Nesfatin-1 enhances vascular smooth muscle calcification through facilitating BMP-2 osteogenic signaling.

Vascular calcification (VC) arises from the accumulation of calcium salts in the intimal or tunica media layer of the aorta, contributing to higher risk of cardiovascular events and mortality. Despite this, the mechanisms driving VC remain incompletely understood. We previously described that nesfatin-1 functioned as a switch for vascular smooth muscle cells (VSMCs) plasticity in hypertension and neointimal hyperplasia. In this study, we sought to investigate the role and mechanism of nesfatin-1 in VC. The expression of nesfatin-1 was measured in calcified VSMCs and aortas, as well as in patients. Loss- and gain-of-function experiments were evaluated the roles of nesfatin-1 in VC pathogenesis. The transcription activation of nesfatin-1 was detected using a mass spectrometry. We found higher levels of nesfatin-1 in both calcified VSMCs and aortas, as well as in patients with coronary calcification. Loss-of-function and gain-of-function experiments revealed that nesfatin-1 was a key regulator of VC by facilitating the osteogenic transformation of VSMCs. Mechanistically, nesfatin-1 promoted the de-ubiquitination and stability of BMP-2 via inhibiting the E3 ligase SYTL4, and the interaction of nesfatin-1 with BMP-2 potentiated BMP-2 signaling and induced phosphorylation of Smad, followed by HDAC4 phosphorylation and nuclear exclusion. The dissociation of HDAC4 from RUNX2 elicited RUNX2 acetylation and subsequent nuclear translocation, leading to the transcription upregulation of OPN, a critical player in VC. From a small library of natural compounds, we identified that Curculigoside and Chebulagic acid reduced VC development via binding to and inhibiting nesfatin-1. Eventually, we designed a mass spectrometry-based DNA-protein interaction screening to identify that STAT3 mediated the transcription activation of nesfatin-1 in the context of VC. Overall, our study demonstrates that nesfatin-1 enhances BMP-2 signaling by inhibiting the E3 ligase SYTL4, thereby stabilizing BMP-2 and facilitating the downstream phosphorylation of SMAD1/5/9 and HDAC4. This signaling cascade leads to RUNX2 activation and the transcriptional upregulation of MSX2, driving VC. These insights position nesfatin-1 as a potential therapeutic target for preventing or treating VC, advancing our understanding of the molecular mechanisms underlying this critical cardiovascular condition.

Gut microbiome and metabolites mediate the benefits of caloric restriction in mice after acute kidney injury.

The role of gut microbiome in acute kidney injury (AKI) is increasing recognized. Caloric restriction (CR) has been shown to enhance the resistance to ischemia/reperfusion injury to the kidneys in rodents. Nonetheless, it is unknown whether intestinal microbiota mediated CR protection against ischemic/reperfusion-induced injury (IRI) in the kidneys. Herein, we showed that CR ameliorated IRI-elicited renal dysfunction, oxidative stress, apoptosis, and inflammation, along with enhanced intestinal barrier function. In addition, gut microbiota depletion blocked the favorable effects of CR in AKI mice. 16S rRNA and metabolomics analysis showed that CR enriched the gut commensal Parabacteroides goldsteinii (P. goldsteinii) and upregulated the level of serum metabolite dodecafluorpentan. Intestinal colonization of P. goldsteinii and oral administration of dodecafluorpentan showed the similar beneficial effects as CR in AKI mice. RNA sequencing and experimental data revealed that dodecafluorpentan protected against AKI-induced renal injury by antagonizing oxidative burst and NFκB-induced NLRP3 inflammasome activation. In addition, we screened and found that Hamaudol improved renal insufficiency by boosting the growth of P. goldsteinii. Our results shed light on the role of intestinal microbiota P. goldsteinii and serum metabolites dodecafluorpentan in CR benefits to AKI.

Network pharmacology combined with molecular docking revealed the potential targets of Coridius chinensis in prostate cancer treatment.

BACKGROUND: Prostate cancer (PCa) has high morbidity and mortality rates in elderly men. With a history of thousands of years, traditional Chinese medicine derived from insects could be an important source for developing cancer-targeted drugs to prevent tumorigenesis, enhance therapeutic effects, and reduce the risk of recurrence and metastasis. Multiple studies have shown that Coridius chinensis (Cc) has anticancer effects. AIM: To elucidate the mechanism of action of Cc against PCa via network pharmacology and molecular docking. METHODS: Potential targets for Cc and PCa were predicted using ChemDraw 19.0 software, the PharmMapper database and the GeneCards database. Then, the STRING database was used to construct the protein-protein interaction network. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and molecular docking analyses were subsequently conducted to identify the key targets, active ingredients and pathways involved. RESULTS: GO and KEGG analyses indicated that the PI3K-Akt signalling pathway was the critical pathway (P value < 1.0 × 10-8). Multiple targeting ingredients that can affect multiple pathways in PCa have been identified in Cc. Seven active compounds (asponguanosines A, asponguanine B, asponguanine C, aspongpyrazine A, N-acetyldopamine, aspongadenine B and aspongpyrazine B) were selected for molecular docking with 9 potential targets, and the results revealed that aspongpyrazine A and asponguanosine A are the main components by which Cc affects PCa (affinity<-5 kcal/mol, hydrogen bonding), but more studies are needed. CONCLUSION: We used network pharmacology to predict the bioactive components and important targets of Cc for the treatment of PCa, supporting the development of Cc as a natural anticancer agent.

Deficiency of neutral cholesterol ester hydrolase 1 (NCEH1) impairs endothelial function in diet-induced diabetic mice.

BACKGROUND: Neutral cholesterol ester hydrolase 1 (NCEH1) plays a critical role in the regulation of cholesterol ester metabolism. Deficiency of NCHE1 accelerated atherosclerotic lesion formation in mice. Nonetheless, the role of NCEH1 in endothelial dysfunction associated with diabetes has not been explored. The present study sought to investigate whether NCEH1 improved endothelial function in diabetes, and the underlying mechanisms were explored. METHODS: The expression and activity of NCEH1 were determined in obese mice with high-fat diet (HFD) feeding, high glucose (HG)-induced mouse aortae or primary endothelial cells (ECs). Endothelium-dependent relaxation (EDR) in aortae response to acetylcholine (Ach) was measured. RESULTS: Results showed that the expression and activity of NCEH1 were lower in HFD-induced mouse aortae, HG-exposed mouse aortae ex vivo, and HG-incubated primary ECs. HG exposure reduced EDR in mouse aortae, which was exaggerated by endothelial-specific deficiency of NCEH1, whereas NCEH1 overexpression restored the impaired EDR. Similar results were observed in HFD mice. Mechanically, NCEH1 ameliorated the disrupted EDR by dissociating endothelial nitric oxide synthase (eNOS) from caveolin-1 (Cav-1), leading to eNOS activation and nitric oxide (NO) release. Moreover, interaction of NCEH1 with the E3 ubiquitin-protein ligase ZNRF1 led to the degradation of Cav-1 through the ubiquitination pathway. Silencing Cav-1 and upregulating ZNRF1 were sufficient to improve EDR of diabetic aortas, while overexpression of Cav-1 and downregulation of ZNRF1 abolished the effects of NCEH1 on endothelial function in diabetes. Thus, NCEH1 preserves endothelial function through increasing NO bioavailability secondary to the disruption of the Cav-1/eNOS complex in the endothelium of diabetic mice, depending on ZNRF1-induced ubiquitination of Cav-1. CONCLUSIONS: NCEH1 may be a promising candidate for the prevention and treatment of vascular complications of diabetes.

Description of a new species of Forcipomyia (Lasiohelea) (Diptera: Ceratopogonidae) and a key to species of the F. (L.) taiwana species group in China.

Forcipomyia (Lasiohelea) (Meigen, Diptera: Ceratopogonidae) penguin sp. nov. is described and illustrated based on male specimens from China. It is characterized by the approximately rectangular aedeagus, which is longitudinally split in the middle, with the apices slightly bending to the outside, making it into the shape of a hook; bilobed aedeagus is very closely connected. The description is provided using scanning electron microscopes, light microscopes, and camera lucida drawing. The specimens were collected from woods near a pond in Liping County, Guizhou Province. We provide both keys to male and female of Forcipomyia (Lasiohelea) taiwana species group in China.

A tale of two cities: Chinese mothers' parental burnout and parenting behaviors in Shanghai and Nanning.

PURPOSE: Parental burnout is a psychological syndrome that develops in response to the chronic stressors in one's role as a parent. It can be detrimental to the health and wellbeing of both parents and children and has been empirically proven to result in more negative parenting behaviours. Based on recent research, parental burnout is more prevalent in individualistic cultures. Considering that parenting norms and practices vary greatly across cultures, there could be different effects of parental burnout on parenting practices in different areas. The present study aimed to determine the relationship between parental burnout and parenting behaviours in Shanghai and Nanning, two cities in China that differ in the extent to which they have been exposed to the cultural influence of Western individualism, and to examine the moderating effect of city on these relationship patterns. METHODS: Three hundred and sixty-eight mothers in Shanghai and 180 mothers in Nanning took part in the survey. RESULTS: On average, mothers in Shanghai had more severe parental burnout than their counterparts in Nanning. Furthermore, parental burnout was associated with positive parenting behaviours (i.e., parental warmth) and negative parenting behaviours (i.e., parental hostility and neglect), and the associations between parental burnout and negative parenting behaviours in Nanning were greater than in Shanghai. CONCLUSIONS: These results can be explained by cultural differences in individualism and collectivism between Shanghai and Nanning. This study extends the knowledge on the role of culture in shaping parental roles.

Bibliometric study of neuroinflammation in autism spectrum disorder.

Background: Neuroinflammation is closely associated with the occurrence and development of autism spectrum disorder (ASD). This study aims to describe the global development history and current status of neuroinflammation in ASD from 2004 to 2021 and reveal the research hotspots and frontiers to provide a reference for scholars in related fields to carry out further research. Methods: Journal articles on ASD and neuroinflammation-related research were obtained from the Web of Science Core Collection (WOSCC) database from its inception to 2021. Literature was analyzed visually by VOSviewer, CiteSpace, and R language, including publication analysis, author, institution, national/regional cooperative network analysis, and keyword analysis. We screened the most accumulatively cited 10 experimental papers in the field and the most cited 10 experimental papers in the last 2 years (2020 and 2021) for combing. Results: A total of 620 publications were included in this study, and the number of publications has increased in recent years. The United States (256, 41.29%) was the country with the largest number of publications. King Saud University (40, 6.45%) was the most published institution; Laila Al-Ayadhi Yousef was the most published researcher; the Brain Behavior and Immunity was the main journal for the study of neuroinflammation in autism, having published 22 related articles. Keyword co-occurrence analysis showed that short chain fatty acid, mast cells, and glial cells have been the focus of recent attention. Burst keywords show that gut microbiota and immune system are the future research trends. Conclusion: This bibliometric study describes the basic framework for the development in the field of neuroinflammation and ASD through an exploration of key indicators (countries, institutions, journals, authors, and keywords). We found that the key role of neuroinflammation in the development of ASD is attracting more and more researchers' attention. Future studies can investigate the changes in cytokines and glial cells and their related pathways in ASD neuroinflammation. Immunotherapy to inhibit neuroinflammation may be intensively studied as a direction for ASD treatment or intervention.

Family functioning and mobile phone addiction in university students: Mediating effect of loneliness and moderating effect of capacity to be alone.

Background: With the increasing popularity of smartphones, mobile phone addiction in university students has attracted widespread societal attention. Previous studies showed that family functioning and mobile phone addiction are related. However, the potential mechanisms involved in this relationship are unknown. This study examined the mediating effect of loneliness and the moderating effect of capacity to be alone on the relationship between family functioning and mobile phone addiction. Methods: A total of 1,580 university students were recruited. A cross-sectional study design and online questionnaire survey were employed to measure demographic variables, family functioning, loneliness, capacity to be alone, and mobile phone addiction in university students. Results: Family functioning is a significantly negative predictor of mobile phone addiction in university students, and loneliness has a mediating effect on the relationship between family functioning and mobile phone addiction. The capacity to be alone has moderating effects on the relationship between family functioning and loneliness and between family functioning and mobile phone addiction, and these correlation is stronger in university students with a low capacity to be alone. Conclusion: The moderated mediation model in this study improves understanding of the correlation between family functioning and mobile phone addiction in university students. Education professionals and parents should pay particular attention to family functioning in mobile phone addiction, particularly university students with low capacity to be alone.

Reduced left dorsolateral prefrontal activation in problematic smartphone users during the Stroop task: An fNIRS study.

Introduction: The widespread use of smartphones has triggered concern over problematic smartphone use (PSPU), as well as the need to elucidate its underlying mechanisms. However, the correlation between cortical activation and deficient inhibitory control in PSPU remains unclear. Methods: This study examined inhibitory control using the color-word matching Stroop task and its cortical-activation responses using functional near-infrared spectroscopy (fNIRS) in college students with PSPU (n = 56) compared with a control group (n = 54). Results: At the behavioral level, Stroop interference, coupled with reaction time, was significantly greater in the PSPU group than in the control group. Changes in oxygenated hemoglobin (Oxy-Hb) signals associated with Stroop interference were significantly increased in the left ventrolateral prefrontal cortex, left frontopolar area, and bilateral dorsolateral prefrontal cortex (DLPFC). Moreover, the PSPU group had lower Oxy-Hb signal changes associated with Stroop interference in the left-DLPFC, relative to controls. Discussion: These results provide first behavioral and neuroscientific evidence using event-related fNIRS method, to our knowledge, that college students with PSPU may have a deficit in inhibitory control associated with lower cortical activation in the left-DLPFC.

Self-assembled aggregations in Coptidis Rhizoma decoction dynamically regulate intestinal tissue permeability through Peyer's patch-associated immunity.

Objective: To investigate the dynamic regulation of self-assembled aggregations (SAA) in Coptidis Rhizoma decoction on the permeability of intestinal tissue and the mechanism underlying. Methods: The effects of SAA on berberine (Ber) absorption were respectively analyzed in an in situ intestinal perfusion model and in an Ussing Chamber jejunum model with or without Peyer's patches (PPs). The expression levels of ZO-1, Occludin and Claudin-1 were detected by immunofluorescence to evaluate the tight junction (TJ) between intestinal epithelium cells. The expression levels of T-box-containing protein expressed in T cells, signal transducers and activators of tranion-6, retinoic acid receptor-related orphan receptor γt and forkhead box P3 in PPs were detected by the reverse transcription-polymerase chain reaction and the secretions of interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-17 (IL-17) and transforming growth factor-ß (TGF-ß) in PPs were evaluated by immunohistochemistry, to reflect the differentiation of T lymphocyte in PPs to helper T (Th) cell 1, Th2, Th17 and regulatory T (Treg) cell. To confirm the correlation between SAA in Coptidis Rhizoma decoction, PPs-associated immunity and intestinal epithelium permeability, SAA were administrated on an Ussing Chamber jejunum model with immunosuppressed PPs and evaluated its influences on intestinal tissue permeability and TJ proteins expression. Results: SAA in Coptidis Rhizoma decoction could dose-dependently promote Ber absorption in jejunum segment, with the participation of PPs. The dose-dependent and dynamical regulations of SAA on permeability of intestinal tissue and TJ proteins expression level between intestinal epithelium cells occurred along with the dynamically changed T lymphocyte differentiation and immune effectors secretion in PPs. The administration of SAA on immunosuppressed PPs exhibited dose-dependent PPs activation, inducing dynamic promotion on intestinal tissue permeability and inhibition on TJ proteins expression. Conclusion: SAA can improve the Ber absorption in small intestine, through the PPs-associated immunity induced dynamic regulation on intestinal tissue permeability and TJ proteins expression. These findings might enlighten the research of traditional Chinese medicine decoction.

Relationship of Physical Activity With Anxiety and Depression Symptoms in Chinese College Students During the COVID-19 Outbreak.

INTRODUCTION: During the COVID-19 outbreak, many citizens were asked to stay at home in self-quarantine, which can pose a significant challenge with respect to remaining physically active and maintaining mental health. This study aimed to evaluate the prevalence of inadequate physical activity, anxiety, and depression and to explore the relationship of physical activity with anxiety and depression symptoms among Chinese college students during quarantine. METHOD: Using a web-based cross-sectional survey, we collected data from 1,396 Chinese college students. Anxiety and depression were assessed with the Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression Scale (SDS), respectively. The data on physical activity were collected by types of physical activity and the International Physical Activity Questionnaire (IPAQ-SF). RESULTS: During the COVID-19 outbreak, about 52.3% of Chinese college students had inadequate physical activity. The rates of anxiety and depression symptoms were 31.0 and 41.8%, respectively. A high level of physical activity (ß = -0.121, P < 0.001) was significantly closely associated with low anxiety, while a moderate (ß = -0.095, P = 0.001), or high (ß = -0.179, P < 0.001) level of physical activity was significantly closely associated with reduced depression after adjusting confounding demographic factors. Moreover, specific types of physical activity, such as stretching and resistance training, were negatively correlated with both anxiety and depression; doing household chores was negatively correlated with depression. CONCLUSION: Our findings highlight specific levels and types of home-based physical activities that need to be taken into consideration to protect the mental health of college students during the COVID-19 epidemic.

A Reciprocal and Dynamic Development Model for the Effects of Siblings on Children's Theory of Mind.

In the field of social influences on Theory of Mind (ToM), more research has focused on the role of parents, but less research has examined the impact of siblings on children's social understanding. We review existing research related to what factors might affect sibling-ToM association and how these potential factors affect ToM. Based on the literature review, we propose an integrative model that unites three categories of factors (i.e., sibling structural variables, sibling individual variables, parental intervening variables) that might have effects on the sibling-ToM association and highlights mental-state talks during sibling interactions at the intersection of sibling-related variables and ToM. Furthermore, we propose some issues arising from this review that need to be clarified in future studies. Specifically, we hope to clarify the specific effects of older and younger siblings on children's understanding of human minds, the similarities and differences of sibling-ToM association under different cultural backgrounds, and the impact of family social disadvantage (e.g., lower SES) on the sibling-ToM association. All these works would benefit from the verification, revision, and expansion of our reciprocal influence model for the sibling-ToM association.

Morphology of the immature stages of Dasyhelea silvatica Wang, Zhang & Yu with redescriptions of adults (Diptera, Ceratopogonidae).

The immatures of the biting midge Dasyhelea silvatica are described and illustrated for the first time and a complete description of the adult male and female are provided using scanning electron and compound microscopes. The specimens were collected from flooded soil near a pond in Guizhou Province, China, and reared in the laboratory.

[The regulation of gonadal somatic cell differentiation during sex determination in mice].

In mammals, the gonad is composed of germ cells and somatic cells. The gonads have the potential of bidirectional differentiation before sex determination. The differentiation of somatic cells in the gonad determines the development of testis or ovary, and this process is regulated by many factors. SRY, SOX9, SOX3, SOX8, SOX10, FGF9/FGFR2, PGD2, AMH, and DMRT1 are involved in the differentiation of testis. By contrast, FOXL2, CTNNB1, RSPO1, WNT4, Follistatin, ERα/ß, and BMP2 play important roles in ovary development. If these molecular regulatory networks are damaged by endogenous or exogenous factors, disorders of sex differentiation, even sex reversal, will occur. In this review, the regulation of somatic cell fate during gonad primordium formation and sex determination in mouse model was discussed.

Description of a New Species of Forcipomyia (Forcipomyia) (Diptera: Ceratopogonidae) and a Key to Species of the Subgenus From the Chinese Mainland.

Forcipomyia (Forcipomyia) makanensis Hou sp. n. (Diptera: Ceratopogonidae) is described and illustrated based on male and female specimens from China. It is characterized by the male aedeagus triangular, with large cone-shaped process at apex, basal arch high, basal arm slender and curved, parameres separate narrower distance at base, cone-shaped apically, and the female subgenital plate pliers-shaped, without lateral process, with two spermathecae, oval, nearly equal. The new species is compared with the similar congener F. (Forcipomyia) lochmocola Zou and Yu, 1991. We provide separate keys for identification of the males and females of the species of subgenus F. (Forcipomyia) Meigen in China.

The Positive Effect of Moderate-Intensity Exercise on the Mirror Neuron System: An fNIRS Study.

A growing number of studies have reported the beneficial effect of exercise on human social behavior. The mirror neuron system (MNS) plays a critical role in a variety of social behaviors from imitation to empathy. However, neuroimaging investigations into the effects of exercise on the MNS remain unexplored. To address this question, our study determined the effect of moderate-intensity exercise on the MNS using functional near-infrared spectroscopy (fNIRS). Specifically, 23 right-handed young individuals were asked to perform a table-setting task that included action execution and action observation before and after a 25-min exercise session on a cycle ergometer at moderate intensity (65% VO2peak). The control condition was the same task performed without exercise. Cortical hemodynamic changes in the four primary brain regions of the MNS were monitored with fNIRS, using a modified probe configuration that covered all four MNS regions in the left hemisphere. We used a region of interest (ROI)-based group analysis to determine which regions were activated during action execution and action observation. Following a session of moderate-intensity exercise, we found a significant increase in activation in all four MNS regions, namely the inferior frontal gyrus (IFG), premotor cortex (PMC), superior parietal lobule (SPL), and rostral inferior parietal lobule (IPL). This result indicated a positive effect of exercise on the MNS, specifically that moderate-intensity exercise could activate the MNS.

First description of the immature stages of Dasyheleaalula and a redescription of adults from China (Diptera, Ceratopogonidae).

The fourth instar larva and pupa of Dasyheleaalula Yu, 2005 are described and illustrated using a Scanning Electron Microscope. The adult male and female of this species are redescribed. Immatures were collected from flooded soil near a pond in Xiaojiawan village, Guizhou province, China and reared in the laboratory. The studied material is deposited in the Insect Collection of Zunyi Medical University.

A species checklist of the subgenus Culicoides (Avaritia) in China, with a description of a new species (Diptera, Ceratopogonidae).

A checklist of the subgenus Culicoides (Avaritia Fox) (Diptera: Ceratopogonidae: Culicoides) in China, currently including 57 species, is provided. Their full citations, more detailed locations of the type locality, and distribution of each species by province, and/or state of each species are also provided. Culicoides (Avaritia) fenggangensis Liu & Hou, sp. n. is described and illustrated, based on both male and female specimens from China. The new species is compared with its similar congeners, C. (A.) comparis Liu & Yu, 2005 and C. (A.) dentiformis McDonald & Lu, 1972.