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Background: Grain size affects not only rice yield but is also an important element in quality of appearance. However, the mechanism for inheritance of grain size is unclear. Results: A rice chromosome segment substitution line Z1392, which harbors three substitution segments and produces grains of increased length, was identified. The three chromosome segments were located on chromosomes 1, 5, and 6, and the average length of the substitution segment was 3.17 Mb. Cytological analysis indicates that the predominant cause of increased grain length in Z1392 could be cell expansion in the glumes. Seven quantitative trait loci (QTLs) for grain size related traits were identified using the secondary F2 population produced by Nipponbare/Z1392. The inheritance of grain length in Z1392 was mainly controlled by two major QTLs, qGL-5 and qGL-6. qGL-6 was localized on a 1.26 Mb region on chromosome 6, and OsARF19 may be its candidate gene. Based on QTL mapping, three single-segment substitution lines (S1, S2, and S3) and two double-segment substitution lines (D1 and D2) were selected, and the mapping accuracy for qGL-5 and qGL-6 was further verified using three single-segment substitution lines. Analysis of QTL additive and epistatic effects revealed that the additive effect of alleles qGL-5 and qGL-6 from 'Xihui 18' was estimated to increase grain length of Z1392 by 0.22 and 0.15 mm, respectively. In addition, a positive epistatic interaction between qGL-5 and qGL-6 was detected, which indicates that the pyramiding of qGL-5 and qGL-6 for grain length produces a novel genotype with longer grains. Conclusions: Inheritance of grain length in the triple-segment substitution line Z1392 is mainly controlled by two major QTLs, qGL-5 and qGL-6. qGL-6 was found to be located in a 1.26 Mb region on chromosome 6, and OsARF19 may be its candidate gene. A positive epistatic interaction between qGL-5 and qGL-6 results in longer grains. The present results can be used to facilitate cloning of the qGL-5 and qGL-6 genes and contribute to improvement of grain yield in rice. [ABSTRACT FROM AUTHOR]

Exopolysaccharides (EPSs) are high-molecular-weight carbohydrates with a wide range of biophysiological activities, such as antioxidant activity, immunostimulatory activity, antitumor activity, hepatoprotective activity, and antifatigue effects. In the present work, two water-soluble EPSs, namely, A14EPS-1 and A14EPS-2, were isolated and purified from the fungal endophytic strain A14 using ethanol precipitation, DEAE-cellulose ion exchange chromatography and Sepharose G-150 gel filtration chromatography. A14EPS-1 (∼2.4 × 104 Da, the major fraction) was mainly composed of mannose, rhamnose, glucose, galactose, xylose and arabinose with a molar ratio of 0.31:0.55:10.00:0.34:0.03:0.06. The major monosaccharide of A14EPS-1 was pyranose, which was connected by α-glycosidic linkages. And the side chains of A14EPS-1 may be composed of rhamnose, arabinose, glucose and galactose; moreover, the backbone of A14EPS-1 may be composed of rhamnose, xylose, arabinose and glucose. A14EPS-2 (∼0.5 × 104 Da) was mainly composed of mannose, rhamnose, glucose, galactose, xylose and arabinose in a ratio of 0.16:0.88:10.00:0.39:0.06:0.06. Pyranose was observed in both the α- and β-configurations in A14EPS-2, and the α configuration was dominant. In addition, the results of the bioactivity assays indicated that both A14EPS-1 and A14EPS-2 had moderate antioxidant activity in vitro , and A14EPS-2 showed a moderate antiproliferation effect on human hepatocellular carcinoma HepG2 cells. [ABSTRACT FROM AUTHOR]

Bone marrow mesenchymal stem cells (BMSCs) exhibit an age-related lineage switch between osteogenic and adipogenic fates, which contributes to bone loss and adiposity. Here we identified a long noncoding RNA, Bmncr, which regulated the fate of BMSCs during aging. Mice depleted of Bmncr (Bmncr-KO) showed decreased bone mass and increased bone marrow adiposity, whereas transgenic overexpression of Bmncr (Bmncr-Tg) alleviated bone loss and bone marrow fat accumulation. Bmncr regulated the osteogenic niche of BMSCs by maintaining extracellular matrix protein fibromodulin (FMOD) and activation of the BMP2 pathway. Bmncr affected local 3D chromatin structure and transcription of Fmod. The absence of Fmod modified the bone phenotype of Bmncr-Tg mice. Further analysis revealed that Bmncr would serve as a scaffold to facilitate the interaction of TAZ and ABL, and thus facilitate the assembly of the TAZ and RUNX2/PPARG transcriptional complex, promoting osteogenesis and inhibiting adipogenesis. Adeno-associated viral-mediated overexpression of Taz in osteoprogenitors alleviated bone loss and marrow fat accumulation in Bmncr-KO mice. Furthermore, restoring BMNCR levels in human BMSCs reversed the age-related switch between osteoblast and adipocyte differentiation. Our findings indicate that Bmncr is a key regulator of the age-related osteogenic niche alteration and cell fate switch of BMSCs. [ABSTRACT FROM AUTHOR]

• The effect of different factors on interfacial bond behavior of PEC was discussed. • Pre-applied concrete strain gauges optimized measuring method of concrete strain. • Prediction model of bond-slip between concrete and H-shaped steel was established. • The bond stress distribution of H-shaped steel was investigated. In this paper, the bond behavior between the section steel and concrete in partially encased composite structural members (PEC) is investigated, and the concrete strength, anchorage length, and amount of expansion agent are considered. The results show that the ultimate bond stress of PEC increased as the concrete, bond length, and amount of expansion agent increased. Quantitative analysis of the bond stress composition between concrete and section steel, revealed that the length of the region where the chemical adhesive force existed was much larger than the length of the region where the friction force existed in the micro-slip stage. In addition, the bond stress distribution gradually transitioned from the H-shaped web to the flanges as the amount of expansion agent increased. Considering different influence factors, the characteristic bond strength formula was obtained through statistical regression. A prediction model of the bond-slip between the concrete and section steel in PEC specimens was established, and the optimized measurement method of the concrete strain value at the bonding interface was used to investigate the bond stress distribution of the H-shaped steel webs and flanges. [ABSTRACT FROM AUTHOR]

• The bacteria producing urease was adopted to induce CaCO 3 precipitation. • Various factors affecting microbial growth and urease activity were studied. • The dynamic process of microbial induced CaCO 3 precipitation was revealed. • The precipitates were analyzed and characterized in detail. • The mineralization mechanism model of MICP was established. Microbial induced calcium carbonate precipitation (MICP) is a widespread phenomenon in nature. In this paper, various factors affecting microbial growth and urease activity were studied, including temperature, initial pH, urea concentration, Ca2+ concentration and gelling solution concentration, and the optimal process conditions for calcium carbonate preparation were determined. Subsequently, the changes of Ca2+ concentration, NH 4 + concentration and pH value in alkaline medium with and without bacteria were studied carefully, and the dynamic process of calcium carbonate deposition was also revealed. Finally, the mineralization mechanism model of MICP was established by characterization and analysis of the precipitates. The results indicated that urease produced by bacteria in the metabolism process of bacteria could accelerate the hydrolysis rate of urea and the formation rate of carbonate. In addition, the bacterial cells themselves were negatively charged, which could adsorb Ca2+ with positive charge. Meanwhile, they could also be used as the nucleation sites to accelerate the generation of calcium carbonate. [ABSTRACT FROM AUTHOR]

Objective: Activating brown adipose tissue (BAT) thermogenesis is a promising approach to combat obesity and metabolic disorders. The post-transcriptional regulation of BAT thermogenesis mediated by RNA-binding proteins (RBPs) is still not fully understood. This study explores the physiological role of novel RBPs in BAT differentiation and thermogenesis., Methods: We used multiple public datasets to screen out novel RBPs responsible for BAT differentiation and thermogenesis. In vitro loss- and gain-of-function experiments were performed in both C3H10T1/2 preadipocytes and mature brown adipocytes to determine the role of Y-box binding protein 3 (YBX3) in brown adipocyte differentiation and thermogenesis. Adeno-associated virus (AAV)-mediated BAT-specific knockdown or overexpression of Ybx3 was applied to investigate the function of YBX3 in vivo., Results: YBX3 is a brown adipocyte-enriched RBP induced by cold stimulation and β-adrenergic signaling. Both in vitro loss- and gain-of-function experiments demonstrate that YBX3 is essential for brown adipocyte differentiation and thermogenesis. BAT-specific loss of Ybx3 dampens thermogenesis and exacerbates diet-induced obesity in mice, while overexpression of Ybx3 promotes thermogenesis and confers protection against diet-induced metabolic dysfunction. Transcriptome analysis and mitochondrial stress test indicate that Ybx3 deficiency compromises the mitochondrial oxidative phosphorylation, leading to thermogenic failure. Mechanistically, YBX3 stabilizes the mRNA of Slc3a2 and Pparg, which facilitates branched-chain amino acid (BCAA) influx and catabolism and fuels brown adipocyte differentiation and thermogenesis., Conclusions: YBX3 facilitates BAT fueling BCAA to boost thermogenesis and energy expenditure, which protects against obesity and metabolic dysfunction. Thus, YBX3 could be a promising therapeutic target for obesity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Objective: This study aims to evaluate the differences between The balloon catheter method and End-hole Catheter Method in measuring hepatic venous pressure gradient (HVPG) among cirrhosis patients., Methods: From October 2017 to January 2024, patients who underwent HVPG measurements using both methods were consecutively included. HVPGs obtained from both methods were compared with the portal vein pressure gradient (PPG) obtained via transjugular intrahepatic portosystemic shunt (TIPS) using paired comparisons. Additionally, the consistency and predictive ability for bleeding risk of the two methods, as well as the impact of intrahepatic veno-venous shunt (IHVS), were analyzed., Results: The study enrolled 145 patients, each of whom had HVPG measured by both methods. PPG was measured in 61 patients. There was a statistically significant difference between the PPGs and HVPGs measured by both the balloon catheter method and the end-hole catheter method (P < 0.001), with the HVPG mean values obtained by the end-hole catheter method being closer to the PPGs. In the non-IHVS group, no significant statistical difference was found between the two methods (P = 0.071). In contrast, the IHVS group showed a significant difference (P < 0.001), with a mean difference of 2.98 ± 4.03 mmHg. When IHVS was absent, the measurement results from the end-hole catheter method and the balloon catheter method were found to be highly correlated. The end-hole catheter method has a higher screening capability for patients at risk of bleeding compared to the balloon catheter method (75.90% vs. 72.86%)., Conclusion: HVPG measurements using either the balloon catheter method or end-hole catheter method showed significant difference with the PPG. The end-hole catheter method has a higher screening capability for patients at risk of bleeding, and IHVS could lead to lower HVPG measurements with The balloon catheter method., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

The dynamic interplay between parenchymal hepatocytes and non-parenchymal cells (NPCs), such as macrophages, is an important mechanism for liver metabolic homeostasis. Although numerous endeavors have been made to identify the mediators of metabolic dysfunction associated steatohepatitis (MASH), the molecular underpinnings of MASH progression remain poorly understood, and therapies to arrest MASH progression remain elusive. Herein, it is revealed that the expression of grancalcin (GCA) is upregulated in the macrophages of patients and rodents with MASH and correlates with MASH progression. Notably, the administration of recombinant GCA aggravates the development of MASH, whereas, Gca deletion in myeloid cells blunts liver steatosis and inflammation in multiple MASH murine models. Mechanistically, GCA activates macrophages via TLR9-NF-κB signaling, and the activated macrophages promote hepatocyte lipid accumulation and apoptosis via secretion of Interleukin-6(IL-6), Tumor Necrosis Factor α (TNFα), and Interleukin-1β(IL-1β), thereby leading to hepatic steatosis and inflammation. Finally, the therapeutic administration of antibody blocking GCA effectively halts the progression of MASH. Collectively, these findings implicate GCA as a crucial mediator of MASH and clarify a new metabolic signaling axis between the hepatocytes and macrophages, implying that GCA can emerge as a particularly interesting putative therapeutic target for reversing MASH progression., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Research on the combined use of ear acupoint embedding beans and warming meridians with cold-dispersing formulas for alleviating resting pain in patients with arteriosclerosis obliterans (ASO) remains limited., Aim: To explore the therapeutic efficacy of auricular point embedding beans combined with Wenjing Sanhan prescription in alleviating resting pain in patients with lower-limb ASO., Methods: A total of 100 patients with ASO experiencing resting pain who were treated at our hospital from January 2022 to January 2023 were enrolled. They were randomly allocated into two groups using a double-blind approach. The control group was treated using a warming meridian with a cold-dispersing formula, while the study group received additional treatment with ear acupoint embedding beans. The clinical efficacy, ankle-brachial artery pressure ratio, hemorheological indicators, and traditional Chinese medicine symptom scores were compared between the two groups., Results: The clinical efficacy rate in the study group was significantly higher (94.00%) than that in the control group (72.00%, P < 0.05). Moreover, the ankle-brachial artery pressure ratio was significantly higher in the study group after treatment ( P < 0.05). Hemorheological parameters, including whole blood viscosity, plasma viscosity (1.83 ± 0.11) mPa/s, fibrinogen levels (3.30 ± 0.21) g/L, platelet adhesion rate (49.87% ± 10.51%), and erythrocyte aggregation index (1.79 ± 0) were improved in the study group compared to the control group. In addition, the scores for decreased skin temperature (1.41 ± 0.26), intermittent claudication (1.30 ± 0.20), and resting pain (1.23 ± 0.31) were significantly lower in the study group than those in the control group (all P < 0.05). The level of oxidative stress in the study group also exhibited significant improvement ( P < 0.05), and the levels of inflammatory factors were considerably lower than those in the control group., Conclusion: The combination of ear point embedding beans and Wenjing Sanhan prescription demonstrates promising clinical efficacy in alleviating resting pain associated with ASO., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Ginsenoside Compound K (GCK) is the main metabolite of natural protopanaxadiol ginsenosides with diverse pharmacological effects. Gut microbiota contributes to the biotransformation of GCK, while the effect of gut microbiota on the pharmacokinetics of GCK in vivo remains unclear. To illustrate the role of gut microbiota in GCK metabolism in vivo, a systematic investigation of the pharmacokinetics of GCK in specific pathogen free (SPF) and pseudo-germ-free (pseudo-GF) rats were conducted. Pseudo-GF rats were treated with non-absorbable antibiotics. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was validated for the quantification of GCK in rat plasma. Compared with SPF rats, the plasma concentration of GCK significantly increased after the gut microbiota depleted. The results showed that GCK absorption slowed down, Tmax delayed by 3.5 h, AUC0-11 increased by 1.3 times, CLz/F decreased by 0.6 times in pseudo-GF rats, and Cmax was 1.6 times higher than that of normal rats. The data indicated that gut microbiota played an important role in the pharmacokinetics of GCK in vivo., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Deng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Individuals diagnosed with gastrointestinal tumors are at an increased risk of developing cardiovascular diseases. Among which, ventricular arrhythmia is a prevalent clinical concern. This suggests that ventricular arrhythmias may have predictive value in the prognosis of patients with gastrointestinal tumors., Aim: To explore the prognostic value of ventricular arrhythmias in patients with gastrointestinal tumors receiving surgery., Methods: We retrospectively analyzed data from 130 patients undergoing gastrointestinal tumor resection. These patients were evaluated by a 24-h ambulatory electrocardiogram (ECG) at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2018 to June 2020. Additionally, 41 general healthy age-matched and sex-matched controls were included. Patients were categorized into survival and non-survival groups. The primary endpoint was all-cause mortality, and secondary endpoints included major adverse cardiovascular events (MACEs)., Results: Colorectal tumors comprised 90% of cases. Preoperative ambulatory ECG monitoring revealed that among the 130 patients with gastrointestinal tumors, 100 (76.92%) exhibited varying degrees of premature ventricular contractions (PVCs). Ten patients (7.69%) manifested non-sustained ventricular tachycardia (NSVT). The patients with gastrointestinal tumors exhibited higher PVCs compared to the healthy controls on both conventional ECG [27 (21.3) vs 1 (2.5), P = 0.012] and 24-h ambulatory ECG [14 (1.0, 405) vs 1 (0, 6.5), P < 0.001]. Non-survivors had a higher PVC count than survivors [150.50 (7.25, 1690.50) vs 9 (0, 229.25), P = 0.020]. During the follow-up period, 24 patients died and 11 patients experienced MACEs. Univariate analysis linked PVC > 35/24 h to all-cause mortality, and NSVT was associated with MACE. However, neither PVC burden nor NSVT independently predicted outcomes according to multivariate analysis., Conclusion: Patients with gastrointestinal tumors exhibited elevated PVCs. PVCs > 35/24 h and NSVT detected by 24-h ambulatory ECG were prognostically significant but were not found to be independent predictors., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Inaccurate Forrest classification may significantly affect clinical outcomes, especially in high risk patients. Therefore, this study aimed to develop a real-time deep convolutional neural network (DCNN) system to assess the Forrest classification of peptic ulcer bleeding (PUB)., Methods: A training dataset (3868 endoscopic images) and an internal validation dataset (834 images) were retrospectively collected from the 900th Hospital, Fuzhou, China. In addition, 521 images collected from four other hospitals were used for external validation. Finally, 46 endoscopic videos were prospectively collected to assess the real-time diagnostic performance of the DCNN system, whose diagnostic performance was also prospectively compared with that of three senior and three junior endoscopists., Results: The DCNN system had a satisfactory diagnostic performance in the assessment of Forrest classification, with an accuracy of 91.2% (95%CI 89.5%-92.6%) and a macro-average area under the receiver operating characteristic curve of 0.80 in the validation dataset. Moreover, the DCNN system could judge suspicious regions automatically using Forrest classification in real-time videos, with an accuracy of 92.0% (95%CI 80.8%-97.8%). The DCNN system showed more accurate and stable diagnostic performance than endoscopists in the prospective clinical comparison test. This system helped to slightly improve the diagnostic performance of senior endoscopists and considerably enhance that of junior endoscopists., Conclusion: The DCNN system for the assessment of the Forrest classification of PUB showed satisfactory diagnostic performance, which was slightly superior to that of senior endoscopists. It could therefore effectively assist junior endoscopists in making such diagnoses during gastroscopy., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Psoriasis is one of several chronic inflammatory skin diseases with a high rate of recurrence, and its pathogenesis remains unclear. Nicotinamide mononucleotide (NMN), as an important precursor of nicotinamide adenine dinucleotide (NAD+), has been reported to be a promising agent in treating various diseases, its positive effects including those induced via its anti-inflammatory and antioxidant properties. For this reason, we have aimed to explore the possible role of NMN in the treatment of psoriasis. Psoriasis models were constructed with imiquimod (IMQ) stimulation for 5 days in vivo and with M5 treatment in keratinocyte cell lines in vitro. NMN treatment during the IMQ application period markedly attenuated excess epidermal proliferation, splenomegaly, and inflammatory responses. According to GEO databases, Sirtuin1 (SIRT1) levels significantly decreased in psoriasis patients' lesion tissues; this was also the case in the IMQ-treated mice, while NMN treatment reversed the SIRT1 decline in the mouse model. Moreover, NMN supplementation also improved the prognoses of the mice after IMQ stimulation, compared to the untreated group with elevated SIRT1 levels. In HEKa and HaCaT cells, the co-culturing of NMN and M5 significantly decreased the expression levels of proinflammation factors, the phosphorylation of NF-κB, stimulator of interferon genes (STING) levels, and reactive oxygen species levels. NMN treatment also recovered the decrease in mitochondrial membrane potential and respiration ability and reduced mtDNA in the cytoplasm, leading to the inhibition of autoimmune inflammation. The knockdown of SIRT1 in vitro eliminated the protective and therapeutic effects of NMN against M5. To conclude, our results indicate that NMN protects against IMQ-induced psoriatic inflammation, oxidative stress, and mitochondrial dysfunction by activating the SIRT1 pathway.

Skeletal stem/progenitor cell (SSPC) senescence is a major cause of decreased bone regenerative potential with aging, but the causes of SSPC senescence remain unclear. In this study, we revealed that macrophages in calluses secrete prosenescent factors, including grancalcin (GCA), during aging, which triggers SSPC senescence and impairs fracture healing. Local injection of human rGCA in young mice induced SSPC senescence and delayed fracture repair. Genetic deletion of Gca in monocytes/macrophages was sufficient to rejuvenate fracture repair in aged mice and alleviate SSPC senescence. Mechanistically, GCA binds to the plexin-B2 receptor and activates Arg2-mediated mitochondrial dysfunction, resulting in cellular senescence. Depletion of Plxnb2 in SSPCs impaired fracture healing. Administration of GCA-neutralizing antibody enhanced fracture healing in aged mice. Thus, our study revealed that senescent macrophages within calluses secrete GCA to trigger SSPC secondary senescence, and GCA neutralization represents a promising therapy for nonunion or delayed union in elderly individuals., (© 2024. The Author(s).)

The crosstalk between the bone and adipose tissue is known to orchestrate metabolic homeostasis, but the underlying mechanisms are largely unknown. Herein, we find that GCA + (grancalcin) immune cells accumulate in the bone marrow and release a considerable amount of GCA into circulation during obesity. Genetic deletion of Gca in myeloid cells attenuates metabolic dysfunction in obese male mice, whereas injection of recombinant GCA into male mice causes adipose tissue inflammation and insulin resistance. Mechanistically, we found that GCA binds to the Prohibitin-2 (PHB2) receptor on adipocytes and activates the innate and adaptive immune response of adipocytes via the PAK1-NF-κB signaling pathway, thus provoking the infiltration of inflammatory immune cells. Moreover, we show that GCA-neutralizing antibodies improve adipose tissue inflammation and insulin sensitivity in obese male mice. Together, these observations define a mechanism whereby bone marrow factor GCA initiates adipose tissue inflammation and insulin resistance, showing that GCA could be a potential target to treat metainflammation., (© 2024. The Author(s).)

Obesity is a process of fat accumulation due to the imbalance between energy intake and consumption. Long noncoding RNA (lncRNA) Hnscr is crucial for metabolic regulation, but its roles in lipid metabolism during obesity are still unknown. In this article, we found that the expression of Hnscr gradually decreased in adipose tissues of diet-induced obese mice. Furthermore, the deletion of Hnscr promoted an increase in body weight and adipose tissue weight by upregulating the expression of lipogenesis genes and downregulating lipolysis genes in inguinal white adipose tissue (iWAT) and brown adipose tissue. In vitro knockdown of Hnscr in adipocytes resulted in reduced lipolysis of adipocytes. Overexpression of Hnscr by adenovirus or drug mimics showed the opposite. Mechanistically, Hnscr regulated adipose lipid metabolism by mediating the cyclic adenosine monophosphate/protein kinase A signaling pathway. This study identifies the initial characterization of Hnscr as a critical modifier that regulates lipid metabolism, suggesting that lncRNA Hnscr is a potential target for treating obesity., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

A high-fat diet (HFD) plays a critical role in hepatocyte insulin resistance. Numerous models and factors have been proposed to elucidate the mechanism of palmitic acid (PA)-induced insulin resistance. However, proteomic studies of insulin resistance by HFD stimulation are usually performed under insulin conditions, leading to an unclear understanding of how a HFD alone affects hepatocytes. Here, we mapped the phosphorylation rewiring events in PA-stimulated HepG2 cells and found PA decreased the phosphorylation level of the eukaryotic translation initiation factor 4E-binding protein 2 (4EBP2) at S65/T70. Further experiments identified 4EBP2 as a key node of insulin resistance in either HFD mice or PA-treated cells. Reduced 4EBP2 levels increased glucose uptake and insulin sensitivity, whereas the 4EBP2&#95;S65A/T70A mutation exacerbated PA-induced insulin resistance. Additionally, the nascent proteome revealed many glycolysis-related proteins translationally regulated by 4EBP2 such as hexokinase-2, pyruvate kinase PKM, TBC1 domain family member 4, and glucose-6-phosphate 1-dehydrogenase. In summary, we report the critical role of 4EBP2 in regulating HFD-stimulated insulin resistance in hepatocytes., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Patients with rheumatoid arthritis (RA) have a much higher incidence of cardiac dysfunction, which contributes to the high mortality rate of RA despite anti-arthritic drug therapy. In this study, we investigated dynamic changes in cardiac function in classic animal models of RA and examined the potential effectors of RA-induced heart failure (HF). Collagen-induced arthritis (CIA) models were established in rats and mice. The cardiac function of CIA animals was dynamically monitored using echocardiography and haemodynamics. We showed that cardiac diastolic and systolic dysfunction occurred in CIA animals and persisted after joint inflammation and that serum proinflammatory cytokine (IL-1β, TNF-α) levels were decreased. We did not find evidence of atherosclerosis (AS) in arthritic animals even though cardiomyopathy was significant. We observed that an impaired cardiac β 1 AR-excitation contraction coupling signal was accompanied by sustained increases in blood epinephrine levels in CIA rats. Furthermore, serum epinephrine concentrations were positively correlated with the heart failure biomarker NT-proBNP in RA patients (r 2  = +0.53, P < 0.0001). In CIA mice, treatment with the nonselective βAR blocker carvedilol (2.5 mg·kg -1 ·d -1 , for 4 weeks) or the specific GRK2 inhibitor paroxetine (2.5 mg·kg -1 ·d -1 , for 4 weeks) effectively rescued heart function. We conclude that chronic and persistent β-adrenergic stress in CIA animals is a significant contributor to cardiomyopathy, which may be a potential target for protecting RA patients against HF., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

SIRT1 functions by regulating the modification of proteins or interacting with other proteins to form complexes. It has been widely studied and found to play significant roles in various biological processes and diseases. However, systematic studies on activated-SIRT1 interactions remain limited. Here, we present a comprehensive SIRT1 interactome under resveratrol stimulation through proximity labeling methods. Our results demonstrated that RanGap1 interacted with SIRT1 in HEK 293T cells and MCF-7 cells. SIRT1 regulated the protein level of RanGap1 and had no obvious effect on RanGap1 transcription. Moreover, the overexpression of Rangap1 increased the ROS level in MCF-7 cells, which sensitized cells to resveratrol and reduced the cell viability. These findings provide evidence that RanGap1 interacts with SIRT1 and influences intracellular ROS, critical signals for mitochondrial functions, cell proliferation and transcription. Additionally, we identified that the SIRT1-RanGap1 interaction affects downstream signals induced by ROS. Overall, our study provides an essential resource for future studies on the interactions of resveratrol-activated SIRT1. There are conflicts about the relationship between resveratrol and ROS in previous reports. However, our data identified the impact of the resveratrol-SIRT1-RanGap1 axis on intracellular ROS.

Background: Long noncoding RNA Gm31629 can regulate hypothalamic neural stem cells (htNSCs) senescence and the aging process. However, the effect of Gm31629 on the senescence of bone marrow mesenchymal stem cells (BMSCs) and bone regeneration is unclear. In the present study, we investigated the effects of Gm31629 on the senescence of BMSCs and bone regeneration., Methods: Gm31629 knockout ( Gm31629 -KO) and wild-type (WT) mice were used to establish a bone regeneration model. The Brdu labelling, CCK8 assay, wound healing assay, β-gal staining and osteogenic differentiation assay were used to assess the effects of Gm31629 on the functions of BMSCs. Micro-computed tomography (CT), histochemical and immunohistochemical staining were used to evaluate the ability of bone regeneration. The mimic of Gm31629 , theaflavin 3-gallate, was used to investigate its role on the senescence of BMSCs and bone regeneration., Results: The expression of Gm31629 reduced in BMSCs of middle-aged mice was compared with that of young mice. The deletion of Gm31629 was sufficient to drive the senescence of BMSCs, resulting in impaired bone regeneration in mice. Mechanistically, Gm31629 could interact with Y-box protein 1(YB-1) and delay its degradation, decreasing the transcription of p16 INK4A of BMSCs. We also found that theaflavin 3-gallate could alleviate the senescence of BMSCs and promote bone regeneration in middle-aged mice., Conclusion: These results indicated that Gm31629 played an important role on BMSCs senescence and bone regeneration and provided a therapeutic target to promote bone regeneration., Competing Interests: The authors declare there are no competing interests., (©2022 Cai et al.)

A specific bone capillary subtype, namely type H vessels, with high expression of CD31 and endomucin, was shown to couple angiogenesis and osteogenesis recently. The number of type H vessels in bone tissue declines with age, and the underlying mechanism for this reduction is unclear. Here, we report that microRNA-188-3p (miR-188-3p) involves this process. miRNA-188-3p expression is upregulated in skeletal endothelium and negatively regulates the formation of type H vessels during ageing. Mice with depletion of miR-188 showed an alleviated age-related decline in type H vessels. In contrast, endothelial-specific overexpression of miR-188-3p reduced the number of type H vessels, leading to decreased bone mass and delayed bone regeneration. Mechanistically, we found that miR-188 inhibits type H vessel formation by directly targeting integrin β3 in endothelial cells. Our findings indicate that miR-188-3p is a key regulator of type H vessel formation and may be a potential therapeutic target for preventing bone loss and accelerating bone regeneration., (© 2022. The Author(s).)

Background: Resveratrol, a well-known natural compound and nutrient, activates the deacetylation ability of SIRT1, demonstrating p53-dependent apoptosis functions in many diseases. However, the nascent proteomic fluctuation caused by resveratrol is still unclear., Objective: In this study, we investigated the effect of resveratrol on the nascent proteome and transcriptome initiated by SIRT1 activation, and we explored the mechanism of resveratrol in HEK 293T cells., Methods: Bioorthogonal noncanonical amino acid tagging (BONCAT) is a method used to metabolically label nascent proteins. In this strategy, L-azidohomoalanine (AHA) was used to replace methionine (Met) under different conditions. Taking advantage of the click reaction between AHA and terminal alkyne- and disulfide-functionalized agarose resin (TAD resin), we were able to efficiently separate stimulation responsive proteins from the pre-existing proteome. Resveratrol responsive proteins were identified by Liquid Chromatograph-Mass Spectrometer/Mass Spectrometer (LC-MS/MS). Furthermore, changes in mRNA levels were analyzed by transcriptome sequencing., Results: Integrational analysis revealed a resveratrol response in HEK 293T cells and showed that Hsp60 was downregulated at both the nascent protein and mRNA levels. Knockdown of SIRT1 and Hsp60 provides evidence that resveratrol downregulated Hsp60 through SIRT1 and that Hsp60 decreased p53 through the Akt pathway., Conclusions: This study revealed dynamic changes in the nascent proteome and transcriptome in response to resveratrol in HEK 293T cells and demonstrated that resveratrol downregulates Hsp60 by activating SIRT1, which may be a possible mechanism by which resveratrol prevents p53-dependent apoptosis by regulating Hsp60., Competing Interests: The authors declare no conflict of interest. This research was supported by research grants from the National Natural Science Foundation of China (grant number 31670781) and Innovation Capability Support Program of Shaanxi Province (grant numbers 2018PT-28, 2017KTPT-04)., (© 2022 Tian Su et al.)

Mucosal healing is a key treatment goal for inflammatory bowel disease, and adequate epithelial regeneration is required for an intact gut epithelium. However, the underlying mechanism for mucosal healing is unclear. Long noncoding RNAs (lncRNAs) have been reported to be involved in the development of inflammatory bowel disease. Here, we report that a lncRNA named Gm31629 decreased in intestinal epithelial cells in response to inflammatory stimulation. Gm31629 deficiency led to exacerbated intestinal inflammation and delayed epithelial regeneration in dextran sulfate sodium-induced (DSS-induced) colitis model. Mechanistically, Gm31629 promoted E2F pathways and cell proliferation by stabilizing Y-box protein 1 (YB-1), thus facilitating epithelial regeneration. Genetic overexpression of Gm31629 protected against DSS-induced colitis in vivo. Theaflavin 3-gallate, a natural compound mimicking Gm31629, alleviated DSS-induced epithelial inflammation and mucosal damage. These results demonstrate an essential role of lncRNA Gm31629 in linking intestinal inflammation and epithelial cell proliferation, providing a potential therapeutic approach to inflammatory bowel disease.

Brown adipose tissue (BAT) is emerging as a target to beat obesity through the dissipation of chemical energy to heat. However, the molecular mechanisms of brown adipocyte thermogenesis remain to be further elucidated. Here, we show that KCTD10, a member of the polymerase delta-interacting protein 1 family, was reduced in BAT by cold stress and a β3 adrenoceptor agonist. Moreover, KCTD10 level increased in the BAT of obese mice, and KCTD10 overexpression attenuates uncoupling protein 1 expression in primary brown adipocytes. BAT-specific KCTD10 knockdown mice had increased thermogenesis and cold tolerance protecting from high-fat diet (HFD)-induced obesity. Conversely, overexpression of KCTD10 in BAT caused reduced thermogenesis, cold intolerance, and obesity. Mechanistically, inhibiting Notch signaling restored the KCTD10 overexpression-suppressed thermogenesis. Our study presents that KCTD10 serves as an upstream regulator of Notch signaling pathway to regulate BAT thermogenesis and whole-body metabolic function.

Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver-related morbidity and mortality whereas the pathogenic mechanism remains largely elusive. DNA N6-methyladenosine (6mA) modification is a recently identified epigenetic mark indicative of transcription in eukaryotic genomes. Here, we aimed to investigate the role and mechanism of DNA 6mA modification in NAFLD progression., Methods: Dot blot and immunohistochemistry were used to detect DNA 6mA levels. Liver-specific AlkB homolog 1 (ALKBH1)-knockout mice and mice with ALKBH1 overexpression in liver were subjected to a high-fat diet or methionine choline-deficient diet to evaluate the critical role of ALKBH1-demethylated DNA 6mA modification in the pathogenesis of hepatic steatosis during NAFLD. RNA sequencing and chromatin immunoprecipitation sequencing were performed to investigate molecular mechanisms underlying this process., Results: The DNA 6mA level was increased significantly with hepatic steatosis, while ALKBH1 expression was down-regulated markedly in both mouse and human fatty liver. Deletion of ALKBH1 in hepatocytes increased genomic 6mA levels and accelerated diet-induced hepatic steatosis and metabolic dysfunction. Comprehensive analyses of transcriptome and chromatin immunoprecipitation sequencing data indicated that ALKBH1 directly bound to and exclusively demethylated 6mA levels of genes involved in fatty acid uptake and lipogenesis, leading to reduced hepatic lipid accumulation. Importantly, ALKBH1 overexpression was sufficient to suppress lipid uptake and synthesis, and alleviated diet-induced hepatic steatosis and insulin resistance., Conclusions: Our findings show an indispensable role of ALKBH1 as an epigenetic suppressor of DNA 6mA in hepatic fatty acid metabolism and offer a potential therapeutic target for NAFLD treatment., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Despite its monotonous structure, sea-island plays a crucial role in sustaining biodiversity and ecosystem functioning. The objectives of this study were to explore the altitudinal variation of soil carbon (C), nitrogen (N), and phosphorus (P) pools in forests across 14 islands spanning temperate zone (TZ), northern subtropical zone (NSZ), mid-subtropical zone (MSZ), and sou-thern subtropical zone (SSZ) in eastern China. The relationships of soil C and nutrient pools with climatic factors and plant species diversity were examined across islands. Our results showed that soil C, N and P pools differed significantly across climatic zones. Soil C and N pools were the lowest in TZ (49.35 and 1.08 t·hm -2 ) and the highest in NSZ (137.25 and 4.63 t·hm -2 ). Soil P pool was the lowest in SSZ (1.3 t·hm -2 ) and the highest in NSZ (5.19 t·hm -2 ). There were significant difference in soil C, N and P pools among vegetation types. Soil C, N and P pools in deciduous forests were significantly higher in subtropical than in temperate islands. Soil C and N pools in evergreen broadleaved forests did not differ among sub-climatic zones, and soil P pool was lower in SSZ than that in NSZ and MSZ. The interactions across mean annual temperature, mean annual precipitation, soil water content, and plant species diversity positively affected latitudinal variation in soil C, N, and P pools. Plant species diversity positively associated with soil N pool, but negatively linked with soil P pool. In conclusion, the latitudinal trend of soil C pool is different, but that of soil N and P pools are identical between sea-island and mainland. The main abiotic and biotic dri-vers of soil C, N and P pools are water availability, temperature and plant species diversity across sea-islands in eastern China.

Bone marrow mesenchymal stem cells (BMSCs) exhibit an age-related lineage switch between osteogenic and adipogenic fates, which contributes to bone loss and adiposity. Here we identified a long noncoding RNA, Bmncr, which regulated the fate of BMSCs during aging. Mice depleted of Bmncr (Bmncr-KO) showed decreased bone mass and increased bone marrow adiposity, whereas transgenic overexpression of Bmncr (Bmncr-Tg) alleviated bone loss and bone marrow fat accumulation. Bmncr regulated the osteogenic niche of BMSCs by maintaining extracellular matrix protein fibromodulin (FMOD) and activation of the BMP2 pathway. Bmncr affected local 3D chromatin structure and transcription of Fmod. The absence of Fmod modified the bone phenotype of Bmncr-Tg mice. Further analysis revealed that Bmncr would serve as a scaffold to facilitate the interaction of TAZ and ABL, and thus facilitate the assembly of the TAZ and RUNX2/PPARG transcriptional complex, promoting osteogenesis and inhibiting adipogenesis. Adeno-associated viral-mediated overexpression of Taz in osteoprogenitors alleviated bone loss and marrow fat accumulation in Bmncr-KO mice. Furthermore, restoring BMNCR levels in human BMSCs reversed the age-related switch between osteoblast and adipocyte differentiation. Our findings indicate that Bmncr is a key regulator of the age-related osteogenic niche alteration and cell fate switch of BMSCs.

Understanding variation of carbon (C), nitrogen (N) and phosphorus (P) stoichiometry in common plant species across islands along a latitude gradient is insightful to reveal the adaptation strategies of plant species to environmental changes. Five common herbaceous species including Artemisia argyi, Setaira viridis, Humulus japonicus, Ophiopog onjaponicus, and Oxalis corniculata were sampled in 125 plots across nine islands in Eastern China. C, N and P contents in leaves, stems, and roots of five plant species were measured, and their relationships with soil C, N and P contents as well as mean annual air temperature (MAT) and mean annual precipitation (MAP) were investigated. The results showed that the range of C, N and P contents in aboveground parts of five species across nine islands was 352.16-518.16, 10.81-34.43, 0.58-2.38 mg·g -1 , while the range of C:N, N:P and C:P was 11.98-38.99, 4.67-27.47, 133.39-748.54, respectively. In terms of roots, the range of C, N and P contents of five species was 312.28-493.34, 9.26-23.27, 0.40-2.10 mg·g -1 , while the range of C:N, N:P and C:P was 18.18-46.79, 8.53-37.38, 174.45-1120.40, respectively. With the increases of latitude, contents of N and P in aboveground parts increased, but N:P decreased. Relative to N content, P content showed higher variation and was largely dependent on environment. Climate factors explained 60% of the variation of N and P contents and N:P across nine islands. In contrast, N and P contents and N:P of roots were independent of latitude, with climatic factors only explained 6%-10% of their variations. The contribution of climatic factors and soil nutrients contributed to the variations of N and P contents differed between above ground parts and roots of five species. Soil N and P had significant effects on P content in roots. Soil P content was positively correlated to aboveground P content. Soil properties explained 37% of the variation in N and P contents of plant roots. Our results suggested that latitude-associated environment shifts were the main drivers of variation in N and P contents and N:P in aboveground parts, and soil nutrients especially affected variation in P in roots of five common plant species, when the effects of plant phylogeny was controlled.

Island vegetation plays an important role in biodiversity research across the world. The study of plant diversity in island is helpful for understanding the mechanism of plant diversity maintenance under land-sea interaction. Here, four typical plant communities (Quercus acutissima community, Robinia pseudoacacia community, Pinus thunbergii community and Vitex negundo community) in Miao Archipelago were selected to examine the species, functional and structural diversities and their responses to environmental factors at the community scale by using species diversity indices, functional diversity indices, as well as structural diversity indices. The results showed that the species richness and Rao index of P. thunbergii community was higher than that of Q. acutissima community and R. pseudoacacia community, but the structural diversity was lower. The species diversity and structural diversity of V. Negundo shrub were lower than that of forest community, but the functional diversity was higher than some forest communities. The relationship between the diversity of typical plant communities in island area illustrated a significant positive correlation between species richness with Rao index and tree height diversity, however the correlation with functional evenness was significantly negative. The structural diversity and functional evenness were determined by slope with negative and positive relationships, respectively. Functional heterogeneity, functional divergence and species diversity were affected largely by soil physical and chemical properties, displaying the positive relationship with soil bulk density and soil total carbon content, and a negative relationship with soil water content. In conclusion, diversity pattern of plant community in Miao Archipelago reflected not only the characteristics in mainland vegetation but also the special nature of the sea island.

The peach fruit moth, Carposina sasakii belongs to Carposinidae in Lepidoptera. In this paper, we described the complete mitogenome of C. sasakii. It is 15,611 bp in length, including 13 PCGs, 2 rRNAs, 22 tRNAs and a major noncoding A + T-rich region, which revealed the typical gene content found in other metazoan mitogenomes. The overall base composition is 42.0% A, 39.5% T, 7.75% G and 10.75% C. The A + T-rich region is located between rrnS and trnM. There is a motif ATAGA in downstream of rrnS followed by a 19 bp Poly-T stretch. The Poly-A is not found in upstream of trnM, and the position of Poly-A is replaced by a stem-loop structure. There are eight mononucleotide repeat sequences (Tn/An) with the length of 7 bp-19bp, three dinucleotide repeat sequences (TA)n/(AT)n, and a longer repeat sequence (AATATATA)5 in A + T-rich region. The mononucleotide repeat sequences occur repeatedly in A + T-rich reigion of C. sasakii, which is special in insects sequenced of Lepidoptera.

Advance on chemical constituents and pharmacological activities of Stellera plants have been conducted. The chemical constituents include terpenes, coumarins, flavonoids, lignans, volatile oils, and other compounds. Pharmacological studies showed that diterpenoids and biflavones showed strong activities, such as antitumor, anti-HIV, and immune regulations. This review hopes to provide a scientific basis for further research and explorations of the medicinal values of the genus.

Understanding the psychobiological basis of relapse remains a challenge in developing therapies for drug addiction. Relapse in cocaine addiction often occurs following exposure to environmental stimuli previously associated with drug taking. The metabotropic glutamate receptor, mGluR5, is potentially important in this respect; it plays a central role in several forms of striatal synaptic plasticity proposed to underpin associative learning and memory processes that enable drug-paired stimuli to acquire incentive motivational properties and trigger relapse. Using cell type-specific RNA interference, we have generated a novel mouse line with a selective knock-down of mGluR5 in dopamine D1 receptor-expressing neurons. Although mutant mice self-administer cocaine, we show that reinstatement of cocaine-seeking induced by a cocaine-paired stimulus is impaired. By examining different aspects of associative learning in the mutant mice, we identify deficits in specific incentive learning processes that enable a reward-paired stimulus to directly reinforce behavior and to become attractive, thus eliciting approach toward it. Our findings show that glutamate signaling through mGluR5 located on dopamine D1 receptor-expressing neurons is necessary for incentive learning processes that contribute to cue-induced reinstatement of cocaine-seeking and which may underpin relapse in drug addiction.

In order to understand the chronic toxicity of a pollutant to an organism in an aquatic environment with different food density, and screen out sensitive endpoints for monitoring Cd2+ pollution with rotifers as test animals, this paper studied the effects of different concentration (2.5, 5.0, 10.0, 20.0 and 40.0 microg x L(-1)) Cd2+ on the life table demography of Bracionus calyciflorus at the Scenedesmus obliquus density being 1.0 x 10(6), 3.0 x 10(6), and 5.0 x 10(6) cells x ml(-1). The results showed that at 25 +/- 1 degrees C, the 24 h LC50 of Cd2+ to B. calyciflorus was 37.7 microg x L(-1). Compared with the controls at the same food density, when the S. obliquus density was 1.0 x 10(6) cells x ml(-1), 20.0 and 40.0 microg x L(-1) of Cd2+ prolonged the generation time of B. calyciflorus significantly, and 5.0 microg x L(-1) of Cd2+ increased the percentage of B. calyciflorus mictic offspring. When the S. obliquus density was 3.0 x 10(6) cells x ml(-1), the Cd2+ at all test concentrations except 5.0 microg x L(-1) decreased the percentage of mictic offspring; when the S. obliquus density was 5.0 x 10(6) cells x ml(-1), all test concentration Cd2+ had no effects on the life table demography (P > 0.05). S. obliquus density had significant effects on the generation time, life expectancy at birth, net reproduction rate, percentage of mictic offspring of B. calyciflorus (P < 0.05), Cd2+ concentration had significant effects on the generation time and the percentage of mictic offspring (P < 0.05), and the interaction of S. obliquus density and Cd2+ concentration had significant effects on the percentage of mictic offspring (P < 0.01). Among all the studied parameters, the generation time and the percentage of mictic offspring were more sensitive to Cd2+ pollution under the algal densities of 1.0 x 10(6) and 3.0 x 10(6) cells x ml(-1), with the latter being the most sensitive.

Toll-like receptor 4 (TLR4) induces two distinct signaling pathways controlled by the TIRAP-MyD88 and TRAM-TRIF pairs of adaptor proteins, which elicit the production of proinflammatory cytokines and type I interferons, respectively. How TLR4 coordinates the activation of these two pathways is unknown. Here we show that TLR4 activated these two signaling pathways sequentially in a process organized around endocytosis of the TLR4 complex. We propose that TLR4 first induces TIRAP-MyD88 signaling at the plasma membrane and is then endocytosed and activates TRAM-TRIF signaling from early endosomes. Our data emphasize a unifying theme in innate immune recognition whereby all type I interferon-inducing receptors signal from an intracellular location.