Olfactory deficit and gastrointestinal dysfunction precede motor abnormalities in alpha-Synuclein G51D knock-in mice.

Parkinson's disease (PD) is typically a sporadic late-onset disorder, which has made it difficult to model in mice. Several transgenic mouse models bearing mutations in SNCA, which encodes alpha-Synuclein (α-Syn), have been made, but these lines do not express SNCA in a physiologically accurate spatiotemporal pattern, which limits the ability of the mice to recapitulate the features of human PD. Here, we generated knock-in mice bearing the G51D SNCA mutation. After establishing that their motor symptoms begin at 9 mo of age, we then sought earlier pathologies. We assessed the phosphorylation at Serine 129 of α-Syn in different tissues and detected phospho-α-Syn in the olfactory bulb and enteric nervous system at 3 mo of age. Olfactory deficit and impaired gut transit followed at 6 mo, preceding motor symptoms. The SncaG51D mice thus parallel the progression of human PD and will enable us to study PD pathogenesis and test future therapies.

Study on ultrasound diagnosis and pathological anatomy of fetal complex congenital heart disease in the first trimester.

PURPOSE: To assess the feasibility of using the stereo-microscope to identify the pathological anatomy of the congenital heart diseases in the first trimester. METHODS: Fifteen fetuses of 8-12 weeks aborted due to prevent miscarriage failure and 42 fetuses of 11-14 weeks with congenital heart diseases were included in the study, we dissected their hearts through a stereo-microscope, then compared with the prenatal ultrasonographic diagnosis. RESULTS: Using stereomicroscopy, the positive view of the heart and the great arteries, the long axis view of the aortic arch, the inflow tract view of the bottom heart, the semilunar valve view of the bottom heart, and the transverse section of the ventricle were showed contented and obtained satisfactory images, but the structure of atrioventricular valve and venous system had a lower rate of display. CONCLUSION: The characteristic pathological changes of cardiac inflow and outflow tract can be obtained by dissecting the heart sequential under the stereo-microscopy. However it is often difficult to obtain satisfactory pathological sections for pulmonary venous abnormalities and Ebstein anomaly.

Lanthanum chloride exerts therapeutic potential for chronic kidney disease by suppressing nanohydroxyapatite-induced mitophagy and mitochondria-mediated apoptosis.

OBJECTIVE: To investigate the protective effect of lanthanum chloride on kidney injury in chronic kidney disease and its mechanism. METHODS: 1. Patients with CKD stage 2-5 were selected to analyze the effect of lanthanum-containing preparations on CKD. 2. Sixty healthy male Wistar rats were randomly divided into control group, model group, lanthanum chloride groups (0.03 ng/kg, 0.1 ng/kg, 0.3 ng/kg, q.3d., i.v.), and lanthanum carbonate group (0.3 g/kg, q.d., p.o.). The model group was given 2 % adenine suspension (200 mg/kg, q.d., p.o.) for the first two weeks, followed by adenine (200 mg/kg, b.i.d., p.o.) for 2 weeks, and all animals were sacrificed after eight weeks of administration. 3. The serum and kidneys of rats in each group were collected to detect the oxidative stress indicators and the expressions of LC3B-Ⅱ/Ⅰ, p62, Bcl-2, Bax, Caspase-3 and Cleaved Caspase-3. 4. Human renal tubular epithelial cells (HK-2 cells) were divided into control group, model group, lanthanum chloride group, pyrophosphate (PPI) group, chloroquine (CQ) group, rapamycin group, doxorubicin (DOX) group and N-acetyl-L-cysteine (NAC) group. The mitochondrial status, mitophagy and apoptosis levels were detected. RESULTS: 1.Lanthanum-containing preparations can significantly reduce the biochemical indexes of kidney injury in patients with CKD. 2. In the model group, the glomerular and renal tubular edema, the mitochondria were short and round, and the expression of LC3B-Ⅱ/Ⅰ and Bax increased, while the expression of P62, Bcl-2 and Caspase-3 decreased, and there was a significant improvement in the administration group, especially the 0.1 ng/kg group and lanthanum carbonate group. 3. In the HK-2 cell model group, mitochondrial membrane potential decreased, morphology changed and the results were reversed by lanthanum chloride. CONCLUSION: Lanthanum chloride may alter the morphology of nano-hydroxyapatite, thereby inhibiting its induced mitophagy and mitochondria-mediated apoptosis, and ultimately improve CKD renal injury effectively.

Machine-learning-derived online prediction models of outcomes for patients with cholelithiasis-induced acute cholangitis: development and validation in two retrospective cohorts.

Background: Cholelithiasis-induced acute cholangitis (CIAC) is an acute inflammatory disease with poor prognosis. This study aimed to create machine-learning (ML) models to predict the outcomes of patients with CIAC. Methods: In this retrospective cohort and ML study, patients who met the both diagnosis of 'cholangitis' and 'calculus of gallbladder or bile duct' according to the International Classification of Disease (ICD) 9th revision, or met the diagnosis of 'calculus of bile duct with acute cholangitis with or without obstruction' according to the ICD 10th revision during a single hospitalization were included from the Medical Information Mart for Intensive Care database, which records patient admissions to Beth Israel Deaconess Medical Center, MA, USA, spanning June 1, 2001 to November 16, 2022. Patients who were neither admitted in an emergency department nor underwent biliary drainage within 24 h after admission, had an age of less than 18, or lost over 20% of the information were excluded. Nine ML methods, including the Logistic Regression, eXtreme Gradient Boosting (XGBoost), Light Gradient Boosting Machine, Adaptive Boosting, Decision Tree, Gradient Boosting Decision Tree, Gaussian Naive Bayes, Multi-Layer Perceptron, and Support Vector Machine were applied for prediction of in-hospital mortality, re-admission within 30 days after discharge, and mortality within 180 days after discharge. Patients from Zhongda Hospital affiliated to Southeast University in China between January 1, 2019 and July 30, 2023 were enrolled as an external validation set. The area under the receiver operating characteristic curve (AUROC) was the main index for model performance assessment. Findings: A total of 1156 patients were included to construct models. We performed stratified analyses on all patients, patients admitted to the intensive care unit (ICU) and those who underwent biliary drainage during ICU treatment. 13-16 features were selected from 186 variables for model training. The XGBoost method demonstrated the most optimal predictive efficacy, as evidenced by training set AUROC of 0.996 (95% CI NaN-NaN) for in-hospital mortality, 0.886 (0.862-0.910) for re-admission within 30 days after discharge, and 0.988 (0.982-0.995) for mortality within 180 days after discharge in all patients, 0.998 (NaN-NaN), 0.933 (0.909-0.957), and 0.988 (0.983-0.993) in patients admitted to the ICU, 0.987 (0.970-0.999), 0.908 (0.873-0.942), and 0.982 (0.971-0.993) in patients underwent biliary drainage during ICU treatment, respectively. Meanwhile, in the internal validation set, the AUROC reached 0.967 (0.933-0.998) for in-hospital mortality, 0.589 (0.502-0.677) for re-admission within 30 days after discharge, and 0.857 (0.782-0.933) for mortality within 180 days after discharge in all patients, 0.963 (NaN-NaN), 0.668 (0.486-0.851), and 0.864 (0.757-0.970) in patients admitted to the ICU, 0.961 (0.922-0.997), 0.669 (0.540-0.799), and 0.828 (0.730-0.925) in patients underwent biliary drainage during ICU treatment, respectively. The AUROC values of external validation set consisting of 61 patients were 0.741 (0.725-0.763), 0.812 (0.798-0.824), and 0.848 (0.841-0.859), respectively. Interpretation: The XGBoost models could be promising tools to predict outcomes in patients with CIAC, and had good clinical applicability. Multi-center validation with a larger sample size is warranted. Funding: The Technological Development Program of Nanjing Healthy Commission, and Zhongda Hospital Affiliated to Southeast University, Jiangsu Province High-Level Hospital Construction Funds.

Retraction to "MiR-223-3p regulates cell viability, migration, invasion, and apoptosis of non-small cell lung cancer cells by targeting RHOB".

[This retracts the article DOI: 10.1515/biol-2020-0040.].

A smartphone-based approach for comprehensive soil microbiome profiling.

The soil microbiome is crucial for nutrient cycling, health, and plant growth. This study presents a smartphone-based approach as a low-cost and portable alternative to traditional methods for classifying bacterial species and characterizing microbial communities in soil samples. By harnessing bacterial autofluorescence detection and machine learning algorithms, the platform achieved an average accuracy of 88% in distinguishing common soil-related bacterial species despite the lack of biomarkers, nucleic acid amplification, or gene sequencing. Furthermore, it successfully identified dominant species within various bacterial mixtures with an accuracy of 76% and three-level soil health identification at an accuracy of 80%-82%, providing insights into microbial community dynamics. The influence of other soil conditions (pH and moisture) was relatively minor, showcasing the platform's robustness. Various field soil samples were also tested with this platform at 80% accuracy compared with the laboratory analyses, demonstrating the practicality and usability of this approach for on-site soil analysis. This study highlights the potential of the smartphone-based system as a valuable tool for soil assessment, microbial monitoring, and environmental management.

A best practices framework for spatial biology studies in drug discovery and development: enabling successful cohort studies using digital spatial profiling.

The discovery of biomarkers, essential for successful drug development, is often hindered by the limited availability of tissue samples, typically obtained through core needle biopsies. Standard 'omics platforms can consume significant amounts of tissue, forcing scientist to trade off spatial context for high-plex assays, such as genome-wide assays. While bulk gene expression approaches and standard single-cell transcriptomics have been valuable in defining various molecular and cellular mechanisms, they do not retain spatial context. As such, they have limited power in resolving tissue heterogeneity and cell-cell interactions. Current spatial transcriptomics platforms offer limited transcriptome coverage and have low throughput, restricting the number of samples that can be analyzed daily or even weekly. While the Digital Spatial Profiling (DSP) method does not provide single-cell resolution, it presents a significant advancement by enabling scalable whole transcriptome and ultrahigh-plex protein analysis from distinct tissue compartments and structures using a single tissue slide. These capabilities overcome significant constraints in biomarker analysis in solid tissue specimens. These advancements in tissue profiling play a crucial role in deepening our understanding of disease biology and in identifying potential therapeutic targets and biomarkers. To enhance the use of spatial biology tools in drug discovery and development, the DSP Scientific Consortium has created best practices guidelines. These guidelines, built on digital spatial profiling data and expertise, offer a practical framework for designing spatial studies and using current and future spatial biology platforms. The aim is to improve tissue analysis in all research areas supporting drug discovery and development.

A pan-cancer analysis of Wnt family member 7B in human cancers.

Background: Previous studies have highlighted the crucial role of Wnt7B in the development of various cancers, including breast, pancreatic, and gastric cancers. However, research into the involvement of Wnt7B is often confined to specific tumor types, with a noticeable lack of comprehensive studies spanning multiple cancer forms. The potential of Wnt7B as a diagnostic or prognostic cancer biomarker has not been fully explored. Methods: In this study, we combined bioinformatics and immunohistochemistry analyses to examine the expression patterns and functions of Wnt7B in cancerous and adjacent noncancerous tissues across a range of tumors. Results: Our data indicate that Wnt7B may serve as a novel prognostic biomarker and therapeutic target in certain cancers. Conclusion: We found significant upregulation of Wnt7B expression levels in the majority of cancer cases examined. Furthermore, Wnt7B can influence cancer prognosis by modulating the tumor microenvironment, immune cell infiltration, and tumor stemness, among other factors. Additionally, we examined the associations between anticancer drug sensitivity and Wnt7B expression, which could aid in the development of more precise clinical therapies.

A multicenter prospective study on the ESC algorithm for the early diagnosis of non-ST-elevation myocardial infarction.

This study aimed to determine the optimal high-sensitivity cardiac troponin I (hs-cTnI)-based algorithm for early diagnosis of non-ST-elevation myocardial infarction (NSTEMI) in Chinese patients. We prospectively enrolled 1,606 patients with suspected NSTEMI from three emergency departments across China, collecting blood samples at 0, 1, and 3 h post-admission. Patients were classified using the 0/1-h and 0/3-h algorithms. The 2015 and 2020 ESC 0/1-h algorithms rapidly triaged 70% of patients with high negative predictive value (NPV) (99.7%) and sensitivity (99.5%). The 0/3-h algorithm showed higher specificity (93.8%) but lower NPV (96.8%) and sensitivity (91.2%). An optimized 0/1-h algorithm improved specificity to 92.1% while maintaining high NPV (99.7%) and sensitivity (99.2%). Low 30-day and 180-day all-cause mortality and major adverse cardiac event (MACE) rates were observed in rule-out groups for all algorithms. The ESC 0/1-h algorithm is a safe and efficient triage method for patients with suspected NSTEMI, with optimization further enhancing specificity and efficiency for the Chinese population.

Asymmetric Osteopenia in Adolescent Idiopathic Scoliosis Based on Hounsfield Unit of Computed Tomography.

Purpose: To characterize the asymmetrical loss of bone mass and identify the association between scoliosis and osteopenia in patients with adolescent idiopathic scoliosis (AIS). Methods: Demographic information, Cobb angle, and Hounsfield unit (HU) of the neutral vertebra (NV) and apical vertebra (apex) of the major curve were collected retrospectively in 54 AIS patients. For 84 control subjects, HU values were measured at T12 and L5. Propensity score matching was performed to balance the interference of age and BMI. Results: In the AIS group, the concave and convex lateral HU of the NV and the convex lateral HU of the apex were negatively correlated with the Cobb angle. The AIS patients had lower bilateral HU. The mean HU and the apex-convex HU were also lower in the AIS group, while the apex-concave HU was slightly higher. After matching, the apex-convex HU of the AIS group remained lower, while the apex-concave HU was higher. Conclusion: Patients with AIS exhibit osteopenia, particularly on the convex side. The severity of scoliosis was found to be directly proportional to the severity of bone loss and the degree of bilateral osteopenia asymmetry. Appropriate intervention for bone loss may be able to curb the progression of scoliosis.

Efficacy and safety of C3 laminectomy combined with open-door laminoplasty versus open-door laminoplasty alone: A systematic review and meta-analysis.

BACKGROUND: To evaluate efficacy and safety between C3 laminectomy + open-door laminoplasty and open-door laminoplasty alone. METHODS: Electronic databases are systematically searched up to January 2024. The authors applied Review Manager 5.4 to manage the data and perform the review. Authors conducted Cochrane Library, Pubmed, OVID and Web of Science, search for studies comparing C3 laminectomy + open-door laminoplasty and open-door laminoplasty alone. Forest plots are constructed for each analysis group. RESULTS: After selection, 9 eligible articles included 10 comparison groups, with a combined 320patients who underwent C3 laminectomy + open-door laminoplasty, 355 who underwent open-door laminoplasty alone. There is no difference in operative time, blood volume, JOA, JOA recovery, VAS, Neck Disability Index(NDI), complications, axial symptoms, T1S, ROM and cSVA. C3 laminectomy + open-door laminoplasty is superior in C2-C7 Cobb angle. CONCLUSION: Although C3 laminectomy + open-door laminoplasty has theoretical advantages, meta-analysis results show that the two surgical procedures are similar in terms of clinical symptoms improvement, sagittal balance, and complications. C3 laminectomy combined + open-door laminoplasty is only superior in the preservation of cervical lordosis. Limited number of studies may affect the reliability and generalizability of the results. Future high-quality, multicenter RCTs are needed to verify efficacy and safety.

Molecular condensates as roadblocks in plant defense.

The molecular mechanism of plant disease tolerance is less studied compared to disease resistance. In this issue of Cell Host &Microbe, Tang et al. revealed that Arabidopsis Hematopoietic protein-1 (HEM1) and Bax-inhibitor 1 (BI-1) condensates diminish disease tolerance by disrupting lipid homeostasis.

A truncated B-box zinc finger transcription factor confers drought sensitivity in modern cultivated tomatoes.

Enhancing drought tolerance in crops and understanding the underlying mechanisms have been subject of intense research. The precise function and molecular mechanisms of B-box zinc finger proteins (BBX) remain elusive. Here, we report a natural allele of BBX18 (BBX18TT) that encodes a C-terminal truncated protein. While most wild tomato germplasms contain the BBX18CC allele and show more drought tolerant, modern cultivated tomatoes mostly carry BBX18TT allele and are more drought sensitive. Knockout of BBX18 leads to improved drought tolerance in transgenic plants of cultivated tomato. Ascorbate peroxidase 1 (APX1) is identified as a BBX18-interacting protein that acts as a positive regulator of drought resistance in tomato. Chromatin immunoprecipitation sequencing analyses reveal that BBX18 binds to a unique cis-acting element of the APX1 promoter and represses its gene expression. This study provides insights into the molecular mechanism underlying drought resistance mediated by the BBX18-APX1 module in plants.

Induced pluripotent stem cell-derived mesenchymal stem cells enhance acellular nerve allografts to promote peripheral nerve regeneration by facilitating angiogenesis.

Previous research has demonstrated the feasibility of repairing nerve defects through acellular allogeneic nerve grafting with bone marrow mesenchymal stem cells. However, adult tissue-derived mesenchymal stem cells encounter various obstacles, including limited tissue sources, invasive acquisition methods, cellular heterogeneity, purification challenges, cellular senescence, and diminished pluripotency and proliferation over successive passages. In this study, we used induced pluripotent stem cell-derived mesenchymal stem cells, known for their self-renewal capacity, multilineage differentiation potential, and immunomodulatory characteristics. We used induced pluripotent stem cell-derived mesenchymal stem cells in conjunction with acellular nerve allografts to address a 10 mm-long defect in a rat model of sciatic nerve injury. Our findings reveal that induced pluripotent stem cell-derived mesenchymal stem cells exhibit survival for up to 17 days in a rat model of peripheral nerve injury with acellular nerve allograft transplantation. Furthermore, the combination of acellular nerve allograft and induced pluripotent stem cell-derived mesenchymal stem cells significantly accelerates the regeneration of injured axons and improves behavioral function recovery in rats. Additionally, our in vivo and in vitro experiments indicate that induced pluripotent stem cell-derived mesenchymal stem cells play a pivotal role in promoting neovascularization. Collectively, our results suggest the potential of acellular nerve allografts with induced pluripotent stem cell-derived mesenchymal stem cells to augment nerve regeneration in rats, offering promising therapeutic strategies for clinical translation.

Increased serum carboxylesterase-1 levels are associated with metabolic dysfunction associated steatotic liver disease and metabolic syndrome in children with obesity.

BACKGROUND: Carboxylesterase 1(CES1) is expressed mainly in the liver and adipose tissue and is highly hypothesized to play an essential role in metabolism. Our study aimed to investigate the association between CES1 and metabolic syndrome (MetS) and metabolic dysfunction associated steatotic liver disease (MASLD) in children with obesity in China. METHODS: This study included 72 children with obesity aged 6-13years (including 25(35%) diagnosed as MetS and 36(50%) diagnosed as MASLD). All subjects were measured in anthropometry, serum level of biochemical parameters related to obesity, circumstance levels of insulin-like growth factor1, adipokines (adiponectin, leptin and growth differentiation factor 15) and CES1. RESULTS: Higher serum CES1 level were found in the MetS group (P = 0.004) and the MASLD group (P < 0.001) of children with obesity. Serum CES1 levels were positively correlated with alanine aminotransferase, aspartate aminotransferase, triglyceride, cholesterol, low-density lipoprotein cholesterol, GDF15, Leptin and negatively correlated with high-density lipoprotein cholesterol, adiponectin and IGF1. We also found a multivariable logistic regression analysis of MASLD and MetS predicted by CES1 significantly (MASLD P < 0.01, MetS P < 0.05). The combination of CES1, sex, age and BMI Z-score showed a sensitivity and specificity of 92.7% for the identification of MASLD and 78.6% for the identification of MetS. The cutoff for CES1 of MASLD is 56.30 ng/mL and of MetS is 97.79 ng/mL. CONCLUSIONS: CES1 is associated with an increasing risk of MetS and MASLD and can be established as a biomarker for metabolic syndrome and MASLD of children with obesity.

Intranasal administration of insulin on the incidence of postoperative delirium in middle-aged patients undergoing elective on-pump cardiac surgery (INIPOD-MOPS): a prospective double-blinded randomized control study protocol.

BACKGROUND: Delirium, marked by acute cognitive decline, poses a life-threatening issue among older individuals, especially after cardiac surgery, with prevalence ranging from 15 to 80%. Postoperative delirium is linked to increased morbidity and mortality. Although clinical trials suggest preventability, there is limited research on intranasal insulin (INI) for cardiac surgery-related delirium. INI has shown promise in managing cognitive disorders. It rapidly elevates brain hormone levels, enhancing memory even in non-impaired individuals. While effective in preventing delirium in gastrointestinal surgery, its impact after cardiac surgery remains understudied, especially for middle-aged patients. METHOD: This is a prospective randomized, double-blind, single-center controlled trial. A total of 76 eligible participants scheduled for elective on-pump cardiac surgery will be enrolled and randomly assigned in a 1:1 ratio to either receive Intranasally administered insulin (INI) or intranasally administered normal saline. The primary outcome of our study is the incidence of postoperative delirium (POD). Secondary outcomes include duration of ICU, postoperative hospital length of stay, all in-hospital mortality, the change in MMSE scores pre- and post-operation, and incidence of postoperative cognitive dysfunction at 1 month, 3 months, and 6 months after operation. Moreover, we will subjectively and objectively evaluate perioperative sleep quality to investigate the potential impact of nasal insulin on the development of delirium by influencing sleep regulation. DISCUSSION: Our study will aim to assess the impact of intranasal administration of insulin on the incidence of postoperative delirium in middle-aged patients undergoing on-pump elective cardiac surgery. If intranasal insulin proves to be more effective, it may be considered as a viable alternative for preventing postoperative delirium. TRIAL REGISTRATION: ChiCTR ChiCTR2400081444. Registered on March 1, 2024.

A hot-emitter transistor based on stimulated emission of heated carriers.

Hot-carrier transistors are a class of devices that leverage the excess kinetic energy of carriers. Unlike regular transistors, which rely on steady-state carrier transport, hot-carrier transistors modulate carriers to high-energy states, resulting in enhanced device speed and functionality. These characteristics are essential for applications that demand rapid switching and high-frequency operations, such as advanced telecommunications and cutting-edge computing technologies1-5. However, the traditional mechanisms of hot-carrier generation are either carrier injection6-11 or acceleration12,13, which limit device performance in terms of power consumption and negative differential resistance14-17. Mixed-dimensional devices, which combine bulk and low-dimensional materials, can offer different mechanisms for hot-carrier generation by leveraging the diverse potential barriers formed by energy-band combinations18-21. Here we report a hot-emitter transistor based on double mixed-dimensional graphene/germanium Schottky junctions that uses stimulated emission of heated carriers to achieve a subthreshold swing lower than 1 millivolt per decade beyond the Boltzmann limit and a negative differential resistance with a peak-to-valley current ratio greater than 100 at room temperature. Multi-valued logic with a high inverter gain and reconfigurable logic states are further demonstrated. This work reports a multifunctional hot-emitter transistor with significant potential for low-power and negative-differential-resistance applications, marking a promising advancement for the post-Moore era.

An unsupervised multi-view contrastive learning framework with attention-based reranking strategy for entity alignment.

Entity alignment is a crucial task in knowledge graphs, aiming to match corresponding entities from different knowledge graphs. Due to the scarcity of pre-aligned entities in real-world scenarios, research focused on unsupervised entity alignment has become more popular. However, current unsupervised entity alignment methods suffer from a lack of informative entity guidance, hindering their ability to accurately predict challenging entities with similar names and structures. To solve these problems, we present an unsupervised multi-view contrastive learning framework with an attention-based reranking strategy for entity alignment, named AR-Align. In AR-Align, two kinds of data augmentation methods are employed to provide a complementary view for neighborhood and attribute, respectively. Next, a multi-view contrastive learning method is introduced to reduce the semantic gap between different views of the augmented entities. Moreover, an attention-based reranking strategy is proposed to rerank the hard entities through calculating their weighted sum of embedding similarities on different structures. Experimental results indicate that AR-Align outperforms most both supervised and unsupervised state-of-the-art methods on three benchmark datasets.

A Chinese individual with DEL phenotype caused by a novel RHD allele.

BACKGROUND: RhD variants are categorized into partial D, weak D, and DEL. The detection of DEL can only be achieved through the adsorption and elution method or molecular techniques. Here, we report a case of DEL phenotypes associated with a novel allele in a Chinese individual. STUDY DESIGN AND METHODS: We used serological methods such as saline, indirect anti-human globulin, and adsorption-elution. The RHD genotype was determined by the PCR-sequence specific primer (PCR-SSP) method as well as the Sanger dideoxy sequencing. RESULTS: RBCs of the sample were found to be DEL phenotype by serological testing, with negative reactions in the saline and indirect anti-human globulin tests while positive reactions by the absorption-elution method. The genotyping results revealed a hemizygous (RHDc .1127 T>G/RHD-). The novel allele sequence has been submitted to GenBank (Accession number: OR608456). CONCLUSION: Our study demonstrates a case of a Chinese individual with DEL phenotype caused by a novel allele RHD c .1127 T > G. It expands the database of the DEL variant.

CircRNA Arf3 suppresses glomerular mesangial cell proliferation and fibrosis in diabetic nephropathy via miR-107-3p/Tmbim6 axis.

Diabetic nephropathy (DN) is one of microvascular complication associated with diabetes. Circular RNAs (circRNAs) have been shown to be involved in DN pathogenesis. Hence, this work aimed to explore the role and mechanism of circ_Arf3 in DN. Mouse mesangial cells (MCs) cultured in high glucose (HG) condition were used for functional analysis. Cell proliferation was determined using 5-ethynyl-2'-deoxyuridine (EdU) and cell counting kit-8 assays. Western blotting was used to measure the levels of proliferation indicator PCNA and fibrosis-related proteins α-smooth muscle actin (α-SMA), collagen I (Col I), fibronectin (FN), and collagen IV (Col IV). The binding interaction between miR-107-3p and circ_Arf3 or Tmbim6 (transmembrane BAX inhibitor motif containing 6) was confirmed using dual-luciferase reporter and pull-down assays. Circ_Arf3 is a stable circRNA, and the expression of circ_Arf3 was decreased after HG treatment in MCs. Functionally, ectopic overexpression of circ_Arf3 protected against HG-induced proliferation and elevation of fibrosis-related proteins in MCs. Mechanistically, circ_Arf3 directly bound to miR-107-3p, and Tmbim6 was a target of miR-107-3p. Further rescue assay showed miR-107-3p reversed the protective action of circ_Arf3 on MCs function under HG condition. Moreover, inhibition of miR-107-3p suppressed HG-induced proliferation and fibrosis, which were attenuated by Tmbim6 knockdown in MCs. CircRNA Arf3 could suppress HG-evoked mesangial cell proliferation and fibrosis via miR-107-3p/Tmbim6 axis, indicating the potential involvement of this axis in DN progression.