5-Hydroxytryptamine 4 Receptor Agonist Attenuates Diabetic Enteric Neuropathy through Inhibition of the Receptor-Interacting Protein Kinase 3 Pathway.

Necroptosis, considered as a form of programmed cell death, contributes to neural loss. The 5-hydroxytryptamine 4 receptor (5-HT4R) is involved in neurogenesis in the enteric nervous system. However, whether the activation of 5-HT4R can alleviate diabetic enteric neuropathy by inhibiting receptor-interacting protein kinase 3 (RIPK3)-mediated necroptosis is unclear. This study aimed to explore the beneficial effects of 5-HT4R agonist on enteric neuropathy in a mouse model of diabetes and the mechanisms underlying these effects. Diabetes developed neural loss in the colon of mice. 5-HT4Rs localized in submucosal and myenteric plexuses were confirmed. Administration of 5-HT4R agonist attenuated diabetes-induced colonic hypomotility and neural loss of the colon in mice. Remarkably, RIPK3, phosphorylated RIPK3, and its downstream target mixed lineage kinase domain-like protein (MLKL), two key proteins regulating necroptosis, were significantly up-regulated in the colon of diabetic mice. Treatment with 5-HT4R agonist appeared to inhibit diabetes-induced elevation of RIPK3, phosphorylated RIPK3, and MLKL in the colon of mice. Diabetes-induced up-regulation of MLKL in both the mucosa and the muscularis of the colon was prevented by Ripk3 deletion. Moreover, diabetes-evoked neural loss and delayed colonic transit were significantly inhibited by Ripk3 removal. These findings suggest that activation of 5-HT4Rs could potentially provide a protective effect against diabetic enteric neuropathy by suppressing RIPK3-mediated necroptosis.

Highly Efficient Electrosynthesis of Glycine over an Atomically Dispersed Iron Catalyst.

Glycine is a nonessential amino acid that plays a vital role in various biological activities. However, the conventional synthesis of glycine requires sophisticated procedures or toxic feedstocks. Herein, we report an electrochemical pathway for glycine synthesis via the reductive coupling of oxalic acid and nitrate or nitrogen oxides over atomically dispersed Fe-N-C catalysts. A glycine selectivity of 70.7% is achieved over Fe-N-C-700 at -1.0 V versus RHE. Synergy between the FeN3C structure and pyrrolic nitrogen in Fe-N-C-700 facilitates the reduction of oxalic acid to glyoxylic acid, which is crucial for producing glyoxylic acid oxime and glycine, and the FeN3C structure could reduce the energy barrier of *HOOCCH2NH2 intermediate formation thus accelerating the glyoxylic acid oxime conversion to glycine. This new synthesis approach for value-added chemicals using simple carbon and nitrogen sources could provide sustainable routes for organonitrogen compound production.

Balanced callose and cellulose biosynthesis in Arabidopsis quorum-sensing signaling and pattern-triggered immunity.

The plant cell wall (CW) is one of the most important physical barriers that phytopathogens must conquer to invade their hosts. This barrier is a dynamic structure that responds to pathogen infection through a complex network of immune receptors, together with CW-synthesizing and CW-degrading enzymes. Callose deposition in the primary CW is a well-known physical response to pathogen infection. Notably, callose and cellulose biosynthesis share an initial substrate, UDP-glucose, which is the main load-bearing component of the CW. However, how these 2 critical biosynthetic processes are balanced during plant-pathogen interactions remains unclear. Here, using 2 different pathogen-derived molecules, bacterial flagellin (flg22) and the diffusible signal factor (DSF) produced by Xanthomonas campestris pv. campestris, we show a negative correlation between cellulose and callose biosynthesis in Arabidopsis (Arabidopsis thaliana). By quantifying the abundance of callose and cellulose under DSF or flg22 elicitation and characterizing the dynamics of the enzymes involved in the biosynthesis and degradation of these 2 polymers, we show that the balance of these 2 CW components is mediated by the activity of a ß-1,3-glucanase (BG2). Our data demonstrate balanced cellulose and callose biosynthesis during plant immune responses.

Cysteine and glycine-rich protein 2 is crucial for maintaining the malignant phenotypes of gliomas through its action on Notch signalling cascade.

Cysteine and glycine-rich protein 2 (CSRP2) is expressed differently in numerous cancers and plays a key role in carcinogenesis. However, the role of CSRP2 in glioma is unknown. This study sought to determine the expression profile and clinical significance of CSRP2 in glioma and explore its biological functions and mechanisms via lentivirus-mediated CSRP2 silencing experiments. Increased CSRP2 was frequently observed in gliomas, which was associated with clinicopathological characteristics and an unfavourable prognosis. Decreasing CSRP2 led to the suppression of malignant proliferation, metastasis and stemness in glioma cells while causing hypersensitivity to chemotherapeutic drugs. Mechanistic investigations revealed that CSRP2 plays a role in mediating the Notch signalling cascade. Silencing CSRP2 decreased the levels of Notch1, cleaved Notch1, HES1 and HEY1, suppressing the Notch signalling cascade. Reactivation of Notch markedly diminished the tumour-inhibiting effects of CSRP2 silencing on the malignant phenotypes of glioma cells. Notably, CSRP2-silencing glioma cells exhibited reduced potential in the formation of xenografts in nude mice in vivo, which was associated with an impaired Notch signalling cascade. These results showed that CSRP2 is overexpressed in glioma and has a crucial role in sustaining the malignant phenotypes of glioma, suggesting that targeting CSRP2 could be a promising strategy for glioma treatment.

CO2 Electrolysis System under Industrially Relevant Conditions.

ConspectusCarbon dioxide emissions from consumption of fossil fuels have caused serious climate issues. Rapid deployment of new energies makes renewable energy driven CO2 electroreduction to chemical feedstocks and carbon-neutral fuels a feasible and cost-effective pathway for achieving net-zero emission. With the urgency of the net-zero goal, we initiated our research on CO2 electrolysis with emphasis on industrial relevance.The CO2 molecules are thermodynamically stable due to high activation energy of the two C═O bonds, and efficient electrocatalysts are required to overcome the sluggish dynamics and competitive hydrogen evolution reaction. The CO2 electrocatalysts that we have explored include molecular catalysts and nanostructured catalysts. Molecular catalysts are centered on earth abundant elements such as Fe and Co for catalyzing CO2 reduction, and using Fe catalysts, we proposed an amidation strategy for reduction of CO2 to methanol, bypassing the inactive formate pathway. For nanostructured catalysts, we developed a carbon enrichment strategy using nitrogen-rich nanomaterials for selective CO2 reduction.Direct CO2 electroreduction from the flue gas stream represents the "holy grail" in the field, because typical CO2 concentration in flue gas is only 6-15%, posing a significant challenge for CO2 electrolysis. On the other hand, direct electroreduction of CO2 in the flue gas eliminates the carbon capture process and simplifies the overall carbon capture and utilization (CCU) scheme. However, direct flue gas reduction is frustrated by the reactive oxygen (5-8%), low CO2 concentration (6-15%), and potentially toxic impurities. Surface CO2 enrichment catalysts with high O2 tolerance could be viable for achieving direct CO2 electroreduction for decarbonization of flue gas.In addition to the electrocatalysts, the incorporation of catalysts into the electrolyzer and development of a suitable process was also investigated to meet industrial demands. A membrane electrode assembly (MEA) is a zero-gap configuration with cathode and anode catalysts coated on either side of an ion exchange membrane. We adopted the MEA configuration due to the structural simplicity, low ohmic resistance, and high efficiency. The electrode factors (for example, membrane type, catalyst layer porosity, and MEA fabrication method) and the electrolyzer factors (for example, flow channels, gas diffusion layer) are critical to highly efficient operation. We separately developed an anion-exchange membrane-based system for CO production and cation-exchange membrane-based system for formate production. The optimized electrolyzer configuration can generate uniform current and voltage distribution in a large-area electrolyzer and operate using an industrial CO2 stream. The optimized process was developed with the targets of long-term continuous operation and no electrolyte consumption.

Tailored Bimetallic Ni-Sn Catalyst for Electrochemical Ammonia Oxidation to Dinitrogen with High Selectivity.

Direct electrochemical ammonia oxidation reaction (eAOR) is an efficient and sustainable strategy to process wastewater containing ammonia, and it endures overoxidation and severely competitive oxygen evolution reaction (OER). Herein, we synthesized a Ni(OH)2/SnO2 composite catalyst by a multistep strategy and applied it to the eAOR process. Ni(OH)2/SnO2 exhibited a N2-N Faradaic efficiency (FEN2-N) of 84.2%, with a N2 partial current density (jN2-N) of 2.7 mA cm-2 at 1.55 V vs reversible hydrogen electrode (RHE) in 0.5 M K2SO4 with 10 mM NH3-N (pH 11). The oxophilic Sn promoted NH3 absorption on Ni sites while suppressing the OER. As the active species, NiOOH accelerated the dimerization of intermediates (*NH2 or *NH) to form N2.

The prevalence and clinical features of fibromyalgia in Chinese hospital patients with primary headache: The survey of fibromyalgia comorbid with headache.

OBJECTIVE: The aims were to explore the prevalence and clinical features of fibromyalgia in Chinese hospital patients with primary headache. BACKGROUND: Studies done in non-Chinese populations suggest that around one-third of patients with primary headache have fibromyalgia, but data from mainland China are limited. Investigations into the prevalence and clinical features of fibromyalgia in Chinese patients with primary headache would improve our understanding of these two complex disease areas and help guide future clinical practice. METHODS: This cross-sectional study included adults with primary headache treated at 23 Chinese hospitals from September 2020 to May 2021. Fibromyalgia was diagnosed using the modified 2010 American College of Rheumatology criteria. Mood and insomnia were evaluated employing the Hospital Anxiety and Depression Scale and the Insomnia Severity Index. RESULTS: A total of 2782 participants were analyzed. The fibromyalgia prevalence was 6.0% (166/2782; 95% confidence interval: 5.1%, 6.8%). Compared to primary headache patients without combined fibromyalgia, patients with primary headache combined with fibromyalgia were more likely to be older (47.8 vs. 41.7 years), women (83.7% [139/166] vs. 72.8% [1904/2616]), less educated (65.1% [108/166] vs. 45.2% [1183/2616]), and with longer-duration headache (10.0 vs. 8.0 years). Such patients were more likely to exhibit comorbid depression (34.3% [57/166] vs. 9.9% [260/2616]), anxiety (16.3% [27/166] vs. 2.7% [70/2612]), and insomnia (58.4% [97/166] vs. 17.1% [447/2616]). Fibromyalgia was more prevalent in those with chronic (rather than episodic) migraine (11.1% [46/414] vs. 4.4% [72/1653], p < 0.001) and chronic (rather than episodic) tension-type headache (11.5% [27/235] vs. 4.6% [19/409], p = 0.001). Most fibromyalgia pain was in the shoulders, neck, and upper back. CONCLUSIONS: The prevalence of fibromyalgia in mainland Chinese patients with primary headache was 6.0%. Fibromyalgia was more common in those with chronic rather than episodic headache. The most common sites of fibromyalgia pain were the neck, shoulders, and back.

Status of diagnosis and preventative treatment for primary headache disorders: real-world data of unmet needs in China.

BACKGROUND: Headache disorders are widely prevalent and pose a considerable economic burden on individuals and society. Globally, misdiagnosis and inadequate treatment of primary headache disorders remain significant challenges, impeding the effective management of such conditions. Despite advancements in headache management over the last decade, a need for comprehensive evaluations of the status of primary headache disorders in China regarding diagnosis and preventative treatments persists. METHODS: In the present study, we analyzed the established queries in the Survey of Fibromyalgia Comorbidity with Headache (SEARCH), focusing on previous diagnoses and preventative treatment regimens for primary headache disorders. This cross-sectional study encompassed adults diagnosed with primary headache disorders who sought treatment at 23 hospitals across China between September 2020 to May 2021. RESULTS: The study comprised 2,868 participants who were systematically examined. Migraine and tension-type headaches (TTH) constituted a majority of the primary headache disorders, accounting for 74.1% (2,124/2,868) and 23.3% (668/2,868) of the participants, respectively. Medication overuse headache (MOH) affected 8.1% (231/2,868) of individuals with primary headache disorders. Over half of the individuals with primary headache disorders (56.6%, 1,624/2,868) remained undiagnosed. The previously correct diagnosis rates for migraine, TTH, TACs, and MOH were 27.3% (580/2,124), 8.1% (54/668), 23.2% (13/56), and 3.5% (8/231), respectively. The misdiagnosis of "Nervous headache" was found to be the most prevalent among individuals with migraine (9.9%, 211/2,124), TTH (10.0%, 67/668), trigeminal autonomic cephalalgias (TACs) (17.9%, 10/56), and other primary headache disorders (10.0%, 2/20) respectively. Only a minor proportion of individuals with migraine (16.5%, 77/468) and TTH (4.7%, 2/43) had received preventive medication before participating in the study. CONCLUSIONS: While there has been progress made in the rate of correct diagnosis of primary headache disorders in China compared to a decade ago, the prevalence of misdiagnosis and inadequate treatment of primary headaches remains a veritable issue. As such, focused efforts are essential to augment the diagnosis and preventive treatment measures related to primary headache disorders in the future.

Elevated c-di-GMP Levels and Expression of the Type III Secretion System Promote Corneal Infection by Pseudomonas aeruginosa.

Pseudomonas aeruginosa is generally believed to establish biofilm-associated infections under the regulation of the secondary messenger c-di-GMP. To evaluate P. aeruginosa biofilm physiology during ocular infections, comparative transcriptomic analysis was performed on wild-type P. aeruginosa PAO1, a ΔwspF mutant strain (high c-di-GMP levels), and a plac-yhjH-containing strain (low c-di-GMP levels) from mouse corneal infection, as well as in vitro biofilm and planktonic cultures. The c-di-GMP content in P. aeruginosa during corneal infection was monitored using a fluorescent c-di-GMP reporter strain. Biofilm-related genes were induced in in vivo PAO1 compared to in vitro planktonic bacteria. Several diguanylate cyclases and phosphodiesterases were commonly regulated in in vivo PAO1 and in vitro biofilm compared to in vitro planktonic bacteria. Several exopolysaccharide genes and motility genes were induced and downregulated, respectively, in in vivo PAO1 and the in vivo ΔwspF mutant compared to the in vivo plac-yhjH-containing strain. Elevation of c-di-GMP levels in P. aeruginosa began as early as 2 h postinfection. The ΔwspF mutant was less susceptible to host clearance than the plac-yhjH-containing strain and could suppress host immune responses. The type III secretion system (T3SS) was induced in in vivo PAO1 compared to in vitro biofilm bacteria. A ΔwspF mutant with a defective T3SS was more susceptible to host clearance than a ΔwspF mutant with a functional T3SS. Our study suggests that elevated intracellular c-di-GMP levels and T3SS activity in P. aeruginosa are necessary for establishment of infection and modulation of host immune responses in mouse cornea.

Dietary carbon loaded with nano-ZnO alters the gut microbiota community to mediate bile acid metabolism and potentiate intestinal immune function in fattening beef cattle.

BACKGROUND: To our knowledge, carbon loaded with nano-ZnO (NZnOC) represents a new nutritional additive for the animal husbandry industry. However, the mechanism by which NZnOC mediates beef cattle growth and intestinal health is not fully understood. This study aimed to investigate the effects of carbon loaded with nano-ZnO (NZnOC) supplementation on growth performance, gut microbiota, bile acid (BAs) metabolism and intestinal immunity in fattening cattle. Twenty cattle (16 ± 0.95 months) were randomly assigned to two dietary groups: CON (control, without feed additive) and NZnOC (diet supplemented with 80 mg NZnOC/kg diet dry matter basic) for 60 d. The colon digesta microbiota composition and BAs concentration were determined by microbiota metagenomics and gas chromatography methods, respectively. RESULTS: The results showed that the NZnOC-supplemented cattle had greater final weight, average daily gain and gain-to-feed ratio than those in the CON group. Cattle fed the NZnOC diet had a higher relative abundance of the secondary BAs synthesizing phyla Firmicutes, Tenericutes and Actinobacteria than those fed the CON diet. Dietary supplementation with NZnOC increased the relative abundance of the secondary BAs synthesis microbiota genera Clostridium, Ruminococcus, Eubacterium, and Brevibacillus in colon digesta. Cattle fed the NZnOC diet had increased activities of 3α-hydroxysteroid dehydrogenase (EC: 1.1.1.52) and bile acid-CoA ligase BaiB (EC: 6.2.1.7) in the colon digesta compared with those fed the CON diet. The primary BAs taurocholic acid, taurochenodeoxycholic acid and taurodeoxycholate acid were significantly decreased by dietary NZnOC supplementation, while the secondary BAs deoxycholic acid, taurolithocholic acid, beta-muricholic acid, 12-ketolithocholic acid and ursodeoxycholic acid were significantly increased. Dietary supplementation with NZnOC increased the mRNA abundance of G protein-coupled bile acid receptor 1, protein kinase cAMP-activated catalytic subunit alpha, cyclic-AMP response element binding protein 1 and interleukin (IL)-10 in the colon mucosa of cattle, while the mRNA abundance of tumor necrosis factor and IL-1ß were significantly decreased. CONCLUSIONS: In summary, dietary supplementation with NZnOC can facilitate the growth performance and intestinal immune function of cattle by improving BAs metabolism. NZnOC can be supplemented in the diet as a safe regulator of gut microbiota and as a feed additive in the ruminants industry.

Synthesis and Biological Evaluation of Novel Synthetic Indolone Derivatives as Anti-Tumor Agents Targeting p53-MDM2 and p53-MDMX.

A series of novel indolone derivatives were synthesized and evaluated for their binding affinities toward MDM2 and MDMX. Some compounds showed potent MDM2 and moderate MDMX activities. Among them, compound A13 exhibited the most potent affinity toward MDM2 and MDMX, with a Ki of 0.031 and 7.24 µM, respectively. A13 was also the most potent agent against HCT116, MCF7, and A549, with IC50 values of 6.17, 11.21, and 12.49 µM, respectively. Western blot analysis confirmed that A13 upregulated the expression of MDM2, MDMX, and p53 by Western blot analysis. These results indicate that A13 is a potent dual p53-MDM2 and p53-MDMX inhibitor and deserves further investigation.

RNF34 ablation promotes cerebrovascular remodeling and hypertension by increasing NADPH-derived ROS generation.

Cerebrovascular remodeling is the most common cause of hypertension and stroke. Ubiquitin E3 ligase RING finger protein 34 (RNF34) is suggested to be associated with the development of multiple neurological diseases. However, the importance of RNF34 in cerebrovascular remodeling and hypertension is poorly understood. Herein, we used mice with a global RNF34 knockout as well as RNF34 floxed mice to delete RNF34 in endothelial cells and smooth muscle cells (SMCs). Our results showed that global RNF34 knockout mice substantially promoted angiotensin II (AngII)-induced middle cerebral artery (MCA) remodeling, hypertension, and neurological dysfunction. Endothelial cell RNF34 did not regulate the development of hypertension. Rather, SMC RNF34 expression is a critical regulator of hypertension and MCA remodeling. Loss of RNF34 enhanced AngII-induced mouse brain vascular SMCs (MBVSMCs) proliferation, migration and invasion. Furthermore, MCA and MBVSMCs from SMC RNF34-deficient mice showed increased superoxide anion and reactive oxygen species (ROS) generation as well as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, but exhibited no marked effect on mitochondria-derived ROS. Knockout of RNF34 promoted p22phox expression, leading to increased binding of p22phox/p47phox and p22phox/NOX2, and eventually NADPH oxidase complex formation. Immunoprecipitation assay identified that RNF34 interacted with p22phox. RNF34 deletion increased p22phox protein stability by inhibiting ubiquitin-mediated degradation. Blockade of NADPH oxidase activity or knockdown of p22phox significantly abolished the effects of RNF34 deletion on cerebrovascular remodeling and hypertension. Collectively, our study demonstrates that SMC RNF34 deficiency promotes cerebrovascular SMC hyperplasia and remodeling by increased NADPH-derived ROS generation via reducing p22phox ubiquitin-dependent degradation.

Isorhynchophylline Relieves Ferroptosis-Induced Nerve Damage after Intracerebral Hemorrhage Via miR-122-5p/TP53/SLC7A11 Pathway.

Isorhynchophylline (IRN), a component of traditional Chinese herb Uncaria rhynchophylla, possesses strong antioxidant activity. Ferroptosis induced by iron overload causes cell oxidative stress after intracerebral hemorrhage (ICH). Therefore, this study aims to explore the effects of IRN on the ferroptosis following ICH. In this study, mouse hippocampal HT-22 cells were treated with ferric ammonium citrate (FAC) alone or together with IRN, and we found IRN reduced the FAC-induced cell damage. Then, cells were treated with IRN following treatment with FAC after transfection with miR-122-5p inhibitor, and the results showed IRN reduced the FAC-induced decrease of miR-122-5p levels and relieved the ferroptosis by detecting ferroptotic marker proteins, iron ion concentration and oxidative stress level; after transfection with miR-122-5p inhibitor, the protective effects of IRN against FAC-induced ferroptosis in these cells were weakened. TP53 (also known as p53) was verified as a target of miR-122-5p by using dual luciferase reporter assay, and restoration of TP53 attenuated the effects of miR-122-5p on ferroptotic marker proteins expression, iron ion concentration and lipid ROS levels, as well as solute carrier family seven member 11 (SLC7A11) mRNA expression. SLC7A11 siRNA reversed the inhibitory effects of IRN on FAC-induced ferroptosis and oxidative stress levels. Subsequently, IRN increased the mNSS score, and decreased brain water content and EB content in ICH model. Moreover, IRN decreased ferroptosis and lipid ROS level, upregulated the expression of miR-122-5p and SLC7A11 mRNA, and inhibited TP53 expression. Our findings reveal that IRN protects neurocyte from ICH-induced ferroptosis via miR-122-5p/TP53/SLC7A11 pathway, which may provide a potential therapeutic mechanism for ICH.

Mitigation of salt stress response in upland cotton (Gossypium hirsutum) by exogenous melatonin.

As a pleiotropic signal molecule, melatonin is ubiquitous throughout the animal and plant kingdoms and plays important roles in the regulation of plant growth, development, and responses to environmental stresses. In this study, we quantified the endogenous melatonin levels in upland cotton (Gossypium hirsutum L.), using high-performance liquid chromatography-tandem mass spectrometry. The melatonin concentrations in root, stem, and leaf were 150.60, 37.92, and 40.58 ng g fresh weight- 1, respectively. The effects of exogenous melatonin (1 µM) on plant growth, photosynthesis, antioxidant enzyme activity, and ion homeostasis in upland cotton seedlings exposed to 100 mM NaCl treatment were determined. Pretreatment (prior to exposure to salt stress) of seedlings with exogenous melatonin significantly alleviated plant growth inhibition by salt stress and maintained an improved photosynthetic capacity. The application of melatonin also significantly reduced the salt-induced oxidative damage, possibly through the accumulation of osmotic regulatory substances and the activation of antioxidant enzymes. We also showed that exogenous melatonin regulated the expression of stress-responsive and ion-channel genes under salinity, which could contribute to improved salt tolerance in cotton. Taken together, our study provides evidence that cotton contains endogenous melatonin, and it may have unraveled crucial evidence of the role of melatonin in cotton against salt stress.

Comprehensive analysis of the Gossypium hirsutum L. respiratory burst oxidase homolog (Ghrboh) gene family.

BACKGROUND: Plant NADPH oxidase (NOX), also known as respiratory burst oxidase homolog (rboh), encoded by the rboh gene, is a key enzyme in the reactive oxygen species (ROS) metabolic network. It catalyzes the formation of the superoxide anion (O2•-), a type of ROS. In recent years, various studies had shown that members of the plant rboh gene family were involved in plant growth and developmental processes as well as in biotic and abiotic stress responses, but little is known about its functional role in upland cotton. RESULTS: In the present study, 26 putative Ghrboh genes were identified and characterized. They were phylogenetically classified into six subfamilies and distributed at different densities across 18 of the 26 chromosomes or scaffolds. Their exon-intron structures, conserved domains, synteny and collinearity, gene family evolution, regulation mediated by cis-acting elements and microRNAs (miRNAs) were predicted and analyzed. Additionally, expression profiles of Ghrboh gene family were analyzed in different tissues/organs and at different developmental stages and under different abiotic stresses, using RNA-Seq data and real-time PCR. These profiling studies indicated that the Ghrboh genes exhibited temporal and spatial specificity with respect to expression, and might play important roles in cotton development and in stress tolerance through modulating NOX-dependent ROS induction and other signaling pathways. CONCLUSIONS: This comprehensive analysis of the characteristics of the Ghrboh gene family determined features such as sequence, synteny and collinearity, phylogenetic and evolutionary relationship, expression patterns, and cis-element- and miRNA-mediated regulation of gene expression. Our results will provide valuable information to help with further gene cloning, evolutionary analysis, and biological function analysis of cotton rbohs.

Detection of CNV in the SH3RF2 gene and its effects on growth and carcass traits in chickens.

BACKGROUND: The SH3RF2 gene is a protein-coding gene located in a quantitative trait locus associated with body weight, and its deletion has been shown to be positively associated with body weight in chickens. RESULTS: In the present study, CNV in the SH3RF2 gene was detected in 4079 individuals from 17 populations, including the "Gushi ×Anka" F2 resource population and populations of Chinese native chickens, commercial layers, and commercial broilers. The F2 resource population was then used to investigate the genetic effects of the chicken SH3RF2 gene. The results showed that the local chickens and commercial layers were all homozygous for the wild-type allele. Deletion mutation individuals were detected in all of the commercial broiler breeds except Hubbard broiler. A total of, 798 individuals in the F2 resource group were used to analyze the effects of genotype (DD/ID/II) on chicken production traits. The results showed that CNV was associated with 2-, 6-, 10-, and 12-week body weight (P = 0.026, 0.042, 0.021 and 0.039 respectively) and significantly associated with 8-week breast bone length (P = 0.045). The mutation was significantly associated with 8-week body weight (P = 0.007) and 4-week breast bone length (P = 0.010). CNV was significantly associated with evisceration weight, leg muscle weight, carcass weight, breast muscle weight and gizzard weight (P = 0.032, 0.033, 0.045, 0.004 and 0.000, respectively). CONCLUSIONS: CNV of the SH3RF2 gene contributed to variation in the growth and weight gain of chickens.

Targeting human Mas-related G protein-coupled receptor X1 to inhibit persistent pain.

Human Mas-related G protein-coupled receptor X1 (MRGPRX1) is a promising target for pain inhibition, mainly because of its restricted expression in nociceptors within the peripheral nervous system. However, constrained by species differences across Mrgprs, drug candidates that activate MRGPRX1 do not activate rodent receptors, leaving no responsive animal model to test the effect on pain in vivo. Here, we generated a transgenic mouse line in which we replaced mouse Mrgprs with human MrgprX1 This humanized mouse allowed us to characterize an agonist [bovine adrenal medulla 8-22 (BAM8-22)] and a positive allosteric modulator (PAM), ML382, of MRGPRX1. Cellular studies suggested that ML382 enhances the ability of BAM8-22 to inhibit high-voltage-activated Ca2+ channels and attenuate spinal nociceptive transmission. Importantly, both BAM8-22 and ML382 effectively attenuated evoked, persistent, and spontaneous pain without causing obvious side effects. Notably, ML382 by itself attenuated both evoked pain hypersensitivity and spontaneous pain in MrgprX1 mice after nerve injury without acquiring coadministration of an exogenous agonist. Our findings suggest that humanized MrgprX1 mice provide a promising preclinical model and that activating MRGPRX1 is an effective way to treat persistent pain.

The Effect of Umbilical Cord Mesenchymal Stem Cells Combined with Tetramethylpyrazine Therapy on Ischemic Brain Injury: A Histological Study.

BACKGROUND: Relatively poor survival and differentiation performance of umbilical cord mesenchymal stem cells (ucMSCs) limits its application of transplantation. The purpose of this study was to investigate the combined effect of ucMSCs and tetramethylpyrazine (TMP) on the histological therapy of ischemia stroke. METHODS: Using a middle cerebral artery occlusion (MCAO) model, we sought to determine the therapeutic effects of ucMSCs combined with TMP on ischemic stroke in rats. 1 × 106 ucMSCs was intracerebral transplanted after 24 hours and TMP (50 mg/kg) was injected intraperitoneally every day. After 7 days, the brain tissues were subjected to infarct weight measurement and preparation for 2,3,5-triphenyltetrazolium chloride (TTC) staining, HE staining, and immunohistochemical analysis. RESULTS: The results showed that TMP combined with ucMSCs treatment significantly decreased the neurological deficit score, as well as the cerebral infarct ratio (from 16.33±3.35 to 7.67±1.19%) compared to TMP or ucMSCs treated alone. Moreover, TMP+ucMSCs treatment improved the morphological architecture of the infarct zone, dramatically up-regulated the expression of α-tubulin and nestin, and down-regulated GFAP and IL-1 expression. CONCLUSIONS: These data suggest that ucMSCs combined with TMP are able to exert therapeutic effects following ischemic injury by improving neurogenesis, inhibiting inflammation, and ameliorating histological damage. This may therefore be a promising future treatment for ischemic stroke.

Rumor spreading in complex networks under stochastic node activity.

The research on rumor spreading has a long history, and its wanton flooding has brought huge impact on people's life. In the process of its spreading, the individual's activity plays an important role. However, in the complex and changeable environment, randomness cannot be ignored, not to mention its influence on individual activity Based on the I S R model of individual activity, this paper explores the stochastic version of the rumor model including fluctuations in the activity. Then, the influence of Stratonovich stochastic noise on the asymptotic behavior of non-linear rumor spreading model is studied. Through the mathematical analysis, we get the critical values to measure whether the deterministic and stochastics models spread or not, as well as the threshold conditions for rumor to spread wantonly. At the same time, the effects of Stratonovich stochastic noise on the asymptotic behavior of rumor-free equilibrium point E 0 and endemic equilibrium point E ∗ are obtained respectively, and the condition that the rumor-free equilibrium is globally asymptotically stable in the presence of noise is given. Finally, the theoretical results are verified by numerical simulation.

The long non-coding RNA lncRNA973 is involved in cotton response to salt stress.

BACKGROUND: Long non-coding (lnc) RNAs are a class of functional RNA molecules greater than 200 nucleotides in length, and lncRNAs play important roles in various biological regulatory processes and response to the biotic and abiotic stresses. LncRNAs associated with salt stress in cotton have been identified through RNA sequencing, but the function of lncRNAs has not been reported. We previously identified salt stress-related lncRNAs in cotton (Gossypium spp.), and discovered the salt-related lncRNA-lncRNA973. RESULTS: In this study, we identified the expression level, localization, function, and preliminary mechanism of action of lncRNA973. LncRNA973, which was localized in the nucleus, was expressed at a low level under nonstress conditions but can be significantly increased by salt treatments. Here lncRNA973 was transformed into Arabidopsis and overexpressed. Along with the increased expression compared with wild type under salt stress conditions in transgenic plants, the seed germination rate, fresh weights and root lengths of the transgenic plants increased. We also knocked down the expression of lncRNA973 using virus-induced gene silencing technology. The lncRNA973 knockdown plants wilted, and the leaves became yellowed and dropped under salt-stress conditions, indicating that the tolerance to salt stress had decreased compared with wild type. LncRNA973 may be involved in the regulation of reactive oxygen species-scavenging genes, transcription factors and genes involved in salt stress-related processes in response to cotton salt stress. CONCLUSIONS: LncRNA973 was localized in the nucleus and its expression was increased by salt treatment. The lncRNA973-overexpression lines had increased salt tolerance compared with the wild type, while the lncRNA973 knockdown plants had reduced salt tolerance. LncRNA973 regulated cotton responses to salt stress by modulating the expression of a series of salt stress-related genes. The data provides a basis for further studies on the mechanisms of lncRNA973-associated responses to salt stress in cotton.