Hesperidin alleviates zinc-induced nephrotoxicity via the gut-kidney axis in swine.

Introduction: Zinc (Zn) is an essential trace element in animals, but excessive intake can lead to renal toxicity damage. Thus, the exploration of effective natural antagonists to reduce the toxicity caused by Zn has become a major scientific problem. Methods: Here, we found that hesperidin could effectively alleviate the renal toxicity induced by Zn in pigs by using hematoxylin-eosin staining, transmission electron microscope, immunohistochemistry, fluorescence quantitative PCR, and microfloral DNA sequencing. Results: The results showed that hesperidin could effectively attenuate the pathological injury in kidney, and reduce autophagy and apoptosis induced by Zn, which evidenced by the downregulation of LC3, ATG5, Bak1, Bax, Caspase-3 and upregulation of p62 and Bcl2. Additionally, hesperidin could reverse colon injury and the decrease of ZO-1 protein expression. Interestingly, hesperidin restored the intestinal flora structure disturbed by Zn, and significantly reduced the abundance of Tenericutes (phylum level) and Christensenella (genus level). Discussion: Thus, altered intestinal flora and intestinal barrier function constitute the gut-kidney axis, which is involved in hesperidin alleviating Zn-induced nephrotoxicity. Our study provides theoretical basis and practical significance of hesperidin for the prevention and treatment of Zn-induced nephrotoxicity through gut-kidney axis.

Dissecting Psychiatric Heterogeneity and Comorbidity with Core Region-Based Machine Learning / 神经科学通报·英文版

Machine learning approaches are increasingly being applied to neuroimaging data from patients with psychiatric disorders to extract brain-based features for diagnosis and prognosis. The goal of this review is to discuss recent practices for evaluating machine learning applications to obsessive-compulsive and related disorders and to advance a novel strategy of building machine learning models based on a set of core brain regions for better performance, interpretability, and generalizability. Specifically, we argue that a core set of co-altered brain regions (namely 'core regions') comprising areas central to the underlying psychopathology enables the efficient construction of a predictive model to identify distinct symptom dimensions/clusters in individual patients. Hypothesis-driven and data-driven approaches are further introduced showing how core regions are identified from the entire brain. We demonstrate a broadly applicable roadmap for leveraging this core set-based strategy to accelerate the pursuit of neuroimaging-based markers for diagnosis and prognosis in a variety of psychiatric disorders.

Biological Implication of Chimeric RNAs in Cancer / 中国生物化学与分子生物学报

Chimeric RNA is a fusion transcript composed of exons from two or more different genes and generated by chromosome rearrangement or RNA splicing. Chimeric RNAs have the potential to encode novel proteins or function as non-coding RNAs. Chimeric RNAs were ubiquitously expressed across different cancers and normal tissues. To date, mechanistic and functional studies of chimeric RNAs still remain unclear. Precise definition and terminology in the research field of chimeric RNA will be discussed in this review. The formation, classification and clinical significance of chimeric RNAs in cancer progression will be summarized. Previous studies showed that products of chimeric RNAs may play important roles in regulating cell proliferation, motility, invasion and apoptosis through encoded fusion proteins or long non-coding chimeric RNAs. In cancer, chimeric RNA and its encoded specific protein or non-coding RNA can regulate tumorigenesis by changing cell phenotypes or directly affecting gene expression or regulatory pathways, which have the potential to be important diagnostic biomarkers and therapeutic targets. In recent years, more and more cancer-specific chimeric RNAs have been discovered from multiple types of cancers and used as therapeutic targets due to their vital roles in disease prognosis. Therefore, this review will focus on the functions and applications of chimeric RNAs in different tumors, which can shed a light on cancer diagnosis and therapeutics from the new perspective.

Coronaviruses using different strategies to antagonize antiviral responses and pyroptosis

Viral infection triggers inflammasome-mediated caspase-1 activation. However, less is known about how viruses use the active caspase-1 to evade host immune response. Here, we use porcine epidemic diarrhea virus (PEDV) as a model of coronaviruses (CoVs) to illustrate the sophisticated regulation of CoVs to counteract IFN-I signaling and pyroptosis. We show that PEDV infection stabilizes caspase-1 expression via papain-like protease PLP2s deubiquitinase activity and the enhanced stabilization of caspase-1 disrupts IFN-I signaling by cleaving RIG-I at D189 residue. Meanwhile, PLP2 can degrade GSDMD-p30 by removing its K27-linked ubiquitin chain at K275 to restrain pyroptosis. Papain-like proteases from other genera of CoVs (PDCoV and SARS-CoV-2) have the similar activity to degrade GSDMD-p30. We further demonstrate that SARS-CoV-2 N protein induced NLRP3 inflammasome activation also uses the active caspase-1 to counter IFN-I signaling by cleaving RIG-I. Therefore, our work unravels a novel antagonistic mechanism employed by CoVs to evade host antiviral response.

The nonstructural protein 5 of coronaviruses antagonizes GSDMD-mediated pyroptosis by cleaving and inactivating its pore-forming p30 fragment

Coronaviruses (CoV) are a family of RNA viruses that typically cause respiratory, enteric and hepatic diseases in animals and humans. Here, we used porcine epidemic diarrhea virus (PEDV) as a model of coronaviruses (CoVs) to illustrate the reciprocal regulation between CoVs infection and pyroptosis. For the first time, we clarified the molecular mechanism of porcine Gasdermin D (pGSDMD)-mediated pyroptosis and demonstrated that amino acids T239 and F240 within pGSDMD-p30 are critical for pyroptosis. Furthermore, 3C-like protease Nsp5 from SARS-CoV-2, MERS-CoV, PDCoV and PEDV can cleave human/porcine GSDMD at the Q193-G194 junction upstream of the caspase-1 cleavage site to produce two fragments which fail to trigger pyroptosis or inhibit viral replication. Thus, we provide clear evidence that coronoviruses may utilize viral Nsp5-GSDMD pathway to help their host cells escaping from pyroptosis, protecting the replication of the virus during the initial period, which suggest an important strategy for coronoviruses infection and sustain.

Reduction of essential amino acid levels and sex-specific alterations in serum amino acid concentration profiles in children with autism spectrum disorder.

BACKGROUND: Existing evidence has shown that metabolic disturbances may be involved in the pathological process of autism spectrum disorder(ASD). This study aimed to investigate the alterations of serum amino acid concentration profiles in Chinese Han children with ASD. METHODS: Serum amino acid levels were measured using tandem mass spectrometry in 60 children with ASD and 30 typically developing (TD) controls. The Chinese Wechsler Young Children Scale of Intelligence (C-WYCSI) was used to evaluate the ASD subjects' intelligence quotient (IQ). RESULTS: The serum levels of essential amino acids and some non-essential amino acids (glutamine, glycine, alanine, citrulline, cysteine, serine, tyrosine, and proline) in the ASD group were significantly lower than those in controls. The serum glutamate/glutamine (Glu/Gln) ratio was elevated in the ASD PIQ≥70 group, while serum levels of alanine, cysteine, phenylalanine, methionine and proline were significantly higher in male children with ASD than that in the female group. CONCLUSION: The study revealed that children with ASD exhibit alterations in the serum levels of certain amino acids, and the divergence can be sex-related or associated with different cognitive function, which might provide clues for further etiological research of ASD.

Prevalence of feline calicivirus and the distribution of serum neutralizing antibody against isolate strains in cats of Hangzhou, China

Background@#Feline calicivirus (FCV) is a common pathogen of felids, and FCV vaccination is regularly practiced. The genetic variability and antigenic diversity of FCV hinder the effective control and prevention of infection by vaccination. Improved knowledge of the epidemiological characteristics of FCV should assist in the development of more effective vaccines. @*Objectives@#This study aims to determine the prevalence of FCV in a population of cats with FCV-suspected clinical signs in Hangzhou and to demonstrate the antigenic and genetic relationships between vaccine status and representative isolated FCV strains. @*Methods@#Cats (n = 516) from Hangzhou were investigated between 2018 and 2020. The association between risk factors and FCV infection was assessed. Phylogenetic analyses based on a capsid coding sequence were performed to identify the genetic relationships between strains. In vitro virus neutralization tests were used to assess antibody levels against isolated FCV strains in client-owned cats. @*Results@#The FCV-positive rate of the examined cats was 43.0%. Risk factors significantly associated with FCV infection were vaccination status and oral symptoms. Phylogenetic analysis revealed a radial phylogeny with no evidence of temporal or countrywide clusters. There was a significant difference in the distribution of serum antibody titers between vaccinated and unvaccinated cats. @*Conclusions@#This study revealed a high prevalence and genetic diversity of FCV in Hangzhou. The results indicate that the efficacy of FCV vaccination is unsatisfactory. More comprehensive and refined vaccination protocols are an urgent and unmet need.

Prevalence of feline calicivirus and the distribution of serum neutralizing antibody against isolate strains in cats of Hangzhou, China

Background@#Feline calicivirus (FCV) is a common pathogen of felids, and FCV vaccination is regularly practiced. The genetic variability and antigenic diversity of FCV hinder the effective control and prevention of infection by vaccination. Improved knowledge of the epidemiological characteristics of FCV should assist in the development of more effective vaccines. @*Objectives@#This study aims to determine the prevalence of FCV in a population of cats with FCV-suspected clinical signs in Hangzhou and to demonstrate the antigenic and genetic relationships between vaccine status and representative isolated FCV strains. @*Methods@#Cats (n = 516) from Hangzhou were investigated between 2018 and 2020. The association between risk factors and FCV infection was assessed. Phylogenetic analyses based on a capsid coding sequence were performed to identify the genetic relationships between strains. In vitro virus neutralization tests were used to assess antibody levels against isolated FCV strains in client-owned cats. @*Results@#The FCV-positive rate of the examined cats was 43.0%. Risk factors significantly associated with FCV infection were vaccination status and oral symptoms. Phylogenetic analysis revealed a radial phylogeny with no evidence of temporal or countrywide clusters. There was a significant difference in the distribution of serum antibody titers between vaccinated and unvaccinated cats. @*Conclusions@#This study revealed a high prevalence and genetic diversity of FCV in Hangzhou. The results indicate that the efficacy of FCV vaccination is unsatisfactory. More comprehensive and refined vaccination protocols are an urgent and unmet need.

Inhibition of bakuchiol and its derivatives in Psoraleae Fructus on nitric oxide production in lipopolysaccharide-activated RAW 264.7 cell lines / 中草药

Objective: To study bakuchiol and its derivatives of cyclohexane soluble part in 70% ethanol aqueous extract of Psoraleae Fructus and their inhibition on nitric oxide (NO) production in lipopolysaccharides (LPS)-activated murine macrophage RAW 264.7 cell lines. Methods: The compounds were separated and purified by silica gel column and high performance liquid chromatographies, and their structures were determined by spectroscopic data analyses. Using LPS-activated RAW 264.7 cell line models in vitro, all of the isolated compounds were evaluated for the inhibition against NO production. Results: Twelve compounds were obtained and identified as bakuchiol (1), 12,13-dihydro-12,13-epoxybakuchiol (2), Δ3,2-hydroxylbakuchiol (3), 12-oxobakuchiol (4), psoracorylifol B (5), psoracorylifol C (6), (12’S)-bisbakuchiol C (7), Δ1,3-bakuchiol (8), 13-methoxyisobakuchiol (9), bisbakuchiol B (10), bisbakuchiol A (11), and 12,13-dihydro-12,13-dihydroxybakuchiol (12), respectively. For the inhibition of NO production in the LPS-activated RAW 264.7 cell line model, a positive inhibitor, L-N6-(1-iminoethyl)-lysine (L-NIL), was used and showed the half maximal inhibitory concentration (IC50) value of (10.29 ± 1.10) μmol/L. The IC50 values of the assayed compounds 1, 3, 5, 10 and 11 were all more than 50 μmol/L, compounds 8, 9 and 12 were comparable to that of L-NIL, whereas the IC50 values of compounds 2, 4 and 7 were less than that of the positive inhibitor with statistically significance. Conclusion: Compound 4 is a new natural product. The results of the bioactivity assays indicated that compounds 2, 4, 7, 8, 9 and 12 are potential anti-inflammatory agents.

Functional Connectivity-Based Modelling Simulates Subject-Specific Network Spreading Effects of Focal Brain Stimulation / 神经科学通报·英文版

Neurostimulation remarkably alleviates the symptoms in a variety of brain disorders by modulating the brain-wide network. However, how brain-wide effects on the direct and indirect pathways evoked by focal neurostimulation elicit therapeutic effects in an individual patient is unknown. Understanding this remains crucial for advancing neural circuit-based guidance to optimize candidate patient screening, pre-surgical target selection, and post-surgical parameter tuning. To address this issue, we propose a functional brain connectome-based modeling approach that simulates the spreading effects of stimulating different brain regions and quantifies the rectification of abnormal network topology in silico. We validated these analyses by pinpointing nuclei in the basal ganglia circuits as top-ranked targets for 43 local patients with Parkinson's disease and 90 patients from a public database. Individual connectome-based analysis demonstrated that the globus pallidus was the best choice for 21.1% and the subthalamic nucleus for 19.5% of patients. Down-regulation of functional connectivity (up to 12%) at these prioritized targets optimally maximized the therapeutic effects. Notably, the priority rank of the subthalamic nucleus significantly correlated with motor symptom severity (Unified Parkinson's Disease Rating Scale III) in the local cohort. These findings underscore the potential of neural network modeling for advancing personalized brain stimulation therapy, and warrant future experimental investigation to validate its clinical utility.

Clincal Value of Ultrasound-guided Transvaginal Radiofrequency Ablation for the Treatment of Symptomatic Uterine Fibroid / 现代生物医学进展

Objective:To investigate the safety and efficacy of ultrasound-guided transvaginal radiofrequency ablation in the treat ment of symptomatic uterine fibroid.Methods:39 patients with symptomatic uterine fibroid underwent transvaginal radiofrequency ablation therapy were selected Before treatment,the fibroid size and volume were measured using ultrasound.The fibroid-related symptom severity and quality of life were scored using uterine fibroid symptom and quality of life survey.The fibroid volume reduction rate,improvement in clinical symptom and quality of life,and ovarian function of patients were observed before treatment and at three,six,nine and 12 months after treatment.Results:The average operation time of radiofrequency ablation was 25 minutes.There was no clear intraand postoperative complication.Preoperative fibroid volume was 65.2± 49.3cm3,which was reduced to 32.2± 27.6 cm3,21.2± 18.2 cm3,15.3± 12.1 cm3 and 10.3± 9.8 cm3 at 3,6,9 and 12 months after treatment,respectively(P＜0.05).The symptom severity score (SSS) was 60.23± 13.2 before treatment,and gradually decreased to 42.2± 11.4,21.1± 10.2,15.4± 10.3 and 12.2± 9.7 at 3,6,9 and 12 months after treatment(P＜0.05).The quality of life (QOL) score gradually increased from 58.24± 16.24 before treatment to 70.3± 20.3,81.4± 8.6,86.3± 7.6 and 88.2± 9.1 at 3,6,9 and 12 months after treatment (P＜0.05).The levels of follicle stimulating hormone,luteinizing hormone and estradiol at 3,6,9 and 12 months after treatment showed no difference compared with these before treatment (P＞0.05).Conclusions:Ultrasound-guided transvaginal radiofrequency therapy was a minimally invasive,safe,and effective therapy for symptomatic uterine fibroid.

Biliverdin protects against cisplatin-induced apoptosis of renal tubular epithelial cells / 华中科技大学学报（医学）（英德文版）

Biliverdin (BV) has long been thought to be a cytotoxic metabolic waste product. It has also been demonstrated to have important cytoprotective functions during oxidative stress. The present study aimed to examine the cytoprotective effect of BV on NRK-52E cells, a proximal tubular cell line derived from rat kidney. Cells were treated with 50 µmol/L cisplatin for 24 h (cisplatin group) or pre-treated with BV for 30 min, then with 50 µmol/L cisplatin for 24 h (cisplatin+BV group). Those given no treatment served as a control. Cell apoptosis was evaluated by flow cytometry and cell viability by Cell Counting Kit-8 (CCK-8). The protein expressions of cleaved caspase3, Bax and Bcl-2 were assessed by Western blotting. Reactive oxygen species (ROS) levels were measured using carboxydichlorodihydrofluorescein diacetate (H2DCF). The results showed that cisplatin induced the apoptosis of NRK-52E cells, decreased cell viability, and increased the formation of ROS by upregulating the expression of cleaved caspase3 and Bax and decreasing Bcl-2 protein expression. These effects could be significantly reversed by pretreatment with BV. It was concluded that BV can protect against cisplatin-induced cell apoptosis through the anti-oxidative effects.

Biliverdin protects against cisplatin-induced apoptosis of renal tubular epithelial cells / 华中科技大学学报（医学）（英德文版）

Biliverdin (BV) has long been thought to be a cytotoxic metabolic waste product. It has also been demonstrated to have important cytoprotective functions during oxidative stress. The present study aimed to examine the cytoprotective effect of BV on NRK-52E cells, a proximal tubular cell line derived from rat kidney. Cells were treated with 50 µmol/L cisplatin for 24 h (cisplatin group) or pre-treated with BV for 30 min, then with 50 µmol/L cisplatin for 24 h (cisplatin+BV group). Those given no treatment served as a control. Cell apoptosis was evaluated by flow cytometry and cell viability by Cell Counting Kit-8 (CCK-8). The protein expressions of cleaved caspase3, Bax and Bcl-2 were assessed by Western blotting. Reactive oxygen species (ROS) levels were measured using carboxydichlorodihydrofluorescein diacetate (H2DCF). The results showed that cisplatin induced the apoptosis of NRK-52E cells, decreased cell viability, and increased the formation of ROS by upregulating the expression of cleaved caspase3 and Bax and decreasing Bcl-2 protein expression. These effects could be significantly reversed by pretreatment with BV. It was concluded that BV can protect against cisplatin-induced cell apoptosis through the anti-oxidative effects.

The Acoustic Characteristics of the Voice of the Sulcus Vocalis Patients with Minimum Glottal Areas / 听力学及言语疾病杂志

Objective To investigate the voicing acoustic characteristics of sulcus vocalis patients with mini-mum glottal area(MGA) .Methods 60 normal subjects (30 male ,30 female) ,and 62 subjects with sulcus vocalis (33 male and 29 female)were recruited .They all had stroboscopic laryngoscopy ,and had MGA measured when say-ing /i:/using software supporting KIPS .The acoustic parameters consisted of vocal cord fundamental frequency (F0) ,jitter and shimmer ,normalized noise energy ( NNE) ,harmony to noise ratio (HNR) and signal noise ratio (SNR) ,maximum phonation time(MPT) and respectively make correlation analysis with voice MGA .Results The voicing MGA of male patients with sulcus vocalis was 434 .74 ± 112 .83 ,larger than the males with normal vocalis 298 .25 ± 93 .63 .This was statistically significant (P<0 .05) .The voicing MGA of females with sulcus vocalis was (484 .75 ± 143 .91) ,significantly larger than those of females with normal vocalis (293 .43 ± 93 .73) and the differ-ence was statistically significant (P<0 .05) .The voicing MGA on both males and females with sulcus vocalis was noticeably relation to the F0 (r=0 .972 ,P<0 .05) and (r=0 .928 ,P<0 .05) ,Jitter (r=0 .978 ,P<0 .05) and (r=0 .910 ,P<0 .910) and Shimmer (r=0 .973 ,P<0 .05) and (r=0 .921 ,P<0 .05) ,normalized noise energy(r=0 .883 ,P<0 .05) and (r=0 .960 ,P<0 .05) ;and negative relation to the signal noise ratio (r= -0 .947 ,P<0 .05) and (r = -0 .957 ,P<0 .05) ,signal noise ratio (r= -0 .959 ,P<0 .05) and (r= -0 .944 ,P<0 .05) ,max-imum phonation time (r= -0 .891 ,P<0 .05) and (r= -0 .936 ,P<0 .05) .Conclusion Patients with pathological sulcus vocalis have glottal areas larger than normal .Acoustic analysis of the voices of the sulcus vocalis can be used as an objective laboratory examination .

Research advances in molecular genetics and treatment of familial hemophagocytic lymphohistiocytosis / 中国当代儿科杂志

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome characterized by pancytopenia and multiple organ infiltrations of lymphocytes and histiocytes with proliferation and hemohpagocytic activity. HLH is classified as primary (or familial) and secondary. Familial HLH is common in infants and young children, and is related to genetic defects. This article aims to review research advances on PRF1, UNC13D, STX11 and STXBP2, as well as the other 5 genes associated with familial HLH based on molecular genetics, and to summarize diagnosis and treatment methods for this disease.

The superior gluteal neurocutaneous flap transfer for sacrococcygeal pressure sores / 中华显微外科杂志

Objective To observe the clinical outcomes of the superior gluteal neurocutaneous flap for sacrococcygeal pressure sores. Methods Twelve cases with sacrococcygeal pressure sores were covered by the superior gluteal neurocutaneous flap from May 2005 to Nov. 2009. The sore size ranged from 15 cm ×30 cm to 5 cm × 8 cm, while the flap size ranged from 17 cm × 32 cm to 10 cm× 12 cm. Results All 12 flaps survived totally with the pressure sores healed. The longest follow-up time was four years, the short follow-up time was half a year, the average time was 2.5 years. The superior gluteal neurocutaneous flap was good blood circulation, pressure sores not recur. Conclusion The superior gluteal neurocutaneous flap is a good treatment for sacrococcygeal pressure sores for its reliable blood supply and simple harvesting.

Overexpression of SERCA2a by gene transfer enhances myocardial systolic function in canines / 生理学报

The present study is aimed to study the effect of sarcoplasmic reticulum Ca(2+)-ATPase 2a (SERCA2a) gene transfer on the contractile function of isolated cardiomyocytes of canines. The cardiomyocytes were isolated with collagenases. The isolated cardiac cells were divided into untransfected group, empty vector group and SERCA2a-transfected group. Recombinant adenovirus vector carrying enhanced green fluorescent protein gene was used for SERCA2a gene delivery. The expression of SERCA2a protein in cardiomyocytes was determined by Western blot. Contractile function of cardiomyocytes was measured with motion edge-detection system of single cell at 48 h after transfection. The results showed, compared with untransfected group, SERCA2a protein level, percentage of peak contraction amplitude under normal condition, percentages of peak contraction amplitude under Ca(2+) or isoproterenol stimulation, time-to-peak contraction (TTP) and time-to-50% relaxation (R50) in SERCA2a-transfected group all increased significantly. While all the above indices in empty vector group did not show any differences with those in untransfected group. These results suggest that the overexpression of SERCA2a by gene transfer may enhance the contraction function of canine myocardial cells.