues obtained in intervertebral disc surgery. Cell morphology was observed by immunocytochemistry staining and toluidine blue staining. NP cell markers were detected by RT-qPCR. Proliferation was detected by MTT assay. Autophagy-related proteins were detected by Western blot. Autophagosome was observed by monodansylcadaverine fluorescence staining. Apoptosis was detected by TUNEL staining and flow cytometry. si-HOTAIR and/or miR-148a inhibitor was introduced into degenerative NP cells. Binding relationships among HOTAIR, miR-148a, and PTEN were predicted and verified by dual-luciferase reporter assay and RNA pull-down. Finally, IDD rat models were established. Rat caudal intervertebral discs were assessed by HE staining. Expressions of HOTAIR, miR-148a, and PTEN were determined by RT-qPCR. RESULTS: HOTAIR was highly expressed in degenerative NP cells (p < 0.05). si-HOTAIR inhibited degenerative NP cell apoptosis and autophagy (p < 0.05). HOTAIR upregulated PTEN as a sponge of miR-148a. miR-148a was poorly expressed in degenerative NP cells. miR-148a deficiency partially reversed the inhibition of si-HOTAIR on degenerative NP cell autophagy and apoptosis (all p < 0.05). In vivo assay confirmed that si-HOTAIR impeded autophagy and apoptosis in intervertebral disc tissues, thus improving pathological injury in IDD rats (all p < 0.05). CONCLUSION: LncRNA HOTAIR promoted NP cell autophagy and apoptosis via promoting PTEN expression as a ceRNA of miR-148a in IDD.

Heparanase promotes endothelial-to-mesenchymal transition in diabetic glomerular endothelial cells through mediating ERK signaling.

Glomerular endothelial cells (GEnCs) dysfunction occurs at the early stage of diabetic nephropathy (DN). One of its characteristics is endothelial-to-mesenchymal transition (EndMT). Heparanase (HPSE) is the only known mammalian endoglycosidase capable of degrading heparin sulfates and has a prominent role in DN pathogenesis. However, whether HPSE induces EndMT of GEnCs remains unknown. This study aimed to determine the effect and potential mechanism of HPSE on GEnCs phenotype under high-glucose conditions. In the early development of streptozotocin (STZ)-induced diabetic mice, HPSE overexpression was positively correlated with renal injury and the number of GEnCs undergoing EndMT, which was characterized by loss of endothelial marker CD31 and gain of mesenchymal markers including α-SMA and Snail1/2 by double immunofluorescence staining. Bioinformatics analysis revealed a positive correlation between HPSE and ERK. The counts of double positive staining of CD31 and p-ERK1/2 was significantly increased in the glomeruli of STZ-induced diabetic mice compared with sham mice. In cultured GEnCs, high glucose dramatically upregulated the expressions of HPSE and p-ERK1/2, both of which were markedly blocked by HPSE siRNA. Furthermore, recombinant mouse HPSE (rmHPSE) promoted the expressions of mesenchymal markers and p-ERK1/2 in a dosage- and time-dependent manner. U0126, a specific MEK/ERK inhibitor, significantly inhibited either high glucose or rmHPSE-induced EndMT of GEnCs. These data indicate that high glucose induces EndMT of GEnCs at least partially through upregulating HPSE and that HPSE promotes EndMT of GEnCs via activating ERK signaling. This study improves understanding the crucial role of HPSE in DN development and progression.

Construction of a series of Ln-MOF luminescent sensors based on a functional "V" shaped ligand.

It is necessary to decrease the application cost of luminescent Ln-MOF sensors to develop multiple functionalities. The ingenious design of ligands and the rational doping of Ln3+ ions are the main approaches to endowing Ln-MOFs with more functionalities. "V" shaped ligands can cause diamond pore channels commonly. "OC-NH" groups as hydrogen bonding sites not only can participate in supramolecular self-assembly but also can achieve molecular recognition. Based on the above considerations, a "V" shaped ligand, H2L, with a suitable triplet state and "OC-NH" groups was designed and synthesized firstly. And the Ln-MOFs (Ln = Eu, Gd, Tb) were obtained by solvothermal reactions. Single crystal X-ray diffraction showed that Ln-MOFs had two types of diamond pore channels where "OC-NH" groups adhered to the surface. "OC-NH" groups not only played an important role in the stacking process of 2D coordinated layers but also can reduce the non-radiative transition resulting from molecular vibration. The Eu-MOF and Tb-MOF not only can emit strong "f-f" transitions characteristic of luminescence but also can detect o-phenylenediamine (OPD) and p-phenylenediamine (PPD) by luminescence quenching. Besides, EuxTb1-x-MOFs (x = 0.02, 0.05, 0.1) were synthesized and can be used as ratio luminescence thermometers whose maximum relative sensitivities were 1.19% K-1 at 400 K. It is pointed out specifically that the relationship between the relative sensitivities and the Eu3+ content was studied. What's more, our work not only developed a series of Ln-MOF luminescent sensors by designing functional ligands and doping Ln3+ rationally but also provided valuable knowledge for the following work.

Expression of response gene to complement-32 in renal tissue of children with immunoglobulin A nephropathy.

OBJECTIVE: This study aimed to investigate the expression and significance of response gene to complement-32 (RGC-32) in renal tissue of children with immunoglobulin A nephropathy (IgAN). MATERIAL AND METHODS: Forty-five patients diagnosed as having IgAN by renal biopsy were enrolled. The expression of RGC-32, α-smooth muscle actin (α-SMA) and transforming growth factor-ß(1) (TGF-ß(1)) was observed by immunohistostaining. The relationshis between the expression of RGC-32, α-SMA, TGF-ß1, degree of renal pathological lesions in IgAN and clinical index were assessed by Spearman correlation. RESULTS: Immunohistostaining analysis showed that RGC-32 protein was present in epithelial cells of renal tubules in normal and IgAN renal tissues. With more severe renal pathological lesions, the expression of RGC-32 in IgAN was increased. The expression of RGC-32 was positively correlated with that of α-SMA, TGF-ß(1) and the degree of renal pathological lesions in children with IgAN (p < 0.05), but had no relationship with serum creatinine, urinary N-acetyl-ß-d-glucosaminidase/creatinine, urinary microalbuminuria/creatinine, urinary microimmunoglobulin/creatinine or urinary α(1)-microglobulin/creatinine ratio (p > 0.05). CONCLUSION: Expression of RGC-32 can reflect the degree of renal pathological lesions in IgAN. RGC-32 may participate in the renal tubulointerstitial lesions in children with IgAN, especially in epithelial -mesenchymal transition induced by TGF-ß(1).

[FAK/c-Src signaling pathway mediates the expression of cell surface HSP90 in cultured human prostate cancer cells and its association with their invasive capability].

OBJECTIVE: To investigate the expression of heat shock protein 90 (HSP90) on the cell surface of highly invasive human prostate cancer cells PC3 and its possible molecular mechanisms of its effect on cell invasion through analyzing FAK/Src signaling pathway. METHODS: The expression of cell surface HSP90 on PC3 cells was studied by immunofluorescence staining and surface biotinylation assay respectively. A specific HSP90 antibody was used to inhibit the cell surface HSP90. In vitro cell invasion was assessed by modified Boyden chambers. Phosphorylated FAK on tyr 397, 576, 577 and 925, and phosphorylated c-Src on tyr 416 were examined by Western blot assay. The association between FAK and c-Src was analyzed by immunoprecipitation. The effects of FAK knockdown by siRNA or Src kinases inhibitor PP2, with or without anti-HSP90 antibody, on PC3 cell invasion were also evaluated. RESULTS: A pool of HSP90 was detected on the cell surface of PC3 cells. A specific HSP90 antibody significantly retarded tumor cell invasion. Concomitant with this finding, targeting cell surface HSP90 significantly inhibited the phosphorylations of FAK and c-Src, and also the interactions between FAK and c-Src. FAK knockdown or PP2 dramatically suppressed cell invasion, however, anti-HSP90 antibody didn't further inhibit cell invasion. CONCLUSIONS: Cell surface HSP90 promotes human prostate cancer cell invasion through a FAK/c-Src signaling, with may be a novel therapeutic target against metastatic tumors.

[Effects of Chinese herbal medicine Huaiqihuang Granule on nephrin and podocin expressions in renal tissues of rats with adriamycin-induced nephrosis].

OBJECT: To investigate the effects of Huaiqihuang Granule, a compound Chinese herbal medicine, on expressions of nephrin and podocin of slit diaphragm of glomerular podocytes in rats with adriamycin-induced nephrosis and to explore the mechanism in reducing the proteinuria. METHODS: Twenty SD rats were randomly divided into five groups: control group, model group, glucocorticoid group, Huaiqihuang Granule group and Huaiqihuang Granule plus glucocorticoid group. The 24-hour urine was collected 7, 14, 21 and 28 days after adriamycin injection respectively to measure 24-hour urinary protein, and all rats were sacrificed after 28-day treatment. Pathological changes in renal tissues were observed under a light microscope and an electron microscope. Expressions of nephrin and podocin mRNAs in renal cortex were determined by real-time polymerase chain reaction, and protein levels of nephrin and podocin were detected by Western blotting. RESULTS: (1) In the model group and the treatment groups, the level of urinary protein increased significantly from the 14th day. (2) Under the light microscope, inflammatory cells and slight fibroplasia were found in renal interstitium of the model group, but there were less inflammatory cells in renal interstitium in the intervention groups than in the model group. Under the electron microscope, 29 days after adriamycin injection, extensive fusion of foot processes was observed. (3) The expressions of nephrin and podocin were higher in treatment groups than in the model group. (4) Proteinuria level was negatively correlated with the expressions of nephrin mRNA and nephrin and podocin proteins. CONCLUSION: The above results indicate that Huaiqihuang Granule can maintain the integrity of the slid diaphragram in podocyte, alleviate the lesion of glomerular filtration membrane, and decrease the proteinuria by up-regulating the expressions of nephrin and podocin. Huaiqihuang Granule plus glucocorticoid maybe has better effects than glucocorticoid alone.

A New RBPs-Related Signature Predicts the Prognosis of Colon Adenocarcinoma Patients.

The dysregulation of RNA binding proteins (RBPs) is closely related to tumorigenesis and development. However, the role of RBPs in Colon adenocarcinoma (COAD) is still poorly understood. We downloaded COAD's RNASeq data from the Cancer Genome Atlas (TCGA) database, screened the differently expressed RBPs in normal tissues and tumor, and constructed a protein interaction network. COAD patients were randomly divided into a training set (N = 315) and a testing set (N = 132). In the training set, univariate Cox analysis identified 12 RBPs significantly related to the prognosis of COAD. By multivariate COX analysis, we constructed a prognostic model composed of five RBPs (CELF4, LRRFIP2, NOP14, PPARGC1A, ZNF385A) based on the lowest Akaike information criterion. Each COAD patient was scored according to the model formula. Further analysis showed that compared with the low-risk group, the overall survival rate (OS) of patients in the high-risk group was significantly lower. The area under the curve of the time-dependent receiver operator characteristic (ROC) curve was 0.722 in the training group and 0.738 in the test group, which confirmed a good prediction feature. In addition, a nomogram was constructed based on clinicopathological characteristics and risk scores. C-index and calibration curve proved the accuracy in predicting the 1-, 3-, and 5-year survival rates of COAD patients. In short, we constructed a superior prognostic and diagnostic signature composed of five RBPs, which indicates new possibilities for individualized treatment of COAD patients.

Ferroptosis-Related Gene Signature Accurately Predicts Survival Outcomes in Patients With Clear-Cell Renal Cell Carcinoma.

As a type of regulated cell death induced by Ras selective lethal (RSL) compounds such as erasti, ferroptosis is characterized by iron-dependent lipid peroxide accumulation to lethal levels. At present, little is known about the role of ferroptosis-related genes in clear-cell renal cell carcinoma (ccRCC). In the present study, the expression data of ferroptosis-related genes in ccRCC were obtained from the Cancer Genome Atlas (TCGA), and COX regression analysis was performed to construct a risk model of ferroptosis prognostic signature. The GEO database was used to verify the accuracy of the model. The following findings were made: the results reveal that the prognostic signature constructed by 11 ferroptosis genes (CARS, CD44, DPP4, GCLC, HMGCR, HSPB1, NCOA4, SAT1, PHKG2, GOT1, HMOX1) was significantly related to the overall survival (OS) of ccRCC patients based on the lowest Akaike information criterion (AIC); multivariate analysis indicates that ferroptosis-related gene prognostic signature was an independent prognostic factor in ccRCC patients; the calibration curve and c-index value (0.77) demonstrate that the nomogram with the signature could predict the survival of ccRCC patients; and enrichment analysis shows that the high-risk group were enriched in humoral immunity and receptor interaction pathways. The aforementioned findings indicate that the ferroptosis-related gene signature can accurately predict the prognosis of ccRCC patients and provide valuable insights for individualized treatment.

Undernutrition when young and the risk of poor renal function in adulthood in women with diabetes in Shanghai, China.

OBJECTIVE: To evaluate the effect of undernutrition when young on the risk of poor renal function in adulthood in women with diabetes mellitus. METHODS: We studied diabetic women born between 1921 and 1958 who were exposed to the 1959-to-1962 Chinese famine when they were 0 to 37 years old. Exposure age was classified as young adulthood (18 to 37 years), adolescence (10 to 17 years), or childhood (0 to 9 years). The Adolescence group, which was provided with the largest amount of food during the famine, was used as the control group, and variance and binary logistic regression analyses were performed. RESULTS: The prevalences of low estimated glomerular filtration rate (eGFR) in the Childhood, Adolescence, and Young adulthood groups were 5.26%, 22.39%, and 79.24%, respectively. The risk of low eGFR for the Young adulthood group (odds ratio [OR] 1.65, 95% confidence interval [CI] 1.10, 2.48), but not for the Childhood group (OR 1.10, 95% CI 0.68, 1.78), was higher than that for the Adolescence group after adjustment for potential confounders. CONCLUSIONS: Undernutrition during young adulthood significantly increases the risk of renal dysfunction in adult women with diabetes. Therefore, the nutrition of less affluent young women should be improved.