Efficacy and safety of low-dose corticosteroids combined with leflunomide for progressive IgA nephropathy: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: The effectiveness of immunosuppressive and corticosteroid treatments for Immunoglobulin A (IgA) nephropathy (IgAN) remains thoroughly evaluated. We undertook a meta-analysis to investigate the efficacy and safety of low-dose corticosteroids plus leflunomide for progressive IgA nephropathy. METHODS: Eligible studies were obtained from PubMed, Embase, and Cochrane Library databases. We also searched the references of the included studies. Our protocol followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist. Eligibility criteria were defined using a PICOS framework. RESULTS: Our study included three articles presenting 342 patient cases. Findings revealed that low-dose corticosteroids combined with the leflunomide group were effective in relieving urine protein excretion (UPE) [mean difference (MD) = -0.35, 95% confidence interval (CI): -0.41 to -0.30, P < 0.00001] compared with the full-dose corticosteroids group. Regarding serum creatinine (SCr), estimated glomerular filtration rate (eGFR), complete remission rate, and overall response rate, there was no difference between the groups (p > 0.05). Regarding safety, low-dose corticosteroids combined with leflunomide significantly reduced the risk of serious adverse events [odds ratio (OR): 0.11, 95% CI: 0.01 to 0.91, P = 0.04]. Besides, no significant differences were observed between the two groups in the incidence of respiratory infection, abnormal liver function, diarrhea, herpes zoster, alopecia, pruritus, insomnia, pneumonia, diabetes, and urinary tract infection (P > 0.05). CONCLUSIONS: Low-dose corticosteroids combined with leflunomide are a safe and effective treatment for progressive IgA nephropathy. TRIAL REGISTRATION: The PROSPERO registration number is CRD42022361883.

Systematic review and meta-analysis of the efficacy of exercise intervention in kidney transplant recipients.

BACKGROUND AND OBJECTIVE: There is uncertainty about the beneficial effects of exercise intervention for kidney transplant recipients. The purpose of our meta-analysis is to estimate the efficacy of exercise intervention in kidney transplant recipients. METHODS: A database search according to the PICOS framework was performed for all published randomized, double-blind, placebo-controlled trials (RCTs) about exercise intervention for kidney transplant recipients. The databases involved include PubMed, Embase, and Cochrane Library. RESULTS: A total of 16 RCTs (involving 827 patients) in compliance with inclusion criteria were included in our study. The results demonstrated that adequate exercise intervention improved statistically in creatinine clearance [mean difference (MD) = - 0.29, 95% confidence interval (CI) - 0.46 to - 0.11, p = 0.001], serum urea (MD = - 21.57, 95% CI - 35.84 to - 7.29, p = 0.003), VO2 peak (MD = 3.20, 95% CI 1.97-4.43, p < 0.00001), high-density lipoprotein-cholesterol (HDL-C) (MD = 0.21, 95% CI 0.04-0.37, p = 0.01), 60-s sit to stand test (60-STS) (MD = 14.47, 95% CI 8.89-20.04, p < 0.00001), 6-min walk distance (6-MWD) (MD = 91.87, 95% CI 38.34-145.39, p = 0.0008), and 6-min walk test (6-MWT) (MD = 44.08, 95% CI 20.30-67.87, p = 0.0003) of patients after kidney transplantation. No between-groups differences (p > 0.05) were observed for anthropometric characteristics, body composition, serum cytokine levels, and quality of life short form-36 questionnaire (SF-36). CONCLUSIONS: In kidney transplant recipients, appropriate exercise intervention improved renal function, cardiopulmonary function, physical performance. TRIAL REGISTRATION: The PROSPERO registration number is CRD42022357574.

The underlying mechanism of metabolic syndrome on benign prostatic hyperplasia and prostate volume.

OBJECTIVE: To investigate the potential mechanism of the effect of metabolic syndrome (MetS) on prostate volume (PV) and the risk of benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) and the relationships of MetS and the major pathogenic factors of MetS with the clinical progression of BPH/LUTS in older Chinese men. SUBJECTS AND METHODS: We analyzed clinical data obtained from 506 ostensibly healthy men who underwent routine health check-ups and recruited 415 subjects from a group of previously studied men after 4 years. We evaluated the associations of major pathological factors of MetS, including insulin resistance, subclinical inflammatory state, and sex hormone changes, with PV, the risk of BPH and the clinical progression of BPH/LUTS by using multiple linear regression and logistic regression. RESULTS: After adjustment for age, insulin, HOMA (homeostatic model assessment) index, leptin, resistin, adiponectin, C-reactive protein, tumor necrosis factor-α (TNF-α), sex hormone-binding globulin, and testosterone levels were significantly associated with PV (all P < .05), and in the age-adjusted logistic regression model, positive associations of resistin and TNF-α with BPH/LUTS were found (OR, 1.662, P = .007 and OR, 1.044, P < .001, respectively). Predictors of BPH/LUTS clinical progression were significantly correlated with MetS and TNF-α. The group with higher TNF-α levels had a higher rate of newly diagnosed BPH (9.5% vs 19.1%, P = .006) and a greater increase in PV levels (0.61 ± 0.08 vs 1.09 ± 0.35 cm3 , P <.001) after 4 years. CONCLUSIONS: MetS and its pathological factors were associated with an increased PV and an increased risk of BPH/LUTS that is more prone to clinical progression. TNF-α may serve as an early biological indicator to identify which patients with BPH/LUTS are at higher risk of unfavorable outcomes.

On-surface Synthesis of a Semiconducting 2D Metal-Organic Framework Cu3 (C6 O6 ) Exhibiting Dispersive Electronic Bands.

A 2D metal-organic framework (2D-MOF) was formed on a Cu(111) substrate using benzenehexol molecules. By means of a combination of scanning tunneling microscopy and spectroscopy, X-ray photoelectron spectroscopy and density-functional theory, the structure of the 2D-MOF is determined to be Cu3 (C6 O6 ), which is stabilized by O-Cu-O bonding motifs. We find that upon adsorption on Cu(111), the 2D-MOF features a semiconductor band structure with a direct band gap of 1.5 eV. The O-Cu-O bonds offer efficient charge delocalization, which gives rise to a highly dispersive conduction band with an effective mass of 0.45 me at the band bottom, implying a high electron mobility in this material.

Rational Design Principles of the Quantum Anomalous Hall Effect in Superlatticelike Magnetic Topological Insulators.

As a paradigmatic phenomenon in condensed matter physics, the quantum anomalous Hall effect (QAHE) in stoichiometric Chern insulators has drawn great interest for years. Using model Hamiltonian analysis and first-principles calculations, we establish a topological phase diagram and map different 2D configurations to it, which are taken from the recently grown magnetic topological insulators MnBi_{4}Te_{7} and MnBi_{6}Te_{10} with superlatticelike stacking patterns. These configurations manifest various topological phases, including the quantum spin Hall effect with and without time-reversal symmetry and QAHE. We then provide design principles to trigger the QAHE by tuning experimentally accessible knobs, such as the slab thickness and magnetization. Our work reveals that superlatticelike magnetic topological insulators with tunable exchange interactions are an ideal platform to realize the long-sought QAHE in pristine compounds, paving a new path within the area of topological materials.

Kinetically Controlled Synthesis of Four- and Six-Member Cyclic Products via Sequential Aryl-Aryl Coupling on a Au(111) Surface.

We synthesize four- and six-member cyclic products via sequential multi-step aryl-aryl coupling reactions of 2,3,6,7,10,11-hexabromotriphenylene molecules on a Au(111) surface. The final products as well as the organo-gold intermediate structures are identified using scanning tunneling microscopy and density-functional theory simulation. By adjusting reaction temperature and post-annealing temperature, we enhance/suppress the yields of the four-member and six-member cyclic products. We propose an underlying mechanism which is associated with different reaction kinetics of the first-order and second-order reactions. This work exemplifies intricate kinetically-controlled on-surface synthesis when multiple reactions of different reaction order are involved.

The association of pathogenic factors of metabolic syndrome on serum prostate-specific antigen levels: a pilot study.

BACKGROUND: Metabolic syndrome (MetS) and serum prostate-specific antigen (PSA) levels are correlated. To investigate the underlying effect of MetS on PSA levels, the relationship between the major pathogenic factors of MetS and serum PSA levels was studied. METHODS: A total of 506 ostensibly healthy men who underwent routine health check-ups were recruited to this study. We evaluated the effect of the major pathogenic factors of MetS, which included insulin resistance, a subclinical inflammatory state and sexual hormone changes, on serum PSA levels by using linear regression analysis and multivariate analysis after adjusting for age, BMI and prostate volume. RESULTS: When simultaneously adjusting for age, BMI, prostate volume and high-density lipoprotein cholesterol, serum insulin levels and SHBG levels were inversely correlated with serum PSA levels (P = 0.049 and P = 0.004, respectively), and testosterone levels were positively correlated with serum PSA levels (P = 0.039). In multivariate regression models, serum insulin levels and serum SHBG levels were significantly associated with serum PSA levels (both P < 0.001). CONCLUSIONS: Among the major pathogenic factors of metabolic syndrome, insulin resistance and sexual hormone changes may be the most significant contributors to the decline in serum PSA levels.

Identifying Multinuclear Organometallic Intermediates in On-Surface [2+2] Cycloaddition Reactions.

We investigate the on-surface [2+2] cycloaddition reaction of 2,3,6,7,10,11-hexabromotriphenylene (HBTP) on Ag(111), Cu(111), Au(111), and Cu-dosed Au(111) surfaces using STM and DFT simulation focusing on the organometallic intermediates. The fully debrominated HBTP molecules form an organo-silver framework on Ag(111) and an organo-copper framework on Cu(111), both incorporating multinuclear metal adatom clusters. The organo-silver framework is converted into porous covalent networks via [2+2] cycloaddition above 240 °C. In contrast, the organo-copper framework is very stable and does not undergo [2+2] cycloaddition even at 300 °C. On Au(111), no organo-gold intermediate of [2+2] cycloaddition is observed. After loading Cu onto Au(111), the partially debrominated HBTP molecules bind to Cu adatom dimers to form multinuclear organo-copper complexes at 100 °C which undergo [2+2] cycloaddition at 140 °C. This study shows that the choice of surface can direct the reaction pathway.

Stabilizing and Organizing Bi3 Cu4 and Bi7 Cu12 Nanoclusters in Two-Dimensional Metal-Organic Networks.

Multinuclear heterometallic nanoclusters with controllable stoichiometry and structure are anticipated to possess promising catalytic, magnetic, and optical properties. Heterometallic nanoclusters with precise stoichiometry of Bi3 Cu4 and Bi7 Cu12 can be stabilized in the scaffold of two-dimensional metal-organic networks on a Cu(111) surface through on-surface metallosupramolecular self-assembly processes. The atomic structures of the nanoclusters were resolved using scanning tunneling microscopy and density functional theory calculations. The nanoclusters feature highly symmetric planar hexagonal shapes and core-shell charge modulation. The clusters are arranged as triangular lattices with a periodicity that can be tuned by choosing molecules of different size. This work shows that on-surface metallosupramolecular self-assembly creates unique possibilities for the design and synthesis of multinuclear heterometallic nanoclusters.

Integration of basement membrane-related genes in a risk signature for prognosis in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is characterized by high heterogeneity and recurrence rates, posing significant challenges for stratification and treatment. Basement membrane-related genes (BMGs) play a crucial role in tumor initiation and progression. Clinical and transcriptomic data of ccRCC patients were extracted from TCGA and GEO databases. We employed univariate regression and LASSO-Cox stepwise regression analysis to construct a BMscore model based on BMGs expression level. A nomogram combining clinical features and BMscore was constructed to predict individual survival probabilities. Further enrichment analysis and immune-related analysis were conducted to explore the enriched pathways and immune features associated with BMGs. High-risk individuals predicted by BMscore exhibited poorer overall survival, which was consistent with the validation dataset. BMscore was identified as an independent risk factor for ccRCC. Functional analysis revealed that BMGs were related to cell-matrix and tumor-associated signaling pathways. Immune profiling suggests that BMGs play a key role in immune interactions and the tumor microenvironment. BMGs serve as a novel prognostic predictor for ccRCC and play a role in the immune microenvironment and treatment response. Targeting the BM may represent an alternative therapeutic approach for ccRCC.

Comprehensive Analysis of a Competing Endogenous RNA Co-Expression Network in Chronic Obstructive Pulmonary Disease.

Purpose: Chronic obstructive pulmonary disease (COPD) is the main cause of mortality world widely. Non-coding RNAs (lncRNAs) and associated competitive endogenous RNAs (ceRNAs) networks were recently proved to lead to mRNA gene expression downregulation but were still unclear in COPD. This study aims to investigate and elucidate the mechanisms underlying the involvement of ceRNA co-expression networks in COPD pathogenesis. Methods: Obtained expression signature of data from the Gene Expression Omnibus database and compared the differentially expression of mRNAs and miRNAs between COPD patients and healthy smokers. Predicted the miRNA-lncRNA and miRNA-mRNA interaction using online library and employed CIBERSORT to measure the proportions of the 22 immune cells in the COPD and control groups. Results: Established a ceRNA-network comprising 11 lncRNAs, 5 miRNAs, and 16 mRNAs. Using the weighted correlation network analysis method, we identified hub genes and hub miRNAs and obtained one core sub-network, XIST, FGD5-AS1, KCNQ1OT1, HOXA11-AS, LINC00667, H19, PRKCQ-AS1, NUTM2A-AS1/has-mir-454-3p/ZNF678, PRRG4. COPD patients had different proportions of immune cells than controls, and these variations were associated with the magnitude of pulmonary function parameters. Conclusion: The ceRNA-network, particularly the core sub-network, may be a putative goal for COPD, in which specific immune cells were involved.

The human microbiome links to prostate cancer risk and treatment (Review).

Prostate cancer (Pca) is the second most common cancer type worldwide. Microorganisms colonized in different body parts may affect the development/progression and treatment of Pca through direct or indirect interactions. The composition of microorganisms in different colonization sites and their effects on Pca may differ. In recent years, several studies have focused on the differences in the microbiota of patients with Pca, and dysbiosis may affect the inflammatory status, hormone levels and microbial metabolites leading to Pca progression. However, little is known about the interaction between Pca treatment and microorganisms; for example, how androgen deprivation therapy and androgen receptor axis­targeting therapeutics for Pca affect microbiota composition and metabolism, and how the microbiota affects treatment response in patients with Pca remain to be understood. The present review explored the current studies on the relevance of microbiota to Pca progression and treatment to provide direction for future microbiome­Pca research. Due to the complexity of the potential interconnections between Pca and the microbiota, further investigation is critical.

Efficacy and Safety of Ketamine Versus Opiates in the Treatment of Patients with Renal Colic: A Systematic Review and Meta-analysis.

INTRODUCTION: Renal colic is one of the most common urological emergencies, and is usually caused by ureteral colic spasms. Pain management in renal colic remains the central focus of emergency treatment. The purpose of this meta-analysis is to identify the efficacy and safety of ketamine versus opioids in the treatment of patients with renal colic. METHODS: We searched PubMed, EMBASE, Cochrane Library, and Web of Science databases for published randomized controlled trials (RCTs) that referred to the use of ketamine and opioids for patients with renal colic. The methodology was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The mean difference (MD) or odds ratio (OR) with a 95% confidence interval (CI) was used to analyze the data. The results were pooled using a fixed-effects model or random-effects model. The primary outcome measure was patient-reported pain scores 5, 15, 30, and 60 min after drug administration. The secondary outcome measure was side effects. RESULTS: The data analysis revealed that ketamine was similar to opioids in pain intensity at the time of 5 min post-dose (MD = - 0.40, 95% CI - 1.82 to 1.01, P = 0.57), 15 min post-dose (MD = - 0.15, 95% CI - 0.82 to 0.52, P = 0.67), 30 min post-dose (MD = 0.38, 95% CI - 0.25 to 1.01, P = 0.24). Also, the pain score of ketamine was better than that of opioids at 60 min after administration (MD = - 0.12, 95% CI - 0.22 to - 0.02, P = 0.02). As for safety, the ketamine group was linked to a significant decrease in the incidence of hypotensive (OR = 0.08, 95% CI 0.01-0.65, P = 0.02). The two groups did not statistically differ in the incidence of nausea, vomiting, and dizziness. CONCLUSIONS: Compared with opioids, ketamine showed a longer duration of analgesia in renal colic, with satisfactory safety. TRIAL REGISTRATION: The PROSPERO registration number is CRD42022355246.

A p-orbital honeycomb-Kagome lattice realized in a two-dimensional metal-organic framework.

The experimental realization of p-orbital systems is desirable because p-orbital lattices have been proposed theoretically to host strongly correlated electrons that exhibit exotic quantum phases. Here, we synthesize a two-dimensional Fe-coordinated bimolecular metal-organic framework which constitutes a honeycomb lattice of 1,4,5,8,9,12-hexaazatriphenylene molecules and a Kagome lattice of 5,15-di(4-pyridyl)-10,20-diphenylporphyrin molecules on a Au(111) substrate. Density-functional theory calculations show that the framework features multiple well-separated spin-polarized Kagome bands, namely Dirac cone bands and Chern flat bands, near the Fermi level. Using tight-binding modelling, we reveal that these bands are originated from two effects: the low-lying molecular orbitals that exhibit p-orbital characteristics and the honeycomb-Kagome lattice. This study demonstrates that p-orbital Kagome bands can be realized in metal-organic frameworks by using molecules with molecular orbitals of p-orbital like symmetry.

Relationship between serum total testosterone and prostate volume in aging men.

Total testosterone levels decline with age, while prostate volume and the prevalence of benign prostatic hyperplasia increase with age. We sought to investigate the correlation of serum testosterone levels with prostate volume in aging men. We analyzed clinical data obtained from 416 ostensibly healthy men who underwent routine health check-ups and recruited and collected data from these subjects 4 years later. We analyzed the correlation between prostate volume and relevant factors, as well as the correlation between changes in prostate volume and low testosterone over a 4-year period. Men with low testosterone had significantly larger prostate volume than those in the normal testosterone group (26.86 ± 8.75 vs. 24.06 ± 6.77 P = 0.02), and subjects with low testosterone had significantly higher levels of obesity-related factors, including waist circumference, body mass index, and insulin (all P < 0.001). After adjustment for age, testosterone level was negatively correlated with prostate volume (P = 0.004), and prostate volume and 4-year changes in prostate volume were associated with low testosterone. With increased testosterone level, prostate volume showed a significant linear decreasing trend. These findings provide evidence of the relationship between testosterone and prostate volume. Additional large studies are needed to confirm these preliminary results.

Highly Degenerate Ground States in a Frustrated Antiferromagnetic Kagome Lattice in a Two-Dimensional Metal-Organic Framework.

Realization of the Kagome antiferromagnetic (KAF) lattice is of high interest because the geometric frustration in the Kagome lattice is expected to give rise to highly degenerated ground states that may host exotic phases such as quantum spin liquid. Here we demonstrate the design and synthesis of a single-layer two-dimensional metal-organic framework (2D-MOF) containing a Kagome lattice of Fe(II) ions assembled on a Au(111) surface. First-principles calculations reveal that the Fe(II) ions are at a high spin state of S = 2 and are coupled antiferromagnetically with nearest-neighboring exchange J1 = 5.8 meV. The ground state comprises various degenerated spin configurations including the well-known q = 0 and q = √3 × âˆš3 phases. Remarkably, we observe a spin excitation at 6 meV using tunneling spectroscopy. This work points out a feasible route toward realizing spin 1/2 KAF, a candidate quantum spin liquid system, by replacing Fe(II) by Cu(II) in the same structure.

Topological Quantum States in Magnetic Oxides.

The realization of topological quantum states in devices is an important subject. According to whether or not the time-reversal symmetry is broken, topological materials can be classified into magnetic and nonmagnetic ones. In particular, magnetic topological materials are of importance, in which the coexistence of nontrivial band topology and magnetic orders gives exotic spintronics-related applications. However, experimental observations of magnetic topological quantum states are extremely difficult. In this Perspective, we review the recent progress to explore and design magnetic topological oxides such as topological semimetals and three-dimensional quantum anomalous Hall insulators, which are robustly stable against oxidation at ambient conditions. Most of these materials possess high Curie temperatures and are widely used in industrial applications, stimulating considerable experimental interest. Moreover, further discussions related to the topological classification and topological transitions are also present.

Isobaric tags for relative and absolute quantitation-based quantitative proteomic analysis of X-linked inhibitor of apoptosis and H2AX in etoposide-induced renal cell carcinoma apoptosis.

BACKGROUND: X-linked inhibitor of apoptosis (XIAP) is a vital factor in the anti-apoptosis mechanism of tumors and is highly expressed in renal cell carcinoma (RCC). However, the mechanism through which XIAP regulates DNA damage repair is unknown. This study investigated the regulatory mechanism of XIAP in etoposide-induced apoptosis in two Caki-1 cell lines with high or low XIAP expression. METHODS: The two cell lines were established using RNA interference technology. The differentially expressed proteins in the two cell lines were globally analyzed through an isobaric tags for relative and absolute quantitation-based quantitative proteomics approach. Proteomic analysis revealed 255, 375, 362, and 5 differentially expressed proteins after 0, 0.5, 3, and 12 h of drug stimulation, respectively, between the two cell lines. The identified differentially expressed proteins were involved in numerous biological processes. In addition, the expression of histone proteins (H1.4, H2AX, H3.1, H3.2, and H3.3) was drastically altered, and the effects of XIAP silencing were accompanied by the marked downregulation of H2AX. Protein-protein interactions were assessed and confirmed through immunofluorescence and Western blot analyses. RESULTS: The results suggested that XIAP may act as a vital cell signal regulator that regulates the expression of DNA repair-related proteins, such as H2AX, and influences the DNA repair process. CONCLUSIONS: Given these functions, XIAP may be the decisive factor in determining the sensitivity of RCC cell apoptosis induction in response to chemotherapeutic agents.

Synthesis and characterization of a single-layer conjugated metal-organic structure featuring a non-trivial topological gap.

We employ an on-surface assembly protocol to synthesize a single layer of a two-dimensional conjugated network (Ni3(HITP)2) on a Au(111) surface. The electronic coupling between the π orbital of the diimine ligand and the d orbital of the metal ion renders efficient π-conjugation. Density-functional theory calculations provide evidence of a non-trivial topological gap in the surface-adsorbed single layer. This work demonstrates that single-layer 2D metal-organic frameworks adsorbed on surfaces are a new class of 2D materials that host quantum phases.

Cell cycle-dependent positive and negative functions of Fun30 chromatin remodeler in DNA damage response.

The evolutionally conserved Fun30 chromatin remodeler in Saccharomyces cerevisiae has been shown to contribute to cellular resistance to genotoxic stress inflicted by camptothecin (CPT), methyl methanesulfonate (MMS) and hydroxyurea (HU). Fun30 aids in extensive DNA resection of DNA double stranded break (DSB) ends, which is thought to underlie its role in CPT-resistance. How Fun30 promotes MMS- or HU-resistance has not been resolved. Interestingly, we have recently found Fun30 to also play a negative role in cellular tolerance to MMS and HU in the absence of the Rad5-dependent DNA damage tolerance pathway. In this report, we show that Fun30 acts to down regulate Rad9-dependent DNA damage checkpoint triggered by CPT or MMS, but does not affect Rad9-independent intra-S phase replication checkpoint induced by MMS or HU. These results support the notion that Fun30 contributes to cellular response to DSBs by preventing excessive DNA damage checkpoint activation in addition to its role in facilitating DNA end resection. On the other hand, we present evidence suggesting that Fun30's negative function in MMS- and HU-tolerance in the absence of Rad5 is not related to its regulation of checkpoint activity. Moreover, we find Fun30 to be cell cycle regulated with its abundance peaking in G2/M phase of the cell cycle. Importantly, we demonstrate that artificially restricting Fun30 expression to G2/M does not affect its positive or negative function in genotoxin-resistance, but confining Fun30 to S phase abolishes its functions. These results indicate that both positive and negative functions of Fun30 in DNA damage response occur mainly in G2/M phase.