A novel candidate gene CLN8 regulates fat deposition in avian

Background The fat deposition has a crucial role in animal meat flavor,and fat deposition-related traits are vital for breeding in the commercial duck industry.Avian fat-related traits are typical complex phenotypes,which need a large amount of data to analyze the genetic loci.Results In this study,we performed a new phenotypic analysis of fat traits and genotyped whole-genome varia-tions for 1,246 ducks,and combed with previous GWAS data to reach 1,880 ducks for following analysis.The carcass composition traits,subcutaneous fat weight(SFW),subcutaneous fat percentage(SFP),abdominal fat weight(AFW),abdominal fat percentage(AFP)and the body weight of day 42(BW42)for each duck were collected.We identified a set of new loci that affect the traits related to fat deposition in avian.Among these loci,ceroid-lipofuscinosis,neuronal 8(CLN8)is a novel candidate gene controlling fat deposition.We investigated its novel function and regulation in avian adipogenesis.Five significant SNPs(the most significant SNP,P-value=21.37E-12)and a single haplotype were detected in the upstream of CLN8 for subcutaneous fat percentage.Subsequently,luciferase assay demonstrated that 5 linked SNPs in the upstream of the CLN8 gene significantly decreased the transcriptional activity of CLN8.Further,ATAC-seq analysis showed that transcription factor binding sites were identified in a region close to the haplotype.A set of luciferase reporter gene vectors that contained different deletion fragments of the CLN8 promoter were con-structed,and the core promoter area of CLN8 was finally identified in the-1,884/-1,207 bp region of the 5′flanking sequences,which contains adipogenesis-related transcription factors binding sites.Moreover,the over-expression of CLN8 can remarkably facilitate adipocyte differentiation in ICPs.Consistent with these,the global transcriptome profiling and functional analysis of the over-expressed CLN8 in the cell line further revealed that the lipid biosynthetic process during the adipogenesis was significantly enriched.Conclusions Our results demonstrated that CLN8 is a positive regulator of avian adipocyte differentiation.These findings identify a novel function of CLN8 in adipocyte differentiation,which provides important clues for the further study of the mechanism of avian fat deposition.

粉煤灰基微滤膜处理二沉池出水的研究

粉煤灰基微滤膜是一种新型的廉价陶瓷膜,本文将其用于生活污水的三级处理。考察了跨膜压差和膜面流速等对渗透通量的影响,利用孔堵模型对膜污染过程进行了污染机理分析。膜过滤出水达到了生活杂用水的标准。发现膜污染的机理主要是滤饼层过滤机理。

Pharmacological inhibition of cation-chloride cotransporters for neurological diseases

γ-Aminobutyric acid（GABA）is a major neurotransmitter and plays important roles in both the developing and mature central nervous system（CNS）.One way that GABA can act is by binding to fast,ionotropic GABAA receptors in neurons.The binding of GABA to GABAA receptors causes a conformational change that opens ion channels.

Immediate-release Mechanism of Dehydrotrametenolic Acid and Dehydroeburicoic Acid in Poriae Cutis Total Triterpenoids Tablets Based on Liquid-solid Compact Technique

[Objectives]To study the immediate-release mechanism of dehydrotrametenolic acid and dehydroeburicoic acid in Poriae Cutis total triterpenoids tablets by liquid-solid compacts technique.[Methods] Taking dehydrotrametenolic acid and dehydroeburicoic acid as indicators,differences in dissolution were compared between liquid-solid compressed tablets and crude drug of total triterpenoids in Poriae Cutis;crude drug,powder of liquid-solid compressed tablets and excipients of liquid-solid compressed tablets were characterized by differential scanning calorimetry( DSC).[Results]Liquid-solid compact technique could significantly improve dissolution rate of dehydrotrametenolic acid and dehydroeburicoic acid. The total dissolution rate of dehydrotrametenolic acid and dehydroeburicoic acid in Poriae Cutis total triterpenoids tablets was 92%,t50( time for 50% total dissolution rate) and t_D( time for 63. 2% total dissolution rate) were 11. 18 min and 22. 71 min; the total dissolution rate of dehydrotrametenolic acid and dehydroeburicoic acid in crude drug of total triterpenoids was 29%,and t50 and t_D were231. 06 min and 359. 23 min. DSC showed that there was no mutual interaction between excipients and total triterpenoids in Poriae Cutis; on the DSC curve for powder of liquid-solid compressed tablets,the absorption peak vanished completely,indicating that the drug exists in the amorphous form in the liquid-solid powder.[Conclusions] Liquid-solid compact technique can increase the dissolution rate of total triterpenoids in Poriae Cutis and allow rapid release of poorly water soluble drugs.

A cyclodextrin-based nanoformulation achieves co-delivery of ginsenoside Rg3 and quercetin for chemo-immunotherapy in colorectal cancer

The immune checkpoint blockade therapy has profoundly revolutionized the field of cancer immunotherapy. However, despite great promise for a variety of cancers, the efficacy of immune checkpoint inhibitors is still low in colorectal cancer(CRC). This is mainly due to the immunosuppressive feature of the tumor microenvironment(TME). Emerging evidence reveals that certain chemotherapeutic drugs induce immunogenic cell death(ICD), demonstrating great potential for remodeling the immunosuppressive TME. In this study, the potential of ginsenoside Rg3(Rg3) as an ICD inducer against CRC cells was confirmed using in vitro and in vivo experimental approaches. The ICD efficacy of Rg3 could be significantly enhanced by quercetin(QTN) that elicited reactive oxygen species(ROS). To amelioratein vivo delivery barriers associated with chemotherapeutic drugs, a folate(FA)-targeted polyethylene glycol(PEG)-modified amphiphilic cyclodextrin nanoparticle(NP) was developed for co-encapsulation of Rg3 and QTN. The resultant nanoformulation(CD-PEG-FA.Rg3.QTN) significantly prolonged blood circulation and enhanced tumor targeting in an orthotopic CRC mouse model, resulting in the conversion of immunosuppressive TME. Furthermore, the CD-PEG-FA.Rg3.QTN achieved significantly longer survival of animals in combination with Anti-PD-L1. The study provides a promising strategy for the treatment of CRC.

Functional exhaustion of antiviral lymphocytes in COVID-19 patients

In December 2019,a novel coronavirus was first reported in Wuhan,China.1 It was named by the World Health Organization as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and is responsible for coronavirus disease 2019(COVID-19).Up to 28 February 2020,79,394 cases have been confirmed according to China’s National Health Commission.Outside China,the virus has spread rapidly to over 36 countries and territories.

Synthesis of a reduction-sensitive Bletilla striata polysaccharide amphiphilic copolymer

Recently, much special attention has been focused on the development of amphiphilic copolymers.Herein, a reduction-sensitive stearic acid grafted-Bletilla striata polysaccharide copolymer（BSP-ss-SA）was synthesized and characterized. BSP-ss-SA copolymer could spontaneously form micelles with an average particle size of（106 ？ 4.36） nm. Particle sizes were dramatically larger under 10 mmol/L dithiothreitol（DTT） than that in absence of 10 mmol/L DTT. Docetaxel loading content and encapsulation efficiency of micelles were 5.94 wt% and 72.75 wt%, respectively. The docetaxel release rate in vitro in micelles could be remarkably accelerated in pH 7.4 phosphate buffer solution（PBS） containing 10 mmol/L DTT compared with that of micelles（0 mmol/L DTT）. Furthermore, MTT results demonstrated the anticancer activities in vitro of docetaxel-loaded BSP-ss-SA micelles on HepG2 were superior to that of docetaxel injection. BSP-ss-SA copolymer might be a promising nanocarrier for cancer chemotherapy drugs.

Corrosion behavior of Ti_(3)AlC_(2) in molten KOH at 700℃

This paper investigated the corrosion behaviors of Ti_(3)AlC_(2) at 700℃in molten KOH with various mass ratios.If the mass ratio of KOH:Ti_(3)AlC_(2)≤2,Ti_(3)AlC_(2) can resist KOH hot corrosion in 2 h.Ti_(3)AlC_(2) suffered serious corrosion attack if the mass ratio≥3.The main compositions of corroded samples were amorphous graphite and potassium titanates(K_(2)O·nTiO_(2)).If the samples were washed by acid and dried,potassium titanates could decompose to K_(2)O and amorphous rutile.Based on the experimental results,a corrosion mechanism of Ti_(3)AlC_(2) in molten KOH was proposed.

Mitochondrial fusion protein 2 regulates endoplasmic reticulum stress in preeclampsia

Preeclampsia(PE)refers to a group of dysfunction syndromes associated with elevated blood pressure and proteinuria in women with previously normal blood pressure after 20 weeks of pregnancy,and it may be accompanied by symptoms including headache。

Comprehensive Control Scheme for an Interlinking Converter in a Hybrid AC/DC Microgrid

This paper presents a comprehensive control scheme for the interlinking converter(ILC)in a hybrid AC/DC microgrid consisting of the outer loop flexible power sharing control and the improved robust inner loop control.The outer loop power control of ILC is presented to achieve flexible power sharing of distributed generations(DGs)in the hybrid microgrid,depending on different power management objectives,which is realized based on the deduced balance state equation,and regulating the frequency and DC voltage at the same time.The improved robust inner loop control of ILC is also presented to suppress external disturbance and system model uncertainties with the improved dynamic response.This improved inner loop control which includes a disturbance observer link,can force the converter current to track the reference value with no steady error and improve the dynamic stability of the microgrid・With the proposed outer loop power sharing control and improved inner loop control,the comprehensive control scheme for the ILC is presented・Simulations cases show the effectiveness and superiority of the proposed comprehensive control scheme.

Discovery of 4-cyclopropyl-3-(2-((1-cyclopropyl-1H-pyrazol-4-yl) amino) quinazolin-6-yl)-N-(3-(trifluoromethyl) phenyl) benzamides as potent discoidin domain receptor inhibitors for the treatment of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis(IPF)is a chronic fatal lung disease with a median survival time of 3–5 years.Inaccurate diagnosis,limited clinical therapy and high mortality together indicate that the development of effective therapeutics for IPF is an urgent need.In recent years,it was reported that DDRs are potential targets in anti-fibrosis treatment.Based on previous work we carried out further structure modifications and led to a more selective inhibitor 47 by averting some fibrosis-unrelated kinases,such as RET,AXL and ALK.Extensive profiling of compound 47 has demonstrated that it has potent DDR1/2 inhibitory activities,low toxicity,good pharmacokinetic properties and reliable in vivo anti-fibrosis efficacy.Therefore,we confirmed that discoidin domain receptors are promising drug targets for IPF,and compound 47 would be a promising candidate for further drug development.

Peptide RL-QN15 promotes wound healing of diabetic foot ulcers through p38 mitogen-activated protein kinase and smad3/miR-4482-3p/vascular endothelial growth factor B axis

Background:Wound management of diabetic foot ulcers(DFUs)is a complex and challenging task,and existing strategies fail to meet clinical needs.Therefore,it is important to develop novel drug candidates and discover new therapeutic targets.However,reports on peptides as molecular probes for resolving issues related to DFUs remain rare.This study utilized peptide RL-QN15 as an exogenous molecular probe to investigate the underlying mechanism of endogenous non-coding RNA in DFU wound healing.The aim was to generate novel insights for the clinical management of DFUs and identify potential drug targets.Methods:We investigated the wound-healing efficiency of peptide RL-QN15 under diabetic con-ditions using in vitro and in vivo experimental models.RNA sequencing,in vitro transfection,quantitative real-time polymerase chain reaction,western blotting,dual luciferase reporter gene detection,in vitro cell scratches,and cell proliferation and migration assays were performed to explore the potential mechanism underlying the promoting effects of RL-QN15 on DFU repair.Results:Peptide RL-QN15 enhanced the migration and proliferation of human immortalized keratinocytes(HaCaT cells)in a high-glucose environment and accelerated wound healing in a DFU rat model.Based on results from RNA sequencing,we defined a new microRNA(miR-4482-3p)related to the promotion of wound healing.The bioactivity of miR-4482-3p was verified by inhibiting and overexpressing miR-4482-3p.Inhibition of miR-4482-3p enhanced the migration and proliferation ability of HaCaT cells as well as the expression of vascular endothelial growth factor B(VEGFB).RLQN15 also promoted the migration and proliferation ability of HaCaT cells,and VEGFB expression was mediated via inhibition of miR-4482-3p expression by the p38 mitogen-activated protein kinase(p38MAPK)and smad3 signaling pathways.Conclusions:RL-QN15 is an effective molecule for the treatment of DFUs,with the underlying mechanism related to the inhibition of miR-4482-3p expression via the p38MAPK and smad3 signaling pathways,ultimately promoting re-epithelialization,angiogenesis and wound healing.This study provides a theoretical basis for the clinical application of RL-QN15 as a molecular probe in promoting DFU wound healing.

Aberrant Hippocampal Development in Early‑onset Mental Disorders and Promising Interventions:Evidence from a Translational Study

Early-onset mental disorders are associated with disrupted neurodevelopmental processes during adolescence.The methylazoxymethanol acetate(MAM)animal model,in which disruption in neurodevelopmental processes is induced,mimics the abnormal neurodevelopment associated with early-onset mental disorders from an etiological perspective.We conducted longitudinal structural magnetic resonance imaging(MRI)scans during childhood,adolescence,and adulthood in MAM rats to identify specific brain regions and critical windows for intervention.Then,the effect of repetitive transcranial magnetic stimulation(rTMS)intervention on the target brain region during the critical window was investigated.In addition,the efficacy of this intervention paradigm was tested in a group of adolescent patients with early-onset mental disorders(diagnosed with major depressive disorder or bipolar disorder)to evaluate its clinical translational potential.The results demonstrated that,compared to the control group,the MAM rats exhibited significantly lower striatal volume from childhood to adulthood(all P<0.001).In contrast,the volume of the hippocampus did not show significant differences during childhood(P>0.05)but was significantly lower than the control group from adolescence to adulthood(both P<0.001).Subsequently,rTMS was applied to the occipital cortex,which is anatomically connected to the hippocampus,in the MAM models during adolescence.The MAM-rTMS group showed a significant increase in hippocampal volume compared to the MAM-sham group(P<0.01),while the volume of the striatum remained unchanged(P>0.05).In the clinical trial,adolescents with early-onset mental disorders showed a significant increase in hippocampal volume after rTMS treatment compared to baseline(P<0.01),and these volumetric changes were associated with improvement in depressive symptoms(r=−0.524,P=0.018).These findings highlight the potential of targeting aberrant hippocampal development during adolescence as a viable intervention for earlyonset mental disorders with neurodevelopmental etiology as well as the promise of rTMS as a therapeutic approach for mitigating aberrant neurodevelopmental processes and alleviating clinical symptoms.