Meet the authors: Meiling Wang, Wenjing Li, and Weixing Zhao.

Molecular Cell talks to co-first authors Meiling Wang and Wenjing Li with co-corresponding author Weixing Zhao about their paper, "Crucial roles of the BRCA1-BARD1 E3 ubiquitin ligase activity in homology-directed DNA repair" (in this issue of Molecular Cell) and what motivates their scientific pursuits.

Crucial roles of the BRCA1-BARD1 E3 ubiquitin ligase activity in homology-directed DNA repair.

The tumor-suppressor breast cancer 1 (BRCA1) in complex with BRCA1-associated really interesting new gene (RING) domain 1 (BARD1) is a RING-type ubiquitin E3 ligase that modifies nucleosomal histone and other substrates. The importance of BRCA1-BARD1 E3 activity in tumor suppression remains highly controversial, mainly stemming from studying mutant ligase-deficient BRCA1-BARD1 species that we show here still retain significant ligase activity. Using full-length BRCA1-BARD1, we establish robust BRCA1-BARD1-mediated ubiquitylation with specificity, uncover multiple modes of activity modulation, and construct a truly ligase-null variant and a variant specifically impaired in targeting nucleosomal histones. Cells expressing either of these BRCA1-BARD1 separation-of-function alleles are hypersensitive to DNA-damaging agents. Furthermore, we demonstrate that BRCA1-BARD1 ligase is not only required for DNA resection during homology-directed repair (HDR) but also contributes to later stages for HDR completion. Altogether, our findings reveal crucial, previously unrecognized roles of BRCA1-BARD1 ligase activity in genome repair via HDR, settle prior controversies regarding BRCA1-BARD1 ligase functions, and catalyze new efforts to uncover substrates related to tumor suppression.

BRCA1/BARD1 intrinsically disordered regions facilitate chromatin recruitment and ubiquitylation.

BRCA1/BARD1 is a tumor suppressor E3 ubiquitin (Ub) ligase with roles in DNA damage repair and in transcriptional regulation. BRCA1/BARD1 RING domains interact with nucleosomes to facilitate mono-ubiquitylation of distinct residues on the C-terminal tail of histone H2A. These enzymatic domains constitute a small fraction of the heterodimer, raising the possibility of functional chromatin interactions involving other regions such as the BARD1 C-terminal domains that bind nucleosomes containing the DNA damage signal H2A K15-Ub and H4 K20me0, or portions of the expansive intrinsically disordered regions found in both subunits. Herein, we reveal novel interactions that support robust H2A ubiquitylation activity mediated through a high-affinity, intrinsically disordered DNA-binding region of BARD1. These interactions support BRCA1/BARD1 recruitment to chromatin and sites of DNA damage in cells and contribute to their survival. We also reveal distinct BRCA1/BARD1 complexes that depend on the presence of H2A K15-Ub, including a complex where a single BARD1 subunit spans adjacent nucleosome units. Our findings identify an extensive network of multivalent BARD1-nucleosome interactions that serve as a platform for BRCA1/BARD1-associated functions on chromatin.

Spatial transcriptomics reveals light-induced chlorenchyma cells involved in promoting shoot regeneration in tomato callus.

Callus is a reprogrammed cell mass involved in plant regeneration and gene transformation in crop engineering. Pluripotent callus cells develop into fertile shoots through shoot regeneration. The molecular basis of the shoot regeneration process in crop callus remains largely elusive. This study pioneers the exploration of the spatial transcriptome of tomato callus during shoot regeneration. The findings reveal the presence of highly heterogeneous cell populations within the callus, including epidermis, vascular tissue, shoot primordia, inner callus, and outgrowth shoots. By characterizing the spatially resolved molecular features of shoot primordia and surrounding cells, specific factors essential for shoot primordia formation are identified. Notably, chlorenchyma cells, enriched in photosynthesis-related processes, play a crucial role in promoting shoot primordia formation and subsequent shoot regeneration. Light is shown to promote shoot regeneration by inducing chlorenchyma cell development and coordinating sugar signaling. These findings significantly advance our understanding of the cellular and molecular aspects of shoot regeneration in tomato callus and demonstrate the immense potential of spatial transcriptomics in plant biology.

MMiKG: a knowledge graph-based platform for path mining of microbiota-mental diseases interactions.

The microbiota-gut-brain axis denotes a two-way system of interactions between the gut and the brain, comprising three key components: (1) gut microbiota, (2) intermediates and (3) mental ailments. These constituents communicate with one another to induce changes in the host's mood, cognition and demeanor. Knowledge concerning the regulation of the host central nervous system by gut microbiota is fragmented and mostly confined to disorganized or semi-structured unrestricted texts. Such a format hinders the exploration and comprehension of unknown territories or the further advancement of artificial intelligence systems. Hence, we collated crucial information by scrutinizing an extensive body of literature, amalgamated the extant knowledge of the microbiota-gut-brain axis and depicted it in the form of a knowledge graph named MMiKG, which can be visualized on the GraphXR platform and the Neo4j database, correspondingly. By merging various associated resources and deducing prospective connections between gut microbiota and the central nervous system through MMiKG, users can acquire a more comprehensive perception of the pathogenesis of mental disorders and generate novel insights for advancing therapeutic measures. As a free and open-source platform, MMiKG can be accessed at http://yangbiolab.cn:8501/ with no login requirement.

Abscisic acid-induced transcription factor PsMYB306 negatively regulates tree peony bud dormancy release.

Bud dormancy is a crucial strategy for perennial plants to withstand adverse winter conditions. However, the regulatory mechanism of bud dormancy in tree peony (Paeonia suffruticosa) remains largely unknown. Here, we observed dramatically reduced and increased accumulation of abscisic acid (ABA) and bioactive gibberellins (GAs) GA1 and GA3, respectively, during bud endodormancy release of tree peony under prolonged chilling treatment. An Illumina RNA sequencing study was performed to identify potential genes involved in the bud endodormancy regulation in tree peony. Correlation matrix, principal component, and interaction network analyses identified a downregulated MYB transcription factor gene, PsMYB306, the expression of which positively correlated with 9-CIS-EPOXYCAROTENOID DIOXYGENASE 3 (PsNCED3) expression. Protein modeling analysis revealed 4 residues within the R2R3 domain of PsMYB306 to possess DNA binding capability. Transcription of PsMYB306 was increased by ABA treatment. Overexpression of PsMYB306 in petunia (Petunia hybrida) inhibited seed germination and plant growth, concomitant with elevated ABA and decreased GA contents. Silencing of PsMYB306 accelerated cold-triggered tree peony bud burst and influenced the production of ABA and GAs and the expression of their biosynthetic genes. ABA application reduced bud dormancy release and transcription of ENT-KAURENOIC ACID OXIDASE 1 (PsKAO1), GA20-OXIDASE 1 (PsGA20ox1), and GA3-OXIDASE 1 (PsGA3ox1) associated with GA biosynthesis in PsMYB306-silenced buds. In vivo and in vitro binding assays confirmed that PsMYB306 specifically transactivated the promoter of PsNCED3. Silencing of PsNCED3 also promoted bud break and growth. Altogether, our findings suggest that PsMYB306 negatively modulates cold-induced bud endodormancy release by regulating ABA production.

Kindlin2 regulates neural crest specification via integrin-independent regulation of the FGF signaling pathway.

The focal adhesion protein Kindlin2 is essential for integrin activation, a process that is fundamental to cell-extracellular matrix adhesion. Kindlin 2 (Fermt2) is widely expressed in mouse embryos, and its absence causes lethality at the peri-implantation stage due to the failure to trigger integrin activation. The function of kindlin2 during embryogenesis has not yet been fully elucidated as a result of this early embryonic lethality. Here, we showed that kindlin2 is essential for neural crest (NC) formation in Xenopus embryos. Loss-of-function assays performed with kindlin2-specific morpholino antisense oligos (MOs) or with CRISPR/Cas9 techniques in Xenopus embryos severely inhibit the specification of the NC. Moreover, integrin-binding-deficient mutants of Kindlin2 rescued the phenotype caused by loss of kindlin2, suggesting that the function of kindlin2 during NC specification is independent of integrins. Mechanistically, we found that Kindlin2 regulates the fibroblast growth factor (FGF) pathway, and promotes the stability of FGF receptor 1. Our study reveals a novel function of Kindlin2 in regulating the FGF signaling pathway and provides mechanistic insights into the function of Kindlin2 during NC specification.

Comparison of two single-pill dual combination antihypertensive therapies in Chinese patients: a randomized, controlled trial.

BACKGROUND: Current hypertension guidelines recommend combination of an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker with a calcium-channel blocker or thiazide diuretic as initial antihypertensive therapy in patients with monotherapy uncontrolled hypertension. However, to what extent these two different combinations are comparable in blood pressure (BP)-lowering efficacy and safety remains under investigation, especially in the Chinese population. We investigated the BP-lowering efficacy and safety of the amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies in Chinese patients. METHODS: In a multi-center, randomized, actively controlled, parallel-group trial, we enrolled patients with stage 1 or 2 hypertension from July 2018 to June 2021 in 20 hospitals and community health centers across China. Of the 894 screened patients, 560 eligible patients were randomly assigned to amlodipine/benazepril 5/10 mg (n = 282) or benazepril/hydrochlorothiazide 10/12.5 mg (n = 278), with 213 and 212 patients, respectively, who completed the study and had a valid repeat ambulatory BP recording during follow-up and were included in the efficacy analysis. The primary outcome was the change from baseline to 24 weeks of treatment in 24-h ambulatory systolic BP. Adverse events including symptoms and clinically significant changes in physical examinations and laboratory findings were recorded for safety analysis. RESULTS: In the efficacy analysis (n = 425), the primary outcome, 24-h ambulatory systolic BP reduction, was - 13.8 ± 1.2 mmHg in the amlodipine/benazepril group and - 12.3 ± 1.2 mmHg in the benazepril/hydrochlorothiazide group, with a between-group difference of - 1.51 (p = 0.36) mmHg. The between-group differences for major secondary outcomes were - 1.47 (p = 0.18) in 24-h diastolic BP, - 2.86 (p = 0.13) and - 2.74 (p = 0.03) in daytime systolic and diastolic BP, and - 0.45 (p = 0.82) and - 0.93 (p = 0.44) in nighttime systolic and diastolic BP. In the safety analysis (n = 560), the incidence rate of dry cough was significantly lower in the amlodipine/benazepril group than in the benazepril/hydrochlorothiazide group (5.3% vs 10.1%, p = 0.04). CONCLUSIONS: The amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies were comparable in ambulatory systolic BP lowering. The former combination, compared with the latter, had a greater BP-lowering effect in the daytime and a lower incidence rate of dry cough. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03682692. Registered on 18 September 2018.

Multi-instance learning based artificial intelligence model to assist vocal fold leukoplakia diagnosis: A multicentre diagnostic study.

OBJECTIVE: To develop a multi-instance learning (MIL) based artificial intelligence (AI)-assisted diagnosis models by using laryngoscopic images to differentiate benign and malignant vocal fold leukoplakia (VFL). METHODS: The AI system was developed, trained and validated on 5362 images of 551 patients from three hospitals. Automated regions of interest (ROI) segmentation algorithm was utilized to construct image-level features. MIL was used to fusion image level results to patient level features, then the extracted features were modeled by seven machine learning algorithms. Finally, we evaluated the image level and patient level results. Additionally, 50 videos of VFL were prospectively gathered to assess the system's real-time diagnostic capabilities. A human-machine comparison database was also constructed to compare the diagnostic performance of otolaryngologists with and without AI assistance. RESULTS: In internal and external validation sets, the maximum area under the curve (AUC) for image level segmentation models was 0.775 (95 % CI 0.740-0.811) and 0.720 (95 % CI 0.684-0.756), respectively. Utilizing a MIL-based fusion strategy, the AUC at the patient level increased to 0.869 (95 % CI 0.798-0.940) and 0.851 (95 % CI 0.756-0.945). For real-time video diagnosis, the maximum AUC at the patient level reached 0.850 (95 % CI, 0.743-0.957). With AI assistance, the AUC improved from 0.720 (95 % CI 0.682-0.755) to 0.808 (95 % CI 0.775-0.839) for senior otolaryngologists and from 0.647 (95 % CI 0.608-0.686) to 0.807 (95 % CI 0.773-0.837) for junior otolaryngologists. CONCLUSIONS: The MIL based AI-assisted diagnosis system can significantly improve the diagnostic performance of otolaryngologists for VFL and help to make proper clinical decisions.

Effects of Phase â Cardiac Rehabilitation Combined with Cognitive Behavioural Therapy on Cardiac Function, Exercise Capacity and Mental Health in Patients after Aortic Valve Replacement: A Retrospective Study.

OBJECTIVE: To explore the application effect of phase Ⅰ cardiac rehabilitation (CR-Ⅰ) combined with cognitive behavioural therapy (CBT) on patients after aortic valve replacement (AVR). METHODS: This study retrospectively analysed the data of 441 patients after AVR in our hospital from January 2020 to May 2023. A total of 38 patients who did not meet the inclusion criteria were excluded. A total of 403 patients were included. In accordance with different postoperative management schemes, the included patients were divided into the reference group (n = 202, received CR-Ⅰ) and the observation group (n = 201, received CR-Ⅰ+CBT). The cardiac function, exercise capacity and mental health of the two groups were compared. RESULTS: Before management, both groups had no significant differences in left ventricular end diastolic diameter (LVEDD), left ventricular end systolic dimension (LVESD), left ventricular ejection fraction (LVEF) and six-minute walking test (6MWT) scores (p > 0.05). At discharge and 3 months after discharge, the observation group had significantly lower LVEDD and LVESD and remarkably higher LVEF and 6MWT scores than the reference group (p < 0.001). The proportions of autonomous activity in bed within 3-4 days after surgery, autonomous out-of-bed activity within 8-10 days after surgery and autonomous walking 200 m within 12-15 days after surgery were distinctly higher (p < 0.001) and the incidence of adverse reactions was overtly lower (p < 0.001) in the observation group than in the reference group. Before management, both groups had no significant difference in their scores on the State-Trait Anxiety Inventory (STAI) (p > 0.05). At discharge and 3 months after discharge, the observation group had lower STAI scores than the reference group (p < 0.001). CONCLUSION: CR-Ⅰ combined with CBT effectively improves the cardiac function, independent exercise capacity and mental health level of patients after AVR and provides a new direction for the formulation and selection of follow-up clinical management.

Physicochemical Synergistic Separator Coating Induces Uniform and Rapid Deposition of Li and Zn Ions.

Li and Zn metal batteries are the most promising candidates to replace conventional Li-ion batteries. However, a series of issues, especially dendrites caused by uneven deposition of cations during charge-discharge cycles, hinder their practical application. Here, we proposed a facile separator modification method which combines physical and chemical forces to regulate uniform and rapid deposition of both Li+ and Zn2+. Physically, the electronegativity of modified separators drives rapid transport of metal ions via a surface diffusion mode. Chemically, the polar surface functional groups on coated separators induce uniform deposition of metal ions so that the dendrite growth is effectively inhibited. As a result, the Li and Zn metal anodes employing modified separators can cycle stably for over 1000 h under a large current density of 10 mA cm-2.

Defect-Engineered VS2 Electrocatalysts for Lithium-Sulfur Batteries.

Defective two-dimensional transition metal dichalcogenides can be effective electrocatalysts for Li-S batteries, but the relationship between defect types and battery performance is unclear. In this work, we designed S vacancy-type SV-VS2 and V self-intercalated-type VI-VS2 and measured their catalytic activities in Li-S batteries. Compared with self-intercalating V atoms, S vacancies accelerated Li+ diffusion and SV-VS2 as a Li+ "reservoir" promoted the sulfur conversion kinetics significantly. In addition, the presence of sulfur vacancies promoted the lithiation behavior of SV-VS2 during discharge, leading to an enhancement of the catalytic ability of SV-VS2. However, this lithiation phenomenon weakened the catalytic activity of VI-VS2. Overall, SV-VS2 had better adsorption and catalytic activity. Li-S batteries with SV-VS2-coated separators delivered high rate performance and excellent cycling stability, with a capacity decay rate of 0.043% over 880 cycles at 1.0 C. This work provides an effective strategy for designing efficient Li-S battery electrocatalysts using defect engineering.

Two-Dimensional Organic-Inorganic Heterostructure as a Multifunctional Protective Layer for High Performance Zinc Metal Anode.

Dendrite growth and side reactions of Zn metal anodes remain unresolved obstacles for practical application of aqueous Zn ion batteries. Herein, a two-dimensional (2D) organic-inorganic heterostructure with controlled thickness was constructed as a protective layer for a Zn metal anode. The reduction of uniformly distributed polyoxometalate in the layer causes a negative charge density gradient, which can accelerate zinc ion transfer, homogenize zinc deposition, and shield sulfates at the electrode interface, while the exposed hydrophobic alkyl chain of the layer can isolate the direct contact of water with the Zn anode. As a result of the synergetic effect, this 2D organic-inorganic heterostructure enables high Zn plating/stripping reversibility, with high average Coulombic efficiencies of 99.97% for 3700 cycles at 2 mA cm-2. Under high Zn utilization conditions, a high areal-capacity full cell with hundreds of cycles was demonstrated.

Hydrophobic, Ultrastable Cuδ+ for Robust CO2 Electroreduction to C2 Products at Ampere-Current Levels.

Copper (Cu) is the only known material that can efficiently electrocatalyze CO2 to value-added multicarbon products. Owing to the instability of the Cuδ+ state and microscopic structure in reactions, Cu catalysts are still facing big challenges with low selectivity and poor durability, particularly at high current densities. Herein, we report a rational one-step surface coordination approach for the synthesis of Cu dendrites with an ultrastable Cuδ+ state and hydrophobicity (Cu CF), even after exposure to air for over 6 months. As a result, Cu CF exhibited a C2 FE of 90.6% at a partial current density of 453.3 mA cm-2 in a flow cell. A 400 h stable electrolysis at 800 mA and even a ground-breaking stable operation at a large industrial current of 10 A were achieved in the membrane electrode assembly (MEA) form. We further demonstrated a continuous production of C2H5OH solution with 90% relative purity at 600 mA over 50 h in a solid-electrolyte reactor. Spectroscopy and computation results suggested that Cu(II) carboxylate coordination species formed on the surface of Cu CF, which ensured the stability of the Cuδ+ state and hydrophobicity. As a result, rich active sites and a stable three-phase interface on the catalyst surface were achieved, along with the optimized *CO adsorption strength and adsorption configuration. The mixed *CO adsorption configurations on Cu CF made the *CO dimerization process easier, which promoted the conversion of CO2 to C2 products. This work provides a promising paradigm for the design and development of Cu-based catalysts with ultrahigh stability under industrial current densities.

Uniform Zinc Deposition Regulated by a Nitrogen-Doped MXene Artificial Solid Electrolyte Interlayer.

The dendrite growth and side reactions of zinc metal anode in mildly acidic electrolytes seriously hinder the practical application of aqueous zinc-ion battery. To address these issues, an artificial protective layer of nitrogen-doped MXene (NMX) is used to protect the zinc anode. The NMX protective layer has high conductivity and uniformly distributed zincophilic sites, which can not only homogenize the local electric field on the electrode interface but also accelerate the kinetics for Zn deposition. As a result, the NMX protective layer induces uniform zinc deposition and reduces the overpotential of the electrode. Encouragingly, this NMX-protected Zn anode can cycle stably for 1900 h at 1 mA cm-2 and 1 mAh cm-2 . In asymmetric cells, it achieves high cycle reversibility with an average Coulomb efficiency of 99.79% for 4800 cycles at 5 mA cm-2 .

A Multifunctional Organic Electrolyte Additive for Aqueous Zinc Ion Batteries Based on Polyaniline Cathode.

The practical applications of aqueous zinc ion batteries are hindered by the formation of dendrites on the anode, the narrow electrochemical window of electrolyte, and the instability of the cathode. To address all these challenges simultaneously, a multi-functional electrolyte additive of 1-phenylethylamine hydrochloride (PEA) is developed for aqueous zinc ion batteries based on polyaniline (PANI) cathode. Experiments and theoretical calculations confirm that the PEA additive can regulate the solvation sheath of Zn2+ and form a protective layer on the surface of the Zn metal anode. This broadens the electrochemical stability window of the aqueous electrolyte and enables uniform deposition of Zn. On the cathode side, the Cl- anions from PEA enter the PANI chain during charge and release fewer water molecules surrounding the oxidized PANI, thus suppressing harmful side reactions. When used in a Zn||PANI battery, this cathode/anode compatible electrolyte exhibits excellent rate performance and long cycle life, making it highly attractive for practical applications.

Identify connectome between genotypes and brain network phenotypes via deep self-reconstruction sparse canonical correlation analysis.

MOTIVATION: As a rising research topic, brain imaging genetics aims to investigate the potential genetic architecture of both brain structure and function. It should be noted that in the brain, not all variations are deservedly caused by genetic effect, and it is generally unknown which imaging phenotypes are promising for genetic analysis. RESULTS: In this work, genetic variants (i.e. the single nucleotide polymorphism, SNP) can be correlated with brain networks (i.e. quantitative trait, QT), so that the connectome (including the brain regions and connectivity features) of functional brain networks from the functional magnetic resonance imaging data is identified. Specifically, a connection matrix is firstly constructed, whose upper triangle elements are selected to be connectivity features. Then, the PageRank algorithm is exploited for estimating the importance of different brain regions as the brain region features. Finally, a deep self-reconstruction sparse canonical correlation analysis (DS-SCCA) method is developed for the identification of genetic associations with functional connectivity phenotypic markers. This approach is a regularized, deep extension, scalable multi-SNP-multi-QT method, which is well-suited for applying imaging genetic association analysis to the Alzheimer's Disease Neuroimaging Initiative datasets. It is further optimized by adopting a parametric approach, augmented Lagrange and stochastic gradient descent. Extensive experiments are provided to validate that the DS-SCCA approach realizes strong associations and discovers functional connectivity and brain region phenotypic biomarkers to guide disease interpretation. AVAILABILITY AND IMPLEMENTATION: The Matlab code is available at https://github.com/meimeiling/DS-SCCA/tree/main. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Shape recovery from fusion of polarization binocular vision and shading.

The shape from polarization can recover the fine texture of the target surface. However, the gradient field for shape recovery by polarization is ambiguous, which is caused by the multi-value of the azimuth angle. In response to the problem, a method of correcting the ambiguity by the fusion of polarization binocular vision and shading information is proposed in this paper. An iterative optimization algorithm is designed to estimate the direction of the light source, which provides the basis for the shading method to calculate the depth map. Additionally. the low-frequency depth map generated by binocular matching is used to correct the polarization gradient field. The polarization gradient field of the holes and small zenith angle regions in the binocular are corrected by the improved shading method. In the experiment, four different material target objects were used for shape recovery and compared with other methods. The results of the fusion method proposed are better in terms of fine texture. At the camera working distance of  700 mm, the resolving power performs well and demonstrates that changes in the depth of at least 0.1 mm can be distinguished from that recovery result.

Discovery of Fibrinogen γ-chain as a potential urinary biomarker for renal interstitial fibrosis in IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is a major cause of chronic kidney disease (CKD). Renal interstitial fibrosis is a hallmark of CKD progression. Non-invasive biomarkers are needed to dynamically evaluate renal fibrosis. Data independent acquisition (DIA)-based liquid chromatography-mass spectrometry (DIA-MS) was used to identify candidate urinary biomarkers in IgAN patients with different renal interstitial fibrosis degrees. METHODS: Eighteen biopsy-proven IgAN patients and six healthy controls were recruited in a discovery cohort. Interstitial fibrosis changes were evaluated according to Oxford MEST-C scores. Urinary samples were analyzed with DIA-MS to identify hub proteins. Hub proteins were then confirmed by enzyme-linked immunosorbent assay (ELISA) in a validation cohort and the associated gene mRNA expression was analyzed using public gene expression omnibus (GEO) datasets. RESULTS: Complement and coagulation cascades pathway was the main KEGG pathway related to the over-expressed proteins. Fibrinogen γ-Chain (FGG) was selected as the potential urinary marker for further validation. Urinary FGG to creatinine ratio (uFGG/Cr) levels were higher in both disease controls and IgAN group than in healthy controls, but were not significantly different between IgAN and disease groups. uFGG/Cr was confirmed to be increased with the extent of renal fibrosis and presented moderate correlations with T score (r = 0.614, p < 0.01) and eGFR (r = -0.682, p < 0.01), and a mild correlation with UTP (r = 0.497, p < 0.01) in IgAN group. In disease control group, uFGG/Cr was higher in patients with T1 + 2 compared to those with T0. uFGG/Cr had a good discriminatory power to distinguish different fibrosis stages in IgAN: interstitial fibrosis ≤ 5% (minimal fibrosis) vs. interstitial fibrosis (mild fibrosis) > 5%, AUC 0.743; T0 vs. T1 + 2, AUC 0.839; T0 + 1 vs. T2, AUC 0.854. In disease control group, uFGG/Cr showed better performance of AUC than UTP between minimal and mild fibrosis (p = 0.038 for Delong's test). Moreover, GSE104954 dataset showed that FGG mRNA expression was up-regulated (fold change 1.20, p = 0.009) in tubulointerstitium of IgAN patients when compared to healthy living kidney donors. CONCLUSION: Urinary FGG is associated with renal interstitial fibrosis and could be used as a noninvasive biomarker for renal fibrosis in IgAN.

A study of the relationship between brachial artery vasodilation and platelet/lymphocyte ratio in diabetic patients with coronary atherosclerosis.

BACKGROUND: To investigate the correlation between brachial artery flow-mediated endothelium-dependent dilation (FMD) and platelet-lymphocyte ratio (PLR) in peripheral blood and coronary atherosclerosis in diabetic patients. METHODS: Seventy-five diabetic patients aged 62 ± 9 years, 68% male and 32% female, who underwent brachial artery endothelial function test and coronary CT scan were collected. Coronary artery calcification (CAC) was observed to assess the presence of coronary atherosclerosis, and high-resolution extravascular ultrasound was used to detect FMD. Platelet count and lymphocyte count were recorded by routine blood tests, and PLR was calculated for each study subject. Statistical methods were used to verify the association of FMD and PLR with CAC assessed by CT, respectively. RESULTS: Patients with coronary atherosclerosis had decreased FMD and increased PLR compared with patients with normal coronary arteries. Univariate logistic regression analysis showed that CAC score was significantly associated with both FMD (odds ratio: 0.167; 95% confidence interval: 0.049-0.565; p = 0.002) and PLR (odds ratio: 0.127; 95% confidence interval: 0.033-0.484; p = 0.001) at FMD < 5.1% or PLR > 130. The area under the ROC curve of FMD and PLR alone was 0.760 and 0.763, respectively. In addition, combined diagnosis of FMD and PLR showed the highest area under the ROC curve (0.830). CONCLUSION: FMD combined with PLR is expected to be a precise diagnostic modality for coronary artery calcification in diabetic patients.