Ae index is an independent predictor of kidney stone recurrence in overweight and obese patients

Abstract Background Finding some convenient and economical indicators to initially screen overweight and obese patients at high risk of kidney stone recurrence can help them prevent stone recurrence with lower medical cost. The purpose of this article is to determine the clinical value of Ae index (Apo B × 1000/eGFR) as an independent predictor for kidney stone recurrence in overweight and obese populations. Methods We queried the electronic medical records of patients with kidney stone operated at our hospital from March 2016 to March 2022, and selected BMI ≥ 25 kg/m2 as the study population and divided the patients into stone recurrence group and non-recurrence group. Relevant parameters of routine blood and biochemical test, glycated serum protein (GSP), and history of hypertension and hyperglycemia were collected. Then the Chi-square test, independent samples t-test or Wilcoxon rank-sum test were used to calculate the differences between the two groups of data. Next, we performed univariate and multivariate logistic regression analysis to screen out the most significant variables Apo B and eGFR, and then we calculated the Ae index using the formula Apo B × 1000/eGFR, and analyzed the relationship between Ae index and kidney stone recurrence. Results Univariate analysis found that Apo B (OR:8.376,95%CI:3.093–22.680), Creatinine (OR:1.012,95%CI:1.003–1.021), Cystatin C(OR:2.747,95%CI:1.369–5.508), LDL-C (OR:1.588,95%CI:1.182–2.134), TC (OR:1.543,95%CI:1.198–1.988) were positively associated, eGFR (OR:0.980,95%CI:0.970–0.991) was negatively associated with kidney stone recurrence. And multivariate logistic regression analysis suggested that Apo B (OR:11.028, 95%CI:3.917–31.047) and eGFR (OR:0.976, 95%CI:0.965–0.988) were the most significant factors. Then we calculated Ae index and analyzed it, the sensitivity was 74.26% and the specificity was 60.00%, higher than either individual variable. Its smoothed curve revealed a non-linear relationship between them with the inflection point of 9.16. And the OR on the left side of the inflection point was 1.574 (95% CI: 1.228–2.018), whereas the OR on the right side of the inflection point was 1.088 (95% CI: 1.007–1.177). Conclusions Ae index is an easily calculated and obtained index that has some predictive value for kidney stone recurrence in overweight and obese patients, which is of interest

Time-dependent analysis of erectile dysfunction in kidney transplant recipients: insights from four distinct time periods

Abstract Background and intention Erectile dysfunction (ED) is an underappreciated clinical condition in men. This study aims to compare the dynamic changes in the distribution of ED among male kidney transplant recipients (mKTRs) in four epochs: end-stage renal disease period (ESRDp), early post-transplant period (EPTP), pre-COVID-19, and post-COVID-19. Methods General information was gathered through interviews, follow-ups, and medical records. The International Index of Erectile Function Questionnaire-5 was used to assess erectile function. The Mann–Whitney U test and chi-square test were used to analyze differences in ED strength. Univariate and logistic regression analyses were conducted to identify risk factors for ED. Results The database contains 230 mKTRs. In the ESRDp, 17.0% had normal erectile function, 53.5% had mild ED, 18.3% had moderate ED, and 11.3% had severe ED. In the EPTP, the distribution was 38.2% normal, 42.6% mild, 10.8% moderate, and 8.2% severe. In the pre-COVID-19 period, it was 34.3%, 47.3%, 10.4%, and 7.8%, and in the post-COVID-19 period, it was 23.0%, 45.6%, 21.3%, and 10.0%. Overall, erectile function improved after kidney transplant (KT). However, post-COVID-19, the proportion of erectile function significantly decreased compared to EPTP and pre-COVID-19 periods. Risk factors for post-pandemic ED included degree, Generalized Anxiexy Disorder-7, kidney donor type, postoperative time, hypertension and hemoglobin concentration. Conclusion KT improves erectile function in mKTRs within 5 years, but post-SARS-CoV-2 viral infection, ED worsens due to altered risk factors. These findings inform future research for comprehensive ED prevention and management strategies in this population

Additional file 1 of Ae index is an independent predictor of kidney stone recurrence in overweight and obese patients

Additional file 1: Table S1. Univariate analysis of patient data of overweight and obesity stone recurrence

Chaperone-mediated autophagy promotes breast cancer angiogenesis via regulation of aerobic glycolysis.

Evidence shows that chaperone-mediated autophagy (CMA) is involved in cancer cell pathogenesis and progression. However, the potential role of CMA in breast cancer angiogenesis remains unknown. We first manipulated CMA activity by knockdown and overexpressing of lysosome-associated membrane protein type 2A (LAMP2A) in MDA-MB-231, MDA-MB-436, T47D and MCF7 cells. We found that the tube formation, migration and proliferation abilities of human umbilical vein endothelial cells (HUVECs) were inhibited after cocultured with tumor-conditioned medium from breast cancer cells of LAMP2A knockdown. While the above changes were promoted after cocultured with tumor-conditioned medium from breast cancer cells of LAMP2A overexpression. Moreover, we found that CMA could promote VEGFA expression in breast cancer cells and in xenograft model through upregulating lactate production. Finally, we found that lactate regulation in breast cancer cells is hexokinase 2 (HK2) dependent, and knockdown of HK2 can significantly reduce the ability of CMA-mediated tube formation capacity of HUVECs. Collectively, these results indicate that CMA could promote breast cancer angiogenesis via regulation of HK2-dependent aerobic glycolysis, which may serve as an attractive target for breast cancer therapies

Noncovalent Immobilization of a Pyrene-Modified Cobalt Corrole on Carbon Supports for Enhanced Electrocatalytic Oxygen Reduction and Oxygen Evolution in Aqueous Solutions

Efficient oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) are the determinants of the realization of a hydrogen-based society, as sluggish OER and ORR are the bottlenecks for the production and utilization of H₂, respectively. A Co complex of 5,15-bis­(pentafluorophenyl)-10-(4)-(1-pyrenyl)­phenylcorrole (<b>1</b>) bearing a pyrene substituent was synthesized. When it was immobilized on multiwalled carbon nanotubes (MWCNTs), the <b>1</b>/MWCNT composite displayed very high electrocatalytic activity and durability for both OER and ORR in aqueous solutions: it catalyzed a direct four-electron reduction of O₂ to H₂O in 0.5 M H₂SO₄ with an onset potential of 0.75 V vs normal hydrogen electrode (NHE), and it catalyzed the oxidation of water to O₂ in neutral aqueous solution with an onset potential of 1.15 V (vs NHE, η = 330 mV). Control studies using a Co complex of 5,10,15-tris­(pentafluorophenyl)­corrole (<b>2</b>) demonstrated that the enhanced catalytic performance of <b>1</b> was due to the strong noncovalent π–π interactions between its pyrene moiety and MWCNTs, which were considered to facilitate the fast electron transfer from the electrode to <b>1</b> and also to increase the adhesion of <b>1</b> on carbon supports. The noncovalent immobilization of molecular complexes on carbon supports through strong π–π interactions appears to be a simple and straightforward strategy to prepare highly efficient electrocatalytic materials

MicroRNA Expression Profile in Penile Cancer Revealed by Next-Generation Small RNA Sequencing.

Penile cancer (PeCa) is a relatively rare tumor entity but possesses higher morbidity and mortality rates especially in developing countries. To date, the concrete pathogenic signaling pathways and core machineries involved in tumorigenesis and progression of PeCa remain to be elucidated. Several studies suggested miRNAs, which modulate gene expression at posttranscriptional level, were frequently mis-regulated and aberrantly expressed in human cancers. However, the miRNA profile in human PeCa has not been reported before. In this present study, the miRNA profile was obtained from 10 fresh penile cancerous tissues and matched adjacent non-cancerous tissues via next-generation sequencing. As a result, a total of 751 and 806 annotated miRNAs were identified in normal and cancerous penile tissues, respectively. Among which, 56 miRNAs with significantly different expression levels between paired tissues were identified. Subsequently, several annotated miRNAs were selected randomly and validated using quantitative real-time PCR. Compared with the previous publications regarding to the altered miRNAs expression in various cancers and especially genitourinary (prostate, bladder, kidney, testis) cancers, the most majority of deregulated miRNAs showed the similar expression pattern in penile cancer. Moreover, the bioinformatics analyses suggested that the putative target genes of differentially expressed miRNAs between cancerous and matched normal penile tissues were tightly associated with cell junction, proliferation, growth as well as genomic instability and so on, by modulating Wnt, MAPK, p53, PI3K-Akt, Notch and TGF-β signaling pathways, which were all well-established to participate in cancer initiation and progression. Our work presents a global view of the differentially expressed miRNAs and potentially regulatory networks of their target genes for clarifying the pathogenic transformation of normal penis to PeCa, which research resource also provides new insights into future investigations aimed to explore the in-depth mechanisms of miRNAs and other small RNAs including piRNAs in penile carcinogenesis regulation and effective target-specific theragnosis

Electrocatalytic Water Oxidation by a Water-Soluble Copper(II) Complex with a Copper-Bound Carbonate Group Acting as a Potential Proton Shuttle

Water-soluble copper­(II) complexes of the dianionic tridentate pincer ligand <i>N</i>,<i>N</i>′-2,6-dimethylphenyl-2,6-pyridinedicarboxamidate (<b>L</b>) are catalysts for water oxidation. In [<b>L</b>-Cu^II-DMF] (<b>1</b>, DMF = dimethylformamide) and [<b>L</b>-Cu^II-OAc]⁻ (<b>2</b>, OAc = acetate), ligand <b>L</b> binds Cu^II through three N atoms, which define an equatorial plane. The fourth coordination site of the equatorial plane is occupied by DMF in <b>1</b> and by OAc^– in <b>2</b>. These two complexes can electrocatalyze water oxidation to evolve O₂ in 0.1 M pH 10 carbonate buffer. Spectroscopic, titration, and crystallographic studies show that both <b>1</b> and <b>2</b> undergo ligand exchange when they are dissolved in carbonate buffer to give [<b>L</b>-Cu^II-CO₃H]⁻ (<b>3</b>). Complex <b>3</b> has a similar structure as those of <b>1</b> and <b>2</b> except for having a carbonate group at the fourth equatorial position. A catalytic cycle for water oxidation by <b>3</b> is proposed based on experimental and theoretical results. The two-electron oxidized form of <b>3</b> is the catalytically active species for water oxidation. Importantly, for these two oxidation events, the calculated potential values of <i>E</i>_p,a = 1.01 and 1.59 V vs normal hydrogen electrode (NHE) agree well with the experimental values of <i>E</i>_p,a = 0.93 and 1.51 V vs NHE in pH 10 carbonate buffer. The potential difference between the two oxidation events is 0.58 V for both experimental and calculated results. With computational evidence, this Cu-bound carbonate group may act as a proton shuttle to remove protons for water activation, a key role resembling intramolecular bases as reported previously

A New Class of Highly Potent and Selective Endomorphin-1 Analogues Containing α-Methylene-β-aminopropanoic Acids (Map)

A new class of endomorphin-1 (EM-1) analogues were synthesized by introduction of novel unnatural α-methylene-β-amino acids (Map) at position 3 or/and position 4. Their binding and functional activity, metabolic stability, and antinociceptive activity were determined and compared. Most of these analogues showed high affinities for the μ-opioid receptor and an increased stability in mouse brain homogenates compared with EM-1. Examination of cAMP accumulation and ERK1/2 phosphorylation in HEK293 cells confirmed the agonist properties of these analogues. Among these new analogues, H-Tyr-Pro-Trp-(2-furyl)­Map-NH₂ (analogue <b>12</b>) exhibited the highest binding potency (<i>K</i>_i^μ = 0.221 nM) and efficacy (EC₅₀ = 0.0334 nM, <i>E</i>_max = 97.14%). This analogue also displayed enhanced antinociceptive activity in vivo in comparison to EM-1. Molecular modeling approaches were then carried out to demonstrate the interaction pattern of these analogues with the opioid receptors. We found that, compared to EM-1, the incorporation of our synthesized Map at position 4 would bring the analogue to a closer binding mode with the μ-opioid receptor