Genome-wide characterization of drought-responsive long non-coding RNAs in sorghum (Sorghum bicolor).

Drought stress strongly affects crop yield. Although knowledge of long non-coding RNAs (lncRNAs) has been updated continuously and rapidly, information about lncRNAs in drought resistance regulation is extremely limited in sorghum. Here, lncRNA-sequencing was performed with seedlings of a sorghum cultivar (Jinza29) under three water control treatments to investigate the mechanism of lncRNAs responsible for drought resistance in sorghum. A total of 377 differentially expressed lncRNAs (DElncRNAs) were identified. We also predicted 4322 and 2827 transcripts as potential cis-target and trans-target genes for drought-responsive lncRNAs, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that those target genes exhibited marked enrichment into "oxidoreductase activity", "signal transducer activity", "DNA repair", "photosynthesis", "glutathione metabolism", and "phenylpropanoid biosynthesis" and other terms associated with abiotic stress resistance. Moreover, several lncRNAs were estimated to modulate the expression of other genes related to stress response and photosynthetic carbon metabolism. Additionally, we found 107 DElncRNAs that might be candidate target mimics for 56 miRNAs. LncRNAs play important roles in drought adaptation of sorghum through interacting with protein-encoding genes. The obtained results provided novel insights into the biological characteristics of lncRNAs and offered potential regulatory factors for genetically enhancing drought resistance in sorghum.

FGF21-dependent alleviation of cholestasis-induced liver fibrosis by sodium butyrate.

Background: The beneficial effects of fibroblast growth factor 21 (FGF21) and sodium butyrate (NaB) on protection against cholestasis-induced liver fibrosis are not well known. This study aimed to explore the effects of FGF21 and NaB on bile duct ligation (BDL)-induced liver fibrosis. Methods: Wild-type (WT) and FGF21 knockout (KO) mice received BDL surgery for 14 days. Liver fibrosis was assessed by Masson's staining for fibrosis marker expressions at the mRNA or protein levels. Adenovirus-mediated FGF21 overexpression in the WT mice was assessed against BDL damage. BDL surgeries were performed in WT and FGF21 KO mice that were administered either phosphate-buffered saline or NaB. The effects of NaB on the energy metabolism and gut microbiota were assessed using stable metabolism detection and 16S rRNA gene sequencing. Results: BDL-induced liver fibrosis in the WT mice was accompanied by high induction of FGF21. Compared to the WT mice, the FGF21 KO mice showed more severe liver fibrosis induced by BDL. FGF21 overexpression protected against BDL-induced liver fibrosis, as proved by the decreasing α-SMA at both the mRNA and protein levels. NaB administration enhanced the glucose and energy metabolisms as well as remodeled the gut microbiota. NaB alleviated BDL-induced liver fibrosis in the WT mice but aggravated the same in FGF21 KO mice. Conclusion: FGF21 plays a key role in alleviating cholestasis-induced liver damage and fibrosis. NaB has beneficial effects on cholestasis in an FGF21-dependent manner. NaB administration can thus be a novel nutritional therapy for treating cholestasis via boosting FGF21 signaling and regulating the gut microbiota.

Bartonella, Blechomonas and Trypanosoma in fleas from the long-tailed ground squirrel (Spermophilus undulatus) in northwestern China.

Fleas are known to be vectors for a variety of pathogens in veterinary medicine. However, no information is available on the presence of Bartonella and Trypanosomatidae in fleas of the long-tailed ground squirrel (LTGR, Spermophilus undulatus). The present study shows detection of these pathogens in LTGR fleas. During 2022-2023, a total of 396 fleas were collected from 91 LTGRs in 4 alpine regions of Xinjiang Uygur Autonomous Region (northwestern China) and grouped into 54 flea pools. Flea species were identified according to morphological characteristics and molecular data. In addition, all flea samples were analyzed for Bartonella with amplification and sequencing of a 380-bp part of the gltA gene and Trypanosomatidae with targeting the 18S rRNA (850-bp) and gGAPDH (820-bp) genes. The flea species included Frontopsylla elatoides elatoides (203), Neopsylla mana (49), and Citellophilus tesquorum dzetysuensis (144). Of 54 flea pools, seven (12.96%) tested positive for Bartonella, and three (5.56%) were positive for Trypanosomatidae. Based on BLASTn and phylogenetic analyses, i) Bartonella washoensis in F. elatoides elatoides and C. tesquorum dzetysuensis, and Bartonella rochalimae in F. elatoides elatoides were identified. Interestingly, a new haplotype within the species Ba. washoensis was discovered in C. tesquorum dzetysuensis; and ii) Blechomonas luni was confirmed in C. tesquorum dzetysuensis and Trypanosoma otospermophili in F. elatoides elatoides. Two Bartonella species and two Trypanosomatidae members were discovered for the first time in fleas from LTGRs. This study broadens our understanding of the geographic distribution and potential vectors for Bartonella and Trypanosomatidae.

Causal effects of hypertensive disorders of pregnancy on structural changes in specific brain regions: a Mendelian randomization study.

This study utilized Mendelian randomization to explore the impact of hypertensive disorders of pregnancy and their subtypes on brain structures, using genome-wide association study data from the FinnGen consortium for hypertensive disorders of pregnancy exposure and brain structure data from the ENIGMA consortium as outcomes. The inverse-variance weighted method, along with Cochran's Q test, Mendelian randomization-Egger regression, Mendelian randomization-PRESSO global test, and the leave-one-out approach, were applied to infer causality and assess heterogeneity and pleiotropy. Findings indicate hypertensive disorders of pregnancy are associated with structural brain alterations, including reduced cortical thickness in areas like the insula, isthmus cingulate gyrus, superior temporal gyrus, temporal pole, and transverse temporal gyrus, and an increased surface area in the superior frontal gyrus. Specific associations were found for hypertensive disorders of pregnancy subtypes: chronic hypertension with superimposed preeclampsia increased cortical thickness in the supramarginal gyrus; preeclampsia/eclampsia led to thinner cortex in the lingual gyrus and larger hippocampal volume and superior parietal lobule surface area. Chronic hypertension was associated with reduced cortical thickness in the caudal and rostral anterior cingulate and increased surface area of the cuneus and thickness of the pars orbitalis cortex. Gestational hypertension showed no significant brain region changes. These insights clarify hypertensive disorders of pregnancies' neurological and cognitive effects by identifying affected brain regions.

Four glycosyltransferase genes are responsible for synthesis and accumulation of different flavonol glycosides in apple tissues.

Flavonols are widely synthesized throughout the plant kingdom, playing essential roles in plant physiology and providing unique health benefits for humans. Their glycosylation plays significant role in improving their stability and solubility, thus their accumulation and function. However, the genes encoding the enzymes catalyze this glycosylation remain largely unknown in apple. This study utilized a combination of methods to identify genes encoding such enzymes. Initially, candidate genes were selected based on their potential to encode UDP-dependent glycosyltransferases (UGTs) and their expression patterns in response to light induction. Subsequently, through testing the in vitro enzyme activity of the proteins produced in Escherichia coli cells, four candidates were confirmed to encode a flavonol 3-O-galactosyltransferase (UGT78T6), flavonol 3-O-glucosyltransferase (UGT78S1), flavonol 3-O-xylosyltransferase/arabinosyltransferase (UGT78T5), and flavonol 3-O-rhamnosyltransferase (UGT76AE22), respectively. Further validation of these genes' functions was conducted by modulating their expression levels in stably transformed apple plants. As anticipated, a positive correlation was observed between the expression levels of these genes and the content of specific flavonol glycosides corresponding to each gene. Moreover, overexpression of a flavonol synthase gene, MdFLS, resulted in increased flavonol glycoside content in apple roots and leaves. These findings provide valuable insights for breeding programs aimed at enriching apple flesh with flavonols and for identifying flavonol 3-O-glycosyltransferases of other plant species.

Effects of Ultrasound-Guided Thoracic Paravertebral Nerve Block Combined with Perineural or IV Dexmedetomidine on Acute and Chronic Pain After Thoracoscopic Resection of Lung Lesions: A Double-Blind Randomized Trial.

Background: Thoracic paravertebral block (TPVB) analgesia can be prolonged by local anesthetic adjuvants such as dexmedetomidine. This study aimed to evaluate the two administration routes of dexmedetomidine on acute pain and chronic neuropathic pain (NeuP) prevention compared with no dexmedetomidine. Methods: A total of 216 patients were randomized to receive TPVB using 0.4% ropivacaine alone (R Group), with perineural dexmedetomidine 0.5 µg·kg-1 (RD0.5 Group) or 1.0 µg·kg-1 (RD1.0 Group), or intravenous (IV) dexmedetomidine 0.5 µg·kg-1·h-1 (RDiv Group). The primary outcome was the incidence of chronic NeuP, defined as a Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain score > 12 points at 3-month after surgery. Results: (1) For the primary outcome, RD0.5 Group and RD1.0 Group demonstrated a decreased incidence of chronic NeuP at 3-month after surgery; (2) Compared with R Group, RDiv Group, RD0.5 Group, and RD1.0 Group can reduce VAS scores at rest and movement and Prince-Henry Pain scores at 12 and 24-h after surgery, the consumption of oral morphine equivalent (OME) and improve QOD-15 at POD1; (3) Compared with RDiv Group, RD0.5 Group and RD1.0 Group can reduce VAS scores at rest and movement and Prince-Henry Pain scores at 12 and 24-h after surgery, the consumption of postoperative OME and improve QOD-15 at POD1; (4) Compared with RD0.5 Group, RD1.0 Group effectively reduced VAS scores at rest at 12 and 24-h after surgery, VAS scores in movement and Prince-Henry Pain scores at 12-h after surgery. However, RD1.0 Group showed an increased incidence of drowsiness. Conclusion: Perineural or IV dexmedetomidine are similarly effective in reducing acute pain, but only perineural dexmedetomidine reduced chronic NeuP. Moreover, considering postoperative complications such as drowsiness, perineural dexmedetomidine (0.5 µg·kg-1) may be a more appropriate choice. Clinical Trial Registration: Chinese Clinical Trial Registry (ChiCTR2200058982).

Human-Wildlife Conflict Mitigation Based on Damage, Distribution, and Activity: A Case Study of Wild Boar in Zhejiang, Eastern China.

Human-wildlife conflicts are becoming increasingly common worldwide and are a challenge to biodiversity management. Compared with compensatory management, which often focuses on solving emergency conflicts, mitigation management allows decision-makers to better understand where the damage is distributed, how the species are distributed and when the species conduct their activity. Here, we integrated data collected from 90 districts/counties' damage surveys and 1271 camera traps to understand the damage status, abundance, density and activity rhythms of wild boar (Sus scrofa) in Zhejiang, Eastern China, from January 2019 to August 2023. We found that (1) wild boar-human conflicts were mainly distributed in the northwest and southwest mountainous regions of Zhejiang Province; (2) the total abundance of wild boar was 115,156 ± 24,072 individuals, indicating a growing trend over the past decade and a higher density in the western and southern regions; (3) wild boar exhibited different activity patterns across different damage regions, and the periods around 7:00, 11:00 and 16:00 represented activity peaks for wild boar in seriously damaged regions. The damage distribution, density, distribution and activity rhythms provide specific priority regions and activity intensity peaks for conflict mitigation. We believe that these findings based on the damage, distribution and activity could provide a scientific basis for mitigation management at the county level and enrich the framework of human-wildlife conflict mitigation.

N-alkane shape distinctive microbial patterns in Kuroshio Extension.

Marine microorganisms are primary drivers of the elemental cycling. The interaction between heterotrophic prokaryotes and biomarker (n-alkane) in Kuroshio Extension (KE) remains unclear. Here, we categorize KE into three characteristic areas based on ocean temperatures and nutrient conditions: Cold Water Area (CWA), Mixed Area (MA), and Warm Water Area (WWA). A total of 49 samples were collected during two-year voyage to identify the source of n-alkane and associated degrading microorganisms. Total n-alkane concentrations (Σn-Alk) in surface water (SW) spanned from 1,308 ng L-1 to 1,890 ng L-1, it was significantly higher (Tukey-Kramer test, p < 0.05) in MA than CWA and WWA. The Σn-Alk in surface sediments (SS) gradually increased from north to south, ranging from 5,982 ng g-1 to 37,857 ng g-1. Bacteria and algae were the primary sources of n-alkane in both SW and SS. Proteobacteria was the most widely distributed among three areas. The presence of Rhodobacteraceae with alkB was the primary reason affecting n-alkane concentrations in SW. The Gammaproteobacteria with alkB and alkR chiefly affected n-alkane concentrations in SS. In summary, n-alkane s serve as an energy source for particular microorganisms, shaping the unique oceanographic patterns.

Clinical features and treatment of heterotopic pancreas in children: a multi-center retrospective study.

OBJECTIVE: Heterotopic pancreas, an uncommon condition in children, can present with diagnostic and treatment challenges. This study aimed to evaluate the clinical features and treatment options for this disorder in pediatric patients. METHODS: We conducted a retrospective analysis, including patients diagnosed with heterotopic pancreas at four tertiary hospitals between January 2000 and June 2022. Patients were categorized into symptomatic and asymptomatic groups based on clinical presentation. Clinical parameters, including age at surgery, lesion size and site, surgical or endoscopic approach, pathological findings, and outcome, were statistically analyzed. RESULTS: The study included 88 patients with heterotopic pancreas. Among them, 22 were symptomatic, and 41 were aged one year or younger. The heterotopic pancreas was commonly located in Meckel's diverticulum (46.59%), jejunum (20.45%), umbilicus (10.23%),ileum (7.95%), and stomach (6.82%). Sixty-six patients had concomitant diseases. Thirty-three patients had heterotopic pancreas located in the Meckel's diverticulum, with 80.49% of cases accompanied by gastric mucosa heterotopia (GMH). Patients without accompanying GMH had a higher prevalence of heterotopic pancreas-related symptoms (75%). Treatment modalities included removal of the lesions by open surgery, laparoscopic or laparoscopic assisted surgery, or endoscopic surgery based on patient's age, the lesion site and size, and coexisting diseases. CONCLUSIONS: Only one-fourth of the patients with heterotopic pancreas presented with symptoms. Those located in the Meckel's diverticulum have commonly accompanying GMH. Open surgical, laparoscopic surgical or endoscopic resection of the heterotopic pancreas is recommended due to potential complications. Future prospective multicenter studies are warranted to establish rational treatment options.

Accommodating detection limits of multiple exposures in environmental mixture analyses: an overview of statistical approaches.

BACKGROUND: Identifying the impact of environmental mixtures on human health is an important topic. However, such studies face challenges when exposure measurements lie below limit of detection (LOD). While various approaches for accommodating a single exposure subject to LOD have been used, their impact on mixture analysis has not been thoroughly investigated. Our study aims to understand the impact of five popular LOD accommodation approaches on mixture analysis results with multiple exposures subject to LOD, including omitting subjects with any exposures below LOD (complete case analysis); single imputations by LOD/ 2 , and by estimates from a censored accelerated failure time (AFT) model; and multiple imputation (MI) with or without truncation based on LOD. METHODS: In extensive simulation studies with high-dimensional and highly correlated exposures and a continuous health outcome, we examined the performance of each LOD approach on three mixture analysis methods: elastic net regression, weighted quantile sum regression (WQS) and Bayesian kernel machine regression (BKMR). We further analyzed data from the National Health and Nutrition Examination Survey (NHANES) on how persistent organic pollutants (POPs) influenced leukocyte telomere length (LTL). RESULTS: Complete case analysis was inefficient and could result in severe bias for some mixture methods. Imputation by LOD/ 2 showed unstable performance across mixture methods. Conventional MI was associated with consistent mild biases, which can be reduced by using a truncated distribution for imputation. Estimating censored values by AFT models had a minimal impact on the results. In the NHANES analysis, imputation by LOD/ 2 , truncated MI and censored AFT models performed similarly, with a positive overall effect of POPs on LTL while PCB126, PCB169 and furan 2,3,4,7,8-pncdf being the most important exposures. CONCLUSIONS: Our study favored using truncated MI and censored AFT models to accommodate values below LOD for the stability of downstream mixture analysis.

Insights into the complexity and functionality of plant virus protein phosphorylation.

Phosphorylation, the most extensive and pleiotropic form of protein post-translation modification, is central to cellular signal transduction. Throughout the extensive co-evolution of plant hosts and viruses, modifications to phosphorylation have served multiple purposes. Such modifications highlight the evolutionary trajectories of viruses and their hosts, with pivotal roles in regulation and refinement of host-virus interactions. In plant hosts, protein phosphorylation orchestrates immune responses, enhancing the activities of defense-related proteins such as kinases and transcription factors, thereby strengthening pathogen resistance in plants. Moreover, phosphorylation influences the interactions between host and viral proteins, altering viral spread and replication within host plants. In the context of plant viruses, protein phosphorylation controls key aspects of the infection cycle, including viral protein functionality and the interplay between viruses and host plant cells, leading to effects on viral accumulation and dissemination within plant tissues. Explorations of the nuances of protein phosphorylation in plant hosts and their interactions with viruses are particularly important. This review provides a systematic summary of the biological roles of the proteins of plant viruses carrying diverse genomes in regulating infection and host responses through changes in the phosphorylation status.

[Characterization of sequences, expression profiling, and natural allelic variation analysis of the MYC gene family in sorghum (Sorghum bicolor)].

Sorghum aphid (Melanaphis sacchari) and head smut fungi (Sporisorium reilianum) infesting sorghum cause delayed growth and development, and reduce yield and quality. This study use bioinformatics and molecular biological approaches to profile the gene expression pattern during sorghum development and under pest infestation, and analyzed the natural allelic DNA variation of sorghum MYC gene family. The findings provide insights for potential application in breeding the stress resistant and high productivity sorghum varieties. The results indicated that there are 28 MYC genes identified in sorghum genome, distributed on 10 chromosomes. The bHLH_MYC_N and HLH domains are the conserved domains of the MYC gene in sorghum. Gene expression analysis showed that SbbHLH35.7g exhibited high expression levels in leaves, SbAbaIn showed strong expression in early grains, and SbMYC2.1g showed high expression levels in mature pollen. In anti-aphid strains at the 5-leaf stage, SbAbaIn, SbLHW.4g and SbLHW.2g were significantly induced in leaves, while SbbHLH35.7g displayed the highest expression level in panicle tissue, which was significantly induced by the infection of head smut. Promoter cis-element analysis identified methyl jasmonate (MJ), abscisic acid (ABA), salicylic acid (SA) and MYB-binding sites related to drought-stress inducibility. Furthermore, genomic resequencing data analysis revealed natural allelic DNA variations such as single nucleotide polymorphism (SNP) and insertion-deletion (INDEL) for the key SbMYCs. Protein interaction network analysis using STRING indicated that SbAbaIn interacts with TIFYdomain protein, and SbbHLH35.7g interacts with MDR and imporin. SbMYCs exhibited temporal and spatial expression patterns and played vital roles during the sorghum development. Infestation by sugarcane aphids and head smut fungi induced the expression of SbAbaIn and SbbHLH35.7g, respectively. SbAbaIn modulated the jasmonic acid (JA) pathway to regulate the expression of defensive genes, conferring resistance to insects. On the other hand, SbbHLH35.7g participated in detoxification reactions to defend against pathogens.

Implementation of a realistic artificial data generator for crash data generation.

In this paper, a framework is outlined to generate realistic artificial data (RAD) as a tool for comparing different models developed for safety analysis. The primary focus of transportation safety analysis is on identifying and quantifying the influence of factors contributing to traffic crash occurrence and its consequences. The current framework of comparing model structures using only observed data has limitations. With observed data, it is not possible to know how well the models mimic the true relationship between the dependent and independent variables. Further, real datasets do not allow researchers to evaluate the model performance for different levels of complexity of the dataset. RAD offers an innovative framework to address these limitations. Hence, we propose a RAD generation framework embedded with heterogeneous causal structures that generates crash data by considering crash occurrence as a trip level event impacted by trip level factors, demographics, roadway and vehicle attributes. Within our RAD generator we employ three specific modules: (a) disaggregate trip information generation, (b) crash data generation and (c) crash data aggregation. For disaggregate trip information generation, we employ a daily activity-travel realization for an urban region generated from an established activity-based model for the Chicago region. We use this data of more than 2 million daily trips to generate a subset of trips with crash data. For trips with crashes crash location, crash type, driver/vehicle characteristics, and crash severity. The daily RAD generation process is repeated for generating crash records at yearly or multi-year resolution. The crash databases generated can be employed to compare frequency models, severity models, crash type and various other dimensions by facility type - possibly establishing a universal benchmarking system for alternative model frameworks in safety literature.

The Role Played by Mitochondria in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) refers to an endocrine disorder syndrome that are correlated with multiple organs and systems. PCOS has an effect on women at all stages of their lives, and it has an incidence nearly ranging from 6% to 20% worldwide. Mitochondrial dysfunctions (e.g., oxidative stress, dynamic imbalance, and abnormal quality control system) have been identified in patients and animal models of PCOS, and the above processes may play a certain role in the development of PCOS and its associated complications. However, their specific pathogenic roles should be investigated in depth. In this review, recent studies on the mechanisms of action of mitochondrial dysfunction in PCOS and its associated clinical manifestations are summarized from the perspective of tissues and organs, and some studies on the treatment of the disease by improving mitochondrial function are reviewed to highlight key role of mitochondrial dysfunction in this syndrome.

[Non-targeted metabolomics of spleen and liver metabolism in mice treated with Pruni Semen processed with different methods].

Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to investigate the impacts of Pruni Semen processed with different methods(raw and fried) on the liver and spleen metabolism in mice. A total of 24 male mice were randomly assigned to three groups: raw Pruni Semen group, fried Pruni Semen group, and control(deionized water) group. Mice in the three groups were orally administrated with 0.01 g·mL~(-1) Pruni Semen decoction or deionized water for one week. After that, the liver and spleen tissues were collected, and liquid chromatography-mass spectrometry(LC-MS)-based metabolomic analysis was carried out to investigate the impact of Pruni Semen on the liver and spleen metabolism in mice. Compared with thte control group, the raw Pruni Semen group showed up-regulation of 11 metabolites and down-regulation of 57 metabolites in the spleen(P<0.05), as well as up-regulation of 15 metabolites and down-regulation of 58 metabolites in the liver(P<0.05). The fried Pruni Semen group showed up-regulation of 31 metabolites and down-regulation of 10 metabolites in the spleen(P<0.05), along with up-regulation of 26 metabolites and down-regulation of 61 metabolites in the liver(P<0.05). The differential metabolites identified in the raw Pruni Semen group were primarily associated with alanine, aspartate, and glutamate metabolism, purine metabolism, amino sugar and nucleotide sugar metabolism, and D-glutamine and D-glutamate metabolism. The differential metabolites identified in the fried Pruni Semen group predominantly involved riboflavin metabolism, amino sugar and nucleotide sugar metabolism, purine metabolism, alanine, aspartate, and glutamate metabolism, D-glutamine and D-glutamate metabolism, and glutathione metabolism. The findings suggest that both raw and fried Pruni Semen have the potential to modulate the metabolism of the liver and spleen in mice by influencing the glutamine and glutamate metabolism.

Molecular detection of Bartonella rochalimae and Hepatozoon canis in red foxes (Vulpes vulpes) from China.

Red foxes (Vulpes vulpes) have been recognized as natural reservoirs for multiple pathogens and a source of infection for domestic animals, wildlife and humans. To date, no reports are available on the Bartonella rochalimae and Hepatozoon canis infection in red foxes from China. In 2018-2022, a total of 16 red foxes were sampled in two counties and a city in Xinjiang Uygur Autonomous Region (XUAR) in northwest China. Subsequently analyzed by DNA extraction amplified by polymerase chain reaction (PCR). In the present study, based on nucleotide sequence and phylogenetic tree analyses, B. rochalimae and H. canis were molecularly identified in red foxes. Our findings provide the first molecular evidence of B. rochalimae and H. canis in red foxes from China.

Nuclear speckle rejuvenation alleviates proteinopathies at the expense of YAP1.

Current treatments targeting individual protein quality control have limited efficacy in alleviating proteinopathies, highlighting the prerequisite for a common upstream druggable target capable of global proteostasis modulation. Building on our prior research establishing nuclear speckles as pivotal organelles responsible for global proteostasis transcriptional control, we aim to alleviate proteinopathies through nuclear speckle rejuvenation. We identified pyrvinium pamoate as a small-molecule nuclear speckle rejuvenator that enhances protein quality control while suppressing YAP1 signaling via decreasing the surface tension of nuclear speckle condensates through interaction with the intrinsically disordered region of nuclear speckle scaffold protein SON. In pre-clinical models, pyrvinium pamoate reduced tauopathy and alleviated retina degeneration by promoting autophagy and ubiquitin-proteasome system. Aberrant nuclear speckle morphology, reduced protein quality control and increased YAP1 activity were also observed in human tauopathies. Our study uncovers novel therapeutic targets for tackling protein misfolding disorders within an expanded proteostasis framework encompassing nuclear speckles and YAP1.

Trace the origin of yak meat in Xizang based on stable isotope combined with multivariate statistics.

In this study, the feasibility of tracing the origin of yak meat in Xizang Autonomous Region based on stable isotope combined with multivariable statistics was researched. The δ13C, δ15N, δ2H and δ18O in yak meat were determined by stable isotope ratio mass spectrometry, and the data were analyzed by analysis of variance, fisher discriminant analysis (FDA), back propagation (BP) neural network and orthogonal partial least squares discrimination analysis (OPLS-DA). The results showed that the δ13C, δ15N, δ2H and δ18O had significant differences among different origins (P < 0.05). The overall original correct discrimination rate of fisher discriminant analysis was 89.7 %, and the correct discrimination rate of cross validation was 88.2 %. The correct classification rate of BP neural network based on training set was 93.38 %, and the correct classification rate of BP neural network based on test set was 89.83 %. The OPLS-DA model interpretation rate parameter R2Y was 0.67, the model prediction rate parameter Q2 was 0.409, which could distinguish yak meat from seven different producing areas in Xizang Autonomous Region. The results showed that the origin of yak meat in Xizang Autonomous Region can be traced based on stable isotope combined with multivariate statistics.

The lncRNA lnc_AABR07044470.1 promotes the mitochondrial-damaged inflammatory response to neuronal injury via miR-214-3p/PERM1 axis in acute ischemic stroke.

PURPOSE: We investigated the role of lnc_AABR07044470.1 on the occurrence and development of acute ischemic stroke (AIS) and neuronal injury by targeting the miR-214-3p/PERM1 axis to find a novel clinical drug target and prediction and treatment of AIS. METHODS: The mouse AIS animal model was used in vivo experiments and hypoxia/reoxygenation cell model in vitro was established. Firstly, infarction volume and pathological changes of mouse hippocampal neurons were detected using HE staining. Secondly, rat primary neuron apoptosis was detected by flow cytometry assay. The numbers of neuron, microglia and astrocytes were detected using immunofluorescence (IF). Furthermore, binding detection was performed by bioinformatics database and double luciferase reporter assay. Lnc_AABR07044470.1 localization was performed using fluorescence in situ hybridization (FISH).Lnc_AABR07044470.1, miR-214-3pand PERM1mRNA expression was performed using RT-qPCR. NLRP3, ASC, Caspase-1 and PERM1 protein expression was performed using Western blotting. IL-1ß was detected by ELISA assay. RESULTS: Mouse four-vessel occlusion could easily establish the animal model, and AIS animal model had an obvious time-dependence. HE staining showed that, compared with the sham group, infarction volume and pathological changes of mouse hippocampal neurons were deteriorated in the model group. Furthermore, compared with the sham group, neurons were significantly reduced, while microglia and astrocytes were significantly activated. Moreover, the bioinformatics prediction and detection of double luciferase reporter confirmed the binding site of lnc_AABR07044470.1 to miR-214-3p and miR-214-3p to Perm1. lnc_AABR07044470.1 and PERM1 expression was significantly down-regulated and miR-214-3pexpression was significantly up-regulated in AIS animal model in vivo. At the same time, the expression of inflammasome NLRP3, ASC, Caspase-1 and pro-inflammatory factor IL-1ß was significantly up-regulated in vivo and in vitro. The over-expression of lnc_AABR07044470.1 and miR-214-3p inhibitor could inhibit the neuron apoptosis and the expression of inflammasome NLRP3, ASC, Caspase-1 and pro-inflammatory factor IL-1ß and up-regulate the expression of PERM1 in vitro. Finally, over-expression of lnc_AABR07044470.1 and miR-214-3p inhibitor transfected cell model was significant in relieving the AIS and neuronal injury. CONCLUSION: Lnc_AABR07044470.1 promotes inflammatory response to neuronal injury via miR-214-3p/PERM1 axis in AIS.