Cbln1 regulates axon growth and guidance in multiple neural regions.

The accurate construction of neural circuits requires the precise control of axon growth and guidance, which is regulated by multiple growth and guidance cues during early nervous system development. It is generally thought that the growth and guidance cues that control the major steps of axon development have been defined. Here, we describe cerebellin-1 (Cbln1) as a novel cue that controls diverse aspects of axon growth and guidance throughout the central nervous system (CNS) by experiments using mouse and chick embryos. Cbln1 has previously been shown to function in late neural development to influence synapse organization. Here, we find that Cbln1 has an essential role in early neural development. Cbln1 is expressed on the axons and growth cones of developing commissural neurons and functions in an autocrine manner to promote axon growth. Cbln1 is also expressed in intermediate target tissues and functions as an attractive guidance cue. We find that these functions of Cbln1 are mediated by neurexin-2 (Nrxn2), which functions as the Cbln1 receptor for axon growth and guidance. In addition to the developing spinal cord, we further show that Cbln1 functions in diverse parts of the CNS with major roles in cerebellar parallel fiber growth and retinal ganglion cell axon guidance. Despite the prevailing role of Cbln1 as a synaptic organizer, our study discovers a new and unexpected function for Cbln1 as a general axon growth and guidance cue throughout the nervous system.

Effects of CEO water shortage experience and power intensity on corporate water performance - Evidence from China.

Corporate water performance and sustainable development are currently vital focus areas for scholars. Therefore, this paper investigates the experience of Chief Executive Officers (CEOs) with water shortage influences corporate water performance by focusing on listed companies in water-intensive and high-water-risk industries in China between 2014 and 2019. This paper manually collected information relative to the cities and provinces where CEOs grew up to evaluate their early exposure to water shortages. Furthermore, this paper develops an evaluation scale, based on the Enterprise Water Conservation Evaluation Guide (GB/T 7119-2006), to compute the enterprise water management practices scores. These results will constitute the enterprise water performance evaluation score. Moreover, this paper focuses on CEOs who have experienced water resource shortages through a positive impact on the water resource performance of their companies. As for the findings, they demonstrate that CEOs who grew up in regions with higher water scarcity have a more pronounced positive effect on their water shortage experience through corporate water performance. Furthermore, CEO power intensity positively moderates the relationship between the CEO's water shortage experience and corporate water resource performance. Further investigation reveals generational differences in the impact of CEO water shortage experience on company water performance. CEOs, who grew up during periods with a higher incidence of droughts, demonstrate a more significant promoting effect on corporate water performance. To sum up, this study expands the understanding of factors influencing corporate water resource performance and deepens the knowledge of the early life experiences of CEOs.

A novel AGK splicing mutation in a patient with Sengers syndrome and left ventricular non-compaction cardiomyopathy.

BACKGROUND: Sengers syndrome characterized by hypertrophic cardiomyopathy is an extremely rare genetic disorder. Sengers syndrome associated with left ventricular non-compaction (LVNC) has not been described. METHODS: Genetic testing was used to identify candidate AGK variants in the proband. The predicted molecular structures were constructed by protein modeling. Exon skipping caused by the identified splicing mutations was verified by in silico analyses and in vitro assays. The genotypic and phenotypic features of patients with AGK splicing mutations were extracted by a systematic review. RESULTS: The proband was characterized by Sengers syndrome and LVNC and caused by a novel compound heterozygous AGK splicing mutation. This compound mutation simultaneously perturbed the protein sequences and spatial conformation of the acylglycerol kinase protein. In silico and in vitro analyses demonstrated skipping of exons 7 and 8 and premature truncation as a result of exon 8 skipping. The systematic review indicated that patients with an AGK splicing mutation may have milder phenotypes of Sengers syndrome. CONCLUSIONS: The genotypic and phenotypic spectrums of Sengers syndrome have been expanded, which will provide essential information for genetic counseling. The molecular mechanism in AGK mutations can offer insights into the potential targets for treatment. IMPACT: First description of a child with Sengers syndrome and left ventricular non-compaction cardiomyopathy. A novel pathogenic compound heterozygous splicing mutation in AGK for Sengers syndrome was identified. The identified mutations led to exons skipping by in silico analyses and in vitro assays.

Association of the lymphocyte-to-monocyte ratio, mean diameter of coronary arteries, and uric acid level with coronary slow flow in isolated coronary artery ectasia.

BACKGROUND: The pathophysiology of isolated coronary artery ectasia (CAE) with the coronary slow flow (CSF) phenomenon is still unclear. The purpose of this study was to investigate the risk factors for isolated CAE complicated with CSF. METHODS: A total of 126 patients with isolated CAE were selected retrospectively. The patients were grouped into the no CSF (NCSF) group (n = 55) and the CSF group (n = 71) according to the corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC). Data on demographics, laboratory measurements, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), CTFC and diameters of three coronary arteries were collected. RESULTS: The proportions of males (84.5% vs. 61.8%, p = 0.004) and patients with a smoking history (63.4% vs. 43.6%, p = 0.021) were higher in the CSF group than in the NCSF group. The neutrophil-to-lymphocyte ratio (NLR) (2.08(1.68-3.21) vs. 1.89 ± 0.58, p = 0.001), mean diameter of coronary arteries (mean D) (5.50 ± 0.85 vs. 5.18 ± 0.91, p < 0.001), and uric acid (URIC) level (370.78 ± 109.79 vs. 329.15 ± 79.71, p = 0.019) were significantly higher in the CSF group, while the lymphocyte-to-monocyte ratio (LMR) (4.81 ± 1.66 vs. 5.96 ± 1.75, p < 0.001) and albumin (ALB) level (44.13 ± 4.10 vs. 45.69 ± 4.11, p = 0.036) were lower. Multivariable logistic analysis showed that the LMR (odds ratio: 0.614, 95% CI: 0.464-0.814, p = 0.001), mean D (odds ratio: 2.643, 95% CI: 1.54-4.51, p < 0.001) and URIC level (odds ratio: 1.006, 95% CI: 1.001-1.012, p = 0.018) were independent predictors of CSF in CAE. CONCLUSIONS: The LMR was a negative independent predictor of CSF in isolated CAE, while URIC level and mean D were positive independent predictors.

Sex-Related Differences in the Impact of Systemic Hypertension on Left Ventricular Remodeling in Patients with Hypertrophic Obstructive Cardiomyopathy.

BACKGROUND: The clinical condition of hypertrophic obstructive cardiomyopathy (HOCM) and concomitant systemic hypertension is growing more and more prevalent, and it brings about a challenging diagnostic and therapeutic dilemma. However, whether systemic hypertension has an impact on HOCM, and whether sex-related differences exist in this impact, remains unclear. METHODS: A total of 453 HOCM patients (age 48.7 ± 12.8 years, 252 [55.6%] males) were recruited in this study. There were 150 patients (33.1%, 81 males and 69 females) with a history of controlled systemic hypertension. Cardiac magnetic resonance (CMR) imaging was performed in all patients. Left ventricular (LV) remodeling index (LVRI) was determined by CMR. LVRI >1.3 g/mL was defined as pathological LV remodeling. RESULTS: Men had significantly greater LVRI (1.40 ± 0.54 vs. 1.15 ± 0.38 g/mL, p < 0.001) and LVRI >1.3 g/mL (p = 0.002), compared with women. The incidence of syncope and 5-year sudden cardiac death risk score were significantly lower in HOCM with hypertension than those without hypertension. LVRI (p = 0.003) and LVRI >1.3 g/mL (p = 0.007) were significantly smaller in males with hypertension, but not in females with hypertension. However, log cardiac troponin I and log N-terminal pro-B-type natriuretic peptide were positively correlated with LVRI in men and women. On multivariable logistic analysis, hypertension (OR 0.172, 95% CI 0.056-0.528, p = 0.002) remained an independent determinant of pathological LV remodeling in males, whereas not in females. CONCLUSIONS: There were significant sex differences in the impact of systemic hypertension on LV remodeling in patients with HOCM. Controlled systemic hypertension may contribute to improving LV remodeling in male patients with HOCM, but not in females.

Giant coronary artery fistula complicated with coronary artery aneurysm and acute myocardial infarction: a case report.

BACKGROUND: Coronary artery fistula (CAF) is an abnormal connection between a coronary artery and either a cardiac chamber or the great vessels. Although most patients are asymptomatic, potential complications such as heart failure, angina pectoris or acute myocardial infarction can be fatal. CASE PRESENTATION: We present here a 62-year-old man diagnosed with giant coronary artery fistula complicated with gross coronary artery aneurysm and acute myocardial infarction. He underwent intravenous thrombolysis treatment at a local hospital, coronary angiography at a regional hospital and complex surgery at a national centre for cardiovascular disease. The patient had no major adverse cardiac events during the 3-year follow-up. CONCLUSION: Early diagnosis of CAF patients and an appropriate treatment plan are the key factors for avoiding serious complications. Because of the rare incidence of this disease, it is necessary to discover and discuss management strategies, including medical management, percutaneous interventions or surgical treatment, for a successful outcome.

Cardiac troponin I is associated with non-sustained ventricular tachycardia in patients with hypertrophic obstructive cardiomyopathy.

As highly sensitive and specific markers of myocardial damage, cardiac troponins were demonstrated to correlate with clinical parameters of patients with hypertrophic cardiomyopathy. However, the relationship between cardiac troponins and presence of non-sustained ventricular tachycardia (NSVT) in hypertrophic cardiomyopathy remains unclear. The aim of our study was to explore the association between serum cardiac troponin I (cTNI) and presence of NSVT in patients with hypertrophic obstructive cardiomyopathy (HOCM). A total of 309 HOCM patients were enrolled in our study. All participants underwent clinical evaluations, including collections of medical history, blood tests, 24-h Holter monitoring, echocardiography, and cardiac magnetic resonance imaging. There were 53 (17.2%) patients with NSVT and 256 patients without it. Compared to patients without NSVT, serum cTNI (P < 0.001) and plasma NT-proBNP (P = 0.042) were significantly higher in patients with NSVT. Moreover, cTNI and NT-proBNP were positively correlated with left atrial diameter, maximum wall thickness (MWT), left ventricular volume index and left ventricular mass index. In multivariable logistic analysis, log cTNI [odds ratio (OR) = 2.408, 95% confidence interval (CI) 1.108-5.325, P = 0.027], left ventricular end-diastole diameter (OR = 0.922, 95%CI 0.856-0.994, P = 0.034), MWT (OR = 1.131, 95%CI 1.035-1.235, P = 0.006) and left ventricular end-systole volume index (OR = 1.060, 95%CI 1.025-1.096, P = 0.001) were independent determinants of NSVT occurrence after adjustment for potential cofounders. Serum cTNI level was elevated in patients with NSVT. And it was independently associated with NSVT in patients with HOCM. Our results suggest that it may be more reasonable for HOCM patients with elevated serum cTNI to extend the time of Holter monitoring.

[A review of progress in B cell receptor (BCR) antigen specificity].

B cell receptor (BCR) is a key molecule involved in B cell specific recognition and the binding of antigens to produce adaptive humoral immune response. Gene rearrangement and high frequency mutation during B cell differentiation are the main mechanisms of BCR diversification. The enormous diversity and unique molecular structure of BCR determine the diversity and specificity of antigen recognition, shaping complex B cell repertoire with extensive collections of antigen specificities. Therefore, BCR antigen-specific information is vital to understanding the adaptive immune characteristics of different diseases. Our ability to connect BCR repertoire and antigen specificity has been enhanced with the development of B cell related research technologies, such as single cell sorting techniques, high-throughput sequencing (HTS), linking B cell receptor to antigen specificity through sequencing (LIBRA-seq). It could help researchers to better understand humoral immune responses, identify disease pathogenesis, monitor disease progression, design vaccines, and develop therapeutic antibodies and drugs. We summarizes recent studies on antigen-specific BCR of infections, vaccinations, autoimmune diseases and cancer. By analyzing autoantibody sequences of SLE as a case, the identification of autoantigens has become potentially possible due to this characterization.

Drug-eluting stent and drug-coated balloon for the treatment of de novo diffuse coronary artery disease lesions: A retrospective case series study.

BACKGROUND: The hybrid strategy of a combination of drug-eluting stent (DES) and drug-coated balloon (DCB) is promising for the treatment of de novo diffuse coronary artery disease (CAD). HYPOTHESIS: To investigate the efficacy and functional results of hybrid strategy. METHODS: This case series study included patients treated with a hybrid approach for de novo diffuse CAD between February 2017 and November 2021. Postprocedural quantitative flow ratio (QFR) was used to evaluate the functional results. The primary endpoint was procedural success rate. The secondary endpoints were major adverse cardiovascular events (MACE) including cardiac death, myocardial infarction (MI) (including peri-procedural MI), and target vessel revascularization. RESULTS: A total of 109 patients with 114 lesions were treated. DES and DCB were commonly used in larger proximal segments and smaller distal segments, respectively. The mean QFR value was 0.9 ± 0.1 and 105 patients (96.3%) had values >0.8 in all the treated vessels. Procedural success was achieved in 106 (97.2%) patients. No cases of cardiac death were reported at a median follow-up of 19 months. Spontaneous MI occurred in three (2.8%) patients and target vessel revascularization in six (5.5%) patients. Estimated 2-year rate of MACE excluding peri-procedural MI was higher in the group with lower QFR value (12.1 ± 5.7% vs. 5.6 ± 4.4%, log-rank p = .035) (cut-off value 0.9). CONCLUSION: Hybrid strategy is a promising approach for the treatment of de novo diffuse CAD. Postprocedural QFR has some implications for prognosis and may be helpful in guiding this approach.

Facilitation of axonal transcriptome analysis with quantitative microfluidic devices.

Microfluidic chambers are powerful tools for studying axonal mRNA localization and translation in neurons. In addition to specific manipulation and measurements of axons, microfluidic chambers are used for collecting axonal materials to perform axonal transcriptome analysis. However, traditional bipartite and tripartite chambers have limitations either in purity or quantity of collected axons. Here, we improved the design of traditional chambers. Moreover, we developed two new quantitative chambers, multi-compartmental quantitative bipartite chamber (MQBC) and long quantitative tripartite chamber (LQTC). Compared with the traditional chambers, MQBC and LQTC could dramatically increase the efficiency in collecting axonal RNA. Finally, we applied these chambers to do comparative axon transcriptome analysis of different types of neurons. Thus, our newly designed quantitative chambers significantly improve axon collection efficiency and facilitate axonal transcriptome analysis.

m6A regulation of cortical and retinal neurogenesis is mediated by the redundant m6A readers YTHDFs.

m6A modification plays an important role in regulating mammalian neurogenesis. However, whether and how the major cytoplasmic m6A readers, YTHDF1, YTHDF2, and YTHDF3 mediate this process is still not clear. Here, we demonstrate that Ythdf1 and Ythdf2 double deletion but not individual knockout recapitulates the phenotype of Mettl14 knockout in cortex. In addition, we find that Mettl14 knockout in retina causes protracted proliferation of retinal progenitors, decreased numbers of retinal neurons, and disturbed laminar structure. This phenotype is only reproduced when Ythdf1, Ythdf2, and Ythdf3 are knocked out simultaneously in retina. Analysis of YTHDF target mRNAs in mouse cortex and retina reveals abundant overlapping mRNAs related to neurogenesis that are recognized and regulated by both YTHDF1 and YTHDF2. Together our results demonstrate that the functionally redundant YTHDFs mediate m6A regulation of cortical and retinal neurogenesis.

A Nomogram for Predicting Survival in Patients With Colorectal Cancer Incorporating Cardiovascular Comorbidities.

Background: Cardiovascular comorbidities (CVCs) affect the overall survival (OS) of patients with colorectal cancer (CRC). However, a prognostic evaluation system for these patients is currently lacking. Objectives: This study aimed to develop and validate a nomogram, which takes CVCs into account, for predicting the survival of patients with CRC. Methods: In total, 21,432 patients with CRC were recruited from four centers in China between January 2011 and December 2017. The nomogram was constructed, based on Cox regression, using a training cohort (19,102 patients), and validated using a validation cohort (2,330 patients). The discrimination and calibration of the model were assessed by the concordance index and calibration curve. The clinical utility of the model was measured by decision curve analysis (DCA). Based on the nomogram, we divided patients into three groups: low, middle, and high risk. Results: Independent risk factors selected into our nomogram for OS included age, metastasis, malignant ascites, heart failure, and venous thromboembolism, whereas dyslipidemia was found to be a protective factor. The c-index of our nomogram was 0.714 (95% CI: 0.708-0.720) in the training cohort and 0.742 (95% CI: 0.725-0.759) in the validation cohort. The calibration curve and DCA showed the reliability of the model. The cutoff values of the three groups were 68.19 and 145.44, which were also significant in the validation cohort (p < 0.001). Conclusion: Taking CVCs into account, an easy-to-use nomogram was provided to estimate OS for patients with CRC, improving the prognostic evaluation ability.

The predictive value of epicardial adipose tissue volume assessed by cardiac magnetic resonance for atrial fibrillation in patients with hypertrophic obstructive cardiomyopathy.

Atrial fibrillation (AF) is the most common arrhythmia and potentially increase the risk of embolic stroke and aggravate progressive heart failure in patients with hypertrophic cardiomyopathy (HCM). Recent studies demonstrated that epicardial adipose tissue (EAT) was closely associated with AF in general population. However, the relationship between EAT and AF in HCM patients remains unclear. A total of 93 consecutive patients with hypertrophic obstructive cardiomyopathy (HOCM) at Fuwai Hospital were enrolled in our study. There were 18 patients with AF and 75 patients without it. Cardiac magnetic resonance (CMR) imaging was performed in all participants. EAT volume (EATV) and left atrial volume (LAV) were determined by E-3D medical model software. HOCM patients with AF had significantly greater EATV index (EATVI, P < 0.001), LAV index (LAVI, P < 0.001) and left ventricular end-systole volume index (LVESVI, P = 0.039), and lower left ventricular ejection fraction (LVEF, P = 0.002). In multivariable logistic regression analysis, EATVI, LAVI, and LVEF remained independent determinants of AF occurrence (OR = 1.023, 95% CI, 1.003-1.043, P = 0.023, OR = 1.043, 95% CI, 1.012-1.075, P = 0.006, and OR = 0.887, 95% CI, 0.818-0.962, P = 0.004, respectively). Furthermore, receiver operating characteristic (ROC) curve analysis demonstrated that integration of EATVI, LAVI and LVEF provided better discriminatory performance for incident AF in HOCM patients with a high sensitivity of 94.4% and a specificity of 69.3% (AUC = 0.864, 95% CI, 0.771-0.958, P < 0.001). EATVI is an independent predictor of the presence of AF, and integration of EATVI, LVEF and LAVI determined by CMR provide greater discriminatory performance for identifying AF in HOCM patients.