Waist circumference glucose, a novel and effective predictor of type 2 diabetes: a prospective cohort study.

Introduction: Waist circumference (WC) and fasting plasma glucose (FPG) have been demonstrated as risk factors for type 2 diabetes mellitus (T2DM). Evidence is limited regarding the association of the combination of WC and FPG (WyG) with the risk of T2DM. The primary aim of the study was to investigate the relationship between WyG and T2DM. Research design and methods: The current study was a population-based cohort study using data from the NAGALA database. Participants were divided into tertiles based on WyG. Cox proportional hazard regression model was applied to identify the association of WyG with T2DM. Results: During a median follow-up of 6.19 years in the normoglycemia group and 5.58 years in the prediabetes group, respectively, 88 and 285 individuals in the two groups received a diagnosis of T2DM. After full adjustment, risk of T2DM increased in step-wise fashion with increasing tertiles of WyG. For a per-SD increase in WyG, the hazard ratios for T2DM were 3.05 (95% CI 2.64 - 3.51) in all populations, 1.94 (95% CI 1.46 - 2.58) in the normoglycemia group and 1.63 (95% CI 1.40 - 1.90) in the prediabetes group. The interaction between WyG and fatty liver on T2DM was statistically significant in the prediabetes group (P for interaction = 0.034). Conclusions: Elevated WyG was independently associated with incident T2DM in Japan. Baseline WyG help identify individuals at high risk of T2DM and implement effective preventive measures.

Acquiring musical knowledge increases music liking: Evidence from a neurophysiological study.

People possessing musical knowledge tend to enjoy music more, but the linkage remains to be determined. Based on the shared affective motion experience model for music appreciation, we hypothesized that acquiring musical knowledge about the music itself, for example, an analytical understanding of music elements and the related emotional expressions, would increase music liking. To test the hypothesis, we asked 48 participants to learn analytical or historical information about a piece of music by watching a pre-recorded teaching video. Learners' physiological responses, such as skin conductance and heart rate, were recorded during learning. The increase of music liking was observed after both types of knowledge acquisition, but more so for analytical knowledge. Notably, acquiring analytical knowledge made learners' skin conductance more similar, indicating the alignment of physiological responses. This physiological similarity, correlated with analytical knowledge similarity, could mediate the effect of knowledge acquisition on music liking. In sum, this study reveals the impact of analytical knowledge on music enjoyment and the associated neurophysiological mechanism. It extends the theoretical framework of shared affective motion experience to explain how musical knowledge influences music appreciation.

Emerging insights into cuproptosis and copper metabolism: implications for age-related diseases and potential therapeutic strategies.

The expanding geriatric population, whose predisposition toward disabling morbidities and age-related diseases (ARD) is well-documented, has become a paramount social issue, exerting an onerous burden on both the healthcare industry and wider society. ARD manifest as the progressive deterioration of bodily tissues and organs, eventually resulting in the failure of these vital components. At present, no efficacious measures exist to hinder the onset of ARD. Copper, an essential trace element, is involved in a wide range of physiological processes across different cell types. In recent research, a novel variant of copper-dependent cell death, termed cuproptosis, has been identified. This mode of cellular demise stands apart from previously recognized types of cell death. Cuproptosis occurs when copper binds with acyl-CoA synthetase in the tricarboxylic acid (TCA) cycle, resulting in protein aggregation and protein toxicity stress, ultimately leading to cell death. In this paper, we provide a concise overview of the current understanding concerning the metabolism of copper, copper-related diseases, the hallmarks of copper toxicity, and the mechanisms that regulate copper toxicity. Additionally, we discuss the implications of cuproptosis mutations in the development of ARD, as well as the potential for targeting cuproptosis as a treatment for ARD.

The combination of body mass index and fasting plasma glucose is associated with type 2 diabetes mellitus in Japan: a secondary retrospective analysis.

Background: Body mass index (BMI) and fasting plasma glucose (FPG) are known risk factors for type 2 diabetes mellitus (T2DM), but data on the prospective association of the combination of BMI and FPG with T2DM are limited. This study sought to characterize the association of the combination of BMI and FPG (ByG) with T2DM. Methods: The current study used the NAGALA database. We categorized participants by tertiles of ByG. The association of ByG with T2DM was expressed with hazard ratios (HRs) with 95% confidence intervals (CIs) after adjustment for potential risk factors. Results: During a median follow-up of 6.19 years in the normoglycemia cohort and 5.58 years in the prediabetes cohort, the incidence of T2DM was 0.75% and 7.79%, respectively. Following multivariable adjustments, there were stepwise increases in T2DM with increasing tertiles of ByG. After a similar multivariable adjustment, the risk of T2DM was 2.57 (95% CI 2.26 - 2.92), 1.97 (95% CI 1.53 - 2.54) and 1.50 (95% CI 1.30 - 1.74) for a per-SD change in ByG in all populations, the normoglycemia cohort and the prediabetes cohort, respectively. Conclusion: ByG was associated with an increased risk of T2DM in Japan. The result reinforced the importance of the combination of BMI and FPG in assessing T2DM risk.

Solid basal adenoid cystic carcinoma of the breast: A case report and literature review.

RATIONALE: Adenoid cystic carcinoma (AdCC) is a rare malignancy of the breast with a low Ki-67 index and good prognosis. Owing to the rarity of breast AdCC, the misdiagnosis rate is as high as 50%, and there is no consensus or recognized guidelines for the treatment of this disease. Therefore, it is necessary to conduct a detailed clinical and pathological analysis in combination with a literature review to improve our understanding, diagnosis, and treatment of the disease. METHODS: A 68-year-old woman sought medical attention due to a recently increasing mass in the breast. The left breast mass was 1.3 cm × 1 cm in size. We analyzed the morphology, immunohistochemistry, and molecular characteristics of the tumor removed by surgery, and reviewed relevant literature. DIAGNOSES: Solid basal AdCC of the breast. INTERVENTIONS: We performed biopsy, immunohistochemistry and molecular testing on surgical resection specimens. OUTCOMES: Combining morphological and immunohistochemical features, it is consistent with solid basal AdCC of the breast, and Fish detected MYB gene break. LESSONS: Due to the high misdiagnosis rate of AdCC, accurate histopathological diagnosis is particularly important. At present, breast conserving surgery and local tumor resection are mainly used for the treatment of breast AdCC, and postoperative adjuvant radiotherapy is feasible.

Transcription Factor EGR1 Facilitates Neovascularization in Mice with Retinopathy of Prematurity by Regulating the miR-182-5p/EFNA5 Axis.

Neovascularization is the hallmark of retinopathy of prematurity (ROP). Early growth response 1 (EGR1) has been reported as an angiogenic factor. This study was conducted to probe the regulatory mechanism of EGR1 in neovascularization in ROP model mice. The ROP mouse model was established, followed by determination of EGR1 expression and assessment of neovascularization [vascular endothelial growth factor-A (VEGF-A) and pigment epithelium-derived factor (PEDF)]. Retinal vascular endothelial cells were cultured and treated with hypoxia, followed by the tube formation assay. The state of oxygen induction was assessed by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot assay to determine hypoxia-inducible factor 1-alpha (HIF-1A). The levels of microRNA (miRNA)-182-5p and ephrin-A5 (EFNA5) in tissues and cells were determined by RT-qPCR. Chromatin immunoprecipitation and dual-luciferase assay were used to validate gene interaction. EGR1 and EFNA5 were upregulated in the retina of ROP mice while miR-182-5p was downregulated. EGR1 knockdown decreased VEGF-A and HIF-1A expression and increased PEDF expression in the retina of ROP mice. In vitro, EGR1 knockdown also reduced neovascularization. EGR1 binding to the miR-182-5p promoter inhibited miR-182-5p transcription and further promoted EFNA5 transcription. miR-182-5p downregulation or EFNA5 overexpression averted the inhibition of neovascularization caused by EGR1 downregulation. Overall, EGR1 bound to the miR-182-5p promoter to inhibit miR-182-5p transcription and further promoted EFNA5 transcription, thus promoting retinal neovascularization in ROP mice.

A U-shaped association between the triglyceride to high-density lipoprotein cholesterol ratio and the risk of incident type 2 diabetes mellitus in Japanese men with normal glycemic levels: a population-based longitudinal cohort study.

Background: Several studies have verified that a high baseline TG/HDL-C ratio is a risk factor for incident type 2 diabetes mellitus (T2DM). However, for low baseline TG/HDL-C levels, the findings were inconsistent with ours. In addition, the association between baseline TG/HDL-C ratio and the risk of incident T2DM in Japanese men with normal glycemic levels is unclear. As a result, our study further investigated the relationship between baseline TG/HDL-C and the risk of incident T2DM in Japanese men with normal glycemic levels. Methods: This was a secondary longitudinal cohort study. We selected 7,684 male participants between 2004 and 2015 from the NAGALA database. A standardized Cox regression model and two piecewise Cox regression models were used to explore the relationship between the baseline high-density lipoprotein cholesterol ratio (TG/HDL-C) and incident T2DM. Results: During a median follow-up of 2,282 days, 162 men developed incident T2DM. In the adjusted model, the baseline TG/HDL-C ratio was strongly associated with the risk of incident T2DM, and no dose-dependent positive association was observed between the baseline TG/HDL-C ratio and incidence of T2DM throughout the baseline TG/HDL-C quartiles. Two-piecewise linear regression analysis showed a U-shaped association between baseline TG/HDL-C ratio and incidence of incident T2DM. A baseline TG/HDL-C ratio below 1.188 was negatively associated with incident T2DM (H.R. = 0.105, 95% CI = 0.025, 0.451; P = 0.002). In contrast, a baseline TG/HDL-C ratio >1.188 was positively associated with incident T2DM (H.R. = 1.248, 95% CI = 1.113, 1.399; P<0.001). The best TG/HDL-C threshold for predicting incident T2DM was 1.8115 (area under the curve, 0.6837). Conclusion: A U-shaped relationship between baseline TG/HDL-C ratio and incident T2DM in Japanese men with normal glycemic levels was found.

Pyogenic liver abscess complicated with endogenous endophthalmitis caused by Klebsiella pneumoniae: A case report and Literature Review.

OBJECTIVE: Pyogenic liver abscess (PLA) is a common surgical infectious disease caused by various pathogens. Klebsiella pneumoniae is a relatively recent cause, often affecting patients with low immunity. Endogenous endophthalmitis (EE), a rare and serious complication of PLA, may appear with eye symptoms before PLA. By reviewing a case of Klebsiella pneumoniae-induced PLA complicated with EE, we want to summarize the information about the characteristics, causes, and complications of PLA based on the literature review. METHODS: This case report describes a 37-year-old male who had fever high to 39°C for 10 days experienced blurred vision followed by nonlight perception vision. He reported a history of diabetes irregularly taking oral medications and insulin therapy. Imaging examination found a large low-density area in the right lobe of the liver with an unclear border and vague surrounding fat gap. The blood culture was not positive. The culture of the drainage fluid from the liver puncture showed Klebsiella pneumonia. Blood and liver puncture drainage fluid were sent for microbial high-throughput gene detection with next-generation sequencing technology (NGS), which confirmed the diagnosis of Klebsiella pneumoniae-induced PLA complicated with EE. RESULTS: The patient's surgical incision had healed well at discharge, and he could feel light at his left eye. But the patient was lost to follow-up since the third month after discharge. CONCLUSION: By reviewing this case and summarize the information about the characteristics, causes, and complications of PLA based on the literature review, we concluded that it is necessary to promptly perform liver puncture drainage and empirically use antibiotics for patients with PLA, especially those with poor glycemic control, to avoid serious complications such as EE.

Relationship between lipid accumulation product and new-onset diabetes in the Japanese population: a retrospective cohort study.

Background: Diabetes has become a global public health problem. Obesity has been established as a risk factor for diabetes. However, it remains unclear which of the obesity indicators (BMI, WC, WhtR, ABSI, BRI, LAP, VAI) is more appropriate for monitoring diabetes. Therefore, the objective of this investigation is to compare the strength of the association of these indicators and diabetes and reveal the relationship between LAP and diabetes. Methods: 15,252 people took part in this research. LAP was quartered and COX proportional risk model was applied to explore the relationship between LAP and new-onset diabetes. Smooth curve fitting was employed to investigate the non-linear link between LAP and diabetes mellitus. Finally, the receiver operating characteristic (ROC) curve was used to evaluate the predictive ability of the aforementioned indicators for diabetes. Results: After adjusting for confounding factors, multiple linear regression analysis showed that each unit increase in LAP was associated with a 76.8% increase in the risk of developing diabetes (HR=1.768, 95% CI: 1.139 to 2.746, P=0.011). In addition, LAP predicted new-onset diabetes better than other indicators, and the AUC was the largest [HR: 0.713, 95% CI: 0.6806-0.7454, P<0.001, in women; HR: 0.7922, 95% CI: 0.7396-0.8447; P<0.001, in men]. When LAP was used as a lone predictor, its AUC area was largest both men and women. However, after adding classical predictors (FPG, HbA1c, SBP, exercise, age) to the model, the LAP is better than the ABSI, but not better than the other indicators when compared in pairs. Conclusions: High levels of LAP correlate very strongly with diabetes and are an important risk factor for diabetes, especially in women, those with fatty liver and current smokers. LAP was superior to other indicators when screening for diabetes susceptibility using a single indicator of obesity, both in men and in women. However, when obesity indicators were added to the model together with classical predictors, LAP did not show a significant advantage over other indicators, except ABSI.

Triglyceride Glucose-Body Mass Index and Risk of Incident Type 2 Diabetes Mellitus in Japanese People With Normal Glycemic Level: A Population-Based Longitudinal Cohort Study.

Background: It has been proved that triglyceride glucose-body mass index (TyG-BMI) is a readily available and clinically significant indicator of insulin resistance (IR). Nevertheless, the association between TyG-BMI and incident Type 2 diabetes mellitus (T2DM) remains uncertain. This study aimed to study the relationship between TyG-BMI and T2DM and explore the predictive characteristics of TyG-BMI. Methods: Our study was conducted as a longitudinal cohort study. 8,430 men and 7,034 women were enrolled and analyzed. They were both non-diabetic subjects with normal glycemic levels. Follow-up lasted for 13 years, from 1994 to 2016. To make the number of TyG-BMI in each group similar, the subjects were divided into four groups with 3866 subjects in each group. Results: During the 13-year follow-up period, 373 subjects were diagnosed with incident T2DM. Our multivariate Cox regression analysis revealed that TyG-BMI was an independent predictor of incident T2DM. In addition, our research identified four specific groups, young people (18-44 years old), women, the non-hypertensive population and non-drinkers were at significantly higher risk of developing TyG-BMI-related diabetes (P-interaction< 0.05). The best threshold TyG-BMI for predicting incident T2DM was 197.2987 (area under the curve 0.7738). Conclusions: Our longitudinal cohort study demonstrated the positive correlation between baseline TyG-BMI and risk of incident T2DM in Japanese with normal glycemic levels, and this risk was significantly higher in the young people, women, the non-hypertensive population and non-drinkers.

Residual Risk of Coronary Atherosclerotic Heart Disease and Severity of Coronary Atherosclerosis Assessed by ApoB and LDL-C in Participants With Statin Treatment: A Retrospective Cohort Study.

Background: Low-density lipoprotein cholesterol (LDL-C) is the primary target of lipid-lowering therapy on the management of hypercholesterolemia in the United States and European guidelines, while apolipoprotein B (apoB) is the secondary target. The objective was to determine if elevated levels of apoB is superior to LDL-C in assessing residual risk of coronary atherosclerotic heart disease and severity of coronary atherosclerosis in participants with statin treatment. Methods: This study included 131 participants with statin treatment. The generalized linear model and relative risk regression (generalized linear Poisson model with robust error variance) were used to analyze the association of the levels of apoB and LDL-C with the severity of coronary atherosclerosis and residual risk of coronary atherosclerotic heart disease. Results: Categorizing apoB and LDL-C based on tertiles, higher levels of apoB were significantly associated with the severity of coronary atherosclerosis (Ptrend = 0.012), whereas no such associations were found for elevated levels of LDL-C (Ptrend = 0.585). After multivariate adjustment, higher levels of apoB were significantly associated with residual risk of coronary atherosclerotic heart disease. When compared with low-level apoB (≤0.66 g/L), the multivariate adjusted RR and 95% CI of intermediate-level apoB (0.67-0.89 g/L) and high-level apoB (≥0.90 g/L) were 1.16 (1.01, 1.33) and 1.31 (1.08, 1.60), respectively (Ptrend = 0.011). There was a 45% increased residual risk of coronary atherosclerotic heart disease per unit increment in natural log-transformed apoB (Ptrend <0.05). However, higher levels of LDL-C were not significantly associated with residual risk of coronary atherosclerotic heart disease. When compared with low-level LDL-C (≤1.56 mmol/L), the multivariate adjusted RR and 95% CI of intermediate-level LDL-C (1.57-2.30 mmol/L) and high-level LDL-C (≥2.31 mmol/L) were 0.99 (0.84, 1.15) and 1.10 (0.86, 1.42), respectively (Ptrend = 0.437). Similar results were observed in the stratified analyses and sensitivity analyses. No significant interactions were detected for both apoB and LDL-C (all Pinteraction>0.05). Conclusions: Elevated apoB are superior in assessing the residual risk of coronary atherosclerotic heart disease and severity of coronary atherosclerosis in participants with statin treatment.

Stromal cell-derived factor-1 exerts opposing roles through CXCR4 and CXCR7 in angiotensin II-induced adventitial remodeling.

Recent studies have emphasized the role of vascular adventitia inflammation and immune response in hypertension. It has been reported that stromal cell-derived factor-1 (SDF-1) plays various biological functions through its receptors C-X-C motif chemokine receptor 4 (CXCR4) and CXCR7 in tumor growth and tissue repair. However, it is unclear that whether SDF-1/CXCR4/CXCR7 axis is involved in hypertensive vascular remodeling. In the present study, the involvement of SDF-1/CXCR4/CXCR7 axis was evaluated with lentivirus-mediated shRNA of SDF-1 and CXCR7, CXCR4 antagonist AMD3100 and CXCR7 agonist VUF11207 in angiotensin II (AngII)-induced hypertensive mice and in cultured adventitial fibroblasts (AFs). Results showed that AngII infusion markedly increased SDF-1 expressed in vascular adventitia, but not in media and endothelium. Importantly, blockade of SDF-1/CXCR4 axis strikingly potentiated AngII-induced adventitial thickening and fibrosis, as indicated by enhanced collagen I deposition. In contrast, CXCR7 shRNA largely attenuated AngII-induced adventitial thickness and fibrosis, whereas CXCR7 activation with VUF11207 significantly potentiated AngII-induced adventitial thickening and fibrosis. In consistent with these in vivo study, CXCR4 inhibition with AMD3100 and CXCR7 activation with VUF11207 aggravated AngII-induced inflammation, proliferation and migration in cultured AFs. In summary, these results suggested that SDF-1 exerted opposing effects through CXCR4 and CXCR7 in AngII-induced vascular adventitial remodeling.

The potential mechanism of Astragali Radix in the treatment of children with nephrotic syndrome.

BACKGROUND: The molecular mechanism of Astragali Radix in the treatment of children with nephrotic syndrome (NS) is unclear. This study aimed to use network pharmacology to explore this potential mechanism. METHODS: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to identify the main active ingredients of Astragali Radix. The PharmMapper, Online Mendelian Inheritance in Man (OMIM), and GeneCards databases were then used to identify the active ingredients of Astragali Radix. The String database and Cytoscape software were used to construct the protein-protein network. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using DAVID Database. RESULTS: In the TCMSP Database, a total of 20 chemical constituents of Astragali Radix were screened. After removing the duplicates and false positive genes, 394 targets of these active ingredients were obtained from PharmMapper. By comparing the NS-related genes in the GeneCards and OMIM Databases, a total of 39 potential NS-related targets were ultimately identified. The protein-protein-interaction network included 39 nodes and 366 edges. The top 5 proteins were albumin (ALB), serine/threonine kinase (AKT1), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase (MAPK), and matrix metallopeptidase 9 (MMP9). The GO analysis showed that the target genes were mainly involved in biological processes (e.g., signal transduction, the positive regulation of cell proliferation, and the positive regulation of migration). The cellular components included a plasma membrane, extracellular exosome, and extracellular space. The molecular functions included protein binding, zinc-ion binding, protein tyrosine kinase activity, and enzyme binding. The KEGG analysis showed that the treatment of NS by Astragali Radix mainly involved pathways in cancer, proteoglycans in cancer, the phosphatidylinositol 3-kinase and protein kinase B (PI3K-Akt) signaling pathway, the rennin-angiotensin-system (Ras) signaling pathways, and Forkhead box protein O1 (FoxO) signaling pathways. CONCLUSIONS: In the present study, the network pharmacology method was used to explore the potential targets and pathways of Astragali Radix in the treatment of NS. We also provided future research directions for the treatment of NS with a complex pathogenesis.

How to Calculate and Validate Inter-brain Synchronization in a fNIRS Hyperscanning Study.

The dynamics between coupled brains of individuals have been increasingly represented by inter-brain synchronization (IBS) when they coordinate with each other, mostly using simultaneous-recording signals of brains (namely hyperscanning) with fNIRS. In fNIRS hyperscanning studies, IBS has been commonly assessed through the wavelet transform coherence (WTC) method because of its advantage on expanding time series into time-frequency space where oscillations can be seen in a highly intuitive way. The observed IBS can be further validated via the permutation-based random pairing of the trial, partner, and condition. Here, a protocol is presented to describe how to obtain brain signals via fNIRS technology, calculate IBS through the WTC method, and validate IBS by permutation in a hyperscanning study. Further, we discuss the critical issues when using the above methods, including the choice of fNIRS signals, methods of data preprocessing, and optional parameters of computations. In summary, using the WTC method and permutation is a potentially standard pipeline for analyzing IBS in fNIRS hyperscanning studies, contributing to both the reproducibility and reliability of IBS.

Optimal timing of coronary angiograms for patients with chronic kidney disease: association between the duration of kidney dysfunction and SYNTAX scores.

BACKGROUND: Chronic kidney disease (CKD) is associated with an increased risk of the progression of coronary artery disease (CAD). However, there are few data on the relationship between CAD severity and the duration of CKD. This study assessed the predictive value of the duration of kidney dysfunction in CKD patients with CAD severity. METHODS: In 145 patients (63.4% male, n = 92; mean age, 68.8 ± 12.8 years) with CKD, severity of CAD was assessed by coronary angiography and quantified by SYNTAX scores, and duration of kidney dysfunction was either assessed by checking historical biochemical parameters of individuals or was based on enquiries. RESULTS: Patients with high SYNTAX scores (≥ 22) had a greater prevalence of cardiovascular risk factors including age, gender, history of heart failure and smoking. In CKD patients, SYNTAX scores were positively correlated to duration of CKD and serum uric acid (UA), and negatively correlated to high-density lipoprotein-cholesterol (HDL-C) and ApoA1 levels. Univariate binary logistic regression and multivariate logistic analyses showed that SYNTAX scores correlated significantly with CKD duration, UA, and HDL-C. Receiver-operating characteristic analysis was used to explore a time point when coronary angiography application was economical and effective and yielded a Youden index of 6.5 years. CONCLUSIONS: Together, our results demonstrated that the duration of kidney dysfunction was an independent correlate of the severity of CAD in patients with CKD. Our findings suggest that coronary angiography should be considered for CKD patients with renal insufficiency having lasted for more than 6.5 years.

Three new steroidal saponins from the roots and rhizomes of Rohdea chinensis (Baker) N.Tanaka (synonym Tupistra chinensis Baker).

Three new steroidal saponins (1-3), together with four known compounds (4-7), were isolated from the roots and rhizomes of Rohdea chinensis Baker, and their structures were determined as (24S, 25 R)-1ß-hydroxy-3ß-[(ß-D-glucopyranoside)oxy]-spirost-5-en-24-yl-ß-D-glucopyranoside (1) and (24S)-spirost-25(27)-en-1ß, 3ß, 4ß, 5ß, 6ß, 24ß-hexahydroxy-24-O-ß-D-glucopyranoside (2), (22S, 25S)-1ß, 3ß, 4ß, 5ß, 26, 27-hexanol-furospirost-5, 26-O-ß-D-glucopyranoside (3), together with four known compounds 3-epi-diosgenin-3-ß-D-glucopyranosid (4), 3-epiruscogenin (5), 25(R)-1ß-hydroxy-spirost-5-en-3α-yl-O-ß-D-glucopyranoside (6) and tupichinin A (7), on the basis of physico-chemical properties and spectral analysis. In this study, compounds 1-3 and 5-7 were evaluated for their cytotoxic activity against SW620, A549 and HepG2 tumor cell lines. Among them, compound 7 showed moderate cytotoxicity against two human cancer cell lines A549 and HepG 2 with IC50 values of 25.3 ± 2.6 and 26.1 ± 2.5 µM, respectively.

Dual brain stimulation enhances interpersonal learning through spontaneous movement synchrony.

Social interactive learning denotes the ability to acquire new information from a conspecific-a prerequisite for cultural evolution and survival. As inspired by recent neurophysiological research, here we tested whether social interactive learning can be augmented by exogenously synchronizing oscillatory brain activity across an instructor and a learner engaged in a naturalistic song-learning task. We used a dual brain stimulation protocol entailing the trans-cranial delivery of synchronized electric currents in two individuals simultaneously. When we stimulated inferior frontal brain regions, with 6 Hz alternating currents being in-phase between the instructor and the learner, the dyad exhibited spontaneous and synchronized body movement. Remarkably, this stimulation also led to enhanced learning performance. These effects were both phase- and frequency-specific: 6 Hz anti-phase stimulation or 10 Hz in-phase stimulation, did not yield comparable results. Furthermore, a mediation analysis disclosed that interpersonal movement synchrony acted as a partial mediator of the effect of dual brain stimulation on learning performance, i.e. possibly facilitating the effect of dual brain stimulation on learning. Our results provide a causal demonstration that inter-brain synchronization is a sufficient condition to improve real-time information transfer between pairs of individuals.

AdipoRon Attenuates Hypertension-Induced Epithelial-Mesenchymal Transition and Renal Fibrosis via Promoting Epithelial Autophagy.

Hypertension-induced epithelial-mesenchymal transition (EMT) is a major mechanism of renal fibrosis. Adiponectin protects against hypertension-induced target organ damage. AdipoRon is an orally active synthetic adiponectin receptor agonist. However, it is unclear whether AdipoRon could attenuate EMT and renal fibrosis in hypertensive mice. C57BJ/6J mice were utilized to induce DOCA-salt-sensitive hypertensive model. Hypertension results in an altered adiponectin expression and promotes EMT in the kidney. In vitro, AdipoRon inhibits aldosterone (Aldo)-induced EMT and promotes autophagic flux in HK-2 epithelial cells. Mechanically, AdipoRon activates AMPK/ULK1 pathway in epithelial cells. Blockade of AMPK activation, as well as inhibition of autophagy, blocks the effects of AdipoRon on Aldo-induced EMT. Moreover, AdipoRon treatment promotes autophagy and improves renal fibrosis in DOCA-salt-hypertensive mice. Our data suggest that AdipoRon could be a potential therapeutic option to prevent renal fibrosis in hypertensive patients. Graphical abstract.

HIF-1α-BNIP3-mediated mitophagy in tubular cells protects against renal ischemia/reperfusion injury.

In the present study, we hypothesized that hypoxia-inducible factor 1α (HIF-1α)-mediated mitophagy plays a protective role in ischemia/reperfusion (I/R)-induced acute kidney injury (AKI). Mitophagy was evaluated by measuring the changes of mitophagy flux, mitochondria DNA copy number, and the changes of mitophagy-related proteins including translocase of outer mitochondrial membrane 20 (TOMM20), cytochrome c oxidase IV (COX IV), microtubule-associated protein 1 light chain 3B (LC3B), and mitochondria adaptor nucleoporin p62 in HK2 cells, a human tubular cell line. Results show that HIF-1α knockout significantly attenuated hypoxia/reoxygenation (H/R)-induced mitophagy, aggravated H/R-induced apoptosis, and increased the production of reactive oxygen species (ROS). Similarly, H/R induced significantly increase in Bcl-2 19-kDa interacting protein 3 (BNIP3), a downstream regulator of HIF-1α. Notably, BNIP3 overexpression reversed the inhibitory effect of HIF-1α knockout on H/R-induced mitophagy, and prevented the enhancing effect of HIF-1α knockout on H/R-induced apoptosis and ROS production. For in vivo study, we established HIF-1αflox/flox; cadherin-16-cre mice in which tubular HIF-1α was specifically knockout. It was found that tubular HIF-1α knockout significantly inhibited I/R-induced mitophagy, and aggravated I/R-induced tubular apoptosis and kidney damage. In contrast, adenovirus-mediated BNIP3 overexpression significantly reversed the decreased mitophagy, and prevented enhanced kidney damage in tubular HIF-1α knockout mice with I/R injury. In summary, our study demonstrated that HIF-1α-BNIP3-mediated mitophagy in tubular cells plays a protective role through inhibition of apoptosis and ROS production in acute kidney damage.